Evaluation of clinical and histopathologic prognostic factors for survival in canine osteosarcoma of the extracranial flat and irregular bones.

PubMed

Kruse, M A; Holmes, E S; Balko, J A; Fernandez, S; Brown, D C; Goldschmidt, M H

2013-07-01

Osteosarcoma is the most common bone tumor in dogs. However, current literature focuses primarily on appendicular osteosarcoma. This study examined the prognostic value of histological and clinical factors in flat and irregular bone osteosarcomas and hypothesized that clinical factors would have a significant association with survival time while histological factors would not. All osteosarcoma biopsy samples of the vertebra, rib, sternum, scapula, or pelvis were reviewed while survival information and clinical data were obtained from medical records, veterinarians, and owners. Forty-six dogs were included in the analysis of histopathological variables and 27 dogs with complete clinical data were included in the analysis of clinical variables. In the histopathologic cox regression model, there was no significant association between any histologic feature of osteosarcoma, including grade, and survival time. In the clinical cox regression model, there was a significant association between the location of the tumor and survival time as well as between the percent elevation of alkaline phosphatase (ALP) above normal and survival time. Controlling for ALP elevation, dogs with osteosarcoma located in the scapula had a significantly greater hazard for death (2.8) compared to dogs with tumors in other locations. Controlling for tumor location, every 100% increase in ALP from normal increased the hazard for death by 1.7. For canine osteosarcomas of the flat and irregular bones, histopathological features, including grade do not appear to be rigorous predictors of survival. Clinical variables such as increased ALP levels and tumor location in the scapula were associated with decreased survival times.

Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries.

PubMed

Tomlinson, Lindsay; Boone, Laura I; Ramaiah, Lila; Penraat, Kelley A; von Beust, Barbara R; Ameri, Mehrdad; Poitout-Belissent, Florence M; Weingand, Kurt; Workman, Heather C; Aulbach, Adam D; Meyer, Dennis J; Brown, Diane E; MacNeill, Amy L; Bolliger, Anne Provencher; Bounous, Denise I

2013-09-01

The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices. © 2013 American Society for Veterinary Clinical Pathology.

Definition of variables required for comprehensive description of drug dosage and clinical pharmacokinetics.

PubMed

Medem, Anna V; Seidling, Hanna M; Eichler, Hans-Georg; Kaltschmidt, Jens; Metzner, Michael; Hubert, Carina M; Czock, David; Haefeli, Walter E

2017-05-01

Electronic clinical decision support systems (CDSS) require drug information that can be processed by computers. The goal of this project was to determine and evaluate a compilation of variables that comprehensively capture the information contained in the summary of product characteristic (SmPC) and unequivocally describe the drug, its dosage options, and clinical pharmacokinetics. An expert panel defined and structured a set of variables and drafted a guideline to extract and enter information on dosage and clinical pharmacokinetics from textual SmPCs as published by the European Medicines Agency (EMA). The set of variables was iteratively revised and evaluated by data extraction and variable allocation of roughly 7% of all centrally approved drugs. The information contained in the SmPC was allocated to three information clusters consisting of 260 variables. The cluster "drug characterization" specifies the nature of the drug. The cluster "dosage" provides information on approved drug dosages and defines corresponding specific conditions. The cluster "clinical pharmacokinetics" includes pharmacokinetic parameters of relevance for dosing in clinical practice. A first evaluation demonstrated that, despite the complexity of the current free text SmPCs, dosage and pharmacokinetic information can be reliably extracted from the SmPCs and comprehensively described by a limited set of variables. By proposing a compilation of variables well describing drug dosage and clinical pharmacokinetics, the project represents a step forward towards the development of a comprehensive database system serving as information source for sophisticated CDSS.

Dropout revisited: patient- and therapist-initiated discontinuation of psychotherapy as a function of organizational instability.

PubMed

Werbart, Andrzej; Andersson, Håkan; Sandell, Rolf

2014-01-01

To explore the association between the stability or instability of services' organizational structure and patient- and therapist-initiated discontinuation of therapy in routine mental health. Three groups, comprising altogether 750 cases in routine mental health care in eight different clinics, were included: cases with patient-initiated discontinuation, therapist-initiated discontinuation, and patients remaining in treatment. Multilevel multinomial regression was used to estimate three models: An initial, unconditional intercept-only model, another one including patient variables, and a final model with significant patient and therapist variables including the organizational stability of the therapists' clinic. High between-therapist variability was noted. Odds ratios and significance tests indicated a strong association of organizational instability with patient-initiated premature termination in particular. The question of how organizational factors influence the treatment results needs further research. Future studies have to be designed in ways that permit clinically meaningful subdivision of the patients' and the therapists' decisions for premature termination.

Heart rate variability measure in breast cancer patients and survivors: A systematic review.

PubMed

Arab, Claudia; Dias, Daniel Penteado Martins; Barbosa, Renata Thaís de Almeida; Carvalho, Tatiana Dias de; Valenti, Vitor Engrácia; Crocetta, Tânia Brusque; Ferreira, Marcelo; Abreu, Luiz Carlos de; Ferreira, Celso

2016-06-01

In the current study, we aimed to review literature findings showing the clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in breast cancer (BC) patients and survivors. We conducted a systematic review according to The PRISMA Statement in Medline, Scopus and Web of Science (_-2015) databases. The search was limited to articles in English language, published in peer-reviewed journals, and with adult age samples only (e.g., women, patients, or survivors, diagnosed with BC in any stage). We included observational studies and randomized trials. Detailed heart rate variability analysis (instruments, data collection protocol, and analysis methods) was required. Search terms included autonomic nervous system, heart rate variability, sympathetic and parasympathetic nervous system, autonomic dysfunction, vagal nervous and breast neoplasms, breast cancer and breast tumor. Twelve studies were included in this review. The clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in BC patients and survivors is demonstrated by association with effects of BC surgery, and treatments, and the adverse effects of surgery and treatments on survivors (e.g., cardiotoxicity, fatigue, and stress). The strength of evidence of included studies is low: small samples size and heterogeneity, presence of confounders, and observational studies design. The heart rate variability analysis could be used as a complementary non-invasive tool for the early diagnosis and better prognosis of autonomic dysfunction, and survival in BC patients. There are many potential clinical applications of heart rate variability analysis in BC patients, and the employment of such approaches could lead to lower impairment of autonomic function in this individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

What makes patients with fibromyalgia feel better? Correlations between Patient Global Impression of Improvement and changes in clinical symptoms and function: a pooled analysis of 4 randomized placebo-controlled trials of duloxetine.

PubMed

Hudson, James I; Arnold, Lesley M; Bradley, Laurence A; Choy, Ernest H S; Mease, Philip J; Wang, Fujun; Ahl, Jonna; Wohlreich, Madelaine M

2009-11-01

To investigate the relationship between changes in clinical rating scale items and endpoint Patient Global Impression of Improvement (PGI-I). Data were pooled from 4 randomized, double-blind, placebo-controlled studies of duloxetine in patients with fibromyalgia (FM). Variables included in the analyses were those that assessed symptoms in FM domains of pain, fatigue, sleep, cognitive difficulties, emotional well-being, physical function, and impact on daily living. The association of endpoint PGI-I with changes from baseline in individual variables was assessed using Pearson product-moment correlations (r). Stepwise linear regression was used to identify those variables for which changes from baseline were statistically significant independent predictors of the endpoint PGI-I ratings. Changes in pain variables and interference of symptoms with the ability to work were highly correlated (r >or= 0.5 or r

Logic Learning Machine and standard supervised methods for Hodgkin's lymphoma prognosis using gene expression data and clinical variables.

PubMed

Parodi, Stefano; Manneschi, Chiara; Verda, Damiano; Ferrari, Enrico; Muselli, Marco

2018-03-01

This study evaluates the performance of a set of machine learning techniques in predicting the prognosis of Hodgkin's lymphoma using clinical factors and gene expression data. Analysed samples from 130 Hodgkin's lymphoma patients included a small set of clinical variables and more than 54,000 gene features. Machine learning classifiers included three black-box algorithms ( k-nearest neighbour, Artificial Neural Network, and Support Vector Machine) and two methods based on intelligible rules (Decision Tree and the innovative Logic Learning Machine method). Support Vector Machine clearly outperformed any of the other methods. Among the two rule-based algorithms, Logic Learning Machine performed better and identified a set of simple intelligible rules based on a combination of clinical variables and gene expressions. Decision Tree identified a non-coding gene ( XIST) involved in the early phases of X chromosome inactivation that was overexpressed in females and in non-relapsed patients. XIST expression might be responsible for the better prognosis of female Hodgkin's lymphoma patients.

The quest to standardize hemodialysis care.

PubMed

Hegbrant, Jörgen; Gentile, Giorgio; Strippoli, Giovanni F M

2011-01-01

A large global dialysis provider's core activities include providing dialysis care with excellent quality, ensuring a low variability across the clinic network and ensuring strong focus on patient safety. In this article, we summarize the pertinent components of the quality assurance and safety program of the Diaverum Renal Services Group. Concerning medical performance, the key components of a successful quality program are setting treatment targets; implementing evidence-based guidelines and clinical protocols; consistently, regularly, prospectively and accurately collecting data from all clinics in the network; processing collected data to provide feedback to clinics in a timely manner, incorporating information on interclinic and intercountry variations; and revising targets, guidelines and clinical protocols based on sound scientific data. The key activities for ensuring patient safety include a standardized approach to education, i.e. a uniform education program including control of theoretical knowledge and clinical competencies; implementation of clinical policies and procedures in the organization in order to reduce variability and potential defects in clinic practice; and auditing of clinical practice on a regular basis. By applying a standardized and systematic continuous quality improvement approach throughout the entire organization, it has been possible for Diaverum to progressively improve medical performance and ensure patient safety. Copyright © 2011 S. Karger AG, Basel.

Factors affecting use of word-of-mouth by dental patients.

PubMed

Jung, Yun-Sook; Yang, Hae-Young; Choi, Youn-Hee; Kim, Eun-Kyong; Jeong, Seong-Hwa; Cho, Min-Jeong; Nam, Soon-Hyeun; Song, Keun-Bae

2018-03-23

Word-of-mouth (WOM) refers to communication among consumers, which greatly influences the marketing strategies of dental clinics. This study aimed to explore factors that affect use of WOM by dental patients and to analyse their pathways. The participants were 520 outpatients from four private dental clinics. Data were obtained from a survey using self-reported questionnaires, which included questions regarding seven latent variables: five exogenous variables, including medical service quality (physical environment, customer service, patient relationship quality) and individual characteristic variables (opinion leader tendency, social hub tendency); and two endogenous variables (intention to recommend, WOM experience). Statistical analysis was performed using structural equation modelling. Significant associations were found in the pathways between relationship quality and intention to recommend, intention to recommend and WOM, and opinion leader tendency and WOM (P < 0.001). Higher patient relationship quality and higher intention to recommend were related to positive WOM, as was higher opinion leader tendency. Improving patient relationship quality can promote positive WOM for dental clinics. Strategies are needed to promote a positive perception of dental clinics by effectively responding to the views of patients with strong opinion leader tendencies. © 2018 FDI World Dental Federation.

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

Methodological requirements for valid tissue-based biomarker studies that can be used in clinical practice.

PubMed

True, Lawrence D

2014-03-01

Paralleling the growth of ever more cost efficient methods to sequence the whole genome in minute fragments of tissue has been the identification of increasingly numerous molecular abnormalities in cancers--mutations, amplifications, insertions and deletions of genes, and patterns of differential gene expression, i.e., overexpression of growth factors and underexpression of tumor suppressor genes. These abnormalities can be translated into assays to be used in clinical decision making. In general terms, the result of such an assay is subject to a large number of variables regarding the characteristics of the available sample, particularities of the used assay, and the interpretation of the results. This review discusses the effects of these variables on assays of tissue-based biomarkers, classified by macromolecule--DNA, RNA (including micro RNA, messenger RNA, long noncoding RNA, protein, and phosphoprotein). Since the majority of clinically applicable biomarkers are immunohistochemically detectable proteins this review focuses on protein biomarkers. However, the principles outlined are mostly applicable to any other analyte. A variety of preanalytical variables impacts on the results obtained, including analyte stability (which is different for different analytes, i.e., DNA, RNA, or protein), period of warm and of cold ischemia, fixation time, tissue processing, sample storage time, and storage conditions. In addition, assay variables play an important role, including reagent specificity (notably but not uniquely an issue concerning antibodies used in immunohistochemistry), technical components of the assay, quantitation, and assay interpretation. Finally, appropriateness of an assay for clinical application is an important issue. Reference is made to publicly available guidelines to improve on biomarker development in general and requirements for clinical use in particular. Strategic goals are formulated in order to improve on the quality of biomarker reporting, including issues of analyte quality, experimental detail, assay efficiency and precision, and assay appropriateness.

Seasonal variation in diagnostic enzymes and biochemical constituents of captive northern bobwhites and passerines

USGS Publications Warehouse

Hill, E.F.; Murray, H.C.

1987-01-01

1. A variety of biochemical measurements were taken periodically in captive northern bobwhite (Colinus virginianus L.), European starlings (Sturnus vulgaris L.), red-winged blackbirds (Agelaius phoeniceus L.) and common grackles (Quiscalus quiscula L.) to determine whether baseline values remain sufficiently stable throughout the year for general clinical use in the absence of concurrent control specimens.2. Variables included whole blood hemotacrit and hemoglobin, plasma lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, aspartate aminotransferase, alinine aminotransferase, creatine kinase, butyrylcholinesterase, alkaline phosphatase, glucose, albumin, total protein, creatinine, urea nitrogen, uric acid, cholesterol, and triglycerides, and brain acetylcholinesterase. Butyrl- and acetylcholinesterase were included because of their specific uses in toxicology.3. Significant seasonal differences were detected for each of the variables except brain acetylcholinesterase in at least one of the species. Significant species differences were detected during at least one season for all of the variables measured.4. All species were maintained outdoors, but only northern bobwhites came into reproductive condition and showed sex-differences in the clinical variables during their normal breeding season.5. It was concluded that reference values for the 18 clinical variables measured could be calculated from our data for adult specimens of the species studied, and that results for one species cannot be extrapolated with certainty to any other species.6. Estimated normal bounds for each of the 18 variables measured by commonly used clinical procedures are presented for reproductively quiescent northern bobwhites, European starlings, red-winged blackbirds, and common grackles.

Prediction of Osteopathic Medical School Performance on the basis of MCAT score, GPA, sex, undergraduate major, and undergraduate institution.

PubMed

Dixon, Donna

2012-04-01

The relationships of students' preadmission academic variables, sex, undergraduate major, and undergraduate institution to academic performance in medical school have not been thoroughly examined. To determine the ability of students' preadmission academic variables to predict osteopathic medical school performance and whether students' sex, undergraduate major, or undergraduate institution influence osteopathic medical school performance. The study followed students who graduated from New York College of Osteopathic Medicine of New York Institute of Technology in Old Westbury between 2003 and 2006. Student preadmission data were Medical College Admission Test (MCAT) scores, undergraduate grade point averages (GPAs), sex, undergraduate major, and undergraduate institutional selectivity. Medical school performance variables were GPAs, clinical performance (ie, clinical subject examinations and clerkship evaluations), and scores on the Comprehensive Osteopathic Medical Licensing Examination-USA (COMLEX-USA) Level 1 and Level 2-Clinical Evaluation (CE). Data were analyzed with Pearson product moment correlation coefficients and multivariate linear regression analyses. Differences between student groups were compared with the independent-samples, 2-tailed t test. A total of 737 students were included. All preadmission academic variables, except nonscience undergraduate GPA, were statistically significant predictors of performance on COMLEX-USA Level 1, and all preadmission academic variables were statistically significant predictors of performance on COMLEX-USA Level 2-CE. The MCAT score for biological sciences had the highest correlation among all variables with COMLEX-USA Level 1 performance (Pearson r=0.304; P<.001) and Level 2-CE performance (Pearson r=0.272; P<.001). All preadmission variables were moderately correlated with the mean clinical subject examination scores. The mean clerkship evaluation score was moderately correlated with mean clinical examination results (Pearson r=0.267; P<.001) and COMLEX-USA Level 2-CE performance (Pearson r=0.301; P<.001). Clinical subject examination scores were highly correlated with COMLEX-USA Level 2-CE scores (Pearson r=0.817; P<.001). No statistically significant difference in medical school performance was found between students with science and nonscience undergraduate majors, nor was undergraduate institutional selectivity a factor influencing performance. Students' preadmission academic variables were predictive of osteopathic medical school performance, including GPAs, clinical performance, and COMLEX-USA Level 1 and Level 2-CE results. Clinical performance was predictive of COMLEX-USA Level 2-CE performance.

Use of Social Desirability Scales in Clinical Psychology: A Systematic Review.

PubMed

Perinelli, Enrico; Gremigni, Paola

2016-06-01

There is still an open debate about the utility of social desirability indicators. This report systematically reviewed the use of social desirability scales in studies addressing social desirability in clinical psychology. A systematic review (January 2010-March 2015) was conducted, including 35 studies meeting the inclusion criteria of being published in peer-reviewed journals and describing quantitative findings about an association of social desirability with clinical psychology variables using a cross-sectional or longitudinal design. Social desirability was associated with self-reports of various clinical-psychological dimensions. Most of the included studies treated social desirability as a 1-dimensional variable and only 10 of 35 disentangled the impression management and self-deception components. Although theoretical literature does not consider social desirability a mere response bias, only 4 of the reviewed articles controlled for the possible suppressor effect of personality variables on social desirability, while the majority focused upon the stylistic (response bias) rather than the substantive (personality) nature of this construct. The present review highlighted some limitations in the use of social desirability scales in recent clinical psychology research and tried to offer a few suggestions for handling this issue. © 2016 Wiley Periodicals, Inc.

Cost-evaluation model for clinical trials in a hospital pharmacy service.

PubMed

Idoate, A; Ortega, A; Carrera, F J; Aldaz, A; Giráldez, J

1995-09-22

A cost-evaluation model was applied to clinical trial protocols to estimate their cost for the hospital pharmacy service. The steps taken in the drug management of clinical research were identified. Fixed costs (common to all clinical trials) and variable costs (peculiar to each clinical trial) were determined for each step. The number of patients, the number of operations, the planned services (receptions, storage, drug dispensing), the timing and difficulty of the study (randomization) were included in the variable costs. The economic assessment of these items was based on the costs of the materials and means used, the cost of staff time and finally the cost of drug storage during the clinical trial. This model was applied to 24 clinical trials carried out in the University Clinic of Navarra. 83% of all pharmacy costs of a clinical trial were variable. Drug dispensing, stock management and return drugs account for 94% of the time expended. The approximate cost of the pharmacy providing investigational services was $1,766 per trial or $174 per patient. Drug storage costs were not an important source of expenditure among the variable costs (7.4%). The best way to determine the cost of a trial is to calculate the number of operations.

Distinct Phenotypes of Cigarette Smokers Identified by Cluster Analysis of Patients with Severe Asthma.

PubMed

Konno, Satoshi; Taniguchi, Natsuko; Makita, Hironi; Nakamaru, Yuji; Shimizu, Kaoruko; Shijubo, Noriharu; Fuke, Satoshi; Takeyabu, Kimihiro; Oguri, Mitsuru; Kimura, Hirokazu; Maeda, Yukiko; Suzuki, Masaru; Nagai, Katsura; Ito, Yoichi M; Wenzel, Sally E; Nishimura, Masaharu

2015-12-01

Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers. We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Five clinical clusters were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 1 year later. This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation. Clinical trial registered with www.umin.ac.jp (000003254).

Clinical Assessment Applications of Ambulatory Biosensors

ERIC Educational Resources Information Center

Haynes, Stephen N.; Yoshioka, Dawn T.

2007-01-01

Ambulatory biosensor assessment includes a diverse set of rapidly developing and increasingly technologically sophisticated strategies to acquire minimally disruptive measures of physiological and motor variables of persons in their natural environments. Numerous studies have measured cardiovascular variables, physical activity, and biochemicals…

Symbolic dynamics marker of heart rate variability combined with clinical variables enhance obstructive sleep apnea screening

NASA Astrophysics Data System (ADS)

Ravelo-García, A. G.; Saavedra-Santana, P.; Juliá-Serdá, G.; Navarro-Mesa, J. L.; Navarro-Esteva, J.; Álvarez-López, X.; Gapelyuk, A.; Penzel, T.; Wessel, N.

2014-06-01

Many sleep centres try to perform a reduced portable test in order to decrease the number of overnight polysomnographies that are expensive, time-consuming, and disturbing. With some limitations, heart rate variability (HRV) has been useful in this task. The aim of this investigation was to evaluate if inclusion of symbolic dynamics variables to a logistic regression model integrating clinical and physical variables, can improve the detection of subjects for further polysomnographies. To our knowledge, this is the first contribution that innovates in that strategy. A group of 133 patients has been referred to the sleep center for suspected sleep apnea. Clinical assessment of the patients consisted of a sleep related questionnaire and a physical examination. The clinical variables related to apnea and selected in the statistical model were age (p < 10-3), neck circumference (p < 10-3), score on a questionnaire scale intended to quantify daytime sleepiness (p < 10-3), and intensity of snoring (p < 10-3). The validation of this model demonstrated an increase in classification performance when a variable based on non-linear dynamics of HRV (p < 0.01) was used additionally to the other variables. For diagnostic rule based only on clinical and physical variables, the corresponding area under the receiver operating characteristic (ROC) curve was 0.907 (95% confidence interval (CI) = 0.848, 0.967), (sensitivity 87.10% and specificity 80%). For the model including the average of a symbolic dynamic variable, the area under the ROC curve was increased to 0.941 (95% = 0.897, 0.985), (sensitivity 88.71% and specificity 82.86%). In conclusion, symbolic dynamics, coupled with significant clinical and physical variables can help to prioritize polysomnographies in patients with a high probability of apnea. In addition, the processing of the HRV is a well established low cost and robust technique.

Culture as a variable in neuroscience and clinical neuropsychology: A comprehensive review

PubMed Central

Wajman, José Roberto; Bertolucci, Paulo Henrique Ferreira; Mansur, Letícia Lessa; Gauthier, Serge

2015-01-01

Culture is a dynamic system of bidirectional influences among individuals and their environment, including psychological and biological processes, which facilitate adaptation and social interaction. One of the main challenges in clinical neuropsychology involves cognitive, behavioral and functional assessment of people with different sociocultural backgrounds. In this review essay, examining culture from a historical perspective to ethical issues in cross-cultural research, including the latest significant and publications, the authors sought to explore the main features related to cultural variables in neuropsychological practice and to debate the challenges found regarding the operational methods currently in use. Literature findings suggest a more comprehensive approach in cognitive and behavioral neuroscience, including an interface between elementary disciplines and applied neuropsychology. Thus, as a basis for discussion on this issue, the authors analyzed key-topics related to the study of new trends in sociocultural neuroscience and the application of their concepts from a clinical perspective. PMID:29213964

Predicting Survival From Large Echocardiography and Electronic Health Record Datasets: Optimization With Machine Learning.

PubMed

Samad, Manar D; Ulloa, Alvaro; Wehner, Gregory J; Jing, Linyuan; Hartzel, Dustin; Good, Christopher W; Williams, Brent A; Haggerty, Christopher M; Fornwalt, Brandon K

2018-06-09

The goal of this study was to use machine learning to more accurately predict survival after echocardiography. Predicting patient outcomes (e.g., survival) following echocardiography is primarily based on ejection fraction (EF) and comorbidities. However, there may be significant predictive information within additional echocardiography-derived measurements combined with clinical electronic health record data. Mortality was studied in 171,510 unselected patients who underwent 331,317 echocardiograms in a large regional health system. We investigated the predictive performance of nonlinear machine learning models compared with that of linear logistic regression models using 3 different inputs: 1) clinical variables, including 90 cardiovascular-relevant International Classification of Diseases, Tenth Revision, codes, and age, sex, height, weight, heart rate, blood pressures, low-density lipoprotein, high-density lipoprotein, and smoking; 2) clinical variables plus physician-reported EF; and 3) clinical variables and EF, plus 57 additional echocardiographic measurements. Missing data were imputed with a multivariate imputation by using a chained equations algorithm (MICE). We compared models versus each other and baseline clinical scoring systems by using a mean area under the curve (AUC) over 10 cross-validation folds and across 10 survival durations (6 to 60 months). Machine learning models achieved significantly higher prediction accuracy (all AUC >0.82) over common clinical risk scores (AUC = 0.61 to 0.79), with the nonlinear random forest models outperforming logistic regression (p < 0.01). The random forest model including all echocardiographic measurements yielded the highest prediction accuracy (p < 0.01 across all models and survival durations). Only 10 variables were needed to achieve 96% of the maximum prediction accuracy, with 6 of these variables being derived from echocardiography. Tricuspid regurgitation velocity was more predictive of survival than LVEF. In a subset of studies with complete data for the top 10 variables, multivariate imputation by chained equations yielded slightly reduced predictive accuracies (difference in AUC of 0.003) compared with the original data. Machine learning can fully utilize large combinations of disparate input variables to predict survival after echocardiography with superior accuracy. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Hyponatremia and fractures: should hyponatremia be further studied as a potential biochemical risk factor to be included in FRAX algorithms?

PubMed

Ayus, J C; Bellido, T; Negri, A L

2017-05-01

The Fracture Risk Assessment Tool (FRAX®) was developed by the WHO Collaborating Centre for metabolic bone diseases to evaluate fracture risk of patients. It is based on patient models that integrate the risk associated with clinical variables and bone mineral density (BMD) at the femoral neck. The clinical risk factors included in FRAX were chosen to include only well-established and independent variables related to skeletal fracture risk. The FRAX tool has acquired worldwide acceptance despite having several limitations. FRAX models have not included biochemical derangements in estimation of fracture risk due to the lack of validation in large prospective studies. Recently, there has been an increasing number of studies showing a relationship between hyponatremia and the occurrence of fractures. Hyponatremia is the most frequent electrolyte abnormality measured in the clinic, and serum sodium concentration is a very reproducible, affordable, and readily obtainable measurement. Thus, we think that hyponatremia should be further studied as a biochemical risk factor for skeletal fractures prediction, particularly those at the hip which carries the greatest morbidity and mortality. To achieve this will require the collection of large patient cohorts from diverse geographical locations that include a measure of serum sodium in addition to the other FRAX variables in large numbers, in both sexes, over a wide age range and with wide geographical representation. It would also require the inclusion of data on duration and severity of hyponatremia. Information will be required both on the risk of fracture associated with the occurrence and length of exposure to hyponatremia and to the relationship with the other risk variables included in FRAX and also the independent effect on the occurrence of death which is increased by hyponatremia.

Perspective: Recommendations for benchmarking pre-clinical studies of nanomedicines

PubMed Central

Dawidczyk, Charlene M.; Russell, Luisa M.; Searson, Peter C.

2015-01-01

Nanoparticle-based delivery systems provide new opportunities to overcome the limitations associated with traditional small molecule drug therapy for cancer, and to achieve both therapeutic and diagnostic functions in the same platform. Pre-clinical trials are generally designed to assess therapeutic potential and not to optimize the design of the delivery platform. Consequently, progress in developing design rules for cancer nanomedicines has been slow, hindering progress in the field. Despite the large number of pre-clinical trials, several factors restrict comparison and benchmarking of different platforms, including variability in experimental design, reporting of results, and the lack of quantitative data. To solve this problem, we review the variables involved in the design of pre-clinical trials and propose a protocol for benchmarking that we recommend be included in in vivo pre-clinical studies of drug delivery platforms for cancer therapy. This strategy will contribute to building the scientific knowledge base that enables development of design rules and accelerates the translation of new technologies. PMID:26249177

Clinical Efficacy and Its Prognostic Factor of Percutaneous Endoscopic Lumbar Annuloplasty and Nucleoplasty for the Treatment of Patients with Discogenic Low Back Pain.

PubMed

Lee, Jung Hwan; Lee, Sang-Ho

2017-09-01

The choice of appropriate treatment of discogenic low back pain (DLBP) frequently is difficult. This study sought to identify the clinical efficacy of percutaneous endoscopic lumbar annuloplasty and nucleoplasty (PELAN) to treat patients with DLBP and to investigate prognostic clinical or radiologic variables. Eighty-nine patients with a diagnosis of DLBP who underwent PELAN were included. Numeric Rating Scale (NRS) for back pain, Oswestry Disability Index % (ODI%), and modified Macnab criteria were measured at short-term (3-4 weeks) and long-term follow-up period (at least 12 months) to investigate clinical efficacy of PELAN. The subjects were defined as successful group in case of 50% or more reduction of NRS, 40% or more reduction of ODI%, and good or excellent response of Macnab criteria. Clinical and radiologic variables were compared between successful and unsuccessful outcomes group to determine prognostic variables. NRS and ODI% were significantly reduced at short- and long-term follow-up after PELAN. Sixty-two (69.7%) and 68 (76.4%) obtained successful NRS reduction and 59 (66.3%) and 68 (76.4%) accomplished successful ODI% reduction at short-term and long-term follow-up, respectively. Successful Mcnab response was found in 61% at short term and 65.2% at long term. Pain during waist flexion among clinical variables was significantly related to good clinical outcomes and Modic change among radiologic variables was significantly related to poor clinical outcomes. PELAN provided favorable outcomes in patients with DLBP who were refractory to conservative treatments. Flexion pain was good prognostic, and Modic change was a poor prognostic variable. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Assessment of Cognitive Function in Patients with Head and Neck Cancer: Prevalence and Correlates.

PubMed

Williams, Amy M; Lindholm, Jamie; Siddiqui, Farzan; Ghanem, Tamer A; Chang, Steven S

2017-11-01

Objective Identify the prevalence and clinical correlates of cognitive impairment in patients presenting for treatment of head and neck cancer (HNC) using brief screening within a multidisciplinary care team. Study Design A case series with planned data collection of cognitive function, quality of life (QoL), and psychosocial variables. Setting Urban Midwest academic medical center. Subjects and Methods In total, 209 consecutive patients with a diagnosis of HNC between August 2015 and September 2016 who had a pretreatment assessment with a clinical health psychologist. At pretreatment assessment, the Montreal Cognitive Assessment (MoCA), a brief screening tool for cognitive function, was administered along with a semistructured interview to gather information on psychiatric symptoms, social support, and substance use. Patient information, including demographics, clinical variables, and psychosocial variables, was extracted via chart review. A subset of patients with HNC completed the Functional Assessment of Cancer Therapy-Head and Neck Cancer at pretreatment assessment and was included in the QoL analyses. Results Cognitive impairment was associated with current alcohol use, past tobacco use and number of pack years, time in radiotherapy, and adherence to treatment recommendations. Social, emotional, and functional QoL scales were associated with cognitive impairment, including executive function, language, and memory. Conclusion Cognitive impairment is common in patients with HNC, and there are important associations between cognitive impairment and psychosocial, QoL, and treatment adherence variables. The results argue for the incorporation of cognitive screening as part of pretreatment assessment for patients, as well as further research into more direct, causal relationships via longitudinal, prospective studies.

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model

PubMed Central

Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo

2017-01-01

Background Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. Methods The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. Results The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. Conclusion The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients. PMID:29020031

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model.

PubMed

Ramírez, Julia; Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo; Laguna, Pablo; Pueyo, Esther

2017-01-01

Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients.

Blood pressure (BP) assessment-from BP level to BP variability.

PubMed

Feber, Janusz; Litwin, Mieczyslaw

2016-07-01

The assessment of blood pressure (BP) can be challenging in children, especially in very young individuals, due to their variable body size and lack of cooperation. In the absence of data relating BP with cardiovascular outcomes in children, there is a need to convert absolute BP values (in mmHg) into age-, gender- and height appropriate BP percentiles or Z-scores in order to compare a patient's BP with the BP of healthy children of the same age, but also of children of different ages. Traditionally, the interpretation of BP has been based mainly on the assessment of the BP level obtained by office, home or 24-h BP monitoring. Recent studies suggest that it is not only BP level (i.e. average BP) but also BP variability that is clinically important for the development of target organ damage, including the progression of chronic kidney disease. In this review we describe current methods to evaluate of BP level, outline available methods for BP variability assessment and discuss the clinical consequences of BP variability, including its potential role in the management of hypertension.

Development of a Core Clinical Dataset to Characterize Serious Illness, Injuries, and Resource Requirements for Acute Medical Responses to Public Health Emergencies.

PubMed

Murphy, David J; Rubinson, Lewis; Blum, James; Isakov, Alexander; Bhagwanjee, Statish; Cairns, Charles B; Cobb, J Perren; Sevransky, Jonathan E

2015-11-01

In developed countries, public health systems have become adept at rapidly identifying the etiology and impact of public health emergencies. However, within the time course of clinical responses, shortfalls in readily analyzable patient-level data limit capabilities to understand clinical course, predict outcomes, ensure resource availability, and evaluate the effectiveness of diagnostic and therapeutic strategies for seriously ill and injured patients. To be useful in the timeline of a public health emergency, multi-institutional clinical investigation systems must be in place to rapidly collect, analyze, and disseminate detailed clinical information regarding patients across prehospital, emergency department, and acute care hospital settings, including ICUs. As an initial step to near real-time clinical learning during public health emergencies, we sought to develop an "all-hazards" core dataset to characterize serious illness and injuries and the resource requirements for acute medical response across the care continuum. A multidisciplinary panel of clinicians, public health professionals, and researchers with expertise in public health emergencies. Group consensus process. The consensus process included regularly scheduled conference calls, electronic communications, and an in-person meeting to generate candidate variables. Candidate variables were then reviewed by the group to meet the competing criteria of utility and feasibility resulting in the core dataset. The 40-member panel generated 215 candidate variables for potential dataset inclusion. The final dataset includes 140 patient-level variables in the domains of demographics and anthropometrics (7), prehospital (11), emergency department (13), diagnosis (8), severity of illness (54), medications and interventions (38), and outcomes (9). The resulting all-hazard core dataset for seriously ill and injured persons provides a foundation to facilitate rapid collection, analyses, and dissemination of information necessary for clinicians, public health officials, and policymakers to optimize public health emergency response. Further work is needed to validate the effectiveness of the dataset in a variety of emergency settings.

Epilepsy-related clinical factors and psychosocial functions in pediatric epilepsy.

PubMed

Eom, Soyong; Eun, So-Hee; Kang, Hoon-Chul; Eun, Baik-Lin; Nam, Sang Ook; Kim, Sun Jun; Chung, Hee Jung; Kwon, Soon Hak; Lee, Young-Mock; Lee, Joon Soo; Kim, Dong Wook; Oh, Kyung Ja; Kim, Heung Dong

2014-08-01

The aim of this study was to identify the different influencing patterns of demographic and epilepsy-related variables on various aspects of psychosocial function in pediatric epilepsy. Five hundred ninety-eight patients with pediatric epilepsy between the ages of 4 and 18 years (boys=360, 60% and girls=238, 40%) and their parents participated in the study. Parents completed the Social Maturity Scale (SMS), the Korean version of the Child Behavior Checklist (K-CBCL), and the Korean version of the Quality of Life in Childhood Epilepsy Questionnaire (K-QOLCE) to assess daily living function, behavior, and quality of life. The Children's Global Assessment Scale (CGAS) was completed by clinicians to assess general adaptive function. Demographic variables, such as age and sex of child, and epilepsy-related clinical variables, including seizure type, seizure frequency, duration of epilepsy, and number of medications, were obtained from medical records. Demographic and epilepsy-related clinical variables had a strong influence (22-32%) on the cognition-related domain such as general adaptive function, school/total competence, and quality of life for cognitive function while a comparatively smaller effect (2-16%) on the more psychological domain including behavioral, emotional, and social variables. Younger age, shorter duration of illness, and smaller number of medications showed a strong positive impact on psychosocial function in pediatric epilepsy, particularly for adaptive function, competence, and quality-of-life aspects. Given the wide range of impact of demographic and clinical variables on various facets of psychosocial functions, more specific understanding of the various aspects of factors and their particular pattern of influence may enable more effective therapeutic approaches that address both the medical and psychological needs in pediatric epilepsy. Copyright © 2014 Elsevier Inc. All rights reserved.

[Individual parameters of general low-frequency magnetic therapy as a possibility for improving the clinical efficacy of the combined treatment of patients with essential arterial hypertension].

PubMed

Fedotov, V D; Maslov, A G; Lobkaeva, E P; Krylov, V N; Obukhova, E O

2012-01-01

A new approach is proposed for the choice of low-frequency magnetic therapy on an individual basis using the results of analysis of heart rhythm variability. The clinical efficiency of low-frequency magnetic therapy incorporated in the combined treatment of 65 patients aged between 25 and 45 years with essential arterial hypertension was estimated. The statistically significant positive effects of the treatment included normalization of blood pressure and characteristics of heart rhythm variability as well as resolution of clinical symptoms of vegetative dysregulation.

PubMed Central

MAGGI, LORENZO; SALERNO, FRANCO; BRAGATO, CINZIA; SAREDI, SIMONA; BLASEVICH, FLAVIA; MACCAGNANO, ELIO; PASANISI, BARBARA; DANESINO, CESARE; MORA, MARINA; MORANDI, LUCIA

2013-01-01

The adult-onset form of Pompe disease had a wide clinical spectrum, ranging from asymptomatic patients with increased CK to muscle cramps and pain syndrome or rigid-spine syndrome. In addition clinical severity and disease progression are greatly variable. We report on a family with 3 siblings characterized by an unusual adult-onset Pompe disease including dysphagia and weakness of tongue, axial and limb-girdle muscles, in association with atypical globular inclusions in muscle fibres. Our study confirms the great clinical and histological variability of adult-onset Pompe disease and further supports the need of careful evaluation of bulbar function in patients affected by this pathology. PMID:24399864

Strategies and methods to study female-specific cardiovascular health and disease: a guide for clinical scientists.

PubMed

Ouyang, Pamela; Wenger, Nanette K; Taylor, Doris; Rich-Edwards, Janet W; Steiner, Meir; Shaw, Leslee J; Berga, Sarah L; Miller, Virginia M; Merz, Noel Bairey

2016-01-01

In 2001, the Institute of Medicine's (IOM) report, "Exploring the Biological Contributions to Human Health: Does Sex Matter?" advocated for better understanding of the differences in human diseases between the sexes, with translation of these differences into clinical practice. Sex differences are well documented in the prevalence of cardiovascular (CV) risk factors, the clinical manifestation and incidence of cardiovascular disease (CVD), and the impact of risk factors on outcomes. There are also physiologic and psychosocial factors unique to women that may affect CVD risk, such as issues related to reproduction. The Society for Women's Health Research (SWHR) CV Network compiled an inventory of sex-specific strategies and methods for the study of women and CV health and disease across the lifespan. References for methods and strategy details are provided to gather and evaluate this information. Some items comprise robust measures; others are in development. To address female-specific CV health and disease in population, physiology, and clinical trial research, data should be collected on reproductive history, psychosocial variables, and other factors that disproportionately affect CVD in women. Variables related to reproductive health include the following: age of menarche, menstrual cycle regularity, hormone levels, oral contraceptive use, pregnancy history/complications, polycystic ovary syndrome (PCOS) components, menopause age, and use and type of menopausal hormone therapy. Other factors that differentially affect women's CV risk include diabetes mellitus, autoimmune inflammatory disease, and autonomic vasomotor control. Sex differences in aging as well as psychosocial variables such as depression and stress should also be considered. Women are frequently not included/enrolled in mixed-sex CVD studies; when they are included, information on these variables is generally not collected. These omissions limit the ability to determine the role of sex-specific contributors to CV health and disease. Lack of sex-specific knowledge contributes to the CVD health disparities that women face. The purpose of this review is to encourage investigators to consider ways to increase the usefulness of physiological and psychosocial data obtained from clinical populations, in an effort to improve the understanding of sex differences in clinical CVD research and health-care delivery for women and men.

Identifying factors which enhance capacity to engage in clinical education among podiatry practitioners: an action research project.

PubMed

Abey, Sally; Lea, Susan; Callaghan, Lynne; Shaw, Steve; Cotton, Debbie

2015-01-01

Health profession students develop practical skills whilst integrating theory with practice in a real world environment as an important component of their training. Research in the area of practice placements has identified challenges and barriers to the delivery of effective placement learning. However, there has been little research in podiatry and the question of which factors impact upon clinical educators' capacity to engage with the role remains an under-researched area. This paper presents the second phase of an action research project designed to determine the factors that impact upon clinical educators' capacity to engage with the mentorship role. An online survey was developed and podiatry clinical educators recruited through National Health Service (NHS) Trusts. The survey included socio-demographic items, and questions relating to the factors identified as possible variables influencing clinical educator capacity; the latter was assessed using the 'Clinical Educator Capacity to Engage' scale (CECE). Descriptive statistics were used to explore demographic data whilst the relationship between the CECE and socio-demographic factors were examined using inferential statistics in relation to academic profile, career profile and organisation of the placement. The survey response rate was 42 % (n = 66). Multiple linear regression identified four independent variables which explain a significant proportion of the variability of the dependent variable, 'capacity to engage with clinical education', with an adjusted R2 of 0.428. The four variables were: protected mentorship time, clinical educator relationship with university, sign-off responsibility, and volunteer status. The identification of factors that impact upon clinical educators' capacity to engage in mentoring of students has relevance for strategic planning and policy-making with the emphasis upon capacity-building at an individual level, so that the key attitudes and characteristics that are linked with good clinical supervision are preserved.

Factors associated with poor functional outcome in bipolar disorder: sociodemographic, clinical, and neurocognitive variables.

PubMed

Sanchez-Moreno, J; Bonnin, C M; González-Pinto, A; Amann, B L; Solé, B; Balanzá-Martinez, V; Arango, C; Jiménez, E; Tabarés-Seisdedos, R; Garcia-Portilla, M P; Ibáñez, A; Crespo, J M; Ayuso-Mateos, J L; Martinez-Aran, A; Torrent, C; Vieta, E

2018-05-03

The current investigation aimed at studying the sociodemographic, clinical, and neuropsychological variables related to functional outcome in a sample of euthymic patients with bipolar disorder(BD) presenting moderate-severe levels of functional impairment. Two-hundred and thirty-nine participants with BD disorders and with Functioning Assessment Short Test(FAST) scores equal or above 18 were administered a clinical and diagnostic interview, and the administration of mood measure scales and a comprehensive neuropsychological battery. Analyses involved preliminary Pearson bivariate correlations to identify sociodemographic and clinical variables associated with the FAST total score. Regarding neuropsychological variables, a principal component analysis (PCA) was performed to group the variables in orthogonal factors. Finally, a hierarchical multiple regression was run. The best fitting model for the variables associated with functioning was a linear combination of gender, age, estimated IQ, Hamilton Depression Rating Scale (HAM-D), number of previous manic episodes, Factor 1 and Factor 2 extracted from the PCA. The model, including all these previous variables, explained up to 29.4% of the observed variance. Male gender, older age, lower premorbid IQ, subdepressive symptoms, higher number of manic episodes, and lower performance in verbal memory, working memory, verbal fluency, and processing speed were associated with lower functioning in patients with BD. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Factors contributing to tooth loss among the elderly: A cross sectional study.

