Adolescent knowledge and attitudes related to clinical trials.

PubMed

Brown, Devin L; Cowdery, Joan E; Jones, Toni Stokes; Langford, Aisha; Gammage, Catherine; Jacobs, Teresa L

2015-06-01

Poor enrollment plagues most clinical trials. Furthermore, despite mandates to improve minority representation in clinical trial participation, little progress has been made. We investigated the knowledge and attitudes of adolescents related to clinical trials and made race/ethnicity comparisons in an attempt to identify a possible educational intervention target. Students aged 13-18 years in southeast Michigan were offered participation through a class at one high school or two academic summer enrichment programs that drew from multiple high schools (73% response). Questionnaires previously validated in adults were administered. Non-Hispanic whites were compared with minorities using Wilcoxon rank-sum tests. Of the 82 respondents, the median age was 16 years (interquartile range: 15-17 years); 22 (28%) were white, 41 (51%) were African American, 11 (14%) were multiracial, 2 (2%) were American Indian or Alaska Native, 1 (1%) was Asian, 3 (4%) were Native Hawaiian or other Pacific Islander, and 2 respondents did not report a race (but did report Hispanic ethnicity). Nine (12%) were Hispanic. Only 27 (33%) had ever heard of a clinical trial. On a scale from 1 (most receptive) to 5 (least receptive) for learning more about a clinical trial for a relevant medical condition, the median score was 2 (interquartile range: 1-3) and for participating in a clinical trial for a relevant medical condition was 2 (interquartile range: 2-3). Overall knowledge was poor, with a median of 46% (interquartile range: 23%-62%) of knowledge answers correct. Knowledge was reduced (p = 0.0006) and attitudes were more negative (p = 0.05) in minorities than non-Hispanic whites, while minorities also endorsed more substantial barriers to trial participation (p = 0.0002). Distrust was similar between minority students and non-Hispanic whites (p = 0.15), and self-efficacy was greater in non-Hispanic whites (p = 0.05). Educational interventions directed toward adolescents that address knowledge, attitudes, and distrust in order to improve clinical trial awareness and receptivity overall are needed and may represent a tool to address disparities in minority enrollment in clinical trials. © The Author(s) 2015.

Clinical Correlations as a Tool in Basic Science Medical Education

PubMed Central

Klement, Brenda J.; Paulsen, Douglas F.; Wineski, Lawrence E.

2016-01-01

Clinical correlations are tools to assist students in associating basic science concepts with a medical application or disease. There are many forms of clinical correlations and many ways to use them in the classroom. Five types of clinical correlations that may be embedded within basic science courses have been identified and described. (1) Correlated examples consist of superficial clinical information or stories accompanying basic science concepts to make the information more interesting and relevant. (2) Interactive learning and demonstrations provide hands-on experiences or the demonstration of a clinical topic. (3) Specialized workshops have an application-based focus, are more specialized than typical laboratory sessions, and range in complexity from basic to advanced. (4) Small-group activities require groups of students, guided by faculty, to solve simple problems that relate basic science information to clinical topics. (5) Course-centered problem solving is a more advanced correlation activity than the others and focuses on recognition and treatment of clinical problems to promote clinical reasoning skills. Diverse teaching activities are used in basic science medical education, and those that include clinical relevance promote interest, communication, and collaboration, enhance knowledge retention, and help develop clinical reasoning skills. PMID:29349328

High-throughput microarray technology in diagnostics of enterobacteria based on genome-wide probe selection and regression analysis.

PubMed

Friedrich, Torben; Rahmann, Sven; Weigel, Wilfried; Rabsch, Wolfgang; Fruth, Angelika; Ron, Eliora; Gunzer, Florian; Dandekar, Thomas; Hacker, Jörg; Müller, Tobias; Dobrindt, Ulrich

2010-10-21

The Enterobacteriaceae comprise a large number of clinically relevant species with several individual subspecies. Overlapping virulence-associated gene pools and the high overall genome plasticity often interferes with correct enterobacterial strain typing and risk assessment. Array technology offers a fast, reproducible and standardisable means for bacterial typing and thus provides many advantages for bacterial diagnostics, risk assessment and surveillance. The development of highly discriminative broad-range microbial diagnostic microarrays remains a challenge, because of marked genome plasticity of many bacterial pathogens. We developed a DNA microarray for strain typing and detection of major antimicrobial resistance genes of clinically relevant enterobacteria. For this purpose, we applied a global genome-wide probe selection strategy on 32 available complete enterobacterial genomes combined with a regression model for pathogen classification. The discriminative power of the probe set was further tested in silico on 15 additional complete enterobacterial genome sequences. DNA microarrays based on the selected probes were used to type 92 clinical enterobacterial isolates. Phenotypic tests confirmed the array-based typing results and corroborate that the selected probes allowed correct typing and prediction of major antibiotic resistances of clinically relevant Enterobacteriaceae, including the subspecies level, e.g. the reliable distinction of different E. coli pathotypes. Our results demonstrate that the global probe selection approach based on longest common factor statistics as well as the design of a DNA microarray with a restricted set of discriminative probes enables robust discrimination of different enterobacterial variants and represents a proof of concept that can be adopted for diagnostics of a wide range of microbial pathogens. Our approach circumvents misclassifications arising from the application of virulence markers, which are highly affected by horizontal gene transfer. Moreover, a broad range of pathogens have been covered by an efficient probe set size enabling the design of high-throughput diagnostics.

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

PubMed

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

2016-04-01

The purpose of our study was to retrospectively evaluate the prevalence and clinical relevance of positive abdominal and pelvic CT findings for patients 65 years of age and older, when compared with all other scanned adult Emergency Department (ED) patients, at a single tertiary care hospital. Our hypothesis was that there is an increased prevalence and clinical relevance of positive abdominal/pelvic CT findings in senior patients. A research ethics board-approved retrospective review of all adult patients who underwent an emergency CT of the abdomen and pelvis for acute nontraumatic abdominal and/or pelvic signs and symptoms was performed. Two thousand one hundred two patients between October 1, 2011, and September 30, 2013, were reviewed. Six hundred thirty-one patients were included in the <65 group (298 men and 333 women; mean age 46, age range 18-64), and 462 were included in the >65 group (209 men and 253 women; mean age 77.6, age range 65-99). Overall, there were more positive CT findings for patients <65 (389 positive cases, 61.6 %) compared with the >65 group (257 positive cases, 55.6 %), which was a statistically significant difference (p < 0.03). Moreover, with the exception of complicated appendicitis cases, which were more common in the >65 group, there were no statistically significant differences in the clinical/surgical relevance of the positive CT findings between the two groups. The findings of our retrospective study therefore refute our hypothesis that there is an increased prevalence of positive abdominal CT findings in patients >65. This may be related to ED physicians at our institution being more hesitant to order CT examinations for the younger population, presumably due to radiation concerns. However, older patients in our series were more likely to present with complicated appendicitis, and a lower threshold for ordering CT examinations of the abdomen and pelvis in this patient population should therefore be considered.

R&D 100 Winner 2010: Acoustic Wave Biosensors

ScienceCinema

Larson, Richard; Branch, Darren; Edwards, Thayne

2018-01-16

The acoustic wave biosensor is innovative device that is a handheld, battery-powered, portable detection system capable of multiplex identification of a wide range of medically relevant pathogens and their biomolecular signatures — viruses, bacteria, proteins, and DNA — at clinically relevant levels. This detection occurs within minutes — not hours — at the point of care, whether that care is in a physician's office, a hospital bed, or at the scene of a biodefense or biomedical emergency.

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

PubMed Central

Gao, Bin; Xu, Ming-Jiang; Bertola, Adeline; Wang, Hua; Zhou, Zhou; Liangpunsakul, Suthat

2017-01-01

Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals. All of these models recapitulate some features of the different stages of ALD and have been widely used by many investigators to study the pathogenesis of ALD and to test for therapeutic drugs/components. However, these models are somewhat variable, depending on mouse genetic background, ethanol dose, and animal facility environment. This review focuses on these models and discusses these variations and some methods to improve the feeding protocol. The pathogenesis, clinical relevance, and translational studies of these models are also discussed. PMID:28411363

A cross-country comparison of intensive care physicians' beliefs about their transfusion behaviour: a qualitative study using the Theoretical Domains Framework.

PubMed

Islam, Rafat; Tinmouth, Alan T; Francis, Jill J; Brehaut, Jamie C; Born, Jennifer; Stockton, Charlotte; Stanworth, Simon J; Eccles, Martin P; Cuthbertson, Brian H; Hyde, Chris; Grimshaw, Jeremy M

2012-09-21

Evidence of variations in red blood cell transfusion practices have been reported in a wide range of clinical settings. Parallel studies in Canada and the United Kingdom were designed to explore transfusion behaviour in intensive care physicians. The aim of this paper is three-fold: first, to explore beliefs that influence Canadian intensive care physicians' transfusion behaviour; second, to systematically select relevant theories and models using the Theoretical Domains Framework (TDF) to inform a future predictive study; and third, to compare its results with the UK study. Ten intensive care unit (ICU) physicians throughout Canada were interviewed. Physicians' responses were coded into theoretical domains, and specific beliefs were generated for each response. Theoretical domains relevant to behaviour change were identified, and specific constructs from the relevant domains were used to select psychological theories. The results from Canada and the United Kingdom were compared. Seven theoretical domains populated by 31 specific beliefs were identified as relevant to the target behaviour. The domains Beliefs about capabilities (confident to not transfuse if patients' clinical condition is stable), Beliefs about consequences (positive beliefs of reducing infection and saving resources and negative beliefs about risking patients' clinical outcome and potentially more work), Social influences (transfusion decision is influenced by team members and patients' relatives), and Behavioural regulation (wide range of approaches to encourage restrictive transfusion) that were identified in the UK study were also relevant in the Canadian context. Three additional domains, Knowledge (it requires more evidence to support restrictive transfusion), Social/professional role and identity (conflicting beliefs about not adhering to guidelines, referring to evidence, believing restrictive transfusion as professional standard, and believing that guideline is important for other professionals), and Motivation and goals (opposing beliefs about the importance of restrictive transfusion and compatibility with other goals), were also identified in this study. Similar to the UK study, the Theory of Planned Behaviour, Social Cognitive Theory, Operant Learning Theory, Action Planning, and Knowledge-Attitude-Behaviour model were identified as potentially relevant theories and models for further study. Personal project analysis was added to the Canadian study to explore the Motivation and goals domain in further detail. A wide range of beliefs was identified by the Canadian ICU physicians as likely to influence their transfusion behaviour. We were able to demonstrate similar though not identical results in a cross-country comparison. Designing targeted behaviour-change interventions based on unique beliefs identified by physicians from two countries are more likely to encourage restrictive transfusion in ICU physicians in respective countries. This needs to be tested in future prospective clinical trials.

A cross-country comparison of intensive care physicians’ beliefs about their transfusion behaviour: A qualitative study using the theoretical domains framework

PubMed Central

2012-01-01

Background Evidence of variations in red blood cell transfusion practices have been reported in a wide range of clinical settings. Parallel studies in Canada and the United Kingdom were designed to explore transfusion behaviour in intensive care physicians. The aim of this paper is three-fold: first, to explore beliefs that influence Canadian intensive care physicians’ transfusion behaviour; second, to systematically select relevant theories and models using the Theoretical Domains Framework (TDF) to inform a future predictive study; and third, to compare its results with the UK study. Methods Ten intensive care unit (ICU) physicians throughout Canada were interviewed. Physicians’ responses were coded into theoretical domains, and specific beliefs were generated for each response. Theoretical domains relevant to behaviour change were identified, and specific constructs from the relevant domains were used to select psychological theories. The results from Canada and the United Kingdom were compared. Results Seven theoretical domains populated by 31 specific beliefs were identified as relevant to the target behaviour. The domains Beliefs about capabilities (confident to not transfuse if patients’ clinical condition is stable), Beliefs about consequences (positive beliefs of reducing infection and saving resources and negative beliefs about risking patients’ clinical outcome and potentially more work), Social influences (transfusion decision is influenced by team members and patients’ relatives), and Behavioural regulation (wide range of approaches to encourage restrictive transfusion) that were identified in the UK study were also relevant in the Canadian context. Three additional domains, Knowledge (it requires more evidence to support restrictive transfusion), Social/professional role and identity (conflicting beliefs about not adhering to guidelines, referring to evidence, believing restrictive transfusion as professional standard, and believing that guideline is important for other professionals), and Motivation and goals (opposing beliefs about the importance of restrictive transfusion and compatibility with other goals), were also identified in this study. Similar to the UK study, the Theory of Planned Behaviour, Social Cognitive Theory, Operant Learning Theory, Action Planning, and Knowledge-Attitude-Behaviour model were identified as potentially relevant theories and models for further study. Personal project analysis was added to the Canadian study to explore the Motivation and goals domain in further detail. Conclusions A wide range of beliefs was identified by the Canadian ICU physicians as likely to influence their transfusion behaviour. We were able to demonstrate similar though not identical results in a cross-country comparison. Designing targeted behaviour-change interventions based on unique beliefs identified by physicians from two countries are more likely to encourage restrictive transfusion in ICU physicians in respective countries. This needs to be tested in future prospective clinical trials. PMID:22999460

Epidemiological characteristics of infectious hematopoietic necrosis virus (IHNV): a review.

PubMed

Dixon, Peter; Paley, Richard; Alegria-Moran, Raul; Oidtmann, Birgit

2016-06-10

Infectious hematopoietic necrosis virus (IHNV, Rhabdoviridae), is the causative agent of infectious hematopoietic necrosis (IHN), a disease notifiable to the World Organisation for Animal Health, and various countries and trading areas (including the European Union). IHNV is an economically important pathogen causing clinical disease and mortalities in a wide variety of salmonid species, including the main salmonid species produced in aquaculture, Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). We reviewed the scientific literature on IHNV on a range of topics, including geographic distribution; host range; conditions required for infection and clinical disease; minimum infectious dose; subclinical infection; shedding of virus by infected fish; transmission via eggs; diagnostic tests; pathogen load and survival of IHNV in host tissues. This information is required for a range of purposes including import risk assessments; parameterisation of disease models; for surveillance planning; and evaluation of the chances of eradication of the pathogen to name just a few. The review focuses on issues that are of relevance for the European context, but many of the data summarised have relevance to IHN globally. Examples for application of the information is presented and data gaps highlighted.

[Formula: see text]Official Position of the American Academy of Clinical Neuropsychology (AACN): Guidelines for Practicum Training in Clinical Neuropsychology.

PubMed

Nelson, Aaron P; Roper, Brad L; Slomine, Beth S; Morrison, Chris; Greher, Michael R; Janusz, Jennifer; Larson, Jennifer C; Meadows, Mary-Ellen; Ready, Rebecca E; Rivera Mindt, Monica; Whiteside, Doug M; Willment, Kim; Wodushek, Thomas R

2015-01-01

Practical experience is central to the education and training of neuropsychologists, beginning in graduate school and extending through postdoctoral fellowship. However, historically, little attention has been given to the structure and requirements of practicum training in clinical neuropsychology. A working group of senior-level neuropsychologists, as well as a current postdoctoral fellow, all from a diverse range of settings (The AACN Practicum Guidelines Workgroup), was formed to propose guidelines for practicum training in clinical neuropsychology. The Workgroup reviewed relevant literature and sought input from professional organizations involved in education and training in neuropsychology. The proposed guidelines provide a definition of practicum training in clinical neuropsychology, detail entry and exit criteria across competencies relevant to practicum training in clinical neuropsychology, and discuss the relationship between doctoral training programs and practicum training sites. The proposed guidelines also provide a methodology for competency-based evaluation of clinical neuropsychology practicum trainees and outline characteristics and features that are integral to an effective training environment. Although the guidelines discussed below may not be implemented in their entirety across all clinical neuropsychology practicum training sites, they are consistent with the latest developments in competency-based education.

Clinical microbiology informatics.

PubMed

Rhoads, Daniel D; Sintchenko, Vitali; Rauch, Carol A; Pantanowitz, Liron

2014-10-01

The clinical microbiology laboratory has responsibilities ranging from characterizing the causative agent in a patient's infection to helping detect global disease outbreaks. All of these processes are increasingly becoming partnered more intimately with informatics. Effective application of informatics tools can increase the accuracy, timeliness, and completeness of microbiology testing while decreasing the laboratory workload, which can lead to optimized laboratory workflow and decreased costs. Informatics is poised to be increasingly relevant in clinical microbiology, with the advent of total laboratory automation, complex instrument interfaces, electronic health records, clinical decision support tools, and the clinical implementation of microbial genome sequencing. This review discusses the diverse informatics aspects that are relevant to the clinical microbiology laboratory, including the following: the microbiology laboratory information system, decision support tools, expert systems, instrument interfaces, total laboratory automation, telemicrobiology, automated image analysis, nucleic acid sequence databases, electronic reporting of infectious agents to public health agencies, and disease outbreak surveillance. The breadth and utility of informatics tools used in clinical microbiology have made them indispensable to contemporary clinical and laboratory practice. Continued advances in technology and development of these informatics tools will further improve patient and public health care in the future. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Clinical Microbiology Informatics

PubMed Central

Sintchenko, Vitali; Rauch, Carol A.; Pantanowitz, Liron

2014-01-01

SUMMARY The clinical microbiology laboratory has responsibilities ranging from characterizing the causative agent in a patient's infection to helping detect global disease outbreaks. All of these processes are increasingly becoming partnered more intimately with informatics. Effective application of informatics tools can increase the accuracy, timeliness, and completeness of microbiology testing while decreasing the laboratory workload, which can lead to optimized laboratory workflow and decreased costs. Informatics is poised to be increasingly relevant in clinical microbiology, with the advent of total laboratory automation, complex instrument interfaces, electronic health records, clinical decision support tools, and the clinical implementation of microbial genome sequencing. This review discusses the diverse informatics aspects that are relevant to the clinical microbiology laboratory, including the following: the microbiology laboratory information system, decision support tools, expert systems, instrument interfaces, total laboratory automation, telemicrobiology, automated image analysis, nucleic acid sequence databases, electronic reporting of infectious agents to public health agencies, and disease outbreak surveillance. The breadth and utility of informatics tools used in clinical microbiology have made them indispensable to contemporary clinical and laboratory practice. Continued advances in technology and development of these informatics tools will further improve patient and public health care in the future. PMID:25278581

Prospective randomized blinded trial of pulmonary function, pain, and cosmetic results after laparoscopic vs. microlaparoscopic cholecystectomy.

PubMed

Schwenk, W; Neudecker, J; Mall, J; Böhm, B; Müller, J M

2000-04-01

The size of laparoscopic instruments has been reduced for use in abdominal video endoscopic surgery. However, it has yet to be proven that microlaparoscopic surgery will actually result in clinically relevant benefits for patients. Fifty patients were randomized in a blinded fashion to receive either elective laparoscopic (MINI), (n = 25) or microlaparoscopic (MICRO) (n = 25) cholecystectomy. Pulmonary function (FVC, FEV (1)), analgesic consumption during patient-controlled analgesia (PCA), pain perception by visual analogue score (VAS), and the cosmetic result (by the patient's self-assessment) were evaluated postoperatively as clinically relevant end points. Age, sex, body mass index (BMI), preoperative pulmonary function, pain perception, and operative time were similar for the two groups. At 8:00 PM on the day of surgery, FVC (MINI: 1.96 L [range, 1.48-2.48]; MICRO: 2.13 L) [(range, 1.61.-2.50)] and FEV (1) (MINI: 1.17 L/sec) [range, 0.87-1. 48]; MICRO: 1.34 L/sec [range, 1.05.-2.14] were also similar (each p = 0.5). From surgery to the 3rd postoperative day, cumulative PCA morphine doses were comparable (MINI: 0.15 mg/kg bw [range, 0.09-0. 23]; MICRO: 0.21 mg/kg bw [range, 0.10-0.42]; p = 0.4), but overall VAS scores for pain while coughing were higher in the laparoscopic group (406 [range, 358-514]) than in the microlaparoscopic group (365 [range, 215-427]; p = 0.02). The cosmetic result was judged to be slightly superior by the microlaparoscopic patients (10 [range, 9-10]), as compared to those in the laparoscopic (9 [range, 8-10]) group (p = 0.04). Because microlaparoscopic cholecystectomy has some minor advantages over laparoscopic surgery, it should be considered for use in selected patients.

In Vitro Longitudinal Relaxivity Profile of Gd(ABE-DTTA), an Investigational Magnetic Resonance Imaging Contrast Agent

PubMed Central

Varga-Szemes, Akos; Kiss, Pal; Rab, Andras; Suranyi, Pal; Lenkey, Zsofia; Simor, Tamas; Bryant, Robert G.; Elgavish, Gabriel A.

2016-01-01

Purpose MRI contrast agents (CA) whose contrast enhancement remains relatively high even at the higher end of the magnetic field strength range would be desirable. The purpose of this work was to demonstrate such a desired magnetic field dependency of the longitudinal relaxivity for an experimental MRI CA, Gd(ABE-DTTA). Materials and Methods The relaxivity of 0.5mM and 1mM Gd(ABE-DTTA) was measured by Nuclear Magnetic Relaxation Dispersion (NMRD) in the range of 0.0002 to 1T. Two MRI and five NMR instruments were used to cover the range between 1.5 to 20T. Parallel measurement of a Gd-DTPA sample was performed throughout as reference. All measurements were carried out at 37°C and pH 7.4. Results The relaxivity values of 0.5mM and 1mM Gd(ABE-DTTA) measured at 1.5, 3, and 7T, within the presently clinically relevant magnetic field range, were 15.3, 11.8, 12.4 s-1mM-1 and 18.1, 16.7, and 13.5 s-1mM-1, respectively. The control 4 mM Gd-DTPA relaxivities at the same magnetic fields were 3.6, 3.3, and 3.0 s-1mM-1, respectively. Conclusions The longitudinal relaxivity of Gd(ABE-DTTA) measured within the presently clinically relevant field range is three to five times higher than that of most commercially available agents. Thus, Gd(ABE-DTTA) could be a practical choice at any field strength currently used in clinical imaging including those at the higher end. PMID:26872055

Can the theoretical domains framework account for the implementation of clinical quality interventions?

PubMed

Lipworth, Wendy; Taylor, Natalie; Braithwaite, Jeffrey

2013-12-21

The health care quality improvement movement is a complex enterprise. Implementing clinical quality initiatives requires attitude and behaviour change on the part of clinicians, but this has proven to be difficult. In an attempt to solve this kind of behavioural challenge, the theoretical domains framework (TDF) has been developed. The TDF consists of 14 domains from psychological and organisational theory said to influence behaviour change. No systematic research has been conducted into the ways in which clinical quality initiatives map on to the domains of the framework. We therefore conducted a qualitative mapping experiment to determine to what extent, and in what ways, the TDF is relevant to the implementation of clinical quality interventions. We conducted a thematic synthesis of the qualitative literature exploring clinicians' perceptions of various clinical quality interventions. We analysed and synthesised 50 studies in total, in five domains of clinical quality interventions: clinical quality interventions in general, structural interventions, audit-type interventions, interventions aimed at making practice more evidence-based, and risk management interventions. Data were analysed thematically, followed by synthesis of these themes into categories and concepts, which were then mapped to the domains of the TDF. Our results suggest that the TDF is highly relevant to the implementation of clinical quality interventions. It can be used to map most, if not all, of the attitudinal and behavioural barriers and facilitators of uptake of clinical quality interventions. Each of these 14 domains appeared to be relevant to many different types of clinical quality interventions. One possible additional domain might relate to perceived trustworthiness of those instituting clinical quality interventions. The TDF can be usefully applied to a wide range of clinical quality interventions. Because all 14 of the domains emerged as relevant, and we did not identify any obvious differences between different kinds of clinical quality interventions, our findings support an initially broad approach to identifying barriers and facilitators, followed by a "drilling down" to what is most contextually salient. In future, it may be possible to establish a model of clinical quality policy implementation using the TDF.

Can the theoretical domains framework account for the implementation of clinical quality interventions?

PubMed Central

2013-01-01

Background The health care quality improvement movement is a complex enterprise. Implementing clinical quality initiatives requires attitude and behaviour change on the part of clinicians, but this has proven to be difficult. In an attempt to solve this kind of behavioural challenge, the theoretical domains framework (TDF) has been developed. The TDF consists of 14 domains from psychological and organisational theory said to influence behaviour change. No systematic research has been conducted into the ways in which clinical quality initiatives map on to the domains of the framework. We therefore conducted a qualitative mapping experiment to determine to what extent, and in what ways, the TDF is relevant to the implementation of clinical quality interventions. Methods We conducted a thematic synthesis of the qualitative literature exploring clinicians’ perceptions of various clinical quality interventions. We analysed and synthesised 50 studies in total, in five domains of clinical quality interventions: clinical quality interventions in general, structural interventions, audit-type interventions, interventions aimed at making practice more evidence-based, and risk management interventions. Data were analysed thematically, followed by synthesis of these themes into categories and concepts, which were then mapped to the domains of the TDF. Results Our results suggest that the TDF is highly relevant to the implementation of clinical quality interventions. It can be used to map most, if not all, of the attitudinal and behavioural barriers and facilitators of uptake of clinical quality interventions. Each of these 14 domains appeared to be relevant to many different types of clinical quality interventions. One possible additional domain might relate to perceived trustworthiness of those instituting clinical quality interventions. Conclusions The TDF can be usefully applied to a wide range of clinical quality interventions. Because all 14 of the domains emerged as relevant, and we did not identify any obvious differences between different kinds of clinical quality interventions, our findings support an initially broad approach to identifying barriers and facilitators, followed by a “drilling down” to what is most contextually salient. In future, it may be possible to establish a model of clinical quality policy implementation using the TDF. PMID:24359085

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

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

Wroe, Andrew; Centre for Medical Radiation Physics, University of Wollongong, Wollongong; Clasie, Ben

2009-01-01

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

Sleep Disorders in Patients with Bronchial Asthma

PubMed Central

Cukic, Vesna; Lovre, Vladimir; Dragisic, Dejan

2011-01-01

Respiratory disturbances during sleep are recognized as extremely common disorders with important clinical consequences. Breathing disorders during sleep can result in broad range of clinical manifestations, the most prevalent of which are unrefreshing sleep, daytime sleepiness and fatigue, and cognitive impairmant. There is also evidence that respiratory-related sleep disturbances can contribute to several common cardiovascular and metabolic disorders, including systemic hypertension, cardiac dysfunction, and insulin-resistance. Correlations are found between asthma-related symptoms and sleep disturbances. Difficulties inducing sleep, sleep fragmentation on polysomnography, early morning awakenings and daytime sleepiness are more common in asthmatics compared with subjects without asthma. The “morning deep” in asthma is relevant for the characterization of asthma severity, and impact drugs’ choices. Sleep and night control of asthma could be relevant to evaluate disease’s control. Appropriate asthma control recovering is guarantor for better sleep quality in these patients and less clinical consequences of respiratory disturbances during sleep. PMID:23678304

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

PubMed

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

2011-12-01

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

Clinical decision support tools for osteoporosis disease management: a systematic review of randomized controlled trials.

PubMed

Kastner, Monika; Straus, Sharon E

2008-12-01

Studies indicate a gap between evidence and clinical practice in osteoporosis management. Tools that facilitate clinical decision making at the point of care are promising strategies for closing these practice gaps. To systematically review the literature to identify and describe the effectiveness of tools that support clinical decision making in osteoporosis disease management. Medline, EMBASE, CINAHL, and EBM Reviews (CDSR, DARE, CCTR, and ACP J Club), and contact with experts in the field. Randomized controlled trials (RCTs) in any language from 1966 to July 2006 investigating disease management interventions in patients at risk for osteoporosis. Outcomes included fractures and bone mineral density (BMD) testing. Two investigators independently assessed articles for relevance and study quality, and extracted data using standardized forms. Of 1,246 citations that were screened for relevance, 13 RCTs met the inclusion criteria. Reported study quality was generally poor. Meta-analysis was not done because of methodological and clinical heterogeneity; 77% of studies included a reminder or education as a component of their intervention. Three studies of reminders plus education targeted to physicians and patients showed increased BMD testing (RR range 1.43 to 8.67) and osteoporosis medication use (RR range 1.60 to 8.67). A physician reminder plus a patient risk assessment strategy found reduced fractures [RR 0.58, 95% confidence interval (CI) 0.37 to 0.90] and increased osteoporosis therapy (RR 2.44, CI 1.43 to 4.17). Multi-component tools that are targeted to physicians and patients may be effective for supporting clinical decision making in osteoporosis disease management.

Validation of computational fluid dynamics-based analysis to evaluate hemodynamic significance of access stenosis.

PubMed

Hoganson, David M; Hinkel, Cameron J; Chen, Xiaomin; Agarwal, Ramesh K; Shenoy, Surendra

2014-01-01

Stenosis in a vascular access circuit is the predominant cause of access dysfunction. Hemodynamic significance of a stenosis identified by angiography in an access circuit is uncertain. This study utilizes computational fluid dynamics (CFD) to model flow through arteriovenous fistula to predict the functional significance of stenosis in vascular access circuits. Three-dimensional models of fistulas were created with a range of clinically relevant stenoses using SolidWorks. Stenoses diameters ranged from 1.0 to 3.0 mm and lengths from 5 to 60 mm within a fistula diameter of 7 mm. CFD analyses were performed using a blood model over a range of blood pressures. Eight patient-specific stenoses were also modeled and analyzed with CFD and the resulting blood flow calculations were validated by comparison with brachial artery flow measured by duplex ultrasound. Predicted flow rates were derived from CFD analysis of a range of stenoses. These stenoses were modeled by CFD and correlated with the ultrasound measured flow rate through the fistula of eight patients. The calculated flow rate using CFD correlated within 20% of ultrasound measured flow for five of eight patients. The mean difference was 17.2% (ranged from 1.3% to 30.1%). CFD analysis-generated flow rate tables provide valuable information to assess the functional significance of stenosis detected during imaging studies. The CFD study can help in determining the clinical relevance of a stenosis in access dysfunction and guide the need for intervention.

The Relevance of Sex Differences in Performance Fatigability

PubMed Central

Hunter, Sandra K.

2016-01-01

Performance fatigability differs between men and women for a range of fatiguing tasks. Women are usually less fatigable than men and this is most widely described for isometric fatiguing contractions, and some dynamic tasks. The sex difference in fatigability is specific to the task demands so that one mechanism is not universal, including any sex differences in skeletal muscle physiology, muscle perfusion and voluntary activation. However, there are substantial knowledge gaps about the task dependency of the sex differences in fatigability, the involved mechanisms and the relevance to clinical populations and with advanced age. The knowledge gaps are in part due to the significant deficits in the number of women included in performance fatigability studies despite a gradual increase in the inclusion of women over the last 20 years. Therefore, this review 1) provides a rationale for the limited knowledge about sex differences in performance fatigability, 2) summarizes the current knowledge on sex differences in fatigability and the potential mechanisms across a range of tasks, 3) highlights emerging areas of opportunity in clinical populations, and 4) suggests strategies to close the knowledge gap and understanding the relevance of sex differences in performance fatigability. The limited understanding about sex differences in fatigability in healthy and clinical populations, presents as a field ripe with opportunity for high impact studies. Such studies will inform on the limitations of men and women during athletic endeavors, ergonomic tasks and daily activities. Because fatigability is required for effective neuromuscular adaptation, sex differences in fatigability studies will also inform on optimal strategies for training and rehabilitation in both men and women. PMID:27015385

Design of a Mechanical-Tunable Filter Spectrometer for Noninvasive Glucose Measurement

NASA Astrophysics Data System (ADS)

Saptari, Vidi; Youcef-Toumi, Kamal

2004-05-01

The development of an accurate and reliable noninvasive near-infrared (NIR) glucose sensor hinges on the success in addressing the sensitivity and the specificity problems associated with the weak glucose signals and the overlapping NIR spectra. Spectroscopic hardware parameters most relevant to noninvasive blood glucose measurement are discussed, which include the optical throughput, integration time, spectral range, and the spectral resolution. We propose a unique spectroscopic system using a continuously rotating interference filter, which produces a signal-to-noise ratio of the order of 10^5 and is estimated to be the minimum required for successful in vivo glucose sensing. Using a classical least-squares algorithm and a spectral range between 2180 and 2312 nm, we extracted clinically relevant glucose concentrations in multicomponent solutions containing bovine serum albumin, triacetin, lactate, and urea.

The role of boldness in psychopathy: A study of academic and clinical perceptions.

PubMed

Berg, Joanna M; Lilienfeld, Scott O; Sellbom, Martin

2017-10-01

The relevance of boldness to psychopathy has recently become a major flashpoint of scientific controversy. Although some authors have contended that boldness is a necessary (although insufficient) component of psychopathy, others have asserted that it is largely or entirely irrelevant to psychopathy. We addressed this issue by examining clinical perceptions of the relevance of the 3 triarchic dimensions (boldness, disinhibition, and meanness) to psychopathy among a sample of mental health professionals and graduate students (N = 228) using a vignette-based, person-centered methodology. A vignette comprising boldness descriptors afforded statistically significant and moderate to large (Cohen's ds ranged from .47 to .99) increases in perceived resemblance to overall psychopathy above and beyond the other triarchic dimensions, both singly and jointly; these findings extended largely to clinical perceptions of Factor 1 (i.e., interpersonal and affective aspects of psychopathy) but not Factor 2 (i.e., impulsive and antisocial aspects of psychopathy) resemblance. Contrary to the claims of some recent authors, boldness alone was perceived as being as relevant to psychopathy as was disinhibition, although both dimensions were perceived as less relevant to psychopathy than was meanness. These findings offer strong support for the contention that boldness is regarded as a key feature of classical psychopathy and are broadly consistent with interpersonal models of psychopathy. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

[Antibiotic management of presumptive bacterial meningitis in adults (rational, methods, course, and follow-up)].

PubMed

Ansart, S

2009-01-01

The annual incidence of community acquired meningitis ranges between 0.6 and four per 100,000 adults in industrialized countries. The most common causative bacteria are Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes. The emergence of resistance to antibiotics, especially for S. pneumoniae, could explain the clinical failure of third generation cephalosporins used to treat adults with S. pneumoniae meningitis. The present therapeutic suggestions are more based on the extrapolation of an experimental model than on relevant clinical trials.

[Use of health resources and loss of productivity in gastroesophageal reflux disease: results of a cross-sectional study in a primary care setting in Spain].

PubMed

Nuevo, Javier; Tafalla, Mónica; Zapardiel, Javier; Gisbert, J P

2011-09-01

To evaluate healthcare resource use and productivity in patients with gastro-esophageal reflux disease (GERD) and the influence of disease severity on these two factors. Sub-analysis of the Spanish population of a multinational study with a 4-month retrospective period for the identification and selection of patients, and a clinical visit to obtain clinical information and data on use of healthcare resources, carried out between October 2007 and January 2008. A total of 477 patients attending a Primary Care centre, with a medical consultation for GERD. Use of healthcare resources, changes in productivity based on the Work Productivity and Activity Impairment Questionnaire for GERD patients (WPAI-GERD). Despite having received pharmacological treatment at the baseline visit, after a median of 5.1 months follow-up (range 2.1-8.1), up to 15.9% (95% CI; 12.8-19.5) patients still showed clinically relevant GERD symptoms. Direct medical costs per year associated with diagnostic tests and medical consultations in patients with or without clinically relevant GERD symptoms were 666 € (SD: 2,097 €) and 370 € (SD: 2,060 €), respectively. The mean annual cost of reduced productivity (17%) was 5,316 € (SD: 8,615 €). This cost was 4 times higher for patients with clinically relevant GERD symptoms than for patients with no relevant symptoms (15,188 € [SD: 11,206 €] vs 3,926 € [SD: 7,232 €]). Patients with GERD use significant healthcare resources, attributable to associated medical costs and marked reduction in productivity, even though they receive pharmacological treatment. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Clinically relevant safety issues associated with St. John's wort product labels.

PubMed

Clauson, Kevin A; Santamarina, Marile L; Rutledge, Jennifer C

2008-07-17

St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA. Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings. Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of a priori safety issues included on a product label was 1.91 (range 0-8) for 23.9% completeness. The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.

Clinically relevant safety issues associated with St. John's wort product labels

PubMed Central

Clauson, Kevin A; Santamarina, Marile L; Rutledge, Jennifer C

2008-01-01

Background St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA. Methods Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings. Results Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of a priori safety issues included on a product label was 1.91 (range 0–8) for 23.9% completeness. Conclusion The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements. PMID:18637192

Repurposing Drugs in Oncology (ReDO)—diclofenac as an anti-cancer agent

PubMed Central

Pantziarka, Pan; Sukhatme, Vidula; Bouche, Gauthier; Meheus, Lydie; Sukhatme, Vikas P

2016-01-01

Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. Based on this evidence the case is made for further clinical investigation of the anticancer effects of DCF, particularly in combination with other agents - with a range of possible multi-drug and multi-modality combinations outlined in the supplementary materials accompanying the main paper. PMID:26823679

Forearm versus upper arm grafts for vascular access.

PubMed

Gage, Shawn M; Lawson, Jeffrey H

2017-03-06

Forearm and upper arm arteriovenous grafts perform similarly in terms of patency and complications. Primary patency at 1 year for forearm arteriovenous grafts versus upper arm grafts ranges from 22%-50% versus 22%-42%, and secondary patency at 1 year ranges from 78%-89% versus 52%-67%), respectively. Secondary patency at 2 years, ranges from 30%-64% versus 35%-60% for forearm and upper arteriovenous graft, respectively. Ample pre-operative planning is essential to improved clinical success and the decision to place a graft at one location versus the other should be based solely on previous access history, physical exam, appropriate venous imaging, and other factors that make up the clinical picture. Operative implant strategies and risk of complications are very similar between the two configurations. Postoperative ischemia due to steal syndrome is a potential complication that requires immediate attention. Utilization of the proximal radial or ulnar artery for inflow for the graft can minimize risk of clinically relevant steal syndrome.

Influence of Antiflatulent Dietary Advice on Intrafraction Motion for Prostate Cancer Radiotherapy

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

Lips, Irene M., E-mail: I.M.Lips@umcutrecht.nl; Kotte, Alexis N.T.J.; Gils, Carla H. van

Purpose: To evaluate the effect of an antiflatulent dietary advice on the intrafraction prostate motion in patients treated with intensity-modulated radiotherapy (IMRT) for prostate cancer. Methods and Materials: Between February 2002 and December 2009, 977 patients received five-beam IMRT for prostate cancer to a dose of 76 Gy in 35 fractions combined with fiducial markers for position verification. In July 2008, the diet, consisting of dietary guidelines to obtain regular bowel movements and to reduce intestinal gas by avoiding certain foods and air swallowing, was introduced to reduce the prostate motion. The intrafraction prostate movement was determined from the portalmore » images of the first segment of all five beams. Clinically relevant intrafraction motion was defined as {>=}50% of the fractions with an intrafraction motion outside a range of 3 mm. Results: A total of 739 patients were treated without the diet and 105 patients were treated with radiotherapy after introduction of the diet. The median and interquartile range of the average intrafraction motion per patient was 2.53 mm (interquartile range, 2.2-3.0) without the diet and 3.00 mm (interquartile range, 2.4-3.5) with the diet (p < .0001). The percentage of patients with clinically relevant intrafraction motion increased statistically significant from 19.1% without diet to 42.9% with a diet (odds ratio, 3.18; 95% confidence interval, 2.07-4.88; p < .0001). Conclusions: The results of the present study suggest that antiflatulent dietary advice for patients undergoing IMRT for prostate cancer does not reduce the intrafraction movement of the prostate. Therefore, antiflatulent dietary advice is not recommended in clinical practice for this purpose.« less

[Actual relevance of Pauwels' classification of femoral neck fractures--a critical review].

PubMed

Schwarz, N

2010-03-01

The aim of this study was to evaluate the validity of Pauwels' classification of femoral neck fractures. A study of literature was performed. It has never been proven that the inclination of the fracture plane has a prognostic relevance. A number of papers prove the contrary, there are no publications where Pauwels' classification has been used successfully in selecting treatment modalities. Pauwels' theory of fracture inclination angle has not been transferred into clinical practice. This discrepancy probably goes back to the fact that the angle cannot be determined preoperatively, that in the majority of femoral neck fractures the angle is within the range of 40 to 60 degrees, that the theoretical angle variations do practically not exist, and that the shearing forces are reduced to an unknown amount by friction resistance due to the uneven fracture plane. The mechanical laws of the pseudarthrosis of the femoral neck cannot be extrapolated to acute fractures. The theory of Pauwels has apparently no clinical relevance for the majority of acute fractures, except for the rare transcervical fractures, and should not be considered any longer as a classification of acute femoral neck fractures due to the lack of prognostic and therapeutic relevance.

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

PubMed Central

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

2014-01-01

Background Voltage-gated potassium channel (VGKC)-complex antibodies can be associated with a range of immunotherapy-responsive clinical presentations including limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. However, there are patients with positive levels in whom the significance is uncertain. Objective To evaluate the clinical significance associated with positive (>100 pM) VGKC-complex antibodies. Methods Over a 4-year period, 1053 samples were sent for testing of which 55 were positive. The clinical presentations, final diagnoses and responses to immunotherapies, when given, were assessed retrospectively and the likelihood of autoimmunity was categorised as definite, possible, unlikely or undetermined (modified from Zuliani et al 2012). Results Only 4 of the 32 patients with low-positive (100–400 pM) levels were considered definitely autoimmune, 3 with peripheral nerve hyperexcitability and 1 with a thymoma; 3 were given immunotherapies. Of the remaining 28 with low-positive levels, 13 (3 of whom had tumours) were considered possibly autoimmune, and 15 were unlikely or undetermined; 1 was given immunotherapy unsuccessfully. Of the 23 patients with high-positive (>400 pM) levels, 12 were given immunotherapies, 11 of whom showed a good response. 11 were considered definitely autoimmune, 10 with limbic encephalitis (antibody specificity: 5 LGI1, 1 contactin2, 2 negative, 2 untested) and 1 with a tumour. In the remaining 12, autoimmunity was considered possible (n=9; most had not received immunotherapies), or unlikely (n=3). Conclusions As antibody testing becomes more widely available, and many samples are referred from patients with less clear-cut diagnoses, it is important to assess the utility of the results. VGKC-complex antibodies in the range of 100–400 pM (0.1–0.4 nM) were considered clinically relevant in rare conditions with peripheral nerve hyperexcitability and appeared to associate with tumours (12.5%). By contrast high-positive (>400 pM; >0.4 nM) levels were considered definitely (38%) or possibly (49%) clinically relevant, but not all patients had a ‘classical’ limbic encephalitis and some did not receive immunotherapies. PMID:23757422

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

PubMed

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

2014-06-01

Voltage-gated potassium channel (VGKC)-complex antibodies can be associated with a range of immunotherapy-responsive clinical presentations including limbic encephalitis, Morvan's syndrome and acquired neuromyotonia. However, there are patients with positive levels in whom the significance is uncertain. To evaluate the clinical significance associated with positive (>100 pM) VGKC-complex antibodies. Over a 4-year period, 1053 samples were sent for testing of which 55 were positive. The clinical presentations, final diagnoses and responses to immunotherapies, when given, were assessed retrospectively and the likelihood of autoimmunity was categorised as definite, possible, unlikely or undetermined (modified from Zuliani et al 2012). Only 4 of the 32 patients with low-positive (100-400 pM) levels were considered definitely autoimmune, 3 with peripheral nerve hyperexcitability and 1 with a thymoma; 3 were given immunotherapies. Of the remaining 28 with low-positive levels, 13 (3 of whom had tumours) were considered possibly autoimmune, and 15 were unlikely or undetermined; 1 was given immunotherapy unsuccessfully. Of the 23 patients with high-positive (>400 pM) levels, 12 were given immunotherapies, 11 of whom showed a good response. 11 were considered definitely autoimmune, 10 with limbic encephalitis (antibody specificity: 5 LGI1, 1 contactin2, 2 negative, 2 untested) and 1 with a tumour. In the remaining 12, autoimmunity was considered possible (n=9; most had not received immunotherapies), or unlikely (n=3). As antibody testing becomes more widely available, and many samples are referred from patients with less clear-cut diagnoses, it is important to assess the utility of the results. VGKC-complex antibodies in the range of 100-400 pM (0.1-0.4 nM) were considered clinically relevant in rare conditions with peripheral nerve hyperexcitability and appeared to associate with tumours (12.5%). By contrast high-positive (>400 pM; >0.4 nM) levels were considered definitely (38%) or possibly (49%) clinically relevant, but not all patients had a 'classical' limbic encephalitis and some did not receive immunotherapies.

Activating Photodynamic Therapy in vitro with Cerenkov Radiation Generated from Yttrium-90

PubMed Central

Hartl, Brad A.; Hirschberg, Henry; Marcu, Laura; Cherry, Simon R.

2017-01-01

The translation of photodynamic therapy (PDT) to the clinical setting has primarily been limited to easily accessible and/or superficial diseases, for which traditional light delivery can be performed noninvasively. Cerenkov radiation, as generated from medically relevant radionuclides, has been suggested as a means to deliver light to deeper tissues noninvasively to overcome this depth limitation. This article investigates the utility of Cerenkov radiation, as generated from the radionuclide yttrium-90, for activating the PDT process using clinically approved aminolevulinic acid at 1.0 mm and also the more efficient porphyrin-based photosensitizer mesotetraphenylporphine with two sulfonate groups on adjacent phenyl rings (TPPS2a) at 1.2 μM. Experiments were conducted with monolayer cultured glioma and breast tumor cell lines. Although aminolevulinic acid proved to be ineffective for generating a therapeutic effect at all but the highest activity levels, TPPS2a produced at least a 20% therapeutic effect at activities ranging from 6 to 60 μCi/well for the C6 glioma cell line. Importantly, these results demonstrate for the first time, to our knowledge, that Cerenkov radiation generated from a radionuclide can be used to activate PDT using clinically relevant photosensitizers. These results therefore provide evidence that it may be possible to generate a phototherapeutic effect in vivo using Cerenkov radiation and clinically relevant photosensitizers. PMID:27481495

Clinical Decision Support Tools for Osteoporosis Disease Management: A Systematic Review of Randomized Controlled Trials

PubMed Central

Straus, Sharon E.

2008-01-01

BACKGROUND Studies indicate a gap between evidence and clinical practice in osteoporosis management. Tools that facilitate clinical decision making at the point of care are promising strategies for closing these practice gaps. OBJECTIVE To systematically review the literature to identify and describe the effectiveness of tools that support clinical decision making in osteoporosis disease management. DATA SOURCES Medline, EMBASE, CINAHL, and EBM Reviews (CDSR, DARE, CCTR, and ACP J Club), and contact with experts in the field. REVIEW METHODS Randomized controlled trials (RCTs) in any language from 1966 to July 2006 investigating disease management interventions in patients at risk for osteoporosis. Outcomes included fractures and bone mineral density (BMD) testing. Two investigators independently assessed articles for relevance and study quality, and extracted data using standardized forms. RESULTS Of 1,246 citations that were screened for relevance, 13 RCTs met the inclusion criteria. Reported study quality was generally poor. Meta-analysis was not done because of methodological and clinical heterogeneity; 77% of studies included a reminder or education as a component of their intervention. Three studies of reminders plus education targeted to physicians and patients showed increased BMD testing (RR range 1.43 to 8.67) and osteoporosis medication use (RR range 1.60 to 8.67). A physician reminder plus a patient risk assessment strategy found reduced fractures [RR 0.58, 95% confidence interval (CI) 0.37 to 0.90] and increased osteoporosis therapy (RR 2.44, CI 1.43 to 4.17). CONCLUSION Multi-component tools that are targeted to physicians and patients may be effective for supporting clinical decision making in osteoporosis disease management. Electronic supplementary material The online version of this article (doi:10.1007/s11606-008-0812-9) contains supplementary material, which is available to authorized users. PMID:18836782

The importance of mean time in therapeutic range for complication rates in warfarin therapy of patients with atrial fibrillation: A systematic review and meta-regression analysis.

PubMed

Vestergaard, Anne Sig; Skjøth, Flemming; Larsen, Torben Bjerregaard; Ehlers, Lars Holger

2017-01-01

\\Anticoagulation is used for stroke prophylaxis in non-valvular atrial fibrillation, amongst other by use of the vitamin K antagonist, warfarin. Quality in warfarin therapy is often summarized by the time patients spend within the therapeutic range (percent time in therapeutic range, TTR). The correlation between TTR and the occurrence of complications during warfarin therapy has been established, but the influence of patient characteristics in that respect remains undetermined. The objective of the present papers was to examine the association between mean TTR and complication rates with adjustment for differences in relevant patient cohort characteristics. A systematic literature search was conducted in MEDLINE and Embase (2005-2015) to identify eligible studies reporting on use of warfarin therapy by patients with non-valvular atrial fibrillation and the occurrence of hemorrhage and thromboembolism. Both randomized controlled trials and observational cohort studies were included. The association between the reported mean TTR and major bleeding and stroke/systemic embolism was analyzed by random-effects meta-regression with and without adjustment for relevant clinical cohort characteristics. In the adjusted meta-regressions, the impact of mean TTR on the occurrence of hemorrhage was adjusted for the mean age and the proportion of populations with prior stroke or transient ischemic attack. In the adjusted analyses on thromboembolism, the proportion of females was, furthermore, included. Of 2169 papers, 35 papers met pre-specified inclusion criteria, holding relevant information on 31 patient cohorts. In univariable meta-regression, increasing mean TTR was significantly associated with a decreased rate of both major bleeding and stroke/systemic embolism. However, after adjustment mean TTR was no longer significantly associated with stroke/systemic embolism. The proportion of residual variance composed by between-study heterogeneity was substantial for all analyses. Although higher mean TTR in warfarin therapy was associated with lower complication rates in atrial fibrillation, the strength of the association was decreased when adjusting for differences in relevant clinical characteristics of the patient cohorts. This study suggests that mainly the safety of warfarin therapy increases with higher mean TTR, whereas effectiveness appears not to be substantially improved. Due to the limitations immanent in the meta-regression methods, the results of the present study should be interpreted with caution. Further research on the association between the quality of warfarin therapy and risk of complications is warranted with adjustment for clinically relevant characteristics.

Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine

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

Annesley, Thomas M.; Cooks, Robert G.; Herold, David A.

Each year the journal Clinical Chemistry publishes a January special issue on a topic that is relevant to the laboratory medicine community. In January 2016 the topic is mass spectrometry, and the issue is entitled “Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine”. One popular feature in our issues is a Q&A on a topic, clearly in this case mass spectrometry. The journal is assembling a panel of 5-6 experts from various areas of mass spectrometry ranging from instrument manufacturing to practicing clinical chemists. Dick Smith is one of the scientist requested to participate in this special issue Q&A onmore » Mass Spectrometry. The Q&A Transcript is attached« less

Clinical relevance in anesthesia journals.

PubMed

Lauritsen, Jakob; Møller, Ann M

2006-04-01

The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles. In the last few years, more attention has been paid to evidence-based medicine in anesthesia. Several articles on the subject have focused on the need to base clinical decisions on sound research employing both methodological rigor and clinically relevant outcomes. The number of systematic reviews in anesthesia literature is increasing as well as the focus on diminishing the number of surrogate outcomes. It has been shown that the impact factor is not a valid measure of establishing the level of clinical relevance to a journal. This review presents definitions of clinically relevant anesthesia articles. A clinically relevant article employs both methodological rigor and a clinically relevant outcome. The terms methodological rigor and clinical outcomes are fully discussed in the review as well as problems with journal impact factors.

Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders

PubMed Central

Pfundt, Rolph; del Rosario, Marisol; Vissers, Lisenka E.L.M.; Kwint, Michael P.; Janssen, Irene M.; de Leeuw, Nicole; Yntema, Helger G.; Nelen, Marcel R.; Lugtenberg, Dorien; Kamsteeg, Erik-Jan; Wieskamp, Nienke; Stegmann, Alexander P.A.; Stevens, Servi J.C.; Rodenburg, Richard J.T.; Simons, Annet; Mensenkamp, Arjen R.; Rinne, Tuula; Gilissen, Christian; Scheffer, Hans; Veltman, Joris A.; Hehir-Kwa, Jayne Y.

2017-01-01

Purpose: Copy-number variation is a common source of genomic variation and an important genetic cause of disease. Microarray-based analysis of copy-number variants (CNVs) has become a first-tier diagnostic test for patients with neurodevelopmental disorders, with a diagnostic yield of 10–20%. However, for most other genetic disorders, the role of CNVs is less clear and most diagnostic genetic studies are generally limited to the study of single-nucleotide variants (SNVs) and other small variants. With the introduction of exome and genome sequencing, it is now possible to detect both SNVs and CNVs using an exome- or genome-wide approach with a single test. Methods: We performed exome-based read-depth CNV screening on data from 2,603 patients affected by a range of genetic disorders for which exome sequencing was performed in a diagnostic setting. Results: In total, 123 clinically relevant CNVs ranging in size from 727 bp to 15.3 Mb were detected, which resulted in 51 conclusive diagnoses and an overall increase in diagnostic yield of ~2% (ranging from 0 to –5.8% per disorder). Conclusions: This study shows that CNVs play an important role in a broad range of genetic disorders and that detection via exome-based CNV profiling results in an increase in the diagnostic yield without additional testing, bringing us closer to single-test genomics. Genet Med advance online publication 27 October 2016 PMID:28574513

Variance associated with walking velocity during force platform gait analysis of a heterogeneous sample of clinically normal dogs.

PubMed

Piazza, Alexander M; Binversie, Emily E; Baker, Lauren A; Nemke, Brett; Sample, Susannah J; Muir, Peter

2017-04-01

OBJECTIVE To determine whether walking at specific ranges of absolute and relative (V*) velocity would aid efficient capture of gait trial data with low ground reaction force (GRF) variance in a heterogeneous sample of dogs. ANIMALS 17 clinically normal dogs of various breeds, ages, and sexes. PROCEDURES Each dog was walked across a force platform at its preferred velocity, with controlled acceleration within 0.5 m/s 2 . Ranges in V* were created for height at the highest point of the shoulders (withers; WHV*). Variance effects from 8 walking absolute velocity ranges and associated WHV* ranges were examined by means of repeated-measures ANCOVA. RESULTS The individual dog effect provided the greatest contribution to variance. Narrow velocity ranges typically resulted in capture of a smaller percentage of valid trials and were not consistently associated with lower variance. The WHV* range of 0.33 to 0.46 allowed capture of valid trials efficiently, with no significant effects on peak vertical force and vertical impulse. CONCLUSIONS AND CLINICAL RELEVANCE Dogs with severe lameness may be unable to trot or may have a decline in mobility with gait trial repetition. Gait analysis involving evaluation of individual dogs at their preferred absolute velocity, such that dogs are evaluated at a similar V*, may facilitate efficient capture of valid trials without significant effects on GRF. Use of individual velocity ranges derived from a WHV* range of 0.33 to 0.46 can account for heterogeneity and appears suitable for use in clinical trials involving dogs at a walking gait.

Cytauxzoonosis: Diagnosis and treatment of an emerging disease.

PubMed

Sherrill, Meredith K; Cohn, Leah A

2015-11-01

Cytauxzoonosis is a life-threatening hematoprotozoal disease with a rapidly progressive clinical course. Once considered a rare disease only relevant to a small geographic area, it is now recognized in more than about a third of the United States. The geographic range seems likely to increase with expansion of the range of the vector tick. Both disease diagnosis and treatment offer challenges. The acute illness is often recognized by characteristic parasitic cellular inclusions, but illness may occur before parasites can be identified, and parasitic inclusions may persist long after illness has resolved. Also, while infection was once considered nearly uniformly fatal, subclinical infections are now recognized. Disease prognosis has improved for many cats through implementation of new therapies, but some pathogens are resistant to these therapies and death from disease is still common. Currently, prevention strategies are limited to ectoparasite control. Cytauxzoonosis caused by Cytauxzoon felis is limited to the Americas, and is especially problematic in southeastern and south central USA. However, other Cytauxzoon species have been recognized in Europe and Asia. This review is aimed at veterinary practitioners and focuses on the diagnosis and treatment of cytauxzoonosis. Disease management is of crucial importance in endemic regions. Furthermore, the expanding geographic range of infection, and the possibility of parasite identification in chronically infected cats with a travel history, make understanding cytauxzoonosis relevant in non-endemic regions as well. The authors draw on evidence from prospective clinical trials, experimental infections, retrospective clinical studies and case reports, as well as their own personal experience with the diagnosis and treatment of cytauxzoonosis. © The Author(s) 2015.

Twice-Daily Enoxaparin among Plastic Surgery Inpatients: An Examination of Pharmacodynamics, 90-Day Venous Thromboembolism, and 90-Day Bleeding.

PubMed

Pannucci, Christopher J; Fleming, Kory I; Momeni, Arash; Prazak, Ann Marie; Agarwal, Jayant; Rockwell, W Bradford

2018-06-01

Low anti-factor Xa level, indicative of inadequate enoxaparin dosing, has a significant association with 90-day venous thromboembolism events. The authors examined the pharmacodynamics of enoxaparin 40 mg twice daily and its correlation with anti-factor Xa level, postoperative venous thromboembolism, and bleeding. Adult patients were admitted after plastic and reconstructive surgery and received enoxaparin 40 mg twice daily. Peak anti-factor Xa levels, which quantify enoxaparin's antithrombotic effect, were drawn, with a goal level of 0.2 to 0.4 IU/ml. Ninety-day symptomatic venous thromboembolism and clinically relevant bleeding were identified. The authors enrolled 118 patients who received enoxaparin 40 mg twice daily. Of these patients, 9.6 percent had low peak anti-factor Xa levels (<0.2 IU/ml), 62.6 percent had in-range peak anti-factor Xa levels (0.2 to 0.4 IU/ml), and 27.8 percent had high anti-factor Xa levels (>0.4 IU/ml). With enoxaparin 40 mg twice daily, 90.4 percent of patients received at least adequate prophylaxis. Patient weight predicted the rapidity of enoxaparin metabolism. Zero acute 90-day venous thromboembolism occurred. Eight patients (6.8 percent) had clinically relevant 90-day bleeding: clinical consequences ranged from cessation of enoxaparin prophylaxis to transfusion to operative hematoma evacuation. When enoxaparin 40 mg twice daily is provided, 90 percent of patients receive at least adequate venous thromboembolism prophylaxis (anti-factor Xa level >0.2 IU/ml). However, 27 percent of the overall population is overtreated (anti-factor Xa level >0.4 IU/ml). These pharmacodynamics data likely explain the low rate of 90-day acute venous thromboembolism (0 percent) and the high rate of clinically relevant bleeding (6.8 percent) observed. Future studies are needed to better optimize the risks and benefits of enoxaparin prophylaxis in plastic and reconstructive surgery patients. Therapeutic, IV.

Clinical Relevance of Vilazodone Treatment in Patients With Major Depressive Disorder: Categorical Improvement in Symptoms

PubMed Central

Culpepper, Larry; Mathews, Maju; Ghori, Razi; Edwards, John

2014-01-01

Objective: To assess clinically relevant symptom improvement in patients with major depressive disorder (MDD) receiving vilazodone by using the Montgomery-Asberg Depression Rating Scale (MADRS), a clinician-rated scale used to measure MDD symptom severity and improvement. Method: Pooled data from 2 positive, phase 3, 8-week, double-blind, randomized, placebo-controlled trials in patients with MDD were analyzed. Patients received vilazodone 40 mg/d or placebo; post hoc analyses were conducted on study completers. Depression symptom improvement was evaluated by analyzing the proportions of patients who shifted from the baseline MADRS single-item symptom severity category of ≥ 2 (mild to severe symptoms) to an end-of-study category < 2 (minimal to no symptoms) or from ≥ 4 (moderate to severe symptoms) to ≤ 2 (mild to no symptoms). The proportion of patients who shifted from anxious depression to no anxious depression was also analyzed. Results: The percentage of patients who completed these studies with severity category shift from baseline ≥ 2 to end of study < 2 was significantly higher for vilazodone versus placebo on all MADRS items (odds ratio [OR] range, 1.4–1.7, P < .05) except reduced appetite (OR = 1.3, P = .232). A significantly greater proportion of vilazodone-treated versus placebo-treated patients shifted from baseline ≥ 4 to end of study ≤ 2 on MADRS items of apparent sadness, reported sadness, inner tension, reduced sleep, and lassitude (OR range, 1.5–2.0, P < .05). Additionally, a significantly greater proportion of vilazodone-treated versus placebo-treated patients shifted from anxious depression at baseline to no anxious depression at end of study (OR = 1.5, P = .031). Conclusions: These results suggest that vilazodone treatment is associated with clinically relevant changes in depression symptoms in patients with MDD. Trial Registration: ClinicalTrials.gov identifiers: NCT00285376 and NCT00683592 PMID:24940525

Brain profiling and clinical-neuroscience.

PubMed

Peled, Avi

2006-01-01

The current psychiatric diagnostic system, the diagnostic statistic manual, has recently come under increasing criticism. The major reason for the shortcomings of the current psychiatric diagnosis is the lack of a scientific brain-related etiological knowledge about mental disorders. The advancement toward such knowledge is further hampered by the lack of a theoretical framework or "language" that translates clinical findings of mental disorders to brain disturbances and insufficiencies. Here such a theoretical construct is proposed based on insights from neuroscience and neural-computation models. Correlates between clinical manifestations and presumed neuronal network disturbances are proposed in the form of a practical diagnostic system titled "Brain Profiling". Three dimensions make-up brain profiling, "neural complexity disorders", "neuronal resilience insufficiency", and "context-sensitive processing decline". The first dimension relates to disturbances occurring to fast neuronal activations in the millisecond range, it incorporates connectivity and hierarchical imbalances appertaining typically to psychotic and schizophrenic clinical manifestations. The second dimension relates to disturbances that alter slower changes namely long-term synaptic modulations, and incorporates disturbances to optimization and constraint satisfactions within relevant neuronal circuitry. Finally, the level of internal representations related to personality disorders is presented by a "context-sensitive process decline" as the third dimension. For practical use of brain profiling diagnosis a consensual list of psychiatric clinical manifestations provides a "diagnostic input vector", clinical findings are coded 1 for "detection" and 0 for "non-detection", 0.5 is coded for "questionable". The entries are clustered according to their presumed neuronal dynamic relationships and coefficients determine their relevance to the specific related brain disturbance. Relevant equations calculate and normalize the different values attributed to relevant brain disturbances culminating in a three-digit estimation representing the three diagnostic dimensions. brain profiling has the promise for a future brain-related diagnosis. It offers testable predictions about the etiology of mental disorders because being brain-related it lends readily to brain imaging investigations. Being presented also as a one-point representation in a three-dimensional space, multiple follow-up diagnoses trace a trajectory representing an easy-to-see clinical history of the patient. Additional, more immediate, advantages involve reduced stigma because it relaters the disorder to the brain not the person, in addition the three-digit diagnostic code is clinically informative unlike the DSM codes that have no clinical relevance. To conclude, brain profiling diagnosis of mental disorders could be a bold new step toward a "clinical-neuroscience" substituting "psychiatry".

Publications in anesthesia journals: quality and clinical relevance.

PubMed

Lauritsen, Jakob; Moller, Ann M

2004-11-01

Clinicians performing evidence-based anesthesia rely on anesthesia journals for clinically relevant information. The objective of this study was to analyze the proportion of clinically relevant articles in five high impact anesthesia journals. We evaluated all articles published in Anesthesiology, Anesthesia & Analgesia, British Journal of Anesthesia, Anesthesia, and Acta Anaesthesiologica Scandinavica from January to June, 2000. Articles were assessed and classified according to type, outcome, and design; 1379 articles consisting of 5468 pages were evaluated and categorized. The most common types of article were animal and laboratory research (31.2%) and randomized clinical trial (20.4%). A clinically relevant article was defined as an article that used a statistically valid method and had a clinically relevant end-point. Altogether 18.6% of the pages had as their subject matter clinically relevant trials. We compared the Journal Impact Factor (a measure of the number of citations per article in a journal) and the proportion of clinically relevant pages and found that they were inversely proportional to each other.

An enhancement of ROC curves made them clinically relevant for diagnostic-test comparison and optimal-threshold determination.

PubMed

Subtil, Fabien; Rabilloud, Muriel

2015-07-01

The receiver operating characteristic curves (ROC curves) are often used to compare continuous diagnostic tests or determine the optimal threshold of a test; however, they do not consider the costs of misclassifications or the disease prevalence. The ROC graph was extended to allow for these aspects. Two new lines are added to the ROC graph: a sensitivity line and a specificity line. Their slopes depend on the disease prevalence and on the ratio of the net benefit of treating a diseased subject to the net cost of treating a nondiseased one. First, these lines help researchers determine the range of specificities within which test comparisons of partial areas under the curves is clinically relevant. Second, the ROC curve point the farthest from the specificity line is shown to be the optimal threshold in terms of expected utility. This method was applied: (1) to determine the optimal threshold of ratio specific immunoglobulin G (IgG)/total IgG for the diagnosis of congenital toxoplasmosis and (2) to select, among two markers, the most accurate for the diagnosis of left ventricular hypertrophy in hypertensive subjects. The two additional lines transform the statistically valid ROC graph into a clinically relevant tool for test selection and threshold determination. Copyright © 2015 Elsevier Inc. All rights reserved.

Microbicide safety/efficacy studies in animals: macaques and small animal models.

PubMed

Veazey, Ronald S

2008-09-01

A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. The unique host and cell specificity of HIV, however, provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models. A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing. Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a prerequisite for advancing additional microbicide candidates to human clinical trials.

Microbicide Safety/Efficacy studies in animals -macaques and small animal models

PubMed Central

Veazey, Ronald S.

2009-01-01

Purpose of review A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. However, the unique host and cell specificity of HIV provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models. Recent findings A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing. Summary Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a pre-requisite for advancing additional microbicide candidates to human clinical trials. PMID:19373023

Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties.

PubMed

Herold, Karl F; Sanford, R Lea; Lee, William; Andersen, Olaf S; Hemmings, Hugh C

2017-03-21

General anesthetics have revolutionized medicine by facilitating invasive procedures, and have thus become essential drugs. However, detailed understanding of their molecular mechanisms remains elusive. A mechanism proposed over a century ago involving unspecified interactions with the lipid bilayer known as the unitary lipid-based hypothesis of anesthetic action, has been challenged by evidence for direct anesthetic interactions with a range of proteins, including transmembrane ion channels. Anesthetic concentrations in the membrane are high (10-100 mM), however, and there is no experimental evidence ruling out a role for the lipid bilayer in their ion channel effects. A recent hypothesis proposes that anesthetic-induced changes in ion channel function result from changes in bilayer lateral pressure that arise from partitioning of anesthetics into the bilayer. We examined the effects of a broad range of chemically diverse general anesthetics and related nonanesthetics on lipid bilayer properties using an established fluorescence assay that senses drug-induced changes in lipid bilayer properties. None of the compounds tested altered bilayer properties sufficiently to produce meaningful changes in ion channel function at clinically relevant concentrations. Even supra-anesthetic concentrations caused minimal bilayer effects, although much higher (toxic) concentrations of certain anesthetic agents did alter lipid bilayer properties. We conclude that general anesthetics have minimal effects on bilayer properties at clinically relevant concentrations, indicating that anesthetic effects on ion channel function are not bilayer-mediated but rather involve direct protein interactions.

Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID)

PubMed Central

Hainsworth, Atticus H; Yeo, Natalie E; Weekman, Erica M; Wilcock, Donna M

2016-01-01

Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3–10µM). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100–200µM), mild-moderate hyperhomocysteinemia ([HCy]: 10–100µM) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID). Here we review the biochemical and cellular actions of HCy related to VCID. Neuronal actions of HCy were at concentrations above the clinically-relevant range. Effects of HCy <100 µM were primarily vascular, including myocyte proliferation, vessel wall fibrosis, impaired nitric oxide signalling, superoxide generation and pro-coagulant actions. HCy-lowering clinical trials relevant to VCID are discussed. Extensive clinical and preclinical data support Hcy as a mediator for VCID. In our view further trails of combined B-vitamin supplementation are called for, incorporating lessons from previous trails and from recent experimental work. To maximise likelihood of treatment effect, a future trial should: supply a high-dose, combination supplement (B6, B12 and folate); target the at-risk age range; target cohorts with low baseline B-vitamin status. PMID:26689889

Mechanisms for pattern specificity of deep-brain stimulation in Parkinson’s disease

PubMed Central

Mato, Germán; Dellavale, Damián

2017-01-01

Deep brain stimulation (DBS) has become a widely used technique for treating advanced stages of neurological and psychiatric illness. In the case of motor disorders related to basal ganglia (BG) dysfunction, several mechanisms of action for the DBS therapy have been identified which might be involved simultaneously or in sequence. However, the identification of a common key mechanism underlying the clinical relevant DBS configurations has remained elusive due to the inherent complexity related to the interaction between the electrical stimulation and the neural tissue, and the intricate circuital structure of the BG-thalamocortical network. In this work, it is shown that the clinically relevant range for both, the frequency and intensity of the electrical stimulation pattern, is an emergent property of the BG anatomy at the system-level that can be addressed using mean-field descriptive models of the BG network. Moreover, it is shown that the activity resetting mechanism elicited by electrical stimulation provides a natural explanation to the ineffectiveness of irregular (i.e., aperiodic) stimulation patterns, which has been commonly observed in previously reported pathophysiology models of Parkinson’s disease. Using analytical and numerical techniques, these results have been reproduced in both cases: 1) a reduced mean-field model that can be thought as an elementary building block capable to capture the underlying fundamentals of the relevant loops constituting the BG-thalamocortical network, and 2) a detailed model constituted by the direct and hyperdirect loops including one-dimensional spatial structure of the BG nuclei. We found that the optimal ranges for the essential parameters of the stimulation patterns can be understood without taking into account biophysical details of the relevant structures. PMID:28813460

Vision-based body tracking: turning Kinect into a clinical tool.

PubMed

Morrison, Cecily; Culmer, Peter; Mentis, Helena; Pincus, Tamar

2016-08-01

Vision-based body tracking technologies, originally developed for the consumer gaming market, are being repurposed to form the core of a range of innovative healthcare applications in the clinical assessment and rehabilitation of movement ability. Vision-based body tracking has substantial potential, but there are technical limitations. We use our "stories from the field" to articulate the challenges and offer examples of how these can be overcome. We illustrate that: (i) substantial effort is needed to determine the measures and feedback vision-based body tracking should provide, accounting for the practicalities of the technology (e.g. range) as well as new environments (e.g. home). (ii) Practical considerations are important when planning data capture so that data is analysable, whether finding ways to support a patient or ensuring everyone does the exercise in the same manner. (iii) Home is a place of opportunity for vision-based body tracking, but what we do now in the clinic (e.g. balance tests) or in the home (e.g. play games) will require modifications to achieve capturable, clinically relevant measures. This article articulates how vision-based body tracking works and when it does not to continue to inspire our clinical colleagues to imagine new applications. Implications for Rehabilitation Vision-based body tracking has quickly been repurposed to form the core of innovative healthcare applications in clinical assessment and rehabilitation, but there are clinical as well as practical challenges to make such systems a reality. Substantial effort needs to go into determining what types of measures and feedback vision-based body tracking should provide. This needs to account for the practicalities of the technology (e.g. range) as well as the opportunities of new environments (e.g. the home). Practical considerations need to be accounted for when planning capture in a particular environment so that data is analysable, whether it be finding a chair substitute, ways to support a patient or ensuring everyone does the exercise in the same manner. The home is a place of opportunity with vision-based body tracking, but it would be naïve to think that we can do what we do now in the clinic (e.g. balance tests) or in the home (e.g. play games), without appropriate modifications to what constitutes a practically capturable, clinically relevant measure.

A methodological approach to identify external factors for indicator-based risk adjustment illustrated by a cataract surgery register

PubMed Central

2014-01-01

Background Risk adjustment is crucial for comparison of outcome in medical care. Knowledge of the external factors that impact measured outcome but that cannot be influenced by the physician is a prerequisite for this adjustment. To date, a universal and reproducible method for identification of the relevant external factors has not been published. The selection of external factors in current quality assurance programmes is mainly based on expert opinion. We propose and demonstrate a methodology for identification of external factors requiring risk adjustment of outcome indicators and we apply it to a cataract surgery register. Methods Defined test criteria to determine the relevance for risk adjustment are “clinical relevance” and “statistical significance”. Clinical relevance of the association is presumed when observed success rates of the indicator in the presence and absence of the external factor exceed a pre-specified range of 10%. Statistical significance of the association between the external factor and outcome indicators is assessed by univariate stratification and multivariate logistic regression adjustment. The cataract surgery register was set up as part of a German multi-centre register trial for out-patient cataract surgery in three high-volume surgical sites. A total of 14,924 patient follow-ups have been documented since 2005. Eight external factors potentially relevant for risk adjustment were related to the outcome indicators “refractive accuracy” and “visual rehabilitation” 2–5 weeks after surgery. Results The clinical relevance criterion confirmed 2 (“refractive accuracy”) and 5 (“visual rehabilitation”) external factors. The significance criterion was verified in two ways. Univariate and multivariate analyses revealed almost identical external factors: 4 were related to “refractive accuracy” and 7 (6) to “visual rehabilitation”. Two (“refractive accuracy”) and 5 (“visual rehabilitation”) factors conformed to both criteria and were therefore relevant for risk adjustment. Conclusion In a practical application, the proposed method to identify relevant external factors for risk adjustment for comparison of outcome in healthcare proved to be feasible and comprehensive. The method can also be adapted to other quality assurance programmes. However, the cut-off score for clinical relevance needs to be individually assessed when applying the proposed method to other indications or indicators. PMID:24965949

Chlamydial partner notification in the British Association for Sexual Health and HIV (BASHH) 2011 UK national audit against the BASHH Medical Foundation for AIDS and Sexual Health Sexually Transmitted Infections Management Standards.

PubMed

McClean, H; Carne, C A; Sullivan, A K; Radcliffe, K W; Ahmed-Jushuf, I

2012-10-01

This paper reports on chlamydial partner notification (PN) performance in the 2011 BASHH national audit against the British Association for Sexual Health and HIV (BASHH) Medical Foundation for AIDS Sexual Health (MedFASH) Sexually Transmitted Infection Management Standards (STIMS). There was wide regional variation in level 3 clinic PN performance against the current standard of index case-reported chlamydial PN, with 43% (regional range 0-80%) of clinics outside London meeting the ≥0.6 contacts seen per index standard, and 85% of clinics (regional range 82-88%) in London meeting the ≥0.4 standard. For level 2 clinics, 39% (regional range 0-100%) of clinics outside London met the ≥0.6 standard, and 43% (regional range 40-50%) of clinics in London met the ≥0.4 standard. Performance for health-care worker (HCW)-verified contact attendance is also reported. New standards for each of these performance measures are proposed for all level 3 clinics: ≥0.6 contacts seen per index case based on index case report, and ≥0.4 contacts seen per index case based on HCW verification, both within four weeks of the first partner notification interview. The results are discussed with regard to the importance of adoption of standards by commissioners of services, relevance to national quality agendas, and the need for development of a national system of PN quality assurance measurement and reporting.

Incidence of milrinone blood levels outside the therapeutic range and their relevance in children after cardiac surgery for congenital heart disease.

PubMed

Garcia Guerra, Gonzalo; Joffe, Ari R; Senthilselvan, Ambikaipakan; Kutsogiannis, Demetrios J; Parshuram, Christopher S

2013-05-01

To evaluate whether variability in milrinone blood levels (MBL) occurs during administration to critically ill children after surgical repair of congenital heart disease, and the clinical relevance of this variability. Prospective cohort study conducted in the pediatric intensive care unit of a tertiary care teaching and referral hospital. MBL were measured at three time periods after starting milrinone infusion (9-12, 18-24, 40-48 h) and at the end of the infusion. MBL were categorized as within (100-300 ng/ml) or outside the therapeutic range. Low cardiac output syndrome was defined by elevation of either lactate (>2 mmol/l) or arteriovenous oxygen difference (>30%). Five other clinical outcomes were evaluated. Regression analyses evaluated the relationships between MBL and outcomes. Sixty-three patients were included with a total of 220 MBL. Quantification of MBL was by high-performance liquid chromatography. Overall, 114 (52%) MBL were outside the therapeutic range: 78 (36%) subtherapeutic, and 36 (16%) supratherapeutic. Repeated-measures analysis found a significant association between supratherapeutic MBL and low cardiac output syndrome (p = 0.02), and supratherapeutic MBL were associated with arterial-central venous oxygen saturation difference >30% at time 3 (p = 0.007). In this cohort, nontherapeutic MBL were common. Further investigation of milrinone dosing recommendations may improve the postoperative outcomes of children.

Benefits of dietary fiber in clinical nutrition.

PubMed

Klosterbuer, Abby; Roughead, Zamzam Fariba; Slavin, Joanne

2011-10-01

Dietary fiber is widely recognized as an important part of a healthy diet and is a common addition to enteral nutrition (EN) formulas. Fiber sources differ in characteristics such as solubility, fermentability, and viscosity, and it is now well known that different types of fiber exert varying physiological effects in the body. Clinical studies suggest fiber can exert a wide range of benefits in areas such as bowel function, gut health, immunity, blood glucose control, and serum lipid levels. Although early clinical nutrition products contained fiber from a single source, it is now thought that blends of fiber from multiple sources more closely resemble a regular diet and may provide a greater range of benefits for the patient. Current recommendations support the use of dietary fiber in clinical nutrition when no contraindications exist, but little information exists about which types and combinations of fibers provide the relevant benefit in certain patient populations. This article summarizes the different types of fiber commonly added to EN products and reviews the current literature on the use of fiber blends in clinical nutrition.

Treatment Considerations for the Cardiometabolic Signs of Polycystic Ovary Syndrome: A Review of the Literature Since the 2013 Endocrine Society Clinical Practice Guidelines.

PubMed

Fields, Errol L; Trent, Maria E

2016-05-01

Polycystic ovary syndrome is characterized by an excess in androgen levels, ovarian dysfunction, and polycystic ovarian morphology but is also associated with metabolic dysfunction and risk factors for cardiovascular disease. To our knowledge, there are few therapeutic recommendations for these cardiometabolic risk factors and little evidence of their long-term clinical relevance to cardiovascular health. To determine metabolic and/or cardiovascular outcomes in polycystic ovary syndrome treatment literature since the publication of the most recent Endocrine Society clinical practice guidelines in 2013. We searched PubMed using a string of variations of polycystic ovary syndrome, therapy/treatment, and adolescence, and we included English-language original research articles published while the 2013 clinical practice guidelines were disseminated (ie, articles published from January 1, 2011, to June 1, 2015). Articles that appeared relevant based on a review of titles and abstracts were read in full to determine relevancy. References from relevant articles were reviewed for additional studies. Four topic areas emerged: (1) lifestyle modification, (2) metformin vs placebo or estrogen-progestin oral contraceptives, (3) insulin-sensitizing agents, and (4) estrogen-progestin formulations. Most studies assessed the role of metformin as a monotherapy or dual therapy supplement and found significant benefit when including metformin in polycystic ovary syndrome treatment regimens. Studies showed improvements in cardiometabolic risk factors and, in several, androgen excess and cutaneous and menstrual symptoms. Studies were limited by sample size (range, 22-171), few adolescent participants, and short-term outcomes. Findings show potential for metformin and estrogen-progestin dual therapy but warrant longitudinal studies examining outcomes from adolescence through middle age to determine the effect on long-term cardiovascular health.

Quality Primary Care and Family Planning Services for LGBT Clients: A Comprehensive Review of Clinical Guidelines.

PubMed

Klein, David A; Malcolm, Nikita M; Berry-Bibee, Erin N; Paradise, Scott L; Coulter, Jessica S; Keglovitz Baker, Kristin; Schvey, Natasha A; Rollison, Julia M; Frederiksen, Brittni N

2018-04-01

LGBT clients have unique healthcare needs but experience a wide range of quality in the care that they receive. This study provides a summary of clinical guideline recommendations related to the provision of primary care and family planning services for LGBT clients. In addition, we identify gaps in current guidelines, and inform future recommendations and guidance for clinical practice and research. PubMed, Cochrane, and Agency for Healthcare Research and Quality electronic bibliographic databases, and relevant professional organizations' websites, were searched to identify clinical guidelines related to the provision of primary care and family planning services for LGBT clients. Information obtained from a technical expert panel was used to inform the review. Clinical guidelines meeting the inclusion criteria were assessed to determine their alignment with Institute of Medicine (IOM) standards for the development of clinical practice guidelines and content relevant to the identified themes. The search parameters identified 2,006 clinical practice guidelines. Seventeen clinical guidelines met the inclusion criteria. Two of the guidelines met all eight IOM criteria. However, many recommendations were consistent regarding provision of services to LGBT clients within the following themes: clinic environment, provider cultural sensitivity and awareness, communication, confidentiality, coordination of care, general clinical principles, mental health considerations, and reproductive health. Guidelines for the primary and family planning care of LGBT clients are evolving. The themes identified in this review may guide professional organizations during guideline development, clinicians when providing care, and researchers conducting LGBT-related studies.

Biologically relevant photoacoustic imaging phantoms with tunable optical and acoustic properties

PubMed Central

Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Joshua Pfefer, T.

2016-01-01

Abstract. Established medical imaging technologies such as magnetic resonance imaging and computed tomography rely on well-validated tissue-simulating phantoms for standardized testing of device image quality. The availability of high-quality phantoms for optical-acoustic diagnostics such as photoacoustic tomography (PAT) will facilitate standardization and clinical translation of these emerging approaches. Materials used in prior PAT phantoms do not provide a suitable combination of long-term stability and realistic acoustic and optical properties. Therefore, we have investigated the use of custom polyvinyl chloride plastisol (PVCP) formulations for imaging phantoms and identified a dual-plasticizer approach that provides biologically relevant ranges of relevant properties. Speed of sound and acoustic attenuation were determined over a frequency range of 4 to 9 MHz and optical absorption and scattering over a wavelength range of 400 to 1100 nm. We present characterization of several PVCP formulations, including one designed to mimic breast tissue. This material is used to construct a phantom comprised of an array of cylindrical, hemoglobin-filled inclusions for evaluation of penetration depth. Measurements with a custom near-infrared PAT imager provide quantitative and qualitative comparisons of phantom and tissue images. Results indicate that our PVCP material is uniquely suitable for PAT system image quality evaluation and may provide a practical tool for device validation and intercomparison. PMID:26886681

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2015-01-01

The origin of carbapenem-hydrolyzing metallo-β-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins were analyzed by antimicrobial selective culture, followed by phenotypic testing and expression of MBL-encoding genes in Escherichia coli, and whole-genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive Pedobacter roseus (PEDO-1), Pedobacter borealis (PEDO-2), Pedobacter kyungheensis (PEDO-3), Chryseobacterium piscium (CPS-1), Epilithonimonas tenax (ESP-1), Massilia oculi (MSI-1), and Sphingomonas sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in Chryseobacterium and Epilithonimonas, as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with a putative OXA β-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in E. coli significantly increased the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin, and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria. PMID:26482314

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.

Empty polyetheretherketone (PEEK) cages in anterior cervical diskectomy and fusion (ACDF) show slow radiographic fusion that reduces clinical improvement: results from the prospective multicenter "PIERCE-PEEK" study.

PubMed

Suess, Olaf; Schomaker, Martin; Cabraja, Mario; Danne, Marco; Kombos, Theodoros; Hanna, Michael

2017-01-01

Anterior cervical diskectomy and fusion (ACDF) is a well-established surgical treatment for radiculopathy and myelopathy. Previous studies showed that empty PEEK cages have lower radiographic fusion rates, but the clinical relevance remains unclear. This paper's aim is to provide high-quality evidence on the outcomes of ACDF with empty PEEK cages and on the relevance of radiographic fusion for clinical outcomes. This large prospective multicenter clinical trial performed single-level ACDF with empty PEEK cages on patients with cervical radiculopathy or myelopathy. The main clinical outcomes were VAS (0-10) for pain and NDI (0-100) for functioning. Radiographic fusion was evaluated by two investigators for three different aspects. The median (range) improvement of the VAS pain score was: 3 (1-6) at 6 months, 3 (2-8) at 12 months, and 4 (2-8) at 18 months. The median (range) improvement of the NDI score was: 12 (2-34) at 6 months, 18 (4-46) at 12 months, and 22 (2-44) at 18 months. Complete radiographic fusion was reached by 126 patients (43%) at 6 months, 214 patients (73%) at 12 months, and 241 patients (83%) at 18 months. Radiographic fusion was a highly significant ( p  < 0.001) predictor of the improvement of VAS and NDI scores. This study provides strong evidence that ACDF is effective treatment, but the overall rate of radiographic fusion with empty PEEK cages is slow and insufficient. Lack of complete radiographic fusion leads to less improvement of pain and disability. We recommend against using empty uncoated pure PEEK cages in ACDF. ISRCTN42774128. Retrospectively registered 14 April 2009.

Comorbidities frequency in Takotsubo syndrome: an international collaborative systematic review including 1109 patients.

PubMed

Pelliccia, Francesco; Parodi, Guido; Greco, Cesare; Antoniucci, David; Brenner, Roman; Bossone, Eduardo; Cacciotti, Luca; Capucci, Alessandro; Citro, Rodolfo; Delmas, Clément; Guerra, Federico; Ionescu, Costin N; Lairez, Olivier; Larrauri-Reyes, Maiteder; Lee, Pil Hyung; Mansencal, Nicolas; Marazzi, Giuseppe; Mihos, Christos G; Morel, Olivier; Nef, Holger M; Nunez Gil, Ivan J; Passaseo, Ilaria; Pineda, Andres M; Rosano, Giuseppe; Santana, Orlando; Schneck, Franziska; Song, Bong Gun; Song, Jae-Kwan; Teh, Andrew W; Ungprasert, Patompong; Valbusa, Alberto; Wahl, Andreas; Yoshida, Tetsuro; Gaudio, Carlo; Kaski, Juan Carlos

2015-06-01

To identify predisposing factors that can result in the onset of takotsubo syndrome, we performed an international, collaborative systematic review focusing on clinical characteristics and comorbidities of patients with takotsubo syndrome. We searched and reviewed cited references up to August 2013 to identify relevant studies. Corresponding authors of selected studies were contacted and asked to provide additional quantitative details. Data from each study were extracted by 2 independent reviewers. The cumulative prevalence of presenting features and comorbidities was assessed. Nineteen studies whose authors sent the requested information were included in the systematic review, with a total of 1109 patients (951 women; mean age, 59-76 years). Evaluation of risk factors showed that obesity was present in 17% of patients (range, 2%-48%), hypertension in 54% (range, 27%-83%), dyslipidemia in 32% (range, 7%-59%), diabetes in 17% (range, 4%-34%), and smoking in 22% (range, 6%-49%). Emotional stressors preceded takotsubo syndrome in 39% of patients and physical stressors in 35%. The most common comorbidities were psychological disorders (24%; range, 0-49%), pulmonary diseases (15%; range, 0-22%), and malignancies (10%; range, 4%-29%). Other common associated disorders were neurologic diseases (7%; range, 0-22%), chronic kidney disease (7%; range, 2%-27%), and thyroid diseases (6%; range, 0-37%). Patients with takotsubo syndrome have a relevant prevalence of cardiovascular risk factors and associated comorbidities. Such of associations needs to be evaluated in further studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Nasal carriage of Staphylococcus aureus in Australian (pre-clinical and clinical) medical students.

PubMed

Stubbs, E; Pegler, M; Vickery, A; Harbour, C

1994-06-01

The nasal carriage of Staphylococcus aureus in 808 Australian medical students was studied. Five groups of students experienced varying degrees of clinical exposure in a hospital environment ranging from 0 to 42 months. The overall percentage of carriers among the five groups did not vary. However, with increasing clinical exposure there was a decrease in the percentage of isolates sensitive to all antibiotics tested, and an increase in the carriage of S. aureus resistant to three or more antibiotics. No carriers of methicillin-resistant S. aureus (MRSA) were detected. The comparative rates of S. aureus carriage between female and male students varied. The relevance of medical students as nasal carriers of S. aureus in the hospital environment today is discussed.

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

PubMed

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

2018-02-01

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

Doors for memory: A searchable database.

PubMed

Baddeley, Alan D; Hitch, Graham J; Quinlan, Philip T; Bowes, Lindsey; Stone, Rob

2016-11-01

The study of human long-term memory has for over 50 years been dominated by research on words. This is partly due to lack of suitable nonverbal materials. Experience in developing a clinical test suggested that door scenes can provide an ecologically relevant and sensitive alternative to the faces and geometrical figures traditionally used to study visual memory. In pursuing this line of research, we have accumulated over 2000 door scenes providing a database that is categorized on a range of variables including building type, colour, age, condition, glazing, and a range of other physical characteristics. We describe an illustrative study of recognition memory for 100 doors tested by yes/no, two-alternative, or four-alternative forced-choice paradigms. These stimuli, together with the full categorized database, are available through a dedicated website. We suggest that door scenes provide an ecologically relevant and participant-friendly source of material for studying the comparatively neglected field of visual long-term memory.

Depression in female adolescents: an IPA analysis.

PubMed

Shaw, Samantha K; Dallos, Rudi; Shoebridge, Philip

2009-04-01

Six female adolescents participated in open-ended interviews regarding their experiences of depression. The transcripts of their interviews were explored using Interpretative Phenomenological Analysis (Smith, 1991). The analysis revealed three inter-connected super-ordinate themes which were: communication, hurt self, and difference. These themes centred on communication processes in participants' families and with peers, issues relating to shifts in identity through adolescence, and feelings of being damaged, distressed, and hurt. Amongst a range of potentially relevant perspectives, an attachment theory (Bowlby, 1969) orientation was found to be particularly relevant and helpful in interpreting the themes that captured these young women's experiences. Some implications for clinical practice are discussed.

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

PubMed

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

2016-05-01

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

Development of Clinically Relevant Implantable Pressure Sensors: Perspectives and Challenges

PubMed Central

Clausen, Ingelin; Glott, Thomas

2014-01-01

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

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

PubMed

Clausen, Ingelin; Glott, Thomas

2014-09-22

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

Incidental findings in multislice computed tomography prior to transcatheter aortic valve implantation: frequency, clinical relevance and outcome.

PubMed

Trenkwalder, Teresa; Lahmann, Anna Lena; Nowicka, Magdalena; Pellegrini, Costanza; Rheude, Tobias; Mayr, N Patrick; Voss, Stephanie; Bleiziffer, Sabine; Lange, Rüdiger; Joner, Michael; Kasel, Albert M; Kastrati, Adnan; Schunkert, Heribert; Husser, Oliver; Hadamitzky, Martin; Hengstenberg, Christian

2018-02-21

Multislice computed tomography (MSCT) has emerged as the mainstay in patients planned for transcatheter aortic valve implantation (TAVI). Incidental findings (IF) in MSCT are common. However, the exact incidence, clinical relevance and further consequences of IF are unclear and it is controversial whether IF adversely affect patients' outcome. We analyzed MSCT data of 1050 patients screened for TAVI between January 2011 and December 2014. Median follow-up of patients was 20 months. In total, 3194 IF were identified, which were classified into clinically non-relevant IF (2872, 90%) and clinically relevant IF (322, 10%). In 25% of patients (258/1050) at least one clinically relevant IF was present. Age (80 ± 7 vs. 80 ± 7 years; p = 0.198) and EuroSCORE II (3.6% [2.1-5.7] vs. 3.6% [2.1-5.9]; p = 0.874) was similar between patients with and without a clinically relevant IF. TAVI was performed less frequently in patients with a clinically relevant IF (76% vs. 85%; p < 0.001), with more patients receiving surgical aortic valve replacement in that group (14% vs. 11%; p = 0.042), possibly due to the high rate of incidental aneurysms of the ascending aorta (n = 48). If TAVI was performed mortality did not differ (30-days: 4% vs. 3%; p = 0.339, 1-year: 11% vs. 14%; p = 0.226) between patients with and without a clinically relevant IF. Our study is the largest study to analyze prevalence, clinical relevance and therapeutic consequences of IF during screening for TAVI. IF in pre-procedural MSCT are common and clinically relevant in one-quarter of patients. However, these findings had no impact on overall mortality.

Quetiapine and its metabolite norquetiapine: translation from in vitro pharmacology to in vivo efficacy in rodent models

PubMed Central

Widzowski, D; Maciag, C; Zacco, A; Hudzik, T; Liu, J; Nyberg, S; Wood, M W

2015-01-01

Background and Purpose Quetiapine has a range of clinical activity distinct from other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in bipolar depression, major depressive disorder and generalized anxiety disorder. The neuropharmacological mechanisms underlying this clinical profile are not completely understood; however, the major active metabolite, norquetiapine, has been shown to have a distinct in vitro pharmacological profile consistent with a broad therapeutic range and may contribute to the clinical profile of quetiapine. Experimental Approach We evaluated quetiapine and norquetiapine, using in vitro binding and functional assays of targets known to be associated with antidepressant and anxiolytic drug actions and compared these activities with a representative range of established antipsychotics and antidepressants. To determine how the in vitro pharmacological properties translate into in vivo activity, we used preclinical animal models with translational relevance to established antidepressant‐like and anxiolytic‐like drug action. Key Results Norquetiapine had equivalent activity to established antidepressants at the noradrenaline transporter (NET), while quetiapine was inactive. Norquetiapine was active in the mouse forced swimming and rat learned helplessness tests. In in vivo receptor occupancy studies, norquetiapine had significant occupancy at NET at behaviourally relevant doses. Both quetiapine and norquetiapine were agonists at 5‐HT1A receptors, and the anxiolytic‐like activity of norquetiapine in rat punished responding was blocked by the 5‐HT1A antagonist, WAY100635. Conclusions and Implications Quetiapine and norquetiapine have multiple in vitro pharmacological actions, and results from preclinical studies suggest that activity at NET and 5‐HT1A receptors contributes to the antidepressant and anxiolytic effects in patients treated with quetiapine. PMID:26436896

Comparative laser-tissue interaction effects at 1.96 and 2.01 um of Cr; Tm:YAG laser

NASA Astrophysics Data System (ADS)

Pankratov, Michail M.; Perrault, Donald F., Jr.; Shapshay, Stanley M.; Pinto, Joseph F.; Esterowitz, Dina; Aretz, H. Thomas

1992-08-01

A pulsed spiking and nonspiking Cr; thulium (Tm):YAG flash lamp pumped laser operating at 1.96 and 2.01 μm was investigated in vitro in the clinically relevant power range for its basic laser-tissue interaction with soft, cartilaginous, and bone tissues. Some explanations of the differences and possible medical applications are discussed.

Parental functioning and pediatric sleep disturbance: an examination of factors associated with parenting stress in children clinically referred for evaluation of insomnia.

PubMed

Byars, Kelly C; Yeomans-Maldonado, Gloria; Noll, Jennie G

2011-10-01

Parenting stress is an aspect of parent functioning relevant in clinical settings. Within the context of behavioral sleep medicine, the role of parenting stress is not well understood. Prospective evaluation of patients 1.5-10 years old with insomnia. Subjects were 156 primary caregiver-child pairs who completed the Parenting Stress Index-Short Form (PSI-SF), Child Sleep Habits Questionnaire (CSHQ) and Child Behavior Checklist (CBCL). (1) determine prevalence of clinically significant parenting stress in primary caregivers of children clinically referred for insomnia; (2) identify childhood sleep problems that play a role in parenting stress; (3) identify relevant correlates of parenting stress within the context of a behavioral sleep medicine clinic; and (4) identify the most salient child sleep and behavioral variables associated with parenting stress. Forty-seven percent of primary caregivers had clinically significant parenting stress. When examining the relationship between child sleep problems and parenting stress, bedtime resistance (p=0.030) and daytime sleepiness (p=0.0003) stood alone as having the most salient associations with parenting stress. When considering a broader range of covariates (child age and child gender) and clinically relevant variables (parent history of sleep problems, parent history of psychiatric conditions, child behavior problems and child sleep problems) in a single regression equation, both child externalizing behavior problems (β=0.570, p<0.0001) and child daytime sleepiness (β=0.152, p=0.028) independently explained significant variability in parenting stress. Many primary caregivers of children clinically-referred for insomnia evaluation and treatment have significant parenting stress. Parenting stress is associated with daytime behavioral problems and sleepiness in children with insomnia. Clinicians working with pediatric insomnia patients should carefully evaluate parenting stress and child daytime behavior as these aspects of functioning may have an impact on service delivery and treatment outcomes. Copyright © 2011 Elsevier B.V. All rights reserved.

Quality Control of Next-generation Sequencing-based In vitro Diagnostic Test for Onco-relevant Mutations Using Multiplex Reference Materials in Plasma.

PubMed

Liu, Donglai; Zhou, Haiwei; Shi, Dawei; Shen, Shu; Tian, Yabin; Wang, Lin; Lou, Jiatao; Cong, Rong; Lu, Juan; Zhang, Henghui; Zhao, Meiru; Zhu, Shida; Cao, Zhisheng; Jin, Ruilin; Wang, Yin; Zhang, Xiaoni; Yang, Guohua; Wang, Youchun; Zhang, Chuntao

2018-01-01

Background: Widespread clinical implementation of next-generation sequencing (NGS)-based cancer in vitro diagnostic tests (IVDs) highlighted the urgency to establish reference materials which could provide full control of the process from nucleic acid extraction to test report generation. The formalin-fixed, paraffin-embedded (FFPE) tissue and blood plasma containing circulating tumor deoxyribonucleic acid (ctDNA) were mostly used for clinically detecting onco-relevant mutations. Methods: We respectively developed multiplex FFPE and plasma reference materials covering three clinically onco-relevant mutations within the epidermal growth factor receptor ( EGFR ) gene at serial allelic frequencies. All reference materials were quantified and validated via droplet digital polymerase chain reaction (ddPCR), and then were distributed to eight domestic manufacturers for the collaborative evaluation of the performance of several domestic NGS-based cancer IVDs covering four major NGS platforms (NextSeq, HiSeq, Ion Proton and BGISEQ). Results: All expected mutations except one at extremely low allelic frequencies were detected, despite some differences in coefficient of variation (CV) which increased with the decrease of allelic frequency (CVs ranging from 18% to 106%). It was worth noting that the CV value seemed to correlate with a particular mutation as well. The repeatability of determination of different mutations was L858R>T790M>19del. Conclusions: The results indicated our reference materials would be pivotal for quality control of NGS-based cancer IVDs and would guide the further development of reference materials covering more onco-relevant mutations.

Melperone but not bisoprolol or metoprolol is a clinically relevant inhibitor of CYP2D6: evidence from a therapeutic drug monitoring survey.

PubMed

Hefner, Gudrun; Unterecker, Stefan; Shams, Mohamed E E; Wolf, Margarete; Falter, Tanja; Haen, Ekkehard; Hiemke, Christoph

2015-11-01

Cytochrome P450 enzymes (CYP) can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. The objective of the study was to analyze the in vivo inhibitory potential of the beta-blockers bisoprolol and metoprolol as well as the low-potency antipsychotic melperone on CYP2D6. By utilizing a large therapeutic drug monitoring database of 2874 samples, data from patients who had been treated with venlafaxine (VEN) either without (control group) or with a concomitant medication with bisoprolol, metoprolol or melperone were evaluated retrospectively to study the CYP2D6-catalyzed O-demethylation to O-desmethylvenlafaxine (ODVEN). Dose-adjusted serum levels (C/D) of VEN and ODVEN as well as the metabolic ratios (ODVEN/VEN) were computed for the four groups and compared using Kruskal-Wallis test. In total, 381 patients could be included for analysis. No significant difference was found in the median C/D (VEN), C/D (ODVEN) or C/D of the active moiety (VEN + ODVEN) in either the metoprolol (N = 103) or bisoprolol group (N = 101), compared to the control group (N = 108). In contrast, a significantly higher median C/D (VEN) (0.79 ng/ml/mg, range 0.13-5.73 ng/ml/mg) (P < 0.01) was found in the melperone group (N = 69), compared to the control group (0.46 ng/ml/mg, range 0.02-7.39 ng/ml/mg). A significant decrease (P < 0.01) was solely found in the median metabolic ratios of ODVEN/VEN between the melperone group (0.90, range 0.14-15.15), compared to the control group (2.39, range 0.06-15.31). The results of this study provided evidence that melperone but not bisoprolol or metoprolol has a clinically relevant inhibitory potential on CYP2D6.

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

PubMed

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

2018-03-28

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

A Predictable Alternative to a Smile in Six Months?

PubMed

Kalantzis, Elizabeth; Waring, David T; Malik, Ovais H

2017-03-01

The aim of this article is to explore the use of Incognito™ Lite as an alternative to competitors advertising a ‘Smile in Six Months’ or rather short-term orthodontics for improving dental appearance through tooth movement. The focus is on the varied clinical use of this appliance system and its comparative advantages, disadvantages and placement techniques. Some alternatives are discussed and appraised. Two cases successfully treated with Incognito™ Lite are then presented. Clinical relevance: A reliable and predictable tool for aesthetic alignment of teeth, creating a broader range of treatment options for both the clinician and the patient.

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

PubMed

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

2018-05-01

Rapidly fabricated, disposable sensor platforms hold tremendous promise for point-of-care detection. Here, we present an inexpensive (< $0.25) fully inkjet printed electrochemical sensor with integrated counter, reference, and working electrodes that is easily scalable for commercial fabrication. The electrochemical sensor platform featured an inkjet printed gold working 8-electrode array (WEA) and counter electrode (CE), along with an inkjet -printed silver electrode that was chlorinated with bleach to produce a Ag/AgCl quasi-reference electrode (RE). As proof of concept, the electrochemical sensor was successfully applied for detection of clinically relevant breast cancer biomarker Human Epidermal Growth Factor Receptor 2 (HER-2). Capture antibodies were bound to a chemically modified surface on the WEA and placed into a microfluidic device. A full sandwich immunoassay was constructed following a simultaneous injection of target protein, biotinylated antibody, and polymerized horseradish peroxide labels into the microfluidic device housing the WEA. With an ultra fast assay time, of only 15mins a clinically relevant limit of detection of 12pgmL -1 was achieved. Excellent reproducibility and sensitivity were observed through recovery assays preformed in human serum with recoveries ranging from 76% to 103%. These easily fabricated and scalable electrochemical sensor platforms can be readily adapted for multiplex detection following this rapid assay protocol for cancer diagnostics. Copyright © 2018 Elsevier B.V. All rights reserved.

Melatonin Effects in REM Sleep Behavior Disorder Associated with Obstructive Sleep Apnea Syndrome: A Case Series.

PubMed

Schaefer, Carolin; Kunz, Dieter; Bes, Frederik

2017-01-01

REM sleep behavior disorder (RBD), with its main clinical symptoms of nightmares with dream-enacting behavior, is considered as a possible precursor of neurodegenerative disease. Obstructive Sleep Apnea Syndrome (OSAS) is known to be capable of provoking RBD-like symptoms by apneic event related arousals. The two sleep related pathologies must coincide in a relevant number of individuals because of overlapping prevalence in similar age groups. Until now RBD symptoms coexisting with OSAS are rarely described in scientific literature and in fact considered as OSAS mimicking RBD. We report four cases with a severe clinical RBD syndrome which were polysomnographically also diagnosed with concomitant OSAS (AHI range: 10.1 -53.2/h). Treatment with 2 mg prolonged release melatonin led to a relevant clinical improvement of RBD symptoms in all patients, so far untreated for the sleep related breathing disorder. Measure of REM sleep without atonia (RSWA) in polysomnography showed values ranging from 5.1 to 20.4% determined with the Montplaisir method. Surprisingly, RSWA values in PSG with melatonin were high, probably because of the still untreated OSAS. We presume that in patients with RBD and OSAS both pathologies contribute in varying degrees to the emergence of RBD symptoms by a destabilization of REM sleep. We suggest by consequence to consider a therapeutic strategy including the treatment of both disorders for an optimal therapeutic response. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties

PubMed Central

Herold, Karl F.; Sanford, R. Lea; Lee, William; Andersen, Olaf S.; Hemmings, Hugh C.

2017-01-01

General anesthetics have revolutionized medicine by facilitating invasive procedures, and have thus become essential drugs. However, detailed understanding of their molecular mechanisms remains elusive. A mechanism proposed over a century ago involving unspecified interactions with the lipid bilayer known as the unitary lipid-based hypothesis of anesthetic action, has been challenged by evidence for direct anesthetic interactions with a range of proteins, including transmembrane ion channels. Anesthetic concentrations in the membrane are high (10–100 mM), however, and there is no experimental evidence ruling out a role for the lipid bilayer in their ion channel effects. A recent hypothesis proposes that anesthetic-induced changes in ion channel function result from changes in bilayer lateral pressure that arise from partitioning of anesthetics into the bilayer. We examined the effects of a broad range of chemically diverse general anesthetics and related nonanesthetics on lipid bilayer properties using an established fluorescence assay that senses drug-induced changes in lipid bilayer properties. None of the compounds tested altered bilayer properties sufficiently to produce meaningful changes in ion channel function at clinically relevant concentrations. Even supra-anesthetic concentrations caused minimal bilayer effects, although much higher (toxic) concentrations of certain anesthetic agents did alter lipid bilayer properties. We conclude that general anesthetics have minimal effects on bilayer properties at clinically relevant concentrations, indicating that anesthetic effects on ion channel function are not bilayer-mediated but rather involve direct protein interactions. PMID:28265069

Animal models of Parkinson's disease: limits and relevance to neuroprotection studies.

PubMed

Bezard, Erwan; Yue, Zhenyu; Kirik, Deniz; Spillantini, Maria Grazia

2013-01-01

Over the last two decades, significant strides has been made toward acquiring a better knowledge of both the etiology and pathogenesis of Parkinson's disease (PD). Experimental models are of paramount importance to obtain greater insights into the pathogenesis of the disease. Thus far, neurotoxin-based animal models have been the most popular tools employed to produce selective neuronal death in both in vitro and in vivo systems. These models have been commonly referred to as the pathogenic models. The current trend in modeling PD revolves around what can be called the disease gene-based models or etiologic models. The value of utilizing multiple models with a different mechanism of insult rests on the premise that dopamine-producing neurons die by stereotyped cascades that can be activated by a range of insults, from neurotoxins to downregulation and overexpression of disease-related genes. In this position article, we present the relevance of both pathogenic and etiologic models as well as the concept of clinically relevant designs that, we argue, should be utilized in the preclinical development phase of new neuroprotective therapies before embarking into clinical trials. Copyright © 2013 Movement Disorders Society.

Standards for gene therapy clinical trials based on pro-active risk assessment in a London NHS Teaching Hospital Trust.

PubMed

Bamford, K B; Wood, S; Shaw, R J

2005-02-01

Conducting gene therapy clinical trials with genetically modified organisms as the vectors presents unique safety and infection control issues. The area is governed by a range of legislation and guidelines, some unique to this field, as well as those pertinent to any area of clinical work. The relevant regulations covering gene therapy using genetically modified vectors are reviewed and illustrated with the approach taken by a large teaching hospital NHS Trust. Key elements were Trust-wide communication and involvement of staff in a pro-active approach to risk management, with specific emphasis on staff training and engagement, waste management, audit and record keeping. This process has led to the development of proposed standards for clinical trials involving genetically modified micro-organisms.

Reprogramming the tumor microenvironment to enhance adoptive cellular therapy.

PubMed

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

2016-02-01

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

Therapist Adherence in Brief Strategic Family Therapy for Adolescent Drug Abusers

PubMed Central

Robbins, Michael S.; Feaster, Daniel J.; Horigian, Viviana E.; Puccinelli, Marc J.; Henderson, Craig; Szapocznik, José

2012-01-01

Objective Therapist adherence has been shown to predict clinical outcomes in family therapy. In prior studies, adherence has been represented broadly by core principles and a consistent family (vs. individual) focus. To date, these studies have not captured the range of clinical skills that are represented in complex family-based approaches or examined how variations in these skills predict different clinically relevant outcomes over the course of treatment. In this study, the authors examined the reliability and validity of an observational adherence measure and the relationship between adherence and outcome in a sample of drug-using adolescents who received brief strategic family therapy within a multisite effectiveness study. Method Participants were 480 adolescents (age 12–17) and their family members, who were randomized to the Brief Strategic Family Therapist treatment condition (J. Szapocznik, U. Hervis, & S. Schwartz, 2003) or treatment as usual. The adolescents were mostly male (377 vs. 103 female) and Hispanic (213), whereas 148 were White, and 110 were Black. Therapists were also randomly assigned to treatment condition within agencies. Results Results supported the proposed factor structure of the adherence measure, providing evidence that it is possible to capture and discriminate between distinct dimensions of family therapy. Analyses demonstrated that the mean levels of the factors varied over time in theoretically and clinically relevant ways and that therapist adherence was associated with engagement and retention in treatment, improvements in family functioning, and reductions in adolescent drug use. Conclusions Clinical implications and future research directions are discussed, including the relevance of these findings on training therapists and studies focusing on mechanisms of action in family therapy. PMID:21261433

An 11-year retrospective experience of antibodies against the voltage-gated potassium channel (VGKC) complex from a tertiary neurological centre.

PubMed

Huda, S; Wong, S H; Pettingill, P; O'Connell, D; Vincent, A; Steiger, M

2015-02-01

Acquired diseases classically associated with VGKC-complex antibodies include peripheral nerve hyperexcitability (PNH), Morvan's syndrome, limbic encephalitis (LE), and epilepsy. However, not all such patients have VGKC-complex antibodies and antibodies have been reported in patients without a defined immune-mediated syndrome. To analyse the clinical relevance of positive VGKC-complex antibodies requested on the basis of initial clinical suspicion. We retrospectively analysed patients with positive VGKC-complex antibodies (>100 pM) referred to our institution between 2001 and 2011. 1,614 VGKC-complex assays were performed in 1,298 patients. Titres >100 pM were detected in 57/1,298 (4 %) patients. A classic VGKC-complex channelopathy (60 %) was associated with VGKC-complex antibody titres >400 pM (p = 0.0004). LGI1 or CASPR2 antibodies were only detected in classic VGKC-complex channelopathies (LE; n = 3/4 and PNH; n = 1/5). VGKC-complex antibody titres <400 pM were seen with PNH (n = 15/22; 68 %) but also a heterogeneous range of central and/or peripheral nervous system disorders. Electromyography was supportive of PNH in 65 % of cases and symptomatic treatment was beneficial in 46 % of patients. Irrespective of titre, the rate of malignancy in patients with VGKC-complex antibodies was higher than the age-matched national incidence of malignancy (OR 19.9, 95 % CI 8.97-44.0 p<0.0001). Clinical phenotyping and antibody titres >400 pM can help determine VGKC-complex antibody relevance. Antibody titres <400 pM are associated with PNH but also a more heterogeneous clinical spectrum. The antibody association in the latter is of doubtful clinical relevance. The rate of malignancy was significantly higher than the national incidence irrespective of titre.

How is feedback from national clinical audits used? Views from English National Health Service trust audit leads.

PubMed

Taylor, Angelina; Neuburger, Jenny; Walker, Kate; Cromwell, David; Groene, Oliver

2016-04-01

To explore how the output of national clinical audits in England is used by professionals and whether and how their impact could be enhanced. A mixed-methods study with the primary recipients of four national clinical audits of cancer care of 607 local audit leads, 274 (45%) completed a questionnaire and 32 participated in an interview. Our questions focused on how the audits were used and whether barriers existed to using the audits for local service improvement. We described variation in questionnaire responses between the audits using chi-squared tests. Results are reported as percentages with their 95% confidence intervals. Qualitative data were analysed using Framework analysis. More than 90% of survey respondents believed that the audit findings were relevant to their clinical work, and interviewees described how they used the audits for a range of purposes. Forty-two percent of survey respondents said they had changed their clinical practice, and 56% had implemented service improvements in response to the audits. The degree of change differed between the four audits, evident in both the questionnaire and the interview data. In the interviews, two recurring barriers emerged: (1) the importance of data quality, which, in turn, influenced the perceived relevance and validity of the audit data and therefore the ability to make changes based on it and (2) the need for clear presentation of benchmarked local performance data. The perceived authority and credibility of the professional bodies supporting the audits was a key factor underpinning the use of the audit findings. National cancer audit and feedback is used to improve services, but their impact could be enhanced by improving the data quality and relevance of feedback. © The Author(s) 2016.

Chapter 3: choosing the important outcomes for a systematic review of a medical test.

PubMed

Segal, Jodi B

2012-06-01

In this chapter of the Evidence-based Practice Centers Methods Guide for Medical Tests, we describe how the decision to use a medical test generates a broad range of outcomes and that each of these outcomes should be considered for inclusion in a systematic review. Awareness of these varied outcomes affects how a decision maker balances the benefits and risks of the test; therefore, a systematic review should present the evidence on these diverse outcomes. The key outcome categories include clinical management outcomes and direct health effects; emotional, social, cognitive, and behavioral responses to testing; legal and ethical outcomes, and costs. We describe the challenges of incorporating these outcomes in a systematic review, suggest a framework for generating potential outcomes for inclusion, and describe the role of stakeholders in choosing the outcomes for study. Finally, we give examples of systematic reviews that either included a range of outcomes or that might have done so. The following are the key messages in this chapter: Consider both the outcomes that are relevant to the process of testing and those that are relevant to the results of the test. Consider inclusion of outcomes in all five domains: clinical management effects, direct test effects; emotional, social, cognitive and behavioral effects; legal and ethical effects, and costs. Consider to which group the outcomes of testing are most relevant. Given resource limitations, prioritize which outcomes to include. This decision depends on the needs of the stakeholder(s), who should be assisted in prioritizing the outcomes for inclusion.

Examining the bleeding incidences associated with targeted therapies used in metastatic renal cell carcinoma.

PubMed

Crist, MacKenzie; Hansen, Elizabeth; Chablani, Lipika; Guancial, Elizabeth

2017-12-01

A systematic review was conducted to illustrate the bleeding risks associated with targeted therapies used in the treatment of metastatic renal cell carcinoma (mRCC). Eligible studies included phase II, III, or IV clinical trials using pazopanib, sunitinib, cabozantinib, lenvatinib, everolimus, temsirolimus, bevacizumab, axitinib, and/or sorafenib in the setting of mRCC. Types of bleeding event(s), bleeding event frequency, and incidence of thrombocytopenia were collected from the relevant articles. ClinicalTrials.gov was also searched for incidence of "Serious bleeding adverse effects" reported in these trials. The incidences of bleeding events ranged from 1 to 36%, and incidences of thrombocytopenia ranged from 2 to 78%. Available serious bleeding adverse events ranged from 1 to 7%. The highest percentage of bleeding incidences were seen with bevacizumab, while the lowest percentage of bleeding incidences were seen with axitinib. All of the included trials were of high quality per Jadad scoring. Copyright © 2017 Elsevier B.V. All rights reserved.

Energy weighting improves dose efficiency in clinical practice: implementation on a spectral photon-counting mammography system

PubMed Central

Berglund, Johan; Johansson, Henrik; Lundqvist, Mats; Cederström, Björn; Fredenberg, Erik

2014-01-01

Abstract. In x-ray imaging, contrast information content varies with photon energy. It is, therefore, possible to improve image quality by weighting photons according to energy. We have implemented and evaluated so-called energy weighting on a commercially available spectral photon-counting mammography system. The technique was evaluated using computer simulations, phantom experiments, and analysis of screening mammograms. The CNR benefit of energy weighting for a number of relevant target-background combinations measured by the three methods fell in the range of 2.2 to 5.2% when using optimal weight factors. This translates to a potential dose reduction at constant CNR in the range of 4.5 to 11%. We expect the choice of weight factor in practical implementations to be straightforward because (1) the CNR improvement was not very sensitive to weight, (2) the optimal weight was similar for all investigated target-background combinations, (3) aluminum/PMMA phantoms were found to represent clinically relevant tasks well, and (4) the optimal weight could be calculated directly from pixel values in phantom images. Reasonable agreement was found between the simulations and phantom measurements. Manual measurements on microcalcifications and automatic image analysis confirmed that the CNR improvement was detectable in energy-weighted screening mammograms. PMID:26158045

Mitochondrial Targets for Pharmacological Intervention in Human Disease

PubMed Central

2015-01-01

Over the past several years, mitochondrial dysfunction has been linked to an increasing number of human illnesses, making mitochondrial proteins (MPs) an ever more appealing target for therapeutic intervention. With 20% of the mitochondrial proteome (312 of an estimated 1500 MPs) having known interactions with small molecules, MPs appear to be highly targetable. Yet, despite these targeted proteins functioning in a range of biological processes (including induction of apoptosis, calcium homeostasis, and metabolism), very few of the compounds targeting MPs find clinical use. Recent work has greatly expanded the number of proteins known to localize to the mitochondria and has generated a considerable increase in MP 3D structures available in public databases, allowing experimental screening and in silico prediction of mitochondrial drug targets on an unprecedented scale. Here, we summarize the current literature on clinically active drugs that target MPs, with a focus on how existing drug targets are distributed across biochemical pathways and organelle substructures. Also, we examine current strategies for mitochondrial drug discovery, focusing on genetic, proteomic, and chemogenomic assays, and relevant model systems. As cell models and screening techniques improve, MPs appear poised to emerge as relevant targets for a wide range of complex human diseases, an eventuality that can be expedited through systematic analysis of MP function. PMID:25367773

The changing face of clinical trials in the personalized medicine and immuno-oncology era: report from the international congress on clinical trials in Oncology & Hemato-Oncology (ICTO 2017).

PubMed

Golan, Talia; Milella, Michele; Ackerstein, Aliza; Berger, Ranaan

2017-12-28

In the past decade, the oncology community has witnessed major advances in the understanding of cancer biology and major breakthroughs in several different therapeutic areas, from solid tumors to hematological malignancies; moreover, the advent of effective immunotherapy approaches, such as immune-checkpoint blockade, is revolutionizing treatment algorithms in almost all oncology disease areas. As knowledge evolves and new weapons emerge in the "war against cancer", clinical and translational research need to adapt to a rapidly changing environment to effectively translate novel concepts into sustainable and accessible therapeutic options for cancer patients.With this in mind, translational cancer researchers, oncology professionals, treatment experts, CRO and industry leaders, as well as patient representatives gathered in London, 16-17 March 2017, for The International Congress on Clinical Trials in Oncology and Hemato-Oncology (ICTO2017), to discuss the changing face of oncology clinical trials in the new era of personalized medicine and immuno-oncology. A wide range of topics, including clinical trial design in immuno-oncology, biomarker-oriented drug development paths, statistical design and endpoint selection, challenges in the design and conduct of personalized medicine clinical trials, risk-based monitoring, financing and reimbursement, as well as best operational practices, were discussed in an open, highly interactive format, favoring networking among all relevant stakeholders. The most relevant data, approaches and issues emerged and discussed during the conference are summarized in this report.

Characterization of the microbunch time structure of proton pencil beams at a clinical treatment facility.

PubMed

Petzoldt, J; Roemer, K E; Enghardt, W; Fiedler, F; Golnik, C; Hueso-González, F; Helmbrecht, S; Kormoll, T; Rohling, H; Smeets, J; Werner, T; Pausch, G

2016-03-21

Proton therapy is an advantageous treatment modality compared to conventional radiotherapy. In contrast to photons, charged particles have a finite range and can thus spare organs at risk. Additionally, the increased ionization density in the so-called Bragg peak close to the particle range can be utilized for maximum dose deposition in the tumour volume. Unfortunately, the accuracy of the therapy can be affected by range uncertainties, which have to be covered by additional safety margins around the treatment volume. A real-time range and dose verification is therefore highly desired and would be key to exploit the major advantages of proton therapy. Prompt gamma rays, produced in nuclear reactions between projectile and target nuclei, can be used to measure the proton's range. The prompt gamma-ray timing (PGT) method aims at obtaining this information by determining the gamma-ray emission time along the proton path using a conventional time-of-flight detector setup. First tests at a clinical accelerator have shown the feasibility to observe range shifts of about 5 mm at clinically relevant doses. However, PGT spectra are smeared out by the bunch time spread. Additionally, accelerator related proton bunch drifts against the radio frequency have been detected, preventing a potential range verification. At OncoRay, first experiments using a proton bunch monitor (PBM) at a clinical pencil beam have been conducted. Elastic proton scattering at a hydrogen-containing foil could be utilized to create a coincident proton-proton signal in two identical PBMs. The selection of coincident events helped to suppress uncorrelated background. The PBM setup was used as time reference for a PGT detector to correct for potential bunch drifts. Furthermore, the corrected PGT data were used to image an inhomogeneous phantom. In a further systematic measurement campaign, the bunch time spread and the proton transmission rate were measured for several beam energies between 69 and 225 MeV as well as for variable momentum limiting slit openings. We conclude that the usage of a PBM increases the robustness of the PGT method in clinical conditions and that the obtained data will help to create reliable range verification procedures in clinical routine.

RELATIONSHIP BETWEEN ISOMETRIC THIGH MUSCLE STRENGTH AND MINIMAL CLINICALLY IMPORTANT DIFFERENCES (MCIDS) IN KNEE FUNCTION IN OSTEOARTHRITIS – DATA FROM THE OSTEOARTHRITIS INITIATIVE

PubMed Central

Ruhdorfer, Anja; Wirth, Wolfgang; Eckstein, Felix

2014-01-01

Objective To determine the relationship between thigh muscle strength and clinically relevant differences in self-assessed lower limb function. Methods Isometric knee extensor and flexor strength of 4553 Osteoarthritis Initiative participants (2651 women/1902 men) was related to Western Ontario McMasters Universities (WOMAC) physical function scores by linear regression. Further, groups of Male and female participant strata with minimal clinically important differences (MCIDs) in WOMAC function scores (6/68) were compared across the full range of observed values, and to participants without functional deficits (WOMAC=0). The effect of WOMAC knee pain and body mass index on the above relationships was explored using stepwise regression. Results Per regression equations, a 3.7% reduction in extensor and a 4.0% reduction in flexor strength were associated with an MCID in WOMAC function in women, and a 3.6%/4.8% reduction in men. For strength divided by body weight, reductions were 5.2%/6.7% in women and 5.8%/6.7% in men. Comparing MCID strata across the full observed range of WOMAC function confirmed the above estimates and did not suggest non-linear relationships across the spectrum of observed values. WOMAC pain correlated strongly with WOMAC function, but extensor (and flexor) muscle strength contributed significant independent information. Conclusion Reductions of approximately 4% in isometric muscle strength and of 6% in strength/weight were related to a clinically relevant difference in WOMAC functional disability. Longitudinal studies will need to confirm these relationships within persons. Muscle extensor (and flexor) strength (per body weight) provided significant independent information in addition to pain in explaining variability in lower limb function. PMID:25303012

Hindfoot arthroscopic surgery for posterior ankle impingement: a systematic surgical approach and case series.

PubMed

Smyth, Niall A; Murawski, Christopher D; Levine, David S; Kennedy, John G

2013-08-01

Hindfoot arthroscopic surgery has been described as a minimally invasive surgical treatment for posterior ankle impingement syndrome. The current article describes a systematic approach for identifying relevant hindfoot structures as well as the clinical results of a case series. To present a structured systematic surgical approach for identifying relevant anatomic structures and abnormalities during hindfoot arthroscopic surgery. In addition, we report the clinical results of a case series. Case series; Level of evidence, 4. The systematic surgical approach divides the extra-articular structures of the hindfoot into quadrants as defined by the intermalleolar ligament. Twenty-two patients underwent hindfoot arthroscopic surgery for the treatment of posterior ankle impingement syndrome. The mean follow-up time was 25 months (range, 14-35 months). Standard patient-reported outcome questionnaires of the foot and ankle outcome score (FAOS) and Short Form-12 (SF-12) general health survey were administered at standard time points after surgery. Return to sporting activities was also calculated as the time period from the date of surgery until the patient was able to participate at their previous level of activity. The mean FAOS score improved from 59 (range, 22-94) preoperatively to 86 (range, 47-100) postoperatively (P < .01). The mean SF-12 score showed similar improvement with a mean of 66 (range, 42-96) preoperatively to 86 (range, 56-98) postoperatively (P < .01). Nineteen patients reported competing at some level of athletic sport before surgery. All patients returned to their previous level of competition after surgery. The mean time to return to sporting activities was 12 weeks (range, 6-16 weeks). Two complications were reported postoperatively: 1 wound infection and 1 case of dysesthesia of the deep peroneal nerve. Hindfoot arthroscopic surgery is a safe and effective treatment strategy for posterior ankle impingement syndrome. In addition, it allows the patients a rapid return to sporting activities.

Validity and Reliability of the Clinical Competency Evaluation Instrument for Use among Physiotherapy Students: Pilot study.

PubMed

Muhamad, Zailani; Ramli, Ayiesah; Amat, Salleh

2015-05-01

The aim of this study was to determine the content validity, internal consistency, test-retest reliability and inter-rater reliability of the Clinical Competency Evaluation Instrument (CCEVI) in assessing the clinical performance of physiotherapy students. This study was carried out between June and September 2013 at University Kebangsaan Malaysia (UKM), Kuala Lumpur, Malaysia. A panel of 10 experts were identified to establish content validity by evaluating and rating each of the items used in the CCEVI with regards to their relevance in measuring students' clinical competency. A total of 50 UKM undergraduate physiotherapy students were assessed throughout their clinical placement to determine the construct validity of these items. The instrument's reliability was determined through a cross-sectional study involving a clinical performance assessment of 14 final-year undergraduate physiotherapy students. The content validity index of the entire CCEVI was 0.91, while the proportion of agreement on the content validity indices ranged from 0.83-1.00. The CCEVI construct validity was established with factor loading of ≥0.6, while internal consistency (Cronbach's alpha) overall was 0.97. Test-retest reliability of the CCEVI was confirmed with a Pearson's correlation range of 0.91-0.97 and an intraclass coefficient correlation range of 0.95-0.98. Inter-rater reliability of the CCEVI domains ranged from 0.59 to 0.97 on initial and subsequent assessments. This pilot study confirmed the content validity of the CCEVI. It showed high internal consistency, thereby providing evidence that the CCEVI has moderate to excellent inter-rater reliability. However, additional refinement in the wording of the CCEVI items, particularly in the domains of safety and documentation, is recommended to further improve the validity and reliability of the instrument.

21 CFR 1271.75 - How do I screen a donor?

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Risk factors for, and clinical evidence of, relevant communicable disease agents and diseases... risk factors for and clinical evidence of relevant cell-associated communicable disease agents and... having either of the following: (1) A risk factor for or clinical evidence of any of the relevant...

Advances in quantitative UV-visible spectroscopy for clinical and pre-clinical application in cancer.

PubMed

Brown, J Quincy; Vishwanath, Karthik; Palmer, Gregory M; Ramanujam, Nirmala

2009-02-01

Methods of optical spectroscopy that provide quantitative, physically or physiologically meaningful measures of tissue properties are an attractive tool for the study, diagnosis, prognosis, and treatment of various cancers. Recent development of methodologies to convert measured reflectance and fluorescence spectra from tissue to cancer-relevant parameters such as vascular volume, oxygenation, extracellular matrix extent, metabolic redox states, and cellular proliferation have significantly advanced the field of tissue optical spectroscopy. The number of publications reporting quantitative tissue spectroscopy results in the UV-visible wavelength range has increased sharply in the past three years, and includes new and emerging studies that correlate optically measured parameters with independent measures such as immunohistochemistry, which should aid in increased clinical acceptance of these technologies.

Managing interoperability and complexity in health systems.

PubMed

Bouamrane, M-M; Tao, C; Sarkar, I N

2015-01-01

In recent years, we have witnessed substantial progress in the use of clinical informatics systems to support clinicians during episodes of care, manage specialised domain knowledge, perform complex clinical data analysis and improve the management of health organisations' resources. However, the vision of fully integrated health information eco-systems, which provide relevant information and useful knowledge at the point-of-care, remains elusive. This journal Focus Theme reviews some of the enduring challenges of interoperability and complexity in clinical informatics systems. Furthermore, a range of approaches are proposed in order to address, harness and resolve some of the many remaining issues towards a greater integration of health information systems and extraction of useful or new knowledge from heterogeneous electronic data repositories.

Neurostimulation systems for deep brain stimulation: in vitro evaluation of magnetic resonance imaging-related heating at 1.5 tesla.

PubMed

Rezai, Ali R; Finelli, Daniel; Nyenhuis, John A; Hrdlicka, Greg; Tkach, Jean; Sharan, Ashwini; Rugieri, Paul; Stypulkowski, Paul H; Shellock, Frank G

2002-03-01

To assess magnetic resonance imaging (MRI)-related heating for a neurostimulation system (Activa Tremor Control System, Medtronic, Minneapolis, MN) used for chronic deep brain stimulation (DBS). Different configurations were evaluated for bilateral neurostimulators (Soletra Model 7426), extensions, and leads to assess worst-case and clinically relevant positioning scenarios. In vitro testing was performed using a 1.5-T/64-MHz MR system and a gel-filled phantom designed to approximate the head and upper torso of a human subject. MRI was conducted using the transmit/receive body and transmit/receive head radio frequency (RF) coils. Various levels of RF energy were applied with the transmit/receive body (whole-body averaged specific absorption rate (SAR); range, 0.98-3.90 W/kg) and transmit/receive head (whole-body averaged SAR; range, 0.07-0.24 W/kg) coils. A fluoroptic thermometry system was used to record temperatures at multiple locations before (1 minute) and during (15 minutes) MRI. Using the body RF coil, the highest temperature changes ranged from 2.5 degrees-25.3 degrees C. Using the head RF coil, the highest temperature changes ranged from 2.3 degrees-7.1 degrees C.Thus, these findings indicated that substantial heating occurs under certain conditions, while others produce relatively minor, physiologically inconsequential temperature increases. The temperature increases were dependent on the type of RF coil, level of SAR used, and how the lead wires were positioned. Notably, the use of clinically relevant positioning techniques for the neurostimulation system and low SARs commonly used for imaging the brain generated little heating. Based on this information, MR safety guidelines are provided. These observations are restricted to the tested neurostimulation system.

Orthodontics is temporomandibular disorder-neutral.

PubMed

Manfredini, Daniele; Stellini, Edoardo; Gracco, Antonio; Lombardo, Luca; Nardini, Luca Guarda; Siciliani, Giuseppe

2016-07-01

To assess if subjects with a clinical diagnosis of temporomandibular disorders (TMDs) have a similar prevalence of orthodontic history as a population of TMD-free individuals and to assess if those subjects who have a history of ideal orthodontics have fewer symptoms than those with a history of nonideal orthodontics. Two groups of age- and sex-matched individuals belonging to either a study ("TMD") or a control group were recruited. Subjects who underwent orthodontic treatment were classified as having a history of ideal or nonideal orthodontics based on the current presence of normal values in five reference occlusal features. The correlation with a history of orthodontic treatment was not clinically significant for any of the TMD diagnoses (ie, muscle pain, joint pain, disc displacement, arthrosis), with Phi (Φ) coefficient values within the -0.120 to 0.058 range. Within the subset of patients with a history of orthodontics, the correlation of ideal or nonideal orthodontic treatment with TMD diagnoses was, in general, not clinically relevant or was weakly relevant. Findings confirmed the substantial absence of clinically significant effects of orthodontics as far as TMD is concerned. The very low correlation values of a negative or positive history of ideal or nonideal orthodontics with the different TMD diagnoses suggest that orthodontic treatment could not have a true role for TMD.

Mutation databases for inherited renal disease: are they complete, accurate, clinically relevant, and freely available?

PubMed

Savige, Judy; Dagher, Hayat; Povey, Sue

2014-07-01

This study examined whether gene-specific DNA variant databases for inherited diseases of the kidney fulfilled the Human Variome Project recommendations of being complete, accurate, clinically relevant and freely available. A recent review identified 60 inherited renal diseases caused by mutations in 132 genes. The disease name, MIM number, gene name, together with "mutation" or "database," were used to identify web-based databases. Fifty-nine diseases (98%) due to mutations in 128 genes had a variant database. Altogether there were 349 databases (a median of 3 per gene, range 0-6), but no gene had two databases with the same number of variants, and 165 (50%) databases included fewer than 10 variants. About half the databases (180, 54%) had been updated in the previous year. Few (77, 23%) were curated by "experts" but these included nine of the 11 with the most variants. Even fewer databases (41, 12%) included clinical features apart from the name of the associated disease. Most (223, 67%) could be accessed without charge, including those for 50 genes (40%) with the maximum number of variants. Future efforts should focus on encouraging experts to collaborate on a single database for each gene affected in inherited renal disease, including both unpublished variants, and clinical phenotypes. © 2014 WILEY PERIODICALS, INC.

Cell-surface central nervous system autoantibodies: Clinical relevance and emerging paradigms

PubMed Central

Irani, Sarosh R; Gelfand, Jeffrey M; Al-Diwani, Adam; Vincent, Angela

2014-01-01

The recent discovery of several potentially pathogenic autoantibodies has helped identify patients with clinically distinctive central nervous system diseases that appear to benefit from immunotherapy. The associated autoantibodies are directed against the extracellular domains of cell-surface–expressed neuronal or glial proteins such as LGI1, N-methyl-D-aspartate receptor, and aquaporin-4. The original descriptions of the associated clinical syndromes were phenotypically well circumscribed. However, as availability of antibody testing has increased, the range of associated patient phenotypes and demographics has expanded. This in turn has led to the recognition of more immunotherapy-responsive syndromes in patients presenting with cognitive and behavioral problems, seizures, movement disorders, psychiatric features, and demyelinating disease. Although antibody detection remains diagnostically important, clinical recognition of these distinctive syndromes should ensure early and appropriate immunotherapy administration. We review the emerging paradigm of cell-surface–directed antibody–mediated neurological diseases, describe how the associated disease spectrums have broadened since the original descriptions, discuss some of the methodological issues regarding techniques for antibody detection and emphasize considerations surrounding immunotherapy administration. As these disorders continue to reach mainstream neurology and even psychiatry, more cell-surface–directed antibodies will be discovered, and their possible relevance to other more common disease presentations should become more clearly defined. PMID:24930434

Who benefits most from THC:CBD spray? Learning from clinical experience.

PubMed

Koehler, Jürgen

2014-01-01

Patients with multiple sclerosis (MS) represent a diverse and heterogeneous population varying in terms of disease type, its severity and variable progression/time-course, and with regard to the wide range of presenting symptoms. Consequently, detailed experience with individual patients is important to provide examples of therapy to specific patient types. In this article, real-life data from clinical practice showing specific aspects relating to use of 9-delta-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®) in patients with moderate to severe spasticity resistant to usual therapy will be presented. Three common clinical scenarios will be considered: MS patients with resistance to usual spasticity therapies; patients with impairment in MS spasticity symptoms; MS patients with relevant impairment in quality of life/activities of daily living (QoL/ADL). These case reports highlight the diverse nature of the MS spasticity population and they show the possible usefulness of THC:CBD oromucosal spray in individual patients with moderate to severe spasticity resistant to existing therapies, within the frame of use approved after large clinical trial results. Perhaps the most important finding is the possibility of obtaining relevant improvements in QoL/ADL in some patients with resistant MS spasticity, allowing them to engage back in physical and social activities. © 2014 S. Karger AG, Basel.

Molecular Phenotyping Combines Molecular Information, Biological Relevance, and Patient Data to Improve Productivity of Early Drug Discovery.

PubMed

Drawnel, Faye Marie; Zhang, Jitao David; Küng, Erich; Aoyama, Natsuyo; Benmansour, Fethallah; Araujo Del Rosario, Andrea; Jensen Zoffmann, Sannah; Delobel, Frédéric; Prummer, Michael; Weibel, Franziska; Carlson, Coby; Anson, Blake; Iacone, Roberto; Certa, Ulrich; Singer, Thomas; Ebeling, Martin; Prunotto, Marco

2017-05-18

Today, novel therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping was applicable to compounds with a range of binding specificities and triaged false positives derived from high-content screening assays. The technique identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. Our results advocate for application of molecular phenotyping in early drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical and pathological implications of miRNA in bladder cancer.

PubMed

Braicu, Cornelia; Cojocneanu-Petric, Roxana; Chira, Sergiu; Truta, Anamaria; Floares, Alexandru; Petrut, Bogdan; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

2015-01-01

MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20-22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer.

What Is the International Classification of Functioning, Disability and Health and Why Is It Relevant to Audiology?

PubMed Central

Meyer, Carly; Grenness, Caitlin; Scarinci, Nerina; Hickson, Louise

2016-01-01

The World Health Organization's International Classification of Functioning, Disability and Health (ICF) is widely used in disability and health sectors as a framework to describe the far-reaching effects of a range of health conditions on individuals. This biopsychosocial framework can be used to describe the experience of an individual in the components of body functions, body structures, and activities and participation, and it considers the influence of contextual factors (environmental and personal) on these components. Application of the ICF in audiology allows the use of a common language between health care professionals in both clinical and research settings. Furthermore, the ICF is promoted as a means of facilitating patient-centered care. In this article, the relevance and application of the ICF to audiology is described, along with clinical examples of its application in the assessment and management of children and adults with hearing loss. Importantly, the skills necessary for clinicians to apply the ICF effectively are discussed. PMID:27489397

Mobile phone interference with medical equipment and its clinical relevance: a systematic review.

PubMed

Lawrentschuk, Nathan; Bolton, Damien M

2004-08-02

To conduct a systematic review of studies on clinically relevant digital mobile phone electromagnetic interference with medical equipment. MEDLINE and SUMSEARCH were searched for the period 1966-2004. The Cochrane Library and Database of Abstracts of Reviews of Effects were also searched for systematic reviews. Studies were eligible if published in a peer-reviewed journal in English, and if they included testing of digital mobile phones for clinically relevant interference with medical equipment used to monitor or treat patients, but not implantable medical devices. As there was considerable heterogeneity in medical equipment studied and the conduct of testing, results were summarised rather than subjected to meta-analysis. Clinically relevant electromagnetic interference (EMI) secondary to mobile phones potentially endangering patients occurred in 45 of 479 devices tested at 900 MHz and 14 of 457 devices tested at 1800 MHz. However, in the largest studies, the prevalence of clinically relevant EMI was low. Most clinically relevant EMI occurred when mobile phones were used within 1 m of medical equipment. Although testing was not standardised between studies and equipment tested was not identical, it is of concern that at least 4% of devices tested in any study were susceptible to clinically relevant EMI. All studies recommend some type of restriction of mobile phone use in hospitals, with use greater than 1 m from equipment and restrictions in clinical areas being the most common.

Comparative evaluation of topographical data of dental implant surfaces applying optical interferometry and scanning electron microscopy.

PubMed

Kournetas, N; Spintzyk, S; Schweizer, E; Sawada, T; Said, F; Schmid, P; Geis-Gerstorfer, J; Eliades, G; Rupp, F

2017-08-01

Comparability of topographical data of implant surfaces in literature is low and their clinical relevance often equivocal. The aim of this study was to investigate the ability of scanning electron microscopy and optical interferometry to assess statistically similar 3-dimensional roughness parameter results and to evaluate these data based on predefined criteria regarded relevant for a favorable biological response. Four different commercial dental screw-type implants (NanoTite Certain Prevail, TiUnite Brånemark Mk III, XiVE S Plus and SLA Standard Plus) were analyzed by stereo scanning electron microscopy and white light interferometry. Surface height, spatial and hybrid roughness parameters (Sa, Sz, Ssk, Sku, Sal, Str, Sdr) were assessed from raw and filtered data (Gaussian 50μm and 5μm cut-off-filters), respectively. Data were statistically compared by one-way ANOVA and Tukey-Kramer post-hoc test. For a clinically relevant interpretation, a categorizing evaluation approach was used based on predefined threshold criteria for each roughness parameter. The two methods exhibited predominantly statistical differences. Dependent on roughness parameters and filter settings, both methods showed variations in rankings of the implant surfaces and differed in their ability to discriminate the different topographies. Overall, the analyses revealed scale-dependent roughness data. Compared to the pure statistical approach, the categorizing evaluation resulted in much more similarities between the two methods. This study suggests to reconsider current approaches for the topographical evaluation of implant surfaces and to further seek after proper experimental settings. Furthermore, the specific role of different roughness parameters for the bioresponse has to be studied in detail in order to better define clinically relevant, scale-dependent and parameter-specific thresholds and ranges. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

The incidence and relevance of site-reported vs. patient-reported angina: insights from the ABSORB II randomized trial comparing Absorb everolimus-eluting bioresorbable scaffold with XIENCE everolimus-eluting metallic stent.

PubMed

Grundeken, Maik J; White, Roseann M; Hernandez, John B; Dudek, Dariusz; Cequier, Angel; Haude, Michael; van Boven, Adrianus J; Piek, Jan J; Helqvist, Steffen; Sabate, Manel; Baumbach, Andreas; Suwannasom, Pannipa; Ishibashi, Yuki; Staehr, Peter; Veldhof, Susan; Cheong, Wai-Fung; de Winter, Robbert J; Garcia-Garcia, Hector M; Wykrzykowska, Joanna J; Onuma, Yoshinobu; Serruys, Patrick W; Chevalier, Bernard

2016-04-01

In the ABSORB II trial, comparing Absorb™ bioresorbable vascular scaffold with metallic XIENCE™ everolimus-eluting stent (EES), a difference was found in site-reported new or worsening angina using adverse event (AE) reporting. However, the clinical relevance of this site-reported angina is unclear. The aim of the present study was therefore to investigate the clinical relevance of site-reported angina by evaluating its relation with cardiac endpoints, cardiovascular resource utilization (including diagnostics and treatment), positive exercise stress tolerance tests (ETTs), and Seattle Angina Questionnaire (SAQ). Site-reported new or worsening angina was captured on cardiac AE forms. There was a wide variation in the total number of days with site-reported angina (overall interquartile range 35-279 days). Patients with site-reported angina showed higher rates of cardiovascular events [including the patient-oriented composite endpoint of all deaths, all myocardial infarctions (MI), or all revascularizations (21.1 vs. 4.2%, P < 0.0001), all MIs (2.3 vs. 0%, P = 0.03), and all revascularizations (21.1 vs. 0.7%, P < 0.0001)], cardiovascular resource utilization (including stress tests, anti-anginal medication, diagnostic angiographies, and hospitalization), and positive ETTs (51.9 vs. 14.9%, P < 0.001), compared with those without site-reported angina. Furthermore, an event-based analysis of the SAQ showed that patients with ongoing angina within the recall period of 4 weeks prior to the SAQ assessment have clinically and statistically significant decrements of >14 points in SAQ scores compared with those with no reported angina. We showed that the site-reported angina through AE reporting may be clinically relevant because of their relation with cardiovascular events (mostly repeat revascularizations), cardiovascular resource utilization, ETT, and SAQ. https://clinicaltrials.gov/ct2/show/NCT01425281; Unique identifier: NCT01425281.

Use of ex vivo and in vitro cultures of the human respiratory tract to study the tropism and host responses of highly pathogenic avian influenza A (H5N1) and other influenza viruses.

PubMed

Chan, Renee W Y; Chan, Michael C W; Nicholls, John M; Malik Peiris, J S

2013-12-05

The tropism of influenza viruses for the human respiratory tract is a key determinant of host-range, and consequently, of pathogenesis and transmission. Insights can be obtained from clinical and autopsy studies of human disease and relevant animal models. Ex vivo cultures of the human respiratory tract and in vitro cultures of primary human cells can provide complementary information provided they are physiologically comparable in relevant characteristics to human tissues in vivo, e.g. virus receptor distribution, state of differentiation. We review different experimental models for their physiological relevance and summarize available data using these cultures in relation to highly pathogenic avian influenza H5N1, in comparison where relevant, with other influenza viruses. Transformed continuous cell-lines often differ in important ways to the corresponding tissues in vivo. The state of differentiation of primary human cells (respiratory epithelium, macrophages) can markedly affect virus tropism and host responses. Ex vivo cultures of human respiratory tissues provide a close resemblance to tissues in vivo and may be used to risk assess animal viruses for pandemic threat. Physiological factors (age, inflammation) can markedly affect virus receptor expression and virus tropism. Taken together with data from clinical studies on infected humans and relevant animal models, data from ex vivo and in vitro cultures of human tissues and cells can provide insights into virus transmission and pathogenesis and may provide understanding that leads to novel therapeutic interventions. Copyright © 2013 Elsevier B.V. All rights reserved.

Agency, Social and Healthcare Supports for Adults with Intellectual Disability at the End of Life in Out-of-Home, Non-Institutional Community Residences in Western Nations: A Literature Review

ERIC Educational Resources Information Center

Moro, Teresa T.; Savage, Teresa A.; Gehlert, Sarah

2017-01-01

Background: The nature and quality of end-of-life care received by adults with intellectual disabilities in out-of-home, non-institutional community agency residences in Western nations is not well understood. Method: A range of databases and search engines were used to locate conceptual, clinical and research articles from relevant peer-reviewed…

Generalized extracellular molecule sensor platform for programming cellular behavior.

PubMed

Scheller, Leo; Strittmatter, Tobias; Fuchs, David; Bojar, Daniel; Fussenegger, Martin

2018-04-23

Strategies for expanding the sensor space of designer receptors are urgently needed to tailor cell-based therapies to respond to any type of medically relevant molecules. Here, we describe a universal approach to designing receptor scaffolds that enables antibody-specific molecular input to activate JAK/STAT, MAPK, PLCG or PI3K/Akt signaling rewired to transgene expression driven by synthetic promoters. To demonstrate its scope, we equipped the GEMS (generalized extracellular molecule sensor) platform with antibody fragments targeting a synthetic azo dye, nicotine, a peptide tag and the PSA (prostate-specific antigen) biomarker, thereby covering inputs ranging from small molecules to proteins. These four GEMS devices provided robust signaling and transgene expression with high signal-to-noise ratios in response to their specific ligands. The sensitivity of the nicotine- and PSA-specific GEMS devices matched the clinically relevant concentration ranges, and PSA-specific GEMS were able to detect pathological PSA levels in the serum of patients diagnosed with prostate cancer.

MO-A-BRB-01: TG191: Clinical Use of Luminescent Dosimeters

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

Kry, S.

This presentation will highlight the upcoming TG-191 report: Clinical Use of Luminescent Dosimeters. Luminescent dosimetry based on TLD and OSLD is a practical, accurate, and precise technique for point dosimetry in medical physics applications. The charges of Task Group 191 were to detail the methodologies for practical and optimal luminescent dosimetry in a clinical setting. This includes (1) To review the variety of TLD/OSL materials available, including features and limitations of each. (2) To outline the optimal steps to achieve accurate and precise dosimetry with luminescent detectors and to evaluate the uncertainty induced when less rigorous procedures are used. (3)more » To develop consensus guidelines on the optimal use of luminescent dosimeters for clinical practice. (4) To develop guidelines for special medically relevant uses of TLDs/OSLs (e.g., mixed field i.e. photon/neutron dosimetry, particle beam dosimetry, skin dosimetry). While this report provides general guidelines for arbitrary TLD and OSLD processes, the report, and therefore this presentation, provide specific guidance for TLD-100 (LiF:Ti,Mg) and nanoDot (Al2O3:C) dosimeters because of their prevalence in clinical practice. Learning Objectives: Understand the available dosimetry systems, and basic theory of their operation Understand the range of dose determination methodologies and the uncertainties associated with them Become familiar with special considerations for TLD/OSLD relevant for special clinical situations Learn recommended commissioning and QA procedures for these dosimetry systems.« less

MO-A-BRB-00: TG191: Clinical Use of Luminescent Dosimeters

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

NONE

This presentation will highlight the upcoming TG-191 report: Clinical Use of Luminescent Dosimeters. Luminescent dosimetry based on TLD and OSLD is a practical, accurate, and precise technique for point dosimetry in medical physics applications. The charges of Task Group 191 were to detail the methodologies for practical and optimal luminescent dosimetry in a clinical setting. This includes (1) To review the variety of TLD/OSL materials available, including features and limitations of each. (2) To outline the optimal steps to achieve accurate and precise dosimetry with luminescent detectors and to evaluate the uncertainty induced when less rigorous procedures are used. (3)more » To develop consensus guidelines on the optimal use of luminescent dosimeters for clinical practice. (4) To develop guidelines for special medically relevant uses of TLDs/OSLs (e.g., mixed field i.e. photon/neutron dosimetry, particle beam dosimetry, skin dosimetry). While this report provides general guidelines for arbitrary TLD and OSLD processes, the report, and therefore this presentation, provide specific guidance for TLD-100 (LiF:Ti,Mg) and nanoDot (Al2O3:C) dosimeters because of their prevalence in clinical practice. Learning Objectives: Understand the available dosimetry systems, and basic theory of their operation Understand the range of dose determination methodologies and the uncertainties associated with them Become familiar with special considerations for TLD/OSLD relevant for special clinical situations Learn recommended commissioning and QA procedures for these dosimetry systems.« less

How Next-Generation Sequencing and Multiscale Data Analysis Will Transform Infectious Disease Management

PubMed Central

Pak, Theodore R.; Kasarskis, Andrew

2015-01-01

Recent reviews have examined the extent to which routine next-generation sequencing (NGS) on clinical specimens will improve the capabilities of clinical microbiology laboratories in the short term, but do not explore integrating NGS with clinical data from electronic medical records (EMRs), immune profiling data, and other rich datasets to create multiscale predictive models. This review introduces a range of “omics” and patient data sources relevant to managing infections and proposes 3 potentially disruptive applications for these data in the clinical workflow. The combined threats of healthcare-associated infections and multidrug-resistant organisms may be addressed by multiscale analysis of NGS and EMR data that is ideally updated and refined over time within each healthcare organization. Such data and analysis should form the cornerstone of future learning health systems for infectious disease. PMID:26251049

Responsiveness of clinical tests for people with neck pain.

PubMed

Jørgensen, René; Ris, Inge; Juhl, Carsten; Falla, Deborah; Juul-Kristensen, Birgit

2017-12-28

Responsiveness of a clinical test is highly relevant in order to evaluate the effect of a given intervention. However, the responsiveness of clinical tests for people with neck pain has not been adequately evaluated. The objective of the present study was to examine the responsiveness of four clinical tests which are low cost and easy to perform in a clinical setting, including the craniocervical flexion test, cervical active range of movement, test for the cervical extensors and pressure pain threshold testing. This study is a secondary analysis of data collected in a previously published randomised controlled trial. Participants were randomized to either physical training, exercises and pain education combined or pain education only. Participants were tested on the clinical tests at baseline and at 4-month follow-up. An anchor-based approach using Receiver Operator Characteristics (ROC) curves was used to evaluate responsiveness of the clinical tests. The Neck Disability Index was used to discriminate between those who had improved and those who were unchanged at the 4-month follow-up. Minimum Clinically Important Difference (MCID), together with sensitivity, specificity, positive and negative predictive values, in addition to positive and negative likelihood ratios were calculated. In total, 164 participants completed the 4 month follow up. One-hundred forty four participants were classified as unchanged whereas 20 patients were considered to be improved. Twenty-six participants didn't complete all of the clinical tests, leaving a total of 138 to be included for analyses. Area Under Curve (AUC) ranged from 0.50-0.62 for the clinical tests, and were all below an acceptable level. MCID was generally large, and the corresponding sensitivity and specificity was low with sensitivity ranging from 20 to 60%, and specificity from 54 to 86%. LR+ (0.8-2.07) and LR- (0.7-1.1) showed low diagnostic value for all variables, with PPV ranging from 12.1 to 26.1 and NPV ranging from 84.7 to 89.2. Responsiveness of the included clinical tests was generally low when using change in NDI score as the anchor from baseline to the 4-month follow up. Further investigations of responsiveness are warranted, possibly using other anchors, which to a higher degree resemble similar dimensions as the clinical tests.

Nurses' views on legalising assisted dying in New Zealand: A cross-sectional study.