PubMed

Natto, Zuhair S; Aladmawy, Majdi; Alasqah, Mohammed; Papas, Athena

2014-12-01

The present study evaluates the influence of several demographic, health, personal, and clinical factors on the number of missing teeth in old age sample. The number of patients included was 259; they received a full mouth examination and answered a questionnaire provided by one examiner. All the variables related to teeth loss based on the literature were included. These variables focused on age, gender, race, marital status, clinical attachment level, pocket depth, year of smoking, number of cigarettes smoked per day, number of medications, root decay, coronal decay, health status, and year of education. Statistical analysis involved stepwise multivariate linear regression. Teeth loss was statistically associated with clinical attachment level (CAL)(p value 0.0001), pocket depth (PD) (0.0007) and education level (0.0048). When smoking was included in the model, age was significantly associated with teeth loss (0.0037). At least one of these four factors was also related to teeth loss in several specific groups such as diabetes mellitus, male, and White. The multiple linear regressions for all the proposed variables showed that they contributed to teeth loss by about 23%. It can be concluded that less education or increased clinical attachment level loss may increase number of missing teeth. Additionally, age may cause teeth loss in the presence of smoking. Copyright © 2014. Published by Elsevier B.V.

Glomerular disease: why is there a dearth of high quality clinical trials?

PubMed

Leaf, David E; Appel, Gerald B; Radhakrishnan, Jai

2010-08-01

There is a paucity of high quality clinical trials in glomerular disease, particularly in non-diabetic kidney disease. The aims of this review include quantifying the extent of this problem and exploring reasons for the scarcity of such trials in primary glomerular disease, with an emphasis on immunoglobulin A nephropathy, minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy in comparison with the more common diseases of diabetic nephropathy and lupus nephritis. Reasons for the dearth of high quality clinical trials in primary glomerular disease include (1) low prevalence of disease; (2) variability in clinical presentation; (3) variability in treatment response; (4) lack of consensus in definitions; (5) difficulty in recruiting patients; (6) high costs of randomized controlled trials; and (7) lack of collaborative efforts. To facilitate greater numbers of high quality clinical trials in glomerular disease, practice guidelines should establish common classification systems of disease and common clinical end points, industry and non-industry sponsored research should find common ground and work together toward advancing science, and national registries should be created to encourage collaborations across institutions and across nations.

Sex Bias Exists in Human Surgical Clinical Research

PubMed Central

Mansukhani, Neel A.; Yoon, Dustin Y.; Teter, Katherine A.; Stubbs, Vanessa C.; Helenowski, Irene B.; Woodruff, Teresa K.; Kibbe, Melina R.

2016-01-01

Importance Sex is a variable that is poorly controlled for in clinical research. Objective Determine if sex bias exists in human surgical clinical research, determine if data are reported and analyzed using sex as an independent variable, and identify specialties where the greatest and least sex biases exist. Design Review and data abstraction from published peer-reviewed manuscripts. Setting All original peer-reviewed manuscripts published in 2011 and 2012 in Annals of Surgery, American Journal of Surgery, JAMA Surgery, Journal of Surgical Research, and Surgery. Main Outcome Measures Study type, location, number and sex of subjects, sex matching, and inclusion of sex-based reporting, statistical analysis, and discussion of data. Results Of 2,347 articles reviewed, 1,668 included human subjects. After excluding 365 articles, 1,303 manuscripts remained: 17 (1%) included only males, 41 (3%) included only females, 1,020 (78%) included males and females, and 225 (17%) did not document the sex of the subjects. While females represent over 50% of the total number of subjects included, considerable variability existed with the number of male, female, and unspecified subjects included among the journals, between US domestic and international studies, and between single versus multi-center studies. For manuscripts included in the study, only 38% reported these data by sex, 33% analyzed these data by sex, and 23% included a discussion of sex-based results. Sex matching of the subjects included in the research was poor, with only 18% of the studies matching the inclusion of both sexes by 80%. Upon analysis of the different surgical specialties, a wide variation in sex-based inclusion, matching, and data reporting existed, with colorectal surgery having the best matching of males and females and cardiac surgery having the worst. Conclusion Our data show that sex bias exists in human surgical clinical research. Few studies included men and women equally, less than one-third performed data analysis by sex, and there was wide variation in inclusion and matching of the sexes among the specialties and the journals reviewed. Because clinical research serves as the foundation for evidence-based medicine, it is imperative that this disparity be addressed so that therapies benefit both sexes. PMID:27551816

P09.62 Towards individualized survival prediction in glioblastoma patients using machine learning methods

PubMed Central

Vera, L.; Pérez-Beteta, J.; Molina, D.; Borrás, J. M.; Benavides, M.; Barcia, J. A.; Velásquez, C.; Albillo, D.; Lara, P.; Pérez-García, V. M.

2017-01-01

Abstract Introduction: Machine learning methods are integrated in clinical research studies due to their strong capability to discover parameters having a high information content and their predictive combined potential. Several studies have been developed using glioblastoma patient’s imaging data. Many of them have focused on including large numbers of variables, mostly two-dimensional textural features and/or genomic data, regardless of their meaning or potential clinical relevance. Materials and methods: 193 glioblastoma patients were included in the study. Preoperative 3D magnetic resonance images were collected and semi-automatically segmented using an in-house software. After segmentation, a database of 90 parameters including geometrical and textural image-based measures together with patients’ clinical data (including age, survival, type of treatment, etc.) was constructed. The criterion for including variables in the study was that they had either shown individual impact on survival in single or multivariate analyses or have a precise clinical or geometrical meaning. These variables were used to perform several machine learning experiments. In a first set of computational cross-validation experiments based on regression trees, those attributes showing the highest information measures were extracted. In the second phase, more sophisticated learning methods were employed in order to validate the potential of the previous variables predicting survival. Concretely support vector machines, neural networks and sparse grid methods were used. Results: Variables showing high information measure in the first phase provided the best prediction results in the second phase. Specifically, patient age, Stupp regimen and a geometrical measure related with the irregularity of contrast-enhancing areas were the variables showing the highest information measure in the first stage. For the second phase, the combinations of patient age and Stupp regimen together with one tumor geometrical measure and one tumor heterogeneity feature reached the best quality prediction. Conclusions: Advanced machine learning methods identified the parameters with the highest information measure and survival predictive potential. The uninformed machine learning methods identified a novel feature measure with direct impact on survival. Used in combination with other previously known variables multi-indexes can be defined that can help in tumor characterization and prognosis prediction. Recent advances on the definition of those multi-indexes will be reported in the conference. Funding: James S. Mc. Donnell Foundation (USA) 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer [Collaborative award 220020450 and planning grant 220020420], MINECO/FEDER [MTM2015-71200-R], JCCM [PEII-2014-031-P].

Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease.

PubMed

Borgarelli, M; Savarino, P; Crosara, S; Santilli, R A; Chiavegato, D; Poggi, M; Bellino, C; La Rosa, G; Zanatta, R; Haggstrom, J; Tarducci, A

2008-01-01

There are few studies evaluating the natural history and prognostic variables in chronic mitral valve disease (CMVI) in a heterogeneous population of dogs. To estimate survival and prognostic value of clinical and echocardiographic variables in dogs with CMVI of varying severity. Five hundred and fifty-eight dogs belonging to 36 breeds were studied. Dogs were included after clinical examination and echocardiography. Long-term outcome was assessed by telephone interview with the owner. The mean follow-up time was 22.7 +/- 13.6 months, and the median survival time was 19.5 +/- 13.2 months. In univariate analysis, age>8 years, syncope, HR>140 bpm, dyspnea, arrhythmias, class of heart failure (International Small Animal Cardiac Health Council), furosemide therapy, end-systolic volume-index (ESV-I)>30 mL/m(2), left atrial to aortic root ratio (LA/Ao)>1.7, E wave transmitral peak velocity (Emax)>1.2 m/s, and bilateral mitral valve leaflet engagement were associated with survival time when all causes of death were included. For the cardiac-related deaths, all the previous variables except dyspnea and EDV-I>100 mL/m(2) were significantly associated with survival time. Significant variables in multivariate analysis (all causes of death) were syncope, LA/Ao>1.7 m/s, and Emax>1.2 m/s. For cardiac-related death, the only significant variable was LA/Ao>1.7. Mild CMVI is a relatively benign condition in dogs. However, some clinical variables can identify dogs at a higher risk of death; these variables might be useful to identify individuals that need more frequent monitoring or therapeutic intervention.

Prediction of early weight gain during psychotropic treatment using a combinatorial model with clinical and genetic markers.

PubMed

Vandenberghe, Frederik; Saigí-Morgui, Núria; Delacrétaz, Aurélie; Quteineh, Lina; Crettol, Séverine; Ansermot, Nicolas; Gholam-Rezaee, Mehdi; von Gunten, Armin; Conus, Philippe; Eap, Chin B

2016-12-01

Psychotropic drugs can induce significant (>5%) weight gain (WG) already after 1 month of treatment, which is a good predictor for major WG at 3 and 12 months. The large interindividual variability of drug-induced WG can be explained in part by genetic and clinical factors. The aim of this study was to determine whether extensive analysis of genes, in addition to clinical factors, can improve prediction of patients at risk for more than 5% WG at 1 month of treatment. Data were obtained from a 1-year naturalistic longitudinal study, with weight monitoring during weight-inducing psychotropic treatment. A total of 248 Caucasian psychiatric patients, with at least baseline and 1-month weight measures, and with compliance ascertained were included. Results were tested for replication in a second cohort including 32 patients. Age and baseline BMI were associated significantly with strong WG. The area under the curve (AUC) of the final model including genetic (18 genes) and clinical variables was significantly greater than that of the model including clinical variables only (AUCfinal: 0.92, AUCclinical: 0.75, P<0.0001). Predicted accuracy increased by 17% with genetic markers (Accuracyfinal: 87%), indicating that six patients must be genotyped to avoid one misclassified patient. The validity of the final model was confirmed in a replication cohort. Patients predicted before treatment as having more than 5% WG after 1 month of treatment had 4.4% more WG over 1 year than patients predicted to have up to 5% WG (P≤0.0001). These results may help to implement genetic testing before starting psychotropic drug treatment to identify patients at risk of important WG.

Negative psychological aspects and survival in lung cancer patients.

PubMed

Nakaya, Naoki; Saito-Nakaya, Kumi; Akechi, Tatsuo; Kuriyama, Shinichi; Inagaki, Masatoshi; Kikuchi, Nobutaka; Nagai, Kanji; Tsugane, Shoichiro; Nishiwaki, Yutaka; Tsuji, Ichiro; Uchitomi, Yosuke

2008-05-01

We conducted a prospective cohort study in Japan to investigate associations between negative psychological aspects and cancer survival. Between July 1999 and July 2004, a total of 1178 lung cancer patients were enrolled. The questionnaire asked about socioeconomic variables, smoking status, clinical symptoms, and psychological aspects after diagnosis. Negative psychological aspects were assessed for the subscales of helplessness/hopelessness and depression. Clinical stage, performance status (PS), and histologic type were obtained from medical charts. The subjects were followed up until December 2004, and 686 had died. A Cox regression model was used to estimate the hazards ratio (HR) of all-cause mortality. After adjustment for socioeconomic variables and smoking status in addition to sex, age, and histologic type, both helplessness/hopelessness and depression subscales showed significant linear positive associations with the risk of mortality (p for trend<0.001 for both). However, after adjustment for clinical state variables in addition to sex, age, and histologic type, these significant linear positive associations were no longer observed (p for trend=0.41 and 0.26, respectively). Our data supported the hypothesis that the association between helplessness/hopelessness and depression and the risk of mortality among lung cancer patients was largely confounded by clinical state variables including clinical stage, PS, and clinical symptoms. (c) 2007 John Wiley & Sons, Ltd.

Clinical, laboratory, and hemostatic findings in cats with naturally occurring sepsis.

PubMed

Klainbart, Sigal; Agi, Limor; Bdolah-Abram, Tali; Kelmer, Efrat; Aroch, Itamar

2017-11-01

OBJECTIVE To characterize clinical and laboratory findings in cats with naturally occurring sepsis, emphasizing hemostasis-related findings, and evaluate these variables for associations with patient outcomes. DESIGN Prospective, observational, clinical study. ANIMALS 31 cats with sepsis and 33 healthy control cats. PROCEDURES Data collected included history; clinical signs; results of hematologic, serum biochemical, and hemostatic tests; diagnosis; and outcome (survival vs death during hospitalization or ≤ 30 days after hospital discharge). Differences between cats with and without sepsis and associations between variables of interest and death were analyzed statistically. RESULTS The sepsis group included cats with pyothorax (n = 10), septic peritonitis (7), panleukopenia virus infection (5), bite wounds (5), abscesses and diffuse cellulitis (3), and pyometra (1). Common clinical abnormalities included dehydration (21 cats), lethargy (21), anorexia (18), pale mucous membranes (15), and dullness (15). Numerous clinicopathologic abnormalities were identified in cats with sepsis; novel findings included metarubricytosis, hypertriglyceridemia, and high circulating muscle enzyme activities. Median activated partial thromboplastin time and plasma D-dimer concentrations were significantly higher, and total protein C and antithrombin activities were significantly lower, in the sepsis group than in healthy control cats. Disseminated intravascular coagulopathy was uncommon (4/22 [18%] cats with sepsis). None of the clinicopathologic abnormalities were significantly associated with death on multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE Cats with sepsis had multiple hematologic, biochemical, and hemostatic abnormalities on hospital admission, including several findings suggestive of hemostatic derangement. Additional research including larger numbers of cats is needed to further investigate these findings and explore associations with outcome.

Cluster Analysis of Clinical Data Identifies Fibromyalgia Subgroups

PubMed Central

Docampo, Elisa; Collado, Antonio; Escaramís, Geòrgia; Carbonell, Jordi; Rivera, Javier; Vidal, Javier; Alegre, José

2013-01-01

Introduction Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. Material and Methods 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. Results Variables clustered into three independent dimensions: “symptomatology”, “comorbidities” and “clinical scales”. Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. Conclusions We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment. PMID:24098674

Effect of mixed mutans streptococci colonization on caries development.

PubMed

Seki, M; Yamashita, Y; Shibata, Y; Torigoe, H; Tsuda, H; Maeno, M

2006-02-01

To evaluate the clinical importance of mixed mutans streptococci colonization in predicting caries in preschool children. Caries prevalence was examined twice, with a 6-month interval, in 410 preschool children aged 3-4 years at baseline. A commercial strip method was used to evaluate the mutans streptococci score in plaque collected from eight selected interdental spaces and in saliva. Mutans streptococci typing polymerase chain reaction (PCR) assays (Streptococcus sobrinus and Streptococcus mutans, including serotypes c, e, and f) were performed using colonies on the strips as template. Twenty variables were examined in a univariate analysis to predict caries development: questionnaire variables, results of clinical examination, mutans streptococci scores, and PCR detection of S. sobrinus and S. mutans (including serotypes c, e, and f). Sixteen variables showed statistically significant associations (P < 0.04) in the univariate analysis. However, when entered into a logistic regression, only five variables remained significant (P < 0.05): caries experience at baseline; mixed colonization of S. sobrinus and S. mutans including S. mutans serotypes; high plaque mutans streptococci score; habitual use of sweet drinks; and nonuse of fluoride toothpaste. 'Mixed mutans streptococci colonization' is a novel measure correlated with caries development in their primary dentition.

Early Clinical Manifestations Associated with Death from Visceral Leishmaniasis

PubMed Central

de Araújo, Valdelaine Etelvina Miranda; Morais, Maria Helena Franco; Reis, Ilka Afonso; Rabello, Ana; Carneiro, Mariângela

2012-01-01

Background In Brazil, lethality from visceral leishmaniasis (VL) is high and few studies have addressed prognostic factors. This historical cohort study was designed to investigate the prognostic factors for death from VL in Belo Horizonte (Brazil). Methodology The analysis was based on data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health) relating to the clinical manifestations of the disease. During the study period (2002–2009), the SINAN changed platform from a Windows to a Net-version that differed with respect to some of the parameters collected. Multivariate logistic regression models were performed to identify variables associated with death from VL, and these were included in prognostic score. Principal Findings Model 1 (period 2002–2009; 111 deaths from VL and 777 cured patients) included the variables present in both SINAN versions, whereas Model 2 (period 2007–2009; 49 deaths from VL and 327 cured patients) included variables common to both SINAN versions plus the additional variables included in the Net version. In Model 1, the variables significantly associated with a greater risk of death from VL were weakness (OR 2.9; 95%CI 1.3–6.4), Leishmania-HIV co-infection (OR 2.4; 95%CI 1.2–4.8) and age ≥60 years (OR 2.5; 95%CI 1.5–4.3). In Model 2, the variables were bleeding (OR 3.5; 95%CI 1.2–10.3), other associated infections (OR 3.2; 95%CI 1.3–7.8), jaundice (OR 10.1; 95%CI 3.7–27.2) and age ≥60 years (OR 3.1; 95%CI 1.4–7.1). The prognosis score was developed using the variables associated with death from VL of the latest version of the SINAN (Model 2). The predictive performance of which was evaluated by sensitivity (71.4%), specificity (73.7%), positive and negative predictive values (28.9% and 94.5%) and area under the receiver operating characteristic curve (75.6%). Conclusions Knowledge regarding the factors associated with death from VL may improve clinical management of patients and contribute to lower mortality. PMID:22347514

BIOCHEMICAL HOMEOSTASIS AND BODY GROWTH ARE RELIABLE END POINTS IN CLINICAL NUTRITION TRIALS

USDA-ARS?s Scientific Manuscript database

Studies of biochemical homeostasis and/or body growth have been included as outcome variables in most nutrition trials in paediatric patients. Moreover, these outcome variables have provided important insights into the nutrient requirements of infants and children, and continue to do so. Examples ...

Clinical outcome of pediatric collagenous gastritis: case series and review of literature.

PubMed

Hijaz, Nadia Mazen; Septer, Seth Steven; Degaetano, James; Attard, Thomas Mario

2013-03-07

Collagenous gastritis (CG) is characterized by patchy subepithelial collagen bands. Effective treatment and the clinical and histological outcome of CG in children are poorly defined. The aim of this study is to summarize the published literature on the clinical outcome and response to therapy of pediatric CG including two new cases. We performed a search in Pubmed, OVID for related terms; articles including management and clinical and/or endo-histologic follow up information were included and abstracted. Reported findings were pooled in a dedicated database including the corresponding data extracted from chart review in our patients with CG. Twenty-four patients were included (17 females) with a mean age of 11.7 years. The clinical presentation included iron deficiency anemia and dyspepsia. The reported duration of follow up (in 18 patients) ranged between 0.2-14 years. Despite most subjects presenting with anemia including one requiring blood transfusion, oral iron therapy was only documented in 12 patients. Other treatment modalities were antisecretory measures in 13 patients; proton pump inhibitors (12), or histamine-2 blockers (3), sucralfate (5), prednisolone (6), oral budesonide in 3 patients where one received it in fish oil and triple therapy (3). Three (13%) patients showed no clinical improvement despite therapy; conversely 19 out of 22 were reported with improved symptoms including 8 with complete symptom resolution. Spontaneous clinical resolution without antisecretory, anti-inflammatory or gastroprotective agents was noted in 5 patients (4 received only supplemental iron). Follow up endo-histopathologic data (17 patients) included persistent collagen band and stable Mononuclear cell infiltrate in 12 patients with histopathologic improvement in 5 patients. Neither collagen band thickness nor mononuclear cell infiltrate correlated with clinical course. Intestinal metaplasia and endocrine cell hyperplasia were reported (1) raising the concern of long term malignant transformation. In summary, CG in children is a chronic disease, typically with a variable clinical response and an indolent course that is distinct from the adult phenotype. Long term therapy usually included iron supplementation but cannot be standardized, given the chronicity of the disease, variability of response and potential for adverse events.

Prostate cancer: role of pretreatment multiparametric 3-T MRI in predicting biochemical recurrence after radical prostatectomy.

PubMed

Park, Jung Jae; Kim, Chan Kyo; Park, Sung Yoon; Park, Byung Kwan; Lee, Hyun Moo; Cho, Seong Whi

2014-05-01

The purpose of this study is to retrospectively investigate whether pretreatment multiparametric MRI findings can predict biochemical recurrence in patients who underwent radical prostatectomy (RP) for localized prostate cancer. In this study, 282 patients with biopsy-proven prostate cancer who received RP underwent pretreatment MRI using a phased-array coil at 3 T, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI (DCE-MRI). MRI variables included apparent tumor presence on combined imaging sequences, extracapsular extension, and tumor size on DWI or DCE-MRI. Clinical variables included baseline prostate-specific antigen (PSA) level, clinical stage, and Gleason score at biopsy. The relationship between clinical and imaging variables and biochemical recurrence was evaluated using Cox regression analysis. After a median follow-up of 26 months, biochemical recurrence developed in 61 patients (22%). Univariate analysis revealed that all the imaging and clinical variables were significantly associated with biochemical recurrence (p < 0.01). On multivariate analysis, however, baseline PSA level (p = 0.002), Gleason score at biopsy (p = 0.024), and apparent tumor presence on combined T2WI, DWI, and DCE-MRI (p = 0.047) were the only significant independent predictors of biochemical recurrence. Of the independent predictors, apparent tumor presence on combined T2WI, DWI, and DCE-MRI showed the highest hazard ratio (2.38) compared with baseline PSA level (hazard ratio, 1.05) and Gleason score at biopsy (hazard ratio, 1.34). The apparent tumor presence on combined T2WI, DWI, and DCE-MRI of pretreatment MRI is an independent predictor of biochemical recurrence after RP. This finding may be used to construct a predictive model for biochemical recurrence after surgery.

Assessing data quality and the variability of source data verification auditing methods in clinical research settings.

PubMed

Houston, Lauren; Probst, Yasmine; Martin, Allison

2018-05-18

Data audits within clinical settings are extensively used as a major strategy to identify errors, monitor study operations and ensure high-quality data. However, clinical trial guidelines are non-specific in regards to recommended frequency, timing and nature of data audits. The absence of a well-defined data quality definition and method to measure error undermines the reliability of data quality assessment. This review aimed to assess the variability of source data verification (SDV) auditing methods to monitor data quality in a clinical research setting. The scientific databases MEDLINE, Scopus and Science Direct were searched for English language publications, with no date limits applied. Studies were considered if they included data from a clinical trial or clinical research setting and measured and/or reported data quality using a SDV auditing method. In total 15 publications were included. The nature and extent of SDV audit methods in the articles varied widely, depending upon the complexity of the source document, type of study, variables measured (primary or secondary), data audit proportion (3-100%) and collection frequency (6-24 months). Methods for coding, classifying and calculating error were also inconsistent. Transcription errors and inexperienced personnel were the main source of reported error. Repeated SDV audits using the same dataset demonstrated ∼40% improvement in data accuracy and completeness over time. No description was given in regards to what determines poor data quality in clinical trials. A wide range of SDV auditing methods are reported in the published literature though no uniform SDV auditing method could be determined for "best practice" in clinical trials. Published audit methodology articles are warranted for the development of a standardised SDV auditing method to monitor data quality in clinical research settings. Copyright © 2018. Published by Elsevier Inc.

Assessment of clinical practice guideline methodology for the treatment of knee osteoarthritis with intra-articular hyaluronic acid.

PubMed

Altman, Roy D; Schemitsch, Emil; Bedi, Asheesh

2015-10-01

Clinical practice guidelines are of increasing importance in the decision making for the treatment of knee osteoarthritis. Inconsistent recommendations regarding the use of intra-articular hyaluronic acid for the treatment of knee osteoarthritis have led to confusion among treating physicians. Literature search to identify clinical practice guidelines that provide recommendations regarding the use of intra-articular hyaluronic acid treatment for knee osteoarthritis was conducted. Included guidelines were appraised using the AGREE II instrument. Guideline development methodologies, how the results were assessed, the recommendation formation, and work group composition were summarized. Overall, 10 clinical practice guidelines were identified that met our inclusion criteria. AGREE II domain scores were variable across the included guidelines. The methodology utilized across the guidelines was heterogeneous regarding the evidence inclusion criteria, analysis of evidence results, formulation of clinical practice recommendations, and work group composition. The recommendations provided by the guidelines for intra-articular hyaluronic acid treatment for knee osteoarthritis are highly inconsistent as a result of the variability in guideline methodology. Overall, 30% of the included guidelines recommended against the use of intra-articular hyaluronic acid in the treatment of knee osteoarthritis, while 30% deemed the treatment an appropriate intervention under certain scenarios. The remaining 40% of the guidelines provided either an uncertain recommendation or no recommendation at all, based on the high variability in reviewed evidence regarding efficacy and trial quality. There is a need for a standard "appropriate methodology" that is agreed upon for osteoarthritis clinical practice guidelines in order to prevent the development of conflicting recommendations for intra-articular hyaluronic acid treatment for knee osteoarthritis, and to assure that treating physicians who are utilizing these guidelines are making their clinical decisions on the best available evidence. At present, the inconsistent recommendations provided for intra-articular hyaluronic acid treatment make it difficult for clinical professionals to determine its appropriateness when treating patients with knee osteoarthritis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Dimensions Underlying Measures of Disability, Personal Factors, and Health Status in Cervical Radiculopathy

PubMed Central

Halvorsen, Marie; Kierkegaard, Marie; Harms-Ringdahl, Karin; Peolsson, Anneli; Dedering, Åsa

2015-01-01

Abstract This cross-sectional study sought to identify dimensions underlying measures of impairment, disability, personal factors, and health status in patients with cervical radiculopathy. One hundred twenty-four patients with magnetic resonance imaging-verified cervical radiculopathy, attending a neurosurgery clinic in Sweden, participated. Data from clinical tests and questionnaires on disability, personal factors, and health status were used in a principal-component analysis (PCA) with oblique rotation. The PCA supported a 3-component model including 14 variables from clinical tests and questionnaires, accounting for 73% of the cumulative percentage. The first component, pain and disability, explained 56%. The second component, health, fear-avoidance beliefs, kinesiophobia, and self-efficacy, explained 9.2%. The third component including anxiety, depression, and catastrophizing explained 7.6%. The strongest-loading variables of each dimension were “present neck pain intensity,” “fear avoidance,” and “anxiety.” The three underlying dimensions identified and labeled Pain and functioning, Health, beliefs, and kinesiophobia, and Mood state and catastrophizing captured aspects of importance for cervical radiculopathy. Since the variables “present neck pain intensity,” “fear avoidance,” and “anxiety” had the strongest loading in each of the three dimensions; it may be important to include them in a reduced multidimensional measurement set in cervical radiculopathy. PMID:26091482

Dimensions Underlying Measures of Disability, Personal Factors, and Health Status in Cervical Radiculopathy: A Cross-Sectional Study.

PubMed

Halvorsen, Marie; Kierkegaard, Marie; Harms-Ringdahl, Karin; Peolsson, Anneli; Dedering, Åsa

2015-06-01

This cross-sectional study sought to identify dimensions underlying measures of impairment, disability, personal factors, and health status in patients with cervical radiculopathy. One hundred twenty-four patients with magnetic resonance imaging-verified cervical radiculopathy, attending a neurosurgery clinic in Sweden, participated. Data from clinical tests and questionnaires on disability, personal factors, and health status were used in a principal-component analysis (PCA) with oblique rotation. The PCA supported a 3-component model including 14 variables from clinical tests and questionnaires, accounting for 73% of the cumulative percentage. The first component, pain and disability, explained 56%. The second component, health, fear-avoidance beliefs, kinesiophobia, and self-efficacy, explained 9.2%. The third component including anxiety, depression, and catastrophizing explained 7.6%. The strongest-loading variables of each dimension were "present neck pain intensity," "fear avoidance," and "anxiety." The three underlying dimensions identified and labeled Pain and functioning, Health, beliefs, and kinesiophobia, and Mood state and catastrophizing captured aspects of importance for cervical radiculopathy. Since the variables "present neck pain intensity," "fear avoidance," and "anxiety" had the strongest loading in each of the three dimensions; it may be important to include them in a reduced multidimensional measurement set in cervical radiculopathy.

Clinical outcome of pediatric collagenous gastritis: Case series and review of literature

PubMed Central

Hijaz, Nadia Mazen; Septer, Seth Steven; Degaetano, James; Attard, Thomas Mario

2013-01-01

Collagenous gastritis (CG) is characterized by patchy subepithelial collagen bands. Effective treatment and the clinical and histological outcome of CG in children are poorly defined. The aim of this study is to summarize the published literature on the clinical outcome and response to therapy of pediatric CG including two new cases. We performed a search in Pubmed, OVID for related terms; articles including management and clinical and/or endo-histologic follow up information were included and abstracted. Reported findings were pooled in a dedicated database including the corresponding data extracted from chart review in our patients with CG. Twenty-four patients were included (17 females) with a mean age of 11.7 years. The clinical presentation included iron deficiency anemia and dyspepsia. The reported duration of follow up (in 18 patients) ranged between 0.2-14 years. Despite most subjects presenting with anemia including one requiring blood transfusion, oral iron therapy was only documented in 12 patients. Other treatment modalities were antisecretory measures in 13 patients; proton pump inhibitors (12), or histamine-2 blockers (3), sucralfate (5), prednisolone (6), oral budesonide in 3 patients where one received it in fish oil and triple therapy (3). Three (13%) patients showed no clinical improvement despite therapy; conversely 19 out of 22 were reported with improved symptoms including 8 with complete symptom resolution. Spontaneous clinical resolution without antisecretory, anti-inflammatory or gastroprotective agents was noted in 5 patients (4 received only supplemental iron). Follow up endo-histopathologic data (17 patients) included persistent collagen band and stable Mononuclear cell infiltrate in 12 patients with histopathologic improvement in 5 patients. Neither collagen band thickness nor mononuclear cell infiltrate correlated with clinical course. Intestinal metaplasia and endocrine cell hyperplasia were reported (1) raising the concern of long term malignant transformation. In summary, CG in children is a chronic disease, typically with a variable clinical response and an indolent course that is distinct from the adult phenotype. Long term therapy usually inclused iron supplementation but cannot be standardized, given the chronicity of the disease, variability of response and potential for adverse events. PMID:23538318

Endoscopic ultrasound as an adjunctive evaluation in patients with esophageal motor disorders subtyped by high-resolution manometry.

PubMed

Krishnan, K; Lin, C-Y; Keswani, R; Pandolfino, J E; Kahrilas, P J; Komanduri, S

2014-08-01

Esophageal motor disorders are a heterogeneous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound (EUS) in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification. We performed a retrospective, single center study of 62 patients with esophageal motor disorders categorized according to the Chicago Classification. All patients underwent standard radial endosonography to assess for extra-esophageal findings or alternative explanations for esophageal outflow obstruction. Secondary outcomes included esophageal wall thickness among the different patient subsets within the Chicago Classification. EUS identified 9/62 (15%) clinically relevant findings that altered patient management and explained the etiology of esophageal outflow obstruction. We further identified substantial variability in esophageal wall thickness in a proportion of patients including some with a significantly thickened non-muscular layer. EUS findings are clinically relevant in a significant number of patients with motor disorders and can alter clinical management. Variability in esophageal wall thickness of the muscularis propria and non-muscular layers identified by EUS may also explain the observed variability in response to standard therapies for achalasia. © 2014 John Wiley & Sons Ltd.

Endoscopic ultrasound as an adjunctive evaluation in patients with esophageal motor disorders subtyped by high-resolution manometry

PubMed Central

Krishnan, Kumar; Lin, Chen-Yuan; Keswani, Rajesh; Pandolfino, John E; Kahrilas, Peter J; Komanduri, Srinadh

2015-01-01

Background and aims Esophageal motor disorders are a heterogenous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification. Methods We performed a retrospective, single center study of 62 patients with esophageal motor disorders categorized according to the Chicago Classification. All patients underwent standard radial endosonography to assess for extra esophageal findings or alternative explanations for esophageal outflow obstruction. Secondary outcomes included esophageal wall thickness among the different patient subsets within the Chicago Classification Key Results EUS identified 9/62 (15%) clinically relevant findings that altered patient management and explained the etiology of esophageal outflow obstruction. We further identified substantial variability in esophageal wall thickness in a proportion of patients including some with a significantly thickened non-muscular layer. Conclusions EUS findings are clinically relevant in a significant number of patients with motor disorders and can alter clinical management. Variability in esophageal wall thickness of the muscularis propria and non-muscular layers identified by EUS may also explain the observed variability in response to standard therapies for achalasia. PMID:25041229

Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1.

PubMed

Tiedt, Hannes O; Benjamin, Beate; Niedeggen, Michael; Lueschow, Andreas

2018-02-22

In rare cases, patients with Alzheimer disease (AD) present at an early age and with a family history suggestive of an autosomal dominant mode of inheritance. Mutations of the presenilin-1 (PSEN1) gene are the most common causes of dementia in these patients. Early-onset and particularly familial AD patients frequently present with variable non-amnestic cognitive symptoms such as visual, language or behavioural changes as well as non-cognitive, e.g. motor, symptoms. To investigate the phenotypic variability in carriers of the PSEN1 S170F mutation. We report a family with 4 patients carrying the S170F mutation of whom 2 underwent detailed clinical examinations. We discuss our current findings in the context of previously reported S170F cases. The clinical phenotype was consistent regarding initial memory impairment and early onset in the late twenties found in all S170F patients. There were frequent non-amnestic cognitive changes and, at early stages of the disease, indications of a more pronounced disturbance of visuospatial abilities as compared to face and object recognition. Non-cognitive symptoms most often included myoclonus and cerebellar ataxia. A review of the available case reports indicates some phenotypic variability associated with the S170F mutation including different constellations of symptoms such as parkinsonism and delusions. The variable clinical findings associated with the S170F mutation highlight the relevance of atypical phenotypes in the context of research and under a clinical perspective. CSF sampling and detection of Aβ species may be essential to indicate AD pathology in unclear cases presenting with cognitive and motor symptoms at a younger age. © 2018 S. Karger AG, Basel.

Warfarin therapy: in need of improvement after all these years

PubMed Central

Kimmel, Stephen E

2010-01-01

Background Warfarin therapy has been used clinically for over 60 years, yet continues to be problematic because of its narrow therapeutic index and large inter-individual variability in patient response. As a result, warfarin is a leading cause of serious medication-related adverse events, and its efficacy is also suboptimal. Objective To review factors that are responsible for variable response to warfarin, including clinical, environmental, and genetic factors, and to explore some possible approaches to improving warfarin therapy. Results Recent efforts have focused on developing dosing algorithms that included genetic information to try to improve warfarin dosing. These dosing algorithms hold promise, but have not been fully validated or tested in rigorous clinical trials. Perhaps equally importantly, adherence to warfarin is a major problem that should be addressed with innovative and cost-effective interventions. Conclusion Additional research is needed to further test whether interventions can be used to improve warfarin dosing and outcomes. PMID:18345947

Waardenburg syndrome in four Mexican patients.

PubMed

Aguilar Caso, Sandra I; Ortiz Nieva, Gabriela

2009-01-01

Waardenburg syndrome is a hereditary auditory-pigmentary syndrome. The major features include pigmentary disturbances and congenital deafness. Clinical findings are extremely variable, not only at the authors' institution but also in the literature. The authors describe four patients who presented with various clinical features and different genetic pedigree penetration.

Financial Management of a Large Multi-site Randomized Clinical Trial

PubMed Central

Sheffet, Alice J.; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E.; Longbottom, Mary E.; Howard, Virginia J.; Marler, John R.; Brott, Thomas G.

2014-01-01

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years’ funding ($21,112,866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2,500 randomized participants at 40 sites. Aims Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Methods Projections of the original grant’s fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant’s fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Results Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2,500 targeted sample size, 138 (5.5%) were randomized during the first five years and 1,387 (55.5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13,845) of the projected per-patient costs ($152,992) of the fixed model. Conclusions Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. PMID:24661748

Financial management of a large multisite randomized clinical trial.

PubMed

Sheffet, Alice J; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E; Longbottom, Mary E; Howard, Virginia J; Marler, John R; Brott, Thomas G

2014-08-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. © 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.

Second thoughts on the final rule: An analysis of baseline participant characteristics reports on ClinicalTrials.gov.

PubMed

Cahan, Amos; Anand, Vibha

2017-01-01

ClinicalTrials.gov is valuable for aggregate-level analysis of trials. The recently published final rule aims to improve reporting of trial results. We aimed to assess variability in ClinicalTirals.gov records reporting participants' baseline measures. The September 2015 edition of the database for Aggregate Analysis of ClinicalTrials.gov (AACT), was used in this study. To date, AACT contains 186,941 trials of which 16,660 trials reporting baseline (participant) measures were analyzed. We also analyzed a subset of 13,818 Highly Likely Applicable Clinical Trials (HLACT), for which reporting of results is likely mandatory and compared a random sample of 30 trial records to their journal articles. We report counts for each mandatory baseline measure and variability reporting in their formats. The AACT dataset contains 8,161 baseline measures with 1206 unique measurement units. However, of these 6,940 (85%) variables appear only once in the dataset. Age and Gender are reported using many different formats (178 and 49 respectively). "Age" as the variable name is reported in 60 different formats. HLACT subset reports measures using 3,931 variables. The most frequent Age format (i.e. mean (years) ± sd) is found in only 45% of trials. Overall only 4 baseline measures (Region of Enrollment, Age, Number of Participants, and Gender) are reported by > 10% of trials. Discrepancies are found in both the types and formats of ClinicalTrials.gov records and their corresponding journal articles. On average, journal articles include twice the number of baseline measures (13.6±7.1 (sd) vs. 6.6±7.6) when compared to the ClinicalTrials.gov records that report any results. We found marked variability in baseline measures reporting. This is not addressed by the final rule. To support secondary use of ClinicalTrials.gov, a uniform format for baseline measures reporting is warranted.

Whole Body Magnetic Resonance Imaging Features in Diffuse Idiopathic Skeletal Hyperostosis in Conjunction with Clinical Variables to Whole Body MRI and Clinical Variables in Ankylosing Spondylitis.

PubMed

Weiss, Bettina G; Bachmann, Lucas M; Pfirrmann, Christian W A; Kissling, Rudolf O; Zubler, Veronika

2016-02-01

Discrimination of diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) can be challenging. Usefulness of whole-body magnetic resonance imaging (WB-MRI) in diagnosing spondyloarthritis has been recently proved. We assessed the value of clinical variables alone and in combination with WB-MRI to distinguish between DISH and AS. Diagnostic case-control study: 33 patients with AS and 15 patients with DISH were included. All patients underwent 1.5 Tesla WB-MRI scanning. MR scans were read by a blinded radiologist using the Canadian-Danish Working Group's recommendation. Imaging and clinical variables were identified using the bootstrap. The most important variables from MR and clinical history were assessed in a multivariate fashion resulting in 3 diagnostic models (MRI, clinical, and combined). The discriminative capacity was quantified using the area under the receiver-operating characteristic (ROC) curve. The strength of diagnostic variables was quantified with OR. Forty-eight patients provided 1545 positive findings (193 DISH/1352 AS). The final MR model contained upper anterior corner fat infiltration (32 DISH/181 AS), ankylosis on the vertebral endplate (4 DISH/60 AS), facet joint ankylosis (4 DISH/49 AS), sacroiliac joint edema (11 DISH/91 AS), sacroiliac joint fat infiltration (2 DISH/114 AS), sacroiliac joint ankylosis (2 DISH/119 AS); area under the ROC curve was 0.71, 95% CI 0.64-0.78. The final clinical model contained patient's age and body mass index (area under the ROC curve 0.90, 95% CI 0.89-0.91). The full diagnostic model containing clinical and MR information had an area under the ROC curve of 0.93 (95% CI 0.92-0.95). WB-MRI features can contribute to the correct diagnosis after a thorough conventional workup of patients with DISH and AS.

Clinical Trials With Large Numbers of Variables: Important Advantages of Canonical Analysis.

PubMed

Cleophas, Ton J

2016-01-01

Canonical analysis assesses the combined effects of a set of predictor variables on a set of outcome variables, but it is little used in clinical trials despite the omnipresence of multiple variables. The aim of this study was to assess the performance of canonical analysis as compared with traditional multivariate methods using multivariate analysis of covariance (MANCOVA). As an example, a simulated data file with 12 gene expression levels and 4 drug efficacy scores was used. The correlation coefficient between the 12 predictor and 4 outcome variables was 0.87 (P = 0.0001) meaning that 76% of the variability in the outcome variables was explained by the 12 covariates. Repeated testing after the removal of 5 unimportant predictor and 1 outcome variable produced virtually the same overall result. The MANCOVA identified identical unimportant variables, but it was unable to provide overall statistics. (1) Canonical analysis is remarkable, because it can handle many more variables than traditional multivariate methods such as MANCOVA can. (2) At the same time, it accounts for the relative importance of the separate variables, their interactions and differences in units. (3) Canonical analysis provides overall statistics of the effects of sets of variables, whereas traditional multivariate methods only provide the statistics of the separate variables. (4) Unlike other methods for combining the effects of multiple variables such as factor analysis/partial least squares, canonical analysis is scientifically entirely rigorous. (5) Limitations include that it is less flexible than factor analysis/partial least squares, because only 2 sets of variables are used and because multiple solutions instead of one is offered. We do hope that this article will stimulate clinical investigators to start using this remarkable method.

Factors influencing delay in the diagnosis of colorectal cancer: a study protocol

PubMed Central

Esteva, Magdalena; Ramos, Maria; Cabeza, Elena; Llobera, Joan; Ruiz, Amador; Pita, Salvador; Segura, Josep M; Cortés, Jose M; González-Lujan, Luis

2007-01-01

Background Colorectal cancer (CRC) is the second most frequent tumor in developed countries. Since survival from CRC depends mostly on disease stage at the time of diagnosis, individuals with symptoms or signs suspicious of CRC should be examined without delay. Many factors, however, intervene between symptom onset and diagnosis. This study was designed to: 1) Describe the diagnostic process of CRC from the onset of first symptoms to diagnosis and treatment. 2) Establish the time interval from initial symptoms to diagnosis and treatment, globally and considering patient's and doctors' delay, with the latter due to family physician and/or hospital services. 3) Identify the factors related to defined types of delay. 4) Assess the concordance between information included in primary health care and hospital clinical records regarding onset of first symptoms. Methods/Design Descriptive study, coordinated, with 5 participant groups of 5 different Spanish regions (Balearic Islands, Galicia, Catalunya, Aragón and Valencia Health Districts), with a total of 8 acute public hospitals and 140 primary care centers. Incident cases of CRC during the study period, as identified from pathology services at the involved hospitals. A sample size of 896 subjects has been estimated, 150 subjects for each participant group. Information will be collected through patient interviews and primary health care and hospital clinical records. Patient variables will include sociodemographic variables, family history of cancer, symptom perception, and confidence in the family physician; tumor variables will include tumor site, histological type, grade and stage; symptom variables will include date of onset, type and number of symptoms; health system variables will include number of patient contacts with family physician, type and content of the referral, hospital services attending the patient, diagnostic modalities and results; and delay intervals, including global delays and delays attributed to the patient, family physician and hospital. Discussion To obtain a nonrestricted sample of patients with CRC we have minimized selection risk by identifying the patients from pathology services. A greater constraint may be associated with information sources based on clinical records. Due to inherent features of coordinated studies, it is important to standardize the collection of information. PMID:17697332

Polymorphisms of genes encoding P2X7R, IL-1B, OPG and RANK in orthodontic-induced apical root resorption.