PubMed

Wilson, Michael; Oliver, Pam; Malpas, Phillipa

2018-04-15

This study investigated New Zealand nurses' views on legalising assisted dying across a range of clinical conditions, nurses' willingness to engage in legal assisted dying, potential deterrents and enablers to such engagement, and nurses' perceptions of the proper role of their professional bodies in relation to legalising assisted dying. A Bill for legalising assisted dying is currently before the New Zealand parliament. Of the 16 jurisdictions where assisted dying has been specifically legislated, only the Canadian federal statute provides nurses with explicit legal protection for their performance of assisted dying-related tasks. An absence of policy development and planning for safe nursing practice prior to legalisation of assisted dying results in a gap in professional support and guidance. Exploratory cross-sectional survey. A self-selected sample of 475 New Zealand nurses responded to an anonymous online survey disseminated through the newsletters and websites of relevant medical and nursing professional bodies. A sub-sample of nurses who expressed support for or ambivalence about legalisation (n = 356): rated their level of support for legalising assisted dying in New Zealand across a range of medical conditions, and their willingness to participate in a range of assisted dying tasks; identified barriers and facilitators to potential participation; and assessed the responsibility of the professional bodies to provide practice supports. Mixed-method approach using descriptive analysis of quantitative data; qualitative data were analysed thematically. Nurses supported legalisation at a rate (67%) significantly greater than that of doctors (37%) and for a diverse range of medical conditions. Most supporting nurses were willing to engage in the full range of relevant assisted dying roles. They identified several practical and ethical supports as essential to safe engagement, in particular practice guidelines, specific training, legal protections, clinical supervision and mentoring, and independent review of assisted dying service provision. They saw the facilitation of these supports as primarily the responsibility of their professional bodies. Nursing bodies should proactively facilitate workforce awareness and development of assisted dying policy and practice supports in anticipation of legalisation. This can be done through information campaigns and by adapting assisted dying policy, practice materials and systems already developed internationally. Nursing bodies need to engage in formulating legislation to ensure inclusion of explicit protections for participating nurses and to delegate relevant responsibilities to regulatory bodies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Duration-dependent effects of clinically relevant oral alendronate doses on cortical bone toughness in beagle dogs

PubMed Central

Burr, David B.; Liu, Ziyue; Allen, Matthew R.

2014-01-01

Bisphosphonates (BPs) have been shown to significantly reduce bone toughness in vertebrae within one year when given at clinical doses to dogs. Although BPs also reduce toughness in cortical bone when given at high doses, their effect on cortical bone material properties when given at clinical doses is less clear. In part, this may be due to the use of small sample sizes that were powered to demonstrate differences in bone mineral density rather than bone’s material properties. Our lab has conducted several studies in which dogs were treated with alendronate at a clinically relevant dose. The goal of this study was to examine these published and unpublished data collectively to determine whether there is a significant time-dependent effect of alendronate on toughness of cortical bone. This analysis seemed particularly relevant given the recent occurrence of atypical femoral fractures in humans. Differences in the toughness of ribs taken from dogs derived from five separate experiments were measured. The dogs were orally administered saline (CON, 1 ml/kg/day) or alendronate (ALN) at a clinical dose (0.2 mg/kg/day). Treatment duration ranged from 3 months to 3 years. Groups were compared using ANOVA, and time trends analyzed with linear regression analysis. Linear regressions of the percent difference in toughness between CON and ALN at each time point revealed a significant reduction in toughness with longer exposure to ALN. The downward trend was primarily driven by a downward trend in post-yield toughness, whereas toughness in the pre-yield region was not changed relative to CON. These data suggest that a longer duration of treatment with clinical doses of ALN results in deterioration of cortical bone toughness in a time-dependent manner. As the duration of treatment is lengthened, the cortical bone exhibits increasingly brittle behavior. This may be important in assessing the role that long-term BP treatments play in the risk of atypical fractures of femoral cortical bone in humans. PMID:25445446

Clinical relevance of findings in trials of CBT for depression.

PubMed

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

2017-09-01

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

Activation of photodynamic therapy in vitro with Cerenkov luminescence generated from Yttrium-90 (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hartl, Brad A.; Hirschberg, Henry; Marcu, Laura; Cherry, Simon R.

2016-03-01

Translation of photodynamic therapy to the clinical setting has primarily been limited to easily accessible and/or superficial diseases where traditional light delivery can be performed noninvasively. Cerenkov luminescence, as generated from medically relevant radionuclides, has been suggested as a means to deliver light to deeper tissues noninvasively in order to overcome this depth limitation. We report on the use of Cerenkov luminescence generated from Yttrium-90 as a means to active the photodynamic therapy process in monolayer tumor cell cultures. The current study investigates the utility of Cerenkov luminescence for activating both the clinically relevant aminolevulinic acid at 1.0 mM and also the more efficient photosensitizer TPPS2a at 1.2 µM. Cells were incubated with aminolevulinic acid for 6 hours prior to radionuclide addition, as well as additional daily treatments for three days. TPPS2a was delivered as a single treatment with an 18 hour incubation time before radionuclide addition. Experiments were completed for both C6 glioma cells and MDA-MB-231 breast tumor cells. Although aminolevulinic acid proved ineffective for generating a therapeutic effect at any activity for either cell line, TPPS2a produced at least a 20% therapeutic effect at activities ranging from 6 to 60 µCi/well for the C6 cell line. Current results demonstrate that it may be possible to generate a therapeutic effect in vivo using Cerenkov luminescence to activate the photodynamic therapy process with clinically relevant photosensitizers.

Reference intervals and allometric scaling of two-dimensional echocardiographic measurements in 150 healthy cats.

PubMed

Karsten, Schober; Stephanie, Savino; Vedat, Yildiz

2017-11-10

The objective of the study was to evaluate the effects of body weight (BW), breed, and sex on two-dimensional (2D) echocardiographic measures, reference ranges, and prediction intervals using allometrically-scaled data of left atrial (LA) and left ventricular (LV) size and LV wall thickness in healthy cats. Study type was retrospective, observational, and clinical cohort. 150 healthy cats were enrolled and 2D echocardiograms analyzed. LA diameter, LV wall thickness, and LV dimension were quantified using three different imaging views. The effect of BW, breed, sex, age, and interaction (BW*sex) on echocardiographic variables was assessed using univariate and multivariate regression and linear mixed model analysis. Standard (using raw data) and allometrically scaled (Y=a × M b ) reference intervals and prediction intervals were determined. BW had a significant (P<0.05) independent effect on 2D variables whereas breed, sex, and age did not. There were clinically relevant differences between reference intervals using mean ± 2SD of raw data and mean and 95% prediction interval of allometrically-scaled variables, most prominent in larger (>6 kg) and smaller (<3 kg) cats. A clinically relevant difference between thickness of the interventricular septum (IVS) and dimension of the LV posterior wall (LVPW) was identified. In conclusion, allometric scaling and BW-based 95% prediction intervals should be preferred over conventional 2D echocardiographic reference intervals in cats, in particular in small and large cats. These results are particularly relevant to screening examinations for feline hypertrophic cardiomyopathy.

Drug development in neuropsychopharmacology.

PubMed

Fritze, Jürgen

2008-03-01

Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

Determining Health-Related Quality-of-Life Outcomes Using the SF-6D Following Total Hip Arthroplasty.

PubMed

Elmallah, Randa K; Chughtai, Morad; Adib, Farshad; Bozic, Kevin J; Kurtz, Steven M; Mont, Michael A

2017-03-15

Following total hip arthroplasty, patients' perception of their postoperative improvement and health plays a large role in satisfaction with and success of the surgical procedure. The Short Form-6D (SF-6D) is a health-related quality-of-life measure that assigns numerical value to the perception of patients' own health. The purpose was to determine SF-6D values of patients after total hip arthroplasty, to determine whether score changes were clinically relevant, and to compare these with postoperative functional improvements. We evaluated 188 patients who underwent primary total hip arthroplasty at 7 institutions and who had a mean age of 69 years (range, 47 to 88 years) and a mean body mass index of 28.8 kg/m (range, 19.8 to 38.9 kg/m). The SF-6D values were obtained from patients' SF-36 scores, and clinical relevance of value changes was determined using effect size. Using previous research, effect sizes were considered small between 0.2 and 0.5, moderate between 0.6 to 0.8, and large at >0.8. Clinical correlation was assessed using the Lower-Extremity Activity Scale and Harris hip scores. Patients were assessed preoperatively and postoperatively at 6 months and 1, 2, 3, and 5 years. The SF-6D scores improved from preoperatively and achieved significance (p < 0.05) at all points. The effect size demonstrated good clinical relevance up to the latest follow-up: 1.27 at 6 months, 1.30 at 1 year, 1.07 at 2 years, 1.08 at 3 years, and 1.05 at 5 years. The Lower-Extremity Activity Scale improved at all follow-up points from preoperatively to 1.8 at 6 months, 2.0 at 1 year, 1.8 at 2 years, 1.5 at 3 years, and 1.6 points at 5 years. The Harris hip score improved to 38 points at 6 months, 40 points at 1 year, 38 points at 2 years, 39 points at 3 years, and 41 points at 5 years postoperatively. The improvements in the Lower-Extremity Activity Scale and the Harris hip score significantly positively correlated (p < 0.01) with the SF-6D scores at all time points. SF-6D scores after total hip arthroplasty correlate with functional outcomes and have clinical relevance, as demonstrated by their effect size. Incorporating this straightforward and easy-to-use measurement tool when evaluating patients following total hip arthroplasty will facilitate future cost-utility analyses. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis

PubMed Central

Alton, Eric W F W; Beekman, Jeffery M; Boyd, A Christopher; Brand, June; Carlon, Marianne S; Connolly, Mary M; Chan, Mario; Conlon, Sinead; Davidson, Heather E; Davies, Jane C; Davies, Lee A; Dekkers, Johanna F; Doherty, Ann; Gea-Sorli, Sabrina; Gill, Deborah R; Griesenbach, Uta; Hasegawa, Mamoru; Higgins, Tracy E; Hironaka, Takashi; Hyndman, Laura; McLachlan, Gerry; Inoue, Makoto; Hyde, Stephen C; Innes, J Alastair; Maher, Toby M; Moran, Caroline; Meng, Cuixiang; Paul-Smith, Michael C; Pringle, Ian A; Pytel, Kamila M; Rodriguez-Martinez, Andrea; Schmidt, Alexander C; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Toshner, Richard; Tsugumine, Shu; Wasowicz, Marguerite W; Zhu, Jie

2017-01-01

We have recently shown that non-viral gene therapy can stabilise the decline of lung function in patients with cystic fibrosis (CF). However, the effect was modest, and more potent gene transfer agents are still required. Fuson protein (F)/Hemagglutinin/Neuraminidase protein (HN)-pseudotyped lentiviral vectors are more efficient for lung gene transfer than non-viral vectors in preclinical models. In preparation for a first-in-man CF trial using the lentiviral vector, we have undertaken key translational preclinical studies. Regulatory-compliant vectors carrying a range of promoter/enhancer elements were assessed in mice and human air–liquid interface (ALI) cultures to select the lead candidate; cystic fibrosis transmembrane conductance receptor (CFTR) expression and function were assessed in CF models using this lead candidate vector. Toxicity was assessed and ‘benchmarked’ against the leading non-viral formulation recently used in a Phase IIb clinical trial. Integration site profiles were mapped and transduction efficiency determined to inform clinical trial dose-ranging. The impact of pre-existing and acquired immunity against the vector and vector stability in several clinically relevant delivery devices was assessed. A hybrid promoter hybrid cytosine guanine dinucleotide (CpG)- free CMV enhancer/elongation factor 1 alpha promoter (hCEF) consisting of the elongation factor 1α promoter and the cytomegalovirus enhancer was most efficacious in both murine lungs and human ALI cultures (both at least 2-log orders above background). The efficacy (at least 14% of airway cells transduced), toxicity and integration site profile supports further progression towards clinical trial and pre-existing and acquired immune responses do not interfere with vector efficacy. The lead rSIV.F/HN candidate expresses functional CFTR and the vector retains 90–100% transduction efficiency in clinically relevant delivery devices. The data support the progression of the F/HN-pseudotyped lentiviral vector into a first-in-man CF trial in 2017. PMID:27852956

PROMIS Fatigue Item Bank had Clinical Validity across Diverse Chronic Conditions.

PubMed

Cella, David; Lai, Jin-Shei; Jensen, Sally E; Christodoulou, Christopher; Junghaenel, Doerte U; Reeve, Bryce B; Stone, Arthur A

2016-05-01

To evaluate the comparability and responsiveness of Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue item bank across six chronic conditions. Individuals (n = 1,430) with chronic obstructive pulmonary disease (n = 125), chronic heart failure (n = 60), chronic back pain (n = 218), major depressive disorder (n = 196), rheumatoid arthritis (n = 521), and cancer (n = 310) completed assessments from the PROMIS fatigue item bank at baseline and a clinically relevant follow-up. The cancer and arthritis samples were followed in observational studies; the other four groups were enrolled immediately before a planned clinical intervention. All participants completed global ratings of change at follow-up. Linear mixed-effects models and standardized response means were estimated to examine clinical validity and responsiveness to change. All patient groups reported more fatigue than the general population (range = 0.2-1.29 standard deviation worse). The four clinical groups with pretreatment baseline data experienced significant improvement in fatigue at follow-up (effect size range = 0.25-0.91). Individuals reporting better overall health usually experienced larger fatigue changes than those reporting worse overall health. The results support the PROMIS fatigue measures's responsiveness to change in six different chronic conditions. In addition, these results support the ability of the PROMIS fatigue measures to compare differences in fatigue across a range of chronic conditions, thereby enabling comparative effectiveness research. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non-Small-Cell Lung Cancer.

PubMed

van Leeuwen, Roelof W F; Peric, Robert; Hussaarts, Koen G A M; Kienhuis, Emma; IJzerman, Nikki S; de Bruijn, Peter; van der Leest, Cor; Codrington, Henk; Kloover, Jeroen S; van der Holt, Bronno; Aerts, Joachim G; van Gelder, Teun; Mathijssen, Ron H J

2016-04-20

Erlotinib depends on stomach pH for its bioavailability. When erlotinib is taken concurrently with a proton pump inhibitor (PPI), stomach pH increases, which results in a clinically relevant decrease of erlotinib bioavailability. We hypothesized that this drug-drug interaction is reversed by taking erlotinib with the acidic beverage cola. The effects of cola on erlotinib bioavailability in patients not treated with a PPI were also studied. In this randomized, cross-over, pharmacokinetic study in patients with non-small-cell lung cancer, we studied intrapatient differences in absorption (area under the plasma concentration time curve [AUC0-12h]) after a 7-day period of concomitant treatment with erlotinib, with or without esomeprazole, with either cola or water. At the 7th and 14th day, patients were hospitalized for 1 day for pharmacokinetic sampling. Twenty-eight evaluable patients were included in the analysis. In patients treated with erlotinib and esomeprazole with cola, the mean AUC0-12h increased 39% (range, -12% to 136%; P = .004), whereas in patients not treated with the PPI, the mean AUC0-12h was only slightly higher (9%; range, -10% to +30%; P = .03) after erlotinib intake with cola. Cola intake led to a clinically relevant and statistically significant increase in the bioavailability of erlotinib during esomeprazole treatment. In patients not treated with the PPI, the effects of cola were marginal. These findings can be used to optimize the management of drug-drug interactions between PPIs and erlotinib. © 2016 by American Society of Clinical Oncology.

Accuracy of the Microsoft Kinect sensor for measuring movement in people with Parkinson's disease.

PubMed

Galna, Brook; Barry, Gillian; Jackson, Dan; Mhiripiri, Dadirayi; Olivier, Patrick; Rochester, Lynn

2014-04-01

The Microsoft Kinect sensor (Kinect) is potentially a low-cost solution for clinical and home-based assessment of movement symptoms in people with Parkinson's disease (PD). The purpose of this study was to establish the accuracy of the Kinect in measuring clinically relevant movements in people with PD. Nine people with PD and 10 controls performed a series of movements which were measured concurrently with a Vicon three-dimensional motion analysis system (gold-standard) and the Kinect. The movements included quiet standing, multidirectional reaching and stepping and walking on the spot, and the following items from the Unified Parkinson's Disease Rating Scale: hand clasping, finger tapping, foot, leg agility, chair rising and hand pronation. Outcomes included mean timing and range of motion across movement repetitions. The Kinect measured timing of movement repetitions very accurately (low bias, 95% limits of agreement <10% of the group mean, ICCs >0.9 and Pearson's r>0.9). However, the Kinect had varied success measuring spatial characteristics, ranging from excellent for gross movements such as sit-to-stand (ICC=.989) to very poor for fine movement such as hand clasping (ICC=.012). Despite this, results from the Kinect related strongly to those obtained with the Vicon system (Pearson's r>0.8) for most movements. The Kinect can accurately measure timing and gross spatial characteristics of clinically relevant movements but not with the same spatial accuracy for smaller movements, such as hand clasping. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Evaluating beneficial drug effects in a non‐interventional setting: a review of effectiveness studies based on Swedish Prescribed Drug Register data

PubMed Central

Hoffmann, Mikael

2017-01-01

Aims To describe and assess current effectiveness studies published up to 2014 using Swedish Prescribed Drug Register (SPDR) data. Methods Study characteristics were extracted. Each study was assessed concerning the clinical relevance of the research question, the risk of bias according to a structured checklist, and as to whether its findings contributed to new knowledge. The biases encountered and ways of handling these were retrieved. Results A total of 24 effectiveness studies were included in the review, the majority on cardiovascular or psychiatric disease (n = 17; 71%). The articles linked data from four (interquartile range: three to four) registers, and were published in 21 different journals with an impact factor ranging from 1.58 to 51.66. All articles had a clinically relevant research question. According to the systematic quality assessments, the overall risk of bias was low in one (4%), moderate in eight (33%) and high in 15 (62%) studies. Overall, two (8%) studies were assessed as contributing to new knowledge. Frequently occurring problems were selection bias making the comparison groups incomparable, treatment bias with suboptimal handling of drug exposure and an intention‐to‐treat approach, and assessment bias including immortal time bias. Good examples of how to handle bias problems included propensity score matching and sensitivity analyses. Conclusion Although this review illustrates that effectiveness studies based on dispensed drug register data can contribute to new evidence of intended effects of drug treatment in clinical practice, the expectations of such data to provide valuable information need to be tempered due to methodological issues. PMID:27928842

Diagnostic tests in HIV management: a review of clinical and laboratory strategies to monitor HIV-infected individuals in developing countries.

PubMed Central

Kimmel, April D.; Losina, Elena; Freedberg, Kenneth A.; Goldie, Sue J.

2006-01-01

We conducted a systematic review on the performance of diagnostic tests for clinical and laboratory monitoring of HIV-infected adults in developing countries. Diagnostic test information collected from computerized databases, bibliographies and the Internet were categorized as clinical (non-laboratory patient information), immunologic (information from immunologic laboratory tests), or virologic (information from virologic laboratory tests). Of the 51 studies selected for the review 28 assessed immunologic tests, 12 virologic tests and seven clinical and immunologic tests. Methods of performance evaluation were primarily sensitivity and specificity for the clinical category and correlation coefficients for immunologic and virologic categories. In the clinical category, the majority of test performance measures was reported as >70% sensitive and >65% specific. In the immunologic category, correlation coefficients ranged from r=0.54 to r=0.99 for different CD4 count enumeration techniques, while correlation for CD4 and total lymphocyte counts was between r=0.23 and r=0.74. In the virologic category, correlation coefficients for different human immunodeficiency virus (HIV) ribonucleic acid (RNA) quantification techniques ranged from r=0.54 to r=0.90. Future research requires consensus on designing studies, and collecting and reporting data useful for decision-makers. We recommend classifying information into clinically relevant categories, using a consistent definition of disease across studies and providing measures of both association and accuracy. PMID:16878233

Improved modeling of clinical data with kernel methods.

PubMed

Daemen, Anneleen; Timmerman, Dirk; Van den Bosch, Thierry; Bottomley, Cecilia; Kirk, Emma; Van Holsbeke, Caroline; Valentin, Lil; Bourne, Tom; De Moor, Bart

2012-02-01

Despite the rise of high-throughput technologies, clinical data such as age, gender and medical history guide clinical management for most diseases and examinations. To improve clinical management, available patient information should be fully exploited. This requires appropriate modeling of relevant parameters. When kernel methods are used, traditional kernel functions such as the linear kernel are often applied to the set of clinical parameters. These kernel functions, however, have their disadvantages due to the specific characteristics of clinical data, being a mix of variable types with each variable its own range. We propose a new kernel function specifically adapted to the characteristics of clinical data. The clinical kernel function provides a better representation of patients' similarity by equalizing the influence of all variables and taking into account the range r of the variables. Moreover, it is robust with respect to changes in r. Incorporated in a least squares support vector machine, the new kernel function results in significantly improved diagnosis, prognosis and prediction of therapy response. This is illustrated on four clinical data sets within gynecology, with an average increase in test area under the ROC curve (AUC) of 0.023, 0.021, 0.122 and 0.019, respectively. Moreover, when combining clinical parameters and expression data in three case studies on breast cancer, results improved overall with use of the new kernel function and when considering both data types in a weighted fashion, with a larger weight assigned to the clinical parameters. The increase in AUC with respect to a standard kernel function and/or unweighted data combination was maximum 0.127, 0.042 and 0.118 for the three case studies. For clinical data consisting of variables of different types, the proposed kernel function--which takes into account the type and range of each variable--has shown to be a better alternative for linear and non-linear classification problems. Copyright © 2011 Elsevier B.V. All rights reserved.

Dissemination of research into clinical nursing literature.

PubMed

Oermann, Marilyn H; Shaw-Kokot, Julia; Knafl, George J; Dowell, Jo

2010-12-01

The purpose of our study was to describe the dissemination of research into the clinical nursing literature. The literature provides a means of transferring knowledge from a research study through citations of the work by other authors. This was a citation analysis study to explore the dissemination of research into the clinical nursing literature, beginning with the publication of an original research study and including all of the citations to that article through 2009. The authors searched five academic nursing research journal titles, using CINAHL, for original research reports that had clinical relevance and were published between 1990-1999. The search process yielded a final data set of 28 research articles. For each of the articles, the authors searched three databases, CINAHL, Web of Science(®) and Google Scholar, to determine the citation patterns from the date of publication to August 2009. All of the research studies were cited in articles published in clinical journals although there was a wide range in the number of citations, from 3-80. The 28 research articles had a total of 759 citations; 717 (94.5%) of those citations were in articles published in clinical nursing journals. The median length of time between publication of the original study and the first citation was 1.5 years. Some of the studies were still being cited for 18 years after publication of the original work. All of the original research reports examined in this study were cited in articles in clinical journals, disseminating the research beyond the original work to reach clinicians. Clinical nursing journals keep readers up-to-date and informed about new practices in nursing and serve another important role: they disseminate research that is clinically relevant by publishing original studies and papers that cite research reports. © 2010 Blackwell Publishing Ltd.

Flexible parametric survival models built on age-specific antimüllerian hormone percentiles are better predictors of menopause.

PubMed

Ramezani Tehrani, Fahimeh; Mansournia, Mohammad Ali; Solaymani-Dodaran, Masoud; Steyerberg, Ewout; Azizi, Fereidoun

2016-06-01

This study aimed to improve existing prediction models for age at menopause. We identified all reproductive aged women with regular menstrual cycles who met our eligibility criteria (n = 1,015) in the Tehran Lipid and Glucose Study-an ongoing population-based cohort study initiated in 1998. Participants were examined every 3 years and their reproductive histories were recorded. Blood levels of antimüllerian hormone (AMH) were measured at the time of recruitment. Age at menopause was estimated based on serum concentrations of AMH using flexible parametric survival models. The optimum model was selected according to Akaike Information Criteria and the realness of the range of predicted median menopause age. We followed study participants for a median of 9.8 years during which 277 women reached menopause and found that a spline-based proportional odds model including age-specific AMH percentiles as the covariate performed well in terms of statistical criteria and provided the most clinically relevant and realistic predictions. The range of predicted median age at menopause for this model was 47.1 to 55.9 years. For those who reached menopause, the median of the absolute mean difference between actual and predicted age at menopause was 1.9 years (interquartile range 2.9). The model including the age-specific AMH percentiles as the covariate and using proportional odds as its covariate metrics meets all the statistical criteria for the best model and provides the most clinically relevant and realistic predictions for age at menopause for reproductive-aged women.

Hypoglycaemia in hospitalised neonatal calves: Prevalence, associated conditions and impact on prognosis.

PubMed

Trefz, F M; Feist, M; Lorenz, I

2016-11-01

Hypoglycaemia has traditionally been associated with neonatal diarrhoea and endotoxaemia in calves, but the clinical relevance of this finding in spontaneously diseased calves has not previously been evaluated. To determine the prevalence and prognostic relevance of severe hypoglycaemia (plasma glucose concentration < 2 mmol/L), data from 10,060 hospitalised calves (≤21 days of age) were retrospectively analysed. Additionally, clinical findings and diagnoses in a subset of 100 calves with severe hypoglycaemia were compared with those in 100 randomly selected calves with initial plasma glucose concentrations in the reference range (4.4-6.9 mmol/L). The prevalence of severe hypoglycaemia in the whole study sample was 6.3%. Severe hypoglycaemia was associated with a poor survival rate of 20.6% vs. 74.0% discharged animals in the group of calves with initial normoglycaemia. Review of medical records revealed that severe hypoglycaemia was significantly associated with clinical or necropsy evidence of septicaemia, hypothermia, history or clinical evidence of malnutrition, and peritonitis of varied origin, but not with the presence of neonatal diarrhoea. Only 10 of 100 calves with severe hypoglycaemia showed central nervous involvement such as seizures and opisthotonus. In conclusion, severe hypoglycaemia has a low prevalence in diseased calves in a hospital setting, but is associated with serious health problems and therefore a high risk of non-survival. Severe hypoglycaemia was not easily diagnosed based on clinical signs, but should be suspected in calves with clinical evidence of septicaemia, hypothermia, acute abdominal emergencies, and a history or clinical evidence of malnutrition. Copyright © 2016. Published by Elsevier Ltd.

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

PubMed

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

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

Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants.

PubMed

Cuker, Adam; Siegal, Deborah M; Crowther, Mark A; Garcia, David A

2014-09-16

Non-vitamin K oral anticoagulants (NOACs) do not require routine laboratory monitoring. However, laboratory measurement may be desirable in special situations and populations. This study's objective was to systematically review and summarize current evidence regarding laboratory measurement of the anticoagulant activity of dabigatran, rivaroxaban, and apixaban. We searched PubMed and Web of Science for studies that reported a relationship between drug levels of dabigatran, rivaroxaban, and apixaban and coagulation assay results. Study quality was evaluated using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). We identified 17 eligible studies for dabigatran, 15 for rivaroxaban, and 4 for apixaban. For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (APTT) and prothrombin time (PT) are less sensitive and may be normal at trough drug levels. The dilute thrombin time (R(2) = 0.92 to 0.99) and ecarin-based assays (R(2) = 0.92 to 1.00) show excellent linearity across on-therapy drug concentrations and may be used for drug quantification. For rivaroxaban and apixaban, anti-Xa activity is linear (R(2) = 0.89 to 1.00) over a wide range of drug levels and may be used for drug quantification. Undetectable anti-Xa activity likely excludes clinically relevant drug concentrations. The PT is less sensitive (especially for apixaban); a normal PT may not exclude clinically relevant levels. The APTT demonstrates insufficient sensitivity and linearity for quantification. Dabigatran, rivaroxaban, and apixaban exhibit variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in NOAC-treated patients. More information on the relationship between drug levels and clinical outcomes is needed. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Resistant starch: a promising dietary agent for the prevention/treatment of inflammatory bowel disease and bowel cancer.

PubMed

Higgins, Janine A; Brown, Ian L

2013-03-01

Resistant starch represents a diverse range of indigestible starch-based dietary carbohydrates. Resistant starch has been investigated in the past for its effects on bowel health (pH, epithelial thickness, and apoptosis of colorectal cancer cells); reduction in postprandial glycemia; increased insulin sensitivity; and effects on the gut microbiome. This review highlights advances as resistant starch gains clinical relevance as a potential treatment/preventive tool for diseases such as colorectal cancer (CRC) and diabetes. Recent articles have evaluated the comparative physiological effects of different types of resistant starch and investigated the effects of resistant starch on blood lipids, body weight, and defining resistant starch-induced changes to the micriobiome that may be important in health and disease. The most novel and relevant recent data describe a role for resistant starch in ameliorating inflammation; the use of resistant starch for optimal bowel health and prevention of CRC; and, further, that the systemic effects of resistant starch may be important for the treatment of other forms of cancer, such as breast cancer. This review describes advances in resistant starch research highlighting the gastrointestinal effects that are now being linked to systemic, whole body effects with clinical relevance. These effects have important implications for overall health and the prevention or amelioration of various chronic diseases.

Genital herpes stigma: Toward the Measurement and Validation of a highly prevalent yet hidden public health problem.

PubMed

Wang, Katie; Merin, Abigail; Rendina, H Jonathon; Pachankis, John E

2018-02-01

Despite its highly prevalent and stigmatizing nature, genital herpes has received little attention from stigma researchers relative to other sexually transmitted infections. This limitation is of great relevance to researchers and practitioners in both clinical and healthcare settings, given that stigma can cause psychological distress and hinder disclosure to sexual partners, hence contributing to the spread of genital herpes. The present research developed and examined the psychometric properties of a quantitative measure of genital herpes stigma. Two hundred individuals diagnosed with genital herpes recruited through online genital herpes support groups completed a survey containing 37 items adapted from the HIV Stigma Scale, questions about demographic and herpes-related characteristics, and measures of relevant psychosocial variables. A confirmatory factor analysis yielded an 18-item scale with four factors: personalized stigma, disclosure concerns, negative self-image, and concern with public attitudes. All subscales demonstrated good internal consistency, with Cronbach alphas ranging from 0.74 to 0.87. Construct validity was supported by correlations with relevant psychosocial variables, including negative affect, rumination, and perceived social support. As a psychometrically sound assessment tool, the Genital Herpes Stigma Scale can be used in both clinical and research settings to facilitate future efforts to alleviate the negative psychological consequences of this incurable viral infection.

Clinicomanometric factors associated with clinically relevant esophagogastric junction outflow obstruction from the Sandhill high-resolution manometry system.

PubMed

Song, B G; Min, Y W; Lee, H; Min, B-H; Lee, J H; Rhee, P-L; Kim, J J

2018-03-01

Integrated relaxation pressure (IRP) is a key metric for diagnosing esophagogastric junction outflow obstruction (EGJOO). However, its normal value might be different according to the manufacturer of high-resolution manometry (HRM). This study aimed to investigate optimal value of IRP for diagnosing EGJOO in Sandhill HRM and to find clinicomanometric variables to segregate clinically relevant EGJOO. We analyzed 262 consecutive subjects who underwent HRM between June 2011 and December 2016 showing elevated median IRP (> 15 mm Hg) but did not satisfy criteria for achalasia. Clinically relevant subjects were defined as follows: (i) subsequent HRM met achalasia criteria during follow-up (early achalasia); (ii) Eckardt score was decreased at least two points without exceeding a score of 3 after pneumatic dilatation (variant achalasia); and (iii) significant passage disturbance on esophagogram without structural abnormality (possible achalasia). Seven subjects were clinically relevant, including two subjects with early achalasia, four subjects with variant achalasia, and one subject with possible achalasia. All clinically relevant subjects had IRP 20 mm Hg or above. Among subjects (n = 122) with IRP 20 mm Hg or more, clinically relevant group (n = 7) had significantly higher rate of dysphagia (100% vs 24.3%, P < .001) and compartmentalized pressurization (85.7% vs 21.7%, P = .001) compared to clinically non-relevant group (n = 115). Our results suggest that IRP of 20 mm Hg or higher could segregate clinically relevant subjects showing EGJOO in Sandhill HRM. Additionally, if subjects have both dysphagia and compartmentalized pressurization, careful follow-up is essential. © 2017 John Wiley & Sons Ltd.

Clinical Benefits of Joint Mobilization on Ankle Sprains: A Systematic Review and Meta-Analysis.

PubMed

Weerasekara, Ishanka; Osmotherly, Peter; Snodgrass, Suzanne; Marquez, Jodie; de Zoete, Rutger; Rivett, Darren A

2018-07-01

To assess the clinical benefits of joint mobilization for ankle sprains. MEDLINE, MEDLINE In-Process, Embase, AMED, PsycINFO, CINAHL, Cochrane Library, PEDro, Scopus, SPORTDiscus, and Dissertations and Theses were searched from inception to June 2017. Studies investigating humans with grade I or II lateral or medial sprains of the ankle in any pathologic state from acute to chronic, who had been treated with joint mobilization were considered for inclusion. Any conservative intervention was considered as a comparator. Commonly reported clinical outcomes were considered such as ankle range of movement, pain, and function. After screening of 1530 abstracts, 56 studies were selected for full-text screening, and 23 were eligible for inclusion. Eleven studies on chronic sprains reported sufficient data for meta-analysis. Data were extracted using the participants, interventions, comparison, outcomes, and study design approach. Clinically relevant outcomes (dorsiflexion range, proprioception, balance, function, pain threshold, pain intensity) were assessed at immediate, short-term, and long-term follow-up points. Methodological quality was assessed independently by 2 reviewers, and most studies were found to be of moderate quality, with no studies rated as poor. Meta-analysis revealed significant immediate benefits of joint mobilization compared with comparators on improving posteromedial dynamic balance (P=.0004), but not for improving dorsiflexion range (P=.16), static balance (P=.96), or pain intensity (P=.45). Joint mobilization was beneficial in the short-term for improving weight-bearing dorsiflexion range (P=.003) compared with a control. Joint mobilization appears to be beneficial for improving dynamic balance immediately after application, and dorsiflexion range in the short-term. Long-term benefits have not been adequately investigated. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

[Blastocystis spp.: Advances, controversies and future challenges].

PubMed

Del Coco, Valeria F; Molina, Nora B; Basualdo, Juan A; Córdoba, María A

Blastocystis spp. is the most common protozoan detected in human stool samples. In developing countries, infection rates are higher than 20%. The presence of this parasite in the feces of several host species suggests its zoonotic potential. The clinical relevance and the pathogenic role of Blastocystis spp. in the intestinal tract remain unclear. There are several clinical reports that recognize it as the etiologic agent of several intestinal disorders such as diarrhea, inflammatory bowel disease and ulcerative colitis, although the pathogenicity of this parasite has not been proved yet. This wide range of clinical manifestations could be related to the genetic diversity exhibited by this parasite. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Spectrometric determination of clinically relevant fatty acids in the blood serum

NASA Astrophysics Data System (ADS)

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

2017-01-01

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

Virulence of Curvularia in a murine model.

PubMed

Paredes, Katihuska; Capilla, Javier; Sutton, Deanna A; Mayayo, Emilio; Fothergill, Annette W; Guarro, Josep

2013-09-01

We have evaluated the virulence of two clinically relevant species of Curvularia; Curvularia spicifera and C. hawaiiensis, using an experimental model of disseminated infection in immunocompromised mice. Several inocula were tested over a range 1 × 10(3) -1 × 10(6) colony-forming units/animal. Both species had a similar behaviour, producing a high mortality. Tissue burden and histopathology studies demonstrated that lung was the organ most affected. © 2013 Blackwell Verlag GmbH.

Estrogen receptor alpha gene amplification in breast cancer: 25 years of debate

PubMed Central

Holst, Frederik

2016-01-01

Twenty-five years ago, Nembrot and colleagues reported amplification of the estrogen receptor alpha gene (ESR1) in breast cancer, initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration, which affects one of the most important genes in breast cancer. Since then, a multitude of studies on this topic has been published, covering a wide range of divergent results and arguments. The reported prevalence of this alteration in breast cancer ranges from 0% to 75%, suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues. To date, two major issues related to ESR1 amplification remain to be conclusively addressed: (1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1, and (2) the clinical relevance of ESR1 amplification: Such relevance is strongly disputed, with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies, or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1. This review provides a comprehensive summary of the various views on ESR1 amplification, and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research. PMID:27081639

Effect of food on the bioavailability of lesogaberan given as an oral solution or as modified-release capsules in healthy male volunteers.

PubMed

Fransson, Bo; Silberg, Debra G; Niazi, Mohammad; Miller, Frank; Ruth, Magnus; Holmberg, Ann Aurell

2012-04-01

The novel Type B gamma-aminobutyric acid (GABAB)-receptor agonist lesogaberan (AZD3355) has been evaluated as an add-on to proton pump inhibitor treatment for gastroesophageal reflux disease, but the effect of food on the bioavailability of this compound has not been assessed. In this openlabel crossover study, healthy males received single 100 mg doses of lesogaberan (oral solution (A) or oral modified release (MR) capsules with a dissolution rate of 50% (B) or 100% (C) over 4 h) with and without food. Blood plasma concentrations of lesogaberan were assessed over 48 h. A log-transformed geometric mean Cmax and AUC ratio within the 90% confidence interval (CI) range (0.80 - 1.25) was defined as excluding a clinically relevant food effect. Overall, 57 subjects completed the study. Only the oral lesogaberan solution had a fed/fasting Cmax ratio outside the 90% CI range (Cmax ratio: 0.76). AUC ratios were within the 90% CI limits for all three lesogaberan formulations. The only substantial change in tmax associated with food intake was observed for the oral solution (1.0 h without food, 1.8 h with food). In conclusion, a clinically relevant food effect could be excluded for the lesogaberan MR formulations, but not for the oral lesogaberan solution.

Are evoked potentials in patients with adult-onset pompe disease indicative of clinically relevant central nervous system involvement?

PubMed

Wirsching, Andreas; Müller-Felber, Wolfgang; Schoser, Benedikt

2014-08-01

Pompe disease is a multisystem autosomal recessive glycogen storage disease. Autoptic findings in patients with classic infantile and late-onset Pompe disease have proven that accumulation of glycogen can also be found in the peripheral and central nervous system. To assess the functional role of these pathologic findings, multimodal sensory evoked potentials were analyzed. Serial recordings for brainstem auditory, visual, and somatosensory evoked potentials of 11 late-onset Pompe patients were reviewed. Data at the onset of the enzyme replacement therapy with alglucosidase alfa were compared with follow-up recordings at 12 and 24 months. Brainstem auditory evoked potentials showed a delayed peak I in 1/10 patients and an increased I-III and I-V interpeak latency in 1/10 patients, respectively. The III-V interpeak latencies were in the normal range. Visual evoked potentials were completely normal. Median somatosensory evoked potentials showed an extended interpeak latency in 3/9 patients. Wilcoxon tests comparing age-matched subgroups found significant differences in brainstem auditory evoked potentials and visual evoked potentials. We found that the majority of recordings for evoked potentials were within the ranges for standard values, therefore reflecting the lack of clinically relevant central nervous system involvement. Regular surveillance by means of evoked potentials does not seem to be appropriate in late-onset Pompe patients.

Evaluation of several ultrasonography scoring systems for synovitis and comparison to clinical examination: results from a prospective multicentre study of rheumatoid arthritis.

PubMed

Dougados, Maxime; Jousse-Joulin, Sandrine; Mistretta, Frederic; d'Agostino, Maria-Antonietta; Backhaus, Marina; Bentin, Jacques; Chalès, Gérard; Chary-Valckenaere, Isabelle; Conaghan, Philip; Etchepare, Fabien; Gaudin, Philippe; Grassi, Walter; van der Heijde, Désirée; Sellam, Jérémie; Naredo, Esperanza; Szkudlarek, Marcin; Wakefield, Richard; Saraux, Alain

2010-05-01

To evaluate different global ultrasonographic (US) synovitis scoring systems as potential outcome measures of rheumatoid arthritis (RA) according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) filter. To study selected global scoring systems, for the clinical, B mode and power Doppler techniques, the following joints were evaluated: 28 joints (28-joint Disease Activity Score (DAS28)), 20 joints (metacarpophalangeals (MCPs) + metatarsophalangeals (MTPs)) and 38 joints (28 joints + MTPs) using either a binary (yes/no) or a 0-3 grade. The study was a prospective, 4-month duration follow-up of 76 patients with RA requiring anti-tumour necrosis factor (TNF) therapy (complete follow-up data: 66 patients). Intraobserver reliability was evaluated using the intraclass correlation coefficient (ICC), construct validity was evaluated using the Cronbach alpha test and external validity was evaluated using level of correlation between scoring system and C reactive protein (CRP). Sensitivity to change was evaluated using the standardised response mean. Discriminating capacity was evaluated using the standardised mean differences in patients considered by the doctor as significantly improved or not at the end of the study. Different clinimetric properties of various US scoring systems were at least as good as the clinical scores with, for example, intraobserver reliability ranging from 0.61 to 0.97 versus from 0.53 to 0.82, construct validity ranging from 0.76 to 0.89 versus from 0.76 to 0.88, correlation with CRP ranging from 0.28 to 0.34 versus from 0.28 to 0.35 and sensitivity to change ranging from 0.60 to 1.21 versus from 0.96 to 1.36 for US versus clinical scoring systems, respectively. This study suggests that US evaluation of synovitis is an outcome measure at least as relevant as physical examination. Further studies are required in order to achieve optimal US scoring systems for monitoring patients with RA in clinical trials and in clinical practice.

A one-year economic evaluation of six alternative strategies in the management of uninvestigated upper gastrointestinal symptoms in Canadian primary care.

PubMed

Barkun, Alan N; Crott, Ralph; Fallone, Carlo A; Kennedy, Wendy A; Lachaine, Jean; Levinton, Carey; Armstrong, David; Chiba, Naoki; Thomson, Alan; Veldhuyzen van Zanten, Sander; Sinclair, Paul; Escobedo, Sergio; Chakraborty, Bijan; Smyth, Sandra; White, Robert; Kalra, Helen; Nevin, Krista

2010-08-01

The cost-effectiveness of initial strategies in managing Canadian patients with uninvestigated upper gastrointestinalsymptoms remains controversial. To assess the cost-effectiveness of six management approaches to uninvestigated upper gastrointestinal symptoms in the Canadian setting. The present study analyzed data from four randomized trials assessing homogeneous and complementary populations of Canadian patients with uninvestigated upper gastrointestinal symptoms with comparable outcomes. Symptom-free months, qualityadjusted life-years (QALYs) and direct costs in Canadian dollars of two management approaches based on the Canadian Dyspepsia Working Group (CanDys) Clinical Management Tool, and four additional strategies (two empirical antisecretory agents, and two prompt endoscopy) were examined and compared. Prevalence data, probabilities, utilities and costs were included in a Markov model, while sensitivity analysis used Monte Carlo simulations. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were determined. Empirical omeprazole cost $226 per QALY ($49 per symptom-free month) per patient. CanDys omeprazole and endoscopy approaches were more effective than empirical omeprazole, but more costly. Alternatives using H2-receptor antagonists were less effective than those using a proton pump inhibitor. No significant differences were found for most incremental cost-effectiveness ratios. As willingness to pay (WTP) thresholds rose from $226 to $24,000 per QALY, empirical antisecretory approaches were less likely to be the most costeffective choice, with CanDys omeprazole progressively becoming a more likely option. For WTP values ranging from $24,000 to $70,000 per QALY, the most clinically relevant range, CanDys omeprazole was the most cost-effective strategy (32% to 46% of the time), with prompt endoscopy-proton pump inhibitor favoured at higher WTP values. Although no strategy was the indisputable cost effective option, CanDys omeprazole may be the strategy of choiceover a clinically relevant range of WTP assumptions in the initial management of Canadian patients with uninvestigated dyspepsia.

Overview of systematic reviews of therapeutic ranges: methodologies and recommendations for practice.

PubMed

Cooney, Lewis; Loke, Yoon K; Golder, Su; Kirkham, Jamie; Jorgensen, Andrea; Sinha, Ian; Hawcutt, Daniel

2017-06-02

Many medicines are dosed to achieve a particular therapeutic range, and monitored using therapeutic drug monitoring (TDM). The evidence base for a therapeutic range can be evaluated using systematic reviews, to ensure it continues to reflect current indications, doses, routes and formulations, as well as updated adverse effect data. There is no consensus on the optimal methodology for systematic reviews of therapeutic ranges. An overview of systematic reviews of therapeutic ranges was undertaken. The following databases were used: Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts and Reviews of Effects (DARE) and MEDLINE. The published methodologies used when systematically reviewing the therapeutic range of a drug were analyzed. Step by step recommendations to optimize such systematic reviews are proposed. Ten systematic reviews that investigated the correlation between serum concentrations and clinical outcomes encompassing a variety of medicines and indications were assessed. There were significant variations in the methodologies used (including the search terms used, data extraction methods, assessment of bias, and statistical analyses undertaken). Therapeutic ranges should be population and indication specific and based on clinically relevant outcomes. Recommendations for future systematic reviews based on these findings have been developed. Evidence based therapeutic ranges have the potential to improve TDM practice. Current systematic reviews investigating therapeutic ranges have highly variable methodologies and there is no consensus of best practice when undertaking systematic reviews in this field. These recommendations meet a need not addressed by standard protocols.

Clinical relevance of gait research applied to clinical trials in spinal cord injury.

PubMed

Ditunno, John; Scivoletto, Giorgio

2009-01-15

The restoration of walking function following SCI is extremely important to consumers and has stimulated a response of new treatments by scientists, the pharmaceutical industry and clinical entrepreneurs. Several of the proposed interventions: (1) the use of functional electrical stimulation (FES) and (2) locomotor training have been examined in clinical trials and recent reviews of the scientific literature. Each of these interventions is based on research of human locomotion. Therefore, the systematic study of walking function and gait in normal individuals and those with injury to the spinal cord has contributed to the identification of the impairments of walking, the development of new treatments and how they will be measured to determine effectiveness. In this context gait research applied to interventions to improve walking function is of high clinical relevance. This research helps identify walking impairments to be corrected and measures of walking function to be utilized as endpoints for clinical trials. The most common impairments following SCI diagnosed by observational gait analysis include inadequate hip extension during stance, persistent plantar flexion and hip/knee flexion during swing and foot placement at heel strike. FES has been employed as one strategy for correcting these impairments based on analysis that range from simple measures of speed, cadence and stride length to more sophisticated systems of three- dimensional video motion analysis and multichannel EMG tracings of integrated walking. A recent review of the entire FES literature identified 36 studies that merit comment and the full range of outcome measures for walking function were used from simple velocity to the video analysis of motion. In addition to measures of walking function developed for FES interventions, the first randomized multicenter clinical trial on locomotor training in subacute SCI was recently published with an extensive review of these measures. In this study outcome measures of motor strength (impairment), balance, Walking Index for SCI (WISCI), speed, 5min walk (walking capacities) and locomotor functional independence measure (L-FIM), a disability measure all showed improvement in walking function based on the strategy of the response of activity based plasticity to step training. Although the scientific basis for this intervention will be covered in other articles in this series, the evolution of clinical outcome measures of walking function continues to be important for the determination of effectiveness in clinical trials.

Pharmacokinetics, Dose Proportionality, and Bioavailability of Bazedoxifene in Healthy Postmenopausal Women.

PubMed

McKeand, William

2017-09-01

Bazedoxifene is a selective estrogen receptor modulator that has estrogen agonist effects on bone and lipid metabolism while having neutral or estrogen antagonist effects on the breast and endometrium. The present report describes findings from 3 Phase I clinical studies that evaluated the single-dose pharmacokinetics (study 1; n = 84), multiple-dose pharmacokinetics (study 2; n = 23), and absolute bioavailability (study 3; n = 18) of bazedoxifene. All 3 studies enrolled healthy postmenopausal women who were either naturally postmenopausal or had undergone bilateral oophorectomy at least 6 months before the start of the study. Study 1 showed that unconjugated and total (unconjugated and conjugated) bazedoxifene levels increased proportionally with ascending oral doses of bazedoxifene (through the dose range of 5-120 mg). Evaluation with or without food intake was conducted at the 10-mg dose, with no clinically relevant effect on pharmacokinetic parameters. Study 2 showed that bazedoxifene achieved steady state in 1 week and exhibited linear pharmacokinetics in doses of 5 to 40 mg with no unexpected accumulation over the dose range. In accordance with a linear pharmacokinetic profile, mean maximum plasma concentration values increased with increasing dose, with values of 1.6, 6.2, and 12.5 ng/mL for the 5-, 20-, and 40-mg doses, respectively. In study 3, tablet and capsule formulations of bazedoxifene formulations had an estimated oral bioavailability of ~6%. The clearance of bazedoxifene was 0.4 (0.1) L/h/kg based on intravenous administration. The oral formulations had comparable exposure profiles with respect to AUC and AUC0-t, and the 90% CIs for these values were within the bioequivalence limits of 80% to 125%. Bazedoxifene was safe and well tolerated in all 3 studies. These pharmacokinetic evaluations in healthy postmenopausal women found that bazedoxifene displayed linear pharmacokinetics with doses ranging from 5 to 40 mg, with no unexpected accumulation. Food did not seem to have any clinically relevant impact on pharmacokinetic parameters. Bazedoxifene had an estimated oral bioavailability of ~6% and was safe and well tolerated in the range of doses evaluated. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Translational epigenetics: clinical approaches to epigenome therapeutics for cancer.

PubMed

Selcuklu, S Duygu; Spillane, Charles

2008-01-01

Cancer epigenetics research is now entering an exciting phase of translational epigenetics whereby novel epigenome therapeutics is being developed for application in clinical settings. Epigenetics refers to all heritable and potentially reversible changes in gene or genome functioning that occurs without altering the nucleotide sequence of the DNA. A range of different epigenetic "marks" can activate or repress gene expression. While epigenetic alterations are associated with most cancers, epigenetic dysregulation can also have a causal role in cancer etiology. Epigenetically disrupted stem or progenitor cells could have an early role in neoplastic transformations, while perturbance of epigenetic regulatory mechanisms controlling gene expression in cancer-relevant pathways will also be a contribution factor. The reversibility of epigenetic marks provides the possibility that the activity of key cancer genes and pathways can be regulated as a therapeutic approach. The growing availability of a range of chemical agents which can affect epigenome functioning has led to a range of epigenetic-therapeutic approaches for cancer and intense interest in the development of second-generation epigenetic drugs (epi-drugs) which would have greater specificity and efficacy in clinical settings. The latest developments in this exciting arena of translational cancer epigenetics were presented at a recent conference on "Epigenetics and New Therapies in Cancer" at the Spanish National Cancer Research Center (CNIO), Spain.

Design and testing of classroom and clinical teaching evaluation tools for nursing education.

PubMed

Emerson, Roberta J; Records, Kathie

2007-01-01

Student evaluations of teaching provide administrators an overall picture of the effectiveness of personnel and contribute data for promotion and merit decisions. These evaluations must be assessed for their relevance, validity, and reliability. This paper describes the development process and psychometric testing for clinical (n = 149) and didactic (n = 148) student evaluation of teaching forms for undergraduate and graduate courses in one college of nursing. Validity and reliability results were quite strong for the instruments, both of which evidenced a one-factor solution with factor loadings ranging from .68-.88 and Cronbach's alphas of .96 (Classroom) and .95 (Clinical). The clinical and classroom evaluation tools are relatively short, decreasing the burden on students who need to complete the instruments for multiple instructors in any one semester. Initial testing of the psychometric properties of the tools supports their continued use in colleges of nursing.

How next-generation sequencing and multiscale data analysis will transform infectious disease management.

PubMed

Pak, Theodore R; Kasarskis, Andrew

2015-12-01

Recent reviews have examined the extent to which routine next-generation sequencing (NGS) on clinical specimens will improve the capabilities of clinical microbiology laboratories in the short term, but do not explore integrating NGS with clinical data from electronic medical records (EMRs), immune profiling data, and other rich datasets to create multiscale predictive models. This review introduces a range of "omics" and patient data sources relevant to managing infections and proposes 3 potentially disruptive applications for these data in the clinical workflow. The combined threats of healthcare-associated infections and multidrug-resistant organisms may be addressed by multiscale analysis of NGS and EMR data that is ideally updated and refined over time within each healthcare organization. Such data and analysis should form the cornerstone of future learning health systems for infectious disease. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Trustworthiness and relevance in web-based clinical question answering.

PubMed

Cruchet, Sarah; Boyer, Célia; van der Plas, Lonneke

2012-01-01

Question answering systems try to give precise answers to a user's question posed in natural language. It is of utmost importance that the answers returned are relevant to the user's question. For clinical QA, the trustworthiness of answers is another important issue. Limiting the document collection to certified websites helps to improve the trustworthiness of answers. On the other hand, limited document collections are known to harm the relevancy of answers. We show, however, in a comparative evaluation, that promoting trustworthiness has no negative effect on the relevance of the retrieved answers in our clinical QA system. On the contrary, the answers found are in general more relevant.

Identifying a clinical signature of suicidality among patients with mood disorders: A pilot study using a machine learning approach.

PubMed

Passos, Ives Cavalcante; Mwangi, Benson; Cao, Bo; Hamilton, Jane E; Wu, Mon-Ju; Zhang, Xiang Yang; Zunta-Soares, Giovana B; Quevedo, Joao; Kauer-Sant'Anna, Marcia; Kapczinski, Flávio; Soares, Jair C

2016-03-15

A growing body of evidence has put forward clinical risk factors associated with patients with mood disorders that attempt suicide. However, what is not known is how to integrate clinical variables into a clinically useful tool in order to estimate the probability of an individual patient attempting suicide. A total of 144 patients with mood disorders were included. Clinical variables associated with suicide attempts among patients with mood disorders and demographic variables were used to 'train' a machine learning algorithm. The resulting algorithm was utilized in identifying novel or 'unseen' individual subjects as either suicide attempters or non-attempters. Three machine learning algorithms were implemented and evaluated. All algorithms distinguished individual suicide attempters from non-attempters with prediction accuracy ranging between 65% and 72% (p<0.05). In particular, the relevance vector machine (RVM) algorithm correctly predicted 103 out of 144 subjects translating into 72% accuracy (72.1% sensitivity and 71.3% specificity) and an area under the curve of 0.77 (p<0.0001). The most relevant predictor variables in distinguishing attempters from non-attempters included previous hospitalizations for depression, a history of psychosis, cocaine dependence and post-traumatic stress disorder (PTSD) comorbidity. Risk for suicide attempt among patients with mood disorders can be estimated at an individual subject level by incorporating both demographic and clinical variables. Future studies should examine the performance of this model in other populations and its subsequent utility in facilitating selection of interventions to prevent suicide. Copyright © 2015 Elsevier B.V. All rights reserved.

Identifying a clinical signature of suicidality among patients with mood disorders: a pilot study using a machine learning approach

PubMed Central

Passos, Ives Cavalcante; Mwangi, Benson; Cao, Bo; Hamilton, Jane E; Wu, Mon-Ju; Zhang, Xiang Yang; Zunta-Soares, Giovana B.; Quevedo, Joao; Kauer-Sant'Anna, Marcia; Kapczinski, Flávio; Soares, Jair C.

2016-01-01

Objective A growing body of evidence has put forward clinical risk factors associated with patients with mood disorders that attempt suicide. However, what is not known is how to integrate clinical variables into a clinically useful tool in order to estimate the probability of an individual patient attempting suicide. Method A total of 144 patients with mood disorders were included. Clinical variables associated with suicide attempts among patients with mood disorders and demographic variables were used to ‘train’ a machine learning algorithm. The resulting algorithm was utilized in identifying novel or ‘unseen’ individual subjects as either suicide attempters or non-attempters. Three machine learning algorithms were implemented and evaluated. Results All algorithms distinguished individual suicide attempters from non-attempters with prediction accuracy ranging between 65%-72% (p<0.05). In particular, the relevance vector machine (RVM) algorithm correctly predicted 103 out of 144 subjects translating into 72% accuracy (72.1% sensitivity and 71.3% specificity) and an area under the curve of 0.77 (p<0.0001). The most relevant predictor variables in distinguishing attempters from non-attempters included previous hospitalizations for depression, a history of psychosis, cocaine dependence and post-traumatic stress disorder (PTSD) comorbidity. Conclusion Risk for suicide attempt among patients with mood disorders can be estimated at an individual subject level by incorporating both demographic and clinical variables. Future studies should examine the performance of this model in other populations and its subsequent utility in facilitating selection of interventions to prevent suicide. PMID:26773901

Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy.

PubMed

Hackert, Thilo; Klaiber, Ulla; Hinz, Ulf; Kehayova, Tzveta; Probst, Pascal; Knebel, Phillip; Diener, Markus K; Schneider, Lutz; Strobel, Oliver; Michalski, Christoph W; Ulrich, Alexis; Sauer, Peter; Büchler, Markus W

2017-05-01

Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0-10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients (P < .004). Preoperative sphincter of Oddi botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of the present trial suggest its efficacy in the prevention of clinically relevant postoperative pancreatic fistula and are validated currently in the German Federal Government-sponsored, multicenter, randomized controlled PREBOT trial. Copyright © 2016 Elsevier Inc. All rights reserved.

Reflections on relevance: Psychotherapy and Psychosomatics in 2004.

PubMed

Balon, Richard

2005-01-01

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

Computational modeling of peripheral pain: a commentary.

PubMed

Argüello, Erick J; Silva, Ricardo J; Huerta, Mónica K; Avila, René S

2015-06-11

This commentary is intended to find possible explanations for the low impact of computational modeling on pain research. We discuss the main strategies that have been used in building computational models for the study of pain. The analysis suggests that traditional models lack biological plausibility at some levels, they do not provide clinically relevant results, and they cannot capture the stochastic character of neural dynamics. On this basis, we provide some suggestions that may be useful in building computational models of pain with a wider range of applications.

Diagnostic value of clinical tests for degenerative rotator cuff disease in medical practice.

PubMed

Lasbleiz, S; Quintero, N; Ea, K; Petrover, D; Aout, M; Laredo, J D; Vicaut, E; Bardin, T; Orcel, P; Beaudreuil, J

2014-06-01

To assess the diagnostic value of clinical tests for degenerative rotator cuff disease (DRCD) in medical practice. Patients with DRCD were prospectively included. Eleven clinical tests of the rotator cuff have been done. One radiologist performed ultrasonography (US) of the shoulder. Results of US were expressed as normal tendon, tendinopathy or full-thickness tear (the reference). For each clinical test and each US criteria, sensitivity, specificity, negative predictive value and positive predictive value, accuracy, negative likelihood ratio (NLR) and positive likelihood ratio (PLR) were calculated. Clinical relevance was defined as PLR ≥2 and NLR ≤0.5. For 35 patients (39 shoulders), Jobe (PLR: 2.08, NLR: 0.31) and full-can (2, 0.5) test results were relevant for diagnosis of supraspinatus tears and resisted lateral rotation (2.42, 0.5) for infraspinatus tears, with weakness as response criteria. The lift-off test (8.50, 0.27) was relevant for subscapularis tears with lag sign as response criteria. Yergason's test (3.7, 0.41) was relevant for tendinopathy of the long head of the biceps with pain as a response criterion. There was no relevant clinical test for diagnosis of tendinopathy of supraspinatus, infraspinatus or subscapularis. Five of 11 clinical tests were relevant for degenerative rotator cuff disease. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Dysmorphic features and developmental outcome of 2-year-old children.

PubMed

Seggers, Jorien; Haadsma, Maaike L; Bos, Arend F; Heineman, Maas Jan; Middelburg, Karin J; van den Heuvel, Edwin R; Hadders-Algra, Mijna

2014-11-01

The aim of this study was to assess the associations between dysmorphic features and neurological, mental, psychomotor, and behavioural development in order to improve our understanding of aetiological pathways leading to minor developmental problems. In our cross-sectional study, 272 generally healthy 2-year-olds (143 males, 129 females; median gestational age 39 weeks, [range 30-43wks]), born after a parental history of subfertility either with or without fertility treatment, were examined. Dysmorphic features were classified as abnormalities (clinically relevant or not), minor anomalies, or common variants according to Merks' classification system. Hempel's neurological assessment resulted in a neurological optimality score (NOS) and fluency score. Mental and psychomotor development were assessed with the Dutch version of the Bayley Scales of Infant Development and behavioural development with the Achenbach Child Behaviour Checklist. Of the different types of dysmorphic feature, clinically relevant abnormalities were most strongly associated with a lower NOS (difference -2.53, 95% confidence interval [CI] -4.23 to -0.83) and fluency score (difference -0.62, 95% CI -1.1 to -0.15). The presence of one or more abnormalities (clinically relevant or not) or one or more common variants was significantly associated with a lower NOS, and the presence of three or more minor anomalies was associated with lower fluency scores. Dysmorphic features were not associated with mental, psychomotor, or behavioural development. As dysmorphic features originate during the first trimester of pregnancy, the association between dysmorphic features and minor alterations in neurodevelopment may suggest an early ontogenetic origin of subtle neurological deviations. © 2014 Mac Keith Press.

A pooled analysis of on-the-road highway driving studies in actual traffic measuring standard deviation of lateral position (i.e., "weaving") while driving at a blood alcohol concentration of 0.5 g/L.

PubMed

Jongen, S; Vermeeren, A; van der Sluiszen, N N J J M; Schumacher, M B; Theunissen, E L; Kuypers, K P C; Vuurman, E F P M; Ramaekers, J G

2017-03-01

The on-the-road highway driving test is generally regarded as a gold standard for assessing drug-induced driving impairment. The primary outcome measure is the standard deviation of lateral position (SDLP), a measure of road tracking error or "weaving". The test has been calibrated for incremental doses of alcohol almost 30 years ago in order to define the impact of drug-induced impairment in terms of blood alcohol concentration (BAC) equivalents. Drug-induced changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant ever since. The present analysis was conducted to assess the robustness of the alcohol effect in a range of on-the-road driving studies which have been conducted since the initial alcohol calibration study. The present study pooled data of 182 participants from nine placebo-controlled crossover studies who performed the highway driving test, while their BAC was at or just below the legal limit for drivers (i.e., 0.5 g/L). Overall, mean SDLP increased with 2.5 cm (95% CI 2.0-2.9 cm). Equivalence testing showed that the clinical relevance criterion value of 2.4 cm fell well within the 95% CI in each individual study. Gender did not affect alcohol-induced changes in SDLP. These results demonstrate the robustness and validity of the clinical relevance criterion for SDLP as measured during on-the-road driving.

[Abortion and medical education in Mexico].

PubMed

de León-Aguirre, Deyanira González; Billings, Deborah L; Ramírez-Sánchez, Rubén

2008-01-01

Medical education in Mexico has significant deficiencies in the area of sexual and reproductive health and does not offer students the information needed for dealing with abortion as a relevant problem in the professional practice of medicine. Medical education does not offer options for the clinical training of future physicians in integrated models for abortion care, which include the use of safe and effective technologies as well as a range of services to respond to women's needs. These limitations are especially relevant in countries such as Mexico where unsafe abortion continues to be a significant public health problem. In addition, the legal context for abortion has begun to change during the current decade; therefore, the search for alternatives to incorporate a broad approach to abortion in medical school programs is a task that cannot be postponed.

Transferrin receptors in human tissues: their distribution and possible clinical relevance.

PubMed

Gatter, K C; Brown, G; Trowbridge, I S; Woolston, R E; Mason, D Y

1983-05-01

The distribution of transferrin receptors (TR) has been studied in a range of normal and malignant tissues using four monoclonal antibodies, BK19.9, B3/25, T56/14 and T58/1. In normal tissues TR was found in a limited number of sites, notably basal epidermis, the endocrine pancreas, hepatocytes, Kupffer cells, testis and pituitary. This restricted pattern of distribution may be relevant to the characteristic pattern of iron deposition in primary haemachromatosis. In contrast to this limited pattern of expression in normal tissue, the receptor was widely distributed in carcinomas, sarcomas and in samples from cases of Hodgkin's disease. This malignancy-associated expression of the receptor may play a role in the anaemia of advanced malignancy by competing with the bone marrow for serum iron.

Transferrin receptors in human tissues: their distribution and possible clinical relevance.

PubMed Central

Gatter, K C; Brown, G; Trowbridge, I S; Woolston, R E; Mason, D Y

1983-01-01

The distribution of transferrin receptors (TR) has been studied in a range of normal and malignant tissues using four monoclonal antibodies, BK19.9, B3/25, T56/14 and T58/1. In normal tissues TR was found in a limited number of sites, notably basal epidermis, the endocrine pancreas, hepatocytes, Kupffer cells, testis and pituitary. This restricted pattern of distribution may be relevant to the characteristic pattern of iron deposition in primary haemachromatosis. In contrast to this limited pattern of expression in normal tissue, the receptor was widely distributed in carcinomas, sarcomas and in samples from cases of Hodgkin's disease. This malignancy-associated expression of the receptor may play a role in the anaemia of advanced malignancy by competing with the bone marrow for serum iron. Images PMID:6302135

Clinical and pathological implications of miRNA in bladder cancer

PubMed Central

Braicu, Cornelia; Cojocneanu-Petric, Roxana; Chira, Sergiu; Truta, Anamaria; Floares, Alexandru; Petrut, Bogdan; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

2015-01-01

MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20–22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer. PMID:25653521

RNA Nanoparticles Derived from Three-Way Junction of Phi29 Motor pRNA Are Resistant to I-125 and Cs-131 Radiation

PubMed Central

Li, Hui; Rychahou, Piotr G.; Cui, Zheng; Pi, Fengmei; Evers, B. Mark; Shu, Dan

2015-01-01

Radiation reagents that specifically target tumors are in high demand for the treatment of cancer. The emerging field of RNA nanotechnology might provide new opportunities for targeted radiation therapy. This study investigates whether chemically modified RNA nanoparticles derived from the packaging RNA (pRNA) three-way junction (3WJ) of phi29 DNA-packaging motor are resistant to potent I-125 and Cs-131 radiation, which is a prerequisite for utilizing these RNA nanoparticles as carriers for targeted radiation therapy. pRNA 3WJ nanoparticles were constructed and characterized, and the stability of these nanoparticles under I-125 and Cs-131 irradiation with clinically relevant doses was examined. RNA nanoparticles derived from the pRNA 3WJ targeted tumors specifically and they were stable under irradiation of I-125 and Cs-131 with clinically relevant doses ranging from 1 to 90 Gy over a significantly long time up to 20 days, while control plasmid DNA was damaged at 20 Gy or higher. PMID:26017686

What is the true clinical relevance of Simkania negevensis and other emerging Chlamydiales members?

PubMed

Vouga, M; Kebbi-Beghdadi, C; Liénard, J; Baskin, L; Baud, D; Greub, G

2018-05-01

Waddlia   chondrophila and Simkania negevensis are emerging Chlamydia- related bacteria. Similar to the pathogenic organisms Chlamydia pneumoniae and Chlamydia trachomatis, these emerging bacteria are implicated in human genital infections and respiratory diseases. We used a screening strategy based on a newly developed S. negevensis -specific quantitative real-time PCR (qPCR) and a pan- Chlamydiales qPCR. We could not detect S. negevensis in 458 respiratory, genitourinary, cardiac and hepatic samples tested. One urethral swab was positive for W. chondrophila. We observed a low prevalence of Chlamydiales in respiratory samples (1/200, 0.5%), which suggests that C. pneumoniae is an uncommon respiratory pathogen. Furthermore, we screened 414 human serum samples from Switzerland, England and Israel and observed a low prevalence (<1%) of exposure to S. negevensis. Conversely, humans were commonly exposed to W. chondrophila, with seroprevalences ranging from 8.6% to 32.5%. S. negevensis is not a clinically relevant pathogen, but further research investigating the role of W. chondrophila is needed.

Retrieval of diagnostic and treatment studies for clinical use through PubMed and PubMed's Clinical Queries filters.

PubMed

Lokker, Cynthia; Haynes, R Brian; Wilczynski, Nancy L; McKibbon, K Ann; Walter, Stephen D

2011-01-01

Clinical Queries filters were developed to improve the retrieval of high-quality studies in searches on clinical matters. The study objective was to determine the yield of relevant citations and physician satisfaction while searching for diagnostic and treatment studies using the Clinical Queries page of PubMed compared with searching PubMed without these filters. Forty practicing physicians, presented with standardized treatment and diagnosis questions and one question of their choosing, entered search terms which were processed in a random, blinded fashion through PubMed alone and PubMed Clinical Queries. Participants rated search retrievals for applicability to the question at hand and satisfaction. For treatment, the primary outcome of retrieval of relevant articles was not significantly different between the groups, but a higher proportion of articles from the Clinical Queries searches met methodologic criteria (p=0.049), and more articles were published in core internal medicine journals (p=0.056). For diagnosis, the filtered results returned more relevant articles (p=0.031) and fewer irrelevant articles (overall retrieval less, p=0.023); participants needed to screen fewer articles before arriving at the first relevant citation (p<0.05). Relevance was also influenced by content terms used by participants in searching. Participants varied greatly in their search performance. Clinical Queries filtered searches returned more high-quality studies, though the retrieval of relevant articles was only statistically different between the groups for diagnosis questions. Retrieving clinically important research studies from Medline is a challenging task for physicians. Methodological search filters can improve search retrieval.

State of the Art: Novel Applications for Deep Brain Stimulation.

PubMed

Roy, Holly A; Green, Alexander L; Aziz, Tipu Z

2018-02-01

Deep brain stimulation (DBS) is a rapidly developing field of neurosurgery with potential therapeutic applications that are relevant to conditions traditionally viewed as beyond the limits of neurosurgery. Our objective, in this review, is to highlight some of the emerging applications of DBS within three distinct but overlapping spheres, namely trauma, neuropsychiatry, and autonomic physiology. An extensive literature review was carried out in MEDLINE, to identify relevant studies and review articles describing applications of DBS in the areas of trauma, neuropsychiatry and autonomic neuroscience. A wide range of applications of DBS in these spheres was identified, some having only been tested in one or two cases, others much better studied. We have identified various avenues for DBS to be applied for patient benefit in cases relevant to trauma, neuropsychiatry and autonomic neuroscience. Further developments in DBS technology and clinical trial design will enable these novel applications to be effectively and rigorously assessed and utilized most effectively. © 2017 International Neuromodulation Society.

[Relevant factors in medico-legal prognosis of whiplash injury].

PubMed

Pujol, Amadeo; Puig, Luisa; Mansilla, Joaquina; Idiaquez, Itziar

2003-07-12

Whiplash injury (WI) is commonly evaluated in medico-legal practice. With the aim of knowing the determining factors of WI's medico-legal prognosis, a prospective and observational study was carried out. One hundred and twenty consecutive patients who were clinically observed and evaluated in the Medico-Legal Clinic of Barcelona were studied. Socio-demographic, clinical, radiographic and evolutive factors were analyzed. We included 120 patients with a mean age of 35.6 (14) years (range, 4-74), with a homogeneous male/female distribution. An earlier cervical pathology was detected in 10% of patients; none of them had previous psychiatric pathology. 95% corresponded to road-traffic accident cases and there were 5 aggression cases. Over 50% of cases involved a rear-end collision. All patients had neck pain, almost 25% had headache and 13% had paresthesia. According to the Whiplash Association Disorders clinical classification, distribution in grades (G) was: G I 51%, G II 32% and G III 17%. Patients reported recovery within a mean time of 71.6 (46) days (range, 4-244), with 51,2 (45) no working days (range, 0-180 days). The 52% of the patients rest with complains. According to the recovery time, the following medico-legal prognostic factors were identified: age (p < 0.001), being female (p = 0.001), clinical grade (p < 0.001) and abnormal cervical MRI exploration (p < 0.001). Patients with previous cervical pathology reported more complaints (p = 0.001). In our study, WI affected young people of both sex mainly during rear-end collision. Worst medico-legal prognostic factors were age, being females, severity of initial clinical symptoms, previous cervical pathology and abnormal cervical MRI/CT.

The effect of neck pain on cervical kinematics, as assessed in a virtual environment.

PubMed

Sarig Bahat, Hilla; Weiss, Patrice L; Laufer, Yocheved

2010-12-01

To compare cervical kinematics during functional motion in patients with neck pain and in asymptomatic participants using a novel virtual reality assessment. Clinical comparative trial. Participants were recruited from university staff and students, and from a local physical therapy clinic. Patients with chronic neck pain (n=25) and asymptomatic participants (n=42). Not applicable. Kinematic measures (response time, peak and mean velocity, number of velocity peaks, time to peak velocity percentage) were sampled while participants were engaged in the virtual game. Group and motion direction differences were assessed with a 2-way repeated-measures analysis of variance, Tukey-Kramer testing, and contrast analysis when relevant. Participants with neck pain had lower peak and mean velocities than the asymptomatic participants (P<.0001). They also demonstrated a greater number of velocity peaks, indicating impaired motion smoothness (P=.0036). No significant group differences were found for response time or for time to peak velocity percentage. Cervical rotations were significantly faster and smoother than flexion and extension movements (P<.05). The overall impairment percentage in velocity and smoothness of cervical motion in patients with neck pain ranged from 22% to 44% compared with asymptomatic participants. Velocity and smoothness of cervical motion were more restricted in patients with chronic neck pain than found previously. Unlike range of motion and other static measurements, these dynamic variables reflect functional cervical motion and therefore contribute to a better understanding of the impairment associated with neck pain. Because the ability to move quickly in response to external stimuli is a commonly occurring phenomenon, this deficit is highly relevant to clinical assessment and management. Copyright © 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Measurement of serum 7α-hydroxy-4-cholesten-3-one as a marker of bile acid malabsorption in dogs with chronic diarrhoea: a pilot study

PubMed Central

Cross, G.; Taylor, D. R.; Sherwood, R. A.; Watson, P. J.

2016-01-01

Bile acid malabsorption is a common cause of chronic diarrhoea in people, however it has never previously been investigated in dogs, despite clinical suspicion of its existence. The goal of this study was to assess the feasibility of measuring serum 7α-hydroxy-4-cholesten-3-one (C4) in dogs, as a potential marker of bile acid malabsorption, and to see whether this is related to clinical disease severity or the presence of hypocobalaminaemia. Serum C4 concentration was measured in 20 clinically healthy control dogs and 17 dogs with chronic diarrhoea. Three of the 17 affected dogs (17.6 per cent) had a C4 concentration significantly above the range of clinically healthy dogs; these dogs were all poorly responsive to conventional therapy. These results suggest that bile acid malabsorption may be a clinically relevant disorder in dogs with chronic diarrhoea and serum C4 may be a useful tool to investigate this further. PMID:27110372

Research methods to change clinical practice for patients with rare cancers.

PubMed

Billingham, Lucinda; Malottki, Kinga; Steven, Neil

2016-02-01

Rare cancers are a growing group as a result of reclassification of common cancers by molecular markers. There is therefore an increasing need to identify methods to assess interventions that are sufficiently robust to potentially affect clinical practice in this setting. Methods advocated for clinical trials in rare diseases are not necessarily applicable in rare cancers. This Series paper describes research methods that are relevant for rare cancers in relation to the range of incidence levels. Strategies that maximise recruitment, minimise sample size, or maximise the usefulness of the evidence could enable the application of conventional clinical trial design to rare cancer populations. Alternative designs that address specific challenges for rare cancers with the aim of potentially changing clinical practice include Bayesian designs, uncontrolled n-of-1 trials, and umbrella and basket trials. Pragmatic solutions must be sought to enable some level of evidence-based health care for patients with rare cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measurement of serum 7α-hydroxy-4-cholesten-3-one as a marker of bile acid malabsorption in dogs with chronic diarrhoea: a pilot study.

PubMed

Kent, A C C; Cross, G; Taylor, D R; Sherwood, R A; Watson, P J

2016-01-01

Bile acid malabsorption is a common cause of chronic diarrhoea in people, however it has never previously been investigated in dogs, despite clinical suspicion of its existence. The goal of this study was to assess the feasibility of measuring serum 7α-hydroxy-4-cholesten-3-one (C4) in dogs, as a potential marker of bile acid malabsorption, and to see whether this is related to clinical disease severity or the presence of hypocobalaminaemia. Serum C4 concentration was measured in 20 clinically healthy control dogs and 17 dogs with chronic diarrhoea. Three of the 17 affected dogs (17.6 per cent) had a C4 concentration significantly above the range of clinically healthy dogs; these dogs were all poorly responsive to conventional therapy. These results suggest that bile acid malabsorption may be a clinically relevant disorder in dogs with chronic diarrhoea and serum C4 may be a useful tool to investigate this further.