PubMed

Pereira, S; Lavado, N; Nogueira, L; Lopez, M; Abreu, J; Silva, H

2014-10-01

Orthodontic-induced external apical root resorption (EARR) is a complex phenotype determined by poorly defined mechanical and patient intrinsic factors. The aim of this work was to construct a multifactorial integrative model, including clinical and genetic susceptibility factors, to analyze the risk of developing this common orthodontic complication. This retrospective study included 195 orthodontic patients. Using a multiple-linear regression model, where the dependent variable was the maximum% of root resorption (%EARRmax) for each patient, we assessed the contribution of nine clinical variables and four polymorphisms of genes involved in bone and tooth root remodeling (rs1718119 from P2RX7, rs1143634 from IL1B, rs3102735 from TNFRSF11B, encoding OPG, and rs1805034 from TNFRSF11A, encoding RANK). Clinical and genetic variables explained 30% of%EARRmax variability. The variables with the most significant unique contribution to the model were: gender (P < 0.05), treatment duration (P < 0.001), premolar extractions (P < 0.01), Hyrax appliance (P < 0.001) and GG genotype of rs1718119 from P2RX7 gene (P < 0.01). Age, overjet, tongue thrust, skeletal class II and the other polymorphisms made minor contributions. This study highlights the P2RX7 gene as a possible factor of susceptibility to EARR. A more extensive genetic profile may improve this model. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Beyond total treatment effects in randomised controlled trials: Baseline measurement of intermediate outcomes needed to reduce confounding in mediation investigations.

PubMed

Landau, Sabine; Emsley, Richard; Dunn, Graham

2018-06-01

Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of the three processes involving baseline measures of intermediate or clinical outcomes is operating. Necessary assumptions for the change score approach (B) to provide unbiased estimates under either process include the independence of baseline measures and change scores of the intermediate variable. Finally, estimates provided by the analysis of covariance approach (C) were found to be unbiased under all the three processes considered here. When applied to the example, there was evidence of mediation under all methods but the estimate of the indirect effect depended on the approach used with the proportion mediated varying from 57% to 86%. Trialists planning mediation analyses should measure baseline values of putative mediators as well as of continuous clinical outcomes. An analysis of covariance approach is recommended to avoid potential biases due to confounding processes involving baseline measures of intermediate or clinical outcomes, and not simply for increased precision.

The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.

PubMed

Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Cruz, David; Hernández, Sandra; Genis, Alma; Carrillo-Guerrero, Mariana Y; Avilés Reyes, Rubén; Guàrdia-Olmos, Joan

2010-12-01

Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

UK Renal Registry 16th annual report: chapter 12 biochemical variables amongst UK adult dialysis patients in 2012: national and centre-specific analyses.

PubMed

Nicholas, Johann; Shaw, Catriona; Pitcher, David; Dawnay, Anne

2013-01-01

The UK Renal Association clinical practice guidelines include clinical performance measures for biochemical variables in dialysis patients. The UK Renal Registry (UKRR) annually audits dialysis centre performance against these measures as part of its role in promoting continuous quality improvement. Cross sectional performance analyses were undertaken to compare dialysis centre achievement of clinical audit measures for prevalent haemodialysis (HD) and peritoneal dialysis (PD) cohorts in 2012. The biochemical variables studied were phosphate, adjusted calcium, parathyroid hormone, bicarbonate and total cholesterol. In addition, longitudinal analyses were performed (2002-2012) to show changes in achievement of clinical performance measures over time. Fifty-six percent of HD and 61% of PD patients achieved a phosphate within the range recommended by the RA clinical practice guidelines. Seventy-seven percent of HD and 78% of PD patients had adjusted calcium between 2.2-2.5 mmol/L. Fifty-eight percent of HD and 65% of PD patients had parathyroid hormone between 16-72 pmol/L. Fifty-nine percent of HD and 80% of PD patients achieved the audit measure for bicarbonate. There was significant inter-centre variation for all variables studied. The UKRR consistently demonstrates significant inter-centre variation in achievement of biochemical clinical audit measures. Understanding the causes of this variation is an important part of improving the care of dialysis patients in the UK.

Chapter 9 Biochemical variables amongst UK adult dialysis patients in 2010: national and centre-specific analyses.

PubMed

Pruthi, Rishi; Pitcher, David; Dawnay, Anne

2012-01-01

The UK Renal Association clinical practice guidelines include clinical performance measures for biochemical variables in dialysis patients. The UK Renal Registry (UKRR) annually audits dialysis centre performance against these measures as part of its role in promoting continuous quality improvement. Cross sectional performance analyses were undertaken to compare dialysis centre achievement of clinical audit measures for prevalent haemodialysis (HD) and peritoneal dialysis (PD) cohorts in 2010. The biochemical variables studied were phosphate, adjusted calcium, parathyroid hormone, bicarbonate and total cholesterol. In addition longitudinal analyses were performed (2000-2010) to show changes in achievement of clinical performance measures over time. Fifty-six percent of HD and 69% of PD patients achieved a phosphate within the range recommended by the RA clinical practice guidelines. Seventy-five percent of HD and 76% of PD patients had adjusted calcium between 2.2-2.5 mmol/L. Twenty-eight percent of HD and 31% of PD patients had parathyroid hormone between 16- 32 pmol/L. Sixty percent of HD and 80% of PD patients achieved the audit measure for bicarbonate. There was significant inter-centre variation for all variables studied. The UKRR consistently demonstrates significant inter-centre variation in achievement of biochemical clinical audit measures. Understanding the causes of this variation is an important part of improving the care of dialysis patients in the UK. Copyright © 2012 S. Karger AG, Basel.

[Mitochondrial disease due to the deficit of Q-cytochrome C oxidoreductase coenzyme in the respiratory chain. Report of a new case].

PubMed

Roldán, S; Lluch, M D; Navarro Quesada, F J; Hevia, A

1995-01-01

Reference has been made in the literature of the variability in the clinical presentation of deficiency of complex III of the respiratory chain, identifying up to the moment, four groups, the first of which is characterized by hipotonia and wearness starting at variable ages. We report a new case of mitochondrial myopathy due to deficiency of this complex and included within this first group, and consider the importance of defining the clinical and histochemical characteristics of this polymorphous entity.

An Analysis of Ambulatory Teaching Situations for Faculty Development.

ERIC Educational Resources Information Center

Simpson, Deborah E.; And Others

1990-01-01

A study identified variables perceived by clinical medical faculty (n=20) to influence the ease or difficulty of teaching in the ambulatory care setting. Characteristics affecting the teaching situation included teacher, student, and patient characteristics. Implications for faculty development on teaching in the clinical setting are discussed.…

Clopidogrel (plavix).

PubMed

Comin, J; Kallmes, D

2011-12-01

Clopidogrel is an inhibitor of platelet aggregation, indicated for the prevention of ischemic stroke and in-stent thrombosis. However, it has a number of drawbacks, including an increased risk of hemorrhage; a clinical effect that is slow in onset and irreversible; a genetically determined variability in its clinical potency; and interactions with other commonly administered drugs.

Molar Functional Relations and Clinical Behavior Analysis: Implications for Assessment and Treatment

ERIC Educational Resources Information Center

Waltz, Thomas J.; Follette, William C.

2009-01-01

The experimental analysis of behavior has identified several molar functional relations that are highly relevant to clinical behavior analysis. These include matching, discounting, momentum, and variability. Matching provides a broader analysis of how multiple sources of reinforcement influence how individuals choose to allocate their time and…

Childhood Depression: Relation to Adaptive, Clinical and Predictor Variables

PubMed Central

Garaigordobil, Maite; Bernarás, Elena; Jaureguizar, Joana; Machimbarrena, Juan M.

2017-01-01

The study had two goals: (1) to explore the relations between self-assessed childhood depression and other adaptive and clinical variables (2) to identify predictor variables of childhood depression. Participants were 420 students aged 7–10 years old (53.3% boys, 46.7% girls). Results revealed: (1) positive correlations between depression and clinical maladjustment, school maladjustment, emotional symptoms, internalizing and externalizing problems, problem behaviors, emotional reactivity, and childhood stress; and (2) negative correlations between depression and personal adaptation, global self-concept, social skills, and resilience (sense of competence and affiliation). Linear regression analysis including the global dimensions revealed 4 predictors of childhood depression that explained 50.6% of the variance: high clinical maladjustment, low global self-concept, high level of stress, and poor social skills. However, upon introducing the sub-dimensions, 9 predictor variables emerged that explained 56.4% of the variance: many internalizing problems, low family self-concept, high anxiety, low responsibility, low personal self-assessment, high social stress, few aggressive behaviors toward peers, many health/psychosomatic problems, and external locus of control. The discussion addresses the importance of implementing prevention programs for childhood depression at early ages. PMID:28572787

Participation of clinical nurses in the practical education of undergraduate nursing students.

PubMed

Cervera-Gasch, Águeda; Gonzalez-Chorda, Víctor M; Mena-Tudela, Desirée; Salas-Medina, Pablo; Folch-Ayora, Ana; Macia-Soler, Loreto

To evaluate the level of participation of clinical nurses from Castellón where Universitat JaumeI nursing students do their clinical clerkship. To identify the variables that may influence clinical nurses' participation in students' clinical mentorship. This observational, cross-sectional and descriptive study was conducted by applying the validated Involvement, Motivation, Satisfaction, Obstacles and Commitment (IMSOC) questionnaire. The variables collected were: age, work environment and previous training. The study was conducted between January and December 2014. The sample included 117 nurses. The overall mean questionnaire score was 122.838 (standard deviation: ±18.692; interquartile range 95%: 119.415-126.26). The variable "previous training for mentorship students" was statistically significant in the overall score and for all dimensions (P<.05). Primary care nurses obtained better scores in the dimension Implication than professionals working at other care levels. The level of participation of the clinical nurses from Castellón is adequate. The previous training that professionals receive for mentoring students improves both their level of participation and primary care level. Extending this research to other national and international environments is recommended. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Four novel connexin 32 mutations in X-linked Charcot-Marie-Tooth disease. Phenotypic variability and central nervous system involvement.

PubMed

Karadima, Georgia; Koutsis, Georgios; Raftopoulou, Maria; Floroskufi, Paraskewi; Karletidi, Karolina-Maria; Panas, Marios

2014-06-15

Charcot-Marie-Tooth (CMT) disease, the most common hereditary neuropathy, is clinically and genetically heterogeneous. X-linked CMT (CMTX) is usually caused by mutations in the gap junction protein b 1 gene (GJB1) coding for connexin 32 (Cx32). The clinical manifestations of CMTX are characterized by significant variability, with some patients exhibiting central nervous system (CNS) involvement. We report four novel mutations in GJB1, c.191G>A (p.Cys64Tyr), c.508G>T (p.Val170Phe), c.778A>G (p.Lys260Glu) and c.300C>G (p.His100Gln) identified in four unrelated Greek families. These mutations were characterized by variable phenotypic expression, including a family with the Roussy-Lévy syndrome, and three of them were associated with mild clinical CNS manifestations. Copyright © 2014. Published by Elsevier B.V.

Clinical outcomes and frontal plane two-dimensional biomechanics during the 30-second single leg stance test in patients before and after hip abductor tendon reconstructive surgery.

PubMed

Huxtable, Rose E; Ackland, Timothy R; Janes, Gregory C; Ebert, Jay R

2017-07-01

Hip abductor tendon tears are a common cause of Greater Trochanteric Pain Syndrome. Conservative treatments are often ineffective and surgical reconstruction may be recommended. This study investigated the improvement in clinical outcomes and frontal plane two-dimensional biomechanics during a 30-second single leg stance test, in patients undergoing reconstruction. We hypothesized that clinical scores and pertinent biomechanical variables would significantly improve post-surgery, and these outcomes would be significantly correlated. Twenty-one patients with symptomatic tendon tears underwent reconstruction. Patients were evaluated pre-surgery, and at 6 and 12months post-surgery, using patient-reported outcome measures, assessment of hip abductor strength and six-minute walk capacity. Frontal plane, two-dimensional, biomechanical variables including pelvis-on-femur angle, pelvic drop, trunk lean and lateral pelvic shift, were evaluated throughout a 30-second single leg stance test. ANOVA evaluated outcomes over time, while Pearson's correlations investigated associations between clinical scores, pain, functional and biomechanical outcome variables. While clinical and functional measures significantly improved (P<0.05) over time, no significant group differences (P>0.05) were observed in biomechanical variables from pre- to post-surgery. While five patients displayed a positive Trendelenburg sign pre-surgery, only one was positive post-surgery. Clinical outcomes and biomechanical variables during the single leg stance test were not correlated. Despite improvements in clinical and functional measures over time, biomechanical changes during a weight bearing single leg stance test were not significantly different following tendon repair. Follow up beyond 12months may be required, whereby symptomatic relief may precede functional and biomechanical improvement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vital signs monitoring to detect patient deterioration: An integrative literature review.

PubMed

Mok, Wen Qi; Wang, Wenru; Liaw, Sok Ying

2015-05-01

Vital signs monitoring is an important nursing assessment. Yet, nurses seem to be doing it as part of a routine and often overlooking their significance in detecting patient deterioration. An integrative literature review was conducted to explore factors surrounding ward nursing practice of vital signs monitoring in detecting and reporting deterioration. Twenty papers were included. The structural component of a Nursing Role Effectiveness Model framework, which comprises of patient, nurse and organizational variables, was used to synthesize the review. Patient variables include signs of deterioration displayed by patients which include physical cues and abnormal vital signs. Nursing variables include clinical knowledge, roles and responsibilities, and reporting of deteriorating vital signs. Organizational variables include heavy workload, technology, and observation chart design. This review has highlighted current nursing practice in vital signs monitoring. A myriad of factors were found to surround ward practice of vital signs monitoring in detecting and reporting deterioration. © 2015 Wiley Publishing Asia Pty Ltd.

Accuracy, calibration and clinical performance of the EuroSCORE: can we reduce the number of variables?

PubMed

Ranucci, Marco; Castelvecchio, Serenella; Menicanti, Lorenzo; Frigiola, Alessandro; Pelissero, Gabriele

2010-03-01

The European system for cardiac operative risk evaluation (EuroSCORE) is currently used in many institutions and is considered a reference tool in many countries. We hypothesised that too many variables were included in the EuroSCORE using limited patient series. We tested different models using a limited number of variables. A total of 11150 adult patients undergoing cardiac operations at our institution (2001-2007) were retrospectively analysed. The 17 risk factors composing the EuroSCORE were separately analysed and ranked for accuracy of prediction of hospital mortality. Seventeen models were created by progressively including one factor at a time. The models were compared for accuracy with a receiver operating characteristics (ROC) analysis and area under the curve (AUC) evaluation. Calibration was tested with Hosmer-Lemeshow statistics. Clinical performance was assessed by comparing the predicted with the observed mortality rates. The best accuracy (AUC 0.76) was obtained using a model including only age, left ventricular ejection fraction, serum creatinine, emergency operation and non-isolated coronary operation. The EuroSCORE AUC (0.75) was not significantly different. Calibration and clinical performance were better in the five-factor model than in the EuroSCORE. Only in high-risk patients were 12 factors needed to achieve a good performance. Including many factors in multivariable logistic models increases the risk for overfitting, multicollinearity and human error. A five-factor model offers the same level of accuracy but demonstrated better calibration and clinical performance. Models with a limited number of factors may work better than complex models when applied to a limited number of patients. Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Frequent hospital admissions in Singapore: clinical risk factors and impact of socioeconomic status.

PubMed

Low, Lian Leng; Tay, Wei Yi; Ng, Matthew Joo Ming; Tan, Shu Yun; Liu, Nan; Lee, Kheng Hock

2018-01-01

Frequent admitters to hospitals are high-cost patients who strain finite healthcare resources. However, the exact risk factors for frequent admissions, which can be used to guide risk stratification and design effective interventions locally, remain unknown. Our study aimed to identify the clinical and sociodemographic risk factors associated with frequent hospital admissions in Singapore. An observational study was conducted using retrospective 2014 data from the administrative database at Singapore General Hospital, Singapore. Variables were identified a priori and included patient demographics, comorbidities, prior healthcare utilisation, and clinical and laboratory variables during the index admission. Multivariate logistic regression analysis was used to identify independent risk factors for frequent admissions. A total of 16,306 unique patients were analysed and 1,640 (10.1%) patients were classified as frequent admitters. On multivariate logistic regression, 16 variables were independently associated with frequent hospital admissions, including age, cerebrovascular disease, history of malignancy, haemoglobin, serum creatinine, serum albumin, and number of specialist outpatient clinic visits, emergency department visits, admissions preceding index admission and medications dispensed at discharge. Patients staying in public rental housing had a 30% higher risk of being a frequent admitter after adjusting for demographics and clinical conditions. Our study, the first in our knowledge to examine the clinical risk factors for frequent admissions in Singapore, validated the use of public rental housing as a sensitive indicator of area-level socioeconomic status in Singapore. These risk factors can be used to identify high-risk patients in the hospital so that they can receive interventions that reduce readmission risk. Copyright: © Singapore Medical Association

Intra-individual variability in tinnitus patients : current thoughts and perspectives.

PubMed

Dauman, N; Erlandsson, S; Lundlin, L; Dauman, R

2015-04-01

Most tinnitus studies have attempted to compare groups of individuals, thus revealing inter-individuals differences, i.e., variations between compared subjects. For methodological reasons, inter-individual studies cannot take into account the variability of tinnitus experience, which has been known for decades to be relevant in daily practice with tinnitus patients. The concept of intra-individual variability has been promoted in the research literature, in order to shed light on this aspect of individual perception. In previous studies, unrelated to hearing, the concept of intra-individual variability implied inclusion of the environment (i.e., physical and social interactions) as a factor of individual performance. In tinnitus research, we believe that the concept of variability (within a person) could find a place beside the concept of variation (between groups of subjects). In this paper, four perspectives of tinnitus experiences from the clinical and research fields are described: (1) ENT consultation; (2) short-term group psychotherapy; (3) psychodynamic psychotherapy; and (4) clinical psychological research. Intra-individual variability stresses the importance of defining tinnitus in a dynamic way, contrary to the current definition of tinnitus as the perception of sound(s). In clinical practice, it is useful to embrace the perspective of the perceiver of tinnitus, and to include social and cultural circumstances as well as audiological/physical changes.

The complexity of interpreting genomic data in patients with acute myeloid leukemia

PubMed Central

Nazha, A; Zarzour, A; Al-Issa, K; Radivoyevitch, T; Carraway, H E; Hirsch, C M; Przychodzen, B; Patel, B J; Clemente, M; Sanikommu, S R; Kalaycio, M; Maciejewski, J P; Sekeres, M A

2016-01-01

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the accumulation of complex genetic alterations responsible for the initiation and progression of the disease. Translating genomic information into clinical practice remained challenging with conflicting results regarding the impact of certain mutations on disease phenotype and overall survival (OS) especially when clinical variables are controlled for when interpreting the result. We sequenced the coding region for 62 genes in 468 patients with secondary AML (sAML) and primary AML (pAML). Overall, mutations in FLT3, DNMT3A, NPM1 and IDH2 were more specific for pAML whereas UTAF1, STAG2, BCORL1, BCOR, EZH2, JAK2, CBL, PRPF8, SF3B1, ASXL1 and DHX29 were more specific for sAML. However, in multivariate analysis that included clinical variables, only FLT3 and DNMT3A remained specific for pAML and EZH2, BCOR, SF3B1 and ASXL1 for sAML. When the impact of mutations on OS was evaluated in the entire cohort, mutations in DNMT3A, PRPF8, ASXL1, CBL EZH2 and TP53 had a negative impact on OS; no mutation impacted OS favorably; however, in a cox multivariate analysis that included clinical data, mutations in DNMT3A, ASXL1, CBL, EZH2 and TP53 became significant. Thus, controlling for clinical variables is important when interpreting genomic data in AML. PMID:27983727

The complexity of interpreting genomic data in patients with acute myeloid leukemia.

PubMed

Nazha, A; Zarzour, A; Al-Issa, K; Radivoyevitch, T; Carraway, H E; Hirsch, C M; Przychodzen, B; Patel, B J; Clemente, M; Sanikommu, S R; Kalaycio, M; Maciejewski, J P; Sekeres, M A

2016-12-16

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the accumulation of complex genetic alterations responsible for the initiation and progression of the disease. Translating genomic information into clinical practice remained challenging with conflicting results regarding the impact of certain mutations on disease phenotype and overall survival (OS) especially when clinical variables are controlled for when interpreting the result. We sequenced the coding region for 62 genes in 468 patients with secondary AML (sAML) and primary AML (pAML). Overall, mutations in FLT3, DNMT3A, NPM1 and IDH2 were more specific for pAML whereas UTAF1, STAG2, BCORL1, BCOR, EZH2, JAK2, CBL, PRPF8, SF3B1, ASXL1 and DHX29 were more specific for sAML. However, in multivariate analysis that included clinical variables, only FLT3 and DNMT3A remained specific for pAML and EZH2, BCOR, SF3B1 and ASXL1 for sAML. When the impact of mutations on OS was evaluated in the entire cohort, mutations in DNMT3A, PRPF8, ASXL1, CBL EZH2 and TP53 had a negative impact on OS; no mutation impacted OS favorably; however, in a cox multivariate analysis that included clinical data, mutations in DNMT3A, ASXL1, CBL, EZH2 and TP53 became significant. Thus, controlling for clinical variables is important when interpreting genomic data in AML.

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study.

PubMed

Pranal, Thibaut; Pereira, Bruno; Berthelin, Pauline; Roszyk, Laurence; Godet, Thomas; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Cayot, Sophie; Gillart, Thierry; Skrzypczak, Yvan; Souweine, Bertrand; Bouvier, Damien; Blanchon, Loic; Sapin, Vincent; Constantin, Jean-Michel; Jabaudon, Matthieu

2018-01-01

Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536.

Identification of Chinese medicine syndromes in persistent insomnia associated with major depressive disorder: a latent tree analysis.

PubMed

Yeung, Wing-Fai; Chung, Ka-Fai; Zhang, Nevin Lian-Wen; Zhang, Shi Ping; Yung, Kam-Ping; Chen, Pei-Xian; Ho, Yan-Yee

2016-01-01

Chinese medicine (CM) syndrome (zheng) differentiation is based on the co-occurrence of CM manifestation profiles, such as signs and symptoms, and pulse and tongue features. Insomnia is a symptom that frequently occurs in major depressive disorder despite adequate antidepressant treatment. This study aims to identify co-occurrence patterns in participants with persistent insomnia and major depressive disorder from clinical feature data using latent tree analysis, and to compare the latent variables with relevant CM syndromes. One hundred and forty-two participants with persistent insomnia and a history of major depressive disorder completed a standardized checklist (the Chinese Medicine Insomnia Symptom Checklist) specially developed for CM syndrome classification of insomnia. The checklist covers symptoms and signs, including tongue and pulse features. The clinical features assessed by the checklist were analyzed using Lantern software. CM practitioners with relevant experience compared the clinical feature variables under each latent variable with reference to relevant CM syndromes, based on a previous review of CM syndromes. The symptom data were analyzed to build the latent tree model and the model with the highest Bayes information criterion score was regarded as the best model. This model contained 18 latent variables, each of which divided participants into two clusters. Six clusters represented more than 50 % of the sample. The clinical feature co-occurrence patterns of these six clusters were interpreted as the CM syndromes Liver qi stagnation transforming into fire, Liver fire flaming upward, Stomach disharmony, Hyperactivity of fire due to yin deficiency, Heart-kidney noninteraction, and Qi deficiency of the heart and gallbladder. The clinical feature variables that contributed significant cumulative information coverage (at least 95 %) were identified. Latent tree model analysis on a sample of depressed participants with insomnia revealed 13 clinical feature co-occurrence patterns, four mutual-exclusion patterns, and one pattern with a single clinical feature variable.

Experimental Design in Clinical 'Omics Biomarker Discovery.

PubMed

Forshed, Jenny

2017-11-03

This tutorial highlights some issues in the experimental design of clinical 'omics biomarker discovery, how to avoid bias and get as true quantities as possible from biochemical analyses, and how to select samples to improve the chance of answering the clinical question at issue. This includes the importance of defining clinical aim and end point, knowing the variability in the results, randomization of samples, sample size, statistical power, and how to avoid confounding factors by including clinical data in the sample selection, that is, how to avoid unpleasant surprises at the point of statistical analysis. The aim of this Tutorial is to help translational clinical and preclinical biomarker candidate research and to improve the validity and potential of future biomarker candidate findings.

Factors affecting interactome-based prediction of human genes associated with clinical signs.

PubMed

González-Pérez, Sara; Pazos, Florencio; Chagoyen, Mónica

2017-07-17

Clinical signs are a fundamental aspect of human pathologies. While disease diagnosis is problematic or impossible in many cases, signs are easier to perceive and categorize. Clinical signs are increasingly used, together with molecular networks, to prioritize detected variants in clinical genomics pipelines, even if the patient is still undiagnosed. Here we analyze the ability of these network-based methods to predict genes that underlie clinical signs from the human interactome. Our analysis reveals that these approaches can locate genes associated with clinical signs with variable performance that depends on the sign and associated disease. We analyzed several clinical and biological factors that explain these variable results, including number of genes involved (mono- vs. oligogenic diseases), mode of inheritance, type of clinical sign and gene product function. Our results indicate that the characteristics of the clinical signs and their related diseases should be considered for interpreting the results of network-prediction methods, such as those aimed at discovering disease-related genes and variants. These results are important due the increasing use of clinical signs as an alternative to diseases for studying the molecular basis of human pathologies.

The value of item response theory in clinical assessment: a review.

PubMed

Thomas, Michael L

2011-09-01

Item response theory (IRT) and related latent variable models represent modern psychometric theory, the successor to classical test theory in psychological assessment. Although IRT has become prevalent in the measurement of ability and achievement, its contributions to clinical domains have been less extensive. Applications of IRT to clinical assessment are reviewed to appraise its current and potential value. Benefits of IRT include comprehensive analyses and reduction of measurement error, creation of computer adaptive tests, meaningful scaling of latent variables, objective calibration and equating, evaluation of test and item bias, greater accuracy in the assessment of change due to therapeutic intervention, and evaluation of model and person fit. The theory may soon reinvent the manner in which tests are selected, developed, and scored. Although challenges remain to the widespread implementation of IRT, its application to clinical assessment holds great promise. Recommendations for research, test development, and clinical practice are provided.

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database.

PubMed

Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

2009-11-01

To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

Factors That Help and Hinder Scientific Training in Counseling and Clinical Psychology Students

ERIC Educational Resources Information Center

Marks, Margaret M.

2011-01-01

The purpose of this dissertation is to better understand scientific training within clinical and counseling psychology doctoral programs. A primary goal is to extend previous research by expanding the scientific training outcome variables from research interest and productivity to include additional characteristics of scientific mindedness such as…

Development of a novel diagnostic algorithm to predict NASH in HCV-positive patients.

PubMed

Gallotta, Andrea; Paneghetti, Laura; Mrázová, Viera; Bednárová, Adriana; Kružlicová, Dáša; Frecer, Vladimir; Miertus, Stanislav; Biasiolo, Alessandra; Martini, Andrea; Pontisso, Patrizia; Fassina, Giorgio

2018-05-01

Non-alcoholic steato-hepatitis (NASH) is a severe disease characterised by liver inflammation and progressive hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that in hepatitis C virus patients steatosis and NASH are associated with faster fibrosis progression and hepatocellular carcinoma. A safe and reliable non-invasive diagnostic method to detect NASH at its early stages is still needed to prevent progression of the disease. We prospectively enrolled 91 hepatitis C virus-positive patients with histologically proven chronic liver disease: 77 patients were included in our study; of these, 10 had NASH. For each patient, various clinical and serological variables were collected. Different algorithms combining squamous cell carcinoma antigen-immunoglobulin-M (SCCA-IgM) levels with other common clinical data were created to provide the probability of having NASH. Our analysis revealed a statistically significant correlation between the histological presence of NASH and SCCA-IgM, insulin, homeostasis model assessment, haemoglobin, high-density lipoprotein and ferritin levels, and smoke. Compared to the use of a single marker, algorithms that combined four, six or seven variables identified NASH with higher accuracy. The best diagnostic performance was obtained with the logistic regression combination, which included all seven variables correlated with NASH. The combination of SCCA-IgM with common clinical data shows promising diagnostic performance for the detection of NASH in hepatitis C virus patients.

Psychogenic dysphonia: diversity of clinical and vocal manifestations in a case series.

PubMed

Martins, Regina Helena Garcia; Tavares, Elaine Lara Mendes; Ranalli, Paula Ferreira; Branco, Anete; Pessin, Adriana Bueno Benito

2014-01-01

Psychogenic dysphonia is a functional disorder with variable clinical manifestations. To assess the clinical and vocal characteristics of patients with psychogenic dysphonia in a case series. The study included 28 adult patients with psychogenic dysphonia, evaluated at a University hospital in the last ten years. Assessed variables included gender, age, occupation, vocal symptoms, vocal characteristics, and videolaryngostroboscopic findings. 28 patients (26 women and 2 men) were assessed. Their occupations included: housekeeper (n=17), teacher (n=4), salesclerk (n=4), nurse (n=1), retired (n=1), and psychologist (n=1). Sudden symptom onset was reported by 16 patients and progressive symptom onset was reported by 12; intermittent evolution was reported by 15; symptom duration longer than three months was reported by 21 patients. Videolaryngostroboscopy showed only functional disorders; no patient had structural lesions or changes in vocal fold mobility. Conversion aphonia, skeletal muscle tension, and intermittent voicing were the most frequent vocal emission manifestation forms. In this case series of patients with psychogenic dysphonia, the most frequent form of clinical presentation was conversion aphonia, followed by musculoskeletal tension and intermittent voicing. The clinical and vocal aspects of 28 patients with psychogenic dysphonia, as well as the particularities of each case, are discussed. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Nursing Home Spending Patterns in the 1990s: The Role of Nursing Home Competition and Excess Demand

PubMed Central

Mukamel, Dana B; Spector, William D; Bajorska, Alina

2005-01-01

Objective To examine nursing home expenditures on clinical, hotel, and administrative activities during the 1990s and to determine the association between nursing home competition and excess demand on expenditures. Data Sources/Study Setting Secondary data sources for 1991, 1996, and 1999 for 500 free-standing nursing homes in New York State. Study Design A retrospective statistical analysis of nursing homes' expenditures. The dependent variables were clinical, hotel, and administrative costs in each year. Independent variables included outputs (inpatient and outpatient), wages, ownership, New York City location, and measures of competition and excess demand. Data Collection/Extraction Method Variables were constructed from annual financial reports submitted by the nursing homes, the Patient Review Instrument and Medicare enrollment data. Principal Findings Clinical and administrative costs have increased over the decade, while hotel expenditures have declined. Increased competition was associated with higher clinical and administrative costs while excess demand was associated with lower clinical and hotel expenditures. Conclusions Nursing home expenditures are sensitive to competition and excess demand conditions. Policies that influence competition in nursing home markets are therefore likely to have an impact on expenditures as well. PMID:16033491

Using a handbook to improve nurses' continence care.

PubMed

Williams, K; Roe, B; Sindhu, F

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

Key factors in children's competence to consent to clinical research.

PubMed

Hein, Irma M; Troost, Pieter W; Lindeboom, Robert; Benninga, Marc A; Zwaan, C Michel; van Goudoever, Johannes B; Lindauer, Ramón J L

2015-10-24

Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children's consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors including the developmental stage, the influence of parents and peers, and life experience. We examined potential determining factors for children's competence to consent to clinical research and to what extent they explain the variation in competence judgments. From January 1, 2012 through January 1, 2014, pediatric patients aged 6 to 18 years, eligible for clinical research studies were enrolled prospectively at various in- and outpatient pediatric departments. Children's competence to consent was assessed by MacArthur Competence Assessment Tool for Clinical Research. Potential determining child variables included age, gender, intelligence, disease experience, ethnicity and socio-economic status (SES). We used logistic regression analysis and change in explained variance in competence judgments to quantify the contribution of a child variable to the total explained variance. Contextual factors included risk and complexity of the decision to participate, parental competence judgment and the child's or parents decision to participate. Out of 209 eligible patients, 161 were included (mean age, 10.6 years, 47.2 % male). Age, SES, intelligence, ethnicity, complexity, parental competence judgment and trial participation were univariately associated with competence (P < 0.05). Total explained variance in competence judgments was 71.5 %. Only age and intelligence significantly and independently explained the variance in competence judgments, explaining 56.6 % and 12.7 % of the total variance respectively. SES, male gender, disease experience and ethnicity each explained less than 1 % of the variance in competence judgments. Contextual factors together explained an extra 2.8 % (P > 0.05). Age is the factor that explaines most of to the variance in children's competence to consent, followed by intelligence. Experience with disease did not affect competence in this study, nor did other variables. Development and use of a standardized instrument for assessing children's competence to consent in drug trials: Are legally established age limits valid?, NTR3918.

Studying physician-adolescent patient communication in community-based practices: recruitment challenges and solutions.

PubMed

Bodner, Michael E; Bilheimer, Alicia; Gao, Xiaomei; Lyna, Pauline; Alexander, Stewart C; Dolor, Rowena J; Østbye, Truls; Bravender, Terrill; Tulsky, James A; Graves, Sidney; Irons, Alexis; Pollak, Kathryn I

2015-11-13

Practice-based studies are needed to assess how physicians communicate health messages about weight to overweight/obese adolescent patients, but successful recruitment to such studies is challenging. This paper describes challenges, solutions, and lessons learned to recruit physicians and adolescents to the Teen Communicating Health Analyzing Talk (CHAT) study, a randomized controlled trial of a communication skills intervention for primary care physicians to enhance communication about weight with overweight/obese adolescents. A "peer-to-peer" approach was used to recruit physicians, including the use of "clinic champions" who liaised between study leaders and physicians. Consistent rapport and cooperative working relationships with physicians and clinic staff were developed and maintained. Adolescent clinic files were reviewed (HIPAA waiver) to assess eligibility. Parents could elect to opt-out for their children. To encourage enrollment, confidentiality of audio recordings was emphasized, and financial incentives were offered to all participants. We recruited 49 physicians and audio-recorded 391 of their overweight/obese adolescents' visits. Recruitment challenges included 1) physician reticence to participate; 2) variability in clinic operating procedures; 3) variability in adolescent accrual rates; 4) clinic open access scheduling; and 5) establishing communication with parents and adolescents. Key solutions included the use of a "clinic champion" to help recruit physicians, pro-active, consistent communication with clinic staff, and adapting calling times to reach parents and adolescents. Recruiting physicians and adolescents to audio-recorded, practice-based health communication studies can be successful. Anticipated challenges to recruiting can be met with advanced planning; however, optimal solutions to challenges evolve as recruitment progresses.

Associations between period 3 gene polymorphisms and sleep- /chronotype-related variables in patients with late-life insomnia.

PubMed

Mansour, Hader A; Wood, Joel; Chowdari, Kodavali V; Tumuluru, Divya; Bamne, Mikhil; Monk, Timothy H; Hall, Martica H; Buysse, Daniel J; Nimgaonkar, Vishwajit L

2017-01-01

A variable number tandem repeat polymorphism (VNTR) in the period 3 (PER3) gene has been associated with heritable sleep and circadian variables, including self-rated chronotypes, polysomnographic (PSG) variables, insomnia and circadian sleep-wake disorders. This report describes novel molecular and clinical analyses of PER3 VNTR polymorphisms to better define their functional consequences. As the PER3 VNTR is located in the exonic (protein coding) region of PER3, we initially investigated whether both alleles (variants) are transcribed into messenger RNA in human fibroblasts. The VNTR showed bi-allelic gene expression. We next investigated genetic associations in relation to clinical variables in 274 older adult Caucasian individuals. Independent variables included genotypes for the PER3 VNTR as well as a representative set of single nucleotide polymorphisms (SNPs) that tag common variants at the PER3 locus (linkage disequilibrium (LD) between genetic variants < 0.5). In order to comprehensively evaluate variables analyzed individually in prior analyses, dependent measures included PSG total sleep time and sleep latency, self-rated chronotype, estimated with the Composite Scale (CS), and lifestyle regularity, estimated using the social rhythm metric (SRM). Initially, genetic polymorphisms were individually analyzed in relation to each outcome variable using analysis of variance (ANOVA). Nominally significant associations were further tested using regression analyses that incorporated individual ANOVA-associated DNA variants as potential predictors and each of the selected sleep/circadian variables as outcomes. The covariates included age, gender, body mass index and an index of medical co-morbidity. Significant genetic associations with the VNTR were not detected with the sleep or circadian variables. Nominally significant associations were detected between SNP rs1012477 and CS scores (p = 0.003) and between rs10462021 and SRM (p = 0.047); rs11579477 and average delta power (p = 0.043) (analyses uncorrected for multiple comparisons). In conclusion, alleles of the VNTR are expressed at the transcript level and may have a functional effect in cells expressing the PER3 gene. PER3 polymorphisms had a modest impact on selected sleep/circadian variables in our sample, suggesting that PER3 is associated with sleep and circadian function beyond VNTR polymorphisms. Further replicate analyses in larger, independent samples are recommended.

Integrating mindfulness in supportive cancer care: a cohort study on a mindfulness-based day care clinic for cancer survivors.

PubMed

Dobos, Gustav; Overhamm, Tatiana; Büssing, Arndt; Ostermann, Thomas; Langhorst, Jost; Kümmel, Sherko; Paul, Anna; Cramer, Holger

2015-10-01

The aim of this study was to investigate the effects of a mindfulness-based day care clinic group program for cancer survivors on health-related quality of life and mental health; and to investigate which psychological variables are associated with changes in health variables. One hundred seventeen cancer survivors (91.0 % female; mean age 53.9 ± 10.7 years; 65.0 % breast cancer; mean time since diagnosis 27.2 ± 46.5 months) participated in an 11-week mindfulness-based day care clinic group program, 6 h per week. The intervention incorporated mindfulness-based meditation, yoga, cognitive-behavioral techniques, and lifestyle modification. Outcome measures including health-related quality of life (EORTC QLQ-C30), depression and anxiety (HADS); and psychological variables including life satisfaction (BMLSS), mindfulness (FMI), adaptive coping styles (AKU), spiritual/religious attitudes in dealing with illness (SpREUK), and interpretation of illness (IIQ) were assessed before, after, and 3 months after the intervention. Using mixed linear models, significant improvements in global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning were found. Cancer-related symptoms, including fatigue, pain, insomnia, constipation, anxiety, and depression, also improved significantly. Mindfulness, life satisfaction, health satisfaction, all coping styles, all spiritual/religious attitudes, and interpretation of illness as something of value increased; interpretation of illness as punishment decreased significantly (all p < 0.05). Improved outcomes were associated with increases in psychological variables, mainly life satisfaction, health satisfaction, and trust in medical help (R (2) = 7.3-43.6 %). Supportive mindfulness-based interventions can be considered as an effective means to improve cancer survivors' physical and mental health. Functional improvements are associated with improved satisfaction and coping styles.

The Influence of Cytochrome P450 Pharmacogenetics on Disposition of Common Antidepressant and Antipsychotic Medications

PubMed Central

van der Weide, Jan; Hinrichs, John WJ

2006-01-01

Since the identification of all the major drug-metabolising cytochrome P450 (CYP) enzymes and their major gene variants, pharmacogenetics has had a major impact on psychotherapeutic drug therapy. CYP enzymes are responsible for the metabolism of most clinically used drugs. Individual variability in CYP activity is an important reason for drug therapy failure. Variability in CYP activity may be caused by various factors, including endogenous factors such as age, gender and morbidity as well as exogenous factors such as co-medication, food components and smoking habit. However, polymorphisms, present in most CYP genes, are responsible for a substantial part of this variability. Although CYP genotyping has been shown to predict the majority of aberrant phenotypes, it is currently rarely performed in clinical practice. PMID:16886044

Factors Influencing M.S.W. Students' Interest in Clinical Practice

ERIC Educational Resources Information Center

Perry, Robin

2009-01-01

This study utilizes linear and log-linear stochastic models to examine the impact that a variety of variables (including graduate education) have on M.S.W. students' desires to work in clinical practice. Data was collected biannually (between 1992 and 1998) from a complete population sample of all students entering and exiting accredited graduate…

Fine Analysis of Genetic Diversity of the tpr Gene Family among Treponemal Species, Subspecies and Strains

PubMed Central

Centurion-Lara, Arturo; Giacani, Lorenzo; Godornes, Charmie; Molini, Barbara J.; Brinck Reid, Tara; Lukehart, Sheila A.

2013-01-01

Background The pathogenic non-cultivable treponemes include three subspecies of Treponema pallidum (pallidum, pertenue, endemicum), T. carateum, T. paraluiscuniculi, and the unclassified Fribourg-Blanc treponeme (Simian isolate). These treponemes are morphologically indistinguishable and antigenically and genetically highly similar, yet cross-immunity is variable or non-existent. Although all of these organisms cause chronic, multistage skin and systemic disease, they have historically been classified by mode of transmission, clinical presentations and host ranges. Whole genome studies underscore the high degree of sequence identity among species, subspecies and strains, pinpointing a limited number of genomic regions for variation. Many of these “hot spots” include members of the tpr gene family, composed of 12 paralogs encoding candidate virulence factors. We hypothesize that the distinct clinical presentations, host specificity, and variable cross-immunity might reside on virulence factors such as the tpr genes. Methodology/Principal Findings Sequence analysis of 11 tpr loci (excluding tprK) from 12 strains demonstrated an impressive heterogeneity, including SNPs, indels, chimeric genes, truncated gene products and large deletions. Comparative analyses of sequences and 3D models of predicted proteins in Subfamily I highlight the striking co-localization of discrete variable regions with predicted surface-exposed loops. A hallmark of Subfamily II is the presence of chimeric genes in the tprG and J loci. Diversity in Subfamily III is limited to tprA and tprL. Conclusions/Significance An impressive sequence variability was found in tpr sequences among the Treponema isolates examined in this study, with most of the variation being consistent within subspecies or species, or between syphilis vs. non-syphilis strains. Variability was seen in the pallidum subspecies, which can be divided into 5 genogroups. These findings support a genetic basis for the classification of these organisms into their respective subspecies and species. Future functional studies will determine whether the identified genetic differences relate to cross-immunity, clinical differences, or host ranges. PMID:23696912

The prognostic value of standardized reference values for speckle-tracking global longitudinal strain in hypertrophic cardiomyopathy.

PubMed

Hartlage, Gregory R; Kim, Jonathan H; Strickland, Patrick T; Cheng, Alan C; Ghasemzadeh, Nima; Pernetz, Maria A; Clements, Stephen D; Williams, B Robinson

2015-03-01

Speckle-tracking left ventricular global longitudinal strain (GLS) assessment may provide substantial prognostic information for hypertrophic cardiomyopathy (HCM) patients. Reference values for GLS have been recently published. We aimed to evaluate the prognostic value of standardized reference values for GLS in HCM patients. An analysis of HCM clinic patients who underwent GLS was performed. GLS was defined as normal (more negative or equal to -16%) and abnormal (less negative than -16%) based on recently published reference values. Patients were followed for a composite of events including heart failure hospitalization, sustained ventricular arrhythmia, and all-cause death. The power of GLS to predict outcomes was assessed relative to traditional clinical and echocardiographic variables present in HCM. 79 HCM patients were followed for a median of 22 months (interquartile range 9-30 months) after imaging. During follow-up, 15 patients (19%) met the primary outcome. Abnormal GLS was the only echocardiographic variable independently predictive of the primary outcome [multivariate Hazard ratio 5.05 (95% confidence interval 1.09-23.4, p = 0.038)]. When combined with traditional clinical variables, abnormal GLS remained independently predictive of the primary outcome [multivariate Hazard ratio 5.31 (95 % confidence interval 1.18-24, p = 0.030)]. In a model including the strongest clinical and echocardiographic predictors of the primary outcome, abnormal GLS demonstrated significant incremental benefit for risk stratification [net reclassification improvement 0.75 (95 % confidence interval 0.21-1.23, p < 0.0001)]. Abnormal GLS is an independent predictor of adverse outcomes in HCM patients. Standardized use of GLS may provide significant incremental value over traditional variables for risk stratification.

Pharmacokinetic variability, efficacy and tolerability of eslicarbazepine acetate-A national approach to the evaluation of therapeutic drug monitoring data and clinical outcome.

PubMed

Svendsen, Torleiv; Brodtkorb, Eylert; Reimers, Arne; Molden, Espen; Sætre, Erik; Johannessen, Svein I; Johannessen Landmark, Cecilie

2017-01-01

Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED), still insufficiently studied regarding pharmacokinetic variability, efficacy and tolerability. The purpose of this study was to evaluate therapeutic drug monitoring (TDM) data in Norway and relate pharmacokinetic variability to clinical efficacy and tolerability in a long-term clinical setting in patients with refractory epilepsy. This retrospective observational study included TDM-data from the main laboratories and population data from the Norwegian Prescription Database in Norway, in addition to clinical data from medical records of adult patients using ESL for up to three years, whenever possible. TDM-data from 168 patients were utilized for assessment of pharmacokinetic variability, consisting of 71% of the total number of patients in Norway using ESL, 2011-14. Median daily dose of ESL was 800mg (range 400-1600mg), and median serum concentration of ESL was 53μmol/L (range 13-132μmol/L). Inter-patient variability of ESL was extensive, with 25-fold variability in concentration/dose ratios. Additional clinical data were available from 104 adult patients out of the 168, all with drug resistant focal epilepsy. After 1, 2 and 3 years follow-up, the retention rate of ESL was 83%, 72% and 64%, respectively. ESL was generally well tolerated as add-on treatment, but sedation, cognitive impairment and hyponatremia were reported. Hyponatremia (sodium <137mmol/L) was present in 36% of the patients, and lead to discontinuation in three. Pharmacokinetic variability of ESL was extensive and the demonstration of usefulness of TDM requires further studies. In patients with drug resistant focal Epilepsy, the high retention rate indicated good efficacy and tolerability. Hyponatremia was observed in one third of the patients. The present results point to a need for individualization of treatment and TDM may be useful. Copyright © 2016 Elsevier B.V. All rights reserved.

Exploring the Association of Hospice Care on Patient Experience and Outcomes of Care

PubMed Central

Kleinpell, Ruth; Vasilevskis, Eduard E.; Fogg, Louis; Ely, E. Wesley

2016-01-01

Objective To examine the association of the use of hospice care on patient experience and outcomes of care. Promoting high-value, safe, and effective care is an international healthcare imperative. However, the extent to which hospice care may improve the value of care is not well characterized. Methods A secondary analysis of variations in care was conducted using the Dartmouth Atlas Report, matched to the American Hospital Association Annual Survey Database to abstract organizational characteristics for 236 US hospitals to examine the relationship between hospice utilization and a number of variables that represent care value including hospital care intensity index, hospital deaths, ICU deaths, patient satisfaction, and a number of patient quality indicators. Structural equation modeling was used to demonstrate the effect of hospice use on patient experience of care variables, clinical outcomes of care variables, and efficiency of care variables. Results Hospice admissions in the last 6 months of life were correlated with a number of variables including increases in patient satisfaction ratings (r=0.448, p=0.01) and better pain control (r=0.491, p=0.01), and reductions in hospital days (r=−0.517, p=0.01), fewer deaths in the hospital (r=−0.842, p=0.01), and fewer deaths occurring with an ICU admission during hospitalization (r=−0.358, p=0.01). The structural equation model identified use of hospice care was inversely related to both hospital mortality (−.885) and ICU mortality rate (−.457). Conclusions The results of this investigation demonstrate that greater utilization of hospice care during the last 6-months of life is associated with improved patient experience of care including satisfaction and pain control, as well as clinical outcomes of care including decreased ICU and hospital mortality. PMID:27531840

Heart rate variability alterations in late life depression: A meta-analysis.

PubMed

Brown, Lydia; Karmakar, Chandan; Gray, Richard; Jindal, Ripu; Lim, Terrence; Bryant, Christina

2018-08-01

There is strong evidence for a bi-directional relationship between heart-health and depression in later life, but the physiological mechanisms underlying this relationship remain unclear. Heart rate variability is one promising factor that might help explain this relationship. We present results of a meta-analysis that considers heart rate variability alterations in older adults with depression. Literature search of Embase, PsychInfo and Medline revealed five clinical studies and six observational studies that examined the relationship between heart rate variability and depression in adults with a mean age over 60. These studies were included in this meta-analysis. Heart rate variability was reduced among older adults with clinical depression (N = 550), relative to healthy controls (Hedges' g = -0.334, 95%CI [-0.579, -0.090], p = .007). When high-frequency and low-frequency heart rate variability were investigated separately, only low-frequency heart rate variability was significantly reduced in depressed patients (Hedges' g = -0.626, 95%CI [-1.083, -0.169], p = .007). A similar but weaker pattern of results was found in the observational studies. Most findings remained significant among unmedicated depressed older adults. Evidence of effect-size heterogeneity was found in the clinical studies, indicating the need for more well-designed research in the area. Heart rate variability is reduced among older adults with depression, and this effect is not fully attributable to antidepressant medication use. Specifically, low-frequency heart rate variability may be reduced in depressed older adults. Heart rate variability warrants further attention, as it could help inform research into the prevention and treatment of depression in later life. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of a computer-based clinical decision support tool for selecting appropriate rehabilitation interventions for injured workers.

PubMed

Gross, Douglas P; Zhang, Jing; Steenstra, Ivan; Barnsley, Susan; Haws, Calvin; Amell, Tyler; McIntosh, Greg; Cooper, Juliette; Zaiane, Osmar

2013-12-01

To develop a classification algorithm and accompanying computer-based clinical decision support tool to help categorize injured workers toward optimal rehabilitation interventions based on unique worker characteristics. Population-based historical cohort design. Data were extracted from a Canadian provincial workers' compensation database on all claimants undergoing work assessment between December 2009 and January 2011. Data were available on: (1) numerous personal, clinical, occupational, and social variables; (2) type of rehabilitation undertaken; and (3) outcomes following rehabilitation (receiving time loss benefits or undergoing repeat programs). Machine learning, concerned with the design of algorithms to discriminate between classes based on empirical data, was the foundation of our approach to build a classification system with multiple independent and dependent variables. The population included 8,611 unique claimants. Subjects were predominantly employed (85 %) males (64 %) with diagnoses of sprain/strain (44 %). Baseline clinician classification accuracy was high (ROC = 0.86) for selecting programs that lead to successful return-to-work. Classification performance for machine learning techniques outperformed the clinician baseline classification (ROC = 0.94). The final classifiers were multifactorial and included the variables: injury duration, occupation, job attachment status, work status, modified work availability, pain intensity rating, self-rated occupational disability, and 9 items from the SF-36 Health Survey. The use of machine learning classification techniques appears to have resulted in classification performance better than clinician decision-making. The final algorithm has been integrated into a computer-based clinical decision support tool that requires additional validation in a clinical sample.

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study

PubMed Central

Pranal, Thibaut; Pereira, Bruno; Berthelin, Pauline; Roszyk, Laurence; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Gillart, Thierry; Skrzypczak, Yvan; Souweine, Bertrand; Bouvier, Damien; Constantin, Jean-Michel

2018-01-01

Rationale Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. Objectives To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. Methods Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. Measurements and Main Results 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. Conclusions We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536. PMID:29861796

High Intrapatient Variability of Tacrolimus Levels and Outpatient Clinic Nonattendance Are Associated With Inferior Outcomes in Renal Transplant Patients

PubMed Central

Goodall, Dawn L.; Willicombe, Michelle; McLean, Adam G.; Taube, David

2017-01-01

Background Nonadherence to immunosuppressants is associated with rejection and allograft loss. Intrapatient variability (IPV) of immunosuppression levels is a marker of nonadherence. This study describes the impact of IPV of tacrolimus levels in patients receiving a tacrolimus monotherapy immunosuppression protocol. Methods We retrospectively analyzed the outpatient tacrolimus levels of kidney-only transplant patients taken between 6 and 12 months posttransplant. IPV was determined using the coefficient of variance. Results Six hundred twenty-eight patients with a mean number of 8.98 ± 3.81 tacrolimus levels and a mean follow-up of 4.72 ± 2.19 years were included. Multivariate analysis showed death was associated with increasing age (1.04 [1.01-1.07], P = 0.0055), diabetes at time of transplant (2.79 [1.44-5.41], P = 0.0024), and rejection (2.34 [1.06-5.19], P = 0.036). Variables associated with graft loss included the highest variability group (2.51 [1.01-6.27], P = 0.048), mean tacrolimus level less than 5 ng/mL (4.32 [1.94-9.63], P = 0.0003), a high clinic nonattendance rate (1.10 [1.01-1.20], P = 0.03), and rejection (9.83 [4.62-20.94], P < 0.0001). Independent risk factors for rejection were de novo donor-specific antibody (3.15 [1.84-5.39], P < 0.0001), mean tacrolimus level less than 5 ng/mL (2.57 [1.27-5.19], P = 0.00860, and a high clinic nonattendance rate (1.11 [1.05-1.18], P = 0.0005). Conclusions This study shows that high tacrolimus IPV and clinic nonattendance are associated with inferior allograft survival. Interventions to minimize the causes of high variability, particularly nonadherence are essential to improve long-term allograft outcomes. PMID:28795143

Predictive power of the grace score in population with diabetes.

PubMed

Baeza-Román, Anna; de Miguel-Balsa, Eva; Latour-Pérez, Jaime; Carrillo-López, Andrés

2017-12-01

Current clinical practice guidelines recommend risk stratification in patients with acute coronary syndrome (ACS) upon admission to hospital. Diabetes mellitus (DM) is widely recognized as an independent predictor of mortality in these patients, although it is not included in the GRACE risk score. The objective of this study is to validate the GRACE risk score in a contemporary population and particularly in the subgroup of patients with diabetes, and to test the effects of including the DM variable in the model. Retrospective cohort study in patients included in the ARIAM-SEMICYUC registry, with a diagnosis of ACS and with available in-hospital mortality data. We tested the predictive power of the GRACE score, calculating the area under the ROC curve. We assessed the calibration of the score and the predictive ability based on type of ACS and the presence of DM. Finally, we evaluated the effect of including the DM variable in the model by calculating the net reclassification improvement. The GRACE score shows good predictive power for hospital mortality in the study population, with a moderate degree of calibration and no significant differences based on ACS type or the presence of DM. Including DM as a variable did not add any predictive value to the GRACE model. The GRACE score has an appropriate predictive power, with good calibration and clinical applicability in the subgroup of diabetic patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Lesch-Nyhan variant syndrome: variable presentation in 3 affected family members.

PubMed

Sarafoglou, Kyriakie; Grosse-Redlinger, Krista; Boys, Christopher J; Charnas, Laurence; Otten, Noelle; Broock, Robyn; Nyhan, William L

2010-06-01

Lesch-Nyhan disease is an inborn error of purine metabolism that results from deficiency of the activity of hypoxanthine phosphoribosyltransferase (HPRT). The heterogeneity of clinical phenotypes seen in HPRT deficiency corresponds to an inverse relationship between HPRT enzyme activity and clinical severity. With rare exception, each mutation produces a stereotypical pattern of clinical disease; onset of neurologic symptoms occurs during infancy and is thought to be nonprogressive. To document a family in which a single HPRT gene mutation has led to 3 different clinical and enzymatic phenotypes. Case report. Settings A university-based outpatient metabolic clinic and a biochemical genetics laboratory. Patients Three males (2 infants and their grandfather) from the same family with Lesch-Nyhan variant, including one of the oldest patients with Lesch-Nyhan variant at diagnosis (65 years). Clinical and biochemical observations. Sequencing of 5 family members revealed a novel mutation c.550G>T in exon 7 of the HPRT gene. The considerably variable clinical phenotype corresponded with the variable enzymatic activity in the 3 males, with the grandfather being the most severely affected. The different phenotypes encountered in the enzymatic analysis of cultured fibroblasts from a single mutation in the same family is unprecedented. The significant decrease in the grandfather's HPRT enzymatic activity compared with that of his grandchildren could be a function of the Hayflick Limit Theory of cell senescence.

TEPAPA: a novel in silico feature learning pipeline for mining prognostic and associative factors from text-based electronic medical records.

PubMed

Lin, Frank Po-Yen; Pokorny, Adrian; Teng, Christina; Epstein, Richard J

2017-07-31

Vast amounts of clinically relevant text-based variables lie undiscovered and unexploited in electronic medical records (EMR). To exploit this untapped resource, and thus facilitate the discovery of informative covariates from unstructured clinical narratives, we have built a novel computational pipeline termed Text-based Exploratory Pattern Analyser for Prognosticator and Associator discovery (TEPAPA). This pipeline combines semantic-free natural language processing (NLP), regular expression induction, and statistical association testing to identify conserved text patterns associated with outcome variables of clinical interest. When we applied TEPAPA to a cohort of head and neck squamous cell carcinoma patients, plausible concepts known to be correlated with human papilloma virus (HPV) status were identified from the EMR text, including site of primary disease, tumour stage, pathologic characteristics, and treatment modalities. Similarly, correlates of other variables (including gender, nodal status, recurrent disease, smoking and alcohol status) were also reliably recovered. Using highly-associated patterns as covariates, a patient's HPV status was classifiable using a bootstrap analysis with a mean area under the ROC curve of 0.861, suggesting its predictive utility in supporting EMR-based phenotyping tasks. These data support using this integrative approach to efficiently identify disease-associated factors from unstructured EMR narratives, and thus to efficiently generate testable hypotheses.

Development of a computerized assessment of clinician adherence to a treatment guideline for patients with bipolar disorder.

PubMed

Dennehy, Ellen B; Suppes, Trisha; John Rush, A; Lynn Crismon, M; Witte, B; Webster, J

2004-01-01

The adoption of treatment guidelines for complex psychiatric illness is increasing. Treatment decisions in psychiatry depend on a number of variables, including severity of symptoms, past treatment history, patient preferences, medication tolerability, and clinical response. While patient outcomes may be improved by the use of treatment guidelines, there is no agreed upon standard by which to assess the degree to which clinician behavior corresponds to those recommendations. This report presents a method to assess clinician adherence to the complex multidimensional treatment guideline for bipolar disorder utilized in the Texas Medication Algorithm Project. The steps involved in the development of this system are presented, including the reliance on standardized documentation, defining core variables of interest, selecting criteria for operationalization of those variables, and computerization of the assessment of adherence. The computerized assessment represents an improvement over other assessment methods, which have relied on laborious and costly chart reviews to extract clinical information and to analyze provider behavior. However, it is limited by the specificity of decisions that guided the adherence scoring process. Preliminary findings using this system with 2035 clinical visits conducted for the bipolar disorder module of TMAP Phase 3 are presented. These data indicate that this system of guideline adherence monitoring is feasible.

A diagnostic model for chronic hypersensitivity pneumonitis

PubMed Central

Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

2017-01-01

The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist’s diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. PMID:27245779

Mandatory implementation of NICE Guidelines for the care of bipolar disorder and other conditions in England and Wales.

PubMed

Morriss, Richard

2015-09-30

Bipolar disorder is a common long-term mental health condition characterised by episodes of mania or hypomania and depression resulting in disability, early death, and high health and society costs. Public money funds the National Institute of Healthcare and Clinical Excellence (NICE) to produce clinical guidelines by systematically identifying the most up to date research evidence and costing its main recommendations for healthcare organisations and professionals to follow in England and Wales. Most governments, including those of England and Wales, need to improve healthcare but at reduced cost. There is evidence, particularly in bipolar disorder, that systematically following clinical guidelines achieves these outcomes. NICE clinical guidelines, including those regarding bipolar disorder, remain variably implemented. They give clinicians and patients a non-prescriptive basis for deciding their care. Despite the passing of the Health and Social Care Act in 2012 in England requiring all healthcare organisations to consider NICE clinical guidelines in commissioning, delivering, and inspecting healthcare services, healthcare organisations in the National Health Service may ignore them with little accountability and few consequences. There is no mechanism to ensure that healthcare professionals know or consider them. Barriers to their implementation include the lack of political and professional leadership, the complexity of the organisation of care and policy, mistrust of some processes and recommendations of clinical guidelines, and a lack of a clear implementation model, strategy, responsibility, or accountability. Mitigation to these barriers is presented herein. The variability, safety, and quality of healthcare might be improved and its cost reduced if the implementation of NICE clinical guidelines, such as those for bipolar disorder, were made the minimum starting point for clinical decision-making and mandatory responsibilities of all healthcare organisations and professionals.

Endodontic and Clinical Considerations in the Management of Variable Anatomy in Mandibular Premolars: A Literature Review

PubMed Central

Hammo, Mohammad

2014-01-01

Mandibular premolars are known to have numerous anatomic variations of their roots and root canals, which are a challenge to treat endodontically. The paper reviews literature to detail the various clinically relevant anatomic considerations with detailed techniques and methods to successfully manage these anomalies. An emphasis and detailed description of every step of treatment including preoperative diagnosis, intraoperative identification and management, and surgical endodontic considerations for the successful management of these complex cases have been included. PMID:24895584

Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability.

PubMed

Fourier, Anthony; Portelius, Erik; Zetterberg, Henrik; Blennow, Kaj; Quadrio, Isabelle; Perret-Liaudet, Armand

2015-09-20

A panel of cerebrospinal fluid (CSF) biomarkers including total Tau (t-Tau), phosphorylated Tau protein at residue 181 (p-Tau) and β-amyloid peptides (Aβ42 and Aβ40), is frequently used as an aid in Alzheimer's disease (AD) diagnosis for young patients with cognitive impairment, for predicting prodromal AD in mild cognitive impairment (MCI) subjects, for AD discrimination in atypical clinical phenotypes and for inclusion/exclusion and stratification of patients in clinical trials. Due to variability in absolute levels between laboratories, there is no consensus on medical cut-off value for the CSF AD signature. Thus, for full implementation of this core AD biomarker panel in clinical routine, this issue has to be solved. Variability can be explained both by pre-analytical and analytical factors. For example, the plastic tubes used for CSF collection and storage, the lack of reference material and the variability of the analytical protocols were identified as important sources of variability. The aim of this review is to highlight these pre-analytical and analytical factors and describe efforts done to counteract them in order to establish cut-off values for core CSF AD biomarkers. This review will give the current state of recommendations. Copyright © 2015. Published by Elsevier B.V.

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST–RA database

PubMed Central

Sokka, T; Kautiainen, H; Pincus, T; Toloza, S; da Rocha Castelar Pinheiro, G; Lazovskis, J; Hetland, M L; Peets, T; Immonen, K; Maillefert, J F; Drosos, A A; Alten, R; Pohl, C; Rojkovich, B; Bresnihan, B; Minnock, P; Cazzato, M; Bombardieri, S; Rexhepi, S; Rexhepi, M; Andersone, D; Stropuviene, S; Huisman, M; Sierakowski, S; Karateev, D; Skakic, V; Naranjo, A; Baecklund, E; Henrohn, D; Gogus, F; Badsha, H; Mofti, A; Taylor, P; McClinton, C; Yazici, Y

2009-01-01

Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST–RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 “high GDP” countries with GDP per capita greater than US$24 000 and 11 “low GDP” countries with GDP per capita less than US$11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r  =  −0.78, 95% CI −0.56 to −0.90, r2  =  61%). Disease activity levels differed substantially between “high GDP” and “low GDP” countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in “low GDP” than in “high GDP” countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries. PMID:19643759

Visit-to-visit cholesterol variability correlates with coronary atheroma progression and clinical outcomes.

PubMed

Clark, Donald; Nicholls, Stephen J; St John, Julie; Elshazly, Mohamed B; Kapadia, Samir R; Tuzcu, E Murat; Nissen, Steven E; Puri, Rishi

2018-04-21

Utilizing serial intravascular ultrasonography (IVUS), we aimed to exam the association of intra-individual lipid variability, coronary atheroma progression, and clinical outcomes. We performed a post hoc patient-level analysis of nine clinical trials involving 4976 patients with coronary artery disease who underwent serial coronary IVUS in the setting of a range of medical therapies. We assessed the associations between progression in percent atheroma volume (ΔPAV), clinical outcomes, and visit-to-visit lipid variability including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC)/HDL-C, and apolipoprotein B (ApoB). Variability of lipid parameters was measured using intra-individual standard deviation over 3, 6, 12, 18, and 24 months. Atherogenic lipoprotein variability significantly associated with ΔPAV [odds ratio (95% confidence interval; P-value), LDL-C: 1.09 (1.02, 1.17, P = 0.01); non-HDL-C: 1.10 (1.02, 1.18, P = 0.01); TC/HDL-C: 1.14 (1.06, 1.24, P = 0.001); ApoB: 1.13 (1.03, 1.24, P = 0.01)]. Survival curves revealed significant stepwise relationships between cumulative major adverse cardiovascular events and increasing quartiles of atherogenic lipoprotein variability at 24-months follow-up (log-rank P < 0.01 for all lipoproteins except HDL-C). Stronger associations were noted between achieved lipoprotein levels and ΔPAV [LDL-C: 1.27 (1.17, 1.39; P < 0.001); non-HDL-C: 1.32 (1.21, 1.45; P < 0.001); TC/HDL-C: 1.31 (1.19, 1.45; P < 0.001); ApoB: 1.20 (1.07, 1.35; P = 0.003)]. Greater visit-to-visit variability in atherogenic lipoprotein levels significantly associates with coronary atheroma progression and clinical outcomes, although the association between achieved atherogenic lipoproteins and atheroma progression appears stronger. These data highlight the importance of achieving low and consistent atherogenic lipoprotein levels to promote plaque regression and improve clinical outcomes.

[Study of echocardiographic parameters of rheumatoid arthritis black African without clinically evident cardiovascular manifestations: A cross-sectional study of 73 cases in Senegal].

PubMed

Dodo-Siddo, M N; Diao, M; Ndiaye, M B; Ndongo, S; Kane, A; Mbaye, A; Bodian, M; Sarr, S A; Sarr, M; Ba, S; Diop, T M

2016-04-01

Research of cardiac involvement in patients with rheumatoid arthritis can prevent complications and place in a logical secondary prevention. The objective of this study was to investigate the echocardiographic parameters in a population of Senegalese patients with rheumatoid arthritis without clinically evident cardiovascular manifestations. We conducted a descriptive cross-sectional study, which included prospectively from outpatients in the internal medicine department of university hospital center Aristide Le Dantec in Dakar, Senegal, with a diagnosis of rheumatoid arthritis without clinically evident cardiovascular disease. It focused on a sample of 73 patients of both sexes aged at least 18 years. Following clinical examination, we conducted laboratory tests (CRP, fibrinogen, ESR, rheumatoid factors: Latex and Waaler-Rose, anti-CCP, antinuclear factors and anti-ENA antibodies), ECG, echocardiography standard. Data were analyzed using a descriptive study of the different variables with the calculation of proportions for categorical variables, and the positional parameters and dispersion for quantitative variables. A total of 73 patients with rheumatoid arthritis without obvious cardiac events and meeting the criteria of definition of the ACR 1987 were included in the study. The mean age was 44.17±14.43 years with extremes of 18 and 75 years. The mean duration of RA was 5.93±4.78 years. The concept of family inflammatory arthritis was reported in 35.60% of cases and almost one in six patients had at least a factor of cardiovascular risk (16.96%). The abnormalities found in Doppler echocardiography were dominated by diastolic LV dysfunction (42.46%), increased left ventricular mass in 35.61%. Valvular leaks of variable grades were highlighted regarding all orifices but were rarely significant. The realization of echocardiography in patients with rheumatoid arthritis without clinically evident cardiovascular manifestations helps to highlight cardiovascular abnormalities related to the natural course of the disease. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Noonan syndrome and clinically related disorders

PubMed Central

Tartaglia, Marco; Gelb, Bruce D.; Zenker, Martin

2010-01-01

Noonan syndrome is a relatively common, clinically variable developmental disorder. Cardinal features include postnatally reduced growth, distinctive facial dysmorphism, congenital heart defects and hypertrophic cardiomyopathy, variable cognitive deficit and skeletal, ectodermal and hematologic anomalies. Noonan syndrome is transmitted as an autosomal dominant trait, and is genetically heterogeneous. So far, heterozygous mutations in nine genes (PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1 and CBL) have been documented to underlie this disorder or clinically related phenotypes. Based on these recent discoveries, the diagnosis can now be confirmed molecularly in approximately 75% of affected individuals. Affected genes encode for proteins participating in the RAS-mitogen-activated protein kinases (MAPK) signal transduction pathway, which is implicated in several developmental processes controlling morphology determination, organogenesis, synaptic plasticity and growth. Here, we provide an overview of clinical aspects of this disorder and closely related conditions, the molecular mechanisms underlying pathogenesis, and major genotype-phenotype correlations. PMID:21396583

Implementing the undergraduate mini-CEX: a tailored approach at Southampton University.

PubMed

Hill, Faith; Kendall, Kathleen; Galbraith, Kevin; Crossley, Jim

2009-04-01

The mini-clinical evaluation exercise (mini-CEX) is widely used in the UK to assess clinical competence, but there is little evidence regarding its implementation in the undergraduate setting. This study aimed to estimate the validity and reliability of the undergraduate mini-CEX and discuss the challenges involved in its implementation. A total of 3499 mini-CEX forms were completed. Validity was assessed by estimating associations between mini-CEX score and a number of external variables, examining the internal structure of the instrument, checking competency domain response rates and profiles against expectations, and by qualitative evaluation of stakeholder interviews. Reliability was evaluated by overall reliability coefficient (R), estimation of the standard error of measurement (SEM), and from stakeholders' perceptions. Variance component analysis examined the contribution of relevant factors to students' scores. Validity was threatened by various confounding variables, including: examiner status; case complexity; attachment specialty; patient gender, and case focus. Factor analysis suggested that competency domains reflect a single latent variable. Maximum reliability can be achieved by aggregating scores over 15 encounters (R = 0.73; 95% confidence interval [CI] +/- 0.28 based on a 6-point assessment scale). Examiner stringency contributed 29% of score variation and student attachment aptitude 13%. Stakeholder interviews revealed staff development needs but the majority perceived the mini-CEX as more reliable and valid than the previous long case. The mini-CEX has good overall utility for assessing aspects of the clinical encounter in an undergraduate setting. Strengths include fidelity, wide sampling, perceived validity, and formative observation and feedback. Reliability is limited by variable examiner stringency, and validity by confounding variables, but these should be viewed within the context of overall assessment strategies.

Protocol for a prospective collaborative systematic review and meta-analysis of individual patient data from randomized controlled trials of vasoactive drugs in acute stroke: The Blood pressure in Acute Stroke Collaboration, stage-3.

PubMed

Sandset, Else Charlotte; Sanossian, Nerses; Woodhouse, Lisa J; Anderson, Craig; Berge, Eivind; Lees, Kennedy R; Potter, John F; Robinson, Thompson G; Sprigg, Nikola; Wardlaw, Joanna M; Bath, Philip M

2018-01-01

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains particularly for ischemic stroke. The "Blood pressure in Acute Stroke Collaboration" commenced in the mid-1990s focussing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, Blood pressure in Acute Stroke Collaboration planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, including both intracerebral hemorrhage and ischemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on hemodynamic variables. Methods and design Individual patient data from randomized controlled trials of blood pressure management in participants with ischemic stroke and/or intracerebral hemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 h), acute (<48 h), and sub-acute (<168 h) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in pre-specified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, hemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration.

Use of Wearable Sensors and Biometric Variables in an Artificial Pancreas System.

PubMed

Turksoy, Kamuran; Monforti, Colleen; Park, Minsun; Griffith, Garett; Quinn, Laurie; Cinar, Ali

2017-03-07

An artificial pancreas (AP) computes the optimal insulin dose to be infused through an insulin pump in people with Type 1 Diabetes (T1D) based on information received from a continuous glucose monitoring (CGM) sensor. It has been recognized that exercise is a major challenge in the development of an AP system. The use of biometric physiological variables in an AP system may be beneficial for prevention of exercise-induced challenges and better glucose regulation. The goal of the present study is to find a correlation between biometric variables such as heart rate (HR), heat flux (HF), skin temperature (ST), near-body temperature (NBT), galvanic skin response (GSR), and energy expenditure (EE), 2D acceleration-mean of absolute difference (MAD) and changes in glucose concentrations during exercise via partial least squares (PLS) regression and variable importance in projection (VIP) in order to determine which variables would be most useful to include in a future artificial pancreas. PLS and VIP analyses were performed on data sets that included seven different types of exercises. Data were collected from 26 clinical experiments. Clinical results indicate ST to be the most consistently important (important for six out of seven tested exercises) variable over all different exercises tested. EE and HR are also found to be important variables over several types of exercise. We also found that the importance of GSR and NBT observed in our experiments might be related to stress and the effect of changes in environmental temperature on glucose concentrations. The use of the biometric measurements in an AP system may provide better control of glucose concentration.

Prevalence of obesity recorded in Primary Care.

PubMed

Gutiérrez Angulo, María Luisa; Amenabar Azurmendi, Miren Dolores; Cuesta Solé, María Lourdes; Prieto Esteban, Irene; Mancebo Martínez, Sara; Iglesias Alonso, Amparo

2014-11-01

To ascertain the prevalence of obesity and overweight recording in primary care (PC) clinical records. A descriptive, cross-sectional study. The study was conducted in three urban, primary care centers in Gipuzkoa. 620 computerized clinical records randomly selected from a population of 63,820. Patient age older than 14 years was the only inclusion criterion. Recording of the clinical episode referring to obesity and/or overweight. Other variables included age, sex, body mass index (BMI), waist circumference, comorbidity (diabetes, hypertension, heart failure, among others), and variability of the record made by healthcre professionals at each center. Statistical analysis included a Chi-square test or a Fisher's test for low frequencies. A value of P<.05 was considered significant. Analysis was performed using SPSS(®) v.21 software. Prevalence of recorded obesity was 6%, and 78.4% of those with recorded obesity were women. Overweight was recorded in 3% of subjects, of which 33.2% were women. BMI was recorded in 170 cases (27%). At least one comorbidity was found in 241 subjects (39%). Association of BMI with presence of comorbidity was statistically significant (P=.0001). Recording of obesity was associated to presence of comorbidity (P =.0002). This study confirmed that prevalence of obesity is underestimated, mainly because it is inadequately recorded in clinical histories; that prevalence increases in the presence of other risk factors; and that there is a significant variability in data collection between healthcare professionals. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Clinical and Molecular Aspects of an Informative Family with Neurofibromatosis Type 1 and Noonan Phenotype

PubMed Central

Stevenson, David A.; Viskochil, David H.; Rope, Alan F.; Carey, John C.

2011-01-01

NF-Noonan syndrome (NFNS) has been described as a unique phenotype, combining manifestations of neurofibromatosis type 1 (NF1) and Noonan syndromes, which are separate syndromes. Potential etiologies of NF-Noonan syndrome include a discrete syndrome of distinct etiology, co-segregation of two mutated common genes, variable clinical expressivity of NF1, and/or allelic heterogeneity. We present an informative family with an unusual NF1 mutation with variable features of NF1 and Noonan syndrome. We hypothesize that an NF1 mutant allele can lead to diagnostic manifestations of Noonan syndrome, supporting the hypothesis that NF1 allelic heterogeneity causes NFNS. PMID:16542390

Variables associated with health-related quality of life in a Brazilian sample of patients from a tertiary outpatient clinic for depression and anxiety disorders.

PubMed

Schwab, Bianca; Daniel, Heloisa Silveira; Lutkemeyer, Carine; Neves, João Arthur Lange Lins; Zilli, Louise Nassif; Guarnieri, Ricardo; Diaz, Alexandre Paim; Michels, Ana Maria Maykot Prates

2015-01-01

Health-related quality of life (HRQOL) assessment tools have been broadly used in the medical context. These tools are used to measure the subjective impact of the disease on patients. The objective of this study was to evaluate the variables associated with HRQOL in a Brazilian sample of patients followed up in a tertiary outpatient clinic for depression and anxiety disorders. Cross-sectional study. Independent variables were those included in a sociodemographic questionnaire and the Hospital Anxiety and Depression Scale (HADS) scores. Dependent variables were those included in the short version of the World Health Organization Quality of Life (WHOQOL-BREF) and the scores for its subdomains (overall quality of life and general health, physical health, psychological health, social relationships, and environment). A multiple linear regression analysis was used to find the variables independently associated with each outcome. Seventy-five adult patients were evaluated. After multiple linear regression analysis, the HADS scores were associated with all outcomes, except social relationships (p = 0.08). Female gender was associated with poor total scores, as well as psychological health and environment. Unemployment was associated with poor physical health. Identifying the factors associated with HRQOL and recognizing that depression and anxiety are major factors are essential to improve the care of patients.

Multilevel analysis of ADHD, anxiety and depression symptoms aggregation in families.

PubMed

Segenreich, Daniel; Paez, Marina Silva; Regalla, Maria Angélica; Fortes, Dídia; Faraone, Stephen V; Sergeant, Joseph; Mattos, Paulo

2015-05-01

A strong genetic role in the etiology of attention-deficit hyperactivity disorder (ADHD) has been demonstrated by several studies using different methodologies. Shortcomings of genetic studies often include the lack of golden standard practices for diagnosis for ADHD, the use of categorical instead of a dimensional approach, and the disregard for assortative mating phenomenon in parents. The current study aimed to overcome these shortcomings and analyze data through a novel statistical approach, using multilevel analyses with Bayesian procedures and a specific mathematical model, which takes into account data with an elevated number of zero responses (expected in samples with few or no ADHD symptoms). Correlations of parental clinical variables (ADHD, anxiety and depression) to offspring psychopathology may vary according to gender and type of symptoms. We aimed to investigate how those variables interact within each other. One hundred families, comprising a proband child or adolescent with ADHD or a typically developing child or adolescent were included and all family members (both biological parents, the proband child or adolescent and their sibling) were examined through semi-structured interviews using DSM-IV criteria. Results indicated that: (a) maternal clinical variables (ADHD, anxiety and depression) were more correlated with offspring variables than paternal ones; (b) maternal inattention (but not hyperactivity) was correlated with both inattention and hyperactivity in the offspring; (c) maternal anxiety was correlated with offspring inattention; on the other hand, maternal inattention was correlated with anxiety in the offspring. Although a family study design limits the possibility of revealing causality and cannot disentangle genetic and environmental factors, our findings suggest that ADHD, anxiety and depression are variables that correlate in families and should be addressed together. Maternal variables significantly correlated with offspring variables, but the paternal variables did not.

Epidemiological, clinical, microbiological and therapeutic differences in tuberculosis disease in patients with and without HIV infection.

PubMed

Martínez-Sanz, Javier; Lago-Gómez, María Rosa; Rodríguez-Zurita, María Elena; Martín-Echevarría, Esteban; Torralba, Miguel

2018-04-23

Our objective is to analyze the incidence of tuberculosis (TB) in our population and to compare the characteristics of patients with and without HIV infection. Clinical-epidemiological retrospective cohort study that included patients diagnosed with TB with and without HIV infection between 2005-2016 in the province of Guadalajara (Spain). Epidemiological, clinical, microbiological and therapeutic variables were assessed, including microbiological resistances. TB was diagnosed in 261 patients. There were 25 patients (9.6%) who had HIV infection. Patients with HIV infection were predominantly males, had higher incidence of hepatitis C virus, a higher percentage of extrapulmonary TB, a higher prevalence of resistance to isoniazid and rifampicin, a greater paradoxical response and a longer average hospital stay. On the other hand, they had a lower percentage of positive tuberculin skin test and positive sputum smear (microscopy). A significant percentage of TB patients had no serology for HIV. Patients with HIV infection show remarkable differences in epidemiological, clinical and resistance variables to antituberculosis drugs. A high percentage of patients with TB were not tested for HIV. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Assessing the clinical utility of cancer genomic and proteomic data across tumor types.

PubMed

Yuan, Yuan; Van Allen, Eliezer M; Omberg, Larsson; Wagle, Nikhil; Amin-Mansour, Ali; Sokolov, Artem; Byers, Lauren A; Xu, Yanxun; Hess, Kenneth R; Diao, Lixia; Han, Leng; Huang, Xuelin; Lawrence, Michael S; Weinstein, John N; Stuart, Josh M; Mills, Gordon B; Garraway, Levi A; Margolin, Adam A; Getz, Gad; Liang, Han

2014-07-01

Molecular profiling of tumors promises to advance the clinical management of cancer, but the benefits of integrating molecular data with traditional clinical variables have not been systematically studied. Here we retrospectively predict patient survival using diverse molecular data (somatic copy-number alteration, DNA methylation and mRNA, microRNA and protein expression) from 953 samples of four cancer types from The Cancer Genome Atlas project. We find that incorporating molecular data with clinical variables yields statistically significantly improved predictions (FDR < 0.05) for three cancers but those quantitative gains were limited (2.2-23.9%). Additional analyses revealed little predictive power across tumor types except for one case. In clinically relevant genes, we identified 10,281 somatic alterations across 12 cancer types in 2,928 of 3,277 patients (89.4%), many of which would not be revealed in single-tumor analyses. Our study provides a starting point and resources, including an open-access model evaluation platform, for building reliable prognostic and therapeutic strategies that incorporate molecular data.

Clinical Geneticists’ Views of VACTERL/VATER Association

PubMed Central

Solomon, Benjamin D.; Bear, Kelly A.; Kimonis, Virginia; de Klein, Annelies; Scott, Daryl A.; Shaw-Smith, Charles; Tibboel, Dick; Reutter, Heiko; Giampietro, Philip F.

2012-01-01

VACTERL association (sometimes termed “VATER association” depending on which component features are included) is typically defined by the presence of at least three of the following congenital malformations, which tend to statistically co-occur in affected individuals: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Although the clinical criteria for VACTERL association may appear to be straightforward, there is wide variability in the way clinical geneticists define the disorder and the genetic testing strategy they use when confronted with an affected patient. In order to describe this variability and determine the most commonly used definitions and testing modalities, we present the results of survey responses by 121 clinical geneticists. We discuss the results of the survey responses, provide a literature review and commentary from a group of physicians who are currently involved in clinical and laboratory-based research on VACTERL association, and offer an algorithm for genetic testing in patients with this association. PMID:23165726

The use of intelligent database systems in acute pancreatitis--a systematic review.

PubMed

van den Heever, Marc; Mittal, Anubhav; Haydock, Matthew; Windsor, John

2014-01-01

Acute pancreatitis (AP) is a complex disease with multiple aetiological factors, wide ranging severity, and multiple challenges to effective triage and management. Databases, data mining and machine learning algorithms (MLAs), including artificial neural networks (ANNs), may assist by storing and interpreting data from multiple sources, potentially improving clinical decision-making. 1) Identify database technologies used to store AP data, 2) collate and categorise variables stored in AP databases, 3) identify the MLA technologies, including ANNs, used to analyse AP data, and 4) identify clinical and non-clinical benefits and obstacles in establishing a national or international AP database. Comprehensive systematic search of online reference databases. The predetermined inclusion criteria were all papers discussing 1) databases, 2) data mining or 3) MLAs, pertaining to AP, independently assessed by two reviewers with conflicts resolved by a third author. Forty-three papers were included. Three data mining technologies and five ANN methodologies were reported in the literature. There were 187 collected variables identified. ANNs increase accuracy of severity prediction, one study showed ANNs had a sensitivity of 0.89 and specificity of 0.96 six hours after admission--compare APACHE II (cutoff score ≥8) with 0.80 and 0.85 respectively. Problems with databases were incomplete data, lack of clinical data, diagnostic reliability and missing clinical data. This is the first systematic review examining the use of databases, MLAs and ANNs in the management of AP. The clinical benefits these technologies have over current systems and other advantages to adopting them are identified. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

A Partial Least-Squares Analysis of Health-Related Quality-of-Life Outcomes After Aneurysmal Subarachnoid Hemorrhage.

PubMed

Young, Julia M; Morgan, Benjamin R; Mišić, Bratislav; Schweizer, Tom A; Ibrahim, George M; Macdonald, R Loch

2015-12-01

Individuals who have aneurysmal subarachnoid hemorrhages (SAHs) experience decreased health-related qualities of life (HRQoLs) that persist after the primary insult. To identify clinical variables that concurrently associate with HRQoL outcomes by using a partial least-squares approach, which has the distinct advantage of explaining multidimensional variance where predictor variables may be highly collinear. Data collected from the CONSCIOUS-1 trial was used to extract 29 clinical variables including SAH presentation, hospital procedures, and demographic information in addition to 5 HRQoL outcome variables for 256 individuals. A partial least-squares analysis was performed by calculating a heterogeneous correlation matrix and applying singular value decomposition to determine components that best represent the correlations between the 2 sets of variables. Bootstrapping was used to estimate statistical significance. The first 2 components accounting for 81.6% and 7.8% of the total variance revealed significant associations between clinical predictors and HRQoL outcomes. The first component identified associations between disability in self-care with longer durations of critical care stay, invasive intracranial monitoring, ventricular drain time, poorer clinical grade on presentation, greater amounts of cerebral spinal fluid drainage, and a history of hypertension. The second component identified associations between disability due to pain and discomfort as well as anxiety and depression with greater body mass index, abnormal heart rate, longer durations of deep sedation and critical care, and higher World Federation of Neurosurgical Societies and Hijdra scores. By applying a data-driven, multivariate approach, we identified robust associations between SAH clinical presentations and HRQoL outcomes. EQ-VAS, EuroQoL visual analog scaleHRQoL, health-related quality of lifeICU, intensive care unitIVH, intraventricular hemorrhagePLS, partial least squaresSAH, subarachnoid hemorrhageSVD, singular value decompositionWFNS, World Federation of Neurosurgical Societies.