Clinical relevance of diagnosing COPD by fixed ratio or lower limit of normal: a systematic review.

PubMed

van Dijk, Wouter D; Gupta, Nisha; Tan, Wan C; Bourbeau, Jean

2014-02-01

Different spirometric criteria in diagnosing COPD have been advocated by different groups, debilitating adequate diagnosis and treatment of COPD. We reviewed the clinical relevance of fixed ratio and lower limit of normal (LLN) in diagnosing COPD and explored if modifying factors may affect their clinical relevance. Two reviewers independently searched PubMed and Embase for papers that compared both criteria on any clinically relevant outcome, published before June 1st, 2012, without any language restriction. Two reviewers independently extracted the study characteristics, including study design, population characteristics and diagnostic criteria used, and summarized the results of clinical relevance. Study quality was assessed by scoring forms for bias and level of evidence. Of 394 studies retrieved, 11 studies were included, with a median of 1,258 participants. Although both criteria appeared related with various clinically relevant outcomes, we were unable to prefer one criterion over the other, with various performances of the criteria for different outcomes. Should the criteria disagree on diagnosis, an alternative diagnosis should be suspected, in particular in those (elderly) with less severe airflow limitation for whom the LLN appears a better criterion. The fixed ratio appears to perform better in subjects with more severe airflow limitation. In diagnosing COPD, severity of airflow limitation appears an important factor for choosing whether the fixed ratio or LLN. Disagreement between the criteria is suggestive for an alternative diagnosis. Future studies on clinical relevance should further reveal the criterion of choice, in order to improve adequate diagnosis and consequent treatments.

Next generation phenotyping using narrative reports in a rare disease clinical data warehouse.

PubMed

Garcelon, Nicolas; Neuraz, Antoine; Salomon, Rémi; Bahi-Buisson, Nadia; Amiel, Jeanne; Picard, Capucine; Mahlaoui, Nizar; Benoit, Vincent; Burgun, Anita; Rance, Bastien

2018-05-31

Secondary use of data collected in Electronic Health Records opens perspectives for increasing our knowledge of rare diseases. The clinical data warehouse (named Dr. Warehouse) at the Necker-Enfants Malades Children's Hospital contains data collected during normal care for thousands of patients. Dr. Warehouse is oriented toward the exploration of clinical narratives. In this study, we present our method to find phenotypes associated with diseases of interest. We leveraged the frequency and TF-IDF to explore the association between clinical phenotypes and rare diseases. We applied our method in six use cases: phenotypes associated with the Rett, Lowe, Silver Russell, Bardet-Biedl syndromes, DOCK8 deficiency and Activated PI3-kinase Delta Syndrome (APDS). We asked domain experts to evaluate the relevance of the top-50 (for frequency and TF-IDF) phenotypes identified by Dr. Warehouse and computed the average precision and mean average precision. Experts concluded that between 16 and 39 phenotypes could be considered as relevant in the top-50 phenotypes ranked by descending frequency discovered by Dr. Warehouse (resp. between 11 and 41 for TF-IDF). Average precision ranges from 0.55 to 0.91 for frequency and 0.52 to 0.95 for TF-IDF. Mean average precision was 0.79. Our study suggests that phenotypes identified in clinical narratives stored in Electronic Health Record can provide rare disease specialists with candidate phenotypes that can be used in addition to the literature. Clinical Data Warehouses can be used to perform Next Generation Phenotyping, especially in the context of rare diseases. We have developed a method to detect phenotypes associated with a group of patients using medical concepts extracted from free-text clinical narratives.

Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia

PubMed Central

Fogel, Brent L.; Lee, Hane; Deignan, Joshua L.; Strom, Samuel P.; Kantarci, Sibel; Wang, Xizhe; Quintero-Rivera, Fabiola; Vilain, Eric; Grody, Wayne W.; Perlman, Susan; Geschwind, Daniel H.; Nelson, Stanley F.

2015-01-01

IMPORTANCE Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. OBJECTIVE To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. DESIGN, SETTING, AND PARTICIPANTS We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. MAIN OUTCOMES AND MEASURES Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. RESULTS We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. CONCLUSIONS AND RELEVANCE This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia. PMID:25133958

Performance assessment of a programmable five degrees-of-freedom motion platform for quality assurance of motion management techniques in radiotherapy.

PubMed

Huang, Chen-Yu; Keall, Paul; Rice, Adam; Colvill, Emma; Ng, Jin Aun; Booth, Jeremy T

2017-09-01

Inter-fraction and intra-fraction motion management methods are increasingly applied clinically and require the development of advanced motion platforms to facilitate testing and quality assurance program development. The aim of this study was to assess the performance of a 5 degrees-of-freedom (DoF) programmable motion platform HexaMotion (ScandiDos, Uppsala, Sweden) towards clinically observed tumor motion range, velocity, acceleration and the accuracy requirements of SABR prescribed in AAPM Task Group 142. Performance specifications for the motion platform were derived from literature regarding the motion characteristics of prostate and lung tumor targets required for real time motion management. The performance of the programmable motion platform was evaluated against (1) maximum range, velocity and acceleration (5 DoF), (2) static position accuracy (5 DoF) and (3) dynamic position accuracy using patient-derived prostate and lung tumor motion traces (3 DoF). Translational motion accuracy was compared against electromagnetic transponder measurements. Rotation was benchmarked with a digital inclinometer. The static accuracy and reproducibility for translation and rotation was <0.1 mm or <0.1°, respectively. The accuracy of reproducing dynamic patient motion was <0.3 mm. The motion platform's range met the need to reproduce clinically relevant translation and rotation ranges and its accuracy met the TG 142 requirements for SABR. The range, velocity and acceleration of the motion platform are sufficient to reproduce lung and prostate tumor motion for motion management. Programmable motion platforms are valuable tools in the investigation, quality assurance and commissioning of motion management systems in radiation oncology.

Infusion of solutions of pre-irradiated components in rats.

PubMed

Pappas, Georgina; Arnaud, Francoise; Haque, Ashraful; Kino, Tomoyuki; Facemire, Paul; Carroll, Erica; Auker, Charles; McCarron, Richard; Scultetus, Anke

2016-06-01

The objective of this study was to conduct a 14-day toxicology assessment for intravenous solutions prepared from irradiated resuscitation fluid components and sterile water. Healthy Sprague Dawley rats (7-10/group) were instrumented and randomized to receive one of the following Field IntraVenous Resuscitation (FIVR) or commercial fluids; Normal Saline (NS), Lactated Ringer's, 5% Dextrose in NS. Daily clinical observation, chemistry and hematology on days 1,7,14, and urinalysis on day 14 were evaluated for equivalence using a two sample t-test (p<0.05). A board-certified pathologist evaluated organ histopathology on day 14. Equivalence was established for all observation parameters, lactate, sodium, liver enzymes, creatinine, WBC and differential, and urinalysis values. Lack of equivalence for hemoglobin (p=0.055), pH (p=0.0955), glucose (p=0.0889), Alanine-Aminotransferase (p=0.1938), albumin (p=0.1311), and weight (p=0.0555, p=0.1896), was deemed not clinically relevant due to means within physiologically normal ranges. Common microscopic findings randomly distributed among animals of all groups were endocarditis/myocarditis and pulmonary lesions. These findings are consistent with complications due to long-term catheter use and suggest no clinically relevant differences in end-organ toxicity between animals infused with FIVR versus commercial fluids. Copyright © 2016 Elsevier GmbH. All rights reserved.

Hybrid Synthetic Receptors on MOSFET Devices for Detection of Prostate Specific Antigen in Human Plasma.

PubMed

Tamboli, Vibha K; Bhalla, Nikhil; Jolly, Pawan; Bowen, Chris R; Taylor, John T; Bowen, Jenna L; Allender, Chris J; Estrela, Pedro

2016-12-06

The study reports the use of extended gate field-effect transistors (FET) for the label-free and sensitive detection of prostate cancer (PCa) biomarkers in human plasma. The approach integrates for the first time hybrid synthetic receptors comprising of highly selective aptamer-lined pockets (apta-MIP) with FETs for sensitive detection of prostate specific antigen (PSA) at clinically relevant concentrations. The hybrid synthetic receptors were constructed by immobilizing an aptamer-PSA complex on gold and subjecting it to 13 cycles of dopamine electropolymerization. The polymerization resulted in the creation of highly selective polymeric cavities that retained the ability to recognize PSA post removal of the protein. The hybrid synthetic receptors were subsequently used in an extended gate FET setup for electrochemical detection of PSA. The sensor was reported to have a limit of detection of 0.1 pg/mL with a linear detection range from 0.1 pg/mL to 1 ng/mL PSA. Detection of 1-10 pg/mL PSA was also achieved in diluted human plasma. The present apta-MIP sensor developed in conjunction with FET devices demonstrates the potential for clinical application of synthetic hybrid receptors for the detection of clinically relevant biomarkers in complex samples.

Is Ureaplasma spp. the leading causative agent of acute chorioamnionitis in women with preterm birth?

PubMed

Kikhney, J; von Schöning, D; Steding, I; Schulze, J; Petrich, A; Hiergeist, A; Reischl, U; Moter, A; Thomas, A

2017-02-01

Aim of this study was to detect microorganisms in fetal membranes and placental tissue in preterm chorioamnionitis by combining fluorescence in situ hybridization (FISH) with broad range PCR. The combination of the two molecular techniques enables identification and localization of the microorganisms within the tissue, confirming their clinical relevance. In a prospective cohort study, we compared 31 women with preterm premature rupture of membranes or preterm labour and preterm delivery by caesarean section with a control group of 26 women undergoing elective caesarean section at term. Fetal membranes and placental tissue were analysed by FISH and broad range 16S rRNA-gene PCR and sequencing. For 20 women in the preterm group, caesarean section was performed because of a clinical diagnosis of chorioamnionitis. Microorganisms were detected in the tissues by both molecular techniques in 11 out of 20 women. Among those, Ureaplasma spp. was most abundant, with five cases that remained culture-negative and would have been missed by routine diagnostic procedures. Other infections were caused by Staphylococcus aureus, Streptococcus mitis or Escherichia coli. FISH and PCR were negative for all women without suspected chorioamnionitis and for the control group. Combination of FISH with broad-range PCR and sequencing permitted unambiguous identification of the causative microorganisms in chorioamnionitis. The high prevalence of Ureaplasma spp. should lead to a re-evaluation of its clinical significance and possible therapeutic consequences. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Effectiveness of exercise therapy and manual mobilisation in ankle sprain and functional instability: a systematic review.

PubMed

van der Wees, Philip J; Lenssen, Anton F; Hendriks, Erik J M; Stomp, Derrick J; Dekker, Joost; de Bie, Rob A

2006-01-01

This study critically reviews the effectiveness of exercise therapy and manual mobilisation in acute ankle sprains and functional instability by conducting a systematic review of randomised controlled trials. Trials were searched electronically and manually from 1966 to March 2005. Randomised controlled trials that evaluated exercise therapy or manual mobilisation of the ankle joint with at least one clinically relevant outcome measure were included. Internal validity of the studies was independently assessed by two reviewers. When applicable, relative risk (RR) or standardised mean differences (SMD) were calculated for individual and pooled data. In total 17 studies were included. In thirteen studies the intervention included exercise therapy and in four studies the effects of manual mobilisation of the ankle joint was evaluated. Average internal validity score of the studies was 3.1 (range 1 to 7) on a 10-point scale. Exercise therapy was effective in reducing the risk of recurrent sprains after acute ankle sprain: RR 0.37 (95% CI 0.18 to 0.74), and with functional instability: RR 0.38 (95% CI 0.23 to 0.62). No effects of exercise therapy were found on postural sway in patients with functional instability: SMD: 0.38 (95% CI -0.15 to 0.91). Four studies demonstrated an initial positive effect of different modes of manual mobilisation on dorsiflexion range of motion. It is likely that exercise therapy, including the use of a wobble board, is effective in the prevention of recurrent ankle sprains. Manual mobilisation has an (initial) effect on dorsiflexion range of motion, but the clinical relevance of these findings for physiotherapy practice may be limited.

Antimicrobial Heteroresistance: an Emerging Field in Need of Clarity

PubMed Central

El-Halfawy, Omar M.

2015-01-01

SUMMARY “Heteroresistance” describes a phenomenon where subpopulations of seemingly isogenic bacteria exhibit a range of susceptibilities to a particular antibiotic. Unfortunately, a lack of standard methods to determine heteroresistance has led to inappropriate use of this term. Heteroresistance has been recognized since at least 1947 and occurs in Gram-positive and Gram-negative bacteria. Its clinical relevance may be considerable, since more resistant subpopulations may be selected during antimicrobial therapy. However, the use of nonstandard methods to define heteroresistance, which are costly and involve considerable labor and resources, precludes evaluating the clinical magnitude and severity of this phenomenon. We review the available literature on antibiotic heteroresistance and propose recommendations for definitions and determination criteria for heteroresistant bacteria. This will help in assessing the global clinical impact of heteroresistance and developing uniform guidelines for improved therapeutic outcomes. PMID:25567227

Transfer of knowledge and skills: some implications for nursing and nurse education.

PubMed

Lauder, W; Reynolds, W; Angus, N

1999-08-01

The construct of transfer has enormous importance to nursing as it begins to highlight potential problems in the transfer of knowledge and skills from the campus to the clinical area, from one part of the clinical area to another (e.g. surgical to medical), and from community to the clinical area. Thus, any adequate conceptualization of transfer must account for problems of practice-practice transfer as well as theory-practice transfer. These potential problems are the concern of educators, students and managers who have a responsibility for agency nurses and bank nurses who may find themselves in different specialities on a regular basis. Transfer has relevance to a whole raft of other issues ranging from the application of theories to nursing practice, through to the validity of claims that courses which develop intellectual skills prepare nurses for lifelong learning.

Insights from clinical research completed during the west Africa Ebola virus disease epidemic

PubMed Central

Rojek, Amanda; Horby, Peter; Dunning, Jake

2018-01-01

The west Africa Ebola virus disease (EVD) epidemic was extraordinary in scale. Now that the epidemic has ended, it is a relevant time to examine published studies with direct relevance to clinical care and, more broadly, to examine the implications of the clinical research response mounted. Clinically relevant research includes literature detailing risk factors for and clinical manifestations of EVD, laboratory and other investigation findings in patients, experimental vaccine and therapeutic clinical trials, and analyses of survivor syndrome. In this Review, we discuss new insights from patient-oriented research completed during the west Africa epidemic, identify ongoing knowledge gaps, and suggest priorities for future research. PMID:28461209

Relationship between isometric thigh muscle strength and minimum clinically important differences in knee function in osteoarthritis: data from the osteoarthritis initiative.

PubMed

Ruhdorfer, Anja; Wirth, Wolfgang; Eckstein, Felix

2015-04-01

To determine the relationship between thigh muscle strength and clinically relevant differences in self-assessed lower leg function. Isometric knee extensor and flexor strength of 4,553 Osteoarthritis Initiative participants (2,651 women and 1,902 men) was related to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function scores by linear regression. Further, groups of male and female participant strata with minimum clinically important differences (MCIDs) in WOMAC function scores (6 of 68 units) were compared across the full range of observed values and to participants without functional deficits (WOMAC score 0). The effect of WOMAC knee pain and body mass index on the above relationships was explored using stepwise regression. Per regression equations, a 3.7% reduction in extensor strength and a 4.0% reduction in flexor strength were associated with an MCID in WOMAC function in women, and, respectively, a 3.6% and 4.8% reduction in men. For strength divided by body weight, reductions were 5.2% and 6.7%, respectively, in women and 5.8% and 6.7%, respectively, in men. Comparing MCID strata across the full observed range of WOMAC function confirmed the above estimates and did not suggest nonlinear relationships across the spectrum of observed values. WOMAC pain correlated strongly with WOMAC function, but extensor (and flexor) muscle strength contributed significant independent information. Reductions of approximately 4% in isometric muscle strength and of 6% in strength per body weight were related to a clinically relevant difference in WOMAC functional disability. Longitudinal studies will need to confirm these relationships within persons. Muscle extensor (and flexor) strength (per body weight) provided significant independent information in addition to pain in explaining variability in lower leg function. Copyright © 2015 by the American College of Rheumatology.

Prevalence and Factors Associated with Hyperkalemia in Predialysis Patients Followed in a Low-Clearance Clinic

PubMed Central

Sarafidis, Pantelis A.; Blacklock, Rochelle; Wood, Eleri; Rumjon, Adam; Simmonds, Shanique; Fletcher-Rogers, Jessica; Ariyanayagam, Rachel; Al-Yassin, Aziza; Sharpe, Claire

2012-01-01

Summary Background and objectives Recent studies evaluated the prevalence of hyperkalemia and related risk factors in patients with CKD of various stages, but there is limited relevant information in predialysis patients. This study aimed to examine the prevalence and factors associated with hyperkalemia in the structured environment of a low-clearance clinic. Design, setting, participants, & measurements In a cross-sectional fashion over a prespecified period of 4 months, information on serum potassium and relevant laboratory variables, comorbidities, medications, and dietician input in patients with advanced CKD under follow-up in the low-clearance clinic of our department was recorded. Univariate and multiple logistic regression analyses were used to identify factors associated with serum potassium≥5.5 meq/L. Results The study population consisted of 238 patients aged 66.2±4.2 years with estimated GFR of 14.5±4.8 ml/min per 1.73 m2. The prevalence of hyperkalemia. defined as potassium>5.0, ≥5.5, and ≥6.0 meq/L., was at 54.2%, 31.5%, and 8.4%, respectively. In univariate comparisons, patients with potassium≥5.5 meq/L had significantly higher urea and lower estimated GFR and serum bicarbonate; also, they were more often using sodium bicarbonate and had received potassium education and attempts for dietary potassium lowering. Use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was not associated with hyperkalemia. In multivariate analyses, estimated GFR<15 ml/min per 1.73 m2 and sodium bicarbonate use were independently associated with hyperkalemia. Conclusions The prevalence of hyperkalemia in predialysis patients with CKD is high. Even at this range of renal function, low estimated GFR seems to be the most important factor associated with hyperkalemia among the wide range of demographic, clinical, and laboratory characteristics studied. PMID:22595825

Identifying Opportunities for Vertical Integration of Biochemistry and Clinical Medicine.

PubMed

Wendelberger, Karen J.; Burke, Rebecca; Haas, Arthur L.; Harenwattananon, Marisa; Simpson, Deborah

1998-01-01

Objectives: Retention of basic science knowledge, as judged by National Board of Medical Examiners' (NBME) data, suffers due to lack of apparent relevance and isolation of instruction from clinical application, especially in biochemistry. However, the literature reveals no systematic process for identifying key biochemical concepts and associated clinical conditions. This study systematically identified difficult biochemical concepts and their common clinical conditions as a critical step towards enhancing relevance and retention of biochemistry.Methods: A multi-step/ multiple stakeholder process was used to: (1) identify important biochemistry concepts; (2) determine students' perceptions of concept difficulty; (3) assess biochemistry faculty, student, and clinical teaching scholars' perceived relevance of identified concepts; and (4) identify associated common clinical conditions for relevant and difficult concepts. Surveys and a modified Delphi process were used to gather data, subsequently analyzed using SPSS for Windows.Results: Sixteen key biochemical concepts were identified. Second year medical students rated 14/16 concepts as extremely difficult while fourth year students rated nine concepts as moderately to extremely difficult. On average, each teaching scholar generated common clinical conditions for 6.2 of the 16 concepts, yielding a set of seven critical concepts and associated clinical conditions.Conclusions: Key stakeholders in the instructional process struggle to identify biochemistry concepts that are critical, difficult to learn and associated with common clinical conditions. However, through a systematic process beginning with identification of concepts and associated clinical conditions, relevance of basic science instruction can be enhanced.

Biological and cognitive correlates of cortical curvature in schizophrenia.

PubMed

Lubeiro, Alba; de Luis-García, Rodrigo; Rodríguez, Margarita; Álvarez, Aldara; de la Red, Henar; Molina, Vicente

2017-10-27

Mean cortical curvature may relate to cortico-cortical connections integrity. We explored the association between prefrontal (PFC) cortical curvature and fractional anisotropy (FA) values for tracts connecting PFC and relevant cortical regions. In schizophrenia Anatomical and diffusion magnetic resonance images were obtained from 34 patients (16 of them first-episodes) and 32 healthy controls. We calculated curvature at rostral lateral prefrontal (RLPF) and superior medial prefrontal (SMPF) areas and mean FA for the tracts respectively connecting RLPF and SMPF areas with anterior caudal cingulate (ACC), superior temporal gyrus (STG) and superior parietal SP regions. Cognitive and clinical data were collected, including baseline symptoms, Clinical Global Impression change scores from baseline to follow-up, illness duration and treatment dosage. Patients showed significantly lower FA values in the tracts linking right RLPF-ACC, right SMPF-SPG and bilaterally PFC-STG. FA values in short-range cortico-cortical connections (linking PFC and ACC) were inversely associated with PFC curvature. In patients, cognitive performance was negatively associated with PFC curvature. Larger curvature values were associated to lack of clinical improvement at follow-up. We conclude that cortical curvature is influenced by integrity in short-range cortico-cortical connections and relates to cognition and clinical outcome in schizophrenia patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Effectiveness of Workplace Weight Management Interventions: a Systematic Review.

PubMed

Weerasekara, Yasoma Kumari; Roberts, Susan B; Kahn, Mira A; LaVertu, Amy E; Hoffman, Ben; Das, Sai Krupa

2016-06-01

A systematic review was conducted of randomized trials of workplace weight management interventions, including trials with dietary, physical activity, environmental, behavioral, and incentive-based components. Main outcomes were defined as change in weight-related measures. Keywords related to weight management and workplace interventions were used to search relevant databases, and 23 eligible studies were reviewed in detail using a data extraction form and quality assessment checklist. The trials were conducted mainly in the USA and Europe, with four additional countries represented. Interventions were mostly multicomponent and were implemented in both sexes and in a range of employment categories. Intervention effectiveness appeared unrelated to region of the world and was highest in 6-12-month trials. The results ranged widely from clinically significant 8.8-kg weight loss in one trial to less effective than the control treatment in others. Some workplace interventions achieve clinically significant benefits, and further studies are needed to replicate those results in wider sociocultural and geographical contexts.

Forecasting malaria in a highly endemic country using environmental and clinical predictors.

PubMed

Zinszer, Kate; Kigozi, Ruth; Charland, Katia; Dorsey, Grant; Brewer, Timothy F; Brownstein, John S; Kamya, Moses R; Buckeridge, David L

2015-06-18

Malaria thrives in poor tropical and subtropical countries where local resources are limited. Accurate disease forecasts can provide public and clinical health services with the information needed to implement targeted approaches for malaria control that make effective use of limited resources. The objective of this study was to determine the relevance of environmental and clinical predictors of malaria across different settings in Uganda. Forecasting models were based on health facility data collected by the Uganda Malaria Surveillance Project and satellite-derived rainfall, temperature, and vegetation estimates from 2006 to 2013. Facility-specific forecasting models of confirmed malaria were developed using multivariate autoregressive integrated moving average models and produced weekly forecast horizons over a 52-week forecasting period. The model with the most accurate forecasts varied by site and by forecast horizon. Clinical predictors were retained in the models with the highest predictive power for all facility sites. The average error over the 52 forecasting horizons ranged from 26 to 128% whereas the cumulative burden forecast error ranged from 2 to 22%. Clinical data, such as drug treatment, could be used to improve the accuracy of malaria predictions in endemic settings when coupled with environmental predictors. Further exploration of malaria forecasting is necessary to improve its accuracy and value in practice, including examining other environmental and intervention predictors, including insecticide-treated nets.

Analytical method for lipoperoxidation relevant reactive aldehydes in human sera by high-performance liquid chromatography-fluorescence detection.

PubMed

El-Maghrabey, Mahmoud H; Kishikawa, Naoya; Ohyama, Kaname; Kuroda, Naotaka

2014-11-01

A validated, simple and sensitive HPLC method was developed for the simultaneous determination of lipoperoxidation relevant reactive aldehydes: glyoxal (GO), acrolein (ACR), malondialdehyde (MDA), and 4-hydroxy-2-nonenal (HNE) in human serum. The studied aldehydes were reacted with 2,2'-furil to form fluorescent difurylimidazole derivatives that were separated on a C18 column using gradient elution and fluorescence detection at excitation and emission wavelengths of 250 and 355nm, respectively. The method showed good linearity over the concentration ranges of 0.100-5.00, 0.200-10.0, 0.200-40.0, and 0.400-10.0nmol/mL for GO, ACR, HNE, and MDA, respectively, with detection limits ranging from 0.030 to 0.11nmol/mL. The percentage RSD of intraday and interday precision did not exceed 5.0 and 6.2%, respectively, and the accuracy (%found) ranged from 95.5 to 103%. The proposed method was applied for monitoring the four aldehydes in sera of healthy, diabetic, and rheumatic human subjects with simple pretreatment steps and without interference from endogenous components. By virtue of its high sensitivity and accuracy, our method enabled detection of differences between analytes concentrations in sera of human subjects under different clinical conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Retention of knowledge and perceived relevance of basic sciences in an integrated case-based learning (CBL) curriculum

PubMed Central

2013-01-01

Background Knowledge and understanding of basic biomedical sciences remain essential to medical practice, particularly when faced with the continual advancement of diagnostic and therapeutic modalities. Evidence suggests, however, that retention tends to atrophy across the span of an average medical course and into the early postgraduate years, as preoccupation with clinical medicine predominates. We postulated that perceived relevance demonstrated through applicability to clinical situations may assist in retention of basic science knowledge. Methods To test this hypothesis in our own medical student cohort, we administered a paper-based 50 MCQ assessment to a sample of students from Years 2 through 5. Covariates pertaining to demographics, prior educational experience, and the perceived clinical relevance of each question were also collected. Results A total of 232 students (Years 2–5, response rate 50%) undertook the assessment task. This sample had comparable demographic and performance characteristics to the whole medical school cohort. In general, discipline-specific and overall scores were better for students in the latter years of the course compared to those in Year 2; male students and domestic students tended to perform better than their respective counterparts in certain disciplines. In the clinical years, perceived clinical relevance was significantly and positively correlated with item performance. Conclusions This study suggests that perceived clinical relevance is a contributing factor to the retention of basic science knowledge and behoves curriculum planners to make clinical relevance a more explicit component of applied science teaching throughout the medical course. PMID:24099045

Does the choice of display system influence perception and visibility of clinically relevant features in digital pathology images?

NASA Astrophysics Data System (ADS)

Kimpe, Tom; Rostang, Johan; Avanaki, Ali; Espig, Kathryn; Xthona, Albert; Cocuranu, Ioan; Parwani, Anil V.; Pantanowitz, Liron

2014-03-01

Digital pathology systems typically consist of a slide scanner, processing software, visualization software, and finally a workstation with display for visualization of the digital slide images. This paper studies whether digital pathology images can look different when presenting them on different display systems, and whether these visual differences can result in different perceived contrast of clinically relevant features. By analyzing a set of four digital pathology images of different subspecialties on three different display systems, it was concluded that pathology images look different when visualized on different display systems. The importance of these visual differences is elucidated when they are located in areas of the digital slide that contain clinically relevant features. Based on a calculation of dE2000 differences between background and clinically relevant features, it was clear that perceived contrast of clinically relevant features is influenced by the choice of display system. Furthermore, it seems that the specific calibration target chosen for the display system has an important effect on the perceived contrast of clinically relevant features. Preliminary results suggest that calibrating to DICOM GSDF calibration performed slightly worse than sRGB, while a new experimental calibration target CSDF performed better than both DICOM GSDF and sRGB. This result is promising as it suggests that further research work could lead to better definition of an optimized calibration target for digital pathology images resulting in a positive effect on clinical performance.

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

PubMed

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

2017-07-05

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

Current Practices in Lumbar Surgery Perioperative Rehabilitation: A Scoping Review.

PubMed

Marchand, Andrée-Anne; O'Shaughnessy, Julie; Châtillon, Claude-Édouard; Sorra, Karin; Descarreaux, Martin

The objective of this review was to identify current practices and relevant patient-reported and objective outcome measures with regard to rehabilitation protocols directed at the lumbar spine in perioperative procedure settings in order to inform clinical practice and future research. A literature search was performed in MEDLINE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), the Cochrane Central Register of Controlled Trials, PEDro (Physiotherapy Evidence Database), and PubMed using terms relevant to surgical interventions, rehabilitation, and the lumbar spine. Twenty-nine studies met the inclusion criteria, and 28 investigated postoperative forms of rehabilitation. Patient-reported outcomes typically used were pain and disability, although a wide range of objective measures based on physical capacities were often reported. Rehabilitation programs, for the most part, included some form of strengthening exercises alone or in combination with stabilization exercises, aerobic conditioning, stretching, or education. Despite most studies reporting statistically significant results between intervention groups, considering clinically significant improvement within intervention groups yielded a different portrait. A wide range of objective and subjective outcomes is used to document changes after active rehabilitation. Program components include both active and assisted interventions combined with various means of education and discussion. Multimodal rehabilitation protocols after lumbar surgery may be used to improve patient-reported and objective outcome measures such as pain, disability, and physical function. Further research should be conducted on the effects of preoperative rehabilitation programs. Copyright © 2016. Published by Elsevier Inc.

Immediate effects of hip mobilization with movement in patients with hip osteoarthritis: A randomised controlled trial.

PubMed

Beselga, Carlos; Neto, Francisco; Alburquerque-Sendín, Francisco; Hall, Toby; Oliveira-Campelo, Natália

2016-04-01

Mobilization with movement (MWM) has been shown to reduce pain, increase range of motion (ROM) and physical function in a range of different musculoskeletal disorders. Despite this evidence, there is a lack of studies evaluating the effects of MWM for hip osteoarthritis (OA). To determine the immediate effects of MWM on pain, ROM and functional performance in patients with hip OA. Randomized controlled trial with immediate follow-up. Forty consenting patients (mean age 78 ± 6 years; 54% female) satisfied the eligibility criteria. All participants completed the study. Two forms of MWM techniques (n = 20) or a simulated MWM (sham) (n = 20) were applied. pain recorded by numerical rating scale (NRS). hip flexion and internal rotation ROM, and physical performance (timed up and go, sit to stand, and 40 m self placed walk test) were assessed before and after the intervention. For the MWM group, pain decreased by 2 points on the NRS, hip flexion increased by 12.2°, internal rotation by 4.4°, and functional tests were also improved with clinically relevant effects following the MWM. There were no significant changes in the sham group for any outcome variable. Pain, hip flexion ROM and physical performance immediately improved after the application of MWM in elderly patients suffering hip OA. The observed immediate changes were of clinical relevance. Future studies are required to determine the long-term effects of this intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Effects of Clinically Relevant Multiple-Choice Items on the Statistical Discrimination of Physician Clinical Competence.

ERIC Educational Resources Information Center

Downing, Steven M.; Maatsch, Jack L.

To test the effect of clinically relevant multiple-choice item content on the validity of statistical discriminations of physicians' clinical competence, data were collected from a field test of the Emergency Medicine Examination, test items for the certification of specialists in emergency medicine. Two 91-item multiple-choice subscales were…

Low absolute neutrophil counts in African infants.

PubMed

Kourtis, Athena P; Bramson, Brian; van der Horst, Charles; Kazembe, Peter; Ahmed, Yusuf; Chasela, Charles; Hosseinipour, Mina; Knight, Rodney; Lugalia, Lebah; Tegha, Gerald; Joaki, George; Jafali, Robert; Jamieson, Denise J

2005-07-01

Infants of African origin have a lower normal range of absolute neutrophil counts than white infants; this fact, however, remains under appreciated by clinical researchers in the United States. During the initial stages of a clinical trial in Malawi, the authors noted an unexpectedly high number of infants with absolute neutrophil counts that would be classifiable as neutropenic using the National Institutes of Health's Division of AIDS toxicity tables. The authors argue that the relevant Division of AIDS table does not take into account the available evidence of low absolute neutrophil counts in African infants and that a systematic collection of data from many African settings might help establish the absolute neutrophil count cutpoints to be used for defining neutropenia in African populations.

[Formula: see text]The statistical crisis in science: how is it relevant to clinical neuropsychology?

PubMed

Gelman, Andrew; Geurts, Hilde M

There is currently increased attention to the statistical (and replication) crisis in science. Biomedicine and social psychology have been at the heart of this crisis, but similar problems are evident in a wide range of fields. We discuss three examples of replication challenges from the field of social psychology and some proposed solutions, and then consider the applicability of these ideas to clinical neuropsychology. In addition to procedural developments such as preregistration and open data and criticism, we recommend that data be collected and analyzed with more recognition that each new study is a part of a learning process. The goal of improving neuropsychological assessment, care, and cure is too important to not take good scientific practice seriously.

EASD Diabetes Technology Meeting

PubMed Central

2014-01-01

The first diabetes technology meeting organized by the European Diabetes Association covers the range from regulatory aspects, patient safety, about registries to clinical studies. After an intensive discussion about the evidence required for registration and reimbursement on new medical devices and in vitro diagnostics it becomes clear that more and better clinical trials will be required in the future. This was also highlighted by representatives of the American Diabetes Association. The 2 associations will be active in this field of research by a joint committee. This meeting is intended not to become a large-scale meeting focused on education but to provide a platform for an open discussion of experts involved in all areas that are relevant to achieve a meaningful usage of diabetes technology. PMID:24876444

Relationship between clinical site of isolation and ability to form biofilms in vitro in nontypeable Haemophilus influenzae.

PubMed

Obaid, Najla A; Jacobson, Glenn A; Tristram, Stephen

2015-03-01

Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen associated with a range of infections, including various lower respiratory infections, otitis media, and conjunctivitis. There is some debate as to whether or not NTHi produces biofilms and, if so, whether or not this is relevant to pathogenesis. Although many studies have examined the association between in vitro biofilm formation and isolates from a specific infection type, few have made comparisons from isolates from a broad range of isolates grouped by clinical source. In our study 50 NTHi from different clinical sources, otitis media, conjunctivitis, lower respiratory tract infections in both cystic fibrosis and non-cystic fibrosis patients, and nasopharyngeal carriage, plus 10 nasopharyngeal isolates of the commensal Haemophilus haemolyticus were tested for the ability to form biofilm by using a static microtitre plate crystal violet assay. A high degree of variation in biofilm forming ability was observed across all isolates, with no statistically significant differences observed between the groups, with the exception of the isolates from conjunctivitis. These isolates had uniformly lower biofilm forming ability compared with isolates from the other groups (p < 0.005).

The clinical, occupational and financial outcomes associated with a bespoke specialist clinic for military aircrew-a cohort study.

PubMed

Pavitt, A J; Pavitt, C W; Harron, K; Jones, M; Timperley, A C; Reid, A N C; Mcloughlin, D; d'Arcy, J; Nicol, E D

2016-05-01

To assess the clinical, occupational and financial outcomes of a new Clinical Aviation Medicine Service (CAMS) for UK military personnel. Consecutive patients over a 2 year period were included. Predictors of flying restrictions at referral and final outcome following consultation were modelled using logistic regression. National Health Service (NHS) Payment by Results tariffs and Defence capitation data were used to assess the financial impact of the service. Eight hundred and sixteen new referrals (94.5% male, median age 45 years (range 19-75)) were received and 1025 consultations performed. Cardiovascular disease was the commonest reason for referral. CAMS clinical activity cost at NHS tariff was £453 310 representing a saving of £316 173 (£137 137 delivery cost). In total, 310/816 (38%) patients had employment restrictions on referral and 49.0% of this group returned to full employment following their initial consultation. Compared with cardiology, general medicine and respiratory patients were more likely to have been occupationally restricted prior to referral (50 vs. 35%, OR 1.81; 95% CI 1.18-2.76, P values=0.006 and 53 vs. 35%, OR 2.12; 95% CI 1.15-3.90, P values = 0.016, respectively). Overall 581/816 (71.2%) of patients returned to unrestricted employment while 98/816 (12.0%) were unable to continue in any aircrew role. The service saved 7000 lost working days per year at an estimated occupational saving of ∼£1 million per annum. This bespoke service has allowed rapid, occupationally relevant clinical care to be delivered with both time and financial savings. The model may have significant occupational and financial relevance for other environmental and occupational medical organizations. © Crown copyright 2015.

The clinical, occupational and financial outcomes associated with a bespoke specialist clinic for military aircrew—a cohort study

PubMed Central

Pavitt, A.J.; Pavitt, C.W.; Harron, K.; Jones, M.; Timperley, A.C.; Reid, A.N.C.; Mcloughlin, D.; d'Arcy, J.

2016-01-01

Objectives: To assess the clinical, occupational and financial outcomes of a new Clinical Aviation Medicine Service (CAMS) for UK military personnel. Methods: Consecutive patients over a 2 year period were included. Predictors of flying restrictions at referral and final outcome following consultation were modelled using logistic regression. National Health Service (NHS) Payment by Results tariffs and Defence capitation data were used to assess the financial impact of the service. Results: Eight hundred and sixteen new referrals (94.5% male, median age 45 years (range 19–75)) were received and 1025 consultations performed. Cardiovascular disease was the commonest reason for referral. CAMS clinical activity cost at NHS tariff was £453 310 representing a saving of £316 173 (£137 137 delivery cost). In total, 310/816 (38%) patients had employment restrictions on referral and 49.0% of this group returned to full employment following their initial consultation. Compared with cardiology, general medicine and respiratory patients were more likely to have been occupationally restricted prior to referral (50 vs. 35%, OR 1.81; 95% CI 1.18–2.76, P values=0.006 and 53 vs. 35%, OR 2.12; 95% CI 1.15–3.90, P values = 0.016, respectively). Overall 581/816 (71.2%) of patients returned to unrestricted employment while 98/816 (12.0%) were unable to continue in any aircrew role. The service saved 7000 lost working days per year at an estimated occupational saving of ∼£1 million per annum. Conclusions: This bespoke service has allowed rapid, occupationally relevant clinical care to be delivered with both time and financial savings. The model may have significant occupational and financial relevance for other environmental and occupational medical organizations. PMID:26424788

A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

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

Lips, Irene M., E-mail: i.m.lips@umcutrecht.nl; Gils, Carla H. van; Kotte, Alexis N.T.J.

2012-06-01

Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondarymore » outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.« less

Impact of a novel teaching method based on feedback, activity, individuality and relevance on students' learning.

PubMed

Edafe, Ovie; Brooks, William S; Laskar, Simone N; Benjamin, Miles W; Chan, Philip

2016-03-20

This study examines the perceived impact of a novel clinical teaching method based on FAIR principles (feedback, activity, individuality and relevance) on students' learning on clinical placement. This was a qualitative research study. Participants were third year and final year medical students attached to one UK vascular firm over a four-year period (N=108). Students were asked to write a reflective essay on how FAIRness approach differs from previous clinical placement, and its advantages and disadvantages. Essays were thematically analysed and globally rated (positive, negative or neutral) by two independent researchers. Over 90% of essays reported positive experiences of feedback, activity, individuality and relevance model. The model provided multifaceted feedback; active participation; longitudinal improvement; relevance to stage of learning and future goals; structured teaching; professional development; safe learning environment; consultant involvement in teaching. Students perceived preparation for tutorials to be time intensive for tutors/students; a lack of teaching on medical sciences and direct observation of performance; more than once weekly sessions would be beneficial; some issues with peer and public feedback, relevance to upcoming exam and large group sizes. Students described negative experiences of "standard" clinical teaching. Progressive teaching programmes based on the FAIRness principles, feedback, activity, individuality and relevance, could be used as a model to improve current undergraduate clinical teaching.

Health promotion in medical education: lessons from a major undergraduate curriculum implementation.

PubMed

Wylie, Ann; Leedham-Green, Kathleen

2017-11-01

Despite the economic, environmental and patient-related imperatives to prepare medical students to become health promoting doctors, health promotion remains relatively deprioritised in medical curricula. This paper uses an in-depth case study of a health promotion curriculum implementation at a large UK medical school to provide insights into the experiences of teachers and learners across a range of topics, pedagogies, and teaching & assessment modalities. Topics included smoking cessation, behavioural change approaches to obesity, exercise prescribing, social prescribing, maternal and child health, public and global health; with pedagogies ranging from e-learning to practice-based project work. Qualitative methods including focus groups, analysis of reflective learning submissions, and evaluation data are used to illuminate motivations, frustrations, practicalities, successes and limiting factors. Over this three year implementation, a range of challenges have been highlighted including: how adequately to prepare and support clinical teachers; the need to establish relevance and importance to strategic learners; the need for experiential learning in clinical environments to support classroom-based activities; and the need to rebalance competing aspects of the curriculum. Conclusions are drawn about heterogeneous deep learning over standardised surface learning, and the impacts, both positive and negative, of different assessment modalities on these types of learning.

[Dentistry and healthcare legislation 2. Differences of opinion concerning professional standards for oral healthcare].

PubMed

Brands, W G; van der Ven, J M; Eijkman, M A J

2013-05-01

With respect to disciplinary and other complaints, it is apparent that they are often based on a difference of opinion concerning professional standards for oral healthcare. Relevant differences of opinion can arise between dentists, but also in the dentist-patient relationship. A large degree of the ambiguity which lies at the basis of such discussions could be removed by the use of clear clinical guidelines. Since these are still scarce in oral healthcare, a dentist will have to rely on adequate communication to avoid conflicts. A dentist must be aware of possible conflicts of interest and of the characteristic range of the professional standards for oral healthcare. Departing from that range at the request of a patient is not an option.

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

PubMed

Wiechmann, Warren; Kwan, Daniel; Bokarius, Andrew; Toohey, Shannon L

2016-03-01

The use of personal mobile devices in the medical field has grown quickly, and a large proportion of physicians use their mobile devices as an immediate resource for clinical decision-making, prescription information and other medical information. The iTunes App Store (Apple, Inc.) contains approximately 20,000 apps in its "Medical" category, providing a robust repository of resources for clinicians; however, this represents only 2% of the entire App Store. The App Store does not have strict criteria for identifying content specific to practicing physicians, making the identification of clinically relevant content difficult. The objective of this study is to quantify the characteristics of existing medical applications in the iTunes App Store that could be used by emergency physicians, residents, or medical students. We found applications related to emergency medicine (EM) by searching the iTunes App Store for 21 terms representing core content areas of EM, such as "emergency medicine," "critical care," "orthopedics," and "procedures." Two physicians independently reviewed descriptions of these applications in the App Store and categorized each as the following: Clinically Relevant, Book/Published Source, Non-English, Study Tools, or Not Relevant. A third physician reviewer resolved disagreements about categorization. Descriptive statistics were calculated. We found a total of 7,699 apps from the 21 search terms, of which 17.8% were clinical, 9.6% were based on a book or published source, 1.6% were non-English, 0.7% were clinically relevant patient education resources, and 4.8% were study tools. Most significantly, 64.9% were considered not relevant to medical professionals. Clinically relevant apps make up approximately 6.9% of the App Store's "Medical" Category and 0.1% of the overall App Store. Clinically relevant apps represent only a small percentage (6.9%) of the total App volume within the Medical section of the App Store. Without a structured search-and-evaluation strategy, it may be difficult for the casual user to identify this potentially useful content. Given the increasing adoption of devices in healthcare, national EM associations should consider curating these resources for their members.

A randomized trial comparing INR monitoring devices in patients with anticoagulation self-management: evaluation of a novel error-grid approach.

PubMed

Hemkens, Lars G; Hilden, Kristian M; Hartschen, Stephan; Kaiser, Thomas; Didjurgeit, Ulrike; Hansen, Roland; Bender, Ralf; Sawicki, Peter T

2008-08-01

In addition to the metrological quality of international normalized ratio (INR) monitoring devices used in patients' self-management of long-term anticoagulation, the effectiveness of self-monitoring with such devices has to be evaluated under real-life conditions with a focus on clinical implications. An approach to evaluate the clinical significance of inaccuracies is the error-grid analysis as already established in self-monitoring of blood glucose. Two anticoagulation monitors were compared in a real-life setting and a novel error-grid instrument for oral anticoagulation has been evaluated. In a randomized crossover study 16 patients performed self-management of anticoagulation using the INRatio and the CoaguChek S system. Main outcome measures were clinically relevant INR differences according to established criteria and to the error-grid approach. A lower rate of clinically relevant disagreements according to Anderson's criteria was found with CoaguChek S than with INRatio without statistical significance (10.77% vs. 12.90%; P = 0.787). Using the error-grid we found principally consistent results: More measurement pairs with discrepancies of no or low clinical relevance were found with CoaguChek S, whereas with INRatio we found more differences with a moderate clinical relevance. A high rate of patients' satisfaction with both of the point of care devices was found with only marginal differences. A principal appropriateness of the investigated point-of-care devices to adequately monitor the INR is shown. The error-grid is useful for comparing monitoring methods with a focus on clinical relevance under real-life conditions beyond assessing the pure metrological quality, but we emphasize that additional trials using this instrument with larger patient populations are needed to detect differences in clinically relevant disagreements.

Important factors to consider when treating children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): perspectives of health professionals from specialist services.

PubMed

Parslow, Roxanne M; Shaw, Alison; Haywood, Kirstie L; Crawley, Esther

2017-02-01

Paediatric Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME) is relatively common and disabling. Improving treatment requires the development of Patient Reported Outcome Measures (PROMs) that enable clinicians and researchers to collect patient-centred evidence on outcomes. Health professionals are well placed to provide clinical insight into the condition, its treatment and possible outcomes. This study aimed to understand the perspectives of specialist paediatric CFS/ME health professionals and identify outcomes that are clinically important. Focus groups and interviews were held with 15 health professionals involved in the care of children with CFS/ME from the four largest specialist paediatric CFS/ME services in the NHS in England. A range of clinical disciplines were included and experience in paediatric CFS/ME ranged from 2 months to 25 years. Ten participants (67%) were female. Focus groups and interviews were recorded, transcribed verbatim and data were analysed using thematic analysis. All health professionals identified the impact of CFS/ME across multiple aspects of health. Health professionals described four areas used to assess the severity of the illness and outcome in children: 1) symptoms; 2) physical function; 3) participation (school, activities and social life); and 4) emotional wellbeing. They also described the complexity of the condition, contextual factors and considerations for treatment to help children to cope with the condition. Clinically important outcomes in paediatric CFS/ME involve a range of aspects of health. Health professionals consider increases in physical function yet maintaining school functioning and participation more widely as important outcomes from treatment. The results are similar to those described by children in a recent study and will be combined to develop a new child-specific PROM that has strong clinical utility and patient relevance.

The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants

PubMed Central

Baumann, Pierre; Ulrich, Sven; Eckermann, Gabriel; Gerlach, Manfred; Kuss, Hans-Joachim; Laux, Gerd; Müller-Oerlinghausen, Bruno; Rao, Marie Luise; Riederer, Peter; Zernig, Gerald; Hiemke, Christoph

2005-01-01

Therapeutic drug monitoring (TDM) of psychotropic drugs such as antidepressants has been widely introduced for optimization of pharmacotherapy in psychiatric patients. The interdisciplinary TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has worked out consensus guidelines with the aim of providing psychiatrists and TDM laboratories with a tool to optimize the use of TDM. Five research-based levels of recommendation were defined with regard to routine monitoring of drug plasma concentrations: (i) strongly recommended; (ii) recommended; (iii) useful; (iv) probably useful; and (v) not recommended. In addition, a list of indications that justify the use of TDM is presented, eg, control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning drug metabolism, and children, adolescents, and elderly patients. For some drugs, studies on therapeutic ranges are lacking, but target ranges for clinically relevant plasma concentrations are presented for most drugs, based on pharmacokinetic studies reported in the literature. For many antidepressants, a thorough analysis of the literature on studies dealing with the plasma concentration–clinical effectiveness relationship allowed inclusion of therapeutic ranges of plasma concentrations. In addition, recommendations are made with regard to the combination of pharmacogenetic (phenotyping or genotyping) tests with TDM, Finally, practical instructions are given for the laboratory practitioners and the treating physicians how to use TDM: preparation of TDM, drug analysis, reporting and interpretation of results, and adequate use of information for patient treatment. TDM is a complex process that needs optimal interdisciplinary coordination of a procedure implicating patients, treating physicians, clinical pharmacologists, and clinical laboratory specialists. These consensus guidelines should be helpful for optimizing TDM of antidepressants. PMID:16156382

Insufficient documentation for clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis, based on a systematic review and meta-analysis.

PubMed

Winther, Kristian Hillert; Wichman, Johanna Eva Märta; Bonnema, Steen Joop; Hegedüs, Laszlo

2017-02-01

By a systematic review and meta-analysis to investigate clinically relevant effects of selenium supplementation in patients with chronic autoimmune thyroiditis. Controlled trials in adults (≥18 years) with autoimmune thyroiditis, comparing selenium with or without levothyroxine substitution, versus placebo and/or levothyroxine substitution, were eligible for inclusion. Identified outcomes were serum thyrotropin (thyroid stimulating hormone) levels in LT4-untreated patients, thyroid ultrasound and health-related quality of life. Eleven publications, covering nine controlled trials, were included in the systematic review. Random effects model meta-analyses were performed in weighted mean difference for thyroid stimulating hormone, ultrasound and health-related quality of life. Quality of evidence was assessed per outcome, using GRADE. Meta-analyses showed no change in thyroid stimulating hormone, or improvements in health-related quality of life or thyroid echogenicity (ultrasound), between levothyroxine substitution-untreated patients assigned to selenium supplementation or placebo. Three trials found some improvement in wellbeing in patients receiving levothyroxine substitution, but could not be synthesized in a meta-analysis. The quality of evidence ranged from very low to low for thyroid stimulating hormone as well as ultrasound outcomes, and low to moderate for health-related quality of life, and was generally downgraded due to small sample sizes. We found no effect of selenium supplementation on thyroid stimulating hormone, health-related quality of life or thyroid ultrasound, in levothyroxine substitution-untreated individuals, and sporadic evaluation of clinically relevant outcomes in levothyroxine substitution-treated patients. Future well-powered RCTs, evaluating e.g. disease progression or health-related quality of life, are warranted before determining the relevance of selenium supplementation in autoimmune thyroiditis.

Gender-, age-, and race/ethnicity-based differential item functioning analysis of the movement disorder society-sponsored revision of the Unified Parkinson's disease rating scale.

PubMed

Goetz, Christopher G; Liu, Yuanyuan; Stebbins, Glenn T; Wang, Lu; Tilley, Barbara C; Teresi, Jeanne A; Merkitch, Douglas; Luo, Sheng

2016-12-01

Assess MDS-UPDRS items for gender-, age-, and race/ethnicity-based differential item functioning. Assessing differential item functioning is a core rating scale validation step. For the MDS-UPDRS, differential item functioning occurs if item-score probability among people with similar levels of parkinsonism differ according to selected covariates (gender, age, race/ethnicity). If the magnitude of differential item functioning is clinically relevant, item-score interpretation must consider influences by these covariates. Differential item functioning can be nonuniform (covariate variably influences an item-score across different levels of parkinsonism) or uniform (covariate influences an item-score consistently over all levels of parkinsonism). Using the MDS-UPDRS translation database of more than 5,000 PD patients from 14 languages, we tested gender-, age-, and race/ethnicity-based differential item functioning. To designate an item as having clinically relevant differential item functioning, we required statistical confirmation by 2 independent methods, along with a McFadden pseudo-R 2 magnitude statistic greater than "negligible." Most items showed no gender-, age- or race/ethnicity-based differential item functioning. When differential item functioning was identified, the magnitude statistic was always in the "negligible" range, and the scale-level impact was minimal. The absence of clinically relevant differential item functioning across all items and all parts of the MDS-UPDRS is strong evidence that the scale can be used confidently. As studies of Parkinson's disease increasingly involve multinational efforts and the MDS-UPDRS has several validated non-English translations, the findings support the scale's broad applicability in populations with varying gender, age, and race/ethnicity distributions. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Shear lag sutures: Improved suture repair through the use of adhesives

PubMed Central

Linderman, Stephen W.; Kormpakis, Ioannis; Gelberman, Richard H.; Birman, Victor; Wegst, Ulrike G. K.; Genin, Guy M.; Thomopoulos, Stavros

2015-01-01

Suture materials and surgical knot tying techniques have improved dramatically since their first use over five millennia ago. However, the approach remains limited by the ability of the suture to transfer load to tissue at suture anchor points. Here, we predict that adhesive-coated sutures can improve mechanical load transfer beyond the range of performance of existing suture methods, thereby strengthening repairs and decreasing the risk of failure. The mechanical properties of suitable adhesives were identified using a shear lag model. Examination of the design space for an optimal adhesive demonstrated requirements for strong adhesion and low stiffness to maximize the strength of the adhesive-coated suture repair construct. To experimentally assess the model, we evaluated single strands of sutures coated with highly flexible cyanoacrylates (Loctite 4903 and 4902), cyanoacrylate (Loctite QuickTite Instant Adhesive Gel), rubber cement, rubber/gasket adhesive (1300 Scotch-Weld Neoprene High Performance Rubber & Gasket Adhesive), an albumin-glutaraldehyde adhesive (BioGlue), or poly(dopamine). As a clinically relevant proof-of-concept, cyanoacrylate-coated sutures were then used to perform a clinically relevant flexor digitorum tendon repair in cadaver tissue. The repair performed with adhesive-coated suture had significantly higher strength compared to the standard repair without adhesive. Notably, cyanoacrylate provides strong adhesion with high stiffness and brittle behavior, and is therefore not an ideal adhesive for enhancing suture repair. Nevertheless, the improvement in repair properties in a clinically relevant setting, even using a non-ideal adhesive, demonstrates the potential for the proposed approach to improve outcomes for treatments requiring suture fixation. Further study is necessary to develop a strongly adherent, compliant adhesive within the optimal design space described by the model. PMID:26022966

Evidence-based management of recurrent miscarriages

PubMed Central

Jeve, Yadava B.; Davies, William

2014-01-01

Recurrent miscarriages are postimplantation failures in natural conception; they are also termed as habitual abortions or recurrent pregnancy losses. Recurrent pregnancy loss is disheartening to the couple and to the treating clinician. There has been a wide range of research from aetiology to management of recurrent pregnancy loss. It is one of the most debated topic among clinicians and academics. The ideal management is unanswered. This review is aimed to produce an evidence-based guidance on clinical management of recurrent miscarriage. The review is structured to be clinically relevant. We have searched electronic databases (PubMed and Embase) using different key words. We have combined the searches and arranged them with the hierarchy of evidences. We have critically appraised the evidence to produce a concise answer for clinical practice. We have graded the evidence from level I to V on which these recommendations are based. PMID:25395740

Experts' Views Regarding the Conceptualization of Narcissism.

PubMed

Ackerman, Robert A; Hands, Aaron J; Donnellan, M Brent; Hopwood, Christopher J; Witt, Edward A

2017-06-01

There is debate over the definition of narcissism across social/personality and clinical psychology. The current article aims to quantify the level of disagreement by measuring experts' opinions concerning the attributes most central to narcissism. Accordingly, we developed a comprehensive list of attributes associated with narcissism and had 49 self-identified experts (among them 17 women, 23 psychologists from clinical psychology and 22 from social/personality psychology) rate these characteristics and provide their opinions on several issues related to the conceptualization of narcissism. Experts generally believe that the grandiose features of narcissism are more central than the vulnerable features. However, differences between clinical and social/personality psychologists were evident, especially regarding the relevance of self-esteem. Given the results, we suggest that researchers specify the kind of narcissism being assessed in a given study and consider using assessments of the full range of narcissistic features in future research to provide a more comprehensive perspective on the construct.

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

PubMed Central

Pantziarka, Pan; Bouche, Gauthier; Sukhatme, Vidula; Meheus, Lydie; Rooman, Ilse; Sukhatme, Vikas P

2016-01-01

Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response. Based on this evidence the case is made for further clinical investigation of the anticancer effects of PRO, particularly in combination with other agents. A number of trials are on-going, in different treatment settings for various cancers. PMID:27899953

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

Baker, Erin Shammel; Burnum-Johnson, Kristin E.; Jacobs, Jon M.

Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is an imperative goal for the field of medicine. While mass spectrometry (MS)-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry (IMS) separations [1, 2] with liquid chromatography (LC) andmore » MS to dramatically increase measurement sensitivity and throughput, further enabling future MS-based clinical applications. An initial application of the LC-IMS-MS platform for the analysis of blood serum samples from stratified post-liver transplant patients with recurrent fibrosis progression illustrates its potential utility for disease characterization and use in personalized medicine [3, 4].« less

Amitriptyline for the treatment of fibromyalgia: a comprehensive review.

PubMed

Rico-Villademoros, Fernando; Slim, Mahmoud; Calandre, Elena P

2015-10-01

Fibromyalgia is characterized by chronic generalized pain accompanied by a wide range of clinical manifestations. Most clinical practice guidelines recommend multidisciplinary treatment using a combination of pharmacological and non-pharmacological therapies. The tricyclic antidepressant amitriptyline has been most thoroughly studied in fibromyalgia. Amitriptyline has been evaluated in placebo-controlled studies, and it has served as an active comparator to other therapeutic interventions in the treatment of fibromyalgia. In addition, several systematic reviews and meta-analyses have evaluated its efficacy and safety for the treatment of fibromyalgia. Data from individual studies as well as from systematic reviews indicate that low doses (10-75 mg/day) of amitriptyline are effective for the treatment of fibromyalgia and, despite the limited quality of the data, they do not seem to be associated with relevant tolerability or safety issues. Consistent with some clinical guidelines, we believe amitriptyline in low doses should be considered a first-line drug for the treatment of fibromyalgia.

Sensitivity and Predictive Value of 15 PubMed Search Strategies to Answer Clinical Questions Rated Against Full Systematic Reviews

PubMed Central

Merglen, Arnaud; Courvoisier, Delphine S; Combescure, Christophe; Garin, Nicolas; Perrier, Arnaud; Perneger, Thomas V

2012-01-01

Background Clinicians perform searches in PubMed daily, but retrieving relevant studies is challenging due to the rapid expansion of medical knowledge. Little is known about the performance of search strategies when they are applied to answer specific clinical questions. Objective To compare the performance of 15 PubMed search strategies in retrieving relevant clinical trials on therapeutic interventions. Methods We used Cochrane systematic reviews to identify relevant trials for 30 clinical questions. Search terms were extracted from the abstract using a predefined procedure based on the population, interventions, comparison, outcomes (PICO) framework and combined into queries. We tested 15 search strategies that varied in their query (PIC or PICO), use of PubMed’s Clinical Queries therapeutic filters (broad or narrow), search limits, and PubMed links to related articles. We assessed sensitivity (recall) and positive predictive value (precision) of each strategy on the first 2 PubMed pages (40 articles) and on the complete search output. Results The performance of the search strategies varied widely according to the clinical question. Unfiltered searches and those using the broad filter of Clinical Queries produced large outputs and retrieved few relevant articles within the first 2 pages, resulting in a median sensitivity of only 10%–25%. In contrast, all searches using the narrow filter performed significantly better, with a median sensitivity of about 50% (all P < .001 compared with unfiltered queries) and positive predictive values of 20%–30% (P < .001 compared with unfiltered queries). This benefit was consistent for most clinical questions. Searches based on related articles retrieved about a third of the relevant studies. Conclusions The Clinical Queries narrow filter, along with well-formulated queries based on the PICO framework, provided the greatest aid in retrieving relevant clinical trials within the 2 first PubMed pages. These results can help clinicians apply effective strategies to answer their questions at the point of care. PMID:22693047

Sensitivity and predictive value of 15 PubMed search strategies to answer clinical questions rated against full systematic reviews.

PubMed

Agoritsas, Thomas; Merglen, Arnaud; Courvoisier, Delphine S; Combescure, Christophe; Garin, Nicolas; Perrier, Arnaud; Perneger, Thomas V

2012-06-12

Clinicians perform searches in PubMed daily, but retrieving relevant studies is challenging due to the rapid expansion of medical knowledge. Little is known about the performance of search strategies when they are applied to answer specific clinical questions. To compare the performance of 15 PubMed search strategies in retrieving relevant clinical trials on therapeutic interventions. We used Cochrane systematic reviews to identify relevant trials for 30 clinical questions. Search terms were extracted from the abstract using a predefined procedure based on the population, interventions, comparison, outcomes (PICO) framework and combined into queries. We tested 15 search strategies that varied in their query (PIC or PICO), use of PubMed's Clinical Queries therapeutic filters (broad or narrow), search limits, and PubMed links to related articles. We assessed sensitivity (recall) and positive predictive value (precision) of each strategy on the first 2 PubMed pages (40 articles) and on the complete search output. The performance of the search strategies varied widely according to the clinical question. Unfiltered searches and those using the broad filter of Clinical Queries produced large outputs and retrieved few relevant articles within the first 2 pages, resulting in a median sensitivity of only 10%-25%. In contrast, all searches using the narrow filter performed significantly better, with a median sensitivity of about 50% (all P < .001 compared with unfiltered queries) and positive predictive values of 20%-30% (P < .001 compared with unfiltered queries). This benefit was consistent for most clinical questions. Searches based on related articles retrieved about a third of the relevant studies. The Clinical Queries narrow filter, along with well-formulated queries based on the PICO framework, provided the greatest aid in retrieving relevant clinical trials within the 2 first PubMed pages. These results can help clinicians apply effective strategies to answer their questions at the point of care.

CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING.

PubMed

Hafler, Brian P

2017-03-01

Inherited retinal dystrophies are a significant cause of vision loss and are characterized by the loss of photoreceptors and the retinal pigment epithelium (RPE). Mutations in approximately 250 genes cause inherited retinal degenerations with a high degree of genetic heterogeneity. New techniques in next-generation sequencing are allowing the comprehensive analysis of all retinal disease genes thus changing the approach to the molecular diagnosis of inherited retinal dystrophies. This review serves to analyze clinical progress in genetic diagnostic testing and implications for retinal gene therapy. A literature search of PubMed and OMIM was conducted to relevant articles in inherited retinal dystrophies. Next-generation genetic sequencing allows the simultaneous analysis of all the approximately 250 genes that cause inherited retinal dystrophies. Reported diagnostic rates range are high and range from 51% to 57%. These new sequencing tools are highly accurate with sensitivities of 97.9% and specificities of 100%. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations. Not only are high diagnostic yields obtained, but mutations in genes with novel clinical phenotypes are also identified. In the era of retinal gene therapy clinical trials, identifying specific genetic defects will increasingly be of use to identify patients who may enroll in clinical studies and benefit from novel therapies.

Clinical chemistry and hematology values in a Caribbean population of African green monkeys.

PubMed

Liddie, Shervin; Goody, Robin J; Valles, Rodrigo; Lawrence, Matthew S

2010-12-01

Hematology and clinical chemistry (HCC) reference values are critical in veterinary practice and in vivo pre-clinical research, enabling detection of health abnormalities, response to therapeutic intervention or adverse toxicological effects, as well as monitoring of clinical management. In this report, reference ranges for 46 HCC parameters were characterized in 331 wild-caught and colony-bred African green monkeys. Effects of sex, weight and duration of captivity were determined by one-way analysis of variance. Significant sex differences were observed for several HCC parameters. Significant differences were also observed for select HCC variables between newly caught animals and those held in captivity for 1-12 months or longer. Comparison of this data with other non-human primate species and humans highlights similarities and disparities between species. Potential causes of interpopulation variability and relevance to the use of the African green monkey as a non-human primate model are discussed. © 2010 John Wiley & Sons A/S.

Clinical impact of migraine for the management of glaucoma patients.

PubMed

Nguyen, Bao N; Lek, Jia Jia; Vingrys, Algis J; McKendrick, Allison M

2016-03-01

Migraine is a common and debilitating primary headache disorder that affects 10-15% of the general population, particularly people of working age. Migraine is relevant to providers of clinical eye-care because migraine attacks are associated with a range of visual sensory symptoms, and because of growing evidence that the results of standard tests of visual function necessary for the diagnosis and monitoring of glaucoma (visual fields, electrophysiology, ocular imaging) can be abnormal due to migraine. These abnormalities are measureable in-between migraine events (the interictal period), despite patients being asymptomatic and otherwise healthy. This picture is further complicated by epidemiological data that suggests an increased prevalence of migraine in patients with glaucoma, particularly in patients with normal tension glaucoma. We discuss how migraine, as a co-morbidity, can confound the results and interpretation of clinical tests that form part of contemporary glaucoma evaluation, and provide practical evidence-based recommendations for the clinical testing and management of patients with migraine who attend eye-care settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

Council Clinical Perspective: Cardiovascular Health of Patients with Cancer and Cancer Survivors: A Roadmap to the Next Level

PubMed Central

Barac, Ana; Murtagh, Gillian; Carver, Joseph R.; Chen, Ming Hui; Freeman, Andrew M.; Herrmann, Joerg; Iliescu, Cezar; Ky, Bonnie; Mayer, Erica L.; Okwuosa, Tochi M.; Plana, Juan Carlos; Ryan, Thomas D.; Rzeszut, Anne K.; Douglas, Pamela S.

2015-01-01

Many existing and emerging cancer therapies have significant impact on the cardiovascular (CV) health of patients with cancer and cancer survivors. This manuscript examines current aspects of interdisciplinary cardio-oncology clinical care delivery and education in the United States and outlines how these data provide a platform for future development of the field. We present the results of the nationwide survey on cardio-oncology services, practices and opinions, conducted among Chiefs of Cardiology and Program Directors, that demonstrate ranges of clinical activities and identify significant interest for increased educational opportunities and expert training of CV physicians in this field. The survey respondents recognized clinical relevance, but emphasized lack of national guidelines, lack of funds, and limited awareness and infrastructure as the main challenges for development and growth of cardio-oncology. We discuss potential solutions to unmet needs through interdisciplinary collaboration and the active roles of professional societies and other stakeholders. PMID:26112199

Potential value of health information exchange for people with epilepsy: crossover patterns and missing clinical data.

PubMed

Grinspan, Zachary M; Abramson, Erika L; Banerjee, Samprit; Kern, Lisa M; Kaushal, Rainu; Shapiro, Jason S

2013-01-01

For people with epilepsy, the potential value of health information exchange (HIE) is unknown. We reviewed two years of clinical encounters for 8055 people with epilepsy from seven Manhattan hospitals. We created network graphs illustrating crossover among these hospitals for multiple encounter types, and calculated a novel metric of care fragmentation: "encounters at risk for missing clinical data." Given two hospitals, a median of 109 [range 46 - 588] patients with epilepsy had visited both. Due to this crossover, recent, relevant clinical data may be missing at the time of care frequently (44.8% of ED encounters, 34.5% inpatient, 24.9% outpatient, and 23.2% radiology). Though a smaller percentage of outpatient encounters were at risk for missing data than ED encounters, the absolute number of outpatient encounters at risk was three times higher (14,579 vs. 5041). People with epilepsy may benefit from HIE. Future HIE initiatives should prioritize outpatient access.

CLINICALLY SIGNIFICANT PSYCHOTROPIC DRUG-DRUG INTERACTIONS IN THE PRIMARY CARE SETTING

PubMed Central

English, Brett A.; Dortch, Marcus; Ereshefsky, Larry; Jhee, Stanford

2014-01-01

In recent years, the growing numbers of patients seeking care for a wide range of psychiatric illnesses in the primary care setting has resulted in an increase in the number of psychotropic medications prescribed. Along with the increased utilization of psychotropic medications, considerable variability is noted in the prescribing patterns of primary care providers and psychiatrists. Because psychiatric patients also suffer from a number of additional medical comorbidities, the increased utilization of psychotropic medications presents an elevated risk of clinically significant drug interactions in these patients. While life-threatening drug interactions are rare, clinically significant drug interactions impacting drug response or appearance of serious adverse drug reactions have been documented and can impact long-term outcomes. Additionally, the impact of genetic variability on the psychotropic drug’s pharmacodynamics and/or pharmacokinetics may further complicate drug therapy. Increased awareness of clinically relevant psychotropic drug interactions can aid clinicians to achieve optimal therapeutic outcomes in patients in the primary care setting. PMID:22707017

Grooming a CAT: customizing CAT administration rules to increase response efficiency in specific research and clinical settings.

PubMed

Kallen, Michael A; Cook, Karon F; Amtmann, Dagmar; Knowlton, Elizabeth; Gershon, Richard C

2018-05-05

To evaluate the degree to which applying alternative stopping rules would reduce response burden while maintaining score precision in the context of computer adaptive testing (CAT). Analyses were conducted on secondary data comprised of CATs administered in a clinical setting at multiple time points (baseline and up to two follow ups) to 417 study participants who had back pain (51.3%) and/or depression (47.0%). Participant mean age was 51.3 years (SD = 17.2) and ranged from 18 to 86. Participants tended to be white (84.7%), relatively well educated (77% with at least some college), female (63.9%), and married or living in a committed relationship (57.4%). The unit of analysis was individual assessment histories (i.e., CAT item response histories) from the parent study. Data were first aggregated across all individuals, domains, and time points in an omnibus dataset of assessment histories and then were disaggregated by measure for domain-specific analyses. Finally, assessment histories within a "clinically relevant range" (score ≥ 1 SD from the mean in direction of poorer health) were analyzed separately to explore score level-specific findings. Two different sets of CAT administration rules were compared. The original CAT (CAT ORIG ) rules required at least four and no more than 12 items be administered. If the score standard error (SE) reached a value < 3 points (T score metric) before 12 items were administered, the CAT was stopped. We simulated applying alternative stopping rules (CAT ALT ), removing the requirement that a minimum four items be administered, and stopped a CAT if responses to the first two items were both associated with best health, if the SE was < 3, if SE change < 0.1 (T score metric), or if 12 items were administered. We then compared score fidelity and response burden, defined as number of items administered, between CAT ORIG and CAT ALT . CAT ORIG and CAT ALT scores varied little, especially within the clinically relevant range, and response burden was substantially lower under CAT ALT (e.g., 41.2% savings in omnibus dataset). Alternate stopping rules result in substantial reductions in response burden with minimal sacrifice in score precision.

Guidelines for Guidelines: Are They Up to the Task? A Comparative Assessment of Clinical Practice Guideline Development Handbooks

PubMed Central

Ansari, Shabnam; Rashidian, Arash

2012-01-01

Objectives We conducted a comparative review of clinical practice guideline development handbooks. We aimed to identify the main guideline development tasks, assign weights to the importance of each task using expert opinions and identify the handbooks that provided a comprehensive coverage of the tasks. Methods We systematically searched and included handbooks published (in English language) by national, international or professional bodies responsible for evidenced-based guideline development. We reviewed the handbooks to identify the main guideline development tasks and scored each handbook for each task from 0 (the handbook did not mention the task) to 2 (the task suitably addressed and explained), and calculated a weighted score for each handbook. The tasks included in over 75% of the handbooks were considered as ‘necessary’ tasks. Result Nineteen guideline development handbooks and twenty seven main tasks were identified. The guideline handbooks’ weighted scores ranged from 100 to 220. Four handbooks scored over 80% of the maximum possible score, developed by the National Institute for Health and Clinical Excellence, Swiss Centre for International Health, Scottish Intercollegiate Guidelines Network and World Health Organization. Necessary tasks were: selecting the guideline topic, determining the guideline scope, identifying relevant existing guidelines, involving the consumers, forming guideline development group,, developing clinical questions, systematic search for evidence, selecting relevant evidence, appraising identifies research evidence, making group decision, grading available evidence, creating recommendations, final stakeholder consultation, guideline implementation strategies, updating recommendations and correcting potential errors. Discussion Adequate details for evidence based development of guidelines were still lacking from many handbooks. The tasks relevant to ethical issues and piloting were missing in most handbooks. The findings help decision makers in identifying the necessary tasks for guideline development, provide an updated comparative list of guideline development handbooks, and provide a checklist to assess the comprehensiveness of guideline development processes. PMID:23189167

Addressing unwarranted clinical variation: A rapid review of current evidence.

PubMed

Harrison, Reema; Manias, Elizabeth; Mears, Stephen; Heslop, David; Hinchcliff, Reece; Hay, Liz

2018-05-15

Unwarranted clinical variation (UCV) can be described as variation that can only be explained by differences in health system performance. There is a lack of clarity regarding how to define and identify UCV and, once identified, to determine whether it is sufficiently problematic to warrant action. As such, the implementation of systemic approaches to reducing UCV is challenging. A review of approaches to understand, identify, and address UCV was undertaken to determine how conceptual and theoretical frameworks currently attempt to define UCV, the approaches used to identify UCV, and the evidence of their effectiveness. Rapid evidence assessment (REA) methodology was used. A range of text words, synonyms, and subject headings were developed for the major concepts of unwarranted clinical variation, standards (and deviation from these standards), and health care environment. Two electronic databases (Medline and Pubmed) were searched from January 2006 to April 2017, in addition to hand searching of relevant journals, reference lists, and grey literature. Results were merged using reference-management software (Endnote) and duplicates removed. Inclusion criteria were independently applied to potentially relevant articles by 3 reviewers. Findings were presented in a narrative synthesis to highlight key concepts addressed in the published literature. A total of 48 relevant publications were included in the review; 21 articles were identified as eligible from the database search, 4 from hand searching published work and 23 from the grey literature. The search process highlighted the voluminous literature reporting clinical variation internationally; yet, there is a dearth of evidence regarding systematic approaches to identifying or addressing UCV. Wennberg's classification framework is commonly cited in relation to classifying variation, but no single approach is agreed upon to systematically explore and address UCV. The instances of UCV that warrant investigation and action are largely determined at a systems level currently, and stakeholder engagement in this process is limited. Lack of consensus on an evidence-based definition for UCV remains a substantial barrier to progress in this field. © 2018 John Wiley & Sons, Ltd.

Occlusal status and prevalence of occlusal malocclusion traits among 9-year-old schoolchildren.

PubMed

Lux, Christopher J; Dücker, Britta; Pritsch, Maria; Komposch, Gerda; Niekusch, Uwe

2009-06-01

The aim of this study was to provide detailed information concerning clinically relevant occlusal traits and the prevalence of occlusal anomalies in an orthodontically relevant period of dental development. Four hundred and ninety-four German schoolchildren (237 males and 257 females), median age 9 years, were orthodontically examined. Overjet and overbite were measured to the nearest 0.5 mm, and sagittal molar relationships were registered clinically to the nearest quarter unit. In addition, crossbites, scissor bites, and midline displacements were evaluated. Descriptive statistics was complemented by testing gender differences and differences between groups with Class I and Class II anomalies (Mann-Whitney U-test) as well as a statistical evaluation of differences between the three dental stages (Kruskal-Wallis test). Overjet exhibited an extreme range between -2 and 12 mm (median values 3-3.5 mm). An increased overjet was more prevalent than a reduced or reverse overjet, and a severely increased overjet greater than 6 mm was a common finding affecting around 5-10 per cent of the children. Similarly, overbite showed considerable variations of between -1 and 9 mm (medians 3-3.5 mm) and males exhibited a significantly larger overbite than females. In Class II malocclusion subjects, overbite was significantly enlarged (on average between 0.5 and 1 mm) when compared with those with a Class I malocclusion. Traumatic contact of the gingiva affected every 14th child. A Class II molar relationship of three-quarter units or more was a frequent finding affecting more than one child in five. In addition, at 9 years of age, 3 per cent of the children exhibited a Class III molar relationship of at least a half unit. The wide range of orthodontically relevant occlusal traits found in the present study underlines the need for orthodontic screening at 9 years of age (or earlier).

Development of an arthroscopically compatible polymer additive layer manufacture technique.

PubMed

Partridge, Simon W; Benning, Matthew J; German, Matthew J; Dalgarno, Kenneth W

2017-06-01

This article describes a proof of concept study designed to evaluate the potential of an in vivo three-dimensional printing route to support minimally invasive repair of the musculoskeletal system. The study uses a photocurable material to additively manufacture in situ a model implant and demonstrates that this can be achieved effectively within a clinically relevant timescale. The approach has the potential to be applied with a wide range of light-curable materials and with development could be applied to create functionally gradient structures in vivo.