Women's perceptions of their male batterers' characteristics and level of violence.

PubMed

Torres, Sara; Han, Hae-Ra

2003-01-01

This article describes the characteristics of male perpetrators of domestic violence and their relationship to the level of violence. The data about the male partners obtained from 151 battered women were used for this analysis. Using multiple regression, demographic variables and three behavioral indicators, including use of alcohol before a violent episode, history of arrests, and the generality of violence, were examined together for their relationship with the violence scores. With the level of violence as measured by the Conflict Tactics Scale (CTS) as the dependent variable, demographic variables explained 19.1% of the variability, with the behavioral indicators accounting for an additional 4.6% of the variability. Several research and clinical implications are addressed.

Psychogenic Tremor: A Video Guide to Its Distinguishing Features

PubMed Central

Thenganatt, Mary Ann; Jankovic, Joseph

2014-01-01

Background Psychogenic tremor is the most common psychogenic movement disorder. It has characteristic clinical features that can help distinguish it from other tremor disorders. There is no diagnostic gold standard and the diagnosis is based primarily on clinical history and examination. Despite proposed diagnostic criteria, the diagnosis of psychogenic tremor can be challenging. While there are numerous studies evaluating psychogenic tremor in the literature, there are no publications that provide a video/visual guide that demonstrate the clinical characteristics of psychogenic tremor. Educating clinicians about psychogenic tremor will hopefully lead to earlier diagnosis and treatment. Methods We selected videos from the database at the Parkinson’s Disease Center and Movement Disorders Clinic at Baylor College of Medicine that illustrate classic findings supporting the diagnosis of psychogenic tremor. Results We include 10 clinical vignettes with accompanying videos that highlight characteristic clinical signs of psychogenic tremor including distractibility, variability, entrainability, suggestibility, and coherence. Discussion Psychogenic tremor should be considered in the differential diagnosis of patients presenting with tremor, particularly if it is of abrupt onset, intermittent, variable and not congruous with organic tremor. The diagnosis of psychogenic tremor, however, should not be simply based on exclusion of organic tremor, such as essential, parkinsonian, or cerebellar tremor, but on positive criteria demonstrating characteristic features. Early recognition and management are critical for good long-term outcome. PMID:25243097

Outpatient rehabilitation care process factors and clinical outcomes among patients discharged home following unilateral total knee arthroplasty.

PubMed

Brennan, Gerard P; Fritz, Julie M; Houck, L T C Kevin M; Hunter, Stephen J

2015-05-01

Research examining care process variables and their relationship to clinical outcomes after total knee arthroplasty has focused primarily on inpatient variables. Care process factors related to outpatient rehabilitation have not been adequately examined. We conducted a retrospective review of 321 patients evaluating outpatient care process variables including use of continuous passive motion, home health physical therapy, number of days from inpatient discharge to beginning outpatient physical therapy, and aspects of outpatient physical therapy (number of visits, length of stay) as possible predictors of pain and disability outcomes of outpatient physical therapy. Only the number of days between inpatient discharge and outpatient physical therapy predicted better outcomes, suggesting that this may be a target for improving outcomes after total knee arthroplasty for patients discharged directly home. Copyright © 2014 Elsevier Inc. All rights reserved.

A Bayesian prediction model between a biomarker and the clinical endpoint for dichotomous variables.

PubMed

Jiang, Zhiwei; Song, Yang; Shou, Qiong; Xia, Jielai; Wang, William

2014-12-20

Early biomarkers are helpful for predicting clinical endpoints and for evaluating efficacy in clinical trials even if the biomarker cannot replace clinical outcome as a surrogate. The building and evaluation of an association model between biomarkers and clinical outcomes are two equally important concerns regarding the prediction of clinical outcome. This paper is to address both issues in a Bayesian framework. A Bayesian meta-analytic approach is proposed to build a prediction model between the biomarker and clinical endpoint for dichotomous variables. Compared with other Bayesian methods, the proposed model only requires trial-level summary data of historical trials in model building. By using extensive simulations, we evaluate the link function and the application condition of the proposed Bayesian model under scenario (i) equal positive predictive value (PPV) and negative predictive value (NPV) and (ii) higher NPV and lower PPV. In the simulations, the patient-level data is generated to evaluate the meta-analytic model. PPV and NPV are employed to describe the patient-level relationship between the biomarker and the clinical outcome. The minimum number of historical trials to be included in building the model is also considered. It is seen from the simulations that the logit link function performs better than the odds and cloglog functions under both scenarios. PPV/NPV ≥0.5 for equal PPV and NPV, and PPV + NPV ≥1 for higher NPV and lower PPV are proposed in order to predict clinical outcome accurately and precisely when the proposed model is considered. Twenty historical trials are required to be included in model building when PPV and NPV are equal. For unequal PPV and NPV, the minimum number of historical trials for model building is proposed to be five. A hypothetical example shows an application of the proposed model in global drug development. The proposed Bayesian model is able to predict well the clinical endpoint from the observed biomarker data for dichotomous variables as long as the conditions are satisfied. It could be applied in drug development. But the practical problems in applications have to be studied in further research.

Compass: a hybrid method for clinical and biobank data mining.

PubMed

Krysiak-Baltyn, K; Nordahl Petersen, T; Audouze, K; Jørgensen, Niels; Angquist, L; Brunak, S

2014-02-01

We describe a new method for identification of confident associations within large clinical data sets. The method is a hybrid of two existing methods; Self-Organizing Maps and Association Mining. We utilize Self-Organizing Maps as the initial step to reduce the search space, and then apply Association Mining in order to find association rules. We demonstrate that this procedure has a number of advantages compared to traditional Association Mining; it allows for handling numerical variables without a priori binning and is able to generate variable groups which act as "hotspots" for statistically significant associations. We showcase the method on infertility-related data from Danish military conscripts. The clinical data we analyzed contained both categorical type questionnaire data and continuous variables generated from biological measurements, including missing values. From this data set, we successfully generated a number of interesting association rules, which relate an observation with a specific consequence and the p-value for that finding. Additionally, we demonstrate that the method can be used on non-clinical data containing chemical-disease associations in order to find associations between different phenotypes, such as prostate cancer and breast cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Recent developments in clopidogrel pharmacology and their relation to clinical outcomes.

PubMed

Gurbel, Paul A; Antonino, Mark J; Tantry, Udaya S

2009-08-01

Oral antiplatelet therapy with clopidogrel and aspirin is an important and widely prescribed strategy to prevent ischemic events in patients with cardiovascular diseases. However, the occurrence of thrombotic events including stent thrombosis is still high (> 10%). Current practice guidelines are mainly based on large-scale trials focusing on clinical endpoints and 'one size fits all' strategies of treating all patients with the same clopidogrel doses. Pharmacodynamic studies have demonstrated that the latter strategy is associated with wide response variability where a substantial percentage of patients show nonresponsivenes. Translational research studies have established the relation between clopidogrel nonresponsivenes or high on-treatment platelet reactivity to adverse clinical events, thereby establishing clopidogrel nonresponsivenes as an important emerging clinical entity. Clopidogrel response variability is primarily a pharmacokinetic phenomenon associated with insufficient active metabolite generation that is secondary to i) limited intestinal absorption affected by an ABCB1 gene polymorphism; ii) functional variability in P450 isoenzyme activity; and iii) a genetic polymorphism of CYP450 isoenzymes. Personalized antiplatelet treatment with higher clopidogrel doses in selected patients or with newer more potent P2Y(12) receptor blockers based on individual platelet function measurement can overcome some of the limitations of current clopidogrel treatment.

Links between behavioral factors and inflammation

PubMed Central

O’Connor, Mary-Frances; Irwin, Michael R.

2010-01-01

This review focuses on those biobehavioral factors that show robust associations with markers of inflammation, including discussion of the following variables: diet, smoking, coffee, alcohol, exercise and sleep disruption. Each of these variables has been assessed in large-scale epidemiological studies, and many in clinical and experimental studies as well. Treatment strategies that target biobehavioral factors have the potential to complement and add to the benefit of anti-inflammatory medicines. PMID:20130566

Individual and contextual determinants of malocclusion in 12-year-old schoolchildren in a Brazilian city.

PubMed

Jordão, Lidia Moraes Ribeiro; Vasconcelos, Daniela Nobre; Moreira, Rafael da Silveira; Freire, Maria do Carmo Matias

2015-01-01

The aim of this study was to describe malocclusion prevalence and its association with individual and contextual factors among Brazilian 12-year-old schoolchildren. This cross-sectional study included data from an oral health survey carried out in Goiânia, Brazil (n = 2,075), and data from the files of the local health authority. The data were collected through oral clinical examinations. The Dental Aesthetic Index (DAI) was used to assess occlusion. The presence of malocclusion (DAI > 25) was used as the dependent variable. The individual independent variables consisted of adolescents' sex and race and their mothers' level of schooling. The clinical variables were caries experience and presence of adverse periodontal condition (calculus and/or gingival bleeding). The contextual variables included type of school and the location of schools in the city's health districts. The Rao-Scott test and multilevel logistic regression were performed. The prevalence of malocclusion was 40.1%. In the final model, significantly higher rates of malocclusion were found among those who attended schools located in less affluent health districts and whose mothers had fewer years of education. Rates were also higher among those presenting calculus and/or gingival bleeding. Malocclusion demonstrated a high prevalence rate and the inequalities in its distribution were determined by individual and contextual factors.

Introduction to the special section on mixture modeling in personality assessment.

PubMed

Wright, Aidan G C; Hallquist, Michael N

2014-01-01

Latent variable models offer a conceptual and statistical framework for evaluating the underlying structure of psychological constructs, including personality and psychopathology. Complex structures that combine or compare categorical and dimensional latent variables can be accommodated using mixture modeling approaches, which provide a powerful framework for testing nuanced theories about psychological structure. This special series includes introductory primers on cross-sectional and longitudinal mixture modeling, in addition to empirical examples applying these techniques to real-world data collected in clinical settings. This group of articles is designed to introduce personality assessment scientists and practitioners to a general latent variable framework that we hope will stimulate new research and application of mixture models to the assessment of personality and its pathology.

Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

PubMed

Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

2017-10-01

Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 2—External Validity and Correlates

PubMed Central

Reddy, L. Felice; Barch, Deanna M.; Buchanan, Robert W.; Dunayevich, Eduardo; Gold, James M.; Marder, Steven R.; Wynn, Jonathan K.; Young, Jared W.; Green, Michael F.

2015-01-01

Effort-based decision making has strong conceptual links to the motivational disturbances that define a key subdomain of negative symptoms. However, the extent to which effort-based decision-making performance relates to negative symptoms, and other clinical and functionally important variables has yet to be systematically investigated. In 94 clinically stable outpatients with schizophrenia, we examined the external validity of 5 effort-based paradigms, including the Effort Expenditure for Rewards, Balloon Effort, Grip Strength Effort, Deck Choice Effort, and Perceptual Effort tasks. These tasks covered 3 types of effort: physical, cognitive, and perceptual. Correlations between effort related performance and 6 classes of variables were examined, including: (1) negative symptoms, (2) clinically rated motivation and community role functioning, (3) self-reported motivational traits, (4) neurocognition, (5) other psychiatric symptoms and clinical/demographic characteristics, and (6) subjective valuation of monetary rewards. Effort paradigms showed small to medium relationships to clinical ratings of negative symptoms, motivation, and functioning, with the pattern more consistent for some measures than others. They also showed small to medium relations with neurocognitive functioning, but were generally unrelated to other psychiatric symptoms, self-reported traits, antipsychotic medications, side effects, and subjective valuation of money. There were relatively strong interrelationships among the effort measures. In conjunction with findings from a companion psychometric article, all the paradigms warrant further consideration and development, and 2 show the strongest potential for clinical trial use at this juncture. PMID:26209546

Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis.

PubMed

Moore, Wendy C; Hastie, Annette T; Li, Xingnan; Li, Huashi; Busse, William W; Jarjour, Nizar N; Wenzel, Sally E; Peters, Stephen P; Meyers, Deborah A; Bleecker, Eugene R

2014-06-01

Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (≥2%) and neutrophil (≥40%) percentages had characteristics of very severe asthma. To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis. Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment. This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation. Published by Mosby, Inc.

Sputum neutrophils are associated with more severe asthma phenotypes using cluster analysis

PubMed Central

Moore, Wendy C.; Hastie, Annette T.; Li, Xingnan; Li, Huashi; Busse, William W.; Jarjour, Nizar N.; Wenzel, Sally E.; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.

2013-01-01

Background Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified five asthma subphenotypes that represent the severity spectrum of early onset allergic asthma, late onset severe asthma and severe asthma with COPD characteristics. Analysis of induced sputum from a subset of SARP subjects showed four sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophils (≥2%) and neutrophils (≥40%) had characteristics of very severe asthma. Objective To better understand interactions between inflammation and clinical subphenotypes we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Methods Participants in SARP at three clinical sites who underwent sputum induction were included in this analysis (n=423). Fifteen variables including clinical characteristics and blood and sputum inflammatory cell assessments were selected by factor analysis for unsupervised cluster analysis. Results Four phenotypic clusters were identified. Cluster A (n=132) and B (n=127) subjects had mild-moderate early onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of Cluster C (n=117) and D (n=47) subjects who had moderate-severe asthma with frequent health care utilization despite treatment with high doses of inhaled or oral corticosteroids, and in Cluster D, reduced lung function. The majority these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophils were the most important variables determining cluster assignment. Conclusion This multivariate approach identified four asthma subphenotypes representing the severity spectrum from mild-moderate allergic asthma with minimal or eosinophilic predominant sputum inflammation to moderate-severe asthma with neutrophilic predominant or mixed granulocytic inflammation. PMID:24332216

Solid Lymph Nodes as an Imaging Biomarker for Risk Stratification in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma.

PubMed

Rath, T J; Narayanan, S; Hughes, M A; Ferris, R L; Chiosea, S I; Branstetter, B F

2017-07-01

Human papillomavirus-related oropharyngeal squamous cell carcinoma is associated with cystic lymph nodes on CT and has a favorable prognosis. A subset of patients with aggressive disease experience treatment failure. Our aim was to determine whether the extent of cystic lymph node burden on staging CT can serve as an imaging biomarker to predict treatment failure in human papillomavirus-related oropharyngeal squamous cell carcinoma. We identified patients with human papilloma virus-related oropharyngeal squamous cell carcinoma and staging neck CTs. Demographic and clinical variables were recorded. We retrospectively classified the metastatic lymph node burden on CT as cystic or solid and assessed radiologic extracapsular spread. Biopsy, subsequent imaging, or clinical follow-up was the reference standard for treatment failure. The primary end point was disease-free survival. Cox proportional hazard regression analyses of clinical, demographic, and anatomic variables for treatment failure were performed. One hundred eighty-three patients were included with a mean follow-up of 38 months. In univariate analysis, the following variables had a statistically significant association with treatment failure: solid-versus-cystic lymph nodes, clinical T-stage, clinical N-stage, and radiologic evidence of extracapsular spread. The multivariate Cox proportional hazard model resulted in a model that included solid-versus-cystic lymph nodes, T-stage, and radiologic evidence of extracapsular spread as independent predictors of treatment failure. Patients with cystic nodal metastasis at staging had significantly better disease-free survival than patients with solid lymph nodes. In human papilloma virus-related oropharyngeal squamous cell carcinoma, patients with solid lymph node metastases are at higher risk for treatment failure with worse disease-free survival. Solid lymph nodes may serve as an imaging biomarker to tailor individual treatment regimens. © 2017 by American Journal of Neuroradiology.

Phosphoglucomutase-1 deficiency: Intrafamilial clinical variability and common secondary adrenal insufficiency.

PubMed

Loewenthal, Neta; Haim, Alon; Parvari, Ruti; Hershkovitz, Eli

2015-12-01

Phosphoglucomutase 1 (PGM1, EC 5.4.2.2) plays a critical role in glucose homeostasis and is also essential for protein N-glycosylation. The main clinical manifestations of PGM1 deficiency (MIM 614921) reported in 19 patients from different ethnic backgrounds include the following: cleft uvula/palate, Pierre Robin sequence, muscle weakness, dilated cardiomyopathy, growth retardation, elevated serum transaminases, hypoglycemia, and various endocrine abnormalities. We report the variable clinical picture of seven patients with PGM1 deficiency from a consanguineous family. Medical records of the patients were reviewed for clinical details and endocrine evaluation. Whole exome sequencing (WES) was performed. Seven patients aged 2-29 years were included, one patient died at 13 years old when getting off the school bus. All patients have an abnormal palatine structure (cleft palate, bifid uvula) and elevated serum transaminases, 4/7 have short stature (<-2 SDS) and one was diagnosed with growth hormone deficiency. Recurrent episodes of ketotic hypoglycemia were present in 6/7 patients. In two patients, hypoglycemic episodes have spontaneously resolved later on. Four out of seven patients have deteriorating adrenal function with abnormally low cortisol and ACTH levels during hypoglycemia and subnormal response of cortisol to low dose ACTH test . Serum electrolytes were within normal range. Hydrocortisone replacement therapy improved, but not entirely eliminated hypoglycemic episodes. WES revealed a previously described homozygous mutation c.112A>T, p.Asn38Tyr in the PGM1 gene. The clinical picture of PGM1 deficiency is variable among patients with the same mutation and genetic background. ACTH deficiency should be considered in any PGM1 deficient patient with hypoglycemia. © 2015 Wiley Periodicals, Inc.

A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score

PubMed Central

Hijazi, Ziad; Oldgren, Jonas; Lindbäck, Johan; Alexander, John H; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Held, Claes; Hylek, Elaine M; Lopes, Renato D; Yusuf, Salim; Granger, Christopher B; Siegbahn, Agneta; Wallentin, Lars

2018-01-01

Abstract Aims In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers. Methods and results The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score. Conclusion A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF. ClinicalTrials.gov identifier NCT00412984 and NCT00262600 PMID:29069359

Clinical applications of the functional connectome

PubMed Central

Castellanos, F. Xavier; Di Martino, Adriana; Craddock, R. Cameron; Mehta, Ashesh D.; Milham, Michael P.

2013-01-01

Central to the development of clinical applications of functional connectomics for neurology and psychiatry is the discovery and validation of biomarkers. Resting state fMRI (R-fMRI) is emerging as a mainstream approach for imaging-based biomarker identification, detecting variations in the functional connectome that can be attributed to clinical variables (e.g., diagnostic status). Despite growing enthusiasm, many challenges remain. Here, we assess evidence of the readiness of R-fMRI based functional connectomics to lead to clinically meaningful biomarker identification through the lens of the criteria used to evaluate clinical tests (i.e., validity, reliability, sensitivity, specificity, and applicability). We focus on current R-fMRI-based prediction efforts, and survey R-fMRI used for neurosurgical planning. We identify gaps and needs for R-fMRI-based biomarker identification, highlighting the potential of emerging conceptual, analytical and cultural innovations (e.g., the Research Domain Criteria Project (RDoC), open science initiatives, and Big Data) to address them. Additionally, we note the need to expand future efforts beyond identification of biomarkers for disease status alone to include clinical variables related to risk, expected treatment response and prognosis. PMID:23631991

Link between immunoexpression of hMLH1 and hMSH2 proteins and clinical-epidemiological aspects of actinic cheilitis*

PubMed Central

Sarmento, Dmitry José de Santana; Godoy, Gustavo Pina; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas

2016-01-01

Background The studies found in the literature associate the immunoexpression of hMLH1 and hMSH2 proteins with histologic aspects, but do not correlate it with clinical and epidemiological data. Objective To evaluate the immunoexpression of hMLH1 and hMSH2 in actinic cheilitis, correlating it with clinical characteristics. Methods We analyzed 40 cases. Histological and immunohistochemical analyses were performed. The following clinical variables were evaluated: gender, age range, ethnicity, clinical aspect and occupational sunlight exposure. Statistical evaluation included the Student t-test, while the significance level was set at 5%. Results Greater immunoexpression of hMLH1 and hMSH2 was observed in females, individuals aged over 40, and mixed-race/black patients. Furthermore, the immunoexpression of these proteins was greater in actinic cheilitis with a white-colored appearance and in patients without occupational sunlight exposure. No statistical differences were observed for the variables studied. Conclusion This study uncovered variations of hMLH1 and hMSH2 protein expression upon evaluation of clinical aspects in actinic cheilitis. PMID:27579741

Link between immunoexpression of hMLH1 and hMSH2 proteins and clinical-epidemiological aspects of actinic cheilitis.

PubMed

Sarmento, Dmitry José de Santana; Godoy, Gustavo Pina; Miguel, Márcia Cristina da Costa; Silveira, Éricka Janine Dantas da

2016-01-01

The studies found in the literature associate the immunoexpression of hMLH1 and hMSH2 proteins with histologic aspects, but do not correlate it with clinical and epidemiological data. To evaluate the immunoexpression of hMLH1 and hMSH2 in actinic cheilitis, correlating it with clinical characteristics. We analyzed 40 cases. Histological and immunohistochemical analyses were performed. The following clinical variables were evaluated: gender, age range, ethnicity, clinical aspect and occupational sunlight exposure. Statistical evaluation included the Student t-test, while the significance level was set at 5%. Greater immunoexpression of hMLH1 and hMSH2 was observed in females, individuals aged over 40, and mixed-race/black patients. Furthermore, the immunoexpression of these proteins was greater in actinic cheilitis with a white-colored appearance and in patients without occupational sunlight exposure. No statistical differences were observed for the variables studied. This study uncovered variations of hMLH1 and hMSH2 protein expression upon evaluation of clinical aspects in actinic cheilitis.

Cardiorespiratory interaction with continuous positive airway pressure

PubMed Central

Bonafini, Sara; Fava, Cristiano; Steier, Joerg

2018-01-01

The treatment of choice for obstructive sleep apnoea (OSA) is continuous positive airway pressure therapy (CPAP). Since its introduction in clinical practice, CPAP has been used in various clinical conditions with variable and heterogeneous outcomes. In addition to the well-known effects on the upper airway CPAP impacts on intrathoracic pressures, haemodynamics and blood pressure (BP) control. However, short- and long-term effects of CPAP therapy depend on multiple variables which include symptoms, underlying condition, pressure used, treatment acceptance, compliance and usage. CPAP can alter long-term cardiovascular risk in patients with cardiorespiratory conditions. Furthermore, the effect of CPAP on the awake patient differs from the effect on the patients while asleep, and this might contribute to discomfort and removal of the use interface. The purpose of this review is to highlight the physiological impact of CPAP on the cardiorespiratory system, including short-term benefits and long-term outcomes. PMID:29445529

Advanced Techniques in Pulmonary Function Test Analysis Interpretation and Diagnosis

PubMed Central

Gildea, T.J.; Bell, C. William

1980-01-01

The Pulmonary Functions Analysis and Diagnostic System is an advanced clinical processing system developed for use at the Pulmonary Division, Department of Medicine at the University of Nebraska Medical Center. The system generates comparative results and diagnostic impressions for a variety of routine and specialized pulmonary functions test data. Routine evaluation deals with static lung volumes, breathing mechanics, diffusing capacity, and blood gases while specialized tests include lung compliance studies, small airways dysfunction studies and dead space to tidal volume ratios. Output includes tabular results of normal vs. observed values, clinical impressions and commentary and, where indicated, a diagnostic impression. A number of pulmonary physiological and state variables are entered or sampled (A to D) with periodic status reports generated for the test supervisor. Among the various physiological variables sampled are respiratory frequency, minute ventilation, oxygen consumption, carbon dioxide production, and arterial oxygen saturation.

Cost and logistics for implementing the American College of Surgeons objective structured clinical examination.

PubMed

Sudan, Ranjan; Clark, Philip; Henry, Brandon

2015-01-01

The American College of Surgeons has developed a reliable and valid OSCE (objective structured clinical examination) to assess the clinical skills of incoming postgraduate year 1 surgery residents, but the cost and logistics of implementation have not been described. Fixed costs included staff time, medical supplies, facility fee, standardized patient (SP) training time, and one OSCE session. Variable costs were incurred for additional OSCE sessions. Costs per resident were calculated and modeled for increasing the number of test takers. American College of Surgeons OSCE materials and examination facilities were free. Fixed costs included training 11 SPs for 4 hours ($1,540), moulage and simulation material ($469), and administrative effort for 44 hours ($2,200). Variable cost for each session was $1,540 (SP time). Total cost for the first session was $6,649 ($664/resident), decreased to $324/resident for 3 sessions, and projected to further decline to $239/resident for 6 sessions. The cost decreased as the number of residents tested increased. To manage costs, testing more trainees by regional collaboration is recommended. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons.

PubMed

Jayaraman, Anusha; Pike, Christian J

2014-03-25

Progesterone and other progestagens are used in combination with estrogens for clinical purposes, including contraception and postmenopausal hormone therapy. Progesterone and estrogens have interactive effects in brain, however interactions between synthetic progestagens and 17β-estradiol (E2) in neurons are not well understood. In this study, we investigated the effects of seven clinically relevant progestagens on estrogen receptor (ER) mRNA expression, E2-induced neuroprotection, and E2-induced BDNF mRNA expression. We found that medroxyprogesterone acetate decreased both ERα and ERβ expression and blocked E2-mediated neuroprotection and BDNF expression. Conversely, levonorgestrel and nesterone increased ERα and or ERβ expression, were neuroprotective, and failed to attenuate E2-mediated increases in neuron survival and BDNF expression. Other progestagens tested, including norethindrone, norethindrone acetate, norethynodrel, and norgestimate, had variable effects on the measured endpoints. Our results demonstrate a range of qualitatively different actions of progestagens in cultured neurons, suggesting significant variability in the neural effects of clinically utilized progestagens. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Health Related Quality of Life in Children with Autism Spectrum Disorders: The Clinical and Demographic Related Factors in Turkey

ERIC Educational Resources Information Center

Kose, Sezen; Erermis, Serpil; Ozturk, Onder; Ozbaran, Burcu; Demiral, Nagehan; Bildik, Tezan; Aydin, Cahide

2013-01-01

We aimed to investigate the Health Related Quality of Life and related clinical variables (HRQoL) of children with Autism Spectrum Disorders (ASD). We included 102 children with ASD (46 with autism, 38 with pervasive developmental disorder not otherwise specified (PDD-NOS) and 18 with Asperger's syndrome (AS)) and 39 typically developing children…

13A. Integrative Cancer Care: The Life Over Cancer Model

PubMed Central

Block, Keith; Block, Penny; Shoham, Jacob

2013-01-01

Focus Areas: Integrative Algorithms of Care Integrative cancer treatment fully blends conventional cancer treatment with integrative therapies such as diet, supplements, exercise and biobehavioral approaches. The Life Over Cancer model comprises three spheres of intervention: improving lifestyle, improving biochemical environment (terrain), and improving tolerance of conventional treatment. These levels are applied within the context of a life-affirming approach to cancer patients and treatment. Clinical staff involved include MDs, psychosocial, physical therapy, and dietetic professionals, all located in a single private clinic, the Block Center for Integrative Cancer Treatment. This session will describe the rationale and operation of the clinical model. An outpatient chemotherapy unit is incorporated in the clinic. Chronomodulated chemotherapy is used for selected chemotherapy drugs. Physical care includes massage, exercise and other therapies as directed by the center's physical therapy staff. Notably, cancer patients who are physically active have lower mortality and recurrence risks. Behavioral approaches are being shown increasingly to affect physiological parameters and expression of genes potentially related to cancer. Thus, biobehavioral approaches such as relaxed abdominal breathing and comfort space imagery are taught to patients by a staff including a clinical psychologist and other practitioners. Nutrition is also emerging as a relevant area of intervention in cancer, with recent guidelines from the American Cancer Society. A team of registered dietitians counsels patients individually and conducts cooking classes. Finally, the Life Over Cancer model includes analysis of multiple biological parameters relevant to cancer and general health, with standard laboratory tests. Inflammation, glycemic variables, immune functioning and other variables are regularly monitored. Dietary changes and where necessary supplements are suggested when laboratory results are abnormal. Interaction of supplements with cancer treatment drugs is monitored. The session will highlight the roles played by both conventional and integrative therapies in the treatment of cancer patients.

Clinical and molecular characterization of duplications encompassing the human SHOX gene reveal a variable effect on stature.

PubMed

Thomas, N Simon; Harvey, John F; Bunyan, David J; Rankin, Julia; Grigelioniene, Giedre; Bruno, Damien L; Tan, Tiong Y; Tomkins, Susan; Hastings, Robert

2009-07-01

Deletions of the SHOX gene are well documented and cause disproportionate short stature and variable skeletal abnormalities. In contrast interstitial SHOX duplications limited to PAR1 appear to be very rare and the clinical significance of the only case report in the literature is unclear. Mapping of this duplication has now shown that it includes the entire SHOX gene but little flanking sequence and so will not encompass any of the long-range enhancers required for SHOX transcription. We now describe the clinical and molecular characterization of three additional cases. The duplications all included the SHOX coding sequence but varied in the amount of flanking sequence involved. The probands were ascertained for a variety of reasons: hypotonia and features of Asperger syndrome, Leri-Weill dyschondrosteosis (LWD), and a family history of cleft palate. However, the presence of a duplication did not correlate with any of these features or with evidence of skeletal abnormality. Remarkably, the proband with LWD had inherited both a SHOX deletion and a duplication. The effect of the duplications on stature was variable: height appeared to be elevated in some carriers, particularly in those with the largest duplications, but was still within the normal range. SHOX duplications are likely to be under ascertained and more cases need to be identified and characterized in detail in order to accurately determine their phenotypic consequences.

How to design and write a clinical research protocol in Cosmetic Dermatology*

PubMed Central

Bagatin, Ediléia; Miot, Helio A.

2013-01-01

Cosmetic Dermatology is a growing subspecialty. High-quality basic science studies have been published; however, few double-blind, randomized controlled clinical trials, which are the major instrument for evidence-based medicine, have been conducted in this area. Clinical research is essential for the discovery of new knowledge, improvement of scientific basis, resolution of challenges, and good clinical practice. Some basic principles for a successful researcher include interest, availability, persistence, and honesty. It is essential to learn how to write a protocol research and to know the international and national regulatory rules. A complete clinical trial protocol should include question, background, objectives, methodology (design, variable description, sample size, randomization, inclusion and exclusion criteria, intervention, efficacy and safety measures, and statistical analysis), consent form, clinical research form, and references. Institutional ethical review board approval and financial support disclosure are necessary. Publication of positive or negative results should be an authors' commitment. PMID:23539006

Clinical and epidemiological correlates of the neurohistology of cases of histologically unconfirmed, clinically suspect bovine spongiform encephalopathy.

PubMed

Wells, G A; Sayers, A R; Wilesmith, J W

1995-03-04

The associations between three major categories of the neurohistological diagnoses and the epidemiological data were examined in unconfirmed cases of clinically suspect bovine spongiform encephalopathy (BSE). The diagnostic categories were focal spongiosis of white matter (37 cases), encephalic listeriosis (13 cases) and no significant lesions (78 cases). An additional control category of 200 confirmed cases of BSE were included for comparison. Epidemiological variables were the frequencies of specific clinical signs, the season of clinical onset, the age, the duration of the clinical signs and the geographical origin of the cases. Discriminant analysis was used to assess the contribution of these variables to the distinction between the diagnostic categories. The analyses characterised the cases of listeriosis by their shortest clinical duration, the greater prevalences of certain clinical signs and their occurrence mainly in winter and spring, consistent with current understanding of the disease. Cases of focal spongiosis, a lesion of unknown significance, but potentially with a metabolic causation, were tentatively separable from cases with no significant lesions by their winter onset. The results also confirmed that among the categories, the cases of BSE had the longest clinical duration. Despite their statistical significance, the findings do not have sufficient predictive power to be of value in making clinical decisions.

Use of Wearable Sensors and Biometric Variables in an Artificial Pancreas System

PubMed Central

Turksoy, Kamuran; Monforti, Colleen; Park, Minsun; Griffith, Garett; Quinn, Laurie; Cinar, Ali

2017-01-01

An artificial pancreas (AP) computes the optimal insulin dose to be infused through an insulin pump in people with Type 1 Diabetes (T1D) based on information received from a continuous glucose monitoring (CGM) sensor. It has been recognized that exercise is a major challenge in the development of an AP system. The use of biometric physiological variables in an AP system may be beneficial for prevention of exercise-induced challenges and better glucose regulation. The goal of the present study is to find a correlation between biometric variables such as heart rate (HR), heat flux (HF), skin temperature (ST), near-body temperature (NBT), galvanic skin response (GSR), and energy expenditure (EE), 2D acceleration-mean of absolute difference (MAD) and changes in glucose concentrations during exercise via partial least squares (PLS) regression and variable importance in projection (VIP) in order to determine which variables would be most useful to include in a future artificial pancreas. PLS and VIP analyses were performed on data sets that included seven different types of exercises. Data were collected from 26 clinical experiments. Clinical results indicate ST to be the most consistently important (important for six out of seven tested exercises) variable over all different exercises tested. EE and HR are also found to be important variables over several types of exercise. We also found that the importance of GSR and NBT observed in our experiments might be related to stress and the effect of changes in environmental temperature on glucose concentrations. The use of the biometric measurements in an AP system may provide better control of glucose concentration. PMID:28272368

Intraindividual Cognitive Variability in Middle Age Predicts Cognitive Impairment 8-10 Years Later: Results from the Wisconsin Registry for Alzheimer's Prevention.

PubMed

Koscik, Rebecca L; Berman, Sara E; Clark, Lindsay R; Mueller, Kimberly D; Okonkwo, Ozioma C; Gleason, Carey E; Hermann, Bruce P; Sager, Mark A; Johnson, Sterling C

2016-11-01

Intraindividual cognitive variability (IICV) has been shown to differentiate between groups with normal cognition, mild cognitive impairment (MCI), and dementia. This study examined whether baseline IICV predicted subsequent mild to moderate cognitive impairment in a cognitively normal baseline sample. Participants with 4 waves of cognitive assessment were drawn from the Wisconsin Registry for Alzheimer's Prevention (WRAP; n=684; 53.6(6.6) baseline age; 9.1(1.0) years follow-up; 70% female; 74.6% parental history of Alzheimer's disease). The primary outcome was Wave 4 cognitive status ("cognitively normal" vs. "impaired") determined by consensus conference; "impaired" included early MCI (n=109), clinical MCI (n=11), or dementia (n=1). Primary predictors included two IICV variables, each based on the standard deviation of a set of scores: "6 Factor IICV" and "4 Test IICV". Each IICV variable was tested in a series of logistic regression models to determine whether IICV predicted cognitive status. In exploratory analyses, distribution-based cutoffs incorporating memory, executive function, and IICV patterns were used to create and test an MCI risk variable. Results were similar for the IICV variables: higher IICV was associated with greater risk of subsequent impairment after covariate adjustment. After adjusting for memory and executive functioning scores contributing to IICV, IICV was not significant. The MCI risk variable also predicted risk of impairment. While IICV in middle-age predicts subsequent impairment, it is a weaker risk indicator than the memory and executive function scores contributing to its calculation. Exploratory analyses suggest potential to incorporate IICV patterns into risk assessment in clinical settings. (JINS, 2016, 22, 1016-1025).

Ruling out Legionella in community-acquired pneumonia.

PubMed

Haubitz, Sebastian; Hitz, Fabienne; Graedel, Lena; Batschwaroff, Marcus; Wiemken, Timothy Lee; Peyrani, Paula; Ramirez, Julio A; Fux, Christoph Andreas; Mueller, Beat; Schuetz, Philipp

2014-10-01

Assessing the likelihood for Legionella sp. in community-acquired pneumonia is important because of differences in treatment regimens. Currently used antigen tests and culture have limited sensitivity with important time delays, making empirical broad-spectrum coverage necessary. Therefore, a score with 6 variables recently has been proposed. We sought to validate these parameters in an independent cohort. We analyzed adult patients with community-acquired pneumonia from a large multinational database (Community Acquired Pneumonia Organization) who were treated between 2001 and 2012 with more than 4 of the 6 prespecified clinical variables available. Association and discrimination were assessed using logistic regression analysis and area under the curve (AUC). Of 1939 included patients, the infectious cause was known in 594 (28.9%), including Streptococcus pneumoniae in 264 (13.6%) and Legionella sp. in 37 (1.9%). The proposed clinical predictors fever, cough, hyponatremia, lactate dehydrogenase, C-reactive protein, and platelet count were all associated or tended to be associated with Legionella cause. A logistic regression analysis including all these predictors showed excellent discrimination with an AUC of 0.91 (95% confidence interval, 0.87-0.94). The original dichotomized score showed good discrimination (AUC, 0.73; 95% confidence interval, 0.65-0.81) and a high negative predictive value of 99% for patients with less than 2 parameters present. With the use of a large independent patient sample from an international database, this analysis validates previously proposed clinical variables to accurately rule out Legionella sp., which may help to optimize initial empiric therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognitive functioning and insight in schizophrenia and in schizoaffective disorder.

PubMed

Birindelli, Nadia; Montemagni, Cristiana; Crivelli, Barbara; Bava, Irene; Mancini, Irene; Rocca, Paola

2014-01-01

The aim of this study was to investigate cognitive functioning and insight of illness in two groups of patients during their stable phases, one with schizophrenia and one with schizoaffective disorder. We recruited 104 consecutive outpatients, 64 with schizophrenia, 40 with schizoaffective disorder, in the period between July 2010 and July 2011. They all fulfilled formal Diagnostic and Statistical Manual of Mental disorders (DSM-IV-TR) diagnostic criteria for schizophrenia and schizoaffective disorder. Psychiatric assessment included the Clinical Global Impression Scale-Severity (CGI-S), the Positive and Negative Sindrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Global Assessment of Functioning (GAF). Insight of illness was evaluated using SUMD. Neuropsychological assessment included Winsconsin Card Sorting Test (WCST), California Verbal Learning Test (CVLT), Stroop Test and Trail Making Test (TMT). Differences between the groups were tested using Chi-square test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. All variables significantly different between the two groups of subjects were subsequently analysed using a logistic regression with a backward stepwise procedure using diagnosis (schizophrenia/schizoaffective disorder) as dependent variable. After backward selection of variables, four variables predicted a schizoaffective disorder diagnosis: marital status, a higher number of admission, better attentive functions and awareness of specific signs or symptoms of disease. The prediction model accounted for 55% of the variance of schizoaffective disorder diagnosis. With replication, our findings would allow higher diagnostic accuracy and have an impact on clinical decision making, in light of an amelioration of vocational functioning.

Resource utilization in home health care: results of a prospective study.

PubMed

Trisolini, M G; Thomas, C P; Cashman, S B; Payne, S M

1994-01-01

Resource utilization in home health care has become an issue of concern due to rising costs and recent initiatives to develop prospective payment systems for home health care. A number of issues remain unresolved for the development of prospective reimbursement in this sector, including the types of variables to be included as payment variables and appropriate measures of resource use. This study supplements previous work on home health case-mix by analyzing the factors affecting one aspect of resource use for skilled nursing visits--visit length--and explores the usefulness of several specially collected variables which are not routinely available in administrative records. A data collection instrument was developed with a focus group of skilled nurses, identifying a range of variables hypothesized to affect visit length. Five categories of variables were studied using multiple regression analysis: provider-related; patient's socio-economic status; patient's clinical status; patient's support services; and visit-specific. The final regression model identifies 9 variables which significantly affect visit time. Five of the 9 are visit-specific variables, a significant finding since these are not routinely collected. Case-mix systems which include visit time as a measure of resource use will need to investigate visit-specific variables, as this study indicates they could have the largest influence on visit time. Two other types of resources used in home health care, supplies and security drivers, were also investigated in less detail.

Associations of medical student personality and health/wellness characteristics with their medical school performance across the curriculum.

PubMed

Haight, Scott J; Chibnall, John T; Schindler, Debra L; Slavin, Stuart J

2012-04-01

To assess the relationships of cognitive and noncognitive performance predictors to medical student preclinical and clinical performance indicators across medical school years 1 to 3 and to evaluate the association of psychological health/wellness factors with performance. In 2010, the authors conducted a cross-sectional, correlational, retrospective study of all 175 students at the Saint Louis University School of Medicine who had just completed their third (first clinical) year. Students were asked to complete assessments of personality, stress, anxiety, depression, social support, and community cohesion. Performance measures included total Medical College Admission Test (MCAT) score, preclinical academic grades, National Board of Medical Examiners subject exam scores, United States Medical Licensing Examination Step 1 score, clinical evaluations, and Humanism in Medicine Honor Society nominations. A total of 152 students (87%) participated. MCAT scores predicted cognitive performance indicators (academic tests), whereas personality variables (conscientiousness, extraversion, empathy) predicted noncognitive indicators (clinical evaluations, humanism nominations). Conscientiousness predicted all clinical skills, extraversion predicted clinical skills reflecting interpersonal behavior, and empathy predicted motivation. Health/wellness variables had limited associations with performance. In multivariate analyses that included control for shelf exam scores, conscientiousness predicted clinical evaluations, and extraversion and empathy predicted humanism nominations. This study identified two sets of skills (cognitive, noncognitive) used during medical school, with minimal overlap across the types of performance (e.g., exam performance versus clinical interpersonal skills) they predict. Medical school admission and evaluation efforts may need to be modified to reflect the importance of personality and other noncognitive factors.

Falsification Testing of Instrumental Variables Methods for Comparative Effectiveness Research.

PubMed

Pizer, Steven D

2016-04-01

To demonstrate how falsification tests can be used to evaluate instrumental variables methods applicable to a wide variety of comparative effectiveness research questions. Brief conceptual review of instrumental variables and falsification testing principles and techniques accompanied by an empirical application. Sample STATA code related to the empirical application is provided in the Appendix. Comparative long-term risks of sulfonylureas and thiazolidinediones for management of type 2 diabetes. Outcomes include mortality and hospitalization for an ambulatory care-sensitive condition. Prescribing pattern variations are used as instrumental variables. Falsification testing is an easily computed and powerful way to evaluate the validity of the key assumption underlying instrumental variables analysis. If falsification tests are used, instrumental variables techniques can help answer a multitude of important clinical questions. © Health Research and Educational Trust.

Social gradients in periodontal diseases among adolescents.