Academic-industrial partnerships in drug discovery in the age of genomics.

PubMed

Harris, Tim; Papadopoulos, Stelios; Goldstein, David B

2015-06-01

Many US FDA-approved drugs have been developed through productive interactions between the biotechnology industry and academia. Technological breakthroughs in genomics, in particular large-scale sequencing of human genomes, is creating new opportunities to understand the biology of disease and to identify high-value targets relevant to a broad range of disorders. However, the scale of the work required to appropriately analyze large genomic and clinical data sets is challenging industry to develop a broader view of what areas of work constitute precompetitive research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modification of the Grood and Suntay Joint Coordinate System equations for knee joint flexion.

PubMed

Dabirrahmani, Danè; Hogg, Michael

2017-01-01

Since its introduction, the Grood and Suntay Joint Coordinate System (JCS) has been embraced by the International Society of Biomechanics (ISB) and been widely used for biomechanical reporting. There is, however, a limitation in its ability to provide correct flexion values over a wide range of clinically relevant flexion angles. This technical note addresses the limitation of the JCS equations and introduces a new set of equations to overcome this problem. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Clinical Laboratory Testing in the Era of Directly Acting Antiviral Therapies for Hepatitis C

PubMed Central

Wilson, Eleanor M.; Rosenthal, Elana S.; Kattakuzhy, Sarah; Tang, Lydia

2016-01-01

SUMMARY Directly acting antiviral (DAA) combination therapies for chronic hepatitis C virus (HCV) infection are highly effective, but treatment decisions remain complex. Laboratory testing is important to evaluate a range of viral, host, and pharmacological factors when considering HCV treatment, and patients must be monitored during and after therapy for safety and to assess the viral response. In this review, we discuss the laboratory tests relevant for the treatment of HCV infection in the era of DAA therapy, grouped according to viral and host factors. PMID:27795306

IL-15/IL-15 receptor biology: a guided tour through an expanding universe.

PubMed

Budagian, Vadim; Bulanova, Elena; Paus, Ralf; Bulfone-Paus, Silvia

2006-08-01

The cytokine interleukin-15 (IL-15) has a key role in promoting survival, proliferation and activation of natural killer (NK) and CD8+ T cells. Despite its functional similarities to IL-2, IL-15 affects a wider range of target cell populations and utilizes different mechanisms of signaling. Here, we review recent advances in the IL-15-mediated signaling, and in the functional properties on cells besides T lymphocytes and NK cells. These are discussed in the context of their potential clinical and therapeutic relevance.

Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 4: Hydrotherapy following rotator cuff repair.

PubMed

Hay, Laura; Wylie, Katherine

2011-07-01

A short cut review was carried out to establish whether hydrotherapy is beneficial in rehabilitation after rotator cuff repair. 27 papers were found using the reported searches, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of that best paper are tabulated. It is concluded that while there may be some short term benefit to passive range of movement, further research is needed.

Structure-based approach for identification of novel phenylboronic acids as serine-β-lactamase inhibitors

NASA Astrophysics Data System (ADS)

Sgrignani, Jacopo; De Luca, Filomena; Torosyan, Hayarpi; Docquier, Jean-Denis; Duan, Da; Novati, Beatrice; Prati, Fabio; Colombo, Giorgio; Grazioso, Giovanni

2016-10-01

β-Lactamases are bacterial enzymes conferring resistance to β-lactam antibiotics in clinically-relevant pathogens, and represent relevant drug targets. Recently, the identification of new boronic acids (i.e. RPX7009) paved the way to the clinical application of these molecules as potential drugs. Here, we screened in silico a library of 1400 boronic acids as potential AmpC β-lactamase inhibitors. Six of the most promising candidates were evaluated in biochemical assays leading to the identification of potent inhibitors of clinically-relevant β-lactamases like AmpC, KPC-2 and CTX-M-15. One of the selected compounds showed nanomolar K i value with the clinically-relevant KPC-2 carbapenemase, while another one exhibited broad spectrum inhibition, being also active on Enterobacter AmpC and the OXA-48 class D carbapenemase.

The Impact of Biosampling Procedures on Molecular Data Interpretation*

PubMed Central

Sköld, Karl; Alm, Henrik; Scholz, Birger

2013-01-01

The separation between biological and technical variation without extensive use of technical replicates is often challenging, particularly in the context of different forms of protein and peptide modifications. Biosampling procedures in the research laboratory are easier to conduct within a shorter time frame and under controlled conditions as compared with clinical sampling, with the latter often having issues of reproducibility. But is the research laboratory biosampling really less variable? Biosampling introduces within minutes rapid tissue-specific changes in the cellular microenvironment, thus inducing a range of different pathways associated with cell survival. Biosampling involves hypoxia and, depending on the circumstances, hypothermia, circumstances for which there are evolutionarily conserved defense strategies in the range of species and also are relevant for the range of biomedical conditions. It remains unclear to what extent such adaptive processes are reflected in different biosampling procedures or how important they are for the definition of sample quality. Lately, an increasing number of comparative studies on different biosampling approaches, post-mortem effects and pre-sampling biological state, have investigated such immediate early biosampling effects. Commonalities between biosampling effects and a range of ischemia/reperfusion- and hypometabolism/anoxia-associated biological phenomena indicate that even small variations in post-sampling time intervals are likely to introduce a set of nonrandom and tissue-specific effects of experimental importance (both in vivo and in vitro). This review integrates the information provided by these comparative studies and discusses how an adaptive biological perspective in biosampling procedures may be relevant for sample quality issues. PMID:23382104

Clinically relevant transmitted drug resistance to first line antiretroviral drugs and implications for recommendations.

PubMed

Monge, Susana; Guillot, Vicente; Alvarez, Marta; Chueca, Natalia; Stella, Natalia; Peña, Alejandro; Delgado, Rafael; Córdoba, Juan; Aguilera, Antonio; Vidal, Carmen; García, Federico

2014-01-01

The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR) defined by the 2009 update of the WHO SDRM list. We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain) between 2007-2011. Using the Stanford algorithm "Low-level resistance", "Intermediate resistance" and "High-level resistance" categories were considered as "Resistant". 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8-7.7)], and 221 harbored TDR using the WHO list [7.9% (6.9-9.0)]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8-2.9) vs. 3.6% (2.9-4.3) by the WHO list] and PIs [0.8% (0.4-1.1) vs. 1.7% (1.2-2.2)], while it was higher for NNRTIs [4.6% (3.8-5.3) vs. 3.7% (3.0-4.7)]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02). Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.

Micrometastases in neuroblastoma: are they clinically important?

PubMed Central

Burchill, S A

2004-01-01

Despite advances in the treatment of neuroblastoma (NBL), recurrence and metastases continue to pose major problems in clinical management. The relation between micrometastases and the development of secondary disease is not fully understood. However, accurate methods to detect low numbers of tumour cells may allow the evaluation of their role in the disease process, and by implication the possible benefits of eliminating them. Although there is substantial evidence for the increased sensitivity of current molecular methods for the detection of NBL cells compared with more conventional cytology, the clinical relevance and usefulness of detecting this disease remain controversial. The primary goal of current translational research must be to evaluate the clinical relevance of micrometastatic disease detected by these methods in multicentre prospective clinical outcome studies. Only then can the clinical usefulness of these methods be defined so that they may be introduced into relevant clinical practice. PMID:14693828

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

PubMed

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

2015-12-01

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

Three-dimensional anterior segment imaging in patients with type 1 Boston Keratoprosthesis with switchable full depth range swept source optical coherence tomography

PubMed Central

Poddar, Raju; Cortés, Dennis E.; Werner, John S.; Mannis, Mark J.

2013-01-01

Abstract. A high-speed (100 kHz A-scans/s) complex conjugate resolved 1 μm swept source optical coherence tomography (SS-OCT) system using coherence revival of the light source is suitable for dense three-dimensional (3-D) imaging of the anterior segment. The short acquisition time helps to minimize the influence of motion artifacts. The extended depth range of the SS-OCT system allows topographic analysis of clinically relevant images of the entire depth of the anterior segment of the eye. Patients with the type 1 Boston Keratoprosthesis (KPro) require evaluation of the full anterior segment depth. Current commercially available OCT systems are not suitable for this application due to limited acquisition speed, resolution, and axial imaging range. Moreover, most commonly used research grade and some clinical OCT systems implement a commercially available SS (Axsun) that offers only 3.7 mm imaging range (in air) in its standard configuration. We describe implementation of a common swept laser with built-in k-clock to allow phase stable imaging in both low range and high range, 3.7 and 11.5 mm in air, respectively, without the need to build an external MZI k-clock. As a result, 3-D morphology of the KPro position with respect to the surrounding tissue could be investigated in vivo both at high resolution and with large depth range to achieve noninvasive and precise evaluation of success of the surgical procedure. PMID:23912759

Physicians' perspective on the clinical meaningfulness of inflammatory bowel disease trial results: an International Organization for the Study of Inflammatory Bowel Disease (IOIBD) survey.

PubMed

Olivera, P; Sandborn, W J; Panés, J; Baumann, C; D'Haens, G; Vermeire, S; Danese, S; Peyrin-Biroulet, L

2018-03-01

Several novel compounds are being developed for inflammatory bowel diseases (IBD). In addition, biosimilar drugs are being approved. An increasing number of head-to-head, superiority and non-inferiority trials in patients with IBD are expected in the future. The clinical relevance of the magnitude of the effect size is often debated. To better understand physicians' perspectives on the clinical meaningfulness of IBD trial results. We conducted an online survey among all IOIBD (International Organization for the Study of Inflammatory Bowel Diseases) members, asking their opinion on the clinical relevance of the results of IBD trials. Forty-six IOIBD members responded to the survey (52.3%). In biologic-naïve ulcerative colitis (UC) and Crohn's disease (CD) patients, most of the participants considered a 15% difference with placebo for clinical remission and endoscopic remission to be clinically relevant. In head-to-head trials, most of participants considerer a 10% difference between groups for clinical remission and endoscopic remission to be clinically relevant. Half of respondents considered 10% to be an adequate margin in non-inferiority trials. In bioequivalence studies, most of the participants considered adequate a ± 5% difference between a biosimilar and the originator for pharmacokinetic parameters, efficacy, safety and immunogenicity. Regarding safety, the difference between two drugs considered clinically relevant varied from 1% to 5%, depending on the type of adverse event. This is the first survey exploring how physicians perceive IBD trial results, providing an estimation of the magnitude of the difference between treatment arms that may directly influence clinical practice. © 2018 John Wiley & Sons Ltd.

RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 6: Post-cardiac arrest care.

PubMed

Smarick, Sean D; Haskins, Steve C; Boller, Manuel; Fletcher, Daniel J

2012-06-01

To systematically examine the evidence for interventions after the return of spontaneous circulation (ROSC) on outcomes from veterinary cardiopulmonary resuscitation and to determine important knowledge gaps. Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality, and development of consensus on conclusions for application of the concepts to clinical post-cardiac arrest care. Academia, referral practice, and general practice. Fifteen standardized clinical questions important for post-cardiac arrest care were asked and research articles relevant to answering these questions were identified through structured, explicit literature database searches. The majority of these articles report research in species other than dogs or cats or consisted of experimental work in canine cardiac arrest models. Outcome metrics reported in these studies widely varied and ranged from quantification of mechanistic endpoints, such as elaboration of reactive oxygen species, to survival, and functional neurologic outcome. Despite the near complete absence of clinical veterinary studies, the process allowed the formulation of statements for several postcardiac arrest treatments that were either supportive, such as mild therapeutic hypothermia or controlled reoxygenation, or neutral, such as for mannitol administration or seizure prophylaxis. Evidence grading allowed transparency in regards to the strength of these recommendations. Moreover, numerous knowledge gaps emerged that will allow generation of a road map for progress in veterinary post-cardiac arrest care. © Veterinary Emergency and Critical Care Society 2012.

Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

PubMed

Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

2015-09-01

Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Antinociception induced by intravenous dipyrone (metamizol) upon dorsal horn neurons: involvement of endogenous opioids at the periaqueductal gray matter, the nucleus raphe magnus, and the spinal cord in rats.

PubMed

Vazquez, Enrique; Hernandez, Norma; Escobar, William; Vanegas, Horacio

2005-06-28

Microinjection of dipyrone (metamizol) into the periaqueductal gray matter (PAG) in rats causes antinociception. This is mediated by endogenous opioidergic circuits located in the PAG itself, in the nucleus raphe magnus and adjacent structures, and in the spinal cord. The clinical relevance of these findings, however, is unclear. Therefore, in the present study, dipyrone was administered intravenously, and the involvement of endogenous opioidergic circuits in the so-induced antinociception was investigated. In rats, responses of dorsal spinal wide-dynamic range neurons to mechanical noxious stimulation of a hindpaw were strongly inhibited by intravenous dipyrone (200 mg/kg). This effect was abolished by microinjection of naloxone (0.5 microg/0.5 microl) into the ventrolateral and lateral PAG or into the nucleus raphe magnus or by direct application of naloxone (50 microg/50 microl) onto the spinal cord surface above the recorded neuron. These results show that dipyrone, a non-opioid analgesic with widespread use in Europe and Latin America, when administered in a clinically relevant fashion causes antinociception by activating endogenous opioidergic circuits along the descending pain control system.

Prolactin--a novel neuroendocrine regulator of human keratin expression in situ.

PubMed

Ramot, Yuval; Bíró, Tamás; Tiede, Stephan; Tóth, Balázs I; Langan, Ewan A; Sugawara, Koji; Foitzik, Kerstin; Ingber, Arieh; Goffin, Vincent; Langbein, Lutz; Paus, Ralf

2010-06-01

The controls of human keratin expression in situ remain to be fully elucidated. Here, we have investigated the effects of the neurohormone prolactin (PRL) on keratin expression in a physiologically and clinically relevant test system: organ-cultured normal human hair follicles (HFs). Not only do HFs express a wide range of keratins, but they are also a source and target of PRL. Microarray analysis revealed that PRL differentially regulated a defined subset of keratins and keratin-associated proteins. Quantitative immunohistomorphometry and quantitative PCR confirmed that PRL up-regulated expression of keratins K5 and K14 and the epithelial stem cell-associated keratins K15 and K19 in organ-cultured HFs and/or isolated HF keratinocytes. PRL also up-regulated K15 promoter activity and K15 protein expression in situ, whereas it inhibited K6 and K31 expression. These regulatory effects were reversed by a pure competitive PRL receptor antagonist. Antagonist alone also modulated keratin expression, suggesting that "tonic stimulation" by endogenous PRL is required for normal expression levels of selected keratins. Therefore, our study identifies PRL as a major, clinically relevant, novel neuroendocrine regulator of both human keratin expression and human epithelial stem cell biology in situ.

Impact of a novel teaching method based on feedback, activity, individuality and relevance on students’ learning

PubMed Central

Brooks, William S.; Laskar, Simone N.; Benjamin, Miles W.; Chan, Philip

2016-01-01

Objectives This study examines the perceived impact of a novel clinical teaching method based on FAIR principles (feedback, activity, individuality and relevance) on students’ learning on clinical placement. Methods This was a qualitative research study. Participants were third year and final year medical students attached to one UK vascular firm over a four-year period (N=108). Students were asked to write a reflective essay on how FAIRness approach differs from previous clinical placement, and its advantages and disadvantages. Essays were thematically analysed and globally rated (positive, negative or neutral) by two independent researchers. Results Over 90% of essays reported positive experiences of feedback, activity, individuality and relevance model.  The model provided multifaceted feedback; active participation; longitudinal improvement; relevance to stage of learning and future goals; structured teaching; professional development; safe learning environment; consultant involvement in teaching. Students perceived preparation for tutorials to be time intensive for tutors/students; a lack of teaching on medical sciences and direct observation of performance; more than once weekly sessions would be beneficial; some issues with peer and public feedback, relevance to upcoming exam and large group sizes. Students described negative experiences of “standard” clinical teaching. Conclusions Progressive teaching programmes based on the FAIRness principles, feedback, activity, individuality and relevance, could be used as a model to improve current undergraduate clinical teaching. PMID:26995588

Clinically Relevant Outcome Measures Following Limb Osseointegration; Systematic Review of the Literature.

PubMed

Al Muderis, Munjed M; Lu, William Y; Li, Jiao Jiao; Kaufman, Kenton; Orendurff, Michael; Highsmith, M Jason; Lunseth, Paul A; Kahle, Jason T

2018-02-01

The current standard of care for an amputee is a socket-based prostheses. An osseointegrated implant (OI) is an alternative for prosthetic attachment. Osseointegration addresses reported problems related to wearing a socket interface, such as skin issues, discomfort, diminished function, quality of life, prosthetic use, and abandonment. The purpose of this report is to systematically review current literature regarding OI to identify and categorize the reported clinically relevant outcome measures, rate the quality of available evidence, and synthesize the findings. A multidisciplinary team used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methods. Search methodology was based on identifying clinically relevant articles. Three databases were searched: PubMed, CINAHL, and Web of Science. Clinical studies with aggregated data reporting at least 1 clinically relevant outcome measure were included. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criterion was used for critical appraisal and recommendations. This review identified 21 clinically relevant observational studies. Outcome measures were categorized into the following 9 categories: vibratory stimulation, complications, biomechanics, economics, patient-reported outcome measures, electromyography, x-ray, physical functional performance, and energy consumption. This systematic review consisted of Level III and IV observational studies. Homogeneous outcome measures with strong psychometric properties across prospective studies do not exist to date. Higher-level, prospective, randomized, long-term, clinically relevant trials are needed to prove efficacy of OI compared with socket prosthetic attachment. Osseointegration was at least equivalent to sockets in most studies. In some cases, it was superior. Osseointegration represents a promising alternative to socket prosthetic attachments for extremity amputees. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

DNA Repair in Prostate Cancer: Biology and Clinical Implications.

PubMed

Mateo, Joaquin; Boysen, Gunther; Barbieri, Christopher E; Bryant, Helen E; Castro, Elena; Nelson, Pete S; Olmos, David; Pritchard, Colin C; Rubin, Mark A; de Bono, Johann S

2017-03-01

For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA damage repair pathway are common in PC, particularly in late-stage disease, and may be relevant for treatment stratification. To review current knowledge on the prevalence and clinical significance of aberrations in DNA repair genes in PC, particularly in metastatic disease. A literature search up to July 2016 was conducted, including clinical trials and preclinical basic research studies. Keywords included DNA repair, BRCA, ATM, CRPC, prostate cancer, PARP, platinum, predictive biomarkers, and hereditary cancer. We review how the DNA repair pathway is relevant to prostate carcinogenesis and progression. Data on how this may be relevant to hereditary cancer and genetic counseling are included, as well as data from clinical trials of PARP inhibitors and platinum therapeutics in PC. Relevant studies have identified genomic defects in DNA repair in PCs in 20-30% of advanced castration-resistant PC cases, a proportion of which are germline aberrations and heritable. Phase 1/2 clinical trial data, and other supporting clinical data, support the development of PARP inhibitors and DNA-damaging agents in this molecularly defined subgroup of PC following success in other cancer types. These studies may be an opportunity to improve patient care with personalized therapeutic strategies. Key literature on how genomic defects in the DNA damage repair pathway are relevant for prostate cancer biology and clinical management is reviewed. Potential implications for future changes in patient care are discussed. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Clinical decision making in cancer care: a review of current and future roles of patient age.

PubMed

Tranvåg, Eirik Joakim; Norheim, Ole Frithjof; Ottersen, Trygve

2018-05-09

Patient age is among the most controversial patient characteristics in clinical decision making. In personalized cancer medicine it is important to understand how individual characteristics do affect practice and how to appropriately incorporate such factors into decision making. Some argue that using age in decision making is unethical, and how patient age should guide cancer care is unsettled. This article provides an overview of the use of age in clinical decision making and discusses how age can be relevant in the context of personalized medicine. We conducted a scoping review, searching Pubmed for English references published between 1985 and May 2017. References concerning cancer, with patients above the age of 18 and that discussed age in relation to diagnostic or treatment decisions were included. References that were non-medical or concerning patients below the age of 18, and references that were case reports, ongoing studies or opinion pieces were excluded. Additional references were collected through snowballing and from selected reports, guidelines and articles. Three hundred and forty-seven relevant references were identified. Patient age can have many and diverse roles in clinical decision making: Contextual roles linked to access (age influences how fast patients are referred to specialized care) and incidence (association between increasing age and increasing incidence rates for cancer); patient-relevant roles linked to physiology (age-related changes in drug metabolism) and comorbidity (association between increasing age and increasing number of comorbidities); and roles related to interventions, such as treatment (older patients receive substandard care) and outcome (survival varies by age). Patient age is integrated into cancer care decision making in a range of ways that makes it difficult to claim age-neutrality. Acknowledging this and being more transparent about the use of age in decision making are likely to promote better clinical decisions, irrespective of one's normative viewpoint. This overview also provides a starting point for future discussions on the appropriate role of age in cancer care decision making, which we see as crucial for harnessing the full potential of personalized medicine.

Detection of Rare Drug Resistance Mutations by Digital PCR in a Human Influenza A Virus Model System and Clinical Samples

PubMed Central

Bushell, Claire A.; Grant, Paul R.; Cowen, Simon; Gutierrez-Aguirre, Ion; O'Sullivan, Denise M.; Žel, Jana; Milavec, Mojca; Foy, Carole A.; Nastouli, Eleni; Garson, Jeremy A.; Huggett, Jim F.

2015-01-01

Digital PCR (dPCR) is being increasingly used for the quantification of sequence variations, including single nucleotide polymorphisms (SNPs), due to its high accuracy and precision in comparison with techniques such as quantitative PCR (qPCR) and melt curve analysis. To develop and evaluate dPCR for SNP detection using DNA, RNA, and clinical samples, an influenza virus model of resistance to oseltamivir (Tamiflu) was used. First, this study was able to recognize and reduce off-target amplification in dPCR quantification, thereby enabling technical sensitivities down to 0.1% SNP abundance at a range of template concentrations, a 50-fold improvement on the qPCR assay used routinely in the clinic. Second, a method was developed for determining the false-positive rate (background) signal. Finally, comparison of dPCR with qPCR results on clinical samples demonstrated the potential impact dPCR could have on clinical research and patient management by earlier (trace) detection of rare drug-resistant sequence variants. Ultimately this could reduce the quantity of ineffective drugs taken and facilitate early switching to alternative medication when available. In the short term such methods could advance our understanding of microbial dynamics and therapeutic responses in a range of infectious diseases such as HIV, viral hepatitis, and tuberculosis. Furthermore, the findings presented here are directly relevant to other diagnostic areas, such as the detection of rare SNPs in malignancy, monitoring of graft rejection, and fetal screening. PMID:26659206

Detection of Rare Drug Resistance Mutations by Digital PCR in a Human Influenza A Virus Model System and Clinical Samples.

PubMed

Whale, Alexandra S; Bushell, Claire A; Grant, Paul R; Cowen, Simon; Gutierrez-Aguirre, Ion; O'Sullivan, Denise M; Žel, Jana; Milavec, Mojca; Foy, Carole A; Nastouli, Eleni; Garson, Jeremy A; Huggett, Jim F

2016-02-01

Digital PCR (dPCR) is being increasingly used for the quantification of sequence variations, including single nucleotide polymorphisms (SNPs), due to its high accuracy and precision in comparison with techniques such as quantitative PCR (qPCR) and melt curve analysis. To develop and evaluate dPCR for SNP detection using DNA, RNA, and clinical samples, an influenza virus model of resistance to oseltamivir (Tamiflu) was used. First, this study was able to recognize and reduce off-target amplification in dPCR quantification, thereby enabling technical sensitivities down to 0.1% SNP abundance at a range of template concentrations, a 50-fold improvement on the qPCR assay used routinely in the clinic. Second, a method was developed for determining the false-positive rate (background) signal. Finally, comparison of dPCR with qPCR results on clinical samples demonstrated the potential impact dPCR could have on clinical research and patient management by earlier (trace) detection of rare drug-resistant sequence variants. Ultimately this could reduce the quantity of ineffective drugs taken and facilitate early switching to alternative medication when available. In the short term such methods could advance our understanding of microbial dynamics and therapeutic responses in a range of infectious diseases such as HIV, viral hepatitis, and tuberculosis. Furthermore, the findings presented here are directly relevant to other diagnostic areas, such as the detection of rare SNPs in malignancy, monitoring of graft rejection, and fetal screening. Copyright © 2016 Whale et al.

Using computer assisted learning for clinical skills education in nursing: integrative review.

PubMed

Bloomfield, Jacqueline G; While, Alison E; Roberts, Julia D

2008-08-01

This paper is a report of an integrative review of research investigating computer assisted learning for clinical skills education in nursing, the ways in which it has been studied and the general findings. Clinical skills are an essential aspect of nursing practice and there is international debate about the most effective ways in which these can be taught. Computer assisted learning has been used as an alternative to conventional teaching methods, and robust research to evaluate its effectiveness is essential. The CINAHL, Medline, BNI, PsycInfo and ERIC electronic databases were searched for the period 1997-2006 for research-based papers published in English. Electronic citation tracking and hand searching of reference lists and relevant journals was also undertaken. Twelve studies met the inclusion criteria. An integrative review was conducted and each paper was explored in relation to: design, aims, sample, outcome measures and findings. Many of the study samples were small and there were weaknesses in designs. There is limited empirical evidence addressing the use of computer assisted learning for clinical skills education in nursing. Computer assisted learning has been used to teach a limited range of clinical skills in a variety of settings. The paucity of evaluative studies indicates the need for more rigorous research to investigate the effect of computer assisted learning for this purpose. Areas that need to be addressed in future studies include: sample size, range of skills, longitudinal follow-up and control of confounding variables.

A virtual phantom library for the quantification of deformable image registration uncertainties in patients with cancers of the head and neck.

PubMed

Pukala, Jason; Meeks, Sanford L; Staton, Robert J; Bova, Frank J; Mañon, Rafael R; Langen, Katja M

2013-11-01

Deformable image registration (DIR) is being used increasingly in various clinical applications. However, the underlying uncertainties of DIR are not well-understood and a comprehensive methodology has not been developed for assessing a range of interfraction anatomic changes during head and neck cancer radiotherapy. This study describes the development of a library of clinically relevant virtual phantoms for the purpose of aiding clinicians in the QA of DIR software. These phantoms will also be available to the community for the independent study and comparison of other DIR algorithms and processes. Each phantom was derived from a pair of kVCT volumetric image sets. The first images were acquired of head and neck cancer patients prior to the start-of-treatment and the second were acquired near the end-of-treatment. A research algorithm was used to autosegment and deform the start-of-treatment (SOT) images according to a biomechanical model. This algorithm allowed the user to adjust the head position, mandible position, and weight loss in the neck region of the SOT images to resemble the end-of-treatment (EOT) images. A human-guided thin-plate splines algorithm was then used to iteratively apply further deformations to the images with the objective of matching the EOT anatomy as closely as possible. The deformations from each algorithm were combined into a single deformation vector field (DVF) and a simulated end-of-treatment (SEOT) image dataset was generated from that DVF. Artificial noise was added to the SEOT images and these images, along with the original SOT images, created a virtual phantom where the underlying "ground-truth" DVF is known. Images from ten patients were deformed in this fashion to create ten clinically relevant virtual phantoms. The virtual phantoms were evaluated to identify unrealistic DVFs using the normalized cross correlation (NCC) and the determinant of the Jacobian matrix. A commercial deformation algorithm was applied to the virtual phantoms to show how they may be used to generate estimates of DIR uncertainty. The NCC showed that the simulated phantom images had greater similarity to the actual EOT images than the images from which they were derived, supporting the clinical relevance of the synthetic deformation maps. Calculation of the Jacobian of the "ground-truth" DVFs resulted in only positive values. As an example, mean error statistics are presented for all phantoms for the brainstem, cord, mandible, left parotid, and right parotid. It is essential that DIR algorithms be evaluated using a range of possible clinical scenarios for each treatment site. This work introduces a library of virtual phantoms intended to resemble real cases for interfraction head and neck DIR that may be used to estimate and compare the uncertainty of any DIR algorithm.

Laser in the management of burn scars.

PubMed

Willows, Brooke M; Ilyas, Muneeb; Sharma, Amit

2017-11-01

Burn scars are associated with significant morbidity ranging from contractures, pruritus, and disfigurement to psychosocial impairment. Traditional therapies include silicone gel, compression garments, corticosteroid injections, massage therapy, and surgical procedures, however, newer and advanced therapies for the treatment of burn scars have been developed. Lasers, specifically ablative fractional lasers, show potential for the treatment of burn scars. Both MeSH and keyword searches of the PubMed, Medline and Embase databases were performed and relevant articles were read in full for the compilation of this review. Fifty-one relevant observational studies, clinical trials, and systematic reviews published in English from 2006 to 2016 were reviewed and summarized. Laser therapy is effective for the treatment of burn scar appearance, including measures such as pigmentation, vascularity, pliability, and thickness. Ablative fractional laser therapy, in particular, shows significant potential for the release of contractures allowing for improved range of motion of affected joints. Patients may benefit from the use of lasers in the treatment of burn scars, and the safety profile of lasers allows the benefits of treatment to outweigh the risks. Laser therapy should be included in burn scar treatment protocols as an adjuvant therapy to traditional interventions. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Multiple biomarkers biosensor with just-in-time functionalization: Application to prostate cancer detection.

PubMed

Parra-Cabrera, C; Samitier, J; Homs-Corbera, A

2016-03-15

We present a novel lab-on-a-chip (LOC) device for the simultaneous detection of multiple biomarkers using simple voltage measurements. The biosensor functionalization is performed in-situ, immediately before its use, facilitating reagents storage and massive devices fabrication. Sensitivity, limit of detection (LOD) and limit of quantification (LOQ) are tunable depending on the in-chip flown sample volumes. As a proof-of-concept, the system has been tested and adjusted to quantify two proteins found in blood that are susceptible to be used combined, as a screening tool, to diagnose prostate cancer (PCa): prostate-specific antigen (PSA) and spondin-2 (SPON2). This combination of biomarkers has been reported to be more specific for PCa diagnostics than the currently accepted but rather controversial PSA indicator. The range of detection for PSA and SPON2 could be adjusted to the clinically relevant range of 1 to 10 ng/ml. The system was tested for specificity to the evaluated biomarkers. This multiplex system can be modified and adapted to detect a larger quantity of biomarkers, or different ones, of relevance to other specific diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Developing a holistic approach to obesity management.

PubMed

Brown, Jenny; Wimpenny, Peter

2011-02-01

The aim of this paper is to discuss the theoretical background and relevance of a holistic approach to obesity management by nurses. There is a global rise in the number of people with obesity, such that it now represents one of the major health challenges. However, nurses are often influenced by physical and dietetic focused approaches and could fail to acknowledge a range of other factors that can impact on weight management. As part of the development of a holistic approach to obesity a literature search was undertaken to establish relevant theoretical perspectives that underpin practice in physical, psychological and social aspects of care (focused on the period 1995-2005). In addition, experiences of working in a secondary care weight management clinic were also drawn upon. Psychobiological, attribution and social support theories were identified that could contribute to a better understanding of obesity. If these theoretical perspectives and supporting evidence can be integrated in a holistic approach to care and management it might be possible to promote better health and well-being in those with obesity. Creating a greater understanding of the range of theoretical perspectives and supporting evidence related to obesity could, it is argued, provide enhanced care and management. © 2011 Blackwell Publishing Asia Pty Ltd.

Embodying compassion: a virtual reality paradigm for overcoming excessive self-criticism.

PubMed

Falconer, Caroline J; Slater, Mel; Rovira, Aitor; King, John A; Gilbert, Paul; Antley, Angus; Brewin, Chris R

2014-01-01

Virtual reality has been successfully used to study and treat psychological disorders such as phobias and posttraumatic stress disorder but has rarely been applied to clinically-relevant emotions other than fear and anxiety. Self-criticism is a ubiquitous feature of psychopathology and can be treated by increasing levels of self-compassion. We exploited the known effects of identification with a virtual body to arrange for healthy female volunteers high in self-criticism to experience self-compassion from an embodied first-person perspective within immersive virtual reality. Whereas observation and practice of compassionate responses reduced self-criticism, the additional experience of embodiment also increased self-compassion and feelings of being safe. The results suggest potential new uses for immersive virtual reality in a range of clinical conditions.

Embodying Compassion: A Virtual Reality Paradigm for Overcoming Excessive Self-Criticism

PubMed Central

Falconer, Caroline J.; Slater, Mel; Rovira, Aitor; King, John A.; Gilbert, Paul; Antley, Angus; Brewin, Chris R.

2014-01-01

Virtual reality has been successfully used to study and treat psychological disorders such as phobias and posttraumatic stress disorder but has rarely been applied to clinically-relevant emotions other than fear and anxiety. Self-criticism is a ubiquitous feature of psychopathology and can be treated by increasing levels of self-compassion. We exploited the known effects of identification with a virtual body to arrange for healthy female volunteers high in self-criticism to experience self-compassion from an embodied first-person perspective within immersive virtual reality. Whereas observation and practice of compassionate responses reduced self-criticism, the additional experience of embodiment also increased self-compassion and feelings of being safe. The results suggest potential new uses for immersive virtual reality in a range of clinical conditions. PMID:25389766

EASD diabetes technology meeting: medical associations are on track.

PubMed

Heinemann, Lutz

2014-07-01

The first diabetes technology meeting organized by the European Diabetes Association covers the range from regulatory aspects, patient safety, about registries to clinical studies. After an intensive discussion about the evidence required for registration and reimbursement on new medical devices and in vitro diagnostics it becomes clear that more and better clinical trials will be required in the future. This was also highlighted by representatives of the American Diabetes Association. The 2 associations will be active in this field of research by a joint committee. This meeting is intended not to become a large-scale meeting focused on education but to provide a platform for an open discussion of experts involved in all areas that are relevant to achieve a meaningful usage of diabetes technology. © 2014 Diabetes Technology Society.

Neuronal and Cardiovascular Potassium Channels as Therapeutic Drug Targets

PubMed Central

Humphries, Edward S. A.

2015-01-01

Potassium (K+) channels, with their diversity, often tissue-defined distribution, and critical role in controlling cellular excitability, have long held promise of being important drug targets for the treatment of dysrhythmias in the heart and abnormal neuronal activity within the brain. With the exception of drugs that target one particular class, ATP-sensitive K+ (KATP) channels, very few selective K+ channel activators or inhibitors are currently licensed for clinical use in cardiovascular and neurological disease. Here we review what a range of human genetic disorders have told us about the role of specific K+ channel subunits, explore the potential of activators and inhibitors of specific channel populations as a therapeutic strategy, and discuss possible reasons for the difficulty in designing clinically relevant K+ channel modulators. PMID:26303307

Mechanisms and disease relevance of neutrophil extracellular trap formation.

PubMed

Van Avondt, Kristof; Hartl, Dominik

2018-03-15

While the microscopic appearance of neutrophil extracellular traps (NETs) has fascinated basic researchers since its discovery, the (patho)physiological mechanisms triggering NET release, the disease relevance and clinical translatability of this unconventional cellular mechanism remained poorly understood. Here, we summarize and discuss current concepts of the mechanisms and disease relevance of NET formation. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Clinical Relevance of IgE to Profilin and/or Polcalcin in Pollen-Sensitized Patients.

PubMed

San Nicoló, Marion; Braun, Thomas; Eder, Katharina; Berghaus, Alexander; Gröger, Moritz

2016-01-01

Component-resolved diagnostics is gaining importance in allergy diagnostics. Allergen extracts contain components with different rates of prevalence and clinical relevance, which can be subdivided at molecular level into major and minor allergens. Clinical complaints are usually triggered by major allergens, while the role of sensitization to the panallergens profilin and polcalcin still remains unclear. Eighty-six patients from southern Bavaria with sensitization to the panallergens profilin (Bet v 2/Phl p 12) and/or polcalcin (Bet v 4/Phl p 7) were examined in regard to their sensitization to the 4 main botanic denominations Betulaceae, Oleaceae, Poaceae and Asteraceae by skin prick test and measurement of specific immunoglobulin E antibodies to natural allergen extracts as well as major allergen components rPhl p 1/5, rBet v 1, rOle e 1 and nArt v 1. Sensitization was rated as clinically relevant or irrelevant depending on anamnesis or intranasal allergen challenge. Regarding the 4 botanic denominations, there was no significant difference in the incidence of sensitization to the panallergens profilin, polcalcin or both. The sensitization pattern does not alter when subdividing the cohort into clinically relevant and silent sensitization. We did not find clinically symptomatic sensitization to panallergens without cosensitization to a major allergen. Our results suggest that sole sensitization to panallergens seems to have no clinical relevance in allergic rhinoconjunctivitis. Clinical complaints seem to be triggered manly by major allergens. Thus, component-resolved allergy diagnostics is crucial in the diagnosis and treatment of polysensitized patients. © 2016 S. Karger AG, Basel.

Edoxaban for the long-term treatment of venous thromboembolism: rationale and design of the Hokusai-venous thromboembolism study--methodological implications for clinical trials.

PubMed

Raskob, G; Büller, H; Prins, M; Segers, A; Shi, M; Schwocho, L; van Kranen, R; Mercuri, M

2013-07-01

New oral anticoagulants may simplify long-term therapy by eliminating the need for laboratory monitoring. Edoxaban is an oral, direct inhibitor of factor Xa that is given in a fixed dose once daily. The Hokusai-VTE study is a randomized, double-blind trial to evaluate whether initial low molecular weight heparin (LMWH) followed by edoxaban (60 mg once daily) is non-inferior to LMWH followed by warfarin (International Normalized Ratio of 2.0-3.0) for the prevention of recurrent thromboembolism in patients with acute symptomatic venous thromboembolism (VTE). The primary efficacy outcome is symptomatic recurrent VTE during the 12-month study period. The principal safety outcome is clinically relevant bleeding (major or non-major) occurring during or within 3 days of stopping study treatment. A clinical events committee adjudicates all suspected outcome events. A unique study design feature is the flexible treatment duration of between 3 and 12 months to simulate usual clinical practice, and enabled by: (i) double-blinding to minimize bias that could occur if knowledge of the patient's treatment influenced the duration of therapy; and (ii) follow-up for 12 months of all patients and inclusion in the primary efficacy analysis, regardless of the duration of therapy received. A second innovative design feature is the strategy for achieving an appropriate time in therapeutic range in the warfarin group, with central tracking for each participating center and feedback to the investigators. The standard methods combined with innovative design features should achieve study results that are both scientifically valid and relevant to clinical practice. © 2013 International Society on Thrombosis and Haemostasis.

Protein Turnover Measurements in Human Serum by Serial Immunoaffinity LC-MS/MS.

PubMed

Farrokhi, Vahid; Chen, Xiaoying; Neubert, Hendrik

2018-02-01

The half-life of target proteins is frequently an important parameter in mechanistic pharmacokinetic and pharmacodynamic (PK/PD) modeling of biotherapeutics. Clinical studies for accurate measurement of physiologically relevant protein turnover can reduce the uncertainty in PK/PD model-based predictions, for example, of the therapeutic dose and dosing regimen in first-in-human clinical trials. We used a targeted mass spectrometry work flow based on serial immunoaffinity enrichment ofmultiple human serum proteins from a [5,5,5- 2 H 3 ]-L-leucine tracer pulse-chase study in healthy volunteers. To confirm the reproducibility of turnover measurements from serial immunoaffinity enrichment, multiple aliquots from the same sample set were subjected to protein turnover analysis in varying order. Tracer incorporation was measured by multiple-reaction-monitoring mass spectrometry and target turnover was calculated using a four-compartment pharmacokinetic model. Five proteins of clinical or therapeutic relevance including soluble tumor necrosis factor receptor superfamily member 12A, tissue factor pathway inhibitor, soluble interleukin 1 receptor like 1, soluble mucosal addressin cell adhesion molecule 1, and muscle-specific creatine kinase were sequentially subjected to turnover analysis from the same human serum sample. Calculated half-lives ranged from 5-15 h; however, no tracer incorporation was observed for mucosal addressin cell adhesion molecule 1. The utility of clinical pulse-chase studies to investigate protein turnover can be extended by serial immunoaffinity enrichment of target proteins. Turnover analysis from serum and subsequently from remaining supernatants provided analytical sensitivity and reproducibility for multiple human target proteins in the same sample set, irrespective of the order of analysis. © 2017 American Association for Clinical Chemistry.

Affect regulation, brain development, and behavioral/emotional health in adolescence.

PubMed

Dahl, R E

2001-01-01

This paper addresses the importance of affect regulation (AR) in relation to a broad range of behavioral and emotional health problems that emerge during adolescence. AR is defined as the adaptive modulation of emotional experience to serve a goal or purpose. This conceptualization of AR emphasizes the use of cognitive skills to guide, inhibit, or modify emotion and behavior, including the expression of emotional responses, in learned, strategic ways-skills that ultimately underpin adult levels of social maturity and the ability to show "responsible" behavior across a range of emotional situations. Neurobehavioral systems that subserve these AR skills include areas of the inferior and orbital prefrontal cortex (PFC), with rich interconnections to several limbic structures and other cortical areas, including the dorsolateral PFC. Adolescence represents an important developmental period in the functional maturation of adult AR skills; it is also a critical time in the development of clinical disorders of AR (eg, rates of depression increase dramatically and gender differences in depression emerge). Maturational changes in AR that occur during adolescence-particularly with respect to the role of emotions influencing responsible decision making-are also relevant to understanding key aspects of the developmental pathways of some behavioral health problems, such as alcohol use and nicotine dependence. A strong case is made for developmental research in affective neuroscience aimed at this important maturational period, particularly the kind of transdisciplinary research leading toward mechanistic understanding of the development of adolescent-onset disorders. Improving understanding in these areas could ultimately lead to the development of early interventions in targeted high-risk populations, and has enormous clinical and social policy relevance.

Measurement of immunofunctional leptin to detect and monitor patients with functional leptin deficiency.

PubMed

Wabitsch, Martin; Pridzun, Lutz; Ranke, Michael; von Schnurbein, Julia; Moss, Anja; Brandt, Stephanie; Kohlsdorf, Katja; Moepps, Barbara; Schaab, Michael; Funcke, Jan-Bernd; Gierschik, Peter; Fischer-Posovszky, Pamela; Flehmig, Bertram; Kratzsch, Jürgen

2017-03-01

Functional leptin deficiency is characterized by high levels of circulating immunoreactive leptin (irLep), but a reduced bioactivity of the hormone due to defective receptor binding. As a result of the fact that affected patients can be successfully treated with metreleptin, it was aimed to develop and validate a diagnostic tool to detect functional leptin deficiency. An immunoassay capable of recognizing the functionally relevant receptor-binding complex with leptin was developed (bioLep). The analytical quality of bioLep was validated and compared to a conventional assay for immune-reactive leptin (irLep). Its clinical relevance was evaluated in a cohort of lean and obese children and adults as well as in children diagnosed with functional leptin deficiency and their parents. In the clinical cohort, a bioLep/irLep ratio of 1.07 (range: 0.80-1.41) was observed. Serum of patients with non-functional leptin due to homozygous amino acid exchanges (D100Y or N103K) revealed high irLep but non-detectable bioLep levels. Upon treatment of these patients with metreleptin, irLep levels decreased, whereas levels of bioLep increased continuously. In patient relatives with heterozygous amino acid exchanges, a bioLep/irLep ratio of 0.52 (range: 0.48-0.55) being distinct from normal was observed. The new bioLep assay is able to diagnose impaired leptin bioactivity in severely obese patients with a homozygous gene defect and in heterozygous carriers of such mutations. The assay serves as a diagnostic tool to monitor leptin bioactivity during treatment of these patients. © 2017 The authors.

Quality in genetic counselling for presymptomatic testing--clinical guidelines for practice across the range of genetic conditions.

PubMed

Skirton, Heather; Goldsmith, Lesley; Jackson, Leigh; Tibben, Aad

2013-03-01

Presymptomatic testing (PST) is the performance of a genetic test on an asymptomatic individual at risk of a condition to determine whether the person has inherited the disease-causing mutation. Although relevant guidelines exist for specific diseases, there is no overarching protocol that can be adapted to any disorder or clinical setting in which such testing is offered. The objective of this European project was to develop a set of coherent guidelines for PST (for adult-onset monogenic conditions) for use by health professionals working in a range of disciplines, countries or contexts. To ensure the guidelines were appropriate and practice based, we organised a workshop attended by an expert group of practitioners with relevant health professional backgrounds from 11 countries. Models of service for offering PST were presented, the group then discussed different aspects of testing and the standard of care required to ensure that patients were prepared to make decisions and deal with results and consequences. After the workshop, several rounds of consultation were used with a wider group of professionals to refine the guidelines. The guidelines include general principles governing the offer of testing (eg, autonomous choice of the patient), objectives of genetic counselling in this context (eg, facilitation of decision making), logistical considerations (eg, use of trained staff) and topics to be included during counselling discussion with the patient (eg, consequences of both positive and negative outcomes). We recommend the adoption of these guidelines to provide an equitable structure for those seeking PST in any country.

Compressive Sensing of Foot Gait Signals and Its Application for the Estimation of Clinically Relevant Time Series.

PubMed

Pant, Jeevan K; Krishnan, Sridhar

2016-07-01

A new signal reconstruction algorithm for compressive sensing based on the minimization of a pseudonorm which promotes block-sparse structure on the first-order difference of the signal is proposed. Involved optimization is carried out by using a sequential version of Fletcher-Reeves' conjugate-gradient algorithm, and the line search is based on Banach's fixed-point theorem. The algorithm is suitable for the reconstruction of foot gait signals which admit block-sparse structure on the first-order difference. An additional algorithm for the estimation of stride-interval, swing-interval, and stance-interval time series from the reconstructed foot gait signals is also proposed. This algorithm is based on finding zero crossing indices of the foot gait signal and using the resulting indices for the computation of time series. Extensive simulation results demonstrate that the proposed signal reconstruction algorithm yields improved signal-to-noise ratio and requires significantly reduced computational effort relative to several competing algorithms over a wide range of compression ratio. For a compression ratio in the range from 88% to 94%, the proposed algorithm is found to offer improved accuracy for the estimation of clinically relevant time-series parameters, namely, the mean value, variance, and spectral index of stride-interval, stance-interval, and swing-interval time series, relative to its nearest competitor algorithm. The improvement in performance for compression ratio as high as 94% indicates that the proposed algorithms would be useful for designing compressive sensing-based systems for long-term telemonitoring of human gait signals.

Polymer coating embolism from intravascular medical devices - a clinical literature review.

PubMed

Chopra, Amitabh M; Mehta, Monik; Bismuth, Jean; Shapiro, Maksim; Fishbein, Michael C; Bridges, Alina G; Vinters, Harry V

Over the past three decades, lubricious (hydrophobic and/or hydrophilic) polymer-coated devices have been increasingly adopted by interventional physicians and vascular surgeons to access and treat a wider range of clinical presentations. Recent clinical literature highlights the presence of polymer coating emboli within the anatomy - a result of coating separation from an intravascular device - and associates it with a range of adverse clinical sequelae. The 2015 U.S. Food and Drug Administration safety communication titled "Lubricious Coating Separation from Intravascular Medical Devices" acknowledges these concerns and concludes that it will work with stakeholders to develop nonclinical test methodologies, establish performance criteria, and identify gaps in current national and international device standards for coating integrity performance. Despite this communication and multiple case reports from interventional physicians, pathologists, dermatologists and other involved physician specialties, polymer coating embolism remains clinically underrecognized. This article consolidates the available literature on polymer coating embolism (1986-2016) and highlights the following relevant information for the physician: (a) the history and elusive nature of polymer coating embolism; (b) potential incidence rates of this phenomenon; (c) reported histologic findings and clinical effects of polymer emboli in the anatomy; (d) the importance of the collaborative clinician-pathologist partnership to report polymer embolism findings; and (e) the importance to study particulate release from intravascular devices so as to further understand and potentially evolve coated interventional technologies. Preliminary research on coatings highlights the potential of using iterations of coatings on medical devices that attain the desired therapeutic result and mitigate or eliminate particulates altogether. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Understanding the quality of life (QOL) issues in survivors of cancer: towards the development of an EORTC QOL cancer survivorship questionnaire.

PubMed

van Leeuwen, Marieke; Husson, Olga; Alberti, Paola; Arraras, Juan Ignacio; Chinot, Olivier L; Costantini, Anna; Darlington, Anne-Sophie; Dirven, Linda; Eichler, Martin; Hammerlid, Eva B; Holzner, Bernhard; Johnson, Colin D; Kontogianni, Meropi; Kjær, Trille Kristina; Morag, Ofir; Nolte, Sandra; Nordin, Andrew; Pace, Andrea; Pinto, Monica; Polz, Katja; Ramage, John; Reijneveld, Jaap C; Serpentini, Samantha; Tomaszewski, Krzysztof A; Vassiliou, Vassilios; Verdonck-de Leeuw, Irma M; Vistad, Ingvild; Young, Teresa E; Aaronson, Neil K; van de Poll-Franse, Lonneke V

2018-06-04

The number of cancer survivors is growing steadily and increasingly, clinical trials are being designed to include long-term follow-up to assess not only survival, but also late effects and health-related quality of life (HRQOL). Therefore it is is essential to develop patient-reported outcome measures (PROMs) that capture the full range of issues relevant to disease-free cancer survivors. The objectives of this project are: 1) to develop a European Organisation for Research and Treatment of Cancer (EORTC) questionnaire that captures the full range of physical, mental and social HRQOL issues relevant to disease-free cancer survivors; and 2) to determine at which minimal time since completion of treatment the questionnaire should be used. We reviewed 134 publications on cancer survivorship and interviewed 117 disease-free cancer survivors with 11 different types of cancer across 14 countries in Europe to generate an exhaustive, provisional list of HRQOL issues relevant to cancer survivors. The resulting issue list, the EORTC core questionnaire (QLQ-C30), and site-specific questionnaire modules were completed by a second group of 458 survivors. We identified 116 generic survivorship issues. These issues covered body image, cognitive functioning, health behaviors, negative and positive outlook, health distress, mental health, fatigue, sleep problems, physical functioning, pain, several physical symptoms, social functioning, and sexual problems. Patients rated most of the acute symptoms of cancer and its treatment (e.g. nausea) as no longer relevant approximately one year after completion of treatment. Compared to existing cancer survivorship questionnaires, our findings underscore the relevance of assessing issues related to chronic physical side effects of treatment such as neuropathy and joint pain. We will further develop a core survivorship questionnaire and three site-specific modules for disease-free adult cancer survivors who are at least one year post-treatment.

Confidence in memory and other cognitive processes in obsessive-compulsive disorder.

PubMed

Nedeljkovic, Maja; Kyrios, Michael

2007-12-01

Previous studies have implicated beliefs about one's memory (i.e., meta-memory), in maintaining the symptoms of obsessive-compulsive disorder (OCD), particularly with respect to checking rituals. However, most research has focused on task- or situation-specific perceptions about memory performance. Expanding on this research, we undertook two studies with analogue and clinical cohorts to examine the relationship between general 'trait' beliefs about memory and related processes and OCD symptoms. Trait meta-memory as measured in the current study was conceptualised as a multi-dimensional construct encompassing a range of beliefs about memory and related processes including confidence in one's general memory abilities, decision-making abilities, concentration and attention, as well as perfectionistic standards regarding one's memory. Meta-memory factors were associated with OCD symptoms, predicting OCD symptoms over-and-above mood and other OCD-relevant cognitions. Meta-memory factors were found to be particularly relevant to checking symptoms. Implications for theory and research are discussed.

PET Timing Performance Measurement Method Using NEMA NEC Phantom

NASA Astrophysics Data System (ADS)

Wang, Gin-Chung; Li, Xiaoli; Niu, Xiaofeng; Du, Huini; Balakrishnan, Karthik; Ye, Hongwei; Burr, Kent

2016-06-01

When comparing the performance of time-of-flight whole-body PET scanners, timing resolution is one important benchmark. Timing performance is heavily influenced by detector and electronics design. Even for the same scanner design, measured timing resolution is a function of many factors including the activity concentration, geometry and positioning of the radioactive source. Due to lack of measurement standards, the timing resolutions reported in the literature may not be directly comparable and may not describe the timing performance under clinically relevant conditions. In this work we introduce a method which makes use of the data acquired during the standard NEMA Noise-Equivalent-Count-Rate (NECR) measurements, and compare it to several other timing resolution measurement methods. The use of the NEMA NEC phantom, with well-defined dimensions and radioactivity distribution, is attractive because it has been widely accepted in the industry and allows for the characterization of timing resolution across a more relevant range of conditions.

Interviews with children about their mental health problems: The congruence and validity of information that children report.

PubMed

Macleod, Emily; Woolford, June; Hobbs, Linda; Gross, Julien; Hayne, Harlene; Patterson, Tess

2017-04-01

To obtain a child's perspective during a mental health assessment, he or she is usually interviewed. Although researchers and clinicians generally agree that it is beneficial to hear a child's account of his or her presenting issues, there is debate about whether children provide reliable or valid clinical information during these interviews. Here, we examined whether children provide clinically and diagnostically relevant information in a clinical setting. In all, 31 children aged 5-12-years undergoing mental health assessments were asked open-ended questions about their presenting problems during a semi-structured interview. We coded the information that children reported to determine whether it was clinically relevant and could be used to diagnose their problems and to formulate and plan treatment. We also coded children's information to determine whether it was congruent with the children's presenting problems and their eventual clinical diagnoses. Most of the information that children reported was clinically relevant and included information about behaviour, affect, temporal details, thoughts, people, the environment, and the child's physical experiences. The information that children reported was also clinically valid; it was congruent with the problems that were discussed (84%) and also with the eventual diagnosis that the child received after a complete assessment (74%). We conclude that children can contribute relevant, clinically useful, valid information during clinical psychological assessments.

Short-term changes in neck pain, widespread pressure pain sensitivity, and cervical range of motion after the application of trigger point dry needling in patients with acute mechanical neck pain: a randomized clinical trial.

PubMed

Mejuto-Vázquez, María J; Salom-Moreno, Jaime; Ortega-Santiago, Ricardo; Truyols-Domínguez, Sebastián; Fernández-de-Las-Peñas, César

2014-04-01

Randomized clinical trial. To determine the effects of trigger point dry needling (TrPDN) on neck pain, widespread pressure pain sensitivity, and cervical range of motion in patients with acute mechanical neck pain and active trigger points in the upper trapezius muscle. TrPDN seems to be effective for decreasing pain in individuals with upper-quadrant pain syndromes. Potential effects of TrPDN for decreasing pain and sensitization in individuals with acute mechanical neck pain are needed. Methods Seventeen patients (53% female) were randomly assigned to 1 of 2 groups: a single session of TrPDN or no intervention (waiting list). Pressure pain thresholds over the C5-6 zygapophyseal joint, second metacarpal, and tibialis anterior muscle; neck pain intensity; and cervical spine range-of-motion data were collected at baseline (pretreatment) and 10 minutes and 1 week after the intervention by an assessor blinded to the treatment allocation of the patient. Mixed-model analyses of variance were used to examine the effects of treatment on each outcome variable. Patients treated with 1 session of TrPDN experienced greater decreases in neck pain, greater increases in pressure pain threshold, and higher increases in cervical range of motion than those who did not receive an intervention at both 10 minutes and 1 week after the intervention (P<.01 for all comparisons). Between-group effect sizes were medium to large immediately after the TrPDN session (standardized mean score differences greater than 0.56) and large at the 1-week follow-up (standardized mean score differences greater than 1.34). The results of the current randomized clinical trial suggest that a single session of TrPDN may decrease neck pain intensity and widespread pressure pain sensitivity, and also increase active cervical range of motion, in patients with acute mechanical neck pain. Changes in pain, pressure pain threshold, and cervical range of motion surpassed their respective minimal detectable change values, supporting clinically relevant treatment effects. Level of Evidence Therapy, level 1b-.

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

PubMed

Pan, Xuequn; Cimino, James J

2014-01-01

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

Nanodiamonds as platforms for biology and medicine.

PubMed

Man, Han B; Ho, Dean

2013-02-01

Nanoparticles possess a wide range of exceptional properties applicable to biology and medicine. In particular, nanodiamonds (NDs) are being studied extensively because they possess unique characteristics that make them suitable as platforms for diagnostics and therapeutics. This carbon-based material (2-8 nm) is medically relevant because it unites several key properties necessary for clinical applications, such as stability and compatibility in biological environments, and scalability in production. Research by the Ho group and others has yielded ND particles with a variety of capabilities ranging from delivery of chemotherapeutic drugs to targeted labeling and uptake studies. In addition, encouraging new findings have demonstrated the ability for NDs to effectively treat chemoresistant tumors in vivo. In this review, we highlight the progress made toward bringing nanodiamonds from the bench to the bedside.

Voice characteristics of children aged between 6 and 13 years: impact of age, gender, and vocal training.

PubMed

Pribuisiene, Ruta; Uloza, Virgilijus; Kardisiene, Vilija

2011-12-01

To determine impact of age, gender, and vocal training on voice characteristics of children aged 6-13 years. Voice acoustic and phonetogram parameters were determined for the group of 44 singing and 31 non-singing children. No impact of gender and/or age on phonetogram, acoustic voice parameters, and maximum phonation time was detected. Voice ranges of all children represented a pre-pubertal soprano type with a voice range of 22 semitones for non-singing and of 26 semitones for singing individuals. The mean maximum voice intensity was 81 dB. Vocal training had a positive impact on voice intensity parameters in girls. The presented data on average voice characteristics may be applicable in the clinical practice and provide relevant support for voice assessment.

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

PubMed

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

2017-07-01

To select relevant and feasible instruments for the revision of the Dutch clinical practice guideline for physical therapy in patients with stroke. In this implementation study a comprehensive proposal for ICF categories and matching instruments was developed, based on reliability and validity. Relevant instruments were then selected in a consensus round by 11 knowledge brokers who were responsible for the implementation of the selected instruments. The feasibility of the selected instruments was tested by 36 physical therapists at different work settings within stroke services. Finally, instruments that were deemed relevant and feasible were included in the revised guideline. A total of 28 instruments were recommended for inclusion in the revised guideline. Nineteen instruments were retained from the previous guideline. Ten new instruments were tested in clinical practice, seven of which were found feasible. Two more instruments were added after critical appraisal of the set of the measurement instruments. The revised guideline contains 28 relevant and feasible instrument selected and tested in clinical practice by physical therapists. Further education and implementation is needed to integrate instruments in clinical practice. Further research is proposed for developing and implementing a core set of measurement instruments to be used at fixed time points to establish data registries that allow for continuous improvement of rehabilitation for stroke patients. Implications for Rehabilitation The revised Dutch Stroke Physical Therapy Guideline recommends a total of 28 instruments, that are relevant and feasible for clinical practice of physical therapist in the different settings of stroke rehabilitation. The selection of instrument in daily practice should be part of the clinical reasoning process of PTs and be tailored to individual patients' needs and the degree of priority of the affected ICF category. Suggested education strategies for further integration of instruments in of the daily practice of PTs in Stroke Rehabilitation are: 'Training on the job' and 'peer assessment in clinical situations'.

High prevalence of Anisakis simplex hypersensitivity and allergy in Sicily, Italy.

PubMed

Heffler, Enrico; Sberna, Maria Eva; Sichili, Stefania; Intravaia, Rossella; Nicolosi, Giuliana; Porto, Morena; Liuzzo, Maria Teresa; Picardi, Giuseppe; Fichera, Silvia; Crimi, Nunzio

2016-02-01

Anisakis simplex can elicit allergic reactions when ingested in raw or marinated fish. The prevalence of A simplex hypersensitivity and allergy in Sicily (Italy), an area where the consumption of raw or marinated fish is very common, has not been investigated thus far. To investigate the prevalence of A simplex sensitization and its clinical relevance in a large group of unselected patients. All consecutive patients referred to the authors' allergy clinic during a 22 month-period were included in the study, evaluated for sensitization to A simplex and other allergens depending on their clinical history, and investigated for allergic symptoms after the ingestion of raw or marinated fish. Of 3,419 patients screened, 527 (15.4%) were sensitized to A simplex and 29 of these (5.5% of sensitized patients) had a history of A simplex allergy. Approximately 30% of patients had mono-sensitization to A simplex. Co-sensitization to house dust mites or molds yielded an odds ratio of 1.98 or 3.18, respectively, for allergy to A simplex. A high prevalence of A simplex sensitization in a large proportion of patients with mono-sensitization was found, confirming that eating habits influence sensitization to this nematode. Allergic symptoms from A simplex ingestion in raw or marinated fish were quite frequent, with symptoms ranging from oral allergy syndrome to anaphylaxis. Patients sensitized to A simplex were more prone to have allergic symptoms when they had co-sensitization to house dust mites or molds, suggesting possible cross-reactive but clinically relevant allergens between these allergenic sources. Copyright © 2016. Published by Elsevier Inc.

Decisional conflict in asthma patients: a cross sectional study.

PubMed

Des Cormiers, Annick; Légaré, France; Simard, Serge; Boulet, Louis-Philippe

2015-01-01

This study aimed at determining the level of decisional conflict in asthmatic individuals facing recommendation-based decisions provided to improve asthma control. This was a cross-sectional study performed on a convenience sample of 50 adults aged between 18 and 65 years with a diagnosis of asthma. They completed a decisional conflict scale (possible range of 0-100%), asthma knowledge and control questionnaires (both 0% and 100%), and a general questionnaire on socio-demographic characteristics. A decisional conflict was considered clinically significant with a score greater than 37.5%. Simple descriptive statistics were used to investigate associations with decisional conflict. Participants were mainly women (76%) and diagnosed with mild asthma (72%). The median age (1st and 3rd quartile) was 25 years (22 and 42). The median score (1st and 3rd quartile) of decisional conflict was 33% (24 and 44). A clinically significant score (>37.5%) was obtained in 36% of subjects. A statistically significant negative correlation between the knowledge score and the decisional conflict score (r(p) = -0.38; p = 0.006) was observed. The level of knowledge was the only statistically independent variable associated with the decisional conflict score (p = 0.0043). A considerable proportion of patients with asthma have a clinically significant level of decisional conflict when facing decisions aimed at improving asthma control. Patients with poor knowledge of asthma are more at risk of clinically significant level of decisional conflict. These findings support the relevance of providing asthmatic patients with relevant information in decision aids.

Propofol preferentially relaxes neurokinin receptor-2-induced airway smooth muscle contraction in guinea pig trachea.

PubMed

Gleason, Neil R; Gallos, George; Zhang, Yi; Emala, Charles W

2010-06-01

Propofol is the anesthetic of choice for patients with reactive airway disease and is thought to reduce intubation- or irritant-induced bronchoconstriction by decreasing the cholinergic component of vagal nerve activation. However, additional neurotransmitters, including neurokinins, play a role in irritant-induced bronchoconstriction. We questioned the mechanistic assumption that the clinically recognized protective effect of propofol against irritant-induced bronchoconstriction during intubation was due to attenuation of airway cholinergic reflexes. Muscle force was continuously recorded from isolated guinea pig tracheal rings in organ baths. Rings were subjected to exogenous contractile agonists (acetylcholine, histamine, endothelin-1, substance P, acetyl-substance P, and neurokinin A) or to electrical field stimulation (EFS) to differentiate cholinergic or nonadrenergic, noncholinergic nerve-mediated contraction with or without cumulatively increasing concentrations of propofol, thiopental, etomidate, or ketamine. Propofol did not attenuate the cholinergic component of EFS-induced contraction at clinically relevant concentrations. In contrast, propofol relaxed nonadrenergic, noncholinergic-mediated EFS contraction at concentrations within the clinical range (20-100 mum, n = 9; P < 0.05), and propofol was more potent against an exogenous selective neurokinin-2 receptor versus neurokinin-1 receptor agonist contraction (n = 6, P < 0.001). Propofol, at clinically relevant concentrations, relaxes airway smooth muscle contracted by nonadrenergic, noncholinergic-mediated EFS and exogenous neurokinins but not contractions elicited by the cholinergic component of EFS. These findings suggest that the mechanism of protective effects of propofol against irritant-induced bronchoconstriction involves attenuation of tachykinins released from nonadrenergic, noncholinergic nerves acting at neurokinin-2 receptors on airway smooth muscle.

Combining the ‘bottom up’ and ‘top down’ approaches in pharmacokinetic modelling: fitting PBPK models to observed clinical data

PubMed Central

Tsamandouras, Nikolaos; Rostami-Hodjegan, Amin; Aarons, Leon

2015-01-01

Pharmacokinetic models range from being entirely exploratory and empirical, to semi-mechanistic and ultimately complex physiologically based pharmacokinetic (PBPK) models. This choice is conditional on the modelling purpose as well as the amount and quality of the available data. The main advantage of PBPK models is that they can be used to extrapolate outside the studied population and experimental conditions. The trade-off for this advantage is a complex system of differential equations with a considerable number of model parameters. When these parameters cannot be informed from in vitro or in silico experiments they are usually optimized with respect to observed clinical data. Parameter estimation in complex models is a challenging task associated with many methodological issues which are discussed here with specific recommendations. Concepts such as structural and practical identifiability are described with regards to PBPK modelling and the value of experimental design and sensitivity analyses is sketched out. Parameter estimation approaches are discussed, while we also highlight the importance of not neglecting the covariance structure between model parameters and the uncertainty and population variability that is associated with them. Finally the possibility of using model order reduction techniques and minimal semi-mechanistic models that retain the physiological-mechanistic nature only in the parts of the model which are relevant to the desired modelling purpose is emphasized. Careful attention to all the above issues allows us to integrate successfully information from in vitro or in silico experiments together with information deriving from observed clinical data and develop mechanistically sound models with clinical relevance. PMID:24033787

Clinical features and laboratory findings of dengue fever in German travellers: A single-centre, retrospective analysis.

PubMed

Tavakolipoor, Pulad; Schmidt-Chanasit, Jonas; Burchard, Gerd Dieter; Jordan, Sabine

2016-01-01

Dengue fever (DF) is one of the most relevant human arboviral infections worldwide and has become a frequent cause of fever in the returning traveller. This retrospective study aimed to characterize epidemiological and clinical features and laboratory findings of dengue fever in German travellers. This descriptive study analyzed medical records of patients diagnosed with DF presenting at the Section of Tropical Medicine of the University Medical Centre Hamburg-Eppendorf from 2007 to 2011. Data were collected and analyzed retrospectively. In total, data of 119 DF patients (52 female, 67 male) were included in this study. The median age of the patients was 35 (range 15-75 years). DF was most frequently acquired in South-East Asia (n = 65; 54.7%), and in particular in Thailand (n = 23; 19.7%). A considerable percentage of DF infections (n = 14; 11.8%) was imported from Africa. Patients predominantly presented with fever, headache, rash, myalgia and arthralgia but also with gastrointestinal symptoms, i.e. diarrhoea. Nine patients showed signs of minor haemorrhagic manifestations. Neurological complications occurred in 13 patients. Low platelet count, leukopenia and elevated liver enzymes were the most relevant laboratory findings. Twenty patients (17.8%) had to be hospitalized. Overall, the clinical course was mostly mild to moderate, 13 patients (10.9%) showed DF warnings signs, no fatalities occurred. DF presented as a mostly mild to moderate disease in this study cohort. Outpatient treatment was adequate for the majority of patients. Still, detailed knowledge of clinical symptoms and laboratory features is essential for appropriate triage. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Cancer.gov

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

From Single Nucleotide Polymorphisms to Constant Immunosuppression: Mesenchymal Stem Cell Therapy for Autoimmune Diseases

PubMed Central

Galipeau, Jacques; Nooka, Ajay K.

2013-01-01

The regenerative abilities and the immunosuppressive properties of mesenchymal stromal cells (MSCs) make them potentially the ideal cellular product of choice for treatment of autoimmune and other immune mediated disorders. Although the usefulness of MSCs for therapeutic applications is in early phases, their potential clinical use remains of great interest. Current clinical evidence of use of MSCs from both autologous and allogeneic sources to treat autoimmune disorders confers conflicting clinical benefit outcomes. These varied results may possibly be due to MSC use across wide range of autoimmune disorders with clinical heterogeneity or due to variability of the cellular product. In the light of recent genome wide association studies (GWAS), linking predisposition of autoimmune diseases to single nucleotide polymorphisms (SNPs) in the susceptible genetic loci, the clinical relevance of MSCs possessing SNPs in the critical effector molecules of immunosuppression is largely undiscussed. It is of further interest in the allogeneic setting, where SNPs in the target pathway of MSC's intervention may also modulate clinical outcome. In the present review, we have discussed the known critical SNPs predisposing to disease susceptibility in various autoimmune diseases and their significance in the immunomodulatory properties of MSCs. PMID:24350294

In Defense of a Social Value Requirement for Clinical Research

PubMed Central

Wendler, David; Rid, Annette

2017-01-01

Many guidelines and commentators endorse the view that clinical research is ethically acceptable only when it has social value, in the sense of collecting data which might be used to improve health. A version of this social value requirement is included in the Declaration of Helsinki and the Nuremberg Code, and is codified in many national research regulations. At the same time, there have been no systematic analyses of why social value is an ethical requirement for clinical research. Recognizing this gap in the literature, recent articles by Alan Wertheimer and David Resnik argue that the extant justifications for the social value requirement are unpersuasive. Both authors conclude, contrary to almost all current guidelines and regulations, that it can be acceptable across a broad range of cases to conduct clinical research which is known prospectively to have no social value. The present paper assesses this conclusion by critically evaluating the ethical and policy considerations relevant to the claim that clinical research must have social value. This analysis supports the standard view that social value is an ethical requirement for the vast majority of clinical research studies and should be mandated by applicable guidelines and policies. PMID:28060427

In Defense of a Social Value Requirement for Clinical Research.

PubMed

Wendler, David; Rid, Annette

2017-02-01

Many guidelines and commentators endorse the view that clinical research is ethically acceptable only when it has social value, in the sense of collecting data which might be used to improve health. A version of this social value requirement is included in the Declaration of Helsinki and the Nuremberg Code, and is codified in many national research regulations. At the same time, there have been no systematic analyses of why social value is an ethical requirement for clinical research. Recognizing this gap in the literature, recent articles by Alan Wertheimer and David Resnik argue that the extant justifications for the social value requirement are unpersuasive. Both authors conclude, contrary to almost all current guidelines and regulations, that it can be acceptable across a broad range of cases to conduct clinical research which is known prospectively to have no social value. The present article assesses this conclusion by critically evaluating the ethical and policy considerations relevant to the claim that clinical research must have social value. This analysis supports the standard view that social value is an ethical requirement for the vast majority of clinical research studies and should be mandated by applicable guidelines and policies. © 2017 John Wiley & Sons Ltd.

Ambiguity Within Nursing Practice: An Evolutionary Concept Analysis.

PubMed

McMahon, Michelle A; Dluhy, Nancy M

2017-02-01

To analyze the concept of ambiguity in a nursing context. Ambiguity is inherent within nursing practice. As health care becomes increasingly complex, nurses must continue to successfully deal with greater amounts of clinical ambiguity. Although ambiguity is discussed in nursing, minimal concept refinement exists to capture the contextual intricacies from a nursing lens. Nurse perception of an ambiguous clinical event, in combination with nurse tolerance level for ambiguity, can impact nurse response. Yet, little is known about what constitutes ambiguity within nursing practice (AWNP). Rodgers evolutionary method was used to explore AWNP, with emphasis on nurse thinking during ambiguous clinical situations. Literature searches across multiple databases yielded 38 articles for analysis. Attributes of AWNP include (a) variations in cues/available information, (b) multiple interpretations, (c) novel/nonroutine presentations, and (d) unpredictable. Antecedents include (a) a context-specific, clinical situation with ambiguous features needing evaluation and (b) an individual to sense a knowledge gap or perceive ambiguity. Consequences include ranges of (a) emotional, (b) behavioral, and (c) cognitive clinician responses. Preliminary findings support AWNP as a distinct concept in which ambiguity perceived by the nurse likely affects judgment, decision making, and clinical interventions. AWNP is a clinically relevant concept requiring continued development.

CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING

PubMed Central

HAFLER, BRIAN P.

2017-01-01

Purpose Inherited retinal dystrophies are a significant cause of vision loss and are characterized by the loss of photoreceptors and the retinal pigment epithelium (RPE). Mutations in approximately 250 genes cause inherited retinal degenerations with a high degree of genetic heterogeneity. New techniques in next-generation sequencing are allowing the comprehensive analysis of all retinal disease genes thus changing the approach to the molecular diagnosis of inherited retinal dystrophies. This review serves to analyze clinical progress in genetic diagnostic testing and implications for retinal gene therapy. Methods A literature search of PubMed and OMIM was conducted to relevant articles in inherited retinal dystrophies. Results Next-generation genetic sequencing allows the simultaneous analysis of all the approximately 250 genes that cause inherited retinal dystrophies. Reported diagnostic rates range are high and range from 51% to 57%. These new sequencing tools are highly accurate with sensitivities of 97.9% and specificities of 100%. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. Conclusion Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations. Not only are high diagnostic yields obtained, but mutations in genes with novel clinical phenotypes are also identified. In the era of retinal gene therapy clinical trials, identifying specific genetic defects will increasingly be of use to identify patients who may enroll in clinical studies and benefit from novel therapies. PMID:27753762

The Green Card Clinic: overview of a brief patient-centred intervention following deliberate self-harm.

PubMed

Wilhelm, Kay; Finch, Adam; Kotze, Beth; Arnold, Karen; McDonald, Geoff; Sternhell, Peter; Hudson, Beaver

2007-02-01

The aim of this study was to present an overview of the Green Card Clinic, a novel brief intervention service for patients presenting to the emergency department following deliberate self-harm (DSH) or with suicidal ideation, to examine its effectiveness in terms of service utilization, and patient and clinician feedback, and to explore the correlates of repeated DSH. The aims and structure of the Green Card Clinic are described. We highlight our patient-centred approach involving self-identification of difficulties from a list of problem areas, coupled with tailored intervention strategies. Relevant data are presented and characteristics of repeat DSH patients are compared to the first-episode group. Between 1998 and 2005, 456 DSH patients were referred to the clinic. Of these, 75% (n = 344) attended the first session, 43% (n = 197) the second session, 26% (n = 117) the third session, and 16% (n = 73) completed a 3-15 month follow-up. Clinic attenders (mean age 31.6 years, 57% female) reported a diverse range of self-identified problems and repeat DSH patients reported worse depression, poorer health-related behaviours, and a greater number of problems than those presenting after first-episode DSH. The clinic achieved high rates of first session attendance. This may have been attributable to the use of a few specific strategies aimed at increasing compliance, such as the green card, next-day appointments and assertive follow-up of non-attenders. For repeat self-harmers, we advocate an approach aimed at 'lifestyle change' rather than based on current psychological stressors. The Green Card Clinic service, involving a range of interventions tailored to meet the multitude of presenting needs, appears to be an acceptable and flexible approach to brief intervention for DSH.

Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism.

PubMed

Fareed, Jawed; Adiguzel, Cafer; Thethi, Indermohan

2011-03-28

The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available. MEDLINE and EMBASE databases were searched to identify relevant original articles. Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding. Parenteral anticoagulants should be prescribed in accordance with recommended dose regimens for each clinical indication, based on the available clinical evidence for each agent to assure optimal safety and efficacy.

Retrieving clinical evidence: a comparison of PubMed and Google Scholar for quick clinical searches.

PubMed

Shariff, Salimah Z; Bejaimal, Shayna Ad; Sontrop, Jessica M; Iansavichus, Arthur V; Haynes, R Brian; Weir, Matthew A; Garg, Amit X

2013-08-15

Physicians frequently search PubMed for information to guide patient care. More recently, Google Scholar has gained popularity as another freely accessible bibliographic database. To compare the performance of searches in PubMed and Google Scholar. We surveyed nephrologists (kidney specialists) and provided each with a unique clinical question derived from 100 renal therapy systematic reviews. Each physician provided the search terms they would type into a bibliographic database to locate evidence to answer the clinical question. We executed each of these searches in PubMed and Google Scholar and compared results for the first 40 records retrieved (equivalent to 2 default search pages in PubMed). We evaluated the recall (proportion of relevant articles found) and precision (ratio of relevant to nonrelevant articles) of the searches performed in PubMed and Google Scholar. Primary studies included in the systematic reviews served as the reference standard for relevant articles. We further documented whether relevant articles were available as free full-texts. Compared with PubMed, the average search in Google Scholar retrieved twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001). Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07). Google Scholar provided significantly greater access to free full-text publications (PubMed: 5%; Google Scholar: 14%; P<.001). For quick clinical searches, Google Scholar returns twice as many relevant articles as PubMed and provides greater access to free full-text articles.

Photobiomodulation for the treatment of retinal diseases: a review.

PubMed

Geneva, Ivayla I

2016-01-01

Photobiomodulation (PBM), also known as low level laser therapy, has recently risen to the attention of the ophthalmology community as a promising new approach to treat a variety of retinal conditions including age-related macular degeneration, retinopathy of prematurity, diabetic retinopathy, Leber's hereditary optic neuropathy, amblyopia, methanol-induced retinal damage, and possibly others. This review evaluates the existing research pertaining to PBM applications in the retina, with a focus on the mechanisms of action and clinical outcomes. All available literature until April 2015 was reviewed using PubMed and the following keywords: "photobiomodulation AND retina", "low level light therapy AND retina", "low level laser therapy AND retina", and "FR/NIR therapy AND retina". In addition, the relevant references listed within the papers identified through PubMed were incorporated. The literature supports the conclusion that the low-cost and non-invasive nature of PBM, coupled with the first promising clinical reports and the numerous preclinical-studies in animal models, make PBM well-poised to become an important player in the treatment of a wide range of retinal disorders. Nevertheless, large-scale clinical trials will be necessary to establish the PBM therapeutic ranges for the various retinal diseases, as well as to gain a deeper understanding of its mechanisms of action.

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

PubMed Central

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

2015-01-01

Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens. PMID:26515599

Clinical Detection of Pre-Cataractous Lens Protein Changes using Dynamic Light Scattering

PubMed Central

Datiles, Manuel B.; Ansari, Rafat R.; Suh, Kwang I.; Vitale, Susan; Reed, George F.; Zigler, J. Samuel; Ferris., Frederick L.

2008-01-01

Purpose To use Dynamic Light Scattering (DLS) to clinically assess early pre-cataractous lens protein changes. Methods We performed a cross sectional study in 380 eyes of 235 subjects aged 7–86 years with AREDS clinical lens nuclear grades ranging from 0–3.8. A DLS device was used to assess α-crystallin, a molecular chaperone protein shown to bind other damaged lens proteins, preventing their aggregation. The outcome measure was the α-crystallin index (ACI), a measure of unbound α-crystallin in each lens. The association of ACI with increasing nuclear opacity and aging was determined. Results There was a significant decrease in ACI associated with increasing grades of lens nuclear opacity (p<0.0001). There are significant losses of α-crystallin even in clinically clear lenses associated with aging (p<0.0001). The standard error of measurement was 3%. Conclusions DLS clinically detects loss of α-crystallin proteins even in clinically clear lenses. ACI measurements may be useful in identifying patients at high risk for developing cataract, and as an outcome variable in clinical lens studies. Clinical Relevance Our studies suggest that the ACI may be a useful measure of the protective α-crystallin molecular chaperone reserve present in a lens, analogous to creatinine clearance in estimating renal function reserve. PMID:19064850

Adaptive semantic tag mining from heterogeneous clinical research texts.

PubMed

Hao, T; Weng, C

2015-01-01

To develop an adaptive approach to mine frequent semantic tags (FSTs) from heterogeneous clinical research texts. We develop a "plug-n-play" framework that integrates replaceable unsupervised kernel algorithms with formatting, functional, and utility wrappers for FST mining. Temporal information identification and semantic equivalence detection were two example functional wrappers. We first compared this approach's recall and efficiency for mining FSTs from ClinicalTrials.gov to that of a recently published tag-mining algorithm. Then we assessed this approach's adaptability to two other types of clinical research texts: clinical data requests and clinical trial protocols, by comparing the prevalence trends of FSTs across three texts. Our approach increased the average recall and speed by 12.8% and 47.02% respectively upon the baseline when mining FSTs from ClinicalTrials.gov, and maintained an overlap in relevant FSTs with the base- line ranging between 76.9% and 100% for varying FST frequency thresholds. The FSTs saturated when the data size reached 200 documents. Consistent trends in the prevalence of FST were observed across the three texts as the data size or frequency threshold changed. This paper contributes an adaptive tag-mining framework that is scalable and adaptable without sacrificing its recall. This component-based architectural design can be potentially generalizable to improve the adaptability of other clinical text mining methods.

The clinical trial landscape in oncology and connectivity of somatic mutational profiles to targeted therapies.

PubMed

Patterson, Sara E; Liu, Rangjiao; Statz, Cara M; Durkin, Daniel; Lakshminarayana, Anuradha; Mockus, Susan M

2016-01-16

Precision medicine in oncology relies on rapid associations between patient-specific variations and targeted therapeutic efficacy. Due to the advancement of genomic analysis, a vast literature characterizing cancer-associated molecular aberrations and relative therapeutic relevance has been published. However, data are not uniformly reported or readily available, and accessing relevant information in a clinically acceptable time-frame is a daunting proposition, hampering connections between patients and appropriate therapeutic options. One important therapeutic avenue for oncology patients is through clinical trials. Accordingly, a global view into the availability of targeted clinical trials would provide insight into strengths and weaknesses and potentially enable research focus. However, data regarding the landscape of clinical trials in oncology is not readily available, and as a result, a comprehensive understanding of clinical trial availability is difficult. To support clinical decision-making, we have developed a data loader and mapper that connects sequence information from oncology patients to data stored in an in-house database, the JAX Clinical Knowledgebase (JAX-CKB), which can be queried readily to access comprehensive data for clinical reporting via customized reporting queries. JAX-CKB functions as a repository to house expertly curated clinically relevant data surrounding our 358-gene panel, the JAX Cancer Treatment Profile (JAX CTP), and supports annotation of functional significance of molecular variants. Through queries of data housed in JAX-CKB, we have analyzed the landscape of clinical trials relevant to our 358-gene targeted sequencing panel to evaluate strengths and weaknesses in current molecular targeting in oncology. Through this analysis, we have identified patient indications, molecular aberrations, and targeted therapy classes that have strong or weak representation in clinical trials. Here, we describe the development and disseminate system methods for associating patient genomic sequence data with clinically relevant information, facilitating interpretation and providing a mechanism for informing therapeutic decision-making. Additionally, through customized queries, we have the capability to rapidly analyze the landscape of targeted therapies in clinical trials, enabling a unique view into current therapeutic availability in oncology.

Newly Identified Gait Patterns in Patients With Multiple Sclerosis May Be Related to Push-off Quality.

PubMed

Kempen, Jiska C E; Doorenbosch, Caroline A M; Knol, Dirk L; de Groot, Vincent; Beckerman, Heleen

2016-11-01

Limited walking ability is an important problem for patients with multiple sclerosis. A better understanding of how gait impairments lead to limited walking ability may help to develop more targeted interventions. Although gait classifications are available in cerebral palsy and stroke, relevant knowledge in MS is scarce. The aims of this study were: (1) to identify distinctive gait patterns in patients with MS based on a combined evaluation of kinematics, gait features, and muscle activity during walking and (2) to determine the clinical relevance of these gait patterns. This was a cross-sectional study of 81 patients with MS of mild-to-moderate severity (Expanded Disability Status Scale [EDSS] median score=3.0, range=1.0-7.0) and an age range of 28 to 69 years. The patients participated in 2-dimensional video gait analysis, with concurrent measurement of surface electromyography and ground reaction forces. A score chart of 73 gait items was used to rate each gait analysis. A single rater performed the scoring. Latent class analysis was used to identify gait classes. Analysis of the 73 gait variables revealed that 9 variables could distinguish 3 clinically meaningful gait classes. The 9 variables were: (1) heel-rise in terminal stance, (2) push-off, (3) clearance in initial swing, (4) plantar-flexion position in mid-swing, (5) pelvic rotation, (6) arm-trunk movement, (7) activity of the gastrocnemius muscle in pre-swing, (8) M-wave, and (9) propulsive force. The EDSS score and gait speed worsened in ascending classes. Most participants had mild-to-moderate limitations in walking ability based on their EDSS scores, and the number of walkers who were severely limited was small. Based on a small set of 9 variables measured with 2-dimensional clinical gait analysis, patients with MS could be divided into 3 different gait classes. The gait variables are suggestive of insufficient ankle push-off. © 2016 American Physical Therapy Association.

The baseline pressure of intracranial pressure (ICP) sensors can be altered by electrostatic discharges.

PubMed

Eide, Per K; Bakken, André

2011-08-22

The monitoring of intracranial pressure (ICP) has a crucial role in the surveillance of patients with brain injury. During long-term monitoring of ICP, we have seen spontaneous shifts in baseline pressure (ICP sensor zero point), which are of technical and not physiological origin. The aim of the present study was to explore whether or not baseline pressures of ICP sensors can be affected by electrostatics discharges (ESD's), when ESD's are delivered at clinically relevant magnitudes. We performed bench-testing of a set of commercial ICP sensors. In our experimental setup, the ICP sensor was placed in a container with 0.9% NaCl solution. A test person was charged 0.5-10 kV, and then delivered ESD's to the sensor by touching a metal rod that was located in the container. The continuous pressure signals were recorded continuously before/after the ESD's, and the pressure readings were stored digitally using a computerized system A total of 57 sensors were tested, including 25 Codman ICP sensors and 32 Raumedic sensors. When charging the test person in the range 0.5-10 kV, typically ESD's in the range 0.5-5 kV peak pulse were delivered to the ICP sensor. Alterations in baseline pressure ≥ 2 mmHg was seen in 24 of 25 (96%) Codman sensors and in 17 of 32 (53%) Raumedic sensors. Lasting changes in baseline pressure > 10 mmHg that in the clinical setting would affect patient management, were seen frequently for both sensor types. The changes in baseline pressure were either characterized by sudden shifts or gradual drifts in baseline pressure. The baseline pressures of commercial solid ICP sensors can be altered by ESD's at discharge magnitudes that are clinically relevant. Shifts in baseline pressure change the ICP levels visualised to the physician on the monitor screen, and thereby reveal wrong ICP values, which likely represent a severe risk to the patient.

The baseline pressure of intracranial pressure (ICP) sensors can be altered by electrostatic discharges

PubMed Central

2011-01-01

Background The monitoring of intracranial pressure (ICP) has a crucial role in the surveillance of patients with brain injury. During long-term monitoring of ICP, we have seen spontaneous shifts in baseline pressure (ICP sensor zero point), which are of technical and not physiological origin. The aim of the present study was to explore whether or not baseline pressures of ICP sensors can be affected by electrostatics discharges (ESD's), when ESD's are delivered at clinically relevant magnitudes. Methods We performed bench-testing of a set of commercial ICP sensors. In our experimental setup, the ICP sensor was placed in a container with 0.9% NaCl solution. A test person was charged 0.5 - 10 kV, and then delivered ESD's to the sensor by touching a metal rod that was located in the container. The continuous pressure signals were recorded continuously before/after the ESD's, and the pressure readings were stored digitally using a computerized system Results A total of 57 sensors were tested, including 25 Codman ICP sensors and 32 Raumedic sensors. When charging the test person in the range 0.5-10 kV, typically ESD's in the range 0.5 - 5 kV peak pulse were delivered to the ICP sensor. Alterations in baseline pressure ≥ 2 mmHg was seen in 24 of 25 (96%) Codman sensors and in 17 of 32 (53%) Raumedic sensors. Lasting changes in baseline pressure > 10 mmHg that in the clinical setting would affect patient management, were seen frequently for both sensor types. The changes in baseline pressure were either characterized by sudden shifts or gradual drifts in baseline pressure. Conclusions The baseline pressures of commercial solid ICP sensors can be altered by ESD's at discharge magnitudes that are clinically relevant. Shifts in baseline pressure change the ICP levels visualised to the physician on the monitor screen, and thereby reveal wrong ICP values, which likely represent a severe risk to the patient. PMID:21859487

Low-frequency quantitative ultrasound imaging of cell death in vivo

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

Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J.

Purpose: Currently, no clinical imaging modality is used routinely to assess tumor response to cancer therapies within hours to days of the delivery of treatment. Here, the authors demonstrate the efficacy of ultrasound at a clinically relevant frequency to quantitatively detect changes in tumors in response to cancer therapies using preclinical mouse models.Methods: Conventional low-frequency and corresponding high-frequency ultrasound (ranging from 4 to 28 MHz) were used along with quantitative spectroscopic and signal envelope statistical analyses on data obtained from xenograft tumors treated with chemotherapy, x-ray radiation, as well as a novel vascular targeting microbubble therapy.Results: Ultrasound-based spectroscopic biomarkers indicatedmore » significant changes in cell-death associated parameters in responsive tumors. Specifically changes in the midband fit, spectral slope, and 0-MHz intercept biomarkers were investigated for different types of treatment and demonstrated cell-death related changes. The midband fit and 0-MHz intercept biomarker derived from low-frequency data demonstrated increases ranging approximately from 0 to 6 dBr and 0 to 8 dBr, respectively, depending on treatments administrated. These data paralleled results observed for high-frequency ultrasound data. Statistical analysis of ultrasound signal envelope was performed as an alternative method to obtain histogram-based biomarkers and provided confirmatory results. Histological analysis of tumor specimens indicated up to 61% cell death present in the tumors depending on treatments administered, consistent with quantitative ultrasound findings indicating cell death. Ultrasound-based spectroscopic biomarkers demonstrated a good correlation with histological morphological findings indicative of cell death (r{sup 2}= 0.71, 0.82; p < 0.001).Conclusions: In summary, the results provide preclinical evidence, for the first time, that quantitative ultrasound used at a clinically relevant frequency, in addition to high-frequency ultrasound, can detect tissue changes associated with cell death in vivo in response to cancer treatments.« less

Do citizens have minimum medical knowledge? A survey

PubMed Central

Bachmann, Lucas M; Gutzwiller, Florian S; Puhan, Milo A; Steurer, Johann; Steurer-Stey, Claudia; Gigerenzer, Gerd

2007-01-01

Background Experts defined a "minimum medical knowledge" (MMK) that people need for understanding typical signs and/or risk factors of four relevant clinical conditions: myocardial infarction, stroke, chronic obstructive pulmonary disease and HIV/AIDS. We tested to what degree Swiss adult citizens satisfy this criterion for MMK and whether people with medical experience have acquired better knowledge than those without. Methods Questionnaire interview in a Swiss urban area with 185 Swiss citizens (median age 29 years, interquartile range 23 to 49, 52% male). We obtained context information on age, gender, highest educational level, (para)medical background and specific health experience with one of the conditions in the social surrounding. We calculated the proportion of MMK and examined whether citizens with medical background (personal or professional) would perform better compared to other groups. Results No single citizen reached the full MMK (100%). The mean MMK was as low as 32% and the range was 0 -72%. Surprisingly, multivariable analysis showed that participants with a university degree (n = 84; β (95% CI) +3.7% MMK (0.4–7.1) p = 0.03), (para)medical background (n = 34; +6.2% MMK (2.0–10.4), p = 0.004) and personal illness experience (n = 96; +4.9% MMK (1.5–8.2), p = 0.004) had only a moderately higher MMK than those without, while age and sex had no effect on the level of MMK. Interaction between university degree and clinical experience (personal or professional) showed no effect suggesting that higher education lacks synergistic effect. Conclusion This sample of Swiss citizens did not know more than a third of the MMK. We found little difference within groups with medical experience (personal or professional), suggesting that there is a consistent and dramatic lack of knowledge in the general public about the typical signs and risk factors of relevant clinical conditions. PMID:17540024

Evaluation of the fibromyalgia impact questionnaire at baseline as a predictor for time to pain improvement in two clinical trials of pregabalin.

PubMed

Bushmakin, A G; Cappelleri, J C; Chandran, A B; Zlateva, G

2013-01-01

The Fibromyalgia Impact Questionnaire (FIQ) is a patient-reported outcome that evaluates the impact of fibromyalgia (FM) on daily life. This study evaluated the relationships between the functional status of FM patients, measured with the FIQ at baseline, and median time to a clinically relevant pain reduction. Data were derived from two randomised, placebo-controlled trials that evaluated pregabalin 300, 450 and 600 mg/day for the treatment of FM. The Kaplan-Meier (nonparametric) method was applied to estimate median times to 'transient' and 'stable' events. The transient event was defined as a ≥ 27.9% improvement on an 11-point daily pain diary scale (0 = no pain, 10 = worst possible pain), and the stable event was defined as the mean of the daily improvements ≥ 27.9% relative to baseline over the subsequent study duration starting on the day of the transient event. A parametric model using time-to-event analysis was developed for evaluating the relationship between baseline FIQ score and the median time to these events. Median time was longer among patients treated with placebo relative to pregabalin for the transient events (11-12 days vs. 5-7 days) and stable events (86 days vs. 13-29 days). A significant association was observed between baseline FIQ scores and median time to transient and stable events (p < 0.001). Median times to events were similar between the studies. For transient pain reduction events, median times ranged from 3.0 to 4.5 days for baseline FIQ scores of 10, and 9.1-9.6 days for FIQ scores of 100; for stable pain reduction events, the median time ranged from 11.0 to 13.0 days and from 27.0 to 28.5 days for baseline FIQ scores of 10 and 100 respectively. Time to a clinically relevant reduction in pain was significantly associated with FM severity at baseline as measured by the FIQ. Such an analysis can inform patient and physician expectations in clinical practice. © 2012 Blackwell Publishing Ltd.

Urokinase-receptor (u-PAR): an essential player in multiple games of cancer: a review on its role in tumor progression, invasion, metastasis, proliferation/dormancy, clinical outcome and minimal residual disease.

PubMed

Laufs, Stephanie; Schumacher, Jens; Allgayer, Heike

2006-08-01

The relevance of the u-PA system in mediating tumor-associated proteolysis, invasion and metastasis, amongst other phenomena associated with tumor progression, has been clearly demonstrated in diverse cancer entities. This review will update on the biological and clinical relevance of the urokinase-receptor (u-PAR). Specifically, the article focuses on the potential importance of u-PAR for the development of minimal residual disease in solid cancer, and in this context reviews the biological relevance of the u-PAR for tumor cell dormancy. Furthermore, transcriptional mechanisms regulating u-PAR in vitro and in vivo, and their potential clinical and therapeutic relevance in gastrointestinal cancers, are elucidated.

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

PubMed

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

2003-09-01

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

77 FR 32975 - AHRQ Workgroups on ICD-10-CM/PCS Conversion of Quality Indicators (QIs)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-04

... relevant clinical expertise (e.g., cardiovascular disease, neurologic disease, orthopedic and musculoskeletal disease, obstetrics and gynecologic disease, surgery, critical care and pulmonary disease... measurement using administrative data in specific, relevant clinical domains (e.g., cardiovascular disease...

Barriers to Retrieving Patient Information from Electronic Health Record Data: Failure Analysis from the TREC Medical Records Track

PubMed Central

Edinger, Tracy; Cohen, Aaron M.; Bedrick, Steven; Ambert, Kyle; Hersh, William

2012-01-01

Objective: Secondary use of electronic health record (EHR) data relies on the ability to retrieve accurate and complete information about desired patient populations. The Text Retrieval Conference (TREC) 2011 Medical Records Track was a challenge evaluation allowing comparison of systems and algorithms to retrieve patients eligible for clinical studies from a corpus of de-identified medical records, grouped by patient visit. Participants retrieved cohorts of patients relevant to 35 different clinical topics, and visits were judged for relevance to each topic. This study identified the most common barriers to identifying specific clinic populations in the test collection. Methods: Using the runs from track participants and judged visits, we analyzed the five non-relevant visits most often retrieved and the five relevant visits most often overlooked. Categories were developed iteratively to group the reasons for incorrect retrieval for each of the 35 topics. Results: Reasons fell into nine categories for non-relevant visits and five categories for relevant visits. Non-relevant visits were most often retrieved because they contained a non-relevant reference to the topic terms. Relevant visits were most often infrequently retrieved because they used a synonym for a topic term. Conclusions: This failure analysis provides insight into areas for future improvement in EHR-based retrieval with techniques such as more widespread and complete use of standardized terminology in retrieval and data entry systems. PMID:23304287

Barriers to retrieving patient information from electronic health record data: failure analysis from the TREC Medical Records Track.

PubMed

Edinger, Tracy; Cohen, Aaron M; Bedrick, Steven; Ambert, Kyle; Hersh, William

2012-01-01

Secondary use of electronic health record (EHR) data relies on the ability to retrieve accurate and complete information about desired patient populations. The Text Retrieval Conference (TREC) 2011 Medical Records Track was a challenge evaluation allowing comparison of systems and algorithms to retrieve patients eligible for clinical studies from a corpus of de-identified medical records, grouped by patient visit. Participants retrieved cohorts of patients relevant to 35 different clinical topics, and visits were judged for relevance to each topic. This study identified the most common barriers to identifying specific clinic populations in the test collection. Using the runs from track participants and judged visits, we analyzed the five non-relevant visits most often retrieved and the five relevant visits most often overlooked. Categories were developed iteratively to group the reasons for incorrect retrieval for each of the 35 topics. Reasons fell into nine categories for non-relevant visits and five categories for relevant visits. Non-relevant visits were most often retrieved because they contained a non-relevant reference to the topic terms. Relevant visits were most often infrequently retrieved because they used a synonym for a topic term. This failure analysis provides insight into areas for future improvement in EHR-based retrieval with techniques such as more widespread and complete use of standardized terminology in retrieval and data entry systems.

Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo-Obstruction in 6 Dogs.

PubMed

Zacuto, A C; Pesavento, P A; Hill, S; McAlister, A; Rosenthal, K; Cherbinsky, O; Marks, S L

2016-01-01

Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo-obstruction in humans and animals. To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Six client-owned dogs. Retrospective case series. Medical records were reviewed to describe signalment, clinicopathologic and imaging findings, histopathologic diagnoses, treatment, and outcome. All biopsy specimens were reviewed by a board-certified pathologist. Median age of dogs was 5.4 years (range, 15 months-9 years). Consistent clinical signs included vomiting (6/6), regurgitation (2/6), and small bowel diarrhea (3/6). Median duration of clinical signs before presentation was 13 days (range, 5-150 days). Diagnostic imaging showed marked gastric distension with dilated small intestines in 4/6 dogs. Full-thickness intestinal biopsies were obtained in all dogs by laparotomy. Histopathology of the stomach and intestines disclosed mononuclear inflammation, myofiber degeneration and necrosis, and fibrosis centered within the region of myofiber loss in the intestinal muscularis propria. All dogs received various combinations of immunomodulatory and prokinetic treatment, antimicrobial agents, antiemetics, and IV fluids, but none of the dogs showed a clinically relevant improvement with treatment. Median survival was 19 days after diagnosis (range, 3-270 days). Intestinal leiomyositis is a cause of intestinal pseudo-obstruction and must be diagnosed by full-thickness intestinal biopsy. This disease should be considered in dogs with acute and chronic vomiting, regurgitation, and small bowel diarrhea. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Assessing clinically meaningful treatment effects in controlled trials: chronic migraine as an example.

PubMed

Dodick, David W; Turkel, Catherine C; DeGryse, Ronald E; Diener, Hans-Christoph; Lipton, Richard B; Aurora, Sheena K; Nolan, Marissa E; Silberstein, Stephen D

2015-02-01

In addition to headache, persons with chronic migraine (CM) experience multiple symptoms, both ictal and interictal, that may contribute to their suffering. Translating clinical trial results into practice requires assessment of the results' clinical meaningfulness. When examining treatment benefit in this disabled patient population, multiple headache-symptom measures should be considered to fully reflect clinical relevance. Currently, only onabotulinumtoxinA is approved specifically for headache prophylaxis in adults with CM. Topiramate is the only other therapeutic agent with double-blind, placebo-controlled evidence in this population. Herein we evaluate the clinical meaningfulness of onabotulinumtoxinA and topiramate as headache prophylaxis in CM by comparing primary endpoints from the placebo-controlled, double-blind phase of the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program and the topiramate clinical trial (frequency of headache days [primary endpoint in PREEMPT; secondary in topiramate trial] and migraine/migrainous days [primary in topiramate trial, or "migraine/probable-migraine days"; secondary in PREEMPT]). Additionally, outcome measures such as responder rates, health-related quality of life, discontinuation rates, safety, and tolerability profiles are important clinical considerations. The clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate. These data support these treatments as meaningful headache prophylaxis in adults with CM. CM is a chronic pain condition. We sought to determine the clinical relevance of recent trials in this disabled population. Clinical data indicate that statistically significant, clinically relevant treatment benefits exist for both onabotulinumtoxinA and topiramate, and support use of these treatments as meaningful headache prophylaxis in CM. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Clinically Relevant Transmitted Drug Resistance to First Line Antiretroviral Drugs and Implications for Recommendations

PubMed Central

Monge, Susana; Guillot, Vicente; Alvarez, Marta; Chueca, Natalia; Stella, Natalia; Peña, Alejandro; Delgado, Rafael; Córdoba, Juan; Aguilera, Antonio; Vidal, Carmen; García, Federico; CoRIS

2014-01-01

Background The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR) defined by the 2009 update of the WHO SDRM list. Methods We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain) between 2007–2011. Using the Stanford algorithm “Low-level resistance”, “Intermediate resistance” and “High-level resistance” categories were considered as “Resistant”. Results 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8–7.7)], and 221 harbored TDR using the WHO list [7.9% (6.9–9.0)]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8–2.9) vs. 3.6% (2.9–4.3) by the WHO list] and PIs [0.8% (0.4–1.1) vs. 1.7% (1.2–2.2)], while it was higher for NNRTIs [4.6% (3.8–5.3) vs. 3.7% (3.0–4.7)]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02). Conclusions Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations. PMID:24637804

Robert Mandell: a pioneer and giant in the art and science of contact lenses.

PubMed

Polse, Kenneth A

2008-10-01

Robert B. Mandell is the quintessential modern clinical scientist. Over his long academic career, he has pioneered many advances in contact lens practice, ranging from a more complete understanding of corneal shape to the effects of contact lenses on corneal health. His classic text, Contact Lens Practice, first published in 1965, was reprinted 14 times in four editions up to 1988. Mandell's contributions to the advancement of the profession of optometry have always been characterized by a genuine concern for the patient and a steadfast belief that his research must have relevance to the practice of optometry.

The discovery of tropane-derived CCR5 receptor antagonists.

PubMed

Armour, Duncan R; de Groot, Marcel J; Price, David A; Stammen, Blanda L C; Wood, Anthony; Perros, Manos; Burt, Catherine

2006-04-01

The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad-spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a-go-go-related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.

Inter-rater reliability of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in critically ill patients: a prospective observational study

PubMed Central

2010-01-01

Introduction The Glasgow Coma Scale (GCS) is the most widely used scoring system for comatose patients in intensive care. Limitations of the GCS include the impossibility to assess the verbal score in intubated or aphasic patients, and an inconsistent inter-rater reliability. The FOUR (Full Outline of UnResponsiveness) score, a new coma scale not reliant on verbal response, was recently proposed. The aim of the present study was to compare the inter-rater reliability of the GCS and the FOUR score among unselected patients in general critical care. A further aim was to compare the inter-rater reliability of neurologists with that of intensive care unit (ICU) staff. Methods In this prospective observational study, scoring of GCS and FOUR score was performed by neurologists and ICU staff on 267 consecutive patients admitted to intensive care. Results In a total of 437 pair wise ratings the exact inter-rater agreement for the GCS was 71%, and for the FOUR score 82% (P = 0.0016); the inter-rater agreement within a range of ± 1 score point for the GCS was 90%, and for the FOUR score 92% (P = ns.). The exact inter-rater agreement among neurologists was superior to that among ICU staff for the FOUR score (87% vs. 79%, P = 0.04) but not for the GCS (73% vs. 73%). Neurologists and ICU staff did not significantly differ in the inter-rater agreement within a range of ± 1 score point for both GCS (88% vs. 93%) and the FOUR score (91% vs. 88%). Conclusions The FOUR score performed better than the GCS for exact inter-rater agreement, but not for the clinically more relevant agreement within the range of ± 1 score point. Though neurologists outperformed ICU staff with regard to exact inter-rater agreement, the inter-rater agreement of ICU staff within the clinically more relevant range of ± 1 score point equalled that of the neurologists. The small advantage in inter-rater reliability of the FOUR score is most likely insufficient to replace the GCS, a score with a long tradition in intensive care. PMID:20398274

On the effectiveness of ion range determination from in-beam PET data

NASA Astrophysics Data System (ADS)

Fiedler, Fine; Shakirin, Georgy; Skowron, Judith; Braess, Henning; Crespo, Paulo; Kunath, Daniela; Pawelke, Jörg; Pönisch, Falk; Enghardt, Wolfgang

2010-04-01

At present, in-beam positron emission tomography (PET) is the only method for in vivo and in situ range verification in ion therapy. At the GSI Helmholtzzentrum für Schwerionenforschung GmbH (GSI) Darmstadt, Germany, a unique in-beam PET installation has been operated from 1997 until the shut down of the carbon ion therapy facility in 2008. Therapeutic irradiation by means of 12C ion beams of more than 400 patients have been monitored. In this paper a first quantitative study on the accuracy of the in-beam PET method to detect range deviations between planned and applied treatment in clinically relevant situations using simulations based on clinical data is presented. Patient treatment plans were used for performing simulations of positron emitter distributions. For each patient a range difference of ± 6 mm in water was applied and compared to simulations without any changes. The comparisons were performed manually by six experienced evaluators for data of 81 patients. The number of patients required for the study was calculated using the outcome of a pilot study. The results indicate a sensitivity of (91 ± 3)% and a specificity of (96 ± 2)% for detecting an overrange, a reduced range is recognized with a sensitivity of (92 ± 3)% and a specificity of (96 ± 2)%. The positive and the negative predictive value of this method are 94% and 87%, respectively. The interobserver coefficient of variation is between 3 and 8%. The in-beam PET method demonstrated a high sensitivity and specificity for the detection of range deviations. As the range is a most indicative factor of deviations in the dose delivery, the promising results shown in this paper confirm the in-beam PET method as an appropriate tool for monitoring ion therapy.

Clinically relevant pharmacokinetic herb-drug interactions in antiretroviral therapy

USDA-ARS?s Scientific Manuscript database

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

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

PubMed

Shneerson, Catherine L; Gale, Nicola K

2015-06-01

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

Borderline Changes on Dysfunctional Renal Allograft Biopsies: Clinical Relevance in a Living Related Renal Transplant Setting.

PubMed

Mubarak, Muhammed; Shakeel, Shaheera; Abbas, Khawar; Aziz, Tahir; Zafar, Mirza Naqi; Naqvi, Syed Anwer; Rizvi, Syed Adibul Hasan

2017-02-01

Our aim was to determine the clinical significance of borderline lymphocytic infiltrates on indicated renal allograft biopsies in a living related renal transplant setting. The study was conducted at the histopathology department of Sindh Institute of Urology and Transplantation. A retrospective review of 421 renal transplant patients was conducted from October 2007 to September 2008 to identify patients in whom a histologic diagnosis of borderline changes was made on dysfunctional renal allograft biopsies. Demographic, clinical, and laboratory data; biopsy findings; treatments given; and responses to treatment were collected and analyzed. Standard biopsy indications determined the need for graft biopsies. Biopsies were reported according to Banff criteria. Mean age was 26.92 ± 9.14 years (range, 10-45) for recipients and 38.46 ± 9.16 years (range, 19-50) for donors. Males were predominant among recipients (84.6% vs 15.4%), and females were predominant among donors (57.7% vs 42.3%). The best serum creatinine levels were 1.79 ± 1.15 mg/dL (range, 0.83-6.12). These were achieved after a median of 3 days (interquartile range, 2-7.25). Dysfunctional biopsies exhibiting borderline infiltrates were performed at a median duration of 5.5 days (interquartile range, 3-14.25). Mean serum creatinine at the time of biopsy was 2.34 ± 1.43 mg/dL (range, 1.25-8.25). The biopsies showed borderline cellular infiltrates (interstitial inflammation 1 [i1] and tubulitis 1 and [t1] lesions). All recipients except one received antirejection treatment (antithymocyte globulin, n = 5; escalation of mycophenolate mofetil dosage, n = 1; pulse steroids, n = 19); all recipients responded with a decline in serum creatinine toward baseline, with a mean serum creatinine of 1.31 ± 0.42 mg/dL (range, 0.40-2.71). This response was achieved at a median duration of 9.73 ± 5.32 days (range, 1-23) after starting treatment. The borderline cellular infiltrates on dysfunctional renal allograft biopsies signify evolving phases of acute cellular rejection. These infiltrates responded favorably to antirejection treatment in our setting.

Evidence-based selection of theories for designing behaviour change interventions: using methods based on theoretical construct domains to understand clinicians' blood transfusion behaviour.

PubMed

Francis, Jill J; Stockton, Charlotte; Eccles, Martin P; Johnston, Marie; Cuthbertson, Brian H; Grimshaw, Jeremy M; Hyde, Chris; Tinmouth, Alan; Stanworth, Simon J

2009-11-01

Many theories of behaviour are potentially relevant to predictive and intervention studies but most studies investigate a narrow range of theories. Michie et al. (2005) agreed 12 'theoretical domains' from 33 theories that explain behaviour change. They developed a 'Theoretical Domains Interview' (TDI) for identifying relevant domains for specific clinical behaviours, but the framework has not been used for selecting theories for predictive studies. It was used here to investigate clinicians' transfusion behaviour in intensive care units (ICU). Evidence suggests that red blood cells transfusion could be reduced for some patients without reducing quality of care. (1) To identify the domains relevant to transfusion practice in ICUs and neonatal intensive care units (NICUs), using the TDI. (2) To use the identified domains to select appropriate theories for a study predicting transfusion behaviour. An adapted TDI about managing a patient with borderline haemoglobin by watching and waiting instead of transfusing red blood cells was used to conduct semi-structured, one-to-one interviews with 18 intensive care consultants and neonatologists across the UK. Relevant theoretical domains were: knowledge, beliefs about capabilities, beliefs about consequences, social influences, behavioural regulation. Further analysis at the construct level resulted in selection of seven theoretical approaches relevant to this context: Knowledge-Attitude-Behaviour Model, Theory of Planned Behaviour, Social Cognitive Theory, Operant Learning Theory, Control Theory, Normative Model of Work Team Effectiveness and Action Planning Approaches. This study illustrated, the use of the TDI to identify relevant domains in a complex area of inpatient care. This approach is potentially valuable for selecting theories relevant to predictive studies and resulted in greater breadth of potential explanations than would be achieved if a single theoretical model had been adopted.

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

PubMed

Haahtela, T; Burbach, G J; Bachert, C; Bindslev-Jensen, C; Bonini, S; Bousquet, J; Bousquet-Rouanet, L; Bousquet, P J; Bresciani, M; Bruno, A; Canonica, G W; Darsow, U; Demoly, P; Durham, S R; Fokkens, W J; Giavi, S; Gjomarkaj, M; Gramiccioni, C; Kowalski, M L; Losonczy, G; Orosz, M; Papadopoulos, N G; Stingl, G; Todo-Bom, A; von Mutius, E; Köhli, A; Wöhrl, S; Järvenpää, S; Kautiainen, H; Petman, L; Selroos, O; Zuberbier, T; Heinzerling, L M

2014-03-01

Within a large prospective study, the Global Asthma and Allergy European Network (GA(2) LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. To improve clinical interpretation of SPT results for inhalant allergens by providing quantitative decision points. The GA(2) LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. Depending on the allergen, from 40% (blatella) to 87-89% (grass, mites) of the positive SPT reactions (wheal size ≥ 3 mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10 mm depending on the allergen. These 'reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form with the standard allergens including mm decision points for each allergen is offered for clinical use. © 2013 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

The future of monitoring in clinical research - a holistic approach: linking risk-based monitoring with quality management principles.

PubMed

Ansmann, Eva B; Hecht, Arthur; Henn, Doris K; Leptien, Sabine; Stelzer, Hans Günther

2013-01-01

Since several years risk-based monitoring is the new "magic bullet" for improvement in clinical research. Lots of authors in clinical research ranging from industry and academia to authorities are keen on demonstrating better monitoring-efficiency by reducing monitoring visits, monitoring time on site, monitoring costs and so on, always arguing with the use of risk-based monitoring principles. Mostly forgotten is the fact, that the use of risk-based monitoring is only adequate if all mandatory prerequisites at site and for the monitor and the sponsor are fulfilled.Based on the relevant chapter in ICH GCP (International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use - Good Clinical Practice) this publication takes a holistic approach by identifying and describing the requirements for future monitoring and the use of risk-based monitoring. As the authors are operational managers as well as QA (Quality Assurance) experts, both aspects are represented to come up with efficient and qualitative ways of future monitoring according to ICH GCP.

Identifying the effective evidence sources to use in developing Clinical Guidelines for Acute Stroke Management: lived experiences of the search specialist and project manager.

PubMed

Parkhill, Anne; Hill, Kelvin

2009-03-01

The Australian National Stroke Foundation appointed a search specialist to find the best available evidence for the second edition of its Clinical Guidelines for Acute Stroke Management. To identify the relative effectiveness of differing evidence sources for the guideline update. We searched and reviewed references from five valid evidence sources for clinical and economic questions: (i) electronic databases; (ii) reference lists of relevant systematic reviews, guidelines, and/or primary studies; (iii) table of contents of a number of key journals for the last 6 months; (iv) internet/grey literature; and (v) experts. Reference sources were recorded, quantified, and analysed. In the clinical portion of the guidelines document, there was a greater use of previous knowledge and sources other than electronic databases for evidence, while there was a greater use of electronic databases for the economic section. The results confirmed that searchers need to be aware of the context and range of sources for evidence searches. For best available evidence, searchers cannot rely solely on electronic databases and need to encompass many different media and sources.

Topical Vitamin C and the Skin: Mechanisms of Action and Clinical Applications.

PubMed

Al-Niaimi, Firas; Chiang, Nicole Yi Zhen

2017-07-01

OBJECTIVE: This review article details the main mechanisms of action and clinical applications of topical vitamin C on the skin, including its antioxidative, photoprotective, antiaging, and antipigmentary effects. DESIGN: A PubMed search for the relevant articles on vitamin C and the skin was conducted using the following key words: "vitamin C," "ascorbic acid," "ascorbyl-6-palmitate,"and "magnesium ascorbyl phosphate." RESULTS: As one of the most powerful antioxidants in the skin, vitamin C has been shown to protect against photoaging, ultraviolet-induced immunosuppression, and photocarcinogenesis. It also has an antiaging effect by increasing collagen synthesis, stabilizing collagen fibers, and decreasing collagen degradation. It decreases melanin formation, thereby reducing pigmentation. Vitamin C is the primary replenisher of vitamin E and works synergistically with vitamin E in the protection against oxidative damage. CONCLUSION: Topical vitamin C has a wide range of clinical applications, from antiaging and antipigmentary to photoprotective. Currently, clinical studies on the efficacy of topical formulations of vitamin C remain limited, and the challenge lies in finding the most stable and permeable formulation in achieving the optimal results.

Appropriate Use Criteria for Amyloid PET

PubMed Central

Johnson, Keith A.; Minoshima, Satoshi; Bohnen, Nicolaas I.; Donohoe, Kevin J.; Foster, Norman L.; Herscovitch, Peter; Karlawish, Jason H.; Rowe, Christopher C.; Carrillo, Maria C.; Hartley, Dean M.; Hedrick, Saima; Mitchell, Kristi; Pappas, Virginia; Thies, William H.

2013-01-01

Positron Emission Tomography (PET) of brain amyloid-beta is a technology that is becoming more available, but its clinical utility in medical practice requires careful definition. In order to provide guidance to dementia care practitioners, patients and caregivers, the Alzheimer Association and the Society of Nuclear Medicine and Molecular Imaging convened the Amyloid Imaging Taskforce (AIT). The AIT considered a broad range of specific clinical scenarios in which amyloid PET could potentially be appropriately used. Peer-reviewed, published literature was searched to ascertain available evidence relevant to these scenarios, and the AIT developed a consensus of expert opinion. While empirical evidence of impact on clinical outcomes is not yet available, a set of specific Appropriate Use Criteria (AUC) were agreed upon that define the types of patients and clinical circumstances in which amyloid PET could be used. Both appropriate and inappropriate uses were considered and formulated, and are reported and discussed here. Because both dementia care and amyloid PET technology are in active development, these AUC will require periodic reassessment. Future research directions are also outlined, including diagnostic utility and patient-centered outcomes. PMID:23360977

Preterm piglets are a clinically relevant model of pediatric GI disease

USDA-ARS?s Scientific Manuscript database

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

77 FR 40620 - AHRQ Workgroups on ICD-10-CM/PCS Conversion of Quality Indicators (QIs) - Extension Date for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

... with relevant clinical expertise (e.g., cardiovascular disease, neurologic disease, orthopedic and... measurement using administrative data in specific, relevant clinical domains (e.g., cardiovascular disease... (e.g., cardiovascular disease, neurologic disease, orthopedic and musculoskeletal disease, obstetrics...

Cognitive and emotional behavioural changes associated with methylphenidate treatment: a review of preclinical studies.

PubMed

Britton, Gabrielle B

2012-02-01

There is evidence from animal studies that repeated exposure to methylphenidate (MPH), a widely used psychostimulant for the treatment of attention deficit hyperactivity disorder (ADHD), produces behavioural, structural and neurochemical changes that persist long after drug administration has ended. However, the translational utility of much of this work is compromised by the use of drug doses and routes of administration that produce plasma and brain MPH levels that fall outside the clinical range, i.e. experimental parameters more relevant to drug abuse than ADHD. We used PubMed to identify pre-clinical studies that employed repeated MPH administration at low doses in young rodents and examined long-term effects on cognition, emotion, and brain structure and function. A review of this work suggests that repeated MPH treatment during early development can modify a number of cognitive, behavioural and brain processes, but these are reduced when low therapeutic doses are employed. Moreover, MPH sites of action extend beyond those implicated in ADHD. Studies that combined neurobiological and behavioural approaches provide important insights into the mechanisms underlying MPH-produced effects on cognitive and behavioural processes, which may be relevant to MPH therapeutic efficacy. There is an emerging consensus that pharmacological treatment of childhood psychiatric disorders produces persistent neuroadaptations, highlighting the need for studies that assess long-term effects of early developmental pharmacotherapy. In this regard, studies that mimic clinical therapy with rodents are useful experimental approaches for defining the behavioural and neural plasticity associated with stimulant therapy in paediatric populations.

Anticoagulation by factor Xa inhibitors.

PubMed

Orfeo, T; Butenas, S; Brummel-Ziedins, K E; Gissel, M; Mann, K G

2010-08-01

Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (F) Xa emerging as a promising approach. To assess anticoagulant strategies targeting FXa. A deterministic computational model of tissue factor (Tf)-initiated thrombin generation and two empirical experimental systems (a synthetic coagulation proteome reconstruction using purified proteins and a whole blood model) were used to evaluate clinically relevant examples of the two available types of FXa-directed anticoagulants [an antithrombin (AT)-dependent agent, fondaparinux, and an AT-independent inhibitor, Rivaroxaban] in experimental regimens relevant to long-term (suppression of new Tf-initiated events) and acute (suppression of ongoing coagulation processes) clinical applications. Computational representations of each anticoagulant's efficacy in suppressing thrombin generation over a range of anticoagulant concentrations in both anticoagulation regimens were validated by results from corresponding empirical reconstructions and were consistent with those recommended for long-term and acute clinical applications, respectively. All three model systems suggested that Rivaroxaban would prove more effective in the suppression of an ongoing coagulation process than fondaparinux, reflecting its much higher reactivity toward the prothrombinase complex. The success of fondaparinux in acute settings in vivo is not explained solely by its properties as an FXa inhibitor. We have reported that FIXa contributes to the long-term capacity of clot-associated catalysts to restart a coagulation process, suggesting that the enhanced anti-FIXa activity of fondaparinux-AT may be critical to its success in acute settings in vivo. © 2010 International Society on Thrombosis and Haemostasis.

Chest physiotherapy can affect the lung clearance index in cystic fibrosis patients.

PubMed

Grosse-Onnebrink, Joerg; Mellies, Uwe; Olivier, Margarete; Werner, Claudius; Stehling, Florian

2017-05-01

The lung clearance index (LCI) is determined by multiple-breath washout lung function (MBW). It is increasingly used as an endpoint in clinical trials. Chest physiotherapy (CP) is part of routine cystic fibrosis (CF) care. Whether the LCI is useful in detecting short-term treatment effects of CP has not been sufficiently investigated. We assessed the short-term influence of CP with highly standardized high-frequency chest wall oscillation (HFCWO) on the LCI in CF patients. In this randomized controlled study, the LCI was obtained in 20 CF patients (7-34 years) hospitalized for infective pulmonary exacerbation prior to and immediately after a single treatment of HFCWO. Twenty-one control group CF patients (7-51 years) received no treatment. We calculated the coefficient of repeatability (CR) to estimate the clinical relevance of possible treatment effects. HFCWO improved (ie, decreased) the LCI by a median of 0.9 (range -0.45; 3.47; P = 0.002); the LCI decreased in 15 of 20 intervention group patients. In five patients the decrease in LCI exceeded the CR (2.15), indicating a clinically relevant treatment effect; in five patients the LCI increased but did not exceed the CR. The LCI did not change significantly in the control group patients. HFCWO can have a short-term decreasing effect on the LCI, but the treatment response is heterogeneous. In future trials using LCI as an endpoint, the timing of CP in relation to MBW should be considered a possible bias. © 2017 Wiley Periodicals, Inc.

Team clinician variability in return-to-play decisions.

PubMed

Shultz, Rebecca; Bido, Jennifer; Shrier, Ian; Meeuwisse, Willem H; Garza, Daniel; Matheson, Gordon O

2013-11-01

To describe the variability in the return-to-play (RTP) decisions of experienced team clinicians and to assess their clinical opinion as to the relevance of 19 factors described in a RTP decision-making model. Survey questionnaire. Advanced Team Physician Course. Sixty-seven of 101 sports medicine clinicians completed the questionnaire. Results were analyzed using descriptive statistics. For categorical variables, we report percentage and frequency. For continuous variables, we report mean (SD) if data were approximately normally distributed and frequencies for clinically relevant categories for skewed data. The average number of years of clinical sports medicine experience was 13.6 (9.8). Of the 62 clinicians who responded fully, 35% (n = 22) would "clear" (vs "not clear") an athlete to participate in sport even if the risk of an acute reinjury or long-term sequelae is increased. When respondents were given 6 different RTP options rather than binary choices, there were increased discrepancies across some injury risk scenarios. For example, 8.1% to 16.1% of respondents who chose to clear an athlete when presented with binary choices, later chose to "not clear" an athlete when given 6 graded RTP options. The respondents often considered factors of potential importance to athletes as nonimportant to the RTP decision process if risk of reinjury was unaffected (range, n = 4 [10%] to n = 19 [45%]). There is a high degree of variability in how different clinicians weight the different factors related to RTP decision making. More precise definitions decrease but do not eliminate this variability.

Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics

PubMed Central

Hanemaaijer, Nicolien M; Sikkema-Raddatz, Birgit; van der Vries, Gerben; Dijkhuizen, Trijnie; Hordijk, Roel; van Essen, Anthonie J; Veenstra-Knol, Hermine E; Kerstjens-Frederikse, Wilhelmina S; Herkert, Johanna C; Gerkes, Erica H; Leegte, Lamberta K; Kok, Klaas; Sinke, Richard J; van Ravenswaaij-Arts, Conny M A

2012-01-01

The correct interpretation of copy number gains in patients with developmental delay and multiple congenital anomalies is hampered by the large number of copy number variations (CNVs) encountered in healthy individuals. The variable phenotype associated with copy number gains makes interpretation even more difficult. Literature shows that inheritence, size and presence in healthy individuals are commonly used to decide whether a certain copy number gain is pathogenic, but no general consensus has been established. We aimed to develop guidelines for interpreting gains detected by array analysis using array CGH data of 300 patients analysed with the 105K Agilent oligo array in a diagnostic setting. We evaluated the guidelines in a second, independent, cohort of 300 patients. In the first 300 patients 797 gains of four or more adjacent oligonucleotides were observed. Of these, 45.4% were de novo and 54.6% were familial. In total, 94.8% of all de novo gains and 87.1% of all familial gains were concluded to be benign CNVs. Clinically relevant gains ranged from 288 to 7912 kb in size, and were significantly larger than benign gains and gains of unknown clinical relevance (P<0.001). Our study showed that a threshold of 200 kb is acceptable in a clinical setting, whereas heritability does not exclude a pathogenic nature of a gain. Evaluation of the guidelines in the second cohort of 300 patients revealed that the interpretation guidelines were clear, easy to follow and efficient. PMID:21934709

Multiparametric MRI of Prostate Cancer: An Update on State-of-the-Art Techniques and Their Performance in Detecting and Localizing Prostate Cancer

PubMed Central

Hegde, John V.; Mulkern, Robert V.; Panych, Lawrence P.; Fennessy, Fiona M.; Fedorov, Andriy; Maier, Stephan E.; Tempany, Clare M.C.

2013-01-01

Magnetic resonance (MR) examinations of men with prostate cancer are most commonly performed for detecting, characterizing, and staging the extent of disease to best determine diagnostic or treatment strategies, which range from biopsy guidance to active surveillance to radical prostatectomy. Given both the exam's importance to individual treatment plans and the time constraints present for its operation at most institutions, it is essential to perform the study effectively and efficiently. This article reviews the most commonly employed modern techniques for prostate cancer MR examinations, exploring the relevant signal characteristics from the different methods discussed and relating them to intrinsic prostate tissue properties. Also, a review of recent articles using these methods to enhance clinical interpretation and assess clinical performance is provided. PMID:23606141

[Pathophysiology and Prognostic Factors of Autoimmune Encephalitis].

PubMed

Prüß, H

2016-05-01

More and more forms of autoimmune encephalitis are being identified with the clinical spectrum ranging from epilepsy over movement disorders to psychosis. The increasing appreciation of clinical symptoms raises questions about the underlying pathophysiological mechanisms and prognostic factors. Numerous novel findings on the aetiology demonstrate that diverse tumours, but also infections of the central nervous system such as Herpes encephalitis can trigger autoimmune encephalitis. Antibodies against neuronal surface epitopes are directly pathogenic in the majority of cases. They act via binding and internalization of target proteins, receptor blockage, or activation of complement. Most relevant for the patients' prognosis are the type and titer of antibodies (e. g. against NMDA, GABA, AMPA receptors or voltage-gated potassium channel complexes), associated tumours, sufficiently aggressive immunotherapies, and imaging as well as cerebrospinal fluid biomarkers. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical skills education for graduate-entry nursing students: enhancing learning using a multimodal approach.

PubMed

Bloomfield, Jacqueline G; Cornish, Jocelyn C; Parry, Angela M; Pegram, Anne; Moore, Jaqualyn S

2013-03-01

This paper discusses the development of a new clinical skills course at a school of nursing and midwifery in London. The course, part of a two year pre-registration programme for graduates in other disciplines, adopted an innovative multimodal approach. This comprised a range of teaching, learning and assessment strategies designed to maximise comprehensiveness, complementarity and flexibility. The background to the development is discussed and each component is described in detail. A brief summary of relevant feedback generated from anonymous student evaluations is included. This provides important insights into the perceived strengths and weakness of the module from a learner perspective. The paper concludes by identifying proposed future developments and recommending wider applications of the multimodal approach within nursing and healthcare education on an international level. Copyright © 2011 Elsevier Ltd. All rights reserved.

Exploration of the Medicinal Peptide Space.

PubMed

Gevaert, Bert; Stalmans, Sofie; Wynendaele, Evelien; Taevernier, Lien; Bracke, Nathalie; D'Hondt, Matthias; De Spiegeleer, Bart

2016-01-01

The chemical properties of peptide medicines, known as the 'medicinal peptide space' is considered a multi-dimensional subset of the global peptide space, where each dimension represents a chemical descriptor. These descriptors can be linked to biofunctional, medicinal properties to varying degrees. Knowledge of this space can increase the efficiency of the peptide-drug discovery and development process, as well as advance our understanding and classification of peptide medicines. For 245 peptide drugs, already available on the market or in clinical development, multivariate dataexploration was performed using peptide relevant physicochemical descriptors, their specific peptidedrug target and their clinical use. Our retrospective analysis indicates that clusters in the medicinal peptide space are located in a relatively narrow range of the physicochemical space: dense and empty regions were found, which can be explored for the discovery of novel peptide drugs.

Developmental procedures for the clinical practice guidelines for conscious sedation in dentistry for the Korean Academy of Dental Sciences.

PubMed

An, So-Youn; Seo, Kwang-Suk; Kim, Seungoh; Kim, Jongbin; Lee, Deok-Won; Hwang, Kyung-Gyun; Kim, Hyun Jeong

2016-12-01

Evidence-based clinical practice guidelines (CPGs) are defined as "statements that are scientifically reviewed about evidence and systematically developed to assist in the doctors' and patients' decision making in certain clinical situations." This recommendation aims to promote good clinical practice for the provision of safe and effective practices of conscious sedation in dentistry. The development of this clinical practice guideline was conducted by performing a systematic search of the literature for evidence-based CPGs. Existing guidelines, relevant systematic reviews, policy documents, legislation, or other recommendations were reviewed and appraised. To supplement this information, key questions were formulated by the Guideline Development Group and used as the basis for designing systematic literature search strategies to identify literature that may address these questions. Guideline documents were evaluated through a review of domestic and international databases for the development of a renewing of existing conscious sedation guidelines for dentistry. Clinical practice guidelines were critically appraised for their methodologies using Appraisal of guidelines for research and evaluation (AGREE) II. A total of 12 existing CPGs were included and 13 recommendations were made in a range of general, adult, and pediatric areas. The clinical practice guidelines for conscious sedation will be reviewed in 5 years' time for further updates to reflect significant changes in the field.

Frequency of Toxocariasis among Patients Clinically Suspected to Have Visceral Toxocariasis: A Retrospective Descriptive Study in Sri Lanka

PubMed Central

Iddawela, Devika; Ehambaram, Kiruthiha; Pethiyagoda, Kalyani; Bandara, Lakmalee

2017-01-01

Introduction Human toxocariasis is caused by several species of the nematode Toxocara. Two common clinical syndromes are ocular and visceral larva migrans. Objectives To determine the Toxocara antibody positivity in clinically suspected VLM patients and to describe demographic factors and clinical manifestations of seropositive patients. Methods 522 clinically suspected patients were studied between 1993 and 2014. Relevant data was gathered from referral letters. Serum samples were subjected to Toxocara antigen ELISA. Results Overall, seropositivity was 50.2% (262), of which 109 (40.8%) were positive at high level of Toxocara antibody carriage and 153 (58.4%) were positive at low levels. The seropositives ranged from 3 months to 70 years (mean = 7.8). Younger age group had higher levels of seropositivity and it was statistically significant. Majority of children under 5 years were seropositive (47.7%, n = 125). Seropositivity was common in males (55.3%, n = 145). Clinical manifestations of seropositives include lymphadenopathy (24.1%) skin rash (22.5%), dyspnoea (21.7%), fever (21%), hepatosplenomegaly (9.2%), and abdominal pain (3.8%). 197 (75.2%) seropositive cases had eosinophilia. These symptoms were not statistically significant. Conclusions This study confirms toxocariasis as an important cause of childhood ill health identifying common clinical symptoms recommending preventive measures to limit transmission. PMID:29362672

Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

PubMed

Healy, D A; Khan, W A; Wong, C S; Moloney, M Clarke; Grace, P A; Coffey, J C; Dunne, C; Walsh, S R; Sadat, U; Gaunt, M E; Chen, S; Tehrani, S; Hausenloy, D J; Yellon, D M; Kramer, R S; Zimmerman, R F; Lomivorotov, V V; Shmyrev, V A; Ponomarev, D N; Rahman, I A; Mascaro, J G; Bonser, R S; Jeon, Y; Hong, D M; Wagner, R; Thielmann, M; Heusch, G; Zacharowski, K; Meybohm, P; Bein, B; Tang, T Y

2014-09-01

A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Financial conflict-of-interest policies in clinical research: issues for clinical investigators.

PubMed

Boyd, Elizabeth A; Cho, Mildred K; Bero, Lisa A

2003-08-01

As industry sponsorship of clinical research grows, investigators' personal financial relationships with those sponsors are under increasing scrutiny. The federal government, some states, and many universities have enacted conflict-of-interest policies to monitor and regulate investigators' financial relationships. Little is known, however, about investigators' awareness of or support for these policies or their attitudes toward regulatory efforts. To explore the possible implications of conflict-of-interest policies for clinical researchers, the authors interviewed active clinical investigators at two institutions where the conflict-of-interest policies differ. The most striking feature of the interviews was the range of perceptions and attitudes expressed by clinical investigators and their implications for administrators, professional societies, and policymakers concerned with conflicts of interest. Fewer than half of the interviewed investigators could accurately describe their campus' conflict-of-interest policy. Many investigators felt that professional societies, the public, and individual investigators were appropriate monitors of conflicts of interest. Many investigators recognized the general risks associated with conflicts of interest, but felt that they personally were not at risk. A fundamental challenge facing administrators and policymakers is to demonstrate to all investigators, both clinical and nonclinical, that the potential for bias, pressure and conflict is relevant to all investigators with industry relationships.

Prevalence and psychosocial correlates of depressive symptoms in urban Chinese women during midlife.

PubMed

Wong, Carmen K M; Liang, Jun; Chan, Man L; Chan, Yin H; Chan, Laam; Wan, Kwong Y; Ng, Ming S; Chan, Dicken C C; Wong, Samuel Y S; Wong, Martin C S

2014-01-01

Depression is common in women with much research focusing on hormonal changes and menopausal symptoms but with little exploration of psychosocial problems in midlife. This study investigates the prevalence of clinically relevant depressive symptoms in midlife Chinese women and its association with psychosocial factors. A cross-sectional, community-based household survey of women aged 45 to 64 years of age was conducted in Hong Kong from September 2010 to March 2011. The structured questionnaire included demographic data, educational status, marital status and household income, as well as perceived current stressful events and significant life events in the past 12 months. Information on clinically relevant depressive symptoms was measured by the validated chinese Patient Health Questionnaire (PHQ-9). A total of 402 participants were recruited in the study period. Of the 393 women who completed the questionnaire, the prevalence of clinically relevant depressive symptoms (PHQ-9 score≧10) was 11.0%. In multiple regression analysis, being single/divorced/separated/widowed, having an educational level of primary school level or below, having multiple chronic diseases, loss of hobby or loss of close social support in the past 12 months in midlife were associated with clinically relevant depressive symptoms. Correlates of clinically relevant depressive symptoms in midlife Chinese women can be used to identify those at increased risk and potentiate further studies to explore early psychosocial and community interventions.

Augmentation in the treatment of restless legs syndrome with transdermal rotigotine.

PubMed

Beneš, Heike; García-Borreguero, Diego; Ferini-Strambi, Luigi; Schollmayer, Erwin; Fichtner, Andreas; Kohnen, Ralf

2012-06-01

To assess the risk of augmentation under treatment with the transdermally delivered dopamine agonist rotigotine for restless legs syndrome (RLS). Experts in RLS augmentation retrospectively reviewed data from two double-blind, placebo-controlled 6-month trials (745 rotigotine and 214 placebo subjects, NCT00136045 and NCT00135993) and from two open-label 1-year trials (620 rotigotine subjects, NCT00498108 and NCT00263068). All study visits were systematically evaluated applying the Max Planck Institute (MPI) criteria for the diagnosis of both augmentation and clinically relevant augmentation. MPI criteria for augmentation were met on at least one visit by 8.2% of all subjects in the double-blind trials with 12 subjects meeting the criteria for clinically relevant augmentation: 11 under rotigotine (1.5%) and one under placebo treatment. In the open-label trials, 9.7% of all subjects met the MPI criteria for augmentation and 2.9% met the criteria for clinically relevant augmentation. None of the patients treated with rotigotine for up to 1.5 years (double-blind plus open-label trial) discontinued prematurely owing to augmentation. Neither could dose-dependency or a time pattern for clinically relevant augmentation episodes be detected. Our analyses suggest that the risk for clinically relevant augmentation for the duration of up to 18 months of rotigotine treatment is low. Copyright © 2012 Elsevier B.V. All rights reserved.

Retrieving Clinical Evidence: A Comparison of PubMed and Google Scholar for Quick Clinical Searches

PubMed Central

Bejaimal, Shayna AD; Sontrop, Jessica M; Iansavichus, Arthur V; Haynes, R Brian; Weir, Matthew A; Garg, Amit X

2013-01-01

Background Physicians frequently search PubMed for information to guide patient care. More recently, Google Scholar has gained popularity as another freely accessible bibliographic database. Objective To compare the performance of searches in PubMed and Google Scholar. Methods We surveyed nephrologists (kidney specialists) and provided each with a unique clinical question derived from 100 renal therapy systematic reviews. Each physician provided the search terms they would type into a bibliographic database to locate evidence to answer the clinical question. We executed each of these searches in PubMed and Google Scholar and compared results for the first 40 records retrieved (equivalent to 2 default search pages in PubMed). We evaluated the recall (proportion of relevant articles found) and precision (ratio of relevant to nonrelevant articles) of the searches performed in PubMed and Google Scholar. Primary studies included in the systematic reviews served as the reference standard for relevant articles. We further documented whether relevant articles were available as free full-texts. Results Compared with PubMed, the average search in Google Scholar retrieved twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001). Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07). Google Scholar provided significantly greater access to free full-text publications (PubMed: 5%; Google Scholar: 14%; P<.001). Conclusions For quick clinical searches, Google Scholar returns twice as many relevant articles as PubMed and provides greater access to free full-text articles. PMID:23948488

Abutment misfit in implant-supported prostheses manufactured by casting technique: An integrative review

PubMed Central

Pereira, Lorena M. S.; Sordi, Mariane B.; Magini, Ricardo S.; Calazans Duarte, Antônio R.; M. Souza, Júlio C.

2017-01-01

The aim of this study was to perform an integrative review of the literature on the clinically usual prosthesis-abutment misfit over implant-supported structures manufactured by conventional casting technique. The present integrative review used the PRISMA methodology. A bibliographical search was conducted on the following electronic databases: MEDLINE/PubMed (National Library of Medicine), Scopus (Elsevier), ScienceDirect (Elsevier), Web of Science (Thomson Reuters Scientific), Latin American and Caribbean Center on Health Sciences Information (BIREME), and Virtual Health Library (BVS). A total of 11 relevant studies were selected for qualitative analysis. The prosthetic-abutment vertical misfit considered clinically usual ranged from 50 to 160 μm. The vertical misfit depends on several steps during technical manufacturing techniques, which includes the materials and technical procedures. Lower values in misfit are recorded when precious metal or titanium alloys are utilized. Although a vertical misfit mean value of 100 μm has been considered clinically usual, most of the previous studies included in this revision showed lower mean values. PMID:29279686

The impact of structural biology in medicine illustrated with four case studies.

PubMed

Hu, Tiancen; Sprague, Elizabeth R; Fodor, Michelle; Stams, Travis; Clark, Kirk L; Cowan-Jacob, Sandra W

2018-01-01

The contributions of structural biology to drug discovery have expanded over the last 20 years from structure-based ligand optimization to a broad range of clinically relevant topics including the understanding of disease, target discovery, screening for new types of ligands, discovery of new modes of action, addressing clinical challenges such as side effects or resistance, and providing data to support drug registration. This expansion of scope is due to breakthroughs in the technology, which allow structural information to be obtained rapidly and for more complex molecular systems, but also due to the combination of different technologies such as X-ray, NMR, and other biophysical methods, which allows one to get a more complete molecular understanding of disease and ways to treat it. In this review, we provide examples of the types of impact molecular structure information can have in the clinic for both low molecular weight and biologic drug discovery and describe several case studies from our own work to illustrate some of these contributions.

From clinical uncertainties to precision medicine: the emerging role of the gut barrier and microbiome in small bowel functional diseases.

PubMed

Marlicz, Wojciech; Yung, Diana E; Skonieczna-Żydecka, Karolina; Loniewski, Igor; van Hemert, Saskia; Loniewska, Beata; Koulaouzidis, Anastasios

2017-10-01

Over the last decade, remarkable progress has been made in the understanding of disease pathophysiology. Many new theories expound on the importance of emerging factors such as microbiome influences, genomics/omics, stem cells, innate intestinal immunity or mucosal barrier complexities. This has introduced a further dimension of uncertainty into clinical decision-making, but equally, may shed some light on less well-understood and difficult to manage conditions. Areas covered: Comprehensive review of the literature on gut barrier and microbiome relevant to small bowel pathology. A PubMed/Medline search from 1990 to April 2017 was undertaken and papers from this range were included. Expert commentary: The scenario of clinical uncertainty is well-illustrated by functional gastrointestinal disorders (FGIDs). The movement towards achieving a better understanding of FGIDs is expressed in the Rome IV guidelines. Novel diagnostic and therapeutic protocols focused on the GB and SB microbiome can facilitate diagnosis, management and improve our understanding of the underlying pathological mechanisms in FGIDs.

Computer-Aided Nodule Assessment and Risk Yield Risk Management of Adenocarcinoma: The Future of Imaging?

PubMed

Foley, Finbar; Rajagopalan, Srinivasan; Raghunath, Sushravya M; Boland, Jennifer M; Karwoski, Ronald A; Maldonado, Fabien; Bartholmai, Brian J; Peikert, Tobias

2016-01-01

Increased clinical use of chest high-resolution computed tomography results in increased identification of lung adenocarcinomas and persistent subsolid opacities. However, these lesions range from very indolent to extremely aggressive tumors. Clinically relevant diagnostic tools to noninvasively risk stratify and guide individualized management of these lesions are lacking. Research efforts investigating semiquantitative measures to decrease interrater and intrarater variability are emerging, and in some cases steps have been taken to automate this process. However, many such methods currently are still suboptimal, require validation and are not yet clinically applicable. The computer-aided nodule assessment and risk yield software application represents a validated tool for the automated, quantitative, and noninvasive tool for risk stratification of adenocarcinoma lung nodules. Computer-aided nodule assessment and risk yield correlates well with consensus histology and postsurgical patient outcomes, and therefore may help to guide individualized patient management, for example, in identification of nodules amenable to radiological surveillance, or in need of adjunctive therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

CANARY Risk Management of Adenocarcinoma: The Future of Imaging?

PubMed Central

Foley, Finbar; Rajagopalan, Srinivasan; Raghunath, Sushravya M; Boland, Jennifer M; Karwoski, Ronald A.; Maldonado, Fabien; Bartholmai, Brian J; Peikert, Tobias

2016-01-01

Increased clinical utilization of chest high resolution computed tomography results in increased identification of lung adenocarcinomas and persistent sub-solid opacities. However, these lesions range from very indolent to extremely aggressive tumors. Clinically relevant diagnostic tools to non-invasively risk stratify and guide individualized management of these lesions are lacking. Research efforts investigating semi-quantitative measures to decrease inter- and intra-rater variability are emerging, and in some cases steps have been taken to automate this process. However, many such methods currently are still sub-optimal, require validation and are not yet clinically applicable. The Computer-Aided Nodule Assessment and Risk Yield (CANARY) software application represents a validated tool for the automated, quantitative, non-invasive tool for risk stratification of adenocarcinoma lung nodules. CANARY correlates well with consensus histology and post-surgical patient outcomes and therefore may help to guide individualized patient management e.g. in identification of nodules amenable to radiological surveillance, or in need of adjunctive therapy. PMID:27568149

Practice innovation: the need for nimble data platforms to implement precision oncology care.

PubMed

Elfiky, Aymen; Zhang, Dongyang; Krishnan Nair, Hari K

2015-01-01

Given the drive toward personalized, value-based, and coordinated cancer care delivery, modern knowledge-based practice is being shaped within the context of an increasingly technology-driven healthcare landscape. The ultimate promise of 'precision medicine' is predicated on taking advantage of the range of new capabilities for integrating disease- and individual-specific data to define new taxonomies as part of a systems-based knowledge network. Specifically, with cancer being a constantly evolving complex disease process, proper care of an individual will require the ability to seamlessly integrate multi-dimensional 'omic' and clinical data. Importantly, however, the challenges of curating knowledge from multiple dynamic data sources and translating to practice at the point-of-care highlight parallel needs. As patients, caregivers, and their environments become more proactive in clinical care and management, practical success of precision medicine is equally dependent on the development of proper infrastructures for evolving data integration, platforms for knowledge representation in a clinically-relevant context, and implementation within a provider's work-life and workflow.

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

PubMed

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

2014-06-01

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

Appraising the methodological quality of the clinical practice guideline for diabetes mellitus using the AGREE II instrument: a methodological evaluation.

PubMed

Radwan, Mahmoud; Akbari Sari, Ali; Rashidian, Arash; Takian, Amirhossein; Abou-Dagga, Sanaa; Elsous, Aymen

2017-02-01

To evaluate the methodological quality of the Palestinian Clinical Practice Guideline for Diabetes Mellitus using the Translated Arabic Version of the AGREE II. Methodological evaluation. A cross-cultural adaptation framework was followed to translate and develop a standardised Translated Arabic Version of the AGREE II. Palestinian Primary Healthcare Centres. Sixteen appraisers independently evaluated the Clinical Practice Guideline for Diabetes Mellitus using the Translated Arabic Version of the AGREE II. Methodological quality of diabetic guideline. The Translated Arabic Version of the AGREE II showed an acceptable reliability and validity. Internal consistency ranged between 0.67 and 0.88 (Cronbach's α). Intra-class coefficient among appraisers ranged between 0.56 and 0.88. The quality of this guideline is low. Both domains 'Scope and Purpose' and 'Clarity of Presentation' had the highest quality scores (66.7% and 61.5%, respectively), whereas the scores for 'Applicability', 'Stakeholder Involvement', 'Rigour of Development' and 'Editorial Independence' were the lowest (27%, 35%, 36.5%, and 40%, respectively). The findings suggest that the quality of this Clinical Practice Guideline is disappointingly low. To improve the quality of current and future guidelines, the AGREE II instrument is extremely recommended to be incorporated as a gold standard for developing, evaluating or updating the Palestinian Clinical Practice Guidelines. Future guidelines can be improved by setting specific strategies to overcome implementation barriers with respect to economic considerations, engaging of all relevant end-users and patients, ensuring a rigorous methodology for searching, selecting and synthesising the evidences and recommendations, and addressing potential conflict of interests within the development group.

Effective implementation of research into practice: an overview of systematic reviews of the health literature.

PubMed

Boaz, Annette; Baeza, Juan; Fraser, Alec

2011-06-22

The gap between research findings and clinical practice is well documented and a range of interventions has been developed to increase the implementation of research into clinical practice. A review of systematic reviews of the effectiveness of interventions designed to increase the use of research in clinical practice. A search for relevant systematic reviews was conducted of Medline and the Cochrane Database of Reviews 1998-2009. 13 systematic reviews containing 313 primary studies were included. Four strategy types are identified: audit and feedback; computerised decision support; opinion leaders; and multifaceted interventions. Nine of the reviews reported on multifaceted interventions. This review highlights the small effects of single interventions such as audit and feedback, computerised decision support and opinion leaders. Systematic reviews of multifaceted interventions claim an improvement in effectiveness over single interventions, with effect sizes ranging from small to moderate. This review found that a number of published systematic reviews fail to state whether the recommended practice change is based on the best available research evidence. This overview of systematic reviews updates the body of knowledge relating to the effectiveness of key mechanisms for improving clinical practice and service development. Multifaceted interventions are more likely to improve practice than single interventions such as audit and feedback. This review identified a small literature focusing explicitly on getting research evidence into clinical practice. It emphasizes the importance of ensuring that primary studies and systematic reviews are precise about the extent to which the reported interventions focus on changing practice based on research evidence (as opposed to other information codified in guidelines and education materials).

Development of a clinical spasticity scale for evaluation of dogs with chronic thoracolumbar spinal cord injury.

PubMed

Lewis, Melissa J; Olby, Natasha J

2017-07-01

OBJECTIVE To develop a spasticity scale for dogs with chronic deficits following severe spinal cord injury (SCI) for use in clinical assessment and outcome measurement in clinical trials. ANIMALS 20 chronically paralyzed dogs with a persistent lack of hind limb pain perception caused by an acute SCI at least 3 months previously. PROCEDURES Spasticity was assessed in both hind limbs via tests of muscle tone, clonus, and flexor and extensor spasms adapted from human scales. Measurement of patellar clonus duration and flexor spasm duration and degree was feasible. These components were used to create a canine spasticity scale (CSS; overall score range, 0 to 18). Temporal variation for individual dogs and interrater reliability were evaluated. Gait was quantified with published gait scales, and CSS scores were compared with gait scores and clinical variables. Owners were questioned regarding spasticity observed at home. RESULTS 20 dogs were enrolled: 18 with no apparent hind limb pain perception and 2 with blunted responses; 5 were ambulatory. Testing was well tolerated, and scores were repeatable between raters. Median overall CSS score was 7 (range, 3 to 11), and flexor spasms were the most prominent finding. Overall CSS score was not associated with age, SCI duration, lesion location, or owner-reported spasticity. Overall CSS score and flexor spasm duration were associated with gait scores. CONCLUSIONS AND CLINICAL RELEVANCE The CSS could be used to quantify hind limb spasticity in dogs with chronic thoracolumbar SCI and might be a useful outcome measure. Flexor spasms may represent an integral part of stepping in dogs with severe SCI.

Antibacterial activity of exogenous glutathione and its synergism on antibiotics sensitize carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

PubMed

Alharbe, Roaa; Almansour, Ayidh; Kwon, Dong H

2017-10-01

A major clinical impact of A. baumannii is hospital-acquired infections including ventilator-associated pneumonia. The treatment of this pathogen is often difficult due to its innate and acquired resistance to almost all commercially available antibiotics. Infections with carbapenem-associated multidrug resistant A. baumannii is the most problematic. Glutathione is a tripeptide thiol-antioxidant and antibacterial activity of exogenous glutathione was reported in some bacteria. However, clinical relevance and molecular details of the antibacterial activity of glutathione are currently unclear. Seventy clinical isolates of A. baumannii including 63 carbapenem-associated multidrug resistant isolates and a type strain A. baumannii ATCC 19606 were used to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Fractional inhibitory concentration (FIC) and time-killing activity with meropenem and/or glutathione were also determined in the carbapenem-associated multidrug resistant isolates. In addition, the roles of exogenous glutathione in multidrug efflux pumps and β-lactamase production were examined. Levels of MIC and MBC were ranged from 10 to 15mM of exogenous glutathione. All tested carbapenem-associated multidrug resistant isolates were sensitized by all tested antibiotics in combination with subinhibitory concentrations of glutathione. FIC levels of glutathione with carbapenem (meropenem) were all<0.5 and the carbapenem-associated multidrug resistant isolates were killed by subinhibitory concentrations of both glutathione and meropenem at>2log10 within 12h, suggesting glutathione synergistically interacts with meropenem. The roles of multidrug efflux pumps and β-lactamase production were excluded for the glutathione-mediated antibiotic susceptibility. Overall results demonstrate that the antibacterial activity of glutathione is clinically relevant and its synergism on antibiotics sensitizes clinical isolates of A. baumannii regardless of their resistance or susceptibility to antibiotics. This finding suggests that exogenous glutathione alone and/or in combination with existing antibiotics may be applicable to treat infections with carbapenem-associated multidrug resistant A. baumannii. Copyright © 2017 Elsevier GmbH. All rights reserved.