PubMed

López, Rodrigo; Fernández, Olaya; Baelum, Vibeke

2006-06-01

To investigate the association between socioeconomic position and periodontal diseases among adolescents. Data were obtained from 9203 Chilean high school students. Clinical examinations included direct recordings of clinical attachment level and the necrotizing ulcerative gingival lesions. Students answered a questionnaire on various dimensions of socioeconomic position. Seven periodontal outcomes were analyzed. Logistic regression analyses were used to identify socioeconomic variables associated with the periodontal outcomes. The occurrence of all periodontal outcomes investigated followed social gradients, and paternal income and parental education were the most influential variables. The study demonstrates the existence of significant social gradients in periodontal diseases already among adolescents. This is worrying, and indicates a new potential for further insight into the mechanisms of periodontal disease causation.

Use of Admission Criteria to Predict Performance of Students in an Entry-Level Master's Program on Fieldwork Placements and in Academic Courses.

PubMed

Kirchner, G L; Stone, R G; Holm, M B

2001-01-01

The relationships among clinical outcomes, academic success, and predictors used to screen applicants for entrance into a Master in Occupational Therapy Program (MOT) were examined. The dependent variables were grade point average in occupational therapy courses (OT-GPA), client therapy outcomes at the clinic, and ratings of MOT students by Level II Fieldwork supervisors. Predictor variables included undergraduate GPA, scores on the Graduate Record Examination (GRE), and an essay. Both undergraduate GPA and scores on the GRE were found to predict OT-GPA. The analytical section of the GRE was also positively correlated with fieldwork supervisors' ratings of students.

Fatigue as a Driver of Overall Quality of Life in Cancer Patients.

PubMed

McCabe, Ryan M; Grutsch, James F; Braun, Donald P; Nutakki, Swetha B

2015-01-01

This manuscript describes an approach for analyzing large amounts of disparate clinical data to elucidate the most impactful factor(s) that relate to a meaningful clinical outcome, in this case, the quality of life of cancer patients. The relationships between clinical and quality of life variables were evaluated using the EORTC QLQ-C30 global health domain--a validated surrogate variable for overall cancer patient well-being. A cross-sectional study design was used to evaluate the determinants of global health in cancer patients who initiated treatment at two regional medical centers between January 2001 and December 2009. Variables analyzed included 15 EORTC QLQ-C30 scales, age at diagnosis, gender, newly diagnosed/ recurrent disease status, and stage. The decision tree algorithm, perhaps unfamiliar to practicing clinicians, evaluates the relative contribution of individual parameters in classifying a clinically meaningful functional endpoint, such as the global health of a patient. Multiple patient characteristics were identified as important contributors. Fatigue, in particular, emerged as the most prevalent indicator of cancer patients' quality of life in 16/23 clinically relevant subsets. This analysis allowed results to be stated in a clinically-intuitive, rule set format using the language and quantities of the Quality of Life (QoL) tool itself. By applying the classification algorithms to a large data set, identification of fatigue as a root factor in driving global health and overall QoL was revealed. The ability to practice mining of clinical data sets to uncover critical clinical insights that are immediately applicable to patient care practices is illustrated.

Fatigue as a Driver of Overall Quality of Life in Cancer Patients

PubMed Central

McCabe, Ryan M.; Grutsch, James F.; Braun, Donald P.; Nutakki, Swetha B.

2015-01-01

Background This manuscript describes an approach for analyzing large amounts of disparate clinical data to elucidate the most impactful factor(s) that relate to a meaningful clinical outcome, in this case, the quality of life of cancer patients. The relationships between clinical and quality of life variables were evaluated using the EORTC QLQ-C30 global health domain—a validated surrogate variable for overall cancer patient well-being. Methods A cross-sectional study design was used to evaluate the determinants of global health in cancer patients who initiated treatment at two regional medical centers between January 2001 and December 2009. Variables analyzed included 15 EORTC QLQ-C30 scales, age at diagnosis, gender, newly diagnosed/ recurrent disease status, and stage. The decision tree algorithm, perhaps unfamiliar to practicing clinicians, evaluates the relative contribution of individual parameters in classifying a clinically meaningful functional endpoint, such as the global health of a patient. Findings Multiple patient characteristics were identified as important contributors. Fatigue, in particular, emerged as the most prevalent indicator of cancer patients’ quality of life in 16/23 clinically relevant subsets. This analysis allowed results to be stated in a clinically-intuitive, rule set format using the language and quantities of the Quality of Life (QoL) tool itself. Interpretation By applying the classification algorithms to a large data set, identification of fatigue as a root factor in driving global health and overall QoL was revealed. The ability to practice mining of clinical data sets to uncover critical clinical insights that are immediately applicable to patient care practices is illustrated. PMID:26070133

Executive function impairments in fibromyalgia syndrome: Relevance of clinical variables and body mass index.

PubMed

Muñoz Ladrón de Guevara, Cristina; Fernández-Serrano, María José; Reyes Del Paso, Gustavo A; Duschek, Stefan

2018-01-01

Several investigations suggest the presence of deterioration of executive function in fibromyalgia syndrome (FMS). The study quantified executive functions in patients with FMS. A wide array of functions was assessed, including updating, shifting and inhibition, as well as decision making and mental planning. Moreover, clinical variables were investigated as possible mediators of executive dysfunction, including pain severity, psychiatric comorbidity, medication and body mass index (BMI). Fifty-two FMS patients and 32 healthy controls completed a battery of 14 neuropsychological tests. Clinical interviews were conducted and the McGill Pain Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventory, Fatigue Severity Scale and Oviedo Quality of Sleep Questionnaire were presented. Patients performed poorer than controls on the Letter Number Sequencing, Arithmetic and Similarities subtests of the Wechsler Adult Intelligence Scale, the Spatial Span subtest of the Wechsler Memory Scale, an N-back task, a verbal fluency task, the Ruff Figural Fluency Test, the Inhibition score of the Stroop Test, the Inhibition and Shifting scores of the Five Digits Test, the Key Search Test and the Zoo Map Task. Moreover, patients exhibited less steep learning curves on the Iowa Gambling Task. Among clinical variables, BMI and pain severity explained the largest proportion of performance variance. This study demonstrated impairments in executive functions of updating, shifting inhibition, decision making and planning in FMS. While the mediating role of pain in cognitive impairments in FMS had been previously established, the influence of BMI is a novel finding. Overweight and obesity should be considered by FMS researchers, and in the treatment of the condition.

Executive function impairments in fibromyalgia syndrome: Relevance of clinical variables and body mass index

PubMed Central

2018-01-01

Background Several investigations suggest the presence of deterioration of executive function in fibromyalgia syndrome (FMS). The study quantified executive functions in patients with FMS. A wide array of functions was assessed, including updating, shifting and inhibition, as well as decision making and mental planning. Moreover, clinical variables were investigated as possible mediators of executive dysfunction, including pain severity, psychiatric comorbidity, medication and body mass index (BMI). Methods Fifty-two FMS patients and 32 healthy controls completed a battery of 14 neuropsychological tests. Clinical interviews were conducted and the McGill Pain Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventory, Fatigue Severity Scale and Oviedo Quality of Sleep Questionnaire were presented. Results Patients performed poorer than controls on the Letter Number Sequencing, Arithmetic and Similarities subtests of the Wechsler Adult Intelligence Scale, the Spatial Span subtest of the Wechsler Memory Scale, an N-back task, a verbal fluency task, the Ruff Figural Fluency Test, the Inhibition score of the Stroop Test, the Inhibition and Shifting scores of the Five Digits Test, the Key Search Test and the Zoo Map Task. Moreover, patients exhibited less steep learning curves on the Iowa Gambling Task. Among clinical variables, BMI and pain severity explained the largest proportion of performance variance. Conclusions This study demonstrated impairments in executive functions of updating, shifting inhibition, decision making and planning in FMS. While the mediating role of pain in cognitive impairments in FMS had been previously established, the influence of BMI is a novel finding. Overweight and obesity should be considered by FMS researchers, and in the treatment of the condition. PMID:29694417

Cultural Factors in Clinical Assessment.

ERIC Educational Resources Information Center

Westermeyer, Joseph

1987-01-01

Examines special issues in cross-cultural psychopathology, including culture-bound syndromes, variable distribution of psychopathology across cultures, and cultural distinctions between belief and delusion and between trance and hallucination. Offers suggestions for educating clinicians about cross-cultural conceptual issues and teaching the…

The dishonest dean's letter: an analysis of 532 dean's letters from 99 U.S. medical schools.

PubMed

Edmond, M; Roberson, M; Hasan, N

1999-09-01

To quantify the censure of potentially negative information in dean's letters. Concordance between 532 dean's letters and the corresponding transcripts was determined for six variables (failing grade in a preclinical course, marginal preclinical course grade, failing grade for a clinical rotation, marginal clinical rotation grade, leave of absence, and requirement to repeat an entire year of medical school). The evaluated variables were not found in the dean's letters 27% to 50% of the time that they were present on the transcripts. In three of nine instances (33%), a failing grade in a clinical rotation was not included. Four students had been required to repeat an entire year, but this was noted in only two cases. In toto, 35 of 104 (34%) of the variables identified on the transcripts were not reported. In addition, deans were significantly less likely to report a student's USMLE 1 score if the score was at or below the 20th percentile (p = .03). Some deans suppress negative information in their letters and potentially obfuscate the residency selection process.

Variability of the institutional review board process within a national research network.

PubMed

Khan, Muhammad A; Barratt, Michelle S; Krugman, Scott D; Serwint, Janet R; Dumont-Driscoll, Marilyn

2014-06-01

To determine the variability of the institutional review board (IRB) process for a minimal risk multicenter study. Participants included 24 Continuity Research Network (CORNET) sites of the Academic Pediatric Association that participated in a cross-sectional study. Each site obtained individual institutional IRB approval. An anonymous questionnaire went to site investigators about the IRB process at their institution. Twenty-two of 24 sites (92%) responded. Preparation time ranged from 1 to 20 hours, mean of 7.1 hours. Individuals submitting ≤3 IRB applications/year required more time for completion than those submitting >3/year (P < .05). Thirteen of 22 (59%) study sites received approval with "exempt" status, and 6 (27%) approved as "expedited" studies. IRB experiences were highly variable across study sites. These findings indicate that multicenter research projects should anticipate barriers to timely study implementation. Improved IRB standardization or centralization for multicenter clinical studies would facilitate this type of practice-based clinical research.

Plasma biochemistry RIs and age effect in European Strigiformes.

PubMed

Agusti Montolio, Susana; Cuenca Valera, Rafaela; Lavín González, Santiago; Cray, Carolyn; Molina López, Rafael; Ferron, Emmanuel Serrano; Francisco, Olga Nicolás; Marco Sánchez, Ignasi; Casas-Díaz, Encarna

2018-03-01

Blood biochemistry and hematology are essential in the laboratory diagnosis of disease. In Strigiformes, little information regarding reference values and influence of different preanalytic factors is available, while age is known to have an effect on some biochemistry analytes, especially in early life characterized by a rapid growth rate and increase in body mass. The objective of this study was to determine baseline data for 29 blood biochemistry variables in 5 species of Iberian Strigiformes assigned to different age classes. Healthy nocturnal birds living in wildlife health centers of Catalonia, Northeastern Spain were assigned to different age classes (chicks, juveniles, adults where possible and available) and their blood was collected and analyzed for different standard biochemistry variables. Species included Tawny owls, Little owls, Long-eared owls, Scop owls, and Barn owls. A total of 276 clinically healthy animals were sampled, including between 179 chicks, 52 juveniles, and 45 adults. The RIs of cholesterol, albumin, and osmolality were the only variables that did not show interspecific variability. Common trends between age class groups were observed in 4 species. Phosphorus and calcium concentrations and ALP activities decreased with increasing age, while concentrations of sodium and γ-globulins tended to increase in the Strigidae family. Differences were concentrated in chicks and no differences were observed between juveniles and adults in any variable. Our results demonstrate the importance of defining biochemical RIs specific for certain age classes. © 2018 American Society for Veterinary Clinical Pathology.

Clinical validity of prototype personality disorder ratings in adolescents.

PubMed

Defife, Jared A; Haggerty, Greg; Smith, Scott W; Betancourt, Luis; Ahmed, Zain; Ditkowsky, Keith

2015-01-01

A growing body of research shows that personality pathology in adolescents is clinically distinctive and frequently stable into adulthood. A reliable and useful method for rating personality pathology in adolescent patients has the potential to enhance conceptualization, dissemination, and treatment effectiveness. The aim of this study is to examine the clinical validity of a prototype matching approach (derived from the Shedler Westen Assessment Procedure-Adolescent Version) for quantifying personality pathology in an adolescent inpatient sample. Sixty-six adolescent inpatients and their parents or legal guardians completed forms of the Child Behavior Checklist (CBCL) assessing emotional and behavioral problems. Clinical criterion variables including suicide history, substance use, and fights with peers were also assessed. Patients' individual and group therapists on the inpatient unit completed personality prototype ratings. Prototype diagnoses demonstrated substantial reliability (median intraclass correlation coefficient =.75) across independent ratings from individual and group therapists. Personality prototype ratings correlated with the CBCL scales and clinical criterion variables in anticipated and meaningful ways. As seen in prior research with adult samples, prototype personality ratings show clinical validity across independent clinician raters previously unfamiliar with the approach, and they are meaningfully related to clinical symptoms, behavioral problems, and adaptive functioning.

Clinical Validity of Prototype Personality Disorder Ratings in Adolescents

PubMed Central

DeFife, Jared A.; Haggerty, Greg; Smith, Scott W.; Betancourt, Luis; Ahmed, Zain; Ditkowsky, Keith

2015-01-01

A growing body of research shows that personality pathology in adolescents is clinically distinctive and frequently stable into adulthood. A reliable and useful method for rating personality pathology in adolescent patients has the potential to enhance conceptualization, dissemination, and treatment effectiveness. The aim of this study is to examine the clinical validity of a prototype matching approach (derived from the Shedler Westen Assessment Procedure – Adolescent Version) for quantifying personality pathology in an adolescent inpatient sample. Sixty-six adolescent inpatients and their parents or legal guardians completed forms of the Child Behavior Checklist (CBCL) assessing emotional and behavioral problems. Clinical criterion variables including suicide history, substance use, and fights with peers were also assessed. Patients’ individual and group therapists on the inpatient unit completed personality prototype ratings. Prototype diagnoses demonstrated substantial reliability (median ICC = .75) across independent ratings from individual and group therapists. Personality prototype ratings correlated with the CBCL scales and clinical criterion variables in anticipated and meaningful ways. As seen in prior research with adult samples, prototype personality ratings show clinical validity across independent clinician raters previously unfamiliar with the approach, and they are meaningfully related to clinical symptoms, behavioral problems, and adaptive functioning. PMID:25457971

Negative Affectivity Predicts Lower Quality of Life and Metabolic Control in Type 2 Diabetes Patients: A Structural Equation Modeling Approach

PubMed Central

Conti, Chiara; Di Francesco, Giulia; Fontanella, Lara; Carrozzino, Danilo; Patierno, Chiara; Vitacolonna, Ester; Fulcheri, Mario

2017-01-01

Introduction: It is essential to consider the clinical assessment of psychological aspects in patients with Diabetes Mellitus (DM), in order to prevent potentially adverse self-management care behaviors leading to diabetes-related complications, including declining levels of Quality of Life (QoL) and negative metabolic control. Purpose: In the framework of Structural Equation Modeling (SEM), the specific aim of this study is to evaluate the influence of distressed personality factors as Negative Affectivity (NA) and Social Inhibition (SI) on diabetes-related clinical variables (i.e., QoL and glycemic control). Methods: The total sample consists of a clinical sample, including 159 outpatients with Type 2 Diabetes Mellitus (T2DM), and a control group composed of 102 healthy respondents. All participants completed the following self- rating scales: The Type D Scale (DS14) and the World Health Organization QoL Scale (WHOQOLBREF). Furthermore, the participants of the clinical group were assessed for HbA1c, disease duration, and BMI. The observed covariates were BMI, gender, and disease duration, while HbA1c was considered an observed variable. Results: SEM analysis revealed significant differences between groups in regards to the latent construct of NA and the Environmental dimension of QoL. For the clinical sample, SEM showed that NA had a negative impact on both QoL dimensions and metabolic control. Conclusions: Clinical interventions aiming to improve medication adherence in patients with T2DM should include the psychological evaluation of Type D Personality traits, by focusing especially on its component of NA as a significant risk factor leading to negative health outcomes. PMID:28596745

Validated surrogate endpoints needed for peri-implantitis.

PubMed

Lee, Dong Won

2011-01-01

Pubmed, Cochrane and Lilac databases, Google, Google Scholar, hand searching of websites of major dental journals. The reference list of five recently published systematic reviews on peri-implantitis treatment were also screened for potential studies. Randomised controlled trials and non-randomised studies in English, German, French, Spanish and Italian on peri-implantitis treatment in humans were included. Case series, case reports and cross sectional or non-therapy studies were excluded from the assessment of endpoints. No minimum follow up time was set for studies that were included. Data were extracted in duplicate by two reviewers and disagreements were resolved by consensus. True endpoints for peri-implantitis treatment were considered only if they provided evidence of tangible benefit to the patient. The outcome variables regarded as true endpoints were implant failure, aesthetic assessment and variables related to quality of life, but these were only considered if they were clearly identified as an objective of the research, not as an outcome of treatment. Surrogate endpoints were considered as those measurements of clinical outcomes such as probing pocket depth and clinical attachment level. Fourteen studies were included in this review with data on implant failure presented solely as consequence of peri-implantitis therapy. No true endpoint was described for any study on peri-implantitis. Mean pocket probing depth, clinical attachment level and bleeding on probing were the three surrogate endpoints cited most often in the literature. All endpoints used in the trials reviewed are surrogates of clinical events, such as implant failure. Clinical surrogate endpoints should be validated to assess the real effect of these measures on true endpoints.

Longitudinal assessment of clinical risk factors for depression in schizophrenia spectrum disorders.

PubMed

Onwuameze, Obiora E; Uga, Aghaegbulam; Paradiso, Sergio

2016-08-01

During initial assessment of individuals with schizophrenia and related disorders (schizophrenia spectrum disorders [SSDs]), clinicians tend to pay greater attention to psychotic symptoms than mood symptoms, including depression. Depression is reported to influence the course of SSDs, but not much is known about the risk factors for depression in SSDs. In the present study, we examined clinical predictors of depression in SSDs. The sample included 71 patients with SSDs followed in a modified Assertive Community Treatment program, the Community Support Network of Springfield, Illinois. The study design was naturalistic, prospective, and longitudinal (mean follow-up = 8.3 years; SD = 7.3). The GENMOD procedure appropriate for repeated measures analysis with dichotomous outcome variables followed longitudinally was computed. Rates of depression ranged from 18% to 41% over the differing assessment periods. Schizophrenia and schizoaffective disorder did not vary by depression rate. Depression independent of SSD diagnosis was associated with greater hospitalization rates. Clinical variables predict- ing depression were auditory hallucinations, delusions, poor insight, and poor judgment. Psychotic symptoms in the course of SSDs are risk factors for depression. As a consequence, the mental status examination of patients with SSDs with active psychosis should include assessment of mood changes. Further research is warranted to determine if treatment of depression among patients with SSDs may reduce their rates of hospitalization.

Anxiety, Depression and Hopelessness in Adolescents: A Structural Equation Model

PubMed Central

Cunningham, Shaylyn; Gunn, Thelma; Alladin, Assen; Cawthorpe, David

2008-01-01

Objective This study tested a structural model, examining the relationship between a latent variable termed demoralization and measured variables (anxiety, depression and hopelessness) in a community sample of Canadian youth. Methods The combined sample consisted of data collected from four independent studies from 2001 to 2005. Nine hundred and seventy one (n=971) participants were high school students (grades 10–12) from three geographic locations: Calgary, Saskatchewan and Lethbridge. Participants completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory-Revised (BDI-II), Beck Hopelessness Scale (BHS), and demographic survey. Structural equation modeling was used for statistical analysis. Results The analysis revealed that the final model, including depression, anxiety and hopelessness and one latent variable demoralization, fit the data (chi-square value, X2 (2) = 7.25, p< .001, goodness of fit indices (CFI=0.99, NFI=0.98) and standardized error (0.05). Overall, the findings suggest that close relationships exist among depression, anxiety, hopelessness and demoralization that is stable across demographic variables. Further, the model explains the relationship between sub-clinical anxiety, depression and hopelessness. Conclusion These findings contribute to a theoretical framework, which has implications for educational and clinical intervention. The present findings will help guide further preventative research on examining demoralization as a precursor to sub-clinical anxiety and depression. PMID:18769644

Pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea treatment for children with sickle cell anemia

PubMed Central

Despotovic, Jenny M.; Mortier, Nicole A.; Flanagan, Jonathan M.; He, Jin; Smeltzer, Matthew P.; Kimble, Amy C.; Aygun, Banu; Wu, Song; Howard, Thad; Sparreboom, Alex

2011-01-01

Hydroxyurea therapy has proven laboratory and clinical efficacies for children with sickle cell anemia (SCA). When administered at maximum tolerated dose (MTD), hydroxyurea increases fetal hemoglobin (HbF) to levels ranging from 10% to 40%. However, interpatient variability of percentage of HbF (%HbF) response is high, MTD itself is variable, and accurate predictors of hydroxyurea responses do not currently exist. HUSTLE (NCT00305175) was designed to provide first-dose pharmacokinetics (PK) data for children with SCA initiating hydroxyurea therapy, to investigate pharmacodynamics (PD) parameters, including HbF response and MTD after standardized dose escalation, and to evaluate pharmacogenetics influences on PK and PD parameters. For 87 children with first-dose PK studies, substantial interpatient variability was observed, plus a novel oral absorption phenotype (rapid or slow) that influenced serum hydroxyurea levels and total hydroxyurea exposure. PD responses in 174 subjects were robust and similar to previous cohorts; %HbF at MTD was best predicted by 5 variables, including baseline %HbF, whereas MTD was best predicted by 5 variables, including serum creatinine. Pharmacogenetics analysis showed single nucleotide polymorphisms influencing baseline %HbF, including 5 within BCL11A, but none influencing MTD %HbF or dose. Accurate prediction of hydroxyurea treatment responses for SCA remains a worthy but elusive goal. PMID:21876119

Blood pressure monitoring: theory and practice. European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability Teaching Course Proceedings.

PubMed

Stergiou, George S; Palatini, Paolo; Asmar, Roland; Bilo, Grzegorz; de la Sierra, Alejandro; Head, Geoff; Kario, Kazuomi; Mihailidou, Anastasia; Wang, Jiguang; Mancia, Giuseppe; O'Brien, Eoin; Parati, Gianfranco

2018-02-01

The European Society of Hypertension (ESH) Working Group on Blood Pressure (BP) Monitoring and Cardiovascular Variability organized a Teaching Course on 'Blood Pressure Monitoring: Theory and Practice' during the 2017 ESH Meeting in Milan, Italy. This course performed by 11 international BP monitoring experts covered key topics of BP monitoring, including office BP measurement, ambulatory BP monitoring, home BP monitoring, ambulatory versus home BP, white-coat and masked hypertension, cuff use, and BP variability. This article presents a summary of the proceedings of the ESH BP Monitoring Teaching Course, including essential information, practical issues, and recommendations on the clinical application of BP monitoring methods, aiming to the optimal management of patients with suspected or diagnosed hypertension.

Efficacy and toxicity differences in lung cancer populations in the era of clinical trials globalization: the 'common arm' approach.

PubMed

Mack, Philip C; Gandara, David R; Lara, Primo N

2012-12-01

Historically, notable variability has been observed in clinical trial outcomes between different regions and populations worldwide, even when employing the same cytotoxic regimen in lung cancer. These divergent results underscore the inherent challenges in interpreting trials conducted abroad and raise questions regarding the general applicability of transnational clinical trials. Various reasons have been postulated to account for these differences in efficacy and toxicity, including trial design, eligibility criteria, patient demographics and, perhaps most intriguingly, population-related pharmacogenomics. However, without methodology to control for such variables, these hypotheses remain largely untested. The authors previously developed the 'common arm' approach in order to directly compare efficacy and toxicity results of trials simultaneously performed in different countries. By standardizing clinical trial-associated variables such as treatment regimens (dose, schedule, and so on), eligibility, staging, response and toxicity criteria, this approach has the potential to determine the underlying reasons for divergences in trial outcomes across countries, and whether population-associated polymorphisms contribute to these differences. In the past decade, Japanese and US investigators have applied the common arm analytic method to trials in both extensive-stage small-cell lung cancer (SCLC) and advanced nonSCLC. In the SCLC analysis, a comparison of the cisplatin/irinotecan arms from both trials revealed significant differences in response rates and overall survival. Significant differences were also observed in the distribution of gender and performance status. The common arm analysis in nonSCLC included two trials from Japan and one from the USA, each containing a 'common' carboplatin/paclitaxel arm. Clinical results were similar in the two Japanese trials, but were significantly different from the US trial with regard to survival, neutropenia, febrile neutropenia and anemia. The underlying basis for these divergent outcomes is discussed. The common arm methodology provides a template for identifying and interpreting patient outcome differences across populations, and is an instructive lesson in the burgeoning era of clinical trials globalization.

Novel approach to characterising individuals with low back-related leg pain: cluster identification with latent class analysis and 12-month follow-up.

PubMed

Stynes, Siobhán; Konstantinou, Kika; Ogollah, Reuben; Hay, Elaine M; Dunn, Kate M

2018-04-01

Traditionally, low back-related leg pain (LBLP) is diagnosed clinically as referred leg pain or sciatica (nerve root involvement). However, within the spectrum of LBLP, we hypothesised that there may be other unrecognised patient subgroups. This study aimed to identify clusters of patients with LBLP using latent class analysis and describe their clinical course. The study population was 609 LBLP primary care consulters. Variables from clinical assessment were included in the latent class analysis. Characteristics of the statistically identified clusters were compared, and their clinical course over 1 year was described. A 5 cluster solution was optimal. Cluster 1 (n = 104) had mild leg pain severity and was considered to represent a referred leg pain group with no clinical signs, suggesting nerve root involvement (sciatica). Cluster 2 (n = 122), cluster 3 (n = 188), and cluster 4 (n = 69) had mild, moderate, and severe pain and disability, respectively, and response to clinical assessment items suggested categories of mild, moderate, and severe sciatica. Cluster 5 (n = 126) had high pain and disability, longer pain duration, and more comorbidities and was difficult to map to a clinical diagnosis. Most improvement for pain and disability was seen in the first 4 months for all clusters. At 12 months, the proportion of patients reporting recovery ranged from 27% for cluster 5 to 45% for cluster 2 (mild sciatica). This is the first study that empirically shows the variability in profile and clinical course of patients with LBLP including sciatica. More homogenous groups were identified, which could be considered in future clinical and research settings.

Incidence of postoperative hypothermia and the relationship to clinical variables.

PubMed

Burns, Shari M; Piotrowski, Kathy; Caraffa, Guy; Wojnakowski, Mary

2010-10-01

A prospective, quantitative, correlational study was conducted to determine the incidence of postoperative hypothermia and the relationship of hypothermia to numerous clinical variables previously studied. The study reflects the researchers' interest in updating previous data regarding the incidence of hypothermia. Although hypothermia remains a significant clinical concern, interventions aimed at minimizing hypothermia have evolved over the past 20 years, thus prompting new interest in determining the extent to which hypothermia exists in today's PACU patients. A convenience sample of 287 adult, nonemergency patients scheduled for surgery were included in the study. Hypothermia (temperature <36°C) was demonstrated in only 4% of the sample (N = 287). Because of the low incidence of hypothermia, correlation statistics were not performed. The study provides a foundation for future research regarding this important clinical phenomenon while offering evidence supporting efforts to avoid hypothermia in today's surgical patients. Copyright © 2010 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Comparison of insight and clinical variables in homeless and non-homeless psychiatric inpatients in China.

PubMed

Fu, Yan-Nan; Cao, Xiao-Lan; Hou, Cai-Lan; Ng, Chee H; Ungvari, Gabor S; Chiu, Helen F K; Lin, Yong-Qiang; Wang, Lihui; Zheng, Xiaocong; Jia, Fu-Jun; Xiang, Yu-Tao

2017-09-01

There are no published data on insight in homeless patients with psychiatric disorders in China. This study examined insight in homeless and non-homeless Chinese psychiatric inpatients in relation to demographic and clinical variables. A total of 278 homeless and 222 non-homeless inpatients matched in age and gender were included in the study. Demographic and clinical characteristics were collected based on a review of medical charts and a clinical interview with standardized instruments. Insight was evaluated with the Insight and Treatment Attitudes Questionnaire. Altogether 20.5% of homeless inpatients and 43.7% of the non-homeless controls had good insight. Compared with homeless inpatients with impaired insight, homeless inpatients with good insight had higher physical quality of life, longer duration of illness and less severe positive and negative symptoms. Impaired insight appeared more common in homeless psychiatric inpatients in China. Further studies should address the need for effective therapeutic interventions that promote homeless patients' insight. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Testing the 4Rs and 2Ss Multiple Family Group intervention: study protocol for a randomized controlled trial.

PubMed

Acri, Mary; Hamovitch, Emily; Mini, Maria; Garay, Elene; Connolly, Claire; McKay, Mary

2017-12-04

Oppositional defiant disorder (ODD) is a major mental health concern and highly prevalent among children living in poverty-impacted communities. Despite that treatments for ODD are among the most effective, few children living in poverty receive these services due to substantial barriers to access, as well as difficulties in the uptake and sustained adoption of evidence-based practices (EBPs) in community settings. The purpose of this study is to examine implementation processes that impact uptake of an evidence-based practice for childhood ODD, and the impact of a Clinic Implementation Team (CIT)-driven structured adaptation to enhance its fit within the public mental health clinic setting. This study, a Hybrid Type II effectiveness-implementation research trial, blends clinical effectiveness and implementation research methods to examine the impact of the 4Rs and 2Ss Multiple Family Group (MFG) intervention, family level mediators of child outcomes, clinic/provider-level mediators of implementation, and the impact of CITs on uptake and long-term utilization of this model. All New York City public outpatient mental health clinics have been invited to participate. A sampling procedure that included randomization at the agency level and a sub-study to examine the impact of clinic choice upon outcomes yielded a distribution of clinics across three study conditions. Quantitative data measuring child outcomes, organizational factors and implementation fidelity will be collected from caregivers and providers at baseline, 8, and 16 weeks from baseline, and 6 months from treatment completion. The expected participation is 134 clinics, 268 providers, and 2688 caregiver/child dyads. We will use mediation analysis with a multi-level Structural Equation Modeling (SEM) (MSEM including family level variables, provider variables, and clinic variables), as well as mediation tests to examine study hypotheses. The aim of the study is to generate knowledge about effectiveness and mediating factors in the treatment of ODDs in children in the context of family functioning, and to propose an innovative approach to the adaptation and implementation of new treatment interventions within clinic settings. The proposed CIT adaptation and implementation model has the potential to enhance implementation and sustainability, and ultimately increase the extent to which effective interventions are available and can impact children and families in need of services for serious behavior problems. ClinicalTrials.gov, ID: NCT02715414 . Registered on 3 March 2016.

[Early drop-outs and retentions in substance abuse outpatient clinics: a cross-sectional comparative study of factors that increase or decrease adherence].

PubMed

Calvo, Fran; Carbonell, Xavier; Valero, Ramón; Costa, Jordi; Turró, Oriol; Giralt, Cristina; Ramírez, Marissa

2017-08-23

The aim of this study is to define the risk factors associated with early discharge in out-patients clinics. Cross-sectional and observational study. Substance abuse clinics in Girona (Catalonia, Spain). A total of 264 individuals were included in the sample, and 34.8% of them abandoned the process within two months of starting the therapy (n=92). Clinical and socio-demographic variables of the clinical history were compared between participants with/without adherence. The Student t test was used to measure the comparison, and the chi-squared test was used for the analysis of qualitative variables. A binary logistic regression model was adjusted, with adherence as the dependent variable. The results indicated that attending the appointments unaccompanied (OR=3.13), being female (OR=2.44), having cocaine related issues (OR=1.14), and being younger (OR=0.89) are the factors which increase the risk early abandonment. Contrarily, being referred to specialists from a Primary Health Centre reduces the risk (OR=0.28). It is concluded that special attention must be devoted to the patients' families, women, and young patients. Moreover, the appropriate coordination between specialist services and basic services increases adherence to treatment among drug users. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

[The clinical picture and stability of non-cognitive symptoms in patients with Alzheimer's disease].

PubMed

Haupt, M; Jänner, M; Stierstorfer, A; Kretschmar, C

1998-05-01

The purpose of this study was to investigate noncognitive symptoms in Alzheimer's disease in order to identify symptom patterns and to study stability of such patterns prospectively. Furthermore, variables were examined which could be associated with certain types of symptom patterns or could be predictors of change of these patterns. Forty-eight patients with the clinical diagnosis of probable Alzheimer's disease were included in this study and were assessed weekly over a three-week period. Noncognitive symptoms were rated according to the Behavioral Abnormalities in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the Dementia Mood Assessment Scale (DMAS) and to a set of items specifically assessing misidentifications. By means of principal component factor analysis different noncognitive symptom patterns were obtained yielding a four-factor solution. They were mapped as rational domains with respect to clinical experience: 'depression', 'apathy', 'psychotic symptoms/aggression', 'misidentifications/agitation'. Demographic and clinical variables were not associated with the factor solutions and did not predict change of the factor values. The results demonstrate that in Alzheimer's disease there are distinct noncognitive symptom patterns with at least short-term prospective stability. None of the examined clinical variables, such as age at entry, the status of the patients (outpatient or inpatient) or dementia severity, exerted substantial influence on the noncognitive symptom patterns. Further investigations should concentrate on the pathological and prognostical correlates of noncognitive symptom patterns in Alzheimer's disease.

Patient-reported outcomes and socioeconomic status as predictors of clinical outcomes following hematopoietic stem cell transplantation: A study from the BMT CTN 0902 trial

PubMed Central

Knight, Jennifer M; Syrjala, Karen L; Majhail, Navneet S; Martens, Michael; Le-Rademacher, Jennifer; Logan, Brent R; Lee, Stephanie J; Jacobsen, Paul B; Wood, William A; Jim, Heather SL; Wingard, John R; Horowitz, Mary M; Abidi, Muneer H; Fei, Mingwei; Rawls, Laura; Rizzo, J Douglas

2016-01-01

This secondary analysis of a large, multi-center Blood and Marrow Transplant Clinical Trials Network (BMT CTN) randomized trial assessed whether patient-reported outcomes (PROs) and socioeconomic status (SES) before hematopoietic stem cell transplantation (HCT) are associated with each other and predictive of clinical outcomes including time to hematopoietic recovery, acute graft-versus-host disease, hospitalization days, and overall survival (OS) among 646 allogeneic and autologous HCT recipients. Pre-transplant Cancer and Treatment Distress (CTXD), Pittsburgh Sleep Quality Index (PSQI), and mental and physical component scores (MCS and PCS) of the SF-36 were correlated with each other and with SES variables. PROs and SES variables were further evaluated as predictors of clinical outcomes, with the PSQI and CTXD evaluated as OS predictors (p<.01 considered significant given multiple testing). Lower attained education was associated with increased distress (p=.002); lower income was related to worse physical functioning (p=.005) and increased distress (p=.008); lack of employment pre-transplant was associated with worse physical functioning (p<.01); unmarried status was associated with worse sleep (p=.003). In this large heterogeneous cohort of HCT recipients, while PROs and SES variables were correlated at baseline, they were not associated with any clinical outcomes. Future research should focus on HCT recipients at greater psychosocial disadvantage. PMID:27565521

H syndrome: the first 79 patients.

PubMed

Molho-Pessach, Vered; Ramot, Yuval; Camille, Frances; Doviner, Victoria; Babay, Sofia; Luis, Siekavizza Juan; Broshtilova, Valentina; Zlotogorski, Abraham

2014-01-01

H syndrome is an autosomal recessive genodermatosis with multisystem involvement caused by mutations in SLC29A3. We sought to investigate the clinical and molecular findings in 79 patients with this disorder. A total of 79 patients were included, of which 13 are newly reported cases. Because of the phenotypic similarity and molecular overlap with H syndrome, we included 18 patients with allelic disorders. For 31 patients described by others, data were gathered from the medical literature. The most common clinical features (>45% of patients) were hyperpigmentation, phalangeal flexion contractures, hearing loss, and short stature. Insulin-dependent diabetes mellitus and lymphadenopathy mimicking Rosai-Dorfman disease were each found in approximately 20%. Additional systemic features were described in less than 15% of cases. Marked interfamilial and intrafamilial clinical variability exists. Twenty mutations have been identified in SLC29A3, with no genotype-phenotype correlation. In the 31 patients described by others, data were collected from the medical literature. H syndrome is a multisystemic disease with clinical variability. Consequently, all SLC29A3-related diseases should be considered a single entity. Recognition of the pleomorphic nature of H syndrome is important for diagnosis of additional patients. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Reporting of research quality characteristics of studies published in 6 major clinical dental specialty journals.

PubMed

Pandis, Nikolaos; Polychronopoulou, Argy; Madianos, Phoebus; Makou, Margarita; Eliades, Theodore

2011-06-01

The objective of this article was to record reporting characteristics related to study quality of research published in major specialty dental journals with the highest impact factor (Journal of Endodontics, Journal of Oral and Maxillofacial Surgery, American Journal of Orthodontics and Dentofacial Orthopedics; Pediatric Dentistry, Journal of Clinical Periodontology, and International Journal of Prosthetic Dentistry). The included articles were classified into the following 3 broad subject categories: (1) cross-sectional (snap-shot), (2) observational, and (3) interventional. Multinomial logistic regression was conducted for effect estimation using the journal as the response and randomization, sample calculation, confounding discussed, multivariate analysis, effect measurement, and confidence intervals as the explanatory variables. The results showed that cross-sectional studies were the dominant design (55%), whereas observational investigations accounted for 13%, and interventions/clinical trials for 32%. Reporting on quality characteristics was low for all variables: random allocation (15%), sample size calculation (7%), confounding issues/possible confounders (38%), effect measurements (16%), and multivariate analysis (21%). Eighty-four percent of the published articles reported a statistically significant main finding and only 13% presented confidence intervals. The Journal of Clinical Periodontology showed the highest probability of including quality characteristics in reporting results among all dental journals. Copyright © 2011 Elsevier Inc. All rights reserved.

Do ictal EEG characteristics predict treatment outcomes in schizophrenic patients undergoing electroconvulsive therapy?

PubMed

Simsek, Gulnihal Gokce; Zincir, Selma; Gulec, Huseyin; Eksioglu, Sevgin; Semiz, Umit Basar; Kurtulmus, Yasemin Sipka

2015-08-01

The aim of this study is to investigate the relationship between features of electroencephalography (EEG), including seizure time, energy threshold level and post-ictal suppression time, and clinical variables, including treatment outcomes and side-effects, among schizophrenia inpatients undergoing electroconvulsive therapy (ECT). This is a naturalistic follow-up study on schizophrenia patients, diagnosed using DSM-IV-TR criteria, treated by a psychosis inpatient service. All participants completed the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning (GAF) scale, the Frontal Assessment Battery (FAB) and a Data Collection Form. Assessments were made before treatment, during ECT and after treatment. Statistically significant improvements in both clinical and cognitive outcome were noted after ECT in all patients. Predictors of improvement were sought by evaluating electrophysiological variables measured at three time points (after the third, fifth and seventh ECT sessions). Logistic regression analysis showed that clinical outcome/improvement did not differ by seizure duration, threshold energy level or post-ictal suppression time. We found that ictal EEG parameters measured at several ECT sessions did not predict clinical recovery/outcomes. This may be because our centre defensively engages in "very specific patient selection" when ECT is contemplated. ECT does not cause short-term cognitive functional impairment and indeed improves cognition, because symptoms of the schizophrenic episode are alleviated.

A Longitudinal Study of Success Versus Failure in Contraceptive Planning

ERIC Educational Resources Information Center

Oskamp, Stuart; And Others

1978-01-01

This is a study of new birth-control patients in four Los Angeles suburban area Planned Parenthood clinics. The data include interviews, tests, questionnaires, and archival and demographic information, focusing particularly on personality, attitude, and motivation variables. (BB)

[Predictive value of history and physical examination for the diagnosis of community-acquired pneumonia in adults].

PubMed

Saldías P, Fernando; Cabrera T, Daniel; de Solminihac L, Ignacio; Hernández A, Pamela; Gederlini G, Alessandra; Díaz F, Alejandro

2007-02-01

Community-acquired pneumonia in adults is a serious health problem in the ambulatory care setting. To define clinical variables associated with the presence of pneumonia in adult patients presenting with fever or respiratory symptoms to the emergency department. Prospective study carried out in the emergency department from the Catholic University Hospital in Santiago, Chile. Three hundred twenty-five patients (53+/-22 years) presenting fever or acute respiratory symptoms were included. After obtaining a clinical history and physical examination, the physician established a tentative diagnosis. Subsequently, a definitive diagnosis was made with the chest X rays. Thirty-four percent of the patients had pneumonia. The clinical diagnosis of pneumonia before X-ray examination was variable among emergency physicians (positive likelihood ratio: 1.5-4.8) and showed only moderate sensitivity (79%) and specificity (66%). The clinical variables significantly associated with the presence of pneumonia were: advanced age (over 75 years), cardiovascular disease, fever, chills, sputum production, orthopnea, altered mental status, cyanosis, dullness on percussion, bronchial breath sounds, crackles, any abnormal vital sign (heart rate>or=100 beats/min, respiratory rate>or=20 breaths/min or temperature>or=38 degrees C) and oxygen saturation below 90% breathing air. Clinical judgment prior to observation of chest X rays had moderate sensitivity and specificity for the diagnosis of pneumonia. There were no individual clinical findings, or combination of findings, that could confirm or exclude the diagnosis of pneumonia for a patient suspected of having this illness.

Patient-Reported Outcomes and Socioeconomic Status as Predictors of Clinical Outcomes after Hematopoietic Stem Cell Transplantation: A Study from the Blood and Marrow Transplant Clinical Trials Network 0902 Trial.

PubMed

Knight, Jennifer M; Syrjala, Karen L; Majhail, Navneet S; Martens, Michael; Le-Rademacher, Jennifer; Logan, Brent R; Lee, Stephanie J; Jacobsen, Paul B; Wood, William A; Jim, Heather S L; Wingard, John R; Horowitz, Mary M; Abidi, Muneer H; Fei, Mingwei; Rawls, Laura; Rizzo, J Douglas

2016-12-01

This secondary analysis of a large, multicenter Blood and Marrow Transplant Clinical Trials Network randomized trial assessed whether patient-reported outcomes (PROs) and socioeconomic status (SES) before hematopoietic stem cell transplantation (HCT) are associated with each other and predictive of clinical outcomes, including time to hematopoietic recovery, acute graft-versus-host disease, hospitalization days, and overall survival (OS) among 646 allogeneic and autologous HCT recipients. Pretransplantation Cancer and Treatment Distress (CTXD), Pittsburgh Sleep Quality Index (PSQI), and mental and physical component scores of the Short-Form 36 were correlated with each other and with SES variables. PROs and SES variables were further evaluated as predictors of clinical outcomes, with the PSQI and CTXD evaluated as OS predictors (P < .01 considered significant given multiple testing). Lower attained education was associated with increased distress (P = .002), lower income was related to worse physical functioning (P = .005) and increased distress (P = .008), lack of employment before transplantation was associated with worse physical functioning (P < .01), and unmarried status was associated with worse sleep (P = .003). In this large heterogeneous cohort of HCT recipients, although PROs and SES variables were correlated at baseline, they were not associated with any clinical outcomes. Future research should focus on HCT recipients at greater psychosocial disadvantage. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Derivation and validation of the Personal Support Algorithm: an evidence-based framework to inform allocation of personal support services in home and community care.

PubMed

Sinn, Chi-Ling Joanna; Jones, Aaron; McMullan, Janet Legge; Ackerman, Nancy; Curtin-Telegdi, Nancy; Eckel, Leslie; Hirdes, John P

2017-11-25

Personal support services enable many individuals to stay in their homes, but there are no standard ways to classify need for functional support in home and community care settings. The goal of this project was to develop an evidence-based clinical tool to inform service planning while allowing for flexibility in care coordinator judgment in response to patient and family circumstances. The sample included 128,169 Ontario home care patients assessed in 2013 and 25,800 Ontario community support clients assessed between 2014 and 2016. Independent variables were drawn from the Resident Assessment Instrument-Home Care and interRAI Community Health Assessment that are standardised, comprehensive, and fully compatible clinical assessments. Clinical expertise and regression analyses identified candidate variables that were entered into decision tree models. The primary dependent variable was the weekly hours of personal support calculated based on the record of billed services. The Personal Support Algorithm classified need for personal support into six groups with a 32-fold difference in average billed hours of personal support services between the highest and lowest group. The algorithm explained 30.8% of the variability in billed personal support services. Care coordinators and managers reported that the guidelines based on the algorithm classification were consistent with their clinical judgment and current practice. The Personal Support Algorithm provides a structured yet flexible decision-support framework that may facilitate a more transparent and equitable approach to the allocation of personal support services.

Evaluation of the Environmental Bias on Accelerometer-Measured Total Daily Activity Counts and Owner Survey Responses in Dogs with Osteoarthritis.

PubMed

Katz, Erin M; Scott, Ruth M; Thomson, Christopher B; Mesa, Eileen; Evans, Richard; Conzemius, Michael G

2017-11-01

Objective  To determine if environmental variables affect the average daily activity counts (AC) of dogs with osteoarthritis (OA) and/or owners' perception of their dog's clinical signs or quality of life. Methods  The AC and Canine Brief Pain Inventory (CBPI) owner questionnaires of 62 dogs with OA were compared with daily environmental variables including the following: average temperature (°C), high temperature (°C), low temperature (°C), relative humidity (%), total precipitation (mm), average barometric pressure (hPa) and total daylight hours. Results  Daily AC significantly correlated with average temperature and total daylight hours, but average temperature and total daylight hours accounted for less than 1% of variation in AC. No other significant relationships were found between daily AC and daily high temperature, low temperature, relative humidity, total precipitation or average barometric pressure. No statistical relationship was found between daily AC and the CBPI, nor between environmental variables and the CBPI. Canine Brief Pain Inventory scores for pain severity and pain interference decreased significantly over the test period. Clinical Significance  The relationship between daily AC and average temperature and total daylight hours was significant, but unlikely to be clinically significant. Thus, environmental variables do not appear to have a clinically relevant bias on AC or owner CBPI questionnaires. The decrease over time in CBPI pain severity and pain interference values suggests owners completing the CBPI in this study were influenced by a caregiver placebo effect. Schattauer GmbH Stuttgart.

The Complexity of Clinical Huntington's Disease: Developments in Molecular Genetics, Neuropathology and Neuroimaging Biomarkers.

PubMed

Tippett, Lynette J; Waldvogel, Henry J; Snell, Russell G; Vonsattel, Jean-Paul; Young, Anne B; Faull, Richard L M

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by extensive neuronal loss in the striatum and cerebral cortex, and a triad of clinical symptoms affecting motor, cognitive/behavioural and mood functioning. The mutation causing HD is an expansion of a CAG tract in exon 1 of the HTT gene. This chapter provides a multifaceted overview of the clinical complexity of HD. We explore recent directions in molecular genetics including the identification of loci that are genetic modifiers of HD that could potentially reveal therapeutic targets beyond the HTT gene transcript and protein. The variability of clinical symptomatology in HD is considered alongside recent findings of variability in cellular and neurochemical changes in the striatum and cerebral cortex in human brain. We review evidence from structural neuroimaging methods of progressive changes of striatum, cerebral cortex and white matter in pre-symptomatic and symptomatic HD, with a particular focus on the potential identification of neuroimaging biomarkers that could be used to test promising disease-specific and modifying treatments. Finally we provide an overview of completed clinical trials in HD and future therapeutic developments.

Organizational correlates of implementation of colocation of mental health and primary care in the Veterans Health Administration.

PubMed

Guerrero, Erick G; Heslin, Kevin C; Chang, Evelyn; Fenwick, Karissa; Yano, Elizabeth

2015-07-01

This study explored the role of organizational factors in the ability of Veterans Health Administration (VHA) clinics to implement colocated mental health care in primary care settings (PC-MH). The study used data from the VHA Clinical Practice Organizational Survey collected in 2007 from 225 clinic administrators across the United States. Clinic degree of implementation of PC-MH was the dependent variable, whereas independent variables included policies and procedures, organizational context, and leaders' perceptions of barriers to change. Pearson bivariate correlations and multivariable linear regression were used to test hypotheses. Results show that depression care training for primary care providers and clinics' flexibility and participation were both positively correlated with implementation of PC-MH. However, after accounting for other factors, regressions show that only training primary care providers in depression care was marginally associated with degree of implementation of PC-MH (p = 0.051). Given the importance of this topic for implementing integrated care as part of health care reform, these null findings underscore the need to improve theory and testing of more proximal measures of colocation in future work.

Pro: 'The usefulness of biomarkers in glomerular diseases'. The problem: moving from syndrome to mechanism--individual patient variability in disease presentation, course and response to therapy.

PubMed

Mariani, Laura H; Kretzler, Matthias

2015-06-01

The diagnosis and treatment decisions in glomerular disease are principally based on renal pathology and nonspecific clinical laboratory measurements such as serum creatinine and urine protein. Using these classification approaches, patients have marked variability in rate of progression and response to therapy, exposing a significant number of patients to toxicity without benefit. Additionally, clinical trials are at risk of not being able to detect an efficacious therapy in relevant subgroups as patients with shared clinical-pathologic diagnoses have heterogeneous underlying pathobiology. To change this treatment paradigm, biomarkers that reflect the molecular mechanisms underlying the clinical-pathologic diagnoses are needed. Recent progress to identify such biomarkers has been aided by advances in molecular profiling, large-scale data generation and multi-scalar data integration, including prospectively collected clinical data. This article reviews the evolving success stories in glomerular disease biomarkers across the genotype-phenotype continuum and highlights opportunities to transition to precision medicine in glomerular disease. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Factors explaining children's responses to intravenous needle insertions.

PubMed

McCarthy, Ann Marie; Kleiber, Charmaine; Hanrahan, Kirsten; Zimmerman, M Bridget; Westhus, Nina; Allen, Susan

2010-01-01

Previous research shows that numerous child, parent, and procedural variables affect children's distress responses to procedures. Cognitive-behavioral interventions such as distraction are effective in reducing pain and distress for many children undergoing these procedures. The purpose of this report was to examine child, parent, and procedural variables that explain child distress during a scheduled intravenous insertion when parents are distraction coaches for their children. A total of 542 children, between 4 and 10 years of age, and their parents participated. Child age, gender, diagnosis, and ethnicity were measured by questions developed for this study. Standardized instruments were used to measure child experience with procedures, temperament, ability to attend, anxiety, coping style, and pain sensitivity. Questions were developed to measure parent variables, including ethnicity, gender, previous experiences, and expectations, and procedural variables, including use of topical anesthetics and difficulty of procedure. Standardized instruments were used to measure parenting style and parent anxiety, whereas a new instrument was developed to measure parent performance of distraction. Children's distress responses were measured with the Observation Scale of Behavioral Distress-Revised (behavioral), salivary cortisol (biological), Oucher Pain Scale (self-report), and parent report of child distress (parent report). Regression methods were used for data analyses. Variables explaining behavioral, child-report and parent-report measures include child age, typical coping response, and parent expectation of distress (p < .01). Level of parents' distraction coaching explained a significant portion of behavioral, biological, and parent-report distress measures (p < .05). Child impulsivity and special assistance at school also significantly explained child self-report of pain (p < .05). Additional variables explaining cortisol response were child's distress in the morning before clinic, diagnoses of attention deficit hyperactivity disorder or anxiety disorder, and timing of preparation for the clinic visit. The findings can be used to identify children at risk for high distress during procedures. This is the first study to find a relationship between child behavioral distress and level of parent distraction coaching.

The Association Between Internet Use and Ambulatory Care-Seeking Behaviors in Taiwan: A Cross-Sectional Study

PubMed Central

Chen, Tsung-Fu; Liang, Jyh-Chong; Lin, Tzu-Bin; Tsai, Chin-Chung

2016-01-01

Background Compared with the traditional ways of gaining health-related information from newspapers, magazines, radio, and television, the Internet is inexpensive, accessible, and conveys diverse opinions. Several studies on how increasing Internet use affected outpatient clinic visits were inconclusive. Objective The objective of this study was to examine the role of Internet use on ambulatory care-seeking behaviors as indicated by the number of outpatient clinic visits after adjusting for confounding variables. Methods We conducted this study using a sample randomly selected from the general population in Taiwan. To handle the missing data, we built a multivariate logistic regression model for propensity score matching using age and sex as the independent variables. The questionnaires with no missing data were then included in a multivariate linear regression model for examining the association between Internet use and outpatient clinic visits. Results We included a sample of 293 participants who answered the questionnaire with no missing data in the multivariate linear regression model. We found that Internet use was significantly associated with more outpatient clinic visits (P=.04). The participants with chronic diseases tended to make more outpatient clinic visits (P<.01). Conclusions The inconsistent quality of health-related information obtained from the Internet may be associated with patients’ increasing need for interpreting and discussing the information with health care professionals, thus resulting in an increasing number of outpatient clinic visits. In addition, the media literacy of Web-based health-related information seekers may also affect their ambulatory care-seeking behaviors, such as outpatient clinic visits. PMID:27927606

Milestones: Critical Elements in Clinical Informatics Fellowship Programs

PubMed Central

Lehmann, Christoph U.; Munger, Benson

2016-01-01

Summary Background Milestones refer to points along a continuum of a competency from novice to expert. Resident and fellow assessment and program evaluation processes adopted by the ACGME include the mandate that programs report the educational progress of residents and fellows twice annually utilizing Milestones developed by a specialty specific ACGME working group of experts. Milestones in clinical training programs are largely unmapped to specific assessment tools. Residents and fellows are mainly assessed using locally derived assessment instruments. These assessments are then reviewed by the Clinical Competency Committee which assigns and reports trainee ratings using the specialty specific reporting Milestones. Methods and Results The challenge and opportunity facing the nascent specialty of Clinical Informatics is how to optimally utilize this framework across a growing number of accredited fellowships. The authors review how a mapped milestone framework, in which each required sub-competency is mapped to a single milestone assessment grid, can enable the use of milestones for multiple uses including individualized learning plans, fellow assessments, and program evaluation. Furthermore, such a mapped strategy will foster the ability to compare fellow progress within and between Clinical Informatics Fellowships in a structured and reliable fashion. Clinical Informatics currently has far less variability across programs and thus could easily utilize a more tightly defined set of milestones with a clear mapping to sub-competencies. This approach would enable greater standardization of assessment instruments and processes across programs while allowing for variability in how those sub-competencies are taught. Conclusions A mapped strategy for Milestones offers significant advantages for Clinical Informatics programs. PMID:27081414

Clinical expression of lolitrem B (perennial ryegrass) intoxication in horses.

PubMed

Johnstone, L K; Mayhew, I G; Fletcher, L R

2012-05-01

Perennial ryegrass staggers is purported to be a common neurological mycotoxicosis of horses but the case description lacks detail and evidence. To describe the clinical syndrome of lolitrem B intoxication in horses, limiting tests to those that are applicable to clinical practice, and to assess the potential value of enzyme-linked immunosorbent assay (ELISA) tests for lolitrem B in horse body fluids. Seven horses in 2 separate groups were fed perennial ryegrass seed and hay containing 2 ppm lolitrem B. Paired data were collected prior to and after 2 weeks exposure to lolitrem B, including video-documented neurological examination and clinical examination. All horses developed a variable degree of tremor and ataxia when exposed to lolitrem B. Tremor depended on the level of activity and included a subtle, rapid tremor of the eyeball. Ataxia was exaggerated by blindfolding and primarily involved a truncal sway and irregular, but predictable, limb placements. No change was detected in urine lolitrem B levels and, although plasma lolitrem B increased during the treatment period, levels did not correlate with the severity of clinical signs displayed. Limb swelling, heel lesions and serous nasal discharge were also observed in horses most severely intoxicated. The clinical effects of lolitrem B intoxication in horses primarily involve action-related tremors and symmetrical vestibular ataxia. Ergovaline may have caused the limb swelling, heel lesions and serous nasal discharge. Plasma ELISA for lolitrem B may be of diagnostic use in the future. This study provides a clearer appreciation of the clinical signs and variability of perennial ryegrass intoxication in horses. © 2011 EVJ Ltd.

Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part 2—External Validity and Correlates.

PubMed

Horan, William P; Reddy, L Felice; Barch, Deanna M; Buchanan, Robert W; Dunayevich, Eduardo; Gold, James M; Marder, Steven R; Wynn, Jonathan K; Young, Jared W; Green, Michael F

2015-09-01

Effort-based decision making has strong conceptual links to the motivational disturbances that define a key subdomain of negative symptoms. However, the extent to which effort-based decision-making performance relates to negative symptoms, and other clinical and functionally important variables has yet to be systematically investigated. In 94 clinically stable outpatients with schizophrenia, we examined the external validity of 5 effort-based paradigms, including the Effort Expenditure for Rewards, Balloon Effort, Grip Strength Effort, Deck Choice Effort, and Perceptual Effort tasks. These tasks covered 3 types of effort: physical, cognitive, and perceptual. Correlations between effort related performance and 6 classes of variables were examined, including: (1) negative symptoms, (2) clinically rated motivation and community role functioning, (3) self-reported motivational traits, (4) neurocognition, (5) other psychiatric symptoms and clinical/demographic characteristics, and (6) subjective valuation of monetary rewards. Effort paradigms showed small to medium relationships to clinical ratings of negative symptoms, motivation, and functioning, with the pattern more consistent for some measures than others. They also showed small to medium relations with neurocognitive functioning, but were generally unrelated to other psychiatric symptoms, self-reported traits, antipsychotic medications, side effects, and subjective valuation of money. There were relatively strong interrelationships among the effort measures. In conjunction with findings from a companion psychometric article, all the paradigms warrant further consideration and development, and 2 show the strongest potential for clinical trial use at this juncture. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Monoclonal protein reference change value as determined by gel-based serum protein electrophoresis.

PubMed

Salamatmanesh, Mina; McCudden, Christopher R; McCurdy, Arleigh; Booth, Ronald A

2018-01-01

The International Myeloma Working Group recommendations for monitoring disease progression or response include quantitation of the involved monoclonal immunoglobulin. They have defined the minimum change criteria of ≧25% with an absolute change of no <5g/L for either minimal response or progression. Limited evidence is available to accurately determine the magnitude of change in a monoclonal protein to reflect a true change in clinical status. Here we determined the analytical and biological variability of monoclonal proteins in stable monoclonal gammopathy of undetermined significance (MGUS) patients. Analytical variability (CVa) of normal protein fractions and monoclonal proteins were assessed agarose gel-based serum protein electrophoresis. Sixteen clinically stable MGUS patients were identified from our clinical hematology database. Individual biological variability (CVi) was determined and used to calculate a monoclonal protein reference change value (RCV). Analytical variability of the normal protein fractions (albumin, alpha-1, alpha-2, beta, total gamma) ranged from 1.3% for albumin to 5.8% for the alpha-1 globulins. CVa of low (5.6g/L) and high (32.2g/L) concentration monoclonal proteins were 3.1% and 22.2%, respectively. Individual CVi of stable patients ranged from 3.5% to 24.5% with a CVi of 12.9%. The reference change value (RCV) at a 95% probability was determined to be 36.7% (low) 39.6% (high) using our CVa and CVi. Serial monitoring of monoclonal protein concentration is important for MGUS and multiple myeloma patients. Accurate criteria for interpreting a change in monoclonal protein concentration are required for appropriate decision making. We used QC results and real-world conditions to assess imprecision of serum protein fractions including low and high monoclonal protein fractions and clinically stable MGUS patients to determine CVi and RCV. The calculated RCVs of 36.7% (low) and 39.6% (high) in this study were greater that reported previously and greater than the established criteria for relapse. Response criteria may be reassessed to increase sensitivity and specificity for detection of response. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Clinical learning environment and supervision: experiences of Norwegian nursing students - a questionnaire survey.

PubMed

Skaalvik, Mari Wolff; Normann, Hans Ketil; Henriksen, Nils

2011-08-01

To measure nursing students' experiences and satisfaction with their clinical learning environments. The primary interest was to compare the results between students with respect to clinical practice in nursing homes and hospital wards. Clinical learning environments are important for the learning processes of nursing students and for preferences for future workplaces. Working with older people is the least preferred area of practice among nursing students in Norway. A cross-sectional design. A validated questionnaire was distributed to all nursing students from five non-randomly selected university colleges in Norway. A total of 511 nursing students completed a Norwegian version of the questionnaire, Clinical Learning Environment, Supervision and Nurse Teacher (CLES+T) evaluation scale in 2009. Data including descriptive statistics were analysed using the Statistical Program for the Social Sciences. Factor structure was analysed by principal component analysis. Differences across sub-groups were tested with chi-square tests and Mann-Whitney U test for categorical variables and t-tests for continuous variables. Ordinal logistic regression analysis of perceptions of the ward as a good learning environment was performed with supervisory relationships and institutional contexts as independent variables, controlling for age, sex and study year. The participating nursing students with clinical placements in nursing homes assessed their clinical learning environment significantly more negatively than those with hospital placements on nearby all sub-dimensions. The evidence found in this study indicates that measures should be taken to strengthen nursing homes as learning environments for nursing students. To recruit more graduated nurses to work in nursing homes, actions to improve the learning environment are needed. © 2011 Blackwell Publishing Ltd.

General anesthesia suppresses normal heart rate variability in humans

NASA Astrophysics Data System (ADS)

Matchett, Gerald; Wood, Philip

2014-06-01

The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

Central sensitization does not identify patients with carpal tunnel syndrome who are likely to achieve short-term success with physical therapy.

PubMed

Fernández-de-Las-Peñas, César; Cleland, Joshua A; Ortega-Santiago, Ricardo; de-la-Llave-Rincon, Ana Isabel; Martínez-Perez, Almudena; Pareja, Juan A

2010-11-01

The aim of the current study was to identify whether hyperexcitability of the central nervous system is a prognostic factor for individuals with carpal tunnel syndrome (CTS) likely to experience rapid and clinical self-reported improvement following a physical therapy program including soft tissue mobilization and nerve slider neurodynamic interventions. Women presenting with clinical and electrophysiological findings of CTS were involved in a prospective single-arm trial. Participants underwent a standardized examination and then a physical therapy session. The physical therapy sessions included both soft tissue mobilization directed at the anatomical sites of potential median nerve entrapment and a passive nerve slider neurodynamic technique targeted to the median nerve. Pressure pain thresholds (PPT) over the median, radial and ulnar nerves, C5-C6 zygapophyseal joint, carpal tunnel and tibialis anterior muscle were assessed bilaterally. Additionally, thermal detection and pain thresholds were measured over the carpal tunnel and thenar eminence bilaterally to evaluate central nervous system excitability. Subjects were classified as responders (having achieved a successful outcome) or non-responders based on self-perceived recovery. Variables were entered into a stepwise logistic regression model to determine the most accurate variables for determining prognosis. Data from 72 women were included in the analysis, of which 35 experienced a successful outcome (48.6%). Three variables including PPT over the C5-C6 joint affected side <137 kPa, HPT carpal tunnel affected side <39.6º and general health >66 points were identified. If 2 out of 3 variables were present (LR + 14.8), the likelihood of success increased from 48.6 to 93.3%. We identified 3 factors that may be associated with a rapid clinical response to both soft tissue mobilization and nerve slider neurodynamic techniques targeted to the median nerve in women presenting with CTS. Our results support that widespread central sensitization may not be present in women with CTS who are likely to achieve a successful outcome with physical therapy. Future studies are now necessary to validate these findings.

Predictive validity of pre-admission assessments on medical student performance.

PubMed

Dabaliz, Al-Awwab; Kaadan, Samy; Dabbagh, M Marwan; Barakat, Abdulaziz; Shareef, Mohammad Abrar; Al-Tannir, Mohamad; Obeidat, Akef; Mohamed, Ayman

2017-11-24

To examine the predictive validity of pre-admission variables on students' performance in a medical school in Saudi Arabia. In this retrospective study, we collected admission and college performance data for 737 students in preclinical and clinical years. Data included high school scores and other standardized test scores, such as those of the National Achievement Test and the General Aptitude Test. Additionally, we included the scores of the Test of English as a Foreign Language (TOEFL) and the International English Language Testing System (IELTS) exams. Those datasets were then compared with college performance indicators, namely the cumulative Grade Point Average (cGPA) and progress test, using multivariate linear regression analysis. In preclinical years, both the National Achievement Test (p=0.04, B=0.08) and TOEFL (p=0.017, B=0.01) scores were positive predictors of cGPA, whereas the General Aptitude Test (p=0.048, B=-0.05) negatively predicted cGPA. Moreover, none of the pre-admission variables were predictive of progress test performance in the same group. On the other hand, none of the pre-admission variables were predictive of cGPA in clinical years. Overall, cGPA strongly predict-ed students' progress test performance (p<0.001 and B=19.02). Only the National Achievement Test and TOEFL significantly predicted performance in preclinical years. However, these variables do not predict progress test performance, meaning that they do not predict the functional knowledge reflected in the progress test. We report various strengths and deficiencies in the current medical college admission criteria, and call for employing more sensitive and valid ones that predict student performance and functional knowledge, especially in the clinical years.

Predictive validity of pre-admission assessments on medical student performance

PubMed Central

Dabaliz, Al-Awwab; Kaadan, Samy; Dabbagh, M. Marwan; Barakat, Abdulaziz; Shareef, Mohammad Abrar; Al-Tannir, Mohamad; Obeidat, Akef

2017-01-01

Objectives To examine the predictive validity of pre-admission variables on students’ performance in a medical school in Saudi Arabia.  Methods In this retrospective study, we collected admission and college performance data for 737 students in preclinical and clinical years. Data included high school scores and other standardized test scores, such as those of the National Achievement Test and the General Aptitude Test. Additionally, we included the scores of the Test of English as a Foreign Language (TOEFL) and the International English Language Testing System (IELTS) exams. Those datasets were then compared with college performance indicators, namely the cumulative Grade Point Average (cGPA) and progress test, using multivariate linear regression analysis. Results In preclinical years, both the National Achievement Test (p=0.04, B=0.08) and TOEFL (p=0.017, B=0.01) scores were positive predictors of cGPA, whereas the General Aptitude Test (p=0.048, B=-0.05) negatively predicted cGPA. Moreover, none of the pre-admission variables were predictive of progress test performance in the same group. On the other hand, none of the pre-admission variables were predictive of cGPA in clinical years. Overall, cGPA strongly predict-ed students’ progress test performance (p<0.001 and B=19.02). Conclusions Only the National Achievement Test and TOEFL significantly predicted performance in preclinical years. However, these variables do not predict progress test performance, meaning that they do not predict the functional knowledge reflected in the progress test. We report various strengths and deficiencies in the current medical college admission criteria, and call for employing more sensitive and valid ones that predict student performance and functional knowledge, especially in the clinical years. PMID:29176032

Predictive factors for clinically actionable computed tomography findings in inflammatory bowel disease patients seen in the emergency department with acute gastrointestinal symptoms.

PubMed

Yarur, Andres J; Mandalia, Amar B; Dauer, Ryan M; Czul, Frank; Deshpande, Amar R; Kerman, David H; Abreu, Maria T; Sussman, Daniel A

2014-06-01

The wide use of abdomino-pelvic computed tomography (APCT) in emergency departments (ED) has raised the concern for radiation exposure, costs and potential reactions to contrast agents. The aim of this study was to determine the yield and predictive factors for clinically actionable findings (CAF) in APCTs performed in patients with inflammatory bowel disease (IBD) who visit the ED. We performed a cross-sectional study including patients with IBD who visited the ED. Variables considered were demographics, IBD phenotype, clinical symptoms, IBD medication use prior to ED visit, laboratory values, and imaging results. The primary outcome was a composite of CAF, defined as new, intra-abdominal abscess or tumor, bowel obstruction, fistulae, diverticulitis, choledocholithiasis, or appendicitis. 354 patients were included. One or more CAF were reported in 26.6% of the APCTs (32.1% in CD and 12.8% in UC [p<0.01]). Independent predictive variables of CAF in CD were: CRP level ≥5mg/dl (p=0.04), previous history of IBD surgery (p=0.037), Black race (p<0.01) and low body mass index (p<0.01). None of the study variables predicted CAF in UC. The yield for CAF with APCT in the ED was high for CD patients but minimal for those with UC and was not improved by the use of contrast. Elevated CRP, low BMI, Black race and previous history of IBD surgery predicted CAF in CD but no variables were predictive of CAF in UC. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Single neuropsychological test scores associated with rate of cognitive decline in early Alzheimer disease.

PubMed

Parikh, Mili; Hynan, Linda S; Weiner, Myron F; Lacritz, Laura; Ringe, Wendy; Cullum, C Munro

2014-01-01

Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in the rate of cognitive decline. For research and clinical purposes it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate. Our objective was to use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in participants with mild AD. We reviewed the records of a series of 96 consecutive participants with mild AD from 1995 to 2011 who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over 2 years, participants were classified as Faster (n = 45) or Slower (n = 51) Progressors. Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed. Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups. Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression.

Prediction of clinical depression scores and detection of changes in whole-brain using resting-state functional MRI data with partial least squares regression

PubMed Central

Shimizu, Yu; Yoshimoto, Junichiro; Takamura, Masahiro; Okada, Go; Okamoto, Yasumasa; Yamawaki, Shigeto; Doya, Kenji

2017-01-01

In diagnostic applications of statistical machine learning methods to brain imaging data, common problems include data high-dimensionality and co-linearity, which often cause over-fitting and instability. To overcome these problems, we applied partial least squares (PLS) regression to resting-state functional magnetic resonance imaging (rs-fMRI) data, creating a low-dimensional representation that relates symptoms to brain activity and that predicts clinical measures. Our experimental results, based upon data from clinically depressed patients and healthy controls, demonstrated that PLS and its kernel variants provided significantly better prediction of clinical measures than ordinary linear regression. Subsequent classification using predicted clinical scores distinguished depressed patients from healthy controls with 80% accuracy. Moreover, loading vectors for latent variables enabled us to identify brain regions relevant to depression, including the default mode network, the right superior frontal gyrus, and the superior motor area. PMID:28700672

Electronic Cigarettes for Smoking Cessation.

PubMed

Orellana-Barrios, Menfil A; Payne, Drew; Medrano-Juarez, Rita M; Yang, Shengping; Nugent, Kenneth

2016-10-01

The use of electronic cigarettes (e-cigarettes) is increasing, but their use as a smoking-cessation aid is controversial. The reporting of e-cigarette studies on cessation is variable and inconsistent. To date, only 1 randomized clinical trial has included an arm with other cessation methods (nicotine patches). The cessation rates for available clinical trials are difficult to compare given differing follow-up periods and broad ranges (4% at 12 months with non-nicotine e-cigarettes to 68% at 4 weeks with concomitant nicotine e-cigarettes and other cessation methods). The average combined abstinence rate for included prospective studies was 29.1% (combination of 6-18 months׳ rates). There are few comparable clinical trials and prospective studies related to e-cigarettes use for smoking cessation, despite an increasing number of citations. Larger randomized clinical trials are essential to determine whether e-cigarettes are effective smoking-cessation devices. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Systematic review of the neural basis of social cognition in patients with mood disorders.

PubMed

Cusi, Andrée M; Nazarov, Anthony; Holshausen, Katherine; Macqueen, Glenda M; McKinnon, Margaret C

2012-05-01

This review integrates neuroimaging studies of 2 domains of social cognition--emotion comprehension and theory of mind (ToM)--in patients with major depressive disorder and bipolar disorder. The influence of key clinical and method variables on patterns of neural activation during social cognitive processing is also examined. Studies were identified using PsycINFO and PubMed (January 1967 to May 2011). The search terms were "fMRI," "emotion comprehension," "emotion perception," "affect comprehension," "affect perception," "facial expression," "prosody," "theory of mind," "mentalizing" and "empathy" in combination with "major depressive disorder," "bipolar disorder," "major depression," "unipolar depression," "clinical depression" and "mania." Taken together, neuroimaging studies of social cognition in patients with mood disorders reveal enhanced activation in limbic and emotion-related structures and attenuated activity within frontal regions associated with emotion regulation and higher cognitive functions. These results reveal an overall lack of inhibition by higher-order cognitive structures on limbic and emotion-related structures during social cognitive processing in patients with mood disorders. Critically, key variables, including illness burden, symptom severity, comorbidity, medication status and cognitive load may moderate this pattern of neural activation. Studies that did not include control tasks or a comparator group were included in this review. Further work is needed to examine the contribution of key moderator variables and to further elucidate the neural networks underlying altered social cognition in patients with mood disorders. The neural networks under lying higher-order social cognitive processes, including empathy, remain unexplored in patients with mood disorders.

Atypical Reactivity of Heart Rate Variability to Stress and Depression: Systematic Review of the Literature and Directions for Future Research

PubMed Central

Hamilton, Jessica L.; Alloy, Lauren B.

2017-01-01

Heart rate variability has received growing attention in the depression literature, with several recent meta-analyses indicating that lower resting heart rate variability is associated with depression. However, the role of fluctuations in heart rate variability (or reactivity) in response to stress in depression remains less clear. The present review provides a systematic examination of the literature on heart rate variability reactivity to a laboratory-induced stressor task and depression, including 26 studies of reactivity in heart rate variability and clinical depression, remitted (or history of) depression, and subthreshold depression (or symptom-level depression) among adults, adolescents, and children. In addition to reviewing the findings of these studies, methodological considerations and conceptual gaps in the literature are addressed. We conclude by highlighting the importance of investigating the potential transactional relationship between heart rate variability reactivity and depression and possible mechanisms underlying this relationship. PMID:27697746

Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease.

PubMed

Lindholm, Daniel; Lindbäck, Johan; Armstrong, Paul W; Budaj, Andrzej; Cannon, Christopher P; Granger, Christopher B; Hagström, Emil; Held, Claes; Koenig, Wolfgang; Östlund, Ollie; Stewart, Ralph A H; Soffer, Joseph; White, Harvey D; de Winter, Robbert J; Steg, Philippe Gabriel; Siegbahn, Agneta; Kleber, Marcus E; Dressel, Alexander; Grammer, Tanja B; März, Winfried; Wallentin, Lars

2017-08-15

Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD). This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD. In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study. During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This "ABC-CHD" model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts. This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Linear data mining the Wichita clinical matrix suggests sleep and allostatic load involvement in chronic fatigue syndrome.

PubMed

Gurbaxani, Brian M; Jones, James F; Goertzel, Benjamin N; Maloney, Elizabeth M

2006-04-01

To provide a mathematical introduction to the Wichita (KS, USA) clinical dataset, which is all of the nongenetic data (no microarray or single nucleotide polymorphism data) from the 2-day clinical evaluation, and show the preliminary findings and limitations, of popular, matrix algebra-based data mining techniques. An initial matrix of 440 variables by 227 human subjects was reduced to 183 variables by 164 subjects. Variables were excluded that strongly correlated with chronic fatigue syndrome (CFS) case classification by design (for example, the multidimensional fatigue inventory [MFI] data), that were otherwise self reporting in nature and also tended to correlate strongly with CFS classification, or were sparse or nonvarying between case and control. Subjects were excluded if they did not clearly fall into well-defined CFS classifications, had comorbid depression with melancholic features, or other medical or psychiatric exclusions. The popular data mining techniques, principle components analysis (PCA) and linear discriminant analysis (LDA), were used to determine how well the data separated into groups. Two different feature selection methods helped identify the most discriminating parameters. Although purely biological features (variables) were found to separate CFS cases from controls, including many allostatic load and sleep-related variables, most parameters were not statistically significant individually. However, biological correlates of CFS, such as heart rate and heart rate variability, require further investigation. Feature selection of a limited number of variables from the purely biological dataset produced better separation between groups than a PCA of the entire dataset. Feature selection highlighted the importance of many of the allostatic load variables studied in more detail by Maloney and colleagues in this issue [1] , as well as some sleep-related variables. Nonetheless, matrix linear algebra-based data mining approaches appeared to be of limited utility when compared with more sophisticated nonlinear analyses on richer data types, such as those found in Maloney and colleagues [1] and Goertzel and colleagues [2] in this issue.

A Prediction Algorithm for Drug Response in Patients with Mesial Temporal Lobe Epilepsy Based on Clinical and Genetic Information

PubMed Central

Carvalho, Benilton S.; Bilevicius, Elizabeth; Alvim, Marina K. M.; Lopes-Cendes, Iscia

2017-01-01

Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy. For this, we divided 237 patients into two groups: 75 responsive and 162 refractory to antiepileptic drug therapy. We genotyped 119 SNPs in ABCB1, ABCC2, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5 genes. We used 98 additional SNPs to evaluate population stratification. We assessed a first scenario using only clinical variables and a second one including SNP information. The random forests algorithm combined with leave-one-out cross-validation was used to identify the best predictive model in each scenario and compared their accuracies using the area under the curve statistic. Additionally, we built a variable importance plot to present the set of most relevant predictors on the best model. The selected best model included the presence of hippocampal sclerosis and 56 SNPs. Furthermore, including SNPs in the model improved accuracy from 0.4568 to 0.8177. Our findings suggest that adding genetic information provided by SNPs, located on drug transport and metabolism genes, can improve the accuracy for predicting which patients with mesial temporal lobe epilepsy are likely to be refractory to drug treatment, making it possible to identify patients who may benefit from epilepsy surgery sooner. PMID:28052106

A method for developing outcome measures in the clinical laboratory.

PubMed

Jones, J

1996-01-01

Measuring and reporting outcomes in health care is becoming more important for quality assessment, utilization assessment, accreditation standards, and negotiating contracts in managed care. How does one develop an outcome measure for the laboratory to assess the value of the services? A method is described which outlines seven steps in developing outcome measures for a laboratory service or process. These steps include the following: 1. Identify the process or service to be monitored for performance and outcome assessment. 2. If necessary, form an multidisciplinary team of laboratory staff, other department staff, physicians, and pathologists. 3. State the purpose of the test or service including a review of published data for the clinical pathological correlation. 4. Prepare a process cause and effect diagram including steps critical to the outcome. 5. Identify key process variables that contribute to positive or negative outcomes. 6. Identify outcome measures that are not process measures. 7. Develop an operational definition, identify data sources, and collect data. Examples, including a process cause and effect diagram, process variables, and outcome measures, are given using the Therapeutic Drug Monitoring service (TDM). A summary of conclusions and precautions for outcome measurement is then provided.

Advanced statistics: linear regression, part I: simple linear regression.

PubMed

Marill, Keith A

2004-01-01

Simple linear regression is a mathematical technique used to model the relationship between a single independent predictor variable and a single dependent outcome variable. In this, the first of a two-part series exploring concepts in linear regression analysis, the four fundamental assumptions and the mechanics of simple linear regression are reviewed. The most common technique used to derive the regression line, the method of least squares, is described. The reader will be acquainted with other important concepts in simple linear regression, including: variable transformations, dummy variables, relationship to inference testing, and leverage. Simplified clinical examples with small datasets and graphic models are used to illustrate the points. This will provide a foundation for the second article in this series: a discussion of multiple linear regression, in which there are multiple predictor variables.

Risk factors for early post-operative neurological deterioration in dogs undergoing a cervical dorsal laminectomy or hemilaminectomy: 100 cases (2002-2014).

PubMed

Taylor-Brown, F E; Cardy, T J A; Liebel, F X; Garosi, L; Kenny, P J; Volk, H A; De Decker, S

2015-12-01

Early post-operative neurological deterioration is a well-known complication following dorsal cervical laminectomies and hemilaminectomies in dogs. This study aimed to evaluate potential risk factors for early post-operative neurological deterioration following these surgical procedures. Medical records of 100 dogs that had undergone a cervical dorsal laminectomy or hemilaminectomy between 2002 and 2014 were assessed retrospectively. Assessed variables included signalment, bodyweight, duration of clinical signs, neurological status before surgery, diagnosis, surgical site, type and extent of surgery and duration of procedure. Outcome measures were neurological status immediately following surgery and duration of hospitalisation. Univariate statistical analysis was performed to identify variables to be included in a multivariate model. Diagnoses included osseous associated cervical spondylomyelopathy (OACSM; n = 41), acute intervertebral disk extrusion (IVDE; 31), meningioma (11), spinal arachnoid diverticulum (10) and vertebral arch anomalies (7). Overall 54% (95% CI 45.25-64.75) of dogs were neurologically worse 48 h post-operatively. Multivariate statistical analysis identified four factors significantly related to early post-operative neurological outcome. Diagnoses of OACSM or meningioma were considered the strongest variables to predict early post-operative neurological deterioration, followed by higher (more severely affected) neurological grade before surgery and longer surgery time. This information can aid in the management of expectations of clinical staff and owners with dogs undergoing these surgical procedures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical Audit of the Radiotherapy Process in Rectal Cancer: Clinical Practice Guidelines and Quality Certification Do Not Avert Variability in Clinical Practice.

PubMed

Torras, M G; Canals, E; Jurado-Bruggeman, D; Marín-Borras, S; Macià, M; Jové, J; Boladeras, A M; Muñoz-Montplet, C; Molero, J; Picón, C; Puigdemont, M; Aliste, L; Torrents, A; Guedea, F; Borras, J M

2018-06-01

The therapeutic approach to cancer is complex and multidisciplinary. Radiotherapy is among the essential treatments, whether used alone or in conjunction with other therapies. This study reports a clinical audit of the radiotherapy process to assess the process of care, evaluate adherence to agreed protocols and measure the variability to improve therapeutic quality for rectal cancer. Multicentre retrospective cohort study in a representative sample of patients diagnosed with rectal cancer in the Institut Català d'Oncologia, a comprehensive cancer centre with three different settings. We developed a set of indicators to assess the key areas of the radiotherapy process. The clinical audit consisted of a review of a random sample of 40 clinical histories for each centre. The demographic profile, histology and staging of patients were similar between centres. The MRI reports did not include the distance from tumour to mesorectal fascia (rCRM) in 38.3% of the cases. 96.7% of patients received the planned dose, and 57.4% received it at the planned time. Surgery followed neoadjuvant treatment in 96.7% of the patients. Among this group, postoperative CRM was recorded in 65.5% of the cases and was negative in 93.4% of these. With regard to the 34.5% (n = 40) of cases where no CRM value was stated, there were differences between the centres. Mean follow-up was 3.4 (SD 0.6) years, and overall survival at four years was 81.7%. The audit revealed a suboptimal degree of adherence to clinical practice guidelines. Significant variability between centres exists from a clinical perspective but especially with regard to organization and process. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Implementation and utilization of genetic testing in personalized medicine

PubMed Central

Abul-Husn, Noura S; Owusu Obeng, Aniwaa; Sanderson, Saskia C; Gottesman, Omri; Scott, Stuart A

2014-01-01

Clinical genetic testing began over 30 years ago with the availability of mutation detection for sickle cell disease diagnosis. Since then, the field has dramatically transformed to include gene sequencing, high-throughput targeted genotyping, prenatal mutation detection, preimplantation genetic diagnosis, population-based carrier screening, and now genome-wide analyses using microarrays and next-generation sequencing. Despite these significant advances in molecular technologies and testing capabilities, clinical genetics laboratories historically have been centered on mutation detection for Mendelian disorders. However, the ongoing identification of deoxyribonucleic acid (DNA) sequence variants associated with common diseases prompted the availability of testing for personal disease risk estimation, and created commercial opportunities for direct-to-consumer genetic testing companies that assay these variants. This germline genetic risk, in conjunction with other clinical, family, and demographic variables, are the key components of the personalized medicine paradigm, which aims to apply personal genomic and other relevant data into a patient’s clinical assessment to more precisely guide medical management. However, genetic testing for disease risk estimation is an ongoing topic of debate, largely due to inconsistencies in the results, concerns over clinical validity and utility, and the variable mode of delivery when returning genetic results to patients in the absence of traditional counseling. A related class of genetic testing with analogous issues of clinical utility and acceptance is pharmacogenetic testing, which interrogates sequence variants implicated in interindividual drug response variability. Although clinical pharmacogenetic testing has not previously been widely adopted, advances in rapid turnaround time genetic testing technology and the recent implementation of preemptive genotyping programs at selected medical centers suggest that personalized medicine through pharmacogenetics is now a reality. This review aims to summarize the current state of implementing genetic testing for personalized medicine, with an emphasis on clinical pharmacogenetic testing. PMID:25206309

US Intergroup Anal Carcinoma Trial: Tumor Diameter Predicts for Colostomy

PubMed Central

Ajani, Jaffer A.; Winter, Kathryn A.; Gunderson, Leonard L.; Pedersen, John; Benson, Al B.; Thomas, Charles R.; Mayer, Robert J.; Haddock, Michael G.; Rich, Tyvin A.; Willett, Christopher G.