[Clinical score to rule out pneumonia due to Mycoplasma pneumoniae].

PubMed

Rodríguez de Ita, J; Torres-Quintanilla, A; Paláu-Dávila, L; Silva-Gburek, J C; Ortiz de Elguea-Lizarraga, J; Chávez Caraza, K L; Santos-Guzman, J

2014-10-01

The gold standard for the diagnosis of pneumonia secondary to Mycoplasma pneumoniae is the serial measurement of IgM, since an isolated test for IgM has a poor sensitivity of 31.8%. A pneumonia due to Mycoplasma pneumoniae could be of clinically different origins, thus it is possible to perform a clinical score for its early diagnosis. To develop a clinical score in order to rule out a pneumoniae secondary to Mycoplasma pneumoniae. A total of 302 patients from 0 to 18 years-old, with a diagnosis of pneumonia were evaluated and divided into two groups: Mycoplasma positive and Mycoplasma negative. Using different variables in the medical records a clinical score was calculated. Of the 302 cases studied, 34 were classified as Mycoplasma positive and 268 as Mycoplasma negative. The variables relevant to the calculation of the score were age, days with fever, and days with cough, thus providing the CAF (Cough, Age, Fever) score. Ranges were assigned for each variable and points were given for each range. A value greater than or equal to 5 meant a positive score. The CAF score was applied to the 302 cases, resulting in 164 cases of Mycoplasma positive and 138 cases of Mycoplasma negative. The CAF score had a sensitivity of 85% and specificity of 49%. The CAF score had better sensitivity than other clinical diagnostic tools. With a negative predictive value of 96% it is possible to rule out a pneumonia secondary to M. pneumoniae. The study requires a prospective study to verify the usefulness of our score. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Is reflective functioning associated with clinical symptoms and long-term course in patients with personality disorders?

PubMed

Antonsen, Bjørnar T; Johansen, Merete S; Rø, Frida G; Kvarstein, Elfrida H; Wilberg, Theresa

2016-01-01

Mentalization is the capacity to understand behavior as the expression of various mental states and is assumed to be important in a range of psychopathologies, especially personality disorders (PDs). The first aim of the present study was to investigate the relationship between mentalization capacity, operationalized as reflective functioning (RF), and clinical manifestations before entering study treatment. The second aim was to investigate the relationship between baseline RF and long-term clinical outcome both independent of treatment (predictor analyses) and dependent on treatment (moderator analyses). Seventy-nine patients from a randomized clinical trial (Ullevål Personality Project) who had borderline and/or avoidant PD were randomly assigned to either a step-down treatment program, comprising short-term day-hospital treatment followed by outpatient combined group and individual psychotherapy, or to outpatient individual psychotherapy. Patients were evaluated on variables including symptomatic distress, psychosocial functioning, personality functioning, and self-esteem at baseline, 8 and 18months, and 3 and 6years. RF was significantly associated with a wide range of variables at baseline. In longitudinal analyses RF was not found to be a predictor of long-term clinical outcome. However, when considering treatment type, there were significant moderator effects of RF. Patients with low RF had better outcomes in outpatient individual therapy compared to the step-down program. In contrast, patients in the medium RF group achieved better results in the step-down program. These findings indicate that RF is associated with core aspects of personality pathology and capture clinically relevant phenomena in adult patients with PDs. Moreover, patients with different capacities for mentalization may need different kinds of therapeutic approaches. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The 50 Most Cited Articles in Invasive Neuromodulation.

PubMed

Ward, Max; Doran, Joseph; Paskhover, Boris; Mammis, Antonios

2018-06-01

Bibliometric analysis is a commonly used analytic tool for objective determination of the most influential and peer-recognized articles within a given field. This study is the first bibliometric analysis of the literature in the field of invasive neuromodulation, excluding deep brain stimulation. The objectives of this study are to identify the 50 most cited articles in invasive neuromodulation, provide an overview of the literature to assist in clinical education, and evaluate the effect of impact factor on manuscript recognition. Bibliometric analysis was performed using the Science Citation Index from the Institute for Scientific Information, accessed through the Web of Science. Search terms relevant to the field of invasive neuromodulation were used to identify the 50 most cited journal articles between 1900 and 2016. The median number of citations was 236 (range, 173-578). The most common topics among the articles were vagus nerve stimulation (n = 24), spinal cord stimulation (n = 9), and motor cortex stimulation (n = 6). Median journal impact factor was 5.57. Most of these articles (n = 19) contained level I, II, or III evidence. This analysis provides a brief look into the most cited articles within the field, many of which evaluated innovated procedures and therapies that helped to drive surgical neuromodulation forward. These landmark articles contain vital clinical and educational information that remains relevant to clinicians and students within the field and provide insight into areas of expanding research. Journal impact factor may play a significant role in determining the literary relevance and general awareness of invasive neuromodulation studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Applicability Analysis of Validation Evidence for Biomedical Computational Models

DOE PAGES

Pathmanathan, Pras; Gray, Richard A.; Romero, Vicente J.; ...

2017-09-07

Computational modeling has the potential to revolutionize medicine the way it transformed engineering. However, despite decades of work, there has only been limited progress to successfully translate modeling research to patient care. One major difficulty which often occurs with biomedical computational models is an inability to perform validation in a setting that closely resembles how the model will be used. For example, for a biomedical model that makes in vivo clinically relevant predictions, direct validation of predictions may be impossible for ethical, technological, or financial reasons. Unavoidable limitations inherent to the validation process lead to challenges in evaluating the credibilitymore » of biomedical model predictions. Therefore, when evaluating biomedical models, it is critical to rigorously assess applicability, that is, the relevance of the computational model, and its validation evidence to the proposed context of use (COU). However, there are no well-established methods for assessing applicability. In this paper, we present a novel framework for performing applicability analysis and demonstrate its use with a medical device computational model. The framework provides a systematic, step-by-step method for breaking down the broad question of applicability into a series of focused questions, which may be addressed using supporting evidence and subject matter expertise. The framework can be used for model justification, model assessment, and validation planning. While motivated by biomedical models, it is relevant to a broad range of disciplines and underlying physics. Finally, the proposed applicability framework could help overcome some of the barriers inherent to validation of, and aid clinical implementation of, biomedical models.« less

Emerging point of care tests for influenza: innovation or status quo.

PubMed

Tayo, Adeoluwa; Ellis, Joanna; Linden Phillips, Luan; Simpson, Sue; Ward, Derek J

2012-07-01

Point of care tests (POCTs) for influenza potentially offer earlier diagnosis, enabling specific treatment, infection control measures and greater patient convenience and satisfaction. Current POCTs have limited sensitivity, some cannot distinguish influenza types, none differentiate subtypes and are relatively expensive.  To identify and characterise influenza POCTs expected to be available for clinical use in the U.K. by mid-2013, highlighting those with potential benefits over existing tests. Potential developers of influenza POCTs were identified through known manufacturers' websites, Medical Technology trade associations, the EuroScan International Network, an expert advisory group and by searching relevant online sources. Identified companies were asked to provide standard information on relevant technologies. Fifty-six companies were identified, and 29 (52%) responded, identifying 57 potentially relevant technologies. Of these, 40 (70%) were already available or had undetermined status and 5 (9%) were excluded as time to results took over 60 minutes. Of the remaining 12 emerging POCTs, 10 (83%) reportedly enabled differentiation of influenza types and eight differentiation of A subtypes. Nasopharyngeal swabs were the most commonly acceptable sample type; the sample volume ranging from 80 μl to 1.4 ml. Most identified emerging influenza POCTs offered differentiation of influenza type and subtype. Tests claiming this capability include several incorporating reverse transcription polymerase chain reaction assays; though, these also had the longest time to result. However, whilst some identified POCTs exhibit high sensitivity and specificity, most lack published clinical data for assessment, and the overall costs of these technologies remains largely unknown. © 2011 Blackwell Publishing Ltd.

Applicability Analysis of Validation Evidence for Biomedical Computational Models

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

Pathmanathan, Pras; Gray, Richard A.; Romero, Vicente J.

Computational modeling has the potential to revolutionize medicine the way it transformed engineering. However, despite decades of work, there has only been limited progress to successfully translate modeling research to patient care. One major difficulty which often occurs with biomedical computational models is an inability to perform validation in a setting that closely resembles how the model will be used. For example, for a biomedical model that makes in vivo clinically relevant predictions, direct validation of predictions may be impossible for ethical, technological, or financial reasons. Unavoidable limitations inherent to the validation process lead to challenges in evaluating the credibilitymore » of biomedical model predictions. Therefore, when evaluating biomedical models, it is critical to rigorously assess applicability, that is, the relevance of the computational model, and its validation evidence to the proposed context of use (COU). However, there are no well-established methods for assessing applicability. In this paper, we present a novel framework for performing applicability analysis and demonstrate its use with a medical device computational model. The framework provides a systematic, step-by-step method for breaking down the broad question of applicability into a series of focused questions, which may be addressed using supporting evidence and subject matter expertise. The framework can be used for model justification, model assessment, and validation planning. While motivated by biomedical models, it is relevant to a broad range of disciplines and underlying physics. Finally, the proposed applicability framework could help overcome some of the barriers inherent to validation of, and aid clinical implementation of, biomedical models.« less

Effects of cobalt and chromium ions at clinically equivalent concentrations after metal-on-metal hip replacement on human osteoblasts and osteoclasts: implications for skeletal health.

PubMed

Andrews, Rebecca E; Shah, Karan M; Wilkinson, J Mark; Gartland, Alison

2011-10-01

Metal-on-metal hip replacement (MOMHR) using large diameter bearings has become a popular alternative to conventional total hip arthroplasty, but is associated with elevated local tissue and circulating levels of chromium (Cr) and cobalt (Co) ions that may affect bone health. We examined the effects of acute and chronic exposure to these metals on human osteoblast and osteoclast formation and function over a clinically relevant concentration range previously reported in serum and within hip synovial fluid in patients after MOMHR. SaOS-2 cells were cultured with Co(2+), Cr(3+) and Cr(6+) for 3 days after which an MTS assay was used to assess cell viability, for 13 days after which alkaline phosphatase and cell viability were assessed and for 21 days after which nodule formation was assessed. Monocytes were isolated from human peripheral blood and settled onto dentine disks then cultured with M-CSF and RANKL plus either Co(2+), Cr(3+) or Cr(6+) ions for 21 days from day 0 or between days 14 and 21. Cells were fixed and stained for TRAP and osteoclast number and amount of resorption per dentine disk determined. Co(2+) and Cr(3+) did not affect osteoblast survival or function over the clinically equivalent concentration range, whilst Cr(6+) reduced osteoblast survival and function at concentrations within the clinically equivalent serum range after MOMHR (IC(50) =2.2 μM). In contrast, osteoclasts were more sensitive to metal ions exposure. At serum levels a mild stimulatory effect on resorption in forming osteoclasts was found for Co(2+) and Cr(3+), whilst at higher serum and synovial equivalent concentrations, and with Cr(6+), a reduction in cell number and resorption was observed. Co(2+) and Cr(6+) within the clinical range reduced cell number and resorption in mature osteoclasts. Our data suggest that metal ions at equivalent concentrations to those found in MOMHR affect bone cell health and may contribute to the observed bone-related complications of these prostheses. Copyright © 2011 Elsevier Inc. All rights reserved.

Scintillator high-gain avalanche rushing photoconductor active-matrix flat panel imager: Zero-spatial frequency x-ray imaging properties of the solid-state SHARP sensor structure

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

Wronski, M.; Zhao, W.; Tanioka, K.

Purpose: The authors are investigating the feasibility of a new type of solid-state x-ray imaging sensor with programmable avalanche gain: scintillator high-gain avalanche rushing photoconductor active matrix flat panel imager (SHARP-AMFPI). The purpose of the present work is to investigate the inherent x-ray detection properties of SHARP and demonstrate its wide dynamic range through programmable gain. Methods: A distributed resistive layer (DRL) was developed to maintain stable avalanche gain operation in a solid-state HARP. The signal and noise properties of the HARP-DRL for optical photon detection were investigated as a function of avalanche gain both theoretically and experimentally, and themore » results were compared with HARP tube (with electron beam readout) used in previous investigations of zero spatial frequency performance of SHARP. For this new investigation, a solid-state SHARP x-ray image sensor was formed by direct optical coupling of the HARP-DRL with a structured cesium iodide (CsI) scintillator. The x-ray sensitivity of this sensor was measured as a function of avalanche gain and the results were compared with the sensitivity of HARP-DRL measured optically. The dynamic range of HARP-DRL with variable avalanche gain was investigated for the entire exposure range encountered in radiography/fluoroscopy (R/F) applications. Results: The signal from HARP-DRL as a function of electric field showed stable avalanche gain, and the noise associated with the avalanche process agrees well with theory and previous measurements from a HARP tube. This result indicates that when coupled with CsI for x-ray detection, the additional noise associated with avalanche gain in HARP-DRL is negligible. The x-ray sensitivity measurements using the SHARP sensor produced identical avalanche gain dependence on electric field as the optical measurements with HARP-DRL. Adjusting the avalanche multiplication gain in HARP-DRL enabled a very wide dynamic range which encompassed all clinically relevant medical x-ray exposures. Conclusions: This work demonstrates that the HARP-DRL sensor enables the practical implementation of a SHARP solid-state x-ray sensor capable of quantum noise limited operation throughout the entire range of clinically relevant x-ray exposures. This is an important step toward the realization of a SHARP-AMFPI x-ray flat-panel imager.« less

Families with burn injury: application in the clinically relevant continuum model.

PubMed

Lehna, Carlee

2011-06-01

This article incorporates the findings from a predominantly qualitative, mixed-method study examining sibling survivors' experiences of a major childhood burn injury into the clinically relevant continuum model as a means of promoting culturally competent and family-centered care. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinical Relevance of Discourse Characteristics after Right Hemisphere Brain Damage

ERIC Educational Resources Information Center

Blake, Margaret Lehman

2006-01-01

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

INR goal attainment and oral anticoagulation knowledge of patients enrolled in an anticoagulation clinic in a Veterans Affairs medical center.

PubMed

Baker, Jennifer W; Pierce, Kristi L; Ryals, Casey A

2011-03-01

In January 2009, the Joint Commission implemented a National Patient Safety Goal (NPSG) for ambulatory care, NPSG 3E, intended to reduce harm associated with the use of anticoagulation therapy. The 2011 NPSG 3E encompasses 8 elements of performance, including requirements that each organization (a) provide education regarding anticoagulation therapy to staff, patients, and families and (b) evaluate its safety practices and take appropriate action to improve its practices. The Alvin C. York (ACY) outpatient anticoagulation clinic provides education to new patients and their families at the initial clinic visit, with follow-up reinforcement of education as needed throughout their care. To (a) assess the knowledge level of patients receiving warfarin therapy in an anticoagulation clinic using the validated Anticoagulation Knowledge Assessment (AKA) questionnaire and (b) examine the relationship between patient anticoagulation knowledge and anticoagulation control as measured by the international normalized ratio (INR). All ACY Veterans Affairs (VA) anticoagulation clinic patients seen during their routine visit within an 8-week recruitment period from February 2010 to April 2010 were asked to complete the AKA questionnaire. Upon voluntary consent, the questionnaire was completed by the patient either during the clinic visit or returned later by mail. Demographic and clinical data were manually extracted from the computerized patient record system and included age, gender, indication for and duration of anticoagulation therapy, goal INR range, and the 10 INR values preceding the date of consent. A passing score was defined as at least 21 correct responses on the 29-item AKA questionnaire (72.4% correct). Statistical analyses included comparisons of demographic and clinical characteristics for patients with passing versus failing scores, assessed with Pearson chi-square and Fisher's exact test, and bivariate analyses of INR control with anticoagulation knowledge, assessed with Spearman's rho correlation. INR control was defined by 3 outcome measures: number of INRs within therapeutic range, time in therapeutic range (TTR) calculated using the Rosendaal method, and standard deviation (SD) of INR values. Anticoagulation knowledge was assessed with 2 measures: total AKA score and count of correct answers to a subset of 15 AKA items deemed by the investigators to be relevant to INR control. Of 447 patients enrolled in the anticoagulation clinic, 260 consented to participate in the survey, of whom 185 patients completed the AKA instrument (n=171 [92.4%] by mail) and were successfully matched to patient record system data. 178 (96.2%) respondents were male with a mean (SD) age of 68 (10.1) years. The majority of patients were undergoing anticoagulation treatment for atrial fibrillation (n=113, 61.1%) or deep venous/pulmonary thromboembolism (n=48, 25.9%). The majority of patients had been treated with warfarin for at least 1 year (n=162, 87.6%). Most patients had goal INR ranges of 2.0 to 3.0 (n=166, 89.7%). Of the 185 patients who completed the questionnaire, 137 (74.1%) achieved a passing score. The mean (SD) AKA questionnaire score was 78.1% (12.1%). There were 8 questions that were answered correctly by less than 70% of patients and identified as potential deficiencies in patient education. For the 167 patients who had been on warfarin therapy for at least 6 months and had 10 previous INR values, there was no significant Spearman's rho correlation between total number of correct questionnaire responses and INR control, defined as the count of the 10 previous INR values within goal range (rho =-0.022, P=0.776), TTR (rho=0.015, P=0.848), and SD (rho=0.047, P=0.550). There was also no significant relationship between number of correct INR-relevant responses and INR control by any of the 3 outcome measures (count in range rho=0.033, P=0.676; TTR rho=0.067, P=0.388; and SD rho=-0.029, P=0.708). Although 74.1% of patients on long-term warfarin therapy achieved a passing score of at least 21 correct answers on the 29-question AKA instrument, there was no significant relationship between patient warfarin knowledge and INR control. Areas for improvement in patient education have been identified and procedures for educational modification are currently in development. Copyright © 2011, Academy of Managed Care Pharmacy. All rights reserved.

Mindfulness-Based Approaches for Children and Youth.

PubMed

Perry-Parrish, Carisa; Copeland-Linder, Nikeea; Webb, Lindsey; Sibinga, Erica M S

2016-06-01

Mindfulness meditation is a useful adjunct to behavioral and medical interventions to manage a range of symptoms, including psychological and physical responses to stress, anxiety, depression, and disruptive behavior. Mindfulness approaches can be taught to children, adolescents, and their parents to improve self-regulation, particularly in response to stress. Mindfulness may be particularly relevant for youth and families who have an increased risk for exposure to chronic stress and unique stressors associated with medical and/or social-contextual considerations. Moreover, mindfulness parenting techniques can augment traditional behavioral approaches to improve children׳s behavior through specific parent-child interactions. A growing body of empirical studies and clinical experience suggest that incorporating mindfulness practices will enable clinicians to more effectively treat youth and their families in coping optimally with a range of challenging symptoms. Copyright © 2016 Mosby, Inc. All rights reserved.

Development of Standardized Material Testing Protocols for Prosthetic Liners

PubMed Central

Cagle, John C.; Reinhall, Per G.; Hafner, Brian J.; Sanders, Joan E.

2017-01-01

A set of protocols was created to characterize prosthetic liners across six clinically relevant material properties. Properties included compressive elasticity, shear elasticity, tensile elasticity, volumetric elasticity, coefficient of friction (CoF), and thermal conductivity. Eighteen prosthetic liners representing the diverse range of commercial products were evaluated to create test procedures that maximized repeatability, minimized error, and provided clinically meaningful results. Shear and tensile elasticity test designs were augmented with finite element analysis (FEA) to optimize specimen geometries. Results showed that because of the wide range of available liner products, the compressive elasticity and tensile elasticity tests required two test maxima; samples were tested until they met either a strain-based or a stress-based maximum, whichever was reached first. The shear and tensile elasticity tests required that no cyclic conditioning be conducted because of limited endurance of the mounting adhesive with some liner materials. The coefficient of friction test was based on dynamic coefficient of friction, as it proved to be a more reliable measurement than static coefficient of friction. The volumetric elasticity test required that air be released beneath samples in the test chamber before testing. The thermal conductivity test best reflected the clinical environment when thermal grease was omitted and when liner samples were placed under pressure consistent with load bearing conditions. The developed procedures provide a standardized approach for evaluating liner products in the prosthetics industry. Test results can be used to improve clinical selection of liners for individual patients and guide development of new liner products. PMID:28233885

Dental magnetic resonance imaging: making the invisible visible.

PubMed

Idiyatullin, Djaudat; Corum, Curt; Moeller, Steen; Prasad, Hari S; Garwood, Michael; Nixdorf, Donald R

2011-06-01

Clinical dentistry is in need of noninvasive and accurate diagnostic methods to better evaluate dental pathosis. The purpose of this work was to assess the feasibility of a recently developed magnetic resonance imaging (MRI) technique, called SWeep Imaging with Fourier Transform (SWIFT), to visualize dental tissues. Three in vitro teeth, representing a limited range of clinical conditions of interest, imaged using a 9.4T system with scanning times ranging from 100 seconds to 25 minutes. In vivo imaging of a subject was performed using a 4T system with a 10-minute scanning time. SWIFT images were compared with traditional two-dimensional radiographs, three-dimensional cone-beam computed tomography (CBCT) scanning, gradient-echo MRI technique, and histological sections. A resolution of 100 μm was obtained from in vitro teeth. SWIFT also identified the presence and extent of dental caries and fine structures of the teeth, including cracks and accessory canals, which are not visible with existing clinical radiography techniques. Intraoral positioning of the radiofrequency coil produced initial images of multiple adjacent teeth at a resolution of 400 μm. SWIFT MRI offers simultaneous three-dimensional hard- and soft-tissue imaging of teeth without the use of ionizing radiation. Furthermore, it has the potential to image minute dental structures within clinically relevant scanning times. This technology has implications for endodontists because it offers a potential method to longitudinally evaluate teeth where pulp and root structures have been regenerated. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Gatekeepers for Pragmatic Clinical Trials

PubMed Central

Whicher, Danielle M.; Miller, Jennifer E.; Dunham, Kelly M.; Joffe, Steven

2015-01-01

To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g., clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the United States clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This manuscript provides a framework to help guide gatekeepers’ decision-making related to the use of resources for pragmatic clinical trials. These include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers’ decisions, including protection from harm and maximization of benefits, (2) advancement of organizational mission and values, and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers’ actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding the use of limited and valuable resources. PMID:26374683

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

PubMed

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

2018-04-26

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

Evaluation of health alerts from an early illness warning system in independent living.

PubMed

Rantz, Marilyn J; Scott, Susan D; Miller, Steven J; Skubic, Marjorie; Phillips, Lorraine; Alexander, Greg; Koopman, Richelle J; Musterman, Katy; Back, Jessica

2013-06-01

Passive sensor networks were deployed in independent living apartments to monitor older adults in their home environments to detect signs of impending illness and alert clinicians so they can intervene and prevent or delay significant changes in health or functional status. A retrospective qualitative deductive content analysis was undertaken to refine health alerts to improve clinical relevance to clinicians as they use alerts in their normal workflow of routine care delivery to older adults. Clinicians completed written free-text boxes to describe actions taken (or not) as a result of each alert; they also rated the clinical significance (relevance) of each health alert on a scale of 1 to 5. Two samples of the clinician's written responses to the health alerts were analyzed after alert algorithms had been adjusted based on results of a pilot study using health alerts to enhance clinical decision-making. In the first sample, a total of 663 comments were generated by seven clinicians in response to 385 unique alerts; there are more comments than alerts because more than one clinician rated the same alert. The second sample had a total of 142 comments produced by three clinicians in response to 88 distinct alerts. The overall clinical relevance of the alerts, as judged by the content of the qualitative comments by clinicians for each alert, improved from 33.3% of the alerts in the first sample classified as clinically relevant to 43.2% in the second. The goal is to produce clinically relevant alerts that clinicians find useful in daily practice. The evaluation methods used are described to assist others as they consider building and iteratively refining health alerts to enhance clinical decision making.

The Quality of Clinical Information in Adverse Drug Reaction Reports by Patients and Healthcare Professionals: A Retrospective Comparative Analysis.

PubMed

Rolfes, Leàn; van Hunsel, Florence; van der Linden, Laura; Taxis, Katja; van Puijenbroek, Eugène

2017-07-01

Clinical information is needed to assess the causal relationship between a drug and an adverse drug reaction (ADR) in a reliable way. Little is known about the level of relevant clinical information about the ADRs reported by patients. The aim was to determine to what extent patients report relevant clinical information about an ADR compared with their healthcare professional. A retrospective analysis of all ADR reports on the same case, i.e., cases with a report from both the patient and the patient's healthcare professional, selected from the database of the Dutch Pharmacovigilance Center Lareb, was conducted. The extent to which relevant clinical information was reported was assessed by trained pharmacovigilance assessors, using a structured tool. The following four domains were assessed: ADR, chronology, suspected drug, and patient characteristics. For each domain, the proportion of reported information in relation to information deemed relevant was calculated. An average score of all relevant domains was determined and categorized as poorly (≤45%), moderately (from 46 to 74%) or well (≥75%) reported. Data were analyzed using a paired sample t test and Wilcoxon signed rank test. A total of 197 cases were included. In 107 cases (54.3%), patients and healthcare professionals reported a similar level of clinical information. Statistical analysis demonstrated no overall differences between the groups (p = 0.126). In a unique study of cases of ADRs reported by patients and healthcare professionals, we found that patients report clinical information at a similar level as their healthcare professional. For an optimal pharmacovigilance, both healthcare professionals and patient should be encouraged to report.

Conducting research in clinical psychology practice: Barriers, facilitators, and recommendations.

PubMed

Smith, Kirsten V; Thew, Graham R

2017-09-01

The combination of clinical psychologists' therapeutic expertise and research training means that they are in an ideal position to be conducting high-quality research projects. However, despite these skills and the documented benefits of research to services and service users, research activity in practice remains low. This article aims to give an overview of the advantages of, and difficulties in conducting research in clinical practice. We reviewed the relevant literature on barriers to research and reflected on our clinical and research experiences in a range of contexts to offer practical recommendations. We considered factors involved in the planning, sourcing support, implementation, and dissemination phases of research, and outline suggestions to improve the feasibility of research projects in post-qualification roles. We suggest that research leadership is particularly important within clinical psychology to ensure the profession's continued visibility and influence within health settings. Clinical implications Emerging evidence suggests that clinical settings that foster research are associated with better patient outcomes. Suggestions to increase the feasibility of research projects in clinical settings are detailed. Limitations The present recommendations are drawn from the authors' practical experience and may need adaptation to individual practitioners' settings. This study does not attempt to assess the efficacy of the strategies suggested. © 2017 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

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

Medicine Based Evidence for Individualized Decision Making: Case Study of Systemic Lupus Erythematosus.

PubMed

Wivel, Ashley E; Lapane, Kate; Kleoudis, Christi; Singer, Burton H; Horwitz, Ralph I

2017-11-01

To guide management decisions for an index patient, evidence is required from comparisons between approximate matches to the profile of the index case, where some matches contain responses to treatment and others act as controls. We describe a method for constructing clinically relevant histories/profiles using data collected but unreported from 2 recent phase 3 randomized controlled trials assessing belimumab in subjects with clinically active and serologically positive systemic lupus erythematosus. Outcome was the Systemic lupus erythematosus Responder Index (SRI) measured at 52 weeks. Among 1175 subjects, we constructed an algorithm utilizing 11 trajectory variables including 4 biological, 2 clinical, and 5 social/behavioral. Across all biological and social/behavioral variables, the proportion of responders based on the SRI whose value indicated clinical worsening or no improvement ranged from 27.5% to 42.3%. Kappa values suggested poor agreement, indicating that each biological and patient-reported outcome provides different information than gleaned from the SRI. The richly detailed patient profiles needed to guide decision-making in clinical practice are sharply at odds with the limited information utilized in conventional randomized controlled trial analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

Rapid high resolution T1 mapping as a marker of brain development: Normative ranges in key regions of interest.

PubMed

Eminian, Sylvain; Hajdu, Steven David; Meuli, Reto Antoine; Maeder, Philippe; Hagmann, Patric

2018-01-01

We studied in a clinical setting the age dependent T1 relaxation time as a marker of normal late brain maturation and compared it to conventional techniques, namely the apparent diffusion coefficient (ADC). Forty-two healthy subjects ranging from ages 1 year to 20 years were included in our study. T1 brain maps in which the intensity of each pixel corresponded to T1 relaxation times were generated based on MR imaging data acquired using a MP2RAGE sequence. During the same session, diffusion tensor imaging data was collected. T1 relaxation times and ADC in white matter and grey matter were measured in seven clinically relevant regions of interest and were correlated to subjects' age. In the basal ganglia, there was a small, yet significant, decrease in T1 relaxation time (-0.45 ≤R≤-0.59, p<10-2) and ADC (-0.60≤R≤-0.65, p<10-4) as a function of age. In the frontal and parietal white matter, there was a significant decrease in T1 relaxation time (-0.62≤R≤-0.68, p<10-4) and ADC (-0.81≤R≤-0.85, p<10-4) as a function of age. T1 relaxation time changes in the corpus callosum and internal capsule were less relevant for this age range. There was no significant difference between the correlation of T1 relaxation time and ADC with respect to age (p-value = 0.39). The correlation between T1 relaxation and ADC is strong in the white matter but only moderate in basal ganglia over this age period. T1 relaxation time is a marker of brain maturation or myelination during late brain development. Between the age of 1 and 20 years, T1 relaxation time decreases as a function of age in the white matter and basal ganglia. The greatest changes occur in frontal and parietal white matter. These regions are known to mature in the final stage of development and are mainly composed of association circuits. Age-correlation is not significantly different between T1 relaxation time and ADC. Therefore, T1 relaxation time does not appear to be a superior marker of brain maturation than ADC but may be considered as complementary owing the intrinsic differences in bio-physical sensitivity. This work may serve as normative ranges in clinical imaging routines.

Why non-invasive maternal hemodynamics assessment is clinically relevant in early pregnancy: a literature review.

PubMed

Vonck, Sharona; Staelens, Anneleen Simone; Bollen, Ine; Broekx, Lien; Gyselaers, Wilfried

2016-10-12

The maternal cardiovascular system adapts quickly when embryo implantation is recognized by the body. Those adaptations play an important role, as a normal cardiovascular adaptation is a requirement for a normal course of pregnancy. Disturbed adaptations predispose to potential hypertensive disorders further in pregnancy [1-3]. This report aims to briefly inform the obstetricians, general practitioners and midwives, who are the key players in detecting and treating hypertensive disorders during pregnancy. The PubMed database was used as main tool to find studies involving clearly defined first trimester hemodynamic changes in normal pregnancies and hypertensive pregnancies. In addition, the bibliographies of these studies were investigated for further relevant literature. A comprehensive overview is given concerning the normal adaptations in the cardiovascular tree in a first trimester pregnancy. Additionally, signs of abnormal cardiovascular changes observed in first trimester are described together with the normal reference range for each non-invasive, easily applicable technique for maternal hemodynamics assessment. With a combination of techniques, it is possible to integrate and evaluate the maternal heart, veins and arteries at 12 weeks of pregnancy. Applying those techniques into the daily clinic opens perspectives to prevention and prophylactic treatment, aiming for a reduction of the risk for hypertension during pregnancy.

Relationships between self-determination theory and theory of planned behavior applied to physical activity and exercise behavior in chronic pain.

PubMed

Brooks, Jessica M; Iwanaga, Kanako; Chiu, Chung-Yi; Cotton, Brandi Parker; Deiches, Jon; Morrison, Blaise; Moser, Erin; Chan, Fong

2017-08-01

This study examined the relationships between self-determination theory (SDT) and theory of planned behavior (TpB) applied to physical activity and exercise behavior (PA&E) in people with chronic pain. Two hundred and eleven adults with chronic musculoskeletal pain (28 males and 183 females, age range 18 to 82 years, mean age 43 years) were recruited from online support groups and clinic networks in the United States. Participants completed SDT measures relevant to PA&E on perceived autonomy support, autonomy, competence, and relatedness, as well as TpB measures relevant to PA&E on intention, attitudes, subjective norms, and perceived behavioral control. Correlational techniques and canonical correlation analysis were performed to examine the relationships and variance within and between theoretical dimensions. Overall, the SDT set accounted for 37% of the TpB variance and the TpB set accounted for 32% of the SDT set variance. The results indicate there are statistical similarities and differences between concepts in SDT and TpB models for PA&E. Using both empirical guidance and clinical expertise, researchers and practitioners should attempt to select and integrate non-redundant and complementary components from SDT, TpB, and other related health behavior theories.

Sound envelope processing in the developing human brain: A MEG study.

PubMed

Tang, Huizhen; Brock, Jon; Johnson, Blake W

2016-02-01

This study investigated auditory cortical processing of linguistically-relevant temporal modulations in the developing brains of young children. Auditory envelope following responses to white noise amplitude modulated at rates of 1-80 Hz in healthy children (aged 3-5 years) and adults were recorded using a paediatric magnetoencephalography (MEG) system and a conventional MEG system, respectively. For children, there were envelope following responses to slow modulations but no significant responses to rates higher than about 25 Hz, whereas adults showed significant envelope following responses to almost the entire range of stimulus rates. Our results show that the auditory cortex of preschool-aged children has a sharply limited capacity to process rapid amplitude modulations in sounds, as compared to the auditory cortex of adults. These neurophysiological results are consistent with previous psychophysical evidence for a protracted maturational time course for auditory temporal processing. The findings are also in good agreement with current linguistic theories that posit a perceptual bias for low frequency temporal information in speech during language acquisition. These insights also have clinical relevance for our understanding of language disorders that are associated with difficulties in processing temporal information in speech. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Psychometric properties of the Beck Depression Inventory-II: a comprehensive review.

PubMed

Wang, Yuan-Pang; Gorenstein, Clarice

2013-01-01

To review the psychometric properties of the Beck Depression Inventory-II (BDI-II) as a self-report measure of depression in a variety of settings and populations. Relevant studies of the BDI-II were retrieved through a search of electronic databases, a hand search, and contact with authors. Retained studies (k = 118) were allocated into three groups: non-clinical, psychiatric/institutionalized, and medical samples. The internal consistency was described as around 0.9 and the retest reliability ranged from 0.73 to 0.96. The correlation between BDI-II and the Beck Depression Inventory (BDI-I) was high and substantial overlap with measures of depression and anxiety was reported. The criterion-based validity showed good sensitivity and specificity for detecting depression in comparison to the adopted gold standard. However, the cutoff score to screen for depression varied according to the type of sample. Factor analysis showed a robust dimension of general depression composed by two constructs: cognitive-affective and somatic-vegetative. The BDI-II is a relevant psychometric instrument, showing high reliability, capacity to discriminate between depressed and non-depressed subjects, and improved concurrent, content, and structural validity. Based on available psychometric evidence, the BDI-II can be viewed as a cost-effective questionnaire for measuring the severity of depression, with broad applicability for research and clinical practice worldwide.

Optical bedside monitoring of cerebral perfusion: technological and methodological advances applied in a study on acute ischemic stroke

NASA Astrophysics Data System (ADS)

Steinkellner, Oliver; Gruber, Clemens; Wabnitz, Heidrun; Jelzow, Alexander; Steinbrink, Jens; Fiebach, Jochen B.; MacDonald, Rainer; Obrig, Hellmuth

2010-11-01

We present results of a clinical study on bedside perfusion monitoring of the human brain by optical bolus tracking. We measure the kinetics of the contrast agent indocyanine green using time-domain near-IR spectroscopy (tdNIRS) in 10 patients suffering from acute unilateral ischemic stroke. In all patients, a delay of the bolus over the affected when compared to the unaffected hemisphere is found (mean: 1.5 s, range: 0.2 s to 5.2 s). A portable time-domain near-IR reflectometer is optimized and approved for clinical studies. Data analysis based on statistical moments of time-of-flight distributions of diffusely reflected photons enables high sensitivity to intracerebral changes in bolus kinetics. Since the second centralized moment, variance, is preferentially sensitive to deep absorption changes, it provides a suitable representation of the cerebral signals relevant for perfusion monitoring in stroke. We show that variance-based bolus tracking is also less susceptible to motion artifacts, which often occur in severely affected patients. We present data that clearly manifest the applicability of the tdNIRS approach to assess cerebral perfusion in acute stroke patients at the bedside. This may be of high relevance to its introduction as a monitoring tool on stroke units.

Adequate Patient Characterization in COPD: Reasons to Go Beyond GOLD Classification

PubMed Central

Verhage, Tewe L; Heijdra, Yvonne F; Molema, Johan; Daudey, Leonie; Dekhuijzen, P.N Richard; Vercoulen, Jan H

2009-01-01

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) serves as a guide to treat and manage different severity classes of patients with COPD. It was suggested that the five categories of FEV1 % predicted (GOLD 0–4), can be applied for selecting different therapeutic approaches. However, validation of these selective properties is very poor. To determine the relevance of the GOLD staging system for estimating the severity of clinical problems, GOLD 2 (n=70) and GOLD 3 (n=65) patients were drawn from a prospective cohort of patients with COPD and evaluated crosssectionally by a newly developed Nijmegen Integral Assessment Framework (NIAF). The NIAF is a detailed assessment of a wide range of aspects of health status (HS). Significant, though small, differences were found in Static Lung Volumes, Exercise Capacity, Subjective Pulmonary Complaints, Subjective Impairment, and Health-Related QoL, besides Airflow of course. Moreover, overlap between scores of these five HS sub-domains was substantial, indicating small clinical relevance for discernment. No significant differences were found in nine other aspects of HS. It is concluded that GOLD stages do not discriminate in any aspect of HS other than airflow obstruction, and therefore do not help the clinician in deciding which treatment modalities are appropriate. PMID:19452033

Research methodology in Dentistry: Part I – The essentials and relevance of research

PubMed Central

Krithikadatta, Jogikalmat

2012-01-01

The need for scientific evidence should be the basis of clinical practice. The field of restorative dentistry and endodontics is evolving at a rapid pace, with the introduction of several materials, instruments, and equipments. However, there is minimal information of their relevance in clinical practice. On the one hand, material and laboratory research is critical, however; its translation into clinical practice is not being substantiated enough with clinical research. This four part review series focuses on methods to improve evidence-based practice, by improving methods to integrate laboratory and clinical research. PMID:22368327

Valerian: no evidence for clinically relevant interactions.

PubMed

Kelber, Olaf; Nieber, Karen; Kraft, Karin

2014-01-01

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

Valerian: No Evidence for Clinically Relevant Interactions

PubMed Central

Nieber, Karen; Kraft, Karin

2014-01-01

In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root) was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients. PMID:25093031

Reliable Change Indices and Standardized Regression-Based Change Score Norms for Evaluating Neuropsychological Change in Children with Epilepsy

PubMed Central

Busch, Robyn M.; Lineweaver, Tara T.; Ferguson, Lisa; Haut, Jennifer S.

2015-01-01

Reliable change index scores (RCIs) and standardized regression-based change score norms (SRBs) permit evaluation of meaningful changes in test scores following treatment interventions, like epilepsy surgery, while accounting for test-retest reliability, practice effects, score fluctuations due to error, and relevant clinical and demographic factors. Although these methods are frequently used to assess cognitive change after epilepsy surgery in adults, they have not been widely applied to examine cognitive change in children with epilepsy. The goal of the current study was to develop RCIs and SRBs for use in children with epilepsy. Sixty-three children with epilepsy (age range 6–16; M=10.19, SD=2.58) underwent comprehensive neuropsychological evaluations at two time points an average of 12 months apart. Practice adjusted RCIs and SRBs were calculated for all cognitive measures in the battery. Practice effects were quite variable across the neuropsychological measures, with the greatest differences observed among older children, particularly on the Children’s Memory Scale and Wisconsin Card Sorting Test. There was also notable variability in test-retest reliabilities across measures in the battery, with coefficients ranging from 0.14 to 0.92. RCIs and SRBs for use in assessing meaningful cognitive change in children following epilepsy surgery are provided for measures with reliability coefficients above 0.50. This is the first study to provide RCIs and SRBs for a comprehensive neuropsychological battery based on a large sample of children with epilepsy. Tables to aid in evaluating cognitive changes in children who have undergone epilepsy surgery are provided for clinical use. An excel sheet to perform all relevant calculations is also available to interested clinicians or researchers. PMID:26043163

Blood pressure and urinary sodium in men and women: the Norfolk Cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk).

PubMed

Khaw, Kay-Tee; Bingham, Sheila; Welch, Ailsa; Luben, Robert; O'Brien, Eoin; Wareham, Nicholas; Day, Nicholas

2004-11-01

Abundant evidence indicates that a high sodium intake is causally related to high blood pressure, but debate over recommendations to reduce dietary sodium in the general population continues. A key issue is whether differences in usual sodium intake within the range feasible in free-living populations have clinical or public health relevance. We examined the relation between blood pressure and urinary sodium as a marker of dietary intake. This was a study of 23104 community-living adults aged 45-79 y. Mean systolic and diastolic blood pressure increased as the ratio of urinary sodium to creatinine increased (as estimated from a casual urine sample), with differences of 7.2 mm Hg for systolic blood pressure and 3.0 mm Hg for diastolic blood pressure (P < 0.0001) between the top and bottom quintiles. This trend was independent of age, body mass index, urinary potassium:creatinine, and smoking and was consistent by sex and history of hypertension. The prevalence of those with systolic blood pressure >/= 160 mm Hg halved from 12% in the top quintile to 6% in the bottom quintile; the odds ratio for having systolic blood pressure >/= 160 mm Hg was 2.48 (95% CI: 1.90, 3.22) for men and 2.67 (95% CI: 2.08, 3.43) for women in the top compared with the bottom quintile of urinary sodium. Estimated mean sodium intakes in the lowest and highest quintiles were approximately 80 and 220 mmol/d, respectively. Within the usual range found in a free-living population, differences in urinary sodium, an indicator of dietary sodium intake, are associated with blood pressure differences of clinical and public health relevance. Our findings reinforce recommendations to lower average sodium intakes in the general population.

Natural Variation of Drug Susceptibility in Wild-Type Human Immunodeficiency Virus Type 1

PubMed Central

Parkin, N. T.; Hellmann, N. S.; Whitcomb, J. M.; Kiss, L.; Chappey, C.; Petropoulos, C. J.

2004-01-01

Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or “biological cutoffs,” for the PhenoSense HIV phenotypic drug susceptibility assay. Definition of the natural variation in drug susceptibility in wild-type human immunodeficiency virus (HIV) type 1 isolates is necessary to determine the prevalence of innate drug resistance and to assess the capability of the PhenoSense assay to reliably measure subtle reductions in drug susceptibility. The biological cutoffs for each drug, defined by the 99th percentile of the fold change in the 50% inhibitory concentration distributions or the mean fold change plus 2 standard deviations, were lower than those previously reported for other phenotypic assays and lower than the clinically relevant cutoffs previously defined for the PhenoSense assay. The 99th percentile fold change values ranged from 1.2 (tenofovir) to 1.8 (zidovudine) for nucleoside reverse transcriptase RT inhibitors (RTIs), from 3.0 (efavirenz) to 6.2 (delavirdine) for nonnucleoside RTIs, and from 1.6 (lopinavir) to 3.6 (nelfinavir) for protease inhibitors. To evaluate the potential role of intrinsic assay variability in the observed variations in the drug susceptibilities of wild-type isolates, 10 reference viruses with different drug susceptibility patterns were tested 8 to 30 times each. The median coefficients of variation in fold change for the reference viruses ranged from 12 to 18% for all drugs except zidovudine (32%), strongly suggesting that the observed differences in wild-type virus susceptibility to the different drugs is related to intrinsic virus variability rather than assay variability. The low biological cutoffs and assay variability suggest that the PhenoSense HIV assay may assist in defining clinically relevant susceptibility cutoffs for resistance to antiretroviral drugs. PMID:14742192

Measurement of immunofunctional leptin to detect and monitor patients with functional leptin deficiency

PubMed Central

Pridzun, Lutz; Ranke, Michael; von Schnurbein, Julia; Moss, Anja; Brandt, Stephanie; Kohlsdorf, Katja; Moepps, Barbara; Schaab, Michael; Funcke, Jan-Bernd; Gierschik, Peter; Fischer-Posovszky, Pamela; Flehmig, Bertram

2016-01-01

Context and aims Functional leptin deficiency is characterized by high levels of circulating immunoreactive leptin (irLep), but a reduced bioactivity of the hormone due to defective receptor binding. As a result of the fact that affected patients can be successfully treated with metreleptin, it was aimed to develop and validate a diagnostic tool to detect functional leptin deficiency. Methods An immunoassay capable of recognizing the functionally relevant receptor-binding complex with leptin was developed (bioLep). The analytical quality of bioLep was validated and compared to a conventional assay for immune-reactive leptin (irLep). Its clinical relevance was evaluated in a cohort of lean and obese children and adults as well as in children diagnosed with functional leptin deficiency and their parents. Results In the clinical cohort, a bioLep/irLep ratio of 1.07 (range: 0.80–1.41) was observed. Serum of patients with non-functional leptin due to homozygous amino acid exchanges (D100Y or N103K) revealed high irLep but non-detectable bioLep levels. Upon treatment of these patients with metreleptin, irLep levels decreased, whereas levels of bioLep increased continuously. In patient relatives with heterozygous amino acid exchanges, a bioLep/irLep ratio of 0.52 (range: 0.48–0.55) being distinct from normal was observed. Conclusions The new bioLep assay is able to diagnose impaired leptin bioactivity in severely obese patients with a homozygous gene defect and in heterozygous carriers of such mutations. The assay serves as a diagnostic tool to monitor leptin bioactivity during treatment of these patients. PMID:28007844

Reliable change indices and standardized regression-based change score norms for evaluating neuropsychological change in children with epilepsy.

PubMed

Busch, Robyn M; Lineweaver, Tara T; Ferguson, Lisa; Haut, Jennifer S

2015-06-01

Reliable change indices (RCIs) and standardized regression-based (SRB) change score norms permit evaluation of meaningful changes in test scores following treatment interventions, like epilepsy surgery, while accounting for test-retest reliability, practice effects, score fluctuations due to error, and relevant clinical and demographic factors. Although these methods are frequently used to assess cognitive change after epilepsy surgery in adults, they have not been widely applied to examine cognitive change in children with epilepsy. The goal of the current study was to develop RCIs and SRB change score norms for use in children with epilepsy. Sixty-three children with epilepsy (age range: 6-16; M=10.19, SD=2.58) underwent comprehensive neuropsychological evaluations at two time points an average of 12 months apart. Practice effect-adjusted RCIs and SRB change score norms were calculated for all cognitive measures in the battery. Practice effects were quite variable across the neuropsychological measures, with the greatest differences observed among older children, particularly on the Children's Memory Scale and Wisconsin Card Sorting Test. There was also notable variability in test-retest reliabilities across measures in the battery, with coefficients ranging from 0.14 to 0.92. Reliable change indices and SRB change score norms for use in assessing meaningful cognitive change in children following epilepsy surgery are provided for measures with reliability coefficients above 0.50. This is the first study to provide RCIs and SRB change score norms for a comprehensive neuropsychological battery based on a large sample of children with epilepsy. Tables to aid in evaluating cognitive changes in children who have undergone epilepsy surgery are provided for clinical use. An Excel sheet to perform all relevant calculations is also available to interested clinicians or researchers. Copyright © 2015 Elsevier Inc. All rights reserved.

[What happens when medical students set their own exam papers?].

PubMed

Baerheim, A; Meland, E

2001-10-20

In the section for general practice at the University of Bergen, Norway, we want to emphasise learning more than control in our work with students. As a step in this direction we invited students to come up with proposals for exam papers, papers that usually include six to nine multiple steps for clinical reasoning. We guaranteed that one out of three proposals would be included as a paper in the written examination, possibly slightly modified. This article is an evaluation of the consequences of letting medical students set some of their own exam papers. The process was evaluated using 1) grades given, 2) students' assessment of whether this mode of setting papers influenced their exam preparations, and 3) students' free-text comments on the process. 57 out of 64 students (89%) took part in the evaluation. All knew that their fellow students had set one of the exam papers, but only 34 (60%) reported that this knowledge had changed the way they prepared for the exam. The mean grade was 9.9 (range 5-12, on a scale from 1 to 12, 6 being the lowest pass grade) for the paper set by students, and 9.5 (range 5-11) for all papers combined. Mean difference in score was 0.32 (95% confidence interval 0.08-0.64). Students' free-text comments showed that they specifically prepared for the three known paper topics. They drew comfort from knowing at least one of the papers set, and the student-set papers were found relevant for general practice. Letting medical students set one of the exam papers makes them feel more confident. Student-set papers were seen as relevant for clinical practice. The control function of the exam seemed to have been preserved.

Hyperglycaemia, Insulin Therapy and Critical Penumbral Regions for Prognosis in Acute Stroke: Further Insights from the INSULINFARCT Trial

PubMed Central

Rosso, Charlotte; Pires, Christine; Corvol, Jean-Christophe; Baronnet, Flore; Crozier, Sophie; Leger, Anne; Deltour, Sandrine; Valabregue, Romain; Amor-Sahli, Mélika; Lehéricy, Stéphane; Dormont, Didier; Samson, Yves

2015-01-01

Background Recently, the concept of ‘clinically relevant penumbra’ was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome. Methods We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome. Findings Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10−6mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome. Conclusion These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction. Trial Registration ClinicalTrials.gov NCT00472381 PMID:25793765

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

PubMed Central

Haahtela, T; Burbach, G J; Bachert, C; Bindslev-Jensen, C; Bonini, S; Bousquet, J; Bousquet-Rouanet, L; Bousquet, P J; Bresciani, M; Bruno, A; Canonica, G W; Darsow, U; Demoly, P; Durham, S R; Fokkens, W J; Giavi, S; Gjomarkaj, M; Gramiccioni, C; Kowalski, M L; Losonczy, G; Orosz, M; Papadopoulos, N G; Stingl, G; Todo-Bom, A; von Mutius, E; Köhli, A; Wöhrl, S; Järvenpää, S; Kautiainen, H; Petman, L; Selroos, O; Zuberbier, T; Heinzerling, L M

2014-01-01

Background Within a large prospective study, the Global Asthma and Allergy European Network (GA2LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. Objective To improve clinical interpretation of SPT results for inhalant allergens by providing quantitative decision points. Methods The GA2LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. Results Depending on the allergen, from 40% (blatella) to 87–89% (grass, mites) of the positive SPT reactions (wheal size ≥ 3 mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10 mm depending on the allergen. Conclusion These ‘reading keys’ for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form with the standard allergens including mm decision points for each allergen is offered for clinical use. PMID:24283409

Attribute Development Using Continuous Stakeholder Engagement to Prioritize Treatment Decisions: A Framework for Patient-Centered Research.

PubMed

dosReis, Susan; Castillo, Wendy Camelo; Ross, Melissa; Fitz-Randolph, Marcy; Vaughn-Lee, Angela; Butler, Beverly

To develop a methodological approach for selecting, validating, and prioritizing attributes for health care decision making. Participants (n = 48) were recruited from community support groups if they had a child aged 26 years or younger diagnosed with a coexisting mental health condition and cognitive impairment. Six in-depth interviews eliciting care management experiences were transcribed and coded into themes following the principles of grounded theory and the constant comparative method. Six focus groups involving 42 participants assessed the relevance, priority, and meaning and inter-relationship among the themes. The positive predictive value and sensitivity assessed agreement on thematic meaning. A final list was selected from the top priorities with good agreement as candidate attributes. Attribute levels reflecting the range of experiences in care management decisions emerged from the verbatim passages within each coded theme. Participants were the child's mother (73%), white (77%), married (69%), and on average 48 years old. The children were on average 14 years old; 44% had an intellectual disability, 25% had autism, and more than half had anxiety or attention-deficit/hyperactivity disorder. All 14 attributes identified from the in-depth interviews were deemed relevant. The positive predictive value exceeded 90%, and the sensitivity ranged from 64% to 89%. The final set of attributes formed the framework for care management decisions consisting of six attributes (medication, behavior, services, social, treatment effects, and school) each with three levels. A systematic approach grounded in qualitative methods produced a framework of relevant, important, and actionable attributes representing competing alternatives in clinical decisions. Copyright © 2016. Published by Elsevier Inc.

Reliability of the American Academy of Sleep Medicine Rules for Assessing Sleep Depth in Clinical Practice.

PubMed

Younes, Magdy; Kuna, Samuel T; Pack, Allan I; Walsh, James K; Kushida, Clete A; Staley, Bethany; Pien, Grace W

2018-02-15

The American Academy of Sleep Medicine has published manuals for scoring polysomnograms that recommend time spent in non-rapid eye movement sleep stages (stage N1, N2, and N3 sleep) be reported. Given the well-established large interrater variability in scoring stage N1 and N3 sleep, we determined the range of time in stage N1 and N3 sleep scored by a large number of technologists when compared to reasonably estimated true values. Polysomnograms of 70 females were scored by 10 highly trained sleep technologists, two each from five different academic sleep laboratories. Range and confidence interval (CI = difference between the 5th and 95th percentiles) of the 10 times spent in stage N1 and N3 sleep assigned in each polysomnogram were determined. Average values of times spent in stage N1 and N3 sleep generated by the 10 technologists in each polysomnogram were considered representative of the true values for the individual polysomnogram. Accuracy of different technologists in estimating delta wave duration was determined by comparing their scores to digitally determined durations. The CI range of the ten N1 scores was 4 to 39 percent of total sleep time (% TST) in different polysomnograms (mean CI ± standard deviation = 11.1 ± 7.1 % TST). Corresponding range for N3 was 1 to 28 % TST (14.4 ± 6.1 % TST). For stage N1 and N3 sleep, very low or very high values were reported for virtually all polysomnograms by different technologists. Technologists varied widely in their assignment of stage N3 sleep, scoring that stage when the digitally determined time of delta waves ranged from 3 to 17 seconds. Manual scoring of non-rapid eye movement sleep stages is highly unreliable among highly trained, experienced technologists. Measures of sleep continuity and depth that are reliable and clinically relevant should be a focus of clinical research. © 2018 American Academy of Sleep Medicine

Therapeutic drug monitoring of quetiapine in adolescents with psychotic disorders.

PubMed

Gerlach, M; Hünnerkopf, R; Rothenhöfer, S; Libal, G; Burger, R; Clement, H-W; Fegert, J M; Wewetzer, Ch; Mehler-Wex, C

2007-03-01

There are developmental and age-dependent differences in the pharmacokinetics and the pharmacodynamics of drugs in children and adolescents. Therefore, there is a need to carry out standardised studies to find out therapeutic ranges of plasma/serum concentrations in psychopharmacotherapy of children and adolescents. The aim of this prospective study was to examine the relationship between quetiapine serum concentration, treatment response, and side effects in a clinical setting to elucidate the age-specific therapeutic range of quetiapine in adolescents. Over a period of two years, therapeutic drug monitoring (TDM) was routinely performed in 21 adolescents (mean age was 15.9+/-1.5 years, 57% male) with psychotic disorders according to the guidelines of the AGNP TDM expert group. The psychopathology was assessed by using the Clinical Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS). Side effects were assessed by using the Dose Record and Treatment Emergent Symptom Scale (DOTES). Trough quetiapine concentrations were determined under steady state conditions after multiple-dose regimes (median 600 mg/day; range 100-800 mg/day). There was a marked variability of the serum concentrations, ranging from 19-877 ng/ml. 40.8% of the determined values were below and 24.5% above the therapeutic range (70-170 ng/ml) recommended for adults. None of the patients had severe side effects. We found a weak correlation between dose and serum concentration of quetiapine and no relationship between serum concentration and treatment response. There are several limitations of this study, and our results should therefore be interpreted with caution. Notwithstanding, differences in the ontogenesis of pharmacokinetics and pharmacodynamics may be the reason for the difference in the relationship between blood concentrations and therapeutic response to psychopharmaca in children, adolescents and adults. Further studies using larger samples, baseline assessment of psychopathology, definition of the treatment interval and investigation of clinically relevant interactions with various co-medications are warranted to improve the limitations of this pilot study.

Second-look arthroscopic findings after repairs of posterior root tears of the medial meniscus.

PubMed

Seo, Hee-Soo; Lee, Su-Chan; Jung, Kwang-Am

2011-01-01

A posterior root tear of the medial meniscus disrupts hoop tension and causes extrusion of the meniscus, which results in progressive cartilage degeneration. To identify the structural integrity of healing after arthroscopic repair of a posterior root tear of the medial meniscus by second-look arthroscopy and to determine the clinical relevance of the findings. Case series; Level of evidence, 4. From December 2006 to August 2008, 21 consecutive patients underwent arthroscopic pullout suture repair for a posterior root tear of the medial meniscus. Eleven were available for second-look arthroscopy evaluation (mean, 13.4 months; range, 10 to 22 months). The healing status of the repaired meniscus was classified as complete healing, lax healing, scar tissue healing, and failed healing. Chondral lesions were reviewed using arthroscopic photographs, and clinical evaluation was based on the Lysholm knee scores and the Hospital for Special Surgery scores. There was no case with complete healing. Five knees had lax healing (symptomatic in 2 and asymptomatic in 3); 4, scar tissue healing (asymptomatic in all 4); and 2, failed healing (symptomatic in 1 and asymptomatic in 1). Progression of the chondral lesion was found in 1 case. Mean Lysholm scores improved from 56.1 preoperatively (range, 41 to 71) to 83.0 at follow-up (range, 69 to 91; P = .003); mean Hospital for Special Surgery score also significantly increased, from 64.1 (range, 50 to 76) to 87.4 (range, 77 to 95; P = .003). Complete healing was not observed in this retrospective case series of posterior horn meniscus repairs performed by 2 surgeons using a single technique. Further research is needed to clarify why all patients showed clinical improvement despite findings of incomplete or failed healing on second-look arthroscopy. Treatment modalities for managing posterior root tears of the medial meniscus require further investigation to determine their efficacy.

[Human papillomavirus infection and its correlates with clinically relevant gynecological and obstetric conditions: A cross-sectional study].

PubMed

López-Hernández, Daniel; Beltrán-Lagunes, Luis; Brito-Aranda, Leticia; López-Hernández, Maria de la Luz

2016-08-05

To analyze the prevalence of human papillomavirus (HPV) infection and the possible epidemiological association with conditions of clinical relevance in women. A cross-sectional study from Mexico City was conducted from January 2012 to December 2014. HPV molecular detection was performed on cervical samples. Data were analyzed with appropriated statistic tests. A total of 1,604 females (median 47, interquartile range 38-54) were analyzed. Global prevalence of infection for any HPV is 9.91% (95% CI 8.6-11.3). An association between infection with 16-HPV and number of abortions (NA) (OR=1.427; 95% CI 1.091-1.866), by univariate regression model (UVRM) was estimated. Moreover, menarche (OR=1.566; 95% CI 1.079-2.272), NA (OR=1.570; 95% CI 1.106-2.227) and number of pregnancies (NP) (OR=0.461; 95% CI 0.260-0.818) have a direct and inverse association with infection by genotype 18 of HPV, respectively. Also, infection with HR-HPV genotypes has an inverse association with NP (OR=0.791; 95% CI 0.707-0.884) by normal labor (OR=0.867; 95% CI 0.767-0.979) and NA (OR=0.715; 95% CI 0.534-0.959) (UVRM), and a direct association with number of sexual partners (OR=1.082; 95% CI 1.015-1.154). Onset of sexual activity has an inverse association with infection by genotype 16- (UVRM: OR=0.814; 95% CI 0.715-0.926; multinomial regression model (MNRM): OR=0.803; 95% CI 0.702-0.918) and HR-HPV (UVRM: OR=0.933; 95% CI 0.889-0.980, and MNRM: OR=0.912; 95% CI 0.867-0.959), all P values were lower than .03. Prevalence of HPV cervical infection is different according to age and it is associated with several medical conditions of clinical relevance in women. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Covalent immobilisation of antibodies in Teflon-FEP microfluidic devices for the sensitive quantification of clinically relevant protein biomarkers.

PubMed

Pivetal, Jeremy; Pereira, Filipa M; Barbosa, Ana I; Castanheira, Ana P; Reis, Nuno M; Edwards, Alexander D

2017-03-13

This study reports for the first time the sensitive colorimetric and fluorescence detection of clinically relevant protein biomarkers by sandwich immunoassays using the covalent immobilisation of antibodies onto the fluoropolymer surface inside Teflon®-FEP microfluidic devices. Teflon®-FEP has outstanding optical transparency ideal for high-sensitivity colorimetric and fluorescence bioassays, however this thermoplastic is regarded as chemically inert and very hydrophobic. Covalent immobilisation can offer benefits over passive adsorption to plastic surfaces by allowing better control over antibody density, orientation and analyte binding capacity, and so we tested a range of different and novel covalent immobilisation strategies. We first functionalised the inner surface of a 10-bore, 200 μm internal diameter FEP microcapillary film with high-molecular weight polyvinyl alcohol (PVOH) without changing the outstanding optical transparency of the device delivered by the matched refractive index of FEP and water. Glutaraldehyde immobilisation was compared with the use of photoactivated linkers and NHS-ester crosslinkers for covalently immobilising capture antibodies onto PVOH. Three clinically relevant sandwich ELISAs were tested against the cytokine IL-1β, the myocardial infarct marker cardiac troponin I (cTnI), and the chronic heart failure marker brain natriuretic peptide (BNP). Overall, glutaraldehyde immobilisation was effective for BNP assays, but yielded unacceptable background for IL-1β and cTnI assays caused by direct binding of the biotinylated detection antibody to the modified PVOH surface. We found NHS-ester groups reacted with APTES-treated PVOH coated fluoropolymers. This facilitated a novel method for capture antibody immobilisation onto fluoropolymer devices using a bifunctional NHS-maleimide crosslinker. The density of covalently immobilised capture antibodies achieved using PVOH/APTES/NHS/maleimide approached levels seen with passive adsorption, and sensitive and quantitative assay performance was achieved using this method. Overall, the PVOH coating provided an excellent surface for controlled covalent antibody immobilisation onto Teflon®-FEP for performing high-sensitivity immunoassays.

Parylene MEMS patency sensor for assessment of hydrocephalus shunt obstruction.

PubMed

Kim, Brian J; Jin, Willa; Baldwin, Alexander; Yu, Lawrence; Christian, Eisha; Krieger, Mark D; McComb, J Gordon; Meng, Ellis

2016-10-01

Neurosurgical ventricular shunts inserted to treat hydrocephalus experience a cumulative failure rate of 80 % over 12 years; obstruction is responsible for most failures with a majority occurring at the proximal catheter. Current diagnosis of shunt malfunction is imprecise and involves neuroimaging studies and shunt tapping, an invasive measurement of intracranial pressure and shunt patency. These patients often present emergently and a delay in care has dire consequences. A microelectromechanical systems (MEMS) patency sensor was developed to enable direct and quantitative tracking of shunt patency in order to detect proximal shunt occlusion prior to the development of clinical symptoms thereby avoiding delays in treatment. The sensor was fabricated on a flexible polymer substrate to eventually allow integration into a shunt. In this study, the sensor was packaged for use with external ventricular drainage systems for clinical validation. Insights into the transduction mechanism of the sensor were obtained. The impact of electrode size, clinically relevant temperatures and flows, and hydrogen peroxide (H2O2) plasma sterilization on sensor function were evaluated. Sensor performance in the presence of static and dynamic obstruction was demonstrated using 3 different models of obstruction. Electrode size was found to have a minimal effect on sensor performance and increased temperature and flow resulted in a slight decrease in the baseline impedance due to an increase in ionic mobility. However, sensor response did not vary within clinically relevant temperature and flow ranges. H2O2 plasma sterilization also had no effect on sensor performance. This low power and simple format sensor was developed with the intention of future integration into shunts for wireless monitoring of shunt state and more importantly, a more accurate and timely diagnosis of shunt failure.

A systematic review of what factors attract and retain nurses in aged and dementia care.

PubMed

Chenoweth, Lynn; Jeon, Yun-Hee; Merlyn, Teri; Brodaty, Henry

2010-01-01

To present evidence-based factors for the recruitment and retention of licensed nurses caring for older people and persons with dementia. The international nurse shortage crisis is intensified in the aged and dementia care sector. Strategies to address this crisis rely on qualitative, quasi-experimental, anecdotal and unsubstantiated literature. Systematic literature review. Search terms 'nurse''nurses''nursing''clinical supervision''staff''staffing''staff mix''staff levels''recruitment''retention''aged care''gerontology''gerontological''dementia care''residential''nursing home,' were used in all possible combinations and applied in a wide range of relevant academic databases, with secondary hand searches of selected bibliographies. Two hundred and twenty-six papers were retrieved and scanned, with 105 chosen for closer examination that were relevant to recruitment and retention strategies for dementia and aged care nursing. Twenty-five of the papers chosen for review were rated at level 2++ to 3, according to the guidelines of the National Institute for Health and Clinical Excellence (The NICE Guidelines Manual, National Institute for Health and Clinical Excellence, London). The 25 critically reviewed papers are organised as promising strategies for (1) nurse recruitment and (2) nurse retention. The intrinsic rewards of the caring role attract nurses to dementia and aged care. Essential strategies linking recruitment with retention are: careful selection of student nurse clinical placements and their ongoing supervision and education, training for skills, leadership and teamwork for new and existing nurses, increased staffing levels, pay parity across different health settings and family friendly policies. A family-friendly, learning environment that values and nurtures its nursing staff, in the same way as nurses are expected to value and care for their patients and residents, is critical in ensuring their retention in dementia and aged care.

Prevalence of sleep breathing complaints reported by treatment-seeking chronic insomnia disorder patients on presentation to a sleep medical center: a preliminary report.

PubMed

Krakow, Barry; Ulibarri, Victor A

2013-03-01

Few studies have examined the co-morbidity between insomnia and sleep-disordered breathing in the clinical setting. This study evaluated treatment-seeking insomnia patients and their self-report of sleep breathing complaints. A retrospective chart review was conducted on 1,035 consecutive treatment-seeking, chronic insomnia patients who reported insomnia as their primary problem upon seeking care at a private, community-based sleep medical center. Measurements included the insomnia severity index, standard subjective sleep measures as well as rankings, attributions, and self-reports about sleep breathing disorders, problems, and symptoms. A total of 1,035 adult, treatment-seeking insomnia patients indicated insomnia interfered with daytime functioning, and their average insomnia severity was in the range of a clinically relevant problem: total sleep time (5.50 h, SD = 1.60), sleep efficiency (71.05 %, SD = 18.26), wake time after sleep onset (120.70 min, SD = 92.56), and an insomnia severity index (18.81, SD = 5.09). Of these 1,035 insomnia patients, 42 % also ranked a sleep breathing disorder among their list of reasons for seeking treatment, another 13 % revealed a concern about a sleep breathing problem, and another 26 % reported awareness of sleep breathing symptoms. Only 19 % of this clinical insomnia sample reported no awareness or concerns about sleep breathing disorders, problems, or symptoms. A greater proportion of men than women reported significantly more sleep breathing disorders, problems, or symptoms. Sleep breathing complaints were extremely common among a large sample of treatment-seeking, self-identified, adult chronic insomnia patients. Prospective prevalence research is needed to corroborate or revise these findings, and polysomnography should be considered in appropriate cohorts to determine the clinical relevance of treatment-seeking chronic insomnia patients' sleep breathing complaints.

Self-reported indications for antidepressant use in a population-based cohort of middle-aged and elderly.

PubMed

Aarts, Nikkie; Noordam, Raymond; Hofman, Albert; Tiemeier, Henning; Stricker, Bruno H; Visser, Loes E

2016-10-01

Background Population-based studies investigating indications for antidepressant prescribing mostly rely on diagnoses from general practitioners. However, diagnostic codes might be incomplete and drugs may be prescribed 'off-label' for indications not investigated in clinical trials. Objective We aimed to study indications for antidepressant use based on self-report. Also, we studied the presence of depressive symptoms associated with the self-reported indications. Setting Our study population of antidepressant users was selected based on interview data between 1997 and 2013 from the prospective population-based Rotterdam Study cohort (age >45 years). Method Antidepressant use, self-reported indication for use, and presence of depressive symptoms (Center for Epidemiological Studies Depression Scale) were based on interview. Self-reported indications were categorized by the researchers into officially approved, clinically-accepted and commonly mentioned off-label indications. Main outcome measures A score of 16 and higher on the Center for Epidemiological Studies Depression Scale was considered as indicator for clinically-relevant depressive symptoms. Results The majority of 914 antidepressant users reported 'depression' (52.4 %) as indication for treatment. Furthermore, anxiety, stress and sleep disorders were reported in selective serotonin reuptake inhibitor and other antidepressant users (ranging from 5.9 to 13.3 %). The indication 'pain' was commonly mentioned by tricyclic antidepressant users (19.0 %). Indications were statistically significantly associated with higher depressive symptom scores when compared to non-users (n = 10,979). Conclusions Depression was the main indication for antidepressant treatment. However, our findings suggest that antidepressants are also used for off-label indications, subthreshold disorders and complex situations, which were all associated with clinically-relevant depressive symptoms in the middle-aged and elderly population.

Curtailing the high rate of late-stage attrition of investigational therapeutics against unprecedented targets in patients with lung and other malignancies.

PubMed

Rowinsky, Eric K

2004-06-15

A greater understanding of the pathogenesis and biology of cancer coupled with major advances in biotechnology has resulted in the identification of rationally designed, target-based (RDTB) anticancer therapeutics, ushering in new therapeutic opportunities and high expectations for the future as well as developmental challenges. Because these agents appear to principally target malignant cells, it is expected that they will produce less toxicity at clinically effective doses than nonspecific cytotoxic agents, but their target requirements are likely to be much more stringent. The innate complexity of the networks that contain elements targeted by these agents also decreases the probability that any single therapeutic manipulation will result in robust clinical activity and success when used alone, particularly in patients with solid malignancies that have multiple relevant signaling aberrations. In contrast, proof of principle and robust antitumor activity may be most efficiently demonstrated in nonrandomized evaluations involving tumors that are principally driven by aberrations of the specific target. The predominant therapeutic manifestation of RDTB agents in preclinical studies is due to decreased tumor growth rates and will likely be similar in the clinic; however, such manifestations are not readily detectable and quantifiable using nonrandomized clinical evaluations. To curtail the increasing rate of late-stage attrition of RDTB agents, which, if maintained, will stymie progress in cancer therapy, the design of initial nonrandomized evaluations, particularly the selection of tumors and patients, must be guided by the principal biological features of the agents. Next, evaluations, some of which must be randomized, can be performed in a wide range of tumor types, depending on the presence and relevance of the target. To validate the concept of RDTB therapeutics and to realize their full potential, radically different development, evaluation, and regulatory paradigms must be adopted.

Validation of the diagnosis of autism in general practitioner records

PubMed Central

Fombonne, Eric; Heavey, Lisa; Smeeth, Liam; Rodrigues, Laura C; Cook, Claire; Smith, Peter G; Meng, Linyan; Hall, Andrew J

2004-01-01

Background We report on the validity of the computerized diagnoses of autism in a large case-control study investigating the possible association between autism and the measles, mumps and rubella vaccine in the UK using the General Practitioner Research Database (GPRD). We examined anonymized copies of all relevant available clinical reports, including general practitioners' (GP) notes, consultant, speech therapy and educational psychologists reports, on 318 subjects born between 1973 and 1997 with a diagnosis of autism or a related disorder recorded in their electronic general practice record. Methods Data were abstracted to a case validation form allowing for the identification of developmental symptoms relevant to the diagnosis of pervasive developmental disorders (PDDs). Information on other background clinical and familial features was also abstracted. A subset of 50 notes was coded independently by 2 raters to derive reliability estimates for key clinical characteristics. Results For 294 subjects (92.5%) the diagnosis of PDD was confirmed after review of the records. Of these, 180 subjects (61.2%) fulfilled criteria for autistic disorder. The mean age at first recording of a PDD diagnosis in the GPRD database was 6.3 years (SD = 4.6). Consistent with previous estimates, the proportion of subjects experiencing regression in the course of their development was 19%. Inter-rater reliability for the presence of a PDD diagnosis was good (kappa = .73), and agreement on clinical features such as regression, age of parental recognition of first symptoms, language delay and presence of epilepsy was also good (kappas ranging from .56 to 1.0). Conclusions This study provides evidence that the positive predictive value of a diagnosis of autism recorded in the GPRD is high. PMID:15113435

A mouse diversity panel approach reveals the potential for clinical kidney injury due to DB289 not predicted by classical rodent models.

PubMed

Harrill, Alison H; Desmet, Kristina D; Wolf, Kristina K; Bridges, Arlene S; Eaddy, J Scott; Kurtz, C Lisa; Hall, J Ed; Paine, Mary F; Tidwell, Richard R; Watkins, Paul B

2012-12-01

DB289 is the first oral drug shown in clinical trials to have efficacy in treating African trypanosomiasis (African sleeping sickness). Mild liver toxicity was noted but was not treatment limiting. However, development of DB289 was terminated when several treated subjects developed severe kidney injury, a liability not predicted from preclinical testing. We tested the hypothesis that the kidney safety liability of DB289 would be detected in a mouse diversity panel (MDP) comprised of 34 genetically diverse inbred mouse strains. MDP mice received 10 days of oral treatment with DB289 or vehicle and classical renal biomarkers blood urea nitrogen (BUN) and serum creatinine (sCr), as well as urine biomarkers of kidney injury were measured. While BUN and sCr remained within reference ranges, marked elevations were observed for kidney injury molecule-1 (KIM-1) in the urine of sensitive mouse strains. KIM-1 elevations were not always coincident with elevations in alanine aminotransferase (ALT), suggesting that renal injury was not linked to hepatic injury. Genome-wide association analyses of KIM-1 elevations indicated that genes participating in cholesterol and lipid biosynthesis and transport, oxidative stress, and cytokine release may play a role in DB289 renal injury. Taken together, the data resulting from this study highlight the utility of using an MDP to predict clinically relevant toxicities, to identify relevant toxicity biomarkers that may translate into the clinic, and to identify potential mechanisms underlying toxicities. In addition, the sensitive mouse strains identified in this study may be useful in screening next-in-class compounds for renal injury.

Sources of inaccuracy in the measurement of adult patients’ resting blood pressure in clinical settings: a systematic review

PubMed Central

Kallioinen, Noa; Hill, Andrew; Horswill, Mark S.; Ward, Helen E.; Watson, Marcus O.

2017-01-01

Background: To interpret blood pressure (BP) data appropriately, healthcare providers need to be knowledgeable of the factors that can potentially impact the accuracy of BP measurement and contribute to variability between measurements. Methods: A systematic review of studies quantifying BP measurement inaccuracy. Medline and CINAHL databases were searched for empirical articles and systematic reviews published up to June 2015. Empirical articles were included if they reported a study that was relevant to the measurement of adult patients’ resting BP at the upper arm in a clinical setting (e.g. ward or office); identified a specific source of inaccuracy; and quantified its effect. Reference lists and reviews were searched for additional articles. Results: A total of 328 empirical studies were included. They investigated 29 potential sources of inaccuracy, categorized as relating to the patient, device, procedure or observer. Significant directional effects were found for 27; however, for some, the effects were inconsistent in direction. Compared with true resting BP, significant effects of individual sources ranged from −23.6 to +33 mmHg SBP and −14 to +23 mmHg DBP. Conclusion: A single BP value outside the expected range should be interpreted with caution and not taken as a definitive indicator of clinical deterioration. Where a measurement is abnormally high or low, further measurements should be taken and averaged. Wherever possible, BP values should be recorded graphically within ranges. This may reduce the impact of sources of inaccuracy and reduce the scope for misinterpretations based on small, likely erroneous or misleading, changes. PMID:27977471

Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice.

PubMed

Scharf, Valery F; Farese, James P; Coomer, Alastair R; Milner, Rowan J; Taylor, David P; Salute, Marc E; Chang, Myron N; Neal, Dan; Siemann, Dietmar W

2013-05-01

Objective-To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals-27 athymic nude mice. Procedures-To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results-Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance-Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine-Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.

Point-of-Care Diagnostics for Niche Applications

PubMed Central

Cummins, Brian M.; Ligler, Frances S.; Walker, Glenn M.