2009-01-01

Purpose The US Gastrointestinal Intergroup Radiation Therapy Oncology Group 98-11 anal carcinoma trial showed that cisplatin-based concurrent chemoradiotherapy resulted in a significantly higher rate of colostomy compared with mitomycin-based therapy. Established prognostic variables for patients with anal carcinoma include tumor diameter, clinical nodal status, and sex, but pretreatment variables that would predict the likelihood of colostomy are unknown. Methods A secondary analysis was performed by combining patients in the two treatment arms to evaluate whether new predictive and prognostic variables would emerge. Univariate and multivariate analyses were carried out to correlate overall survival (OS), disease-free survival, and time to colostomy (TTC) with pretreatment and treatment variables. Results Of 682 patients enrolled, 644 patients were assessable and analyzed. In the multivariate analysis, tumor-related prognosticators for poorer OS included node-positive cancer (P ≤ .0001), large (> 5 cm) tumor diameter (P = .01), and male sex (P = .016). In the treatment-related categories, cisplatin-based therapy was statistically significantly associated with a higher rate of colostomy (P = .03) than was mitomycin-based therapy. In the pretreatment variables category, only large tumor diameter independently predicted for TTC (P = .008). Similarly, the cumulative 5-year colostomy rate was statistically significantly higher for large tumor diameter than for small tumor diameter (Gray's test; P = .0074). Clinical nodal status and sex were not predictive of TTC. Conclusion The combined analysis of the two arms of RTOG 98-11, representing the largest prospective database, reveals that tumor diameter (irrespective of the nodal status) is the only independent pretreatment variable that predicts TTC and 5-year colostomy rate in patients with anal carcinoma. PMID:19139424

Heart rate variability in patients with systemic lupus erythematosus: a systematic review and methodological considerations.

PubMed

Matusik, P S; Matusik, P T; Stein, P K

2018-07-01

Aim The aim of this review was to summarize current knowledge about the scientific findings and potential clinical utility of heart rate variability measures in patients with systemic lupus erythematosus. Methods PubMed, Embase and Scopus databases were searched for the terms associated with systemic lupus erythematosus and heart rate variability, including controlled vocabulary, when appropriate. Articles published in English and available in full text were considered. Finally, 11 publications were selected, according to the systematic review protocol and were analyzed. Results In general, heart rate variability, measured in the time and frequency domains, was reported to be decreased in patients with systemic lupus erythematosus compared with controls. In some systemic lupus erythematosus studies, heart rate variability was found to correlate with inflammatory markers and albumin levels. A novel heart rate variability measure, heart rate turbulence onset, was shown to be increased, while heart rate turbulence slope was decreased in systemic lupus erythematosus patients. Reports of associations of changes in heart rate variability parameters with increasing systemic lupus erythematosus activity were inconsistent, showing decreasing heart rate variability or no relationship. However, the low/high frequency ratio was, in some studies, reported to increase with increasing disease activity or to be inversely correlated with albumin levels. Conclusions Patients with systemic lupus erythematosus have abnormal heart rate variability, which reflects cardiac autonomic dysfunction and may be related to inflammatory cytokines but not necessarily to disease activity. Thus measurement of heart rate variability could be a useful clinical tool for monitoring autonomic dysfunction in systemic lupus erythematosus, and may potentially provide prognostic information.

Twenty-four-hour ambulatory electrocardiography characterization of heart rhythm in Vipera berus-envenomed dogs.

PubMed

Vestberg, Anna Rave; Tidholm, Anna; Ljungvall, Ingrid

2017-05-03

Vipera berus has a worldwide distribution and causes high morbidity in dogs annually. A complication to envenomation may be cardiac arrhythmias. The purpose of this study was to investigate the prevalence, types, and timing of arrhythmias, using 24-h ambulatory electrocardiography (24-AECG), in dogs bitten by V. berus in the first 24-32 h after envenomation. In addition, this study aimed to investigate if there were differences in selected clinical and hematological- and biochemical variables (including cardiac troponin I) at admission between V. berus-envenomed dogs with and without detected pathologic arrhythmias. Seventeen prospectively recruited client-owned dogs acutely envenomed by V. berus, were therefore examined clinically and echocardiographically, sampled for blood, hospitalized, and monitored by 24-AECG. Clinically significant pathologic arrhythmias in this study were of ventricular origin, such as frequent single ventricular premature contractions (VPCs) and couplets of VPCs, episodes of ventricular tachycardia and idioventricular rhythm, and "R-on-T phenomenon". Variations of these arrhythmias were detected by 24-AECG in eight (47%) of included dogs. No arrhythmias were detected by cardiac auscultation. Twenty-four hours following envenomation, four out of eight dogs experienced decreases (all P < 0.039), and three out of eight dogs experienced increases (all P < 0.034), in arrhythmic episodes. All four dogs bitten on a limb developed pathologic arrhythmias. Otherwise, no significant differences in clinical, hematological or biochemical variables were seen between dogs with pathologic arrhythmias and those without. Forty-seven percent of dogs bitten by V. berus included in this study experienced pathologic arrhythmias of abnormal ventricular depolarization. During the first 24-32 h from the snakebite, some dogs experienced a decrease in arrhythmic episodes and others an increase in arrhythmic episodes. These findings indicate a potential value of repeated or prolonged electrocardiography monitoring of envenomed dogs for identification of which dogs that might benefit the most from prolonged hospitalization for optimal monitoring and treatment of cardiac abnormalities. In the present study, dogs that developed arrhythmias could not be differentiated from dogs that did not based on clinical findings or hematological or biochemical variables obtained at admission.

Prospective memory, level of disability, and return to work in severe mental illness.

PubMed

Burton, Cynthia Z; Vella, Lea; Twamley, Elizabeth W

2018-02-25

Prospective memory (the ability to remember to do things) has clear implications for everyday functioning, including employment, in people with severe mental illnesses (SMI). This study aimed to evaluate prospective memory performance and its relationship to real-world functional variables in an employment-seeking sample of people with SMI (Clinical Trial registration number NCT00895258). 153 individuals with DSM-IV diagnosis of depression (n = 58), bipolar disorder (n = 37), or schizophrenia (n = 58) who were receiving outpatient psychiatric care at a university clinic enrolled in a trial of supported employment and completed a baseline assessment. Prospective memory was measured with the Memory for Intentions Test (MIST); real-world functional status included work history variables, clinical history variables, baseline functional capacity (UCSD Performance-based Skills Assessment-Brief), and work outcomes (weeks worked and wages earned during two years of supported employment). Participants with schizophrenia performed worse on the MIST than did those with affective disorders. Independent of diagnosis, education, and estimated intellectual functioning, prospective memory significantly predicted variance in measures of disability and illness burden (disability benefits, hospitalization history, current functional capacity), and work outcomes over two years of supported employment (weeks worked). Worse prospective memory appears to be associated with greater illness burden and functional disability in SMI. Mental health clinicians and employment specialists may counsel clients to use compensatory prospective memory strategies to improve work performance and decrease functional disability associated with SMI.

Sub-Optimal Treatment of Bacterial Biofilms

PubMed Central

Song, Tianyan; Duperthuy, Marylise; Wai, Sun Nyunt

2016-01-01

Bacterial biofilm is an emerging clinical problem recognized in the treatment of infectious diseases within the last two decades. The appearance of microbial biofilm in clinical settings is steadily increasing due to several reasons including the increased use of quality of life-improving artificial devices. In contrast to infections caused by planktonic bacteria that respond relatively well to standard antibiotic therapy, biofilm-forming bacteria tend to cause chronic infections whereby infections persist despite seemingly adequate antibiotic therapy. This review briefly describes the responses of biofilm matrix components and biofilm-associated bacteria towards sub-lethal concentrations of antimicrobial agents, which may include the generation of genetic and phenotypic variabilities. Clinical implications of bacterial biofilms in relation to antibiotic treatments are also discussed. PMID:27338489

Predictors of physical and mental health-related quality of life outcomes among myocardial infarction patients

PubMed Central

2013-01-01

Background Health-related quality of life (HRQoL) is an important outcome for patients diagnosed with coronary heart disease. This report describes predictors of physical and mental HRQoL at six months post-hospitalisation for myocardial infarction. Methods Participants were myocardial infarction patients (n=430) admitted to two tertiary referral centres in Brisbane, Australia who completed a six month coronary heart disease secondary prevention trial (ProActive Heart). Outcome variables were HRQoL (Short Form-36) at six months, including a physical and mental summary score. Baseline predictors included demographics and clinical variables, health behaviours, and psychosocial variables. Stepwise forward multiple linear regression analyses were used to identify significant independent predictors of six month HRQoL. Results Physical HRQoL was lower in participants who: were older (p<0.001); were unemployed (p=0.03); had lower baseline physical and mental HRQoL scores (p<0.001); had lower confidence levels in meeting sufficient physical activity recommendations (p<0.001); had no intention to be physically active in the next six months (p<0.001); and were more sedentary (p=0.001). Mental HRQoL was lower in participants who: were younger (p=0.01); had lower baseline mental HRQoL (p<0.001); were more sedentary (p=0.01) were depressed (p<0.001); and had lower social support (p=0.001). Conclusions This study has clinical implications as identification of indicators of lower physical and mental HRQoL outcomes for myocardial infarction patients allows for targeted counselling or coronary heart disease secondary prevention efforts. Trial registration Australian Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, CTRN12607000595415. PMID:24020831

Clinical trials with velnacrine: (PROPP) the physician reference of predicted probabilities--a statistical model for the estimation of hepatotoxicity risk with velnacrine maleate.

PubMed

Hardiman, S; Miller, K; Murphy, M

1993-01-01

Safety observations during the clinical development of Mentane (velnacrine maleate) have included the occurrence of generally asymptomatic liver enzyme elevations confined to patients with Alzheimer's disease (AD). The clinical presentation of this reversible hepatocellular injury is analogous to that reported for tetrahydroaminoacridine (THA). Direct liver injury, possibly associated with the production of a toxic metabolite, would be consistent with reports of aberrant xenobiotic metabolism in Alzheimer's disease patients. Since a patient related aberration in drug metabolism was suspected, a biostatistical strategy was developed with the objective of predicting hepatotoxicity in individual patients prior to exposure to velnacrine maleate. The method used logistic regression techniques with variable selection restricted to those items which could be routinely and inexpensively accessed at screen evaluation for potential candidates for treatment. The model was to be predictive (a marker for eventual hepatotoxicity) rather than a causative model, and techniques employed "goodness of fit", percentage correct, and positive and negative predictive values. On the basis of demographic and baseline laboratory data from 942 patients, the PROPP statistic was developed (the Physician Reference Of Predicted Probabilities). Main effect variables included age, gender, and nine hematological and serum chemistry variables. The sensitivity of the current model is approximately 49%, specificity approximately 88%. Using prior probability estimates, however, in which the patient's likelihood of liver toxicity is presumed to be at least 30%, the positive predictive value ranged between 64-77%. Although the clinical utility of this statistic will require refinements and additional prospective confirmation, its potential existence speaks to the possibility of markers for idiosyncratic drug metabolism in patients with Alzheimer's disease.

Preferential Cyclooxygenase 2 Inhibitors as a Nonhormonal Method of Emergency Contraception: A Look at the Evidence.

PubMed

Weiss, Erich A; Gandhi, Mona

2016-04-01

To review the literature surrounding the use of preferential cyclooxygenase 2 (COX-2) inhibitors as an alternative form of emergency contraception. MEDLINE (1950 to February 2014) was searched using the key words cyclooxygenase or COX-2 combined with contraception, emergency contraception, or ovulation. Results were limited to randomized control trials, controlled clinical trials, and clinical trials. Human trials that measured the effects of COX inhibition on female reproductive potential were included for review. The effects of the COX-2 inhibitors rofecoxib, celecoxib, and meloxicam were evaluated in 6 trials. Each of which was small in scope, enrolled women of variable fertility status, used different dosing regimens, included multiple end points, and had variable results. Insufficient evidence exists to fully support the use of preferential COX-2 inhibitors as a form of emergency contraception. Although all trials resulted in a decrease in ovulatory cycles, outcomes varied between dosing strategies and agents used. A lack of homogeneity in these studies makes comparisons difficult. However, success of meloxicam in multiple trials warrants further study. Larger human trials are necessary before the clinical utility of this method of emergency contraception can be fully appreciated. © The Author(s) 2014.

Gait impairment precedes clinical symptoms in spinocerebellar ataxia type 6.

PubMed

Rochester, Lynn; Galna, Brook; Lord, Sue; Mhiripiri, Dadirayi; Eglon, Gail; Chinnery, Patrick F

2014-02-01

Spinocerebellar ataxia type 6 (SCA6) is an inherited ataxia with no established treatment. Gait ataxia is a prominent feature causing substantial disability. Understanding the evolution of the gait disturbance is a key step in developing treatment strategies. We studied 9 gait variables in 24 SCA6 (6 presymptomatic; 18 symptomatic) and 24 controls and correlated gait with clinical severity (presymptomatic and symptomatic). Discrete gait characteristics precede symptoms in SCA6 with significantly increased variability of step width and step time, whereas a more global gait deficit was evident in symptomatic individuals. Gait characteristics discriminated between presymptomatic and symptomatic individuals and were selectively associated with disease severity. This is the largest study to include a detailed characterization of gait in SCA6, including presymptomatic subjects, allowing changes across the disease spectrum to be compared. Selective gait disturbance is already present in SCA6 before clinical symptoms appear and gait characteristics are also sensitive to disease progression. Early gait disturbance likely reflects primary pathology distinct from secondary changes. These findings open the opportunity for early evaluation and sensitive measures of therapeutic efficacy using instrumented gait analysis which may have broader relevance for all degenerative ataxias. © 2013 Movement Disorder Society.

[Clinical factors associated with invasive pulmonary aspergillosis in patients with chronic pneumopathies and respiratory isolation of Aspergillus spp].

PubMed

Castón, Juan José; Linares, María José; Rivero, Antonio; Casal, Manuel; Torre-Cisneros, Julián

2012-12-15

To determine clinical variables to distinguish invasive pulmonary aspergillosis (IPA) from colonization in patients with chronic pneumopathies with positive culture of Aspergillus spp. in respiratory samples. Retrospective cohort study including patients with respiratory isolations of Aspergillus spp. during a period of 10 years. IPA was evaluated according to the Bulpa criteria. Clinical variables were collected and a multiple logistic regression analysis was carried out. Eighty-three patients with isolation of Aspergillus spp. from respiratory samples were included; 68.7% (n=57) of the patients had chronic obstructive pulmonary disease, 18% (n=15) pulmonary fibrosis and 13.3% (n=11) bronchial asthma. Twenty-two patients (26.6%) had IPA. The use of fluconazole (OR 4.49; CI 95% 1.5-13.4; P=.007), severe respiratory failure (OR 4.64; CI 95% 1.46-14.72; P=.009) and hospitalization time (OR 1.05; CI 95% 1.01-1.1; P=.006) were associated with IPA. Prior use of fluconazole, severe respiratory failure and hospitalization time are associated with IPA in patients with chronic pneumopathies with respiratory isolation of Aspergillus spp. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Biasogram: Visualization of Confounding Technical Bias in Gene Expression Data

PubMed Central

Krzystanek, Marcin; Szallasi, Zoltan; Eklund, Aron C.

2013-01-01

Gene expression profiles of clinical cohorts can be used to identify genes that are correlated with a clinical variable of interest such as patient outcome or response to a particular drug. However, expression measurements are susceptible to technical bias caused by variation in extraneous factors such as RNA quality and array hybridization conditions. If such technical bias is correlated with the clinical variable of interest, the likelihood of identifying false positive genes is increased. Here we describe a method to visualize an expression matrix as a projection of all genes onto a plane defined by a clinical variable and a technical nuisance variable. The resulting plot indicates the extent to which each gene is correlated with the clinical variable or the technical variable. We demonstrate this method by applying it to three clinical trial microarray data sets, one of which identified genes that may have been driven by a confounding technical variable. This approach can be used as a quality control step to identify data sets that are likely to yield false positive results. PMID:23613961

gHRV: Heart rate variability analysis made easy.

PubMed

Rodríguez-Liñares, L; Lado, M J; Vila, X A; Méndez, A J; Cuesta, P

2014-08-01

In this paper, the gHRV software tool is presented. It is a simple, free and portable tool developed in python for analysing heart rate variability. It includes a graphical user interface and it can import files in multiple formats, analyse time intervals in the signal, test statistical significance and export the results. This paper also contains, as an example of use, a clinical analysis performed with the gHRV tool, namely to determine whether the heart rate variability indexes change across different stages of sleep. Results from tests completed by researchers who have tried gHRV are also explained: in general the application was positively valued and results reflect a high level of satisfaction. gHRV is in continuous development and new versions will include suggestions made by testers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Addressing the Needs of Preschool Children in the Context of Disasters and Terrorism: Clinical Pictures and Moderating Factors.

PubMed

Hamiel, Daniel; Wolmer, Leo; Pardo-Aviv, Lee; Laor, Nathaniel

2017-07-01

This paper surveys the existent theoretical and research literature regarding the needs of preschool children in the context of disasters and terrorism with the aim of understanding (a) the consequences of such events for young children and (b) the main moderating variables influencing the event-consequence association to learn how to enhance their resilience. Consequences include a variety of emotional, behavioral, and biological outcomes. Implications for refugee children are discussed. Main moderating variables were mother's sensitivity and mother's PTSD symptoms. Exposure to disasters and terrorism may have severe effects on the mental health and development among preschool children. Future research should explore the implications of different levels of exposure and the effects of moderating psychosocial and biological variables, including the parent-child triad, on the event-consequence relationship.

Optimizing the Anti-VEGF Treatment Strategy for Neovascular Age-Related Macular Degeneration: From Clinical Trials to Real-Life Requirements.

PubMed

Mantel, Irmela

2015-06-01

This Perspective discusses the pertinence of variable dosing regimens with anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) with regard to real-life requirements. After the initial pivotal trials of anti-VEGF therapy, the variable dosing regimens pro re nata (PRN), Treat-and-Extend, and Observe-and-Plan, a recently introduced regimen, aimed to optimize the anti-VEGF treatment strategy for nAMD. The PRN regimen showed good visual results but requires monthly monitoring visits and can therefore be difficult to implement. Moreover, application of the PRN regimen revealed inferior results in real-life circumstances due to problems with resource allocation. The Treat-and-Extend regimen uses an interval based approach and has become widely accepted for its ease of preplanning and the reduced number of office visits required. The parallel development of the Observe-and-Plan regimen demonstrated that the future need for retreatment (interval) could be reliably predicted. Studies investigating the observe-and-plan regimen also showed that this could be used in individualized fixed treatment plans, allowing for dramatically reduced clinical burden and good outcomes, thus meeting the real life requirements. This progressive development of variable dosing regimens is a response to the real-life circumstances of limited human, technical, and financial resources. This includes an individualized treatment approach, optimization of the number of retreatments, a minimal number of monitoring visits, and ease of planning ahead. The Observe-and-Plan regimen achieves this goal with good functional results. Translational Relevance: This perspective reviews the process from the pivotal clinical trials to the development of treatment regimens which are adjusted to real life requirements. The article discusses this translational process which- although not the classical interpretation of translation from fundamental to clinical research, but a subsequent process after the pivotal clinical trials - represents an important translational step from the clinical proof of efficacy to optimization in terms of patients' and clinics' needs. The related scientific procedure includes the exploration of the concept, evaluation of security, and finally proof of efficacy.

Clinical pharmacology in Russia-historical development and current state.

PubMed

Zagorodnikova Goryachkina, Ksenia; Burbello, Aleksandra; Sychev, Dmitry; Frolov, Maxim; Kukes, Vladimir; Petrov, Vladimir

2015-02-01

Clinical pharmacology in Russia has long history and is currently active, but rather unrecognized internationally. It is governmentally approved as a teaching/scientific specialty since 1983 and as a medical specialty since 1997. Courses of clinical pharmacology are included in the undergraduate curricula in the 5th and/or 6th year of education at all medical schools in the Russian Federation. Postgraduate education includes initial specialization in internal medicine with further residency in clinical pharmacology. Governmental legislation recommends that every healthcare institution has either a department or a single position of clinical pharmacologist. Major routine duties include information about and monitoring of medication use, consultations in difficult clinical situations, pharmacogenetic counseling, therapeutic drug monitoring, pharmacovigilance, and participation in drug and therapeutics (formulary) committees. There are official experts in clinical pharmacology in Russia responsible for coordinating relevant legislative issues. The chief expert clinical pharmacologist represents the discipline directly at the Ministry of Health. Research in clinical pharmacology in Russia is extensive and variable, but only some of it is published internationally. Russia is a participant of international societies of clinical pharmacology and therapeutics and collaboration is actively ongoing. There are still certain problems related to the development of the discipline in Russia-some healthcare institutions do not see the need for clinical pharmacology. However, the number of clinical pharmacologists in Russia is increasing as well as their role in physicians' education, national healthcare, and research.

Comparison of three-dimensional multi-segmental foot models used in clinical gait laboratories.

PubMed

Nicholson, Kristen; Church, Chris; Takata, Colton; Niiler, Tim; Chen, Brian Po-Jung; Lennon, Nancy; Sees, Julie P; Henley, John; Miller, Freeman

2018-05-16

Many skin-mounted three-dimensional multi-segmented foot models are currently in use for gait analysis. Evidence regarding the repeatability of models, including between trial and between assessors, is mixed, and there are no between model comparisons of kinematic results. This study explores differences in kinematics and repeatability between five three-dimensional multi-segmented foot models. The five models include duPont, Heidelberg, Oxford Child, Leardini, and Utah. Hind foot, forefoot, and hallux angles were calculated with each model for ten individuals. Two physical therapists applied markers three times to each individual to assess within and between therapist variability. Standard deviations were used to evaluate marker placement variability. Locally weighted regression smoothing with alpha-adjusted serial T tests analysis was used to assess kinematic similarities. All five models had similar variability, however, the Leardini model showed high standard deviations in plantarflexion/dorsiflexion angles. P-value curves for the gait cycle were used to assess kinematic similarities. The duPont and Oxford models had the most similar kinematics. All models demonstrated similar marker placement variability. Lower variability was noted in the sagittal and coronal planes compared to rotation in the transverse plane, suggesting a higher minimal detectable change when clinically considering rotation and a need for additional research. Between the five models, the duPont and Oxford shared the most kinematic similarities. While patterns of movement were very similar between all models, offsets were often present and need to be considered when evaluating published data. Copyright © 2018 Elsevier B.V. All rights reserved.

Myocardial infarction in the elderly.

PubMed

Carro, Amelia; Kaski, Juan Carlos

2011-04-01

Advances in pharmacological treatment and effective early myocardial revascularization have -in recent years- led to improved clinical outcomes in patients with acute myocardial infarction (AMI). However, it has been suggested that compared to younger subjects, elderly AMI patients are less likely to receive evidence-based treatment, including myocardial revascularization therapy. Several reasons have been postulated to explain this trend, including uncertainty regarding the true benefits of the interventions commonly used in this setting as well as increased risk mainly associated with comorbidities. The diagnosis, management, and post-hospitalization care of elderly patients presenting with an acute coronary syndrome pose many difficulties at present. A complex interplay of variables such as comorbidities, functional and socioeconomic status, side effects associated with multiple drug administration, and individual biologic variability, all contribute to creating a complex clinical scenario. In this complex setting, clinicians are often required to extrapolate evidence-based results obtained in cardiovascular trials from which older patients are often, implicitly or explicitly, excluded. This article reviews current recommendations regarding management of AMI in the elderly.

Myocardial Infarction in the Elderly

PubMed Central

Carro, Amelia; Kaski, Juan Carlos

2011-01-01

Advances in pharmacological treatment and effective early myocardial revascularization have –in recent years- led to improved clinical outcomes in patients with acute myocardial infarction (AMI). However, it has been suggested that compared to younger subjects, elderly AMI patients are less likely to receive evidence-based treatment, including myocardial revascularization therapy. Several reasons have been postulated to explain this trend, including uncertainty regarding the true benefits of the interventions commonly used in this setting as well as increased risk mainly associated with comorbidities. The diagnosis, management, and post-hospitalization care of elderly patients presenting with an acute coronary syndrome pose many difficulties at present. A complex interplay of variables such as comorbidities, functional and socioeconomic status, side effects associated with multiple drug administration, and individual biologic variability, all contribute to creating a complex clinical scenario. In this complex setting, clinicians are often required to extrapolate evidence-based results obtained in cardiovascular trials from which older patients are often, implicitly or explicitly, excluded. This article reviews current recommendations regarding management of AMI in the elderly. PMID:22396870

Analysis of model development strategies: predicting ventral hernia recurrence.

PubMed

Holihan, Julie L; Li, Linda T; Askenasy, Erik P; Greenberg, Jacob A; Keith, Jerrod N; Martindale, Robert G; Roth, J Scott; Liang, Mike K

2016-11-01

There have been many attempts to identify variables associated with ventral hernia recurrence; however, it is unclear which statistical modeling approach results in models with greatest internal and external validity. We aim to assess the predictive accuracy of models developed using five common variable selection strategies to determine variables associated with hernia recurrence. Two multicenter ventral hernia databases were used. Database 1 was randomly split into "development" and "internal validation" cohorts. Database 2 was designated "external validation". The dependent variable for model development was hernia recurrence. Five variable selection strategies were used: (1) "clinical"-variables considered clinically relevant, (2) "selective stepwise"-all variables with a P value <0.20 were assessed in a step-backward model, (3) "liberal stepwise"-all variables were included and step-backward regression was performed, (4) "restrictive internal resampling," and (5) "liberal internal resampling." Variables were included with P < 0.05 for the Restrictive model and P < 0.10 for the Liberal model. A time-to-event analysis using Cox regression was performed using these strategies. The predictive accuracy of the developed models was tested on the internal and external validation cohorts using Harrell's C-statistic where C > 0.70 was considered "reasonable". The recurrence rate was 32.9% (n = 173/526; median/range follow-up, 20/1-58 mo) for the development cohort, 36.0% (n = 95/264, median/range follow-up 20/1-61 mo) for the internal validation cohort, and 12.7% (n = 155/1224, median/range follow-up 9/1-50 mo) for the external validation cohort. Internal validation demonstrated reasonable predictive accuracy (C-statistics = 0.772, 0.760, 0.767, 0.757, 0.763), while on external validation, predictive accuracy dipped precipitously (C-statistic = 0.561, 0.557, 0.562, 0.553, 0.560). Predictive accuracy was equally adequate on internal validation among models; however, on external validation, all five models failed to demonstrate utility. Future studies should report multiple variable selection techniques and demonstrate predictive accuracy on external data sets for model validation. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of tocolytic drugs on fetal heart rate variability: a systematic review.

PubMed

Verdurmen, Kim M J; Hulsenboom, Alexandra D J; van Laar, Judith O E H; Oei, S Guid

2017-10-01

Tocolytics may cause changes in fetal heart rate (HR) pattern, while fetal heart rate variability (HRV) is an important marker of fetal well-being. We aim to systematically review the literature on how tocolytic drugs affect fetal HRV. We searched CENTRAL, PubMed and EMBASE up to June 2016. Studies published in English, using computerized or visual analysis to describe the effect of tocolytics on HRV in human fetuses were included. Studies describing tocolytics during labor, external cephalic version, pre-eclampsia and infection were excluded. Eventually, we included six studies, describing 169 pregnant women. Nifedipine, atosiban and indomethacin administration show no clinically important effect on fetal HRV. Following administration of magnesium sulfate decreased variability and cases of bradycardia are described. Fenoterol administration results in a slight increase in fetal HR with no changes in variability. After ritodrine administration increased fetal HR and decreased variability is seen. The effect of co-administration of corticosteroids should be taken into account. In order to prevent iatrogenic preterm labor, the effects of tocolytic drugs on fetal HRV should be taken into account when monitoring these fetuses.

Critical discussion of evaluation parameters for inter-observer variability in target definition for radiation therapy.

PubMed

Fotina, I; Lütgendorf-Caucig, C; Stock, M; Pötter, R; Georg, D

2012-02-01

Inter-observer studies represent a valid method for the evaluation of target definition uncertainties and contouring guidelines. However, data from the literature do not yet give clear guidelines for reporting contouring variability. Thus, the purpose of this work was to compare and discuss various methods to determine variability on the basis of clinical cases and a literature review. In this study, 7 prostate and 8 lung cases were contoured on CT images by 8 experienced observers. Analysis of variability included descriptive statistics, calculation of overlap measures, and statistical measures of agreement. Cross tables with ratios and correlations were established for overlap parameters. It was shown that the minimal set of parameters to be reported should include at least one of three volume overlap measures (i.e., generalized conformity index, Jaccard coefficient, or conformation number). High correlation between these parameters and scatter of the results was observed. A combination of descriptive statistics, overlap measure, and statistical measure of agreement or reliability analysis is required to fully report the interrater variability in delineation.

Clinical, histopathological and immunohistochemical characterization of a novel equine ocular disorder: heterochromic iridocyclitis with secondary keratitis in adult horses.

PubMed

Pinto, Nelson I; McMullen, Richard J; Linder, Keith E; Cullen, John M; Gilger, Brian C

2015-11-01

To describe the clinical, histopathologic and immunohistochemical characteristics of an equine ocular inflammatory disease resulting in anterior uveitis and corneal endothelial inflammation associated with iris pigment dispersion and retrocorneal fibrous membrane (RFM) formation. Retrospective study. Sixteen horses with evidence of pigmented keratic precipitates (KPs), corneal edema, and/or iris depigmentation. Information collected from the medical records included signalment, clinical signs, prereferral treatment duration and response to therapy, ophthalmic examination findings, postreferral treatment, response to therapy, and outcome. Twenty-one eyes from 16 horses were affected. Age ranged between 9 and 25 years (Average 16.1 years). Blepharospasm, epiphora, and/or corneal opacification were the first clinical signs noted. At the time of referral pigmented KPs, corneal edema, iridal depigmentation, and retrocorneal membranes were commonly seen. Treatment included topical and/or systemic anti-inflammatories and antibiotics with variable response. Reduction or cessation of anti-inflammatory therapy resulted in worsening of clinical signs and disease progression. Eight eyes ultimately required enucleation. Histopathology changes include iridal pigment loss and dispersion, RFM formation, and keratitis. Variable degrees of lymphoplasmacytic inflammation were dominated by T-cells within the corneal stroma, RFM, iris, and ciliary body with occasional multinucleated giant cells. Heterochromic iridocyclitis with secondary keratitis (HIK) is characterized by uveal inflammation with pigment dispersion and suspected corneal endothelial dysfunction. Horses being treated for HIK require diligent and frequent follow-up examinations in combination with aggressive local immune suppression to control the disease. However, HIK may not respond to therapy and enucleation may ultimately be required to ensure the horse's comfort. © 2014 American College of Veterinary Ophthalmologists.

[Does the Youth Psychopathic Traits Inventory (YPI) identify a clinically relevant subgroup among young offenders?].

PubMed

Mingers, Daniel; Köhler, Denis; Huchzermeier, Christian; Hinrichs, Günter

2017-01-01

Does the Youth Psychopathic Traits Inventory identify one or more high-risk subgroups among young offenders? Which recommendations for possible courses of action can be derived for individual clinical or forensic cases? Method: Model-based cluster analysis (Raftery, 1995) was conducted on a sample of young offenders (N = 445, age 14–22 years, M = 18.5, SD = 1.65). The resulting model was then tested for differences between clusters with relevant context variables of psychopathy. The variables included measures of intelligence, social competence, drug use, and antisocial behavior. Results: Three clusters were found (Low Trait, Impulsive/Irresponsible, Psychopathy) that differ highly significantly concerning YPI scores and the variables mentioned above. The YPI Scores Δ Low = 4.28 (Low Trait – Impulsive/Irresponsible) and Δ High = 6.86 (Impulsive/Irresponsible – Psychopathy) were determined to be thresholds between the clusters. The allocation of a person to be assessed within the calculated clusters allows for an orientation of consequent tests beyond the diagnosis of psychopathy. We conclude that the YPI is a valuable instrument for the assessment of young offenders, as it yields clinically and forensically relevant information concerning the cause and expected development of psychopathological behavior.

The many ways sputum flows - Dealing with high within-subject variability in cystic fibrosis sputum rheology.

PubMed

Radtke, Thomas; Böni, Lukas; Bohnacker, Peter; Fischer, Peter; Benden, Christian; Dressel, Holger

2018-04-21

We evaluated test-retest reliability of sputum viscoelastic properties in clinically stable patients with cystic fibrosis (CF). Data from a prospective, randomized crossover study was used to determine within-subject variability of sputum viscoelasticity (G', storage modulus and G", loss modulus at 1 and 10 rad s -1 ) and solids content over three consecutive visits. Precision of sputum properties was quantified by within-subject standard deviation (SD ws ), coefficient of variation (CV) and intraclass correlation coefficients (ICC). Fifteen clinically stable adults with CF (FEV 1 range 24-94% predicted) were included. No differences between study visits (mean ± SD 8 ± 2 days) were observed for any sputum rheology measure. CV's for G', G" and solids content ranged between 40.3-45.3% and ICC's between 0.21-0.42 indicating poor to fair test-retest reliability. Short-term within-subject variability of sputum properties is high in clinically stable adults with CF. Investigators applying shear rheology experiments in future prospective studies should consider using multiple measurements aiming to increase precision of sputum rheological outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

A diagnostic model for chronic hypersensitivity pneumonitis.

PubMed

Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

2016-10-01

The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist's diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. 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/

When to trust our learners? Clinical teachers' perceptions of decision variables in the entrustment process.

PubMed

Duijn, Chantal C M A; Welink, Lisanne S; Bok, Harold G J; Ten Cate, Olle T J

2018-06-01

Clinical training programs increasingly use entrustable professional activities (EPAs) as focus of assessment. However, questions remain about which information should ground decisions to trust learners. This qualitative study aimed to identify decision variables in the workplace that clinical teachers find relevant in the elaboration of the entrustment decision processes. The findings can substantiate entrustment decision-making in the clinical workplace. Focus groups were conducted with medical and veterinary clinical teachers, using the structured consensus method of the Nominal Group Technique to generate decision variables. A ranking was made based on a relevance score assigned by the clinical teachers to the different decision variables. Field notes, audio recordings and flip chart lists were analyzed and subsequently translated and, as a form of axial coding, merged into one list, combining the decision variables that were similar in their meaning. A list of 11 and 17 decision variables were acknowledged as relevant by the medical and veterinary teacher groups, respectively. The focus groups yielded 21 unique decision variables that were considered relevant to inform readiness to perform a clinical task on a designated level of supervision. The decision variables consisted of skills, generic qualities, characteristics, previous performance or other information. We were able to group the decision variables into five categories: ability, humility, integrity, reliability and adequate exposure. To entrust a learner to perform a task at a specific level of supervision, a supervisor needs information to support such a judgement. This trust cannot be credited on a single case at a single moment of assessment, but requires different variables and multiple sources of information. This study provides an overview of decision variables giving evidence to justify the multifactorial process of making an entrustment decision.

Randomized controlled trials in mild cognitive impairment

PubMed Central

Thomas, Ronald G.; Aisen, Paul S.; Mohs, Richard C.; Carrillo, Maria C.; Albert, Marilyn S.

2017-01-01

Objective: To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI). Methods: Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil. The data were collated for common measurement instruments. The performance of the placebo participants from these studies was tracked on the Alzheimer's Disease Assessment Scale–cognitive subscale, Mini-Mental State Examination, and Clinical Dementia Rating–sum of boxes, and for progression on these measures to prespecified clinical study endpoints. APOE status, where available, was also analyzed for its effects. Results: The progression to clinical endpoints varied a great deal among the trials. The expected performances were seen for the participants in the 2 NIA trials, ADCS and ADNI, with generally worsening of performance over time; however, the industry-sponsored trials largely showed stable or improved performance in their placebo participants. APOE4 carrier status influenced results in an expected fashion on the study outcomes, including rates of progression and cognitive subscales. Conclusions: In spite of apparently similar criteria for MCI being adopted by the 7 studies, the implementation of the criteria varied a great deal. Several explanations including instruments used to characterize participants and variability among study populations contributed to the findings. PMID:28381516

Network Analysis to Risk Stratify Patients With Exercise Intolerance.

PubMed

Oldham, William M; Oliveira, Rudolf K F; Wang, Rui-Sheng; Opotowsky, Alexander R; Rubins, David M; Hainer, Jon; Wertheim, Bradley M; Alba, George A; Choudhary, Gaurav; Tornyos, Adrienn; MacRae, Calum A; Loscalzo, Joseph; Leopold, Jane A; Waxman, Aaron B; Olschewski, Horst; Kovacs, Gabor; Systrom, David M; Maron, Bradley A

2018-03-16

Current methods assessing clinical risk because of exercise intolerance in patients with cardiopulmonary disease rely on a small subset of traditional variables. Alternative strategies incorporating the spectrum of factors underlying prognosis in at-risk patients may be useful clinically, but are lacking. Use unbiased analyses to identify variables that correspond to clinical risk in patients with exercise intolerance. Data from 738 consecutive patients referred for invasive cardiopulmonary exercise testing at a single center (2011-2015) were analyzed retrospectively (derivation cohort). A correlation network of invasive cardiopulmonary exercise testing parameters was assembled using |r|>0.5. From an exercise network of 39 variables (ie, nodes) and 98 correlations (ie, edges) corresponding to P <9.5e -46 for each correlation, we focused on a subnetwork containing peak volume of oxygen consumption (pVo 2 ) and 9 linked nodes. K-mean clustering based on these 10 variables identified 4 novel patient clusters characterized by significant differences in 44 of 45 exercise measurements ( P <0.01). Compared with a probabilistic model, including 23 independent predictors of pVo 2 and pVo 2 itself, the network model was less redundant and identified clusters that were more distinct. Cluster assignment from the network model was predictive of subsequent clinical events. For example, a 4.3-fold ( P <0.0001; 95% CI, 2.2-8.1) and 2.8-fold ( P =0.0018; 95% CI, 1.5-5.2) increase in hazard for age- and pVo 2 -adjusted all-cause 3-year hospitalization, respectively, were observed between the highest versus lowest risk clusters. Using these data, we developed the first risk-stratification calculator for patients with exercise intolerance. When applying the risk calculator to patients in 2 independent invasive cardiopulmonary exercise testing cohorts (Boston and Graz, Austria), we observed a clinical risk profile that paralleled the derivation cohort. Network analyses were used to identify novel exercise groups and develop a point-of-care risk calculator. These data expand the range of useful clinical variables beyond pVo 2 that predict hospitalization in patients with exercise intolerance. © 2018 American Heart Association, Inc.

Laboratory-Based Biomarkers and Liver Metastases in Metastatic Castration-Resistant Prostate Cancer.

PubMed

Cotogno, Patrick M; Ranasinghe, Lahiru K; Ledet, Elisa M; Lewis, Brian E; Sartor, Oliver

2018-04-26

Metastatic castrate-resistant prostate cancer (mCRPC) patients with liver metastases have a poor prognosis. No large studies have investigated the clinical and biochemical parameters associated with liver metastases in this population. Patient data made available via Project Data Sphere were collected from 1,281 men with mCRPC who were enrolled on to three phase III clinical trials for the treatment of their disease. Multiple logistic regression was performed on eight clinical and biochemical baseline variables to test their association with the presence of liver metastases on baseline radiographic imaging. Variables of interest included prior docetaxel exposure, Eastern Cooperative Oncology Group performance status, albumin, alkaline phosphatase, alanine transaminase, aspartate transaminase (AST), hemoglobin (HGB), lactate dehydrogenase (LDH), prostate-specific antigen, and total bilirubin. Final models were compared when treating the variables as either continuous or categorized. Multiple variable analysis demonstrated that an increasing serum AST or LDH or a decreasing HGB was associated with an increased probability of having documented radiographic liver metastases ( p  < .0001). The area under the curve for the continuous model was 0.6842 and 0.6890 for the categorical one, with the latter model containing a dichotomized AST and LDH based on the upper limit of normal and tertile ranges of HGB based on the distribution of the outcome. Our analysis demonstrated a significant association between the presence of liver metastases and laboratory levels of AST, LDH, and HGB. These have implications for patient management. More research is needed to validate these biomarkers and prospectively determine their application in the clinical setting. The purpose of this study was to evaluate biochemical and clinical biomarkers associated with the presence of liver metastases in men diagnosed with metastatic castrate-resistant prostate cancer. The results indicate that quantitative assessments of aspartate transaminase, lactate dehydrogenase, and hemoglobin are significantly associated with an increased probability of having documented radiographic liver metastases. Analysis of these simple variables can alert clinicians to those at high risk for prostate cancer that has spread to the liver, a finding of clear importance for clinical management. © AlphaMed Press 2018.

Primary outcome indices in illicit drug dependence treatment research: systematic approach to selection and measurement of drug use end-points in clinical trials

PubMed Central

Donovan, Dennis M.; Bigelow, George E.; Brigham, Gregory S.; Carroll, Kathleen M.; Cohen, Allan J.; Gardin, John G.; Hamilton, John A.; Huestis, Marilyn A.; Hughes, John R.; Lindblad, Robert; Marlatt, G. Alan; Preston, Kenzie L.; Selzer, Jeffrey A.; Somoza, Eugene C.; Wakim, Paul G.; Wells, Elizabeth A.

2012-01-01

Aims Clinical trials test the safety and efficacy of behavioral and pharmacological interventions in drug-dependent individuals. However, there is no consensus about the most appropriate outcome(s) to consider in determining treatment efficacy or on the most appropriate methods for assessing selected outcome(s). We summarize the discussion and recommendations of treatment and research experts, convened by the US National Institute on Drug Abuse, to select appropriate primary outcomes for drug dependence treatment clinical trials, and in particular the feasibility of selecting a common outcome to be included in all or most trials. Methods A brief history of outcomes employed in prior drug dependence treatment research, incorporating perspectives from tobacco and alcohol research, is included. The relative merits and limitations of focusing on drug-taking behavior, as measured by self-report and qualitative or quantitative biological markers, are evaluated. Results Drug-taking behavior, measured ideally by a combination of self-report and biological indicators, is seen as the most appropriate proximal primary outcome in drug dependence treatment clinical trials. Conclusions We conclude that the most appropriate outcome will vary as a function of salient variables inherent in the clinical trial, such as the type of intervention, its target, treatment goals (e.g. abstinence or reduction of use) and the perspective being taken (e.g. researcher, clinical program, patient, society). It is recommended that a decision process, based on such trial variables, be developed to guide the selection of primary and secondary outcomes as well as the methods to assess them. PMID:21781202

Standardizing clinical laboratory data for secondary use.

PubMed

Abhyankar, Swapna; Demner-Fushman, Dina; McDonald, Clement J

2012-08-01

Clinical databases provide a rich source of data for answering clinical research questions. However, the variables recorded in clinical data systems are often identified by local, idiosyncratic, and sometimes redundant and/or ambiguous names (or codes) rather than unique, well-organized codes from standard code systems. This reality discourages research use of such databases, because researchers must invest considerable time in cleaning up the data before they can ask their first research question. Researchers at MIT developed MIMIC-II, a nearly complete collection of clinical data about intensive care patients. Because its data are drawn from existing clinical systems, it has many of the problems described above. In collaboration with the MIT researchers, we have begun a process of cleaning up the data and mapping the variable names and codes to LOINC codes. Our first step, which we describe