2016-01-01

Point-of-care or point-of-use diagnostics are analytical devices that provide clinically relevant information without the need for a core clinical laboratory. In this review we define point-of-care diagnostics as portable versions of assays performed in a traditional clinical chemistry laboratory. This review discusses five areas relevant to human and animal health where increased attention could produce significant impact: veterinary medicine, space travel, sports medicine, emergency medicine, and operating room efficiency. For each of these areas, clinical need, available commercial products, and ongoing research into new devices are highlighted. PMID:26837054

Investigation of critical inter-related factors affecting the efficacy of pulsed light for inactivating clinically relevant bacterial pathogens.

PubMed

Farrell, H P; Garvey, M; Cormican, M; Laffey, J G; Rowan, N J

2010-05-01

To investigate critical electrical and biological factors governing the efficacy of pulsed light (PL) for the in vitro inactivation of bacteria isolated from the clinical environment. Development of this alternative PL decontamination approach is timely, as the incidence of health care-related infections remains unacceptably high. Predetermined cell numbers of clinically relevant Gram-positive and Gram-negative bacteria were inoculated separately on agar plates and were flashed with

Prevalence and relevance of the positivity of skin prick testing in patients with chronic urticaria.

PubMed

Kulthanan, Kanokvalai; Jiamton, Sukhum; Rutnin, Ni-on; Insawang, Metavee; Pinkaew, Sumrauy

2008-06-01

Many patients with chronic urticaria (CU) worry that foods or other allergens are responsible for their urticaria. Skin prick testing (SPT) may be one of the investigations used to provide a clear illustration. The purpose of our study was to assess the prevalence of positivity of SPT to food allergens and aeroallergens and their relevance in patients with CU, in order to demonstrate the diagnostic value of SPT in CU. We retrospectively reviewed case record forms of patients with chronic ordinary urticaria who underwent SPT in the Urticaria Clinic, Siriraj Hospital, during the period 2000-2004. The studied allergens included 16 food allergens and 12 aeroallergens. Eighty-eight patients were enrolled. The prevalence of positive SPT among patients with CU was 47.7%. Patients who had personal histories of atopy had statistically significant positive SPT results compared with patients who had negative SPT. Of 88 patients, 26 patients (30%) gave positive results to food allergens, 36 patients (41%) gave positive results to aeroallergens and 20 patients (22.7%) gave positive results to both food and aeroallergens. One-third of the subjects (34.6%) who had positive SPT results to food allergens had clinical relevance of food allergy in some systems but only one patient had clinical relevance of food-induced urticaria. Half of the patients who had a history of aeroallergen sensitivity gave a positive SPT response for aeroallergens; however, there was no clinical relevance to their CU. Our study showed that the prevalence of positive SPT to food allergens and aeroallergens in patients with CU was common but had little clinical relevance to CU.

Applications of mid-infrared spectroscopy in the clinical laboratory setting.

PubMed

De Bruyne, Sander; Speeckaert, Marijn M; Delanghe, Joris R

2018-01-01

Fourier transform mid-infrared (MIR-FTIR) spectroscopy is a nondestructive, label-free, highly sensitive and specific technique that provides complete information on the chemical composition of biological samples. The technique both can offer fundamental structural information and serve as a quantitative analysis tool. Therefore, it has many potential applications in different fields of clinical laboratory science. Although considerable technological progress has been made to promote biomedical applications of this powerful analytical technique, most clinical laboratory analyses are based on spectroscopic measurements in the visible or ultraviolet (UV) spectrum and the potential role of FTIR spectroscopy still remains unexplored. In this review, we present some general principles of FTIR spectroscopy as a useful method to study molecules in specimens by MIR radiation together with a short overview of methods to interpret spectral data. We aim at illustrating the wide range of potential applications of the proposed technique in the clinical laboratory setting with a focus on its advantages and limitations and discussing the future directions. The reviewed applications of MIR spectroscopy include (1) quantification of clinical parameters in body fluids, (2) diagnosis and monitoring of cancer and other diseases by analysis of body fluids, cells, and tissues, (3) classification of clinically relevant microorganisms, and (4) analysis of kidney stones, nails, and faecal fat.

THE GAP BETWEEN ECONOMIC EVALUATIONS AND CLINICAL PRACTICE: A SYSTEMATIC REVIEW OF ECONOMIC EVALUATIONS ON DABIGATRAN FOR ATRIAL FIBRILLATION.

PubMed

Rolden, Herbert J A; van der Wilt, Gert Jan; Maas, Angela H E M; Grutters, Janneke P C

2018-06-18

As model-based economic evaluations (MBEEs) are widely used to make decisions in the context of policy, it is imperative that they represent clinical practice. Here, we assess the relevance of MBEEs on dabigatran for the prevention of stroke in patients with atrial fibrillation (AF). We performed a systematic review on the basis of a developed questionnaire, tailored to oral anticoagulation in patients with AF. Included studies had a full body text in English, compared dabigatran with a vitamin K antagonist, were not dedicated to one or more subgroup(s), and yielded an incremental cost-effectiveness ratio. The relevance of all MBEEs was assessed on the basis of ten context-independent factors, which encompassed clinical outcomes and treatment duration. The MBEEs performed for the United States were assessed on the basis of seventeen context-dependent factors, which were related to the country's target population and clinical environment. The search yielded twenty-nine MBEEs, of which six were performed for the United States. On average, 54 percent of the context-independent factors were included per study, and 37 percent of the seventeen context-dependent factors in the U.S. The share of relevant factors per study did not increase over time. MBEEs on dabigatran leave out several relevant factors, limiting their usefulness to decision makers. We strongly urge health economic researchers to improve the relevance of their MBEEs by including context-independent relevance factors, and modeling context-dependent factors befitting the decision context concerned.

Clinical relevance of pharmacist intervention in an emergency department.

PubMed

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

2017-08-01

To evaluate the clinical relevance of pharmacist intervention on patient care in emergencies, to determine the severity of detected errors. Second, to analyse the most frequent types of interventions and type of drugs involved and to evaluate the clinical pharmacist's activity. A 6-month observational prospective study of pharmacist intervention in the Emergency Department (ED) at a 400-bed hospital in Spain was performed to record interventions carried out by the clinical pharmacists. We determined whether the intervention occurred in the process of medication reconciliation or another activity, and whether the drug involved belonged to the High-Alert Medications Institute for Safe Medication Practices (ISMP) list. To evaluate the severity of the errors detected and clinical relevance of the pharmacist intervention, a modified assessment scale of Overhage and Lukes was used. Relationship between clinical relevance of pharmacist intervention and the severity of medication errors was assessed using ORs and Spearman's correlation coefficient. During the observation period, pharmacists reviewed the pharmacotherapy history and medication orders of 2984 patients. A total of 991 interventions were recorded in 557 patients; 67.2% of the errors were detected during medication reconciliation. Medication errors were considered severe in 57.2% of cases and 64.9% of pharmacist intervention were considered relevant. About 10.9% of the drugs involved are in the High-Alert Medications ISMP list. The severity of the medication error and the clinical significance of the pharmacist intervention were correlated (Spearman's ρ=0.728/p<0.001). In this single centre study, the clinical pharmacists identified and intervened on a high number of severe medication errors. This suggests that emergency services will benefit from pharmacist-provided drug therapy services. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Cancer Genome Atlas Clinical Explorer: a web and mobile interface for identifying clinical-genomic driver associations.

PubMed

Lee, HoJoon; Palm, Jennifer; Grimes, Susan M; Ji, Hanlee P

2015-10-27

The Cancer Genome Atlas (TCGA) project has generated genomic data sets covering over 20 malignancies. These data provide valuable insights into the underlying genetic and genomic basis of cancer. However, exploring the relationship among TCGA genomic results and clinical phenotype remains a challenge, particularly for individuals lacking formal bioinformatics training. Overcoming this hurdle is an important step toward the wider clinical translation of cancer genomic/proteomic data and implementation of precision cancer medicine. Several websites such as the cBio portal or University of California Santa Cruz genome browser make TCGA data accessible but lack interactive features for querying clinically relevant phenotypic associations with cancer drivers. To enable exploration of the clinical-genomic driver associations from TCGA data, we developed the Cancer Genome Atlas Clinical Explorer. The Cancer Genome Atlas Clinical Explorer interface provides a straightforward platform to query TCGA data using one of the following methods: (1) searching for clinically relevant genes, micro RNAs, and proteins by name, cancer types, or clinical parameters; (2) searching for genomic/proteomic profile changes by clinical parameters in a cancer type; or (3) testing two-hit hypotheses. SQL queries run in the background and results are displayed on our portal in an easy-to-navigate interface according to user's input. To derive these associations, we relied on elastic-net estimates of optimal multiple linear regularized regression and clinical parameters in the space of multiple genomic/proteomic features provided by TCGA data. Moreover, we identified and ranked gene/micro RNA/protein predictors of each clinical parameter for each cancer. The robustness of the results was estimated by bootstrapping. Overall, we identify associations of potential clinical relevance among genes/micro RNAs/proteins using our statistical analysis from 25 cancer types and 18 clinical parameters that include clinical stage or smoking history. The Cancer Genome Atlas Clinical Explorer enables the cancer research community and others to explore clinically relevant associations inferred from TCGA data. With its accessible web and mobile interface, users can examine queries and test hypothesis regarding genomic/proteomic alterations across a broad spectrum of malignancies.

Clinical-decision support based on medical literature: A complex network approach

NASA Astrophysics Data System (ADS)

Jiang, Jingchi; Zheng, Jichuan; Zhao, Chao; Su, Jia; Guan, Yi; Yu, Qiubin

2016-10-01

In making clinical decisions, clinicians often review medical literature to ensure the reliability of diagnosis, test, and treatment because the medical literature can answer clinical questions and assist clinicians making clinical decisions. Therefore, finding the appropriate literature is a critical problem for clinical-decision support (CDS). First, the present study employs search engines to retrieve relevant literature about patient records. However, the result of the traditional method is usually unsatisfactory. To improve the relevance of the retrieval result, a medical literature network (MLN) based on these retrieved papers is constructed. Then, we show that this MLN has small-world and scale-free properties of a complex network. According to the structural characteristics of the MLN, we adopt two methods to further identify the potential relevant literature in addition to the retrieved literature. By integrating these potential papers into the MLN, a more comprehensive MLN is built to answer the question of actual patient records. Furthermore, we propose a re-ranking model to sort all papers by relevance. We experimentally find that the re-ranking model can improve the normalized discounted cumulative gain of the results. As participants of the Text Retrieval Conference 2015, our clinical-decision method based on the MLN also yields higher scores than the medians in most topics and achieves the best scores for topics: #11 and #12. These research results indicate that our study can be used to effectively assist clinicians in making clinical decisions, and the MLN can facilitate the investigation of CDS.

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma

PubMed Central

Medeiros, Felipe A.

2017-01-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials. PMID:28475699

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma.

PubMed

Medeiros, Felipe A

2017-05-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials.

The development and validation of a meta-tool for quality appraisal of public health evidence: Meta Quality Appraisal Tool (MetaQAT).

PubMed

Rosella, L; Bowman, C; Pach, B; Morgan, S; Fitzpatrick, T; Goel, V

2016-07-01

Most quality appraisal tools were developed for clinical medicine and tend to be study-specific with a strong emphasis on risk of bias. In order to be more relevant to public health, an appropriate quality appraisal tool needs to be less reliant on the evidence hierarchy and consider practice applicability. Given the broad range of study designs used in public health, the objective of this study was to develop and validate a meta-tool that combines public health-focused principles of appraisal coupled with a set of design-specific companion tools. Several design methods were used to develop and validate the tool including literature review, synthesis, and validation with a reference standard. A search of critical appraisal tools relevant to public health was conducted; core concepts were collated. The resulting framework was piloted during three feedback sessions with public health practitioners. Following subsequent revisions, the final meta-tool, the Meta Quality Appraisal Tool (MetaQAT), was then validated through a content analysis of appraisals conducted by two groups of experienced public health researchers (MetaQAT vs generic appraisal form). The MetaQAT framework consists of four domains: relevancy, reliability, validity, and applicability. In addition, a companion tool was assembled from existing critical appraisal tools to provide study design-specific guidance on validity appraisal. Content analysis showed similar methodological and generalizability concerns were raised by both groups; however, the MetaQAT appraisers commented more extensively on applicability to public health practice. Critical appraisal tools designed for clinical medicine have limitations for use in the context of public health. The meta-tool structure of the MetaQAT allows for rigorous appraisal, while allowing users to simultaneously appraise the multitude of study designs relevant to public health research and assess non-standard domains, such as applicability. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Suspected zonisamide-related anticonvulsant hypersensitivity syndrome in a cat.

PubMed

Collinet, Audrey; Sammut, Veronique

2017-12-15

CASE DESCRIPTION A 2-year-old neutered male domestic shorthair cat was evaluated for sudden onset of cluster seizures. CLINICAL FINDINGS At an emergency clinic, the cat had hyperimmunoglobulinemia and thrombocytopenia. On referral, treatment with levetiracetam, zonisamide, and phenobarbital initially provided good control of cluster seizure activity (attributable to epilepsy of unknow origin). Two weeks later, assessments revealed that serum phenobarbital concentration was within the ideal range but serum zonisamide concentration exceeded the recommended therapeutic range. The dosage of zonisamide was therefore decreased. Four days after dosage reduction, the cat developed generalized lymphadenopathy. Cytologic analysis of lymph node aspirate samples revealed a heterogeneous population of well-differentiated lymphocytes, interpreted as marked reactivity. Although neoplasia could not be ruled out, hypersensitivity to phenobarbital was suspected, and this treatment was discontinued. TREATMENT AND OUTCOME Despite cessation of phenobarbital administration, generalized peripheral lymphadenopathy progressed and hyperglobulinemia and cytopenias developed. These abnormalities resolved after discontinuation of zonisamide administration. The cat remained seizure free with no recurrence of the aforementioned concerns after reinstitution of phenobarbital treatment. CLINICAL RELEVANCE To the authors' knowledge, this is the first reported case of zonisamide-related lymphadenopathy, hyperglobulinemia, and cytopenias in a cat. Anticonvulsant hypersensitivity syndrome is well documented in human medicine, but little information has been published in the veterinary medical literature. Although the effects of anticonvulsant hypersensitivity syndrome in this cat were serious, these effects were reversible with treatment discontinuation.

Cost utility of maintenance treatment of recurrent depression with sertraline versus episodic treatment with dothiepin.

PubMed

Hatziandreu, E J; Brown, R E; Revicki, D A; Turner, R; Martindale, J; Levine, S; Siegel, J E

1994-03-01

The objective of this study was to model, for patients at risk of recurrent depression, the cost-utility of maintenance therapy with sertraline compared with treatment of acute episodes with dothiepin ('episodic treatment'). Using clinical decision analysis techniques, a Markov state-transition model was constructed to estimate the lifetime costs and quality-adjusted life-years (QALYs) of the 2 therapeutic strategies. The model follows 2 cohorts of 35-year-old women at high risk for recurrent depression over their lifetimes. Model construction and relevant data (probabilities) for performing the analysis were based on existing clinical knowledge. Two physician panels were used to obtain estimates of recurrence probabilities not available in the literature, health utilities, and resource consumption. Costs were obtained from published sources. The baseline analysis showed that it costs 2172 British pounds sterling ($US3692, 1991 currency) to save an additional QALY with sertraline maintenance treatment. Sensitivity analysis showed that the incremental cost-utility ratio ranged from 557 British pounds sterling to 5260 British pounds sterling per QALY. Overall, the resulting ratios are considered to be well within the range of cost-utility ratios that support the adoption and appropriate utilisation of a technology. Based on the study assumptions, long term maintenance treatment with sertraline appears to be clinically and economically justified choice for patients at high risk of recurrent depression.

Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions.

PubMed

Whitlow, Jonathan; Pacelli, Settimio; Paul, Arghya

2017-09-10

With recent advances in the field of nanomedicine, many new strategies have emerged for diagnosing and treating diseases. At the forefront of this multidisciplinary research, carbon nanomaterials have demonstrated unprecedented potential for a variety of regenerative medicine applications including novel drug delivery platforms that facilitate the localized and sustained release of therapeutics. Nanodiamonds (NDs) are a unique class of carbon nanoparticles that are gaining increasing attention for their biocompatibility, highly functional surfaces, optical properties, and robust physical properties. Their remarkable features have established NDs as an invaluable regenerative medicine platform, with a broad range of clinically relevant applications ranging from targeted delivery systems for insoluble drugs, bioactive substrates for stem cells, and fluorescent probes for long-term tracking of cells and biomolecules in vitro and in vivo. This review introduces the synthesis techniques and the various routes of surface functionalization that allow for precise control over the properties of NDs. It also provides an in-depth overview of the current progress made toward the use of NDs in the fields of drug delivery, tissue engineering, and bioimaging. Their future outlook in regenerative medicine including the current clinical significance of NDs, as well as the challenges that must be overcome to successfully translate the reviewed technologies from research platforms to clinical therapies will also be discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Is Dysfunctional Use of the Mobile Phone a Behavioural Addiction? Confronting Symptom-Based Versus Process-Based Approaches.

PubMed

Billieux, Joël; Philippot, Pierre; Schmid, Cécile; Maurage, Pierre; De Mol, Jan; Van der Linden, Martial

2015-01-01

Dysfunctional use of the mobile phone has often been conceptualized as a 'behavioural addiction' that shares most features with drug addictions. In the current article, we challenge the clinical utility of the addiction model as applied to mobile phone overuse. We describe the case of a woman who overuses her mobile phone from two distinct approaches: (1) a symptom-based categorical approach inspired from the addiction model of dysfunctional mobile phone use and (2) a process-based approach resulting from an idiosyncratic clinical case conceptualization. In the case depicted here, the addiction model was shown to lead to standardized and non-relevant treatment, whereas the clinical case conceptualization allowed identification of specific psychological processes that can be targeted with specific, empirically based psychological interventions. This finding highlights that conceptualizing excessive behaviours (e.g., gambling and sex) within the addiction model can be a simplification of an individual's psychological functioning, offering only limited clinical relevance. The addiction model, applied to excessive behaviours (e.g., gambling, sex and Internet-related activities) may lead to non-relevant standardized treatments. Clinical case conceptualization allowed identification of specific psychological processes that can be targeted with specific empirically based psychological interventions. The biomedical model might lead to the simplification of an individual's psychological functioning with limited clinical relevance. Copyright © 2014 John Wiley & Sons, Ltd.

Dental Blogs, Podcasts, and Associated Social Media: Descriptive Mapping and Analysis

PubMed Central

Hicks, Diana; Rosenblum, Simone; Isett, Kimberley R; Elliott, Jacqueline

2017-01-01

Background Studies of social media in both medicine and dentistry have largely focused on the value of social media for marketing to and communicating with patients and for clinical education. There is limited evidence of how dental clinicians contribute to and use social media to disseminate and access information relevant to clinical care. Objective The purpose of this study was to inventory and assess the entry, growth, sources, and content of clinically relevant social media in dentistry. Methods We developed an inventory of blogs, podcasts, videos, and associated social media disseminating clinical information to dentists. We assessed hosts’ media activity in terms of their combinations of modalities, entry and exit dates, frequency of posting, types of content posted, and size of audience. Results Our study showed that clinically relevant information is posted by dentists and hygienists on social media. Clinically relevant information was provided in 89 blogs and podcasts, and topic analysis showed motives for blogging by host type: 55% (49 hosts) were practicing dentists or hygienists, followed by consultants (27 hosts, 30%), media including publishers and discussion board hosts (8 hosts, 9%), and professional organizations and corporations. Conclusions We demonstrated the participation of and potential for practicing dentists and hygienists to use social media to share clinical and other information with practicing colleagues. There is a clear audience for these social media sites, suggesting a changing mode of information diffusion in dentistry. This study was a first effort to fill the gap in understanding the nature and potential role of social media in clinical dentistry. PMID:28747291

Epidermal mechano-acoustic sensing electronics for cardiovascular diagnostics and human-machine interfaces.

PubMed

Liu, Yuhao; Norton, James J S; Qazi, Raza; Zou, Zhanan; Ammann, Kaitlyn R; Liu, Hank; Yan, Lingqing; Tran, Phat L; Jang, Kyung-In; Lee, Jung Woo; Zhang, Douglas; Kilian, Kristopher A; Jung, Sung Hee; Bretl, Timothy; Xiao, Jianliang; Slepian, Marvin J; Huang, Yonggang; Jeong, Jae-Woong; Rogers, John A

2016-11-01

Physiological mechano-acoustic signals, often with frequencies and intensities that are beyond those associated with the audible range, provide information of great clinical utility. Stethoscopes and digital accelerometers in conventional packages can capture some relevant data, but neither is suitable for use in a continuous, wearable mode, and both have shortcomings associated with mechanical transduction of signals through the skin. We report a soft, conformal class of device configured specifically for mechano-acoustic recording from the skin, capable of being used on nearly any part of the body, in forms that maximize detectable signals and allow for multimodal operation, such as electrophysiological recording. Experimental and computational studies highlight the key roles of low effective modulus and low areal mass density for effective operation in this type of measurement mode on the skin. Demonstrations involving seismocardiography and heart murmur detection in a series of cardiac patients illustrate utility in advanced clinical diagnostics. Monitoring of pump thrombosis in ventricular assist devices provides an example in characterization of mechanical implants. Speech recognition and human-machine interfaces represent additional demonstrated applications. These and other possibilities suggest broad-ranging uses for soft, skin-integrated digital technologies that can capture human body acoustics.

Ultrasonic propulsion of kidney stones.

PubMed

May, Philip C; Bailey, Michael R; Harper, Jonathan D

2016-05-01

Ultrasonic propulsion is a novel technique that uses short bursts of focused ultrasonic pulses to reposition stones transcutaneously within the renal collecting system and ureter. The purpose of this review is to discuss the initial testing of effectiveness and safety, directions for refinement of technique and technology, and opinions on clinical application. Preclinical studies with a range of probes, interfaces, and outputs have demonstrated feasibility and consistent safety of ultrasonic propulsion with room for increased outputs and refinement toward specific applications. Ultrasonic propulsion was used painlessly and without adverse events to reposition stones in 14 of 15 human study participants without restrictions on patient size, stone size, or stone location. The initial feasibility study showed applicability in a range of clinically relevant situations, including facilitating passage of residual fragments following ureteroscopy or shock wave lithotripsy, moving a large stone at the ureteropelvic junction with relief of pain, and differentiating large stones from a collection of small fragments. Ultrasonic propulsion shows promise as an office-based system for transcutaneously repositioning kidney stones. Potential applications include facilitating expulsion of residual fragments following ureteroscopy or shock wave lithotripsy, repositioning stones prior to treatment, and repositioning obstructing ureteropelvic junction stones into the kidney to alleviate acute renal colic.

Ultrasonic propulsion of kidney stones

PubMed Central

May, Philip C.; Bailey, Michael R.; Harper, Jonathan D.

2016-01-01

Purpose of review Ultrasonic propulsion is a novel technique that uses short bursts of focused ultrasonic pulses to reposition stones transcutaneously within the renal collecting system and ureter. The purpose of this review is to discuss the initial testing of effectiveness and safety, directions for refinement of technique and technology, and opinions on clinical application. Recent findings Preclinical studies with a range of probes, interfaces, and outputs have demonstrated feasibility and consistent safety of ultrasonic propulsion with room for increased outputs and refinement toward specific applications. Ultrasonic propulsion was used painlessly and without adverse events to reposition stones in 14 of 15 human study participants without restrictions on patient size, stone size, or stone location. The initial feasibility study showed applicability in a range of clinically relevant situations, including facilitating passage of residual fragments following ureteroscopy or shock wave lithotripsy, moving a large stone at the UPJ with relief of pain, and differentiating large stones from a collection of small fragments. Summary Ultrasonic propulsion shows promise as an office-based system for transcutaneously repositioning kidney stones. Potential applications include facilitating expulsion of residual fragments following ureteroscopy or shock wave lithotripsy, repositioning stones prior to treatment, and repositioning obstructing UPJ stones into the kidney to alleviate acute renal colic. PMID:26845428

Si-strip photon counting detectors for contrast-enhanced spectral mammography

NASA Astrophysics Data System (ADS)

Chen, Buxin; Reiser, Ingrid; Wessel, Jan C.; Malakhov, Nail; Wawrzyniak, Gregor; Hartsough, Neal E.; Gandhi, Thulasi; Chen, Chin-Tu; Iwanczyk, Jan S.; Barber, William C.

2015-08-01

We report on the development of silicon strip detectors for energy-resolved clinical mammography. Typically, X-ray integrating detectors based on scintillating cesium iodide CsI(Tl) or amorphous selenium (a-Se) are used in most commercial systems. Recently, mammography instrumentation has been introduced based on photon counting Si strip detectors. The required performance for mammography in terms of the output count rate, spatial resolution, and dynamic range must be obtained with sufficient field of view for the application, thus requiring the tiling of pixel arrays and particular scanning techniques. Room temperature Si strip detector, operating as direct conversion x-ray sensors, can provide the required speed when connected to application specific integrated circuits (ASICs) operating at fast peaking times with multiple fixed thresholds per pixel, provided that the sensors are designed for rapid signal formation across the X-ray energy ranges of the application. We present our methods and results from the optimization of Si-strip detectors for contrast enhanced spectral mammography. We describe the method being developed for quantifying iodine contrast using the energy-resolved detector with fixed thresholds. We demonstrate the feasibility of the method by scanning an iodine phantom with clinically relevant contrast levels.

[Clinical recommendations for sport practice in diabetic patients (RECORD Guide). Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition (SEEN)].

PubMed

Gargallo-Fernández, Manuel; Escalada San Martín, Javier; Gómez-Peralta, Fernando; Rozas Moreno, Pedro; Marco Martínez, Amparo; Botella-Serrano, Marta; Tejera Pérez, Cristina; López Fernández, Judith

2015-01-01

Sporting activity is becoming a common practice in patients with diabetes mellitus (DM). This situation requires both a preliminary medical assessment and a wide range of changes in treatment which have scarcely been addressed in medical literature. To prepare a clinical guideline on the medical approach to patients with diabetes who practice sport regularly. An expert panel from the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition (SEEN) reviewed the most relevant literature in each of the sections. Based both on this review and on data from the experience of a number of athletes with DM, a number of recommendations were agreed within each section. Finally, the Working Group and representatives of the SEEN jointly discussed all these recommendations. The guideline provides recommendations ranging from medical assessment before patients with DM start to practice sport to actions during and after physical activity. Recommendations are also given on aspects such as the impact of sport on blood glucose control, training schemes, or special risk situations. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

General error analysis in the relationship between free thyroxine and thyrotropin and its clinical relevance.

PubMed

Goede, Simon L; Leow, Melvin Khee-Shing

2013-01-01

This treatise investigates error sources in measurements applicable to the hypothalamus-pituitary-thyroid (HPT) system of analysis for homeostatic set point computation. The hypothalamus-pituitary transfer characteristic (HP curve) describes the relationship between plasma free thyroxine [FT4] and thyrotropin [TSH]. We define the origin, types, causes, and effects of errors that are commonly encountered in TFT measurements and examine how we can interpret these to construct a reliable HP function for set point establishment. The error sources in the clinical measurement procedures are identified and analyzed in relation to the constructed HP model. The main sources of measurement and interpretation uncertainties are (1) diurnal variations in [TSH], (2) TFT measurement variations influenced by timing of thyroid medications, (3) error sensitivity in ranges of [TSH] and [FT4] (laboratory assay dependent), (4) rounding/truncation of decimals in [FT4] which in turn amplify curve fitting errors in the [TSH] domain in the lower [FT4] range, (5) memory effects (rate-independent hysteresis effect). When the main uncertainties in thyroid function tests (TFT) are identified and analyzed, we can find the most acceptable model space with which we can construct the best HP function and the related set point area.

Epidermal mechano-acoustic sensing electronics for cardiovascular diagnostics and human-machine interfaces

PubMed Central

Liu, Yuhao; Norton, James J. S.; Qazi, Raza; Zou, Zhanan; Ammann, Kaitlyn R.; Liu, Hank; Yan, Lingqing; Tran, Phat L.; Jang, Kyung-In; Lee, Jung Woo; Zhang, Douglas; Kilian, Kristopher A.; Jung, Sung Hee; Bretl, Timothy; Xiao, Jianliang; Slepian, Marvin J.; Huang, Yonggang; Jeong, Jae-Woong; Rogers, John A.

2016-01-01

Physiological mechano-acoustic signals, often with frequencies and intensities that are beyond those associated with the audible range, provide information of great clinical utility. Stethoscopes and digital accelerometers in conventional packages can capture some relevant data, but neither is suitable for use in a continuous, wearable mode, and both have shortcomings associated with mechanical transduction of signals through the skin. We report a soft, conformal class of device configured specifically for mechano-acoustic recording from the skin, capable of being used on nearly any part of the body, in forms that maximize detectable signals and allow for multimodal operation, such as electrophysiological recording. Experimental and computational studies highlight the key roles of low effective modulus and low areal mass density for effective operation in this type of measurement mode on the skin. Demonstrations involving seismocardiography and heart murmur detection in a series of cardiac patients illustrate utility in advanced clinical diagnostics. Monitoring of pump thrombosis in ventricular assist devices provides an example in characterization of mechanical implants. Speech recognition and human-machine interfaces represent additional demonstrated applications. These and other possibilities suggest broad-ranging uses for soft, skin-integrated digital technologies that can capture human body acoustics. PMID:28138529

Proton beam characterization in the experimental room of the Trento Proton Therapy facility

NASA Astrophysics Data System (ADS)

Tommasino, F.; Rovituso, M.; Fabiano, S.; Piffer, S.; Manea, C.; Lorentini, S.; Lanzone, S.; Wang, Z.; Pasini, M.; Burger, W. J.; La Tessa, C.; Scifoni, E.; Schwarz, M.; Durante, M.

2017-10-01

As proton therapy is becoming an established treatment methodology for cancer patients, the number of proton centres is gradually growing worldwide. The economical effort for building these facilities is motivated by the clinical aspects, but might be also supported by the potential relevance for the research community. Experiments with high-energy protons are needed not only for medical physics applications, but represent also an essential part of activities dedicated to detector development, space research, radiation hardness tests, as well as of fundamental research in nuclear and particle physics. Here we present the characterization of the beam line installed in the experimental room of the Trento Proton Therapy Centre (Italy). Measurements of beam spot size and envelope, range verification and proton flux were performed in the energy range between 70 and 228 MeV. Methods for reducing the proton flux from typical treatments values of 106-109 particles/s down to 101-105 particles/s were also investigated. These data confirm that a proton beam produced in a clinical centre build by a commercial company can be exploited for a broad spectrum of experimental activities. The results presented here will be used as a reference for future experiments.

Aberrant connections between climbing fibres and Purkinje cells induce alterations in the timing of an instrumental response in the rat.

PubMed

Gaytán-Tocavén, Lorena; López-Vázquez, Miguel Ángel; Guevara, Miguel Ángel; Olvera-Cortés, María Esther

2017-09-01

Cerebellar participation in timing and sensory-motor sequences has been supported by several experimental and clinical studies. A relevant role of the cerebellum in timing of conditioned responses in the range of milliseconds has been demonstrated, but less is known regarding the role of the cerebellum in supra-second timing of operant responses. A dissociated role of the cerebellum and striatum in timing in the millisecond and second range had been reported, respectively. The climbing fibre-Purkinje cell synapse is crucial in timing models; thus, the aberrant connection between these cellular elements is a suitable model for evaluating the contribution of the cerebellum in timing in the supra-second range. The aberrant connection between climbing fibres and Purkinje cells was induced by administration of the antagonist of NMDA receptors MK-801 to Sprague-Dawley rats at postnatal days 7-14. The timing of an operant response with two fixed intervals (5 and 8 s) and egocentric sequential learning was evaluated in 60-day-old adult rats. The aberrant connections caused a reduced accuracy in the timing of the instrumental response that was more evident in the 8-s interval and a reduced number of successive correct responses (responses emitted in the correct second without any other response between them) in the 8-s interval. In addition, an inability to incorporate new information in a sequence previously learned in egocentric-based sequence learning was apparent in rats with aberrant CF-PC synapses. These results support a relevant role for the cerebellum in the fine-tuning of the timing of operant responses in the supra-second range.

The Juggling Act of Supervision in Community Mental Health: Implications for Supporting Evidence-Based Treatment.

PubMed

Dorsey, Shannon; Pullmann, Michael D; Kerns, Suzanne E U; Jungbluth, Nathaniel; Meza, Rosemary; Thompson, Kelly; Berliner, Lucy

2017-11-01

Supervisors are an underutilized resource for supporting evidence-based treatments (EBTs) in community mental health. Little is known about how EBT-trained supervisors use supervision time. Primary aims were to describe supervision (e.g., modality, frequency), examine functions of individual supervision, and examine factors associated with time allocation to supervision functions. Results from 56 supervisors and 207 clinicians from 25 organizations indicate high prevalence of individual supervision, often alongside group and informal supervision. Individual supervision serves a wide range of functions, with substantial variation at the supervisor-level. Implementation climate was the strongest predictor of time allocation to clinical and EBT-relevant functions.

Consensus Conference Follow-up: Inter-rater Reliability Assessment of the Best Evidence in Emergency Medicine (BEEM) Rater Scale, a Medical Literature Rating Tool for Emergency Physicians

PubMed Central

Worster, Andrew; Kulasegaram, Kulamakan; Carpenter, Christopher R.; Vallera, Teresa; Upadhye, Suneel; Sherbino, Jonathan; Haynes, R. Brian

2011-01-01

Background Studies published in general and specialty medical journals have the potential to improve emergency medicine (EM) practice, but there can be delayed awareness of this evidence because emergency physicians (EPs) are unlikely to read most of these journals. Also, not all published studies are intended for or ready for clinical practice application. The authors developed “Best Evidence in Emergency Medicine” (BEEM) to ameliorate these problems by searching for, identifying, appraising, and translating potentially practice-changing studies for EPs. An initial step in the BEEM process is the BEEM rater scale, a novel tool for EPs to collectively evaluate the relative clinical relevance of EM-related studies found in more than 120 journals. The BEEM rater process was designed to serve as a clinical relevance filter to identify those studies with the greatest potential to affect EM practice. Therefore, only those studies identified by BEEM raters as having the highest clinical relevance are selected for the subsequent critical appraisal process and, if found methodologically sound, are promoted as the best evidence in EM. Objectives The primary objective was to measure inter-rater reliability (IRR) of the BEEM rater scale. Secondary objectives were to determine the minimum number of EP raters needed for the BEEM rater scale to achieve acceptable reliability and to compare performance of the scale against a previously published evidence rating system, the McMaster Online Rating of Evidence (MORE), in an EP population. Methods The authors electronically distributed the title, conclusion, and a PubMed link for 23 recently published studies related to EM to a volunteer group of 134 EPs. The volunteers answered two demographic questions and rated the articles using one of two randomly assigned seven-point Likert scales, the BEEM rater scale (n = 68) or the MORE scale (n = 66), over two separate administrations. The IRR of each scale was measured using generalizability theory. Results The IRR of the BEEM rater scale ranged between 0.90 (95% confidence interval [CI] = 0.86 to 0.93) to 0.92 (95% CI = 0.89 to 0.94) across administrations. Decision studies showed a minimum of 12 raters is required for acceptable reliability of the BEEM rater scale. The IRR of the MORE scale was 0.82 to 0.84. Conclusions The BEEM rater scale is a highly reliable, single-question tool for a small number of EPs to collectively rate the relative clinical relevance within the specialty of EM of recently published studies from a variety of medical journals. It compares favorably with the MORE system because it achieves a high IRR despite simply requiring raters to read each article’s title and conclusion. PMID:22092904

A Systematic Approach for Discovering Novel, Clinically Relevant Bacteria

PubMed Central

Simmon, Keith E.; Fisher, Mark A.

2012-01-01

Sequencing of the 16S rRNA gene (16S) is a reference method for bacterial identification. Its expanded use has led to increased recognition of novel bacterial species. In most clinical laboratories, novel species are infrequently encountered, and their pathogenic potential is often difficult to assess. We reviewed partial 16S sequences from >26,000 clinical isolates, analyzed during February 2006–June 2010, and identified 673 that have <99% sequence identity with valid reference sequences and are thus possibly novel species. Of these 673 isolates, 111 may represent novel genera (<95% identity). Isolates from 95 novel taxa were recovered from multiple patients, indicating possible clinical relevance. Most repeatedly encountered novel taxa belonged to the genera Nocardia (14 novel taxa, 42 isolates) and Actinomyces (12 novel taxa, 52 isolates). This systematic approach for recognition of novel species with potential diagnostic or therapeutic relevance provides a basis for epidemiologic surveys and improvement of sequence databases and may lead to identification of new clinical entities. PMID:22377371

A systematic approach for discovering novel, clinically relevant bacteria.

PubMed

Schlaberg, Robert; Simmon, Keith E; Fisher, Mark A

2012-03-01

Sequencing of the 16S rRNA gene (16S) is a reference method for bacterial identification. Its expanded use has led to increased recognition of novel bacterial species. In most clinical laboratories, novel species are infrequently encountered, and their pathogenic potential is often difficult to assess. We reviewed partial 16S sequences from >26,000 clinical isolates, analyzed during February 2006-June 2010, and identified 673 that have <99% sequence identity with valid reference sequences and are thus possibly novel species. Of these 673 isolates, 111 may represent novel genera (<95% identity). Isolates from 95 novel taxa were recovered from multiple patients, indicating possible clinical relevance. Most repeatedly encountered novel taxa belonged to the genera Nocardia (14 novel taxa, 42 isolates) and Actinomyces (12 novel taxa, 52 isolates). This systematic approach for recognition of novel species with potential diagnostic or therapeutic relevance provides a basis for epidemiologic surveys and improvement of sequence databases and may lead to identification of new clinical entities.

Relevance of randomised controlled trials in oncology.

PubMed

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

2016-12-01

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

Severe community-acquired pneumonia: timely management measures in the first 24 hours.

PubMed

Phua, Jason; Dean, Nathan C; Guo, Qi; Kuan, Win Sen; Lim, Hui Fang; Lim, Tow Keang

2016-08-28

Mortality rates for severe community-acquired pneumonia (CAP) range from 17 to 48 % in published studies.In this review, we searched PubMed for relevant papers published between 1981 and June 2016 and relevant files. We explored how early and aggressive management measures, implemented within 24 hours of recognition of severe CAP and carried out both in the emergency department and in the ICU, decrease mortality in severe CAP.These measures begin with the use of severity assessment tools and the application of care bundles via clinical decision support tools. The bundles include early guideline-concordant antibiotics including macrolides, early haemodynamic support (lactate measurement, intravenous fluids, and vasopressors), and early respiratory support (high-flow nasal cannulae, lung-protective ventilation, prone positioning, and neuromuscular blockade for acute respiratory distress syndrome).While the proposed interventions appear straightforward, multiple barriers to their implementation exist. To successfully decrease mortality for severe CAP, early and close collaboration between emergency medicine and respiratory and critical care medicine teams is required. We propose a workflow incorporating these interventions.

The impact of water intake on energy intake and weight status: a systematic review

PubMed Central

Daniels, Melissa C.; Popkin, Barry M.

2010-01-01

The effects of consuming water with meals rather than drinking no beverage or various other beverages remains under-studied. This systematic review of English language studies compared the effects of drinking water and various beverage alternatives on energy intake and/or weight status. We collected relevant clinical trials, epidemiologic, and intervention studies and summarized findings across the literature. Using clinical trials, average differences in total energy intake at test meals (ΔTEI) were calculated across studies for each of several beverage categories compared to water. The literature for these comparisons is sparse and somewhat inconclusive. One of the most consistent sets of findings comes from comparing adults drinking sugar-sweetened beverages (SSB’s) vs. water before a single meal. Total energy intakes were increased 7.8% (ΔTEI range −7.5 to 18.9) when SSBs were consumed. Studies comparing nonnutritive sweeteners with water were also relatively consistent and found no impact on energy intake among adults (ΔTEI = −1.3, range −9 to13.8). Much less conclusive evidence replacing water with milk and juice estimated increases in TEI of 14.9% (range 10.9 to 23.9). These findings, along with epidemiologic and intervention studies suggested a potentially important role for water in reducing energy intakes, and by this means a role in obesity prevention. A need for randomized-controlled trials exists. PMID:20796216

Reassessment of ABO blood group, sex, and age on laboratory parameters used to diagnose von Willebrand disorder: potential influence on the diagnosis vs the potential association with risk of thrombosis.

PubMed

Favaloro, Emmanuel J; Soltani, Soma; McDonald, Jane; Grezchnik, Ella; Easton, Leanne; Favaloro, James W C

2005-12-01

We reassessed the influence of ABO blood group, sex, and age on plasma levels of von Willebrand factor (vWF) antigen, vWF:ristocetin cofactor, vWF:collagen binding assay, and factor VIII coagulant (FVIII:C). Data show that levels of vWF and FVIII:C increase with increasing age (P < .001 for all parameters) and that the ABO blood group influences plasma levels such that O group levels are significantly less than non-O group levels. There was no significant association with sex and Rh status. The selection of normal ranges based on ABO blood groups may influence the clinical diagnosis of von Willebrand disease (vWD) but might not be clinically relevant or help identify people at increased risk of bleeding. Differences in ABO-related ranges were more extensive at the high end of the ranges. This is of particular interest because high levels of vWF and FVIII are associated with thrombosis risk, and an ABO relationship also has been described. O group individuals may or may not be at greater risk for bleeding (they have lower levels of vWF and FVIII:C) and are more likely to be diagnosed with vWD. It also is possible that O group status may be protective for thrombosis.

Multiple keratocysts of the mandible in association with Gorlin-Goltz syndrome: A rare case report

PubMed Central

Kulkarni, Gayithri Harish; Khaji, Shahanavaj I.; Metkari, Suryakant; Kulkarni, Harish S.; Kulkarni, Reshma

2014-01-01

Nevoid basal cell carcinoma syndrome is a syndrome with wide variety of manifestations ranging from oral lesions to skeletal deformities. It calls for due responsibility of maxillofacial surgeon to diagnose the syndrome because very often they are the first health professionals to see the patient for the treatment of keratocystic odontogenic tumor. Keratocystic odontogenic tumor has been the topic of numerous investigators, is known for its potentially aggressive behavior, significant rate of recurrences. KCOT often occurs as a solitary lesion, in some instances multiple keratocysts may occur in association with a syndrome called Gorlin-Goltz syndrome (nevoid BCC, jaw cyst bifid rib basal cell nevus syndrome). Here, we present a case of multiple keratocysts in the mandible in association with skeletal, ocular, cutaneous anomalies in the given clinical scenario, which has profound relevance in the clinical dental practice. PMID:25191087

Multiple keratocysts of the mandible in association with Gorlin-Goltz syndrome: A rare case report.

PubMed

Kulkarni, Gayithri Harish; Khaji, Shahanavaj I; Metkari, Suryakant; Kulkarni, Harish S; Kulkarni, Reshma

2014-07-01

Nevoid basal cell carcinoma syndrome is a syndrome with wide variety of manifestations ranging from oral lesions to skeletal deformities. It calls for due responsibility of maxillofacial surgeon to diagnose the syndrome because very often they are the first health professionals to see the patient for the treatment of keratocystic odontogenic tumor. Keratocystic odontogenic tumor has been the topic of numerous investigators, is known for its potentially aggressive behavior, significant rate of recurrences. KCOT often occurs as a solitary lesion, in some instances multiple keratocysts may occur in association with a syndrome called Gorlin-Goltz syndrome (nevoid BCC, jaw cyst bifid rib basal cell nevus syndrome). Here, we present a case of multiple keratocysts in the mandible in association with skeletal, ocular, cutaneous anomalies in the given clinical scenario, which has profound relevance in the clinical dental practice.

Time for a change to assess and evaluate body temperature in clinical practice.

PubMed

Sund-Levander, Märtha; Grodzinsky, Ewa

2009-08-01

The definition of normal body temperature as 37 degrees C still is considered the norm worldwide, but in practice there is a widespread confusion of the evaluation of body temperature, especially in elderly individuals. In this paper, we discuss the relevance of normal body temperature as 37 degrees C and consequences in clinical practice. Our conclusion is that body temperature should be evaluated in relation to the individual variability and that the best approach is to use the same site, and an unadjusted mode without adjustments to other sites. If the baseline value is not known, it is important to notice that frail elderly individuals are at risk of a low body temperature. In addition, what should be regarded as fever is closely related to what is considered as normal body temperature. That is, as normal body temperature shows individual variations, it is reasonable that the same should hold true for the febrile range.

Psychological Characteristics in Acute Mild Traumatic Brain Injury: An MMPI-2 Study.

PubMed

Gass, Carlton S; Rogers, David; Kinne, Erica

2017-01-01

The psychological characteristics of acute traumatic brain injury (TBI) have received limited research focus, despite empirical evidence of their relevance for subsequent psychological adjustment and early therapeutic intervention. This study addressed a wide range of psychological features in 47 individuals who were hospitalized as a result of acute mild TBI (mTBI). Participants were screened from amongst consecutive TBI admissions for moderate to severe brain injury, and for pre-injury neurological, psychiatric, or substance abuse histories. Clinical and content scale scores on the MMPI-2 were explored in relation to patient gender, age, level of education, and extent of cognitive complaints. The results revealed diverse psychosocial problem areas across the sample, the most common of which were somatic and cognitive complaints, compromised insight, and a naively optimistic self-perception. The mediating roles of injury severity and demographic variables are discussed. Clinical implications and specific recommendations are presented.

Dry eye disease as an inflammatory disorder.

PubMed

Calonge, Margarita; Enríquez-de-Salamanca, Amalia; Diebold, Yolanda; González-García, María J; Reinoso, Roberto; Herreras, José M; Corell, Alfredo

2010-08-01

Dry eye disease (DED) is a prevalent inflammatory disorder of the lacrimal functional unit of multifactorial origin leading to chronic ocular surface disease, impaired quality of vision, and a wide range of complications, eventually causing a reduction in quality of life. It still is a frustrating disease because of the present scarcity of therapies that can reverse, or at least stop, its progression. A comprehensive literature survey of English-written scientific publications on the role of inflammation in DED. New investigations have demonstrated that a chronic inflammatory response plays a key role in the pathogenesis of human DED. Additionally, correlations between inflammatory molecules and clinical data suggest that inflammation can be responsible for some of the clinical symptoms and signs. Research efforts to clarify its pathophysiology are leading to a better understanding of DED, demonstrating that inflammation, in addition to many other factors, plays a relevant role.

Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents

PubMed Central

Botkin, Jeffrey R.; Belmont, John W.; Berg, Jonathan S.; Berkman, Benjamin E.; Bombard, Yvonne; Holm, Ingrid A.; Levy, Howard P.; Ormond, Kelly E.; Saal, Howard M.; Spinner, Nancy B.; Wilfond, Benjamin S.; McInerney, Joseph D.

2015-01-01

In 1995, the American Society of Human Genetics (ASHG) and American College of Medical Genetics and Genomics (ACMG) jointly published a statement on genetic testing in children and adolescents. In the past 20 years, much has changed in the field of genetics, including the development of powerful new technologies, new data from genetic research on children and adolescents, and substantial clinical experience. This statement represents current opinion by the ASHG on the ethical, legal, and social issues concerning genetic testing in children. These recommendations are relevant to families, clinicians, and investigators. After a brief review of the 1995 statement and major changes in genetic technologies in recent years, this statement offers points to consider on a broad range of test technologies and their applications in clinical medicine and research. Recommendations are also made for record and communication issues in this domain and for professional education. PMID:26140447

A practical guide to diagnostic transcranial magnetic stimulation: Report of an IFCN committee

PubMed Central

Groppa, S.; Oliviero, A.; Eisen, A.; Quartarone, A.; Cohen, L.G.; Mall, V.; Kaelin-Lang, A.; Mima, T.; Rossi, S.; Thickbroom, G.W.; Rossini, P.M.; Ziemann, U.; Valls-Solé, J.; Siebner, H.R.

2016-01-01

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS. PMID:22349304

Thioaptamer Diagnostic System (TDS)

NASA Technical Reports Server (NTRS)

Yang, Xianbin

2015-01-01

AM Biotechnologies, LLC, in partnership with Sandia National Laboratories, has developed a diagnostic device that quickly detects sampled biomarkers. The TDS quickly quantifies clinically relevant biomarkers using only microliters of a single sample. The system combines ambient-stable, long shelf-life affinity assays with handheld, microfluidic gel electrophoresis affinity assay quantification technology. The TDS is easy to use, operates in microgravity, and permits simultaneous quantification of 32 biomarkers. In Phase I of the project, the partners demonstrated that a thioaptamer assay used in the microfluidic instrument could quantify a specific biomarker in serum in the low nanomolar range. The team also identified novel affinity agents to bone-specific alkaline phosphatase (BAP) and demonstrated their ability to detect BAP with the microfluidic instrument. In Phase II, AM Biotech expanded the number of ambient affinity agents and demonstrated a TDS prototype. In the long term, the clinical version of the TDS will provide a robust, flight-tested diagnostic capability for space exploration missions.

[Treatment of attention deficit disorders in adulthood using psychostimulants and low-dose neuroleptics--a critical case report].

PubMed

Schmidt, L G; Schlünder, M; Reischies, F M

1988-03-01

Psychiatric research and therapy recently evinced increasing interest in patients suffering from attention deficit disorder. "Attention deficit disorder" is a category of mental disorders listed in DSM III, with a separate diagnostic subgroup for attention deficit disorders persisting in adults who had been hyperkinetic in childhood ("attention deficit disorder-residual type"); however, this does not feature in a corresponding manner in the ICD 9 version. Since there are practically no therapy studies in existence within the ICD range that can be relevant for such disorders, we studied the treatment of an adult patient with the psychostimulant fenetylline under clinical conditions and found a significant improvement in attention performance. However, on integration in a long-term day-clinic rehabilitation programme we found that low-dose neuroleptic treatment was on the whole of greater benefit than fenetylline treatment.

Cryotherapy and ankle motion in chronic venous disorders

PubMed Central

Kelechi, Teresa J.; Mueller, Martina; Zapka, Jane G.; King, Dana E.

2013-01-01

This study compared ankle range of motion (AROM) including dorsiflexion, plantar flexion, inversion and eversion, and venous refill time (VRT) in leg skin inflamed by venous disorders, before and after a new cryotherapy ulcer prevention treatment. Fifty-seven-individuals participated in the randomized clinical trial; 28 in the experimental group and 29 received usual care only. Results revealed no statistically significant differences between the experimental and usual care groups although AROM measures in the experimental group showed a consistent, non-clinically relevant decrease compared to the usual care group except for dorsiflexion. Within treatment group comparisons of VRT results showed a statistically significant increase in both dorsiflexion and plantar flexion for patients with severe VRT in the experimental group (6.9 ± 6.8; p = 0.002 and 5.8 ± 12.6; p = 0.02, respectively). Cryotherapy did not further restrict already compromised AROM, and in some cases, there were minor improvements. PMID:23516043

Antidrug Antibody Formation in Oncology: Clinical Relevance and Challenges.

PubMed

van Brummelen, Emilie M J; Ros, Willeke; Wolbink, Gertjan; Beijnen, Jos H; Schellens, Jan H M

2016-10-01

: In oncology, an increasing number of targeted anticancer agents and immunotherapies are of biological origin. These biological drugs may trigger immune responses that lead to the formation of antidrug antibodies (ADAs). ADAs are directed against immunogenic parts of the drug and may affect efficacy and safety. In other medical fields, such as rheumatology and hematology, the relevance of ADA formation is well established. However, the relevance of ADAs in oncology is just starting to be recognized, and literature on this topic is scarce. In an attempt to fill this gap in the literature, we provide an up-to-date status of ADA formation in oncology. In this focused review, data on ADAs was extracted from 81 clinical trials with biological anticancer agents. We found that most biological anticancer drugs in these trials are immunogenic and induce ADAs (63%). However, it is difficult to establish the clinical relevance of these ADAs. In order to determine this relevance, the possible effects of ADAs on pharmacokinetics, efficacy, and safety parameters need to be investigated. Our data show that this was done in fewer than 50% of the trials. In addition, we describe the incidence and consequences of ADAs for registered agents. We highlight the challenges in ADA detection and argue for the importance of validating, standardizing, and describing well the used assays. Finally, we discuss prevention strategies such as immunosuppression and regimen adaptations. We encourage the launch of clinical trials that explore these strategies in oncology. Because of the increasing use of biologicals in oncology, many patients are at risk of developing antidrug antibodies (ADAs) during therapy. Although clinical consequences are uncertain, ADAs may affect pharmacokinetics, patient safety, and treatment efficacy. ADA detection and reporting is currently highly inconsistent, which makes it difficult to evaluate the clinical consequences. Standardized reporting of ADA investigations in the context of the aforementioned parameters is critical to understanding the relevance of ADA formation for each drug. Furthermore, the development of trials that specifically aim to investigate clinical prevention strategies in oncology is needed. ©AlphaMed Press.

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

PubMed

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

2017-07-01

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

Clinical Evidence: a useful tool for promoting evidence-based practice?

PubMed

Formoso, Giulio; Moja, Lorenzo; Nonino, Francesco; Dri, Pietro; Addis, Antonio; Martini, Nello; Liberati, Alessandro

2003-12-23

Research has shown that many healthcare professionals have problems with guidelines as they would prefer to be given all relevant information relevant to decision-making rather than being told what they should do. This study assesses doctors' judgement of the validity, relevance, clarity and usability of the Italian translation of Clinical Evidence (CE) after its free distribution launched by the Italian Ministry of Health. Opinions elicited using a standardised questionnaire delivered either by mail or during educational or professional meetings. Twenty percent (n = 1350) doctors participated the study. Most of them found CE's content valid, useful and relevant for their clinical practice, and said CE can foster communications among clinicians, particularly among GPs and specialists. Hospital doctors (63%) more often than GPs (48%) read the detailed presentation of individual chapters. Twenty-nine percent said CE brought changes in their clinical practice. Doctors appreciated CE's nature of an evidence-based information compendium and would have not preferred a collection of practice guidelines. Overall, the pilot initiative launched by the Italian Ministry of Health seems to have been well received and to support the subsequent decision to make the Italian edition of Clinical Evidence concise available to all doctors practising in the country. Local implementation initiatives should be warranted to favour doctor's use of CE.

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

ERIC Educational Resources Information Center

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

2012-01-01

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

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

PubMed

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

2012-12-21

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

Influence of hyaluronic acid on bacterial and fungal species, including clinically relevant opportunistic pathogens.

PubMed

Ardizzoni, Andrea; Neglia, Rachele G; Baschieri, Maria C; Cermelli, Claudio; Caratozzolo, Manuela; Righi, Elena; Palmieri, Beniamino; Blasi, Elisabetta

2011-10-01

Hyaluronic acid (HA) has several clinical applications (aesthetic surgery, dermatology, orthopaedics and ophtalmology). Following recent evidence, suggesting antimicrobial and antiviral properties for HA, we investigated its effects on 15 ATCC strains, representative of clinically relevant bacterial and fungal species. The in vitro system employed allowed to assess optical density of broth cultures as a measure of microbial load in a time-dependent manner. The results showed that different microbial species and, sometimes, different strains belonging to the same species, are differently affected by HA. In particular, staphylococci, enterococci, Streptococcus mutans, two Escherichia coli strains, Pseudomonas aeruginosa, Candida glabrata and C. parapsilosis displayed a HA dose-dependent growth inhibition; no HA effects were detected in E. coli ATCC 13768 and C. albicans; S. sanguinis was favoured by the highest HA dose. Therefore, the influence of HA on bacteria and fungi warrants further studies aimed at better establishing its relevance in clinical applications.

Rapid Bacterial Whole-Genome Sequencing to Enhance Diagnostic and Public Health Microbiology

PubMed Central

Reuter, Sandra; Ellington, Matthew J.; Cartwright, Edward J. P.; Köser, Claudio U.; Török, M. Estée; Gouliouris, Theodore; Harris, Simon R.; Brown, Nicholas M.; Holden, Matthew T. G.; Quail, Mike; Parkhill, Julian; Smith, Geoffrey P.; Bentley, Stephen D.; Peacock, Sharon J.

2014-01-01

IMPORTANCE The latest generation of benchtop DNA sequencing platforms can provide an accurate whole-genome sequence (WGS) for a broad range of bacteria in less than a day. These could be used to more effectively contain the spread of multidrug-resistant pathogens. OBJECTIVE To compare WGS with standard clinical microbiology practice for the investigation of nosocomial outbreaks caused by multidrug-resistant bacteria, the identification of genetic determinants of antimicrobial resistance, and typing of other clinically important pathogens. DESIGN, SETTING, AND PARTICIPANTS A laboratory-based study of hospital inpatients with a range of bacterial infections at Cambridge University Hospitals NHS Foundation Trust, a secondary and tertiary referral center in England, comparing WGS with standard diagnostic microbiology using stored bacterial isolates and clinical information. MAIN OUTCOMES AND MEASURES Specimens were taken and processed as part of routine clinical care, and cultured isolates stored and referred for additional reference laboratory testing as necessary. Isolates underwent DNA extraction and library preparation prior to sequencing on the Illumina MiSeq platform. Bioinformatic analyses were performed by persons blinded to the clinical, epidemiologic, and antimicrobial susceptibility data. RESULTS We investigated 2 putative nosocomial outbreaks, one caused by vancomycin-resistant Enterococcus faecium and the other by carbapenem-resistant Enterobacter cloacae; WGS accurately discriminated between outbreak and nonoutbreak isolates and was superior to conventional typing methods. We compared WGS with standard methods for the identification of the mechanism of carbapenem resistance in a range of gram-negative bacteria (Acinetobacter baumannii, E cloacae, Escherichia coli, and Klebsiella pneumoniae). This demonstrated concordance between phenotypic and genotypic results, and the ability to determine whether resistance was attributable to the presence of carbapenemases or other resistance mechanisms. Whole-genome sequencing was used to recapitulate reference laboratory typing of clinical isolates of Neisseria meningitidis and to provide extended phylogenetic analyses of these. CONCLUSIONS AND RELEVANCE The speed, accuracy, and depth of information provided by WGS platforms to confirm or refute outbreaks in hospitals and the community, and to accurately define transmission of multidrug-resistant and other organisms, represents an important advance. PMID:23857503

Lumbar Disc Replacement for Junctional Decompensation After Fusion Surgery: Clinical and Radiological Outcome at an Average Follow-Up of 33 Months

PubMed Central

Sliwa, Karen; Weinberg, Ian R.; Sweet, Barry MBE; de Villiers, Malan; Candy, Geoffrey P.

2007-01-01

Background Failed fusion surgery remains difficult to treat. Few published data on disc replacement surgery after failed fusion procedures exist. Our objective was to evaluate outcomes of junctional lumbar disc replacement after previous fusion surgery and to correlate outcome with radiological changes to parameters of sagittal balance. Methods Out of a single-center prospective registry of 290 patients with 404 lumbar disc replacements, 27 patients had had a previous lumbar fusion operation on 1 to 4 lumbar segments and had completed a mean follow- up of 33 months (range: 18–56). We correlated the clinical outcome measures (patient satisfaction, 10-point pain score, and Oswestry Disability Index [ODI] score) to parameters of spinal sagittal alignment (sacral tilt, pelvic tilt, pelvic incidence, and lumbar lordosis). Results Postoperative hospital stay averaged 3.3 days (range: 2–8). Previously-employed patients went back to their jobs with a mean of 32 days (range: 21–42) after the procedure. At the latest follow-up, 1 of the patients considered the outcome to be poor, 3 fair, 8 good, and 15 excellent. Twenty-four patients “would undergo the operation again.” Average pain score decreased from 9.1 ± 1.0 (SD) to 3.2 ± 2.1 (P < .01). Average ODI decreased from 50.2 ± 9.9 preoperatively to 21.7 ± 14.2 (P ≤ .01). We found the change in pelvic tilt to be an independent predictor of better clinical outcome by multivariate analysis (P < .05). Conclusions In patients with junctional failure adjacent to a previous posterolateral fusion, disc replacement at the junctional level(s), compared with osteotomy and fusion surgery, offers the advantage of maintaining segmental mobility and correcting the flat-back deformity through a single approach with less operative time and blood loss. Early- to intermediate-term results are promising. The influence of changes in spinal sagittal alignment on clinical outcome needs to be addressed in future research. Clinical Relevance This is the first study on “junctional disc replacement patients” correlating clinical outcome to changes in spinal/pelvic alignment. PMID:25802584

An informatics approach to analyzing the incidentalome.

PubMed

Berg, Jonathan S; Adams, Michael; Nassar, Nassib; Bizon, Chris; Lee, Kristy; Schmitt, Charles P; Wilhelmsen, Kirk C; Evans, James P

2013-01-01

Next-generation sequencing has transformed genetic research and is poised to revolutionize clinical diagnosis. However, the vast amount of data and inevitable discovery of incidental findings require novel analytic approaches. We therefore implemented for the first time a strategy that utilizes an a priori structured framework and a conservative threshold for selecting clinically relevant incidental findings. We categorized 2,016 genes linked with Mendelian diseases into "bins" based on clinical utility and validity, and used a computational algorithm to analyze 80 whole-genome sequences in order to explore the use of such an approach in a simulated real-world setting. The algorithm effectively reduced the number of variants requiring human review and identified incidental variants with likely clinical relevance. Incorporation of the Human Gene Mutation Database improved the yield for missense mutations but also revealed that a substantial proportion of purported disease-causing mutations were misleading. This approach is adaptable to any clinically relevant bin structure, scalable to the demands of a clinical laboratory workflow, and flexible with respect to advances in genomics. We anticipate that application of this strategy will facilitate pretest informed consent, laboratory analysis, and posttest return of results in a clinical context.

Point-of-care diagnostics for niche applications.

PubMed

Cummins, Brian M; Ligler, Frances S; Walker, Glenn M

2016-01-01

Point-of-care or point-of-use diagnostics are analytical devices that provide clinically relevant information without the need for a core clinical laboratory. In this review we define point-of-care diagnostics as portable versions of assays performed in a traditional clinical chemistry laboratory. This review discusses five areas relevant to human and animal health where increased attention could produce significant impact: veterinary medicine, space travel, sports medicine, emergency medicine, and operating room efficiency. For each of these areas, clinical need, available commercial products, and ongoing research into new devices are highlighted. Copyright © 2016 Elsevier Inc. All rights reserved.

RBE, reference RBE and clinical RBE: applications of these concepts in hadron therapy.

PubMed

Wambersie, A

1999-06-01

Introduction of heavy particles (hadrons) into radiation therapy aims at improving the physical selectivity of the irradiation (e.g. proton beams), or the radiobiological differential effect (e.g. fast neutrons), or both (e.g. heavy-ion beams). Each of these new therapy modalities requires several types of information before prescribing safely the doses to patients, as well as for recording and reporting the treatments: (i) absorbed dose measured in a homogeneous phantom in reference conditions; (ii) dose distribution computed at the level of the target volume(s) and the normal tissues at risk; (iii) radiation quality from which a RBE evaluation could be predicted and (iv) RBE measured on biological systems or derived from clinical observation. In hadron therapy, the RBE of the different beams raises specific problems. For fast neutrons, the RBE varies within wide limits (about 2 to 5) depending on the neutron energy spectrum, dose, and biological system. For protons, the RBE values range between smaller limits (about 1.0 to 1.2). A clinical benefit can thus not be expected from RBE differences. However, the proton RBE problem cannot be ignored since dose differences of about 5% can be detected clinically in some cases. The situation is most complex with heavy ions since RBE variations are at least as large as for fast neutrons, as a function of particle type and energy, dose and biological system. In addition, RBE varies with depth. Radiation quality thus has to be taken into account when prescribing and reporting a treatment. This can be done in different ways: (a) description of the method of beam production; (b) computed LET spectra and/or measured microdosimetric spectra at the points clinically relevant; (c) RBE determination. The most relevant RBE data are those obtained for late tolerance of normal tissues at 2 Gy per fraction ("reference RBE"). The "clinical RBE" selected by the radiation oncologist when prescribing the treatment will be close to the reference RBE, but other factors (such as heterogeneity in dose distribution) may influence the selection of the clinical RBE. Combination of microdosimetric data and experimental RBE values improves the confidence in both sets of data.

Minimum clinically important differences in chronic pain vary considerable by baseline pain and methodological factors: systematic review of empirical studies.

PubMed

Frahm Olsen, Mette; Bjerre, Eik; Hansen, Maria Damkjær; Tendal, Britta; Hilden, Jørgen; Hróbjartsson, Asbjørn

2018-05-21

The minimum clinically important difference (MCID) is used to interpret the relevance of treatment effects, e.g., when developing clinical guidelines, evaluating trial results or planning sample sizes. There is currently no agreement on an appropriate MCID in chronic pain and little is known about which contextual factors cause variation. This is a systematic review. We searched PubMed, EMBASE, and Cochrane Library. Eligible studies determined MCID for chronic pain based on a one-dimensional pain scale, a patient-reported transition scale of perceived improvement, and either a mean change analysis (mean difference in pain among minimally improved patients) or a threshold analysis (pain reduction associated with best sensitivity and specificity for identifying minimally improved patients). Main results were descriptively summarized due to considerable heterogeneity, which were quantified using meta-analyses and explored using subgroup analyses and metaregression. We included 66 studies (31.254 patients). Median absolute MCID was 23 mm on a 0-100 mm scale (interquartile range [IQR] 12-39) and median relative MCID was 34% (IQR 22-45) among studies using the mean change approach. In both cases, heterogeneity was very high: absolute MCID I 2  = 99% and relative MCID I 2  = 96%. High variation was also seen among studies using the threshold approach: median absolute MCID was 20 mm (IQR 15-30) and relative MCID was 32% (IQR 15-41). Absolute MCID was strongly associated with baseline pain, explaining approximately two-thirds of the variation, and to a lesser degree with the operational definition of minimum pain relief and clinical condition. A total of 15 clinical and methodological factors were assessed as possible causes for variation in MCID. MCID for chronic pain relief vary considerably. Baseline pain is strongly associated with absolute, but not relative, measures. To a much lesser degree, MCID is also influenced by the operational definition of relevant pain relief and possibly by clinical condition. Explicit and conscientious reflections on the choice of an MCID are required when classifying effect sizes as clinically important or trivial. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

Del Rosso, James Q; Zeichner, Joshua

2014-01-01

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

Consultant paediatric outreach clinics--a practical step in integration.

PubMed

Spencer, N J

1993-04-01

Ten years' experience of paediatric outreach clinics is reviewed and evaluated. The advantages and disadvantages of paediatric outreach and its possible place in the new era of contracting and more developed community paediatric services are discussed. It is concluded that paediatric outreach increases parental and professional choice and access to paediatric consultant services, increases service flexibility, reduces unnecessary hospital visits, and enables more rational and relevant clinical decision making. Outreach is particularly relevant in areas of deprivation where paediatric needs are greatest.

Consultant paediatric outreach clinics--a practical step in integration.

PubMed Central

Spencer, N J

1993-01-01

Ten years' experience of paediatric outreach clinics is reviewed and evaluated. The advantages and disadvantages of paediatric outreach and its possible place in the new era of contracting and more developed community paediatric services are discussed. It is concluded that paediatric outreach increases parental and professional choice and access to paediatric consultant services, increases service flexibility, reduces unnecessary hospital visits, and enables more rational and relevant clinical decision making. Outreach is particularly relevant in areas of deprivation where paediatric needs are greatest. PMID:8503675

T-wave alternans and beat-to-beat variability of repolarization: pathophysiological backgrounds and clinical relevance.

PubMed

Floré, Vincent; Willems, Rik

2012-12-01

In this review, we focus on temporal variability of cardiac repolarization. This phenomenon has been related to a higher risk for ventricular arrhythmia and is therefore interesting as a marker of sudden cardiac death risk. We review two non-invasive clinical techniques quantifying repolarization variability: T-wave alternans (TWA) and beat-to-beat variability of repolarization (BVR). We discuss their pathophysiological link with ventricular arrhythmia and the current clinical relevance of these techniques.

Serotonin-related pathways and developmental plasticity: relevance for psychiatric disorders

PubMed Central

Dayer, Alexandre

2014-01-01

Risk for adult psychiatric disorders is partially determined by early-life alterations occurring during neural circuit formation and maturation. In this perspective, recent data show that the serotonin system regulates key cellular processes involved in the construction of cortical circuits. Translational data for rodents indicate that early-life serotonin dysregulation leads to a wide range of behavioral alterations, ranging from stress-related phenotypes to social deficits. Studies in humans have revealed that serotonin-related genetic variants interact with early-life stress to regulate stress-induced cortisol responsiveness and activate the neural circuits involved in mood and anxiety disorders. Emerging data demonstrate that early-life adversity induces epigenetic modifications in serotonin-related genes. Finally, recent findings reveal that selective serotonin reuptake inhibitors can reinstate juvenile-like forms of neural plasticity, thus allowing the erasure of long-lasting fear memories. These approaches are providing new insights on the biological mechanisms and clinical application of antidepressants. PMID:24733969

Prognostic value of the new Grade Groups in Prostate Cancer: a multi-institutional European validation study.

PubMed

Mathieu, R; Moschini, M; Beyer, B; Gust, K M; Seisen, T; Briganti, A; Karakiewicz, P; Seitz, C; Salomon, L; de la Taille, A; Rouprêt, M; Graefen, M; Shariat, S F

2017-06-01

We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP). Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index. Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model). We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.

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

PubMed

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

2014-07-01

Pharmacogenomics (PGx) is positioned to have a widespread impact on the practice of medicine, yet physician acceptance is low. The presentation of context-specific PGx information, in the form of clinical decision support (CDS) alerts embedded in a computerized provider order entry (CPOE) system, can aid uptake. Usability evaluations can inform optimal design, which, in turn, can spur adoption. The study objectives were to: (1) evaluate an early prototype, commercial CPOE system with PGx-CDS alerts in a simulated environment, (2) identify potential improvements to the system user interface, and (3) understand the contexts under which PGx knowledge embedded in an electronic health record is useful to prescribers. Using a mixed methods approach, we presented seven cardiologists and three oncologists with five hypothetical clinical case scenarios. Each scenario featured a drug for which a gene encoding drug metabolizing enzyme required consideration of dosage adjustment. We used Morae(®) to capture comments and on-screen movements as participants prescribed each drug. In addition to PGx-CDS alerts, 'Infobutton(®)' and 'Evidence' icons provided participants with clinical knowledge resources to aid decision-making. Nine themes emerged. Five suggested minor improvements to the CPOE user interface; two suggested presenting PGx information through PGx-CDS alerts using an 'Infobutton' or 'Evidence' icon. The remaining themes were strong recommendations to provide succinct, relevant guidelines and dosing recommendations of phenotypic information from credible and trustworthy sources; any more information was overwhelming. Participants' median rating of PGx-CDS system usability was 2 on a Likert scale ranging from 1 (strongly agree) to 7 (strongly disagree). Usability evaluation results suggest that participants considered PGx information important for improving prescribing decisions; and that they would incorporate PGx-CDS when information is presented in relevant and useful ways. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Use of 16S rRNA gene for identification of a broad range of clinically relevant bacterial pathogens

DOE PAGES

Srinivasan, Ramya; Karaoz, Ulas; Volegova, Marina; ...

2015-02-06

According to World Health Organization statistics of 2011, infectious diseases remain in the top five causes of mortality worldwide. However, despite sophisticated research tools for microbial detection, rapid and accurate molecular diagnostics for identification of infection in humans have not been extensively adopted. Time-consuming culture-based methods remain to the forefront of clinical microbial detection. The 16S rRNA gene, a molecular marker for identification of bacterial species, is ubiquitous to members of this domain and, thanks to ever-expanding databases of sequence information, a useful tool for bacterial identification. In this study, we assembled an extensive repository of clinical isolates (n =more » 617), representing 30 medically important pathogenic species and originally identified using traditional culture-based or non-16S molecular methods. This strain repository was used to systematically evaluate the ability of 16S rRNA for species level identification. To enable the most accurate species level classification based on the paucity of sequence data accumulated in public databases, we built a Naïve Bayes classifier representing a diverse set of high-quality sequences from medically important bacterial organisms. We show that for species identification, a model-based approach is superior to an alignment based method. Overall, between 16S gene based and clinical identities, our study shows a genus-level concordance rate of 96% and a species-level concordance rate of 87.5%. We point to multiple cases of probable clinical misidentification with traditional culture based identification across a wide range of gram-negative rods and gram-positive cocci as well as common gram-negative cocci.« less

Thyrotoxicosis induced by excessive 3,5,3'-triiodothyronine in a dog.

PubMed

Morré, Wendy A; Panciera, David L; Daniel, Gregory B; Refsal, Kent R; Rick, Markus; Arrington, Kathy

2017-06-15

CASE DESCRIPTION A 7-year-old castrated male Havanese was evaluated at a veterinary teaching hospital because of a 12-week history of hyperactivity, aggression, and progressive weight loss despite a healthy appetite. CLINICAL FINDINGS Tachycardia was the only remarkable finding during physical examination. Serum 3,5,3'-triiodothyronine (T3) and free T3 concentrations were markedly increased, and thyroxine (T4), free T4, and thyroid-stimulating hormone concentrations were at or decreased from the respective reference ranges. Thyroid scintigraphy revealed suppressed uptake of sodium pertechnetate Tc 99m by the thyroid gland but no ectopic thyroid tissue, which was indicative of thyrotoxicosis induced by an exogenous source of T3. TREATMENT AND OUTCOME The dog was hospitalized for 24 hours, and its diet was changed, after which the clinical signs rapidly resolved and serum T3 and free T3 concentrations returned to within the respective reference ranges. This raised suspicion of an exogenous source of T3 in the dog's home environment. Analysis of the commercial beef-based canned food the dog was being fed revealed a high concentration of T3 (1.39 μg/g) and an iodine (82.44 μg/g) concentration that exceeded industry recommendations. No other source of T3 was identified in the dog's environment. CLINICAL RELEVANCE To our knowledge, this is the first report of clinical thyrotoxicosis in a dog induced by exogenous T3, although the source of exogenous T3 was not identified. This case highlights the importance of measuring serum T3 and thyroid-stimulating hormone concentrations in addition to T4 and free T4 concentrations when there is incongruity between clinical findings and thyroid function test results.

Use of 16S rRNA Gene for Identification of a Broad Range of Clinically Relevant Bacterial Pathogens

PubMed Central

Srinivasan, Ramya; Karaoz, Ulas; Volegova, Marina; MacKichan, Joanna; Kato-Maeda, Midori; Miller, Steve; Nadarajan, Rohan; Brodie, Eoin L.; Lynch, Susan V.

2015-01-01

According to World Health Organization statistics of 2011, infectious diseases remain in the top five causes of mortality worldwide. However, despite sophisticated research tools for microbial detection, rapid and accurate molecular diagnostics for identification of infection in humans have not been extensively adopted. Time-consuming culture-based methods remain to the forefront of clinical microbial detection. The 16S rRNA gene, a molecular marker for identification of bacterial species, is ubiquitous to members of this domain and, thanks to ever-expanding databases of sequence information, a useful tool for bacterial identification. In this study, we assembled an extensive repository of clinical isolates (n = 617), representing 30 medically important pathogenic species and originally identified using traditional culture-based or non-16S molecular methods. This strain repository was used to systematically evaluate the ability of 16S rRNA for species level identification. To enable the most accurate species level classification based on the paucity of sequence data accumulated in public databases, we built a Naïve Bayes classifier representing a diverse set of high-quality sequences from medically important bacterial organisms. We show that for species identification, a model-based approach is superior to an alignment based method. Overall, between 16S gene based and clinical identities, our study shows a genus-level concordance rate of 96% and a species-level concordance rate of 87.5%. We point to multiple cases of probable clinical misidentification with traditional culture based identification across a wide range of gram-negative rods and gram-positive cocci as well as common gram-negative cocci. PMID:25658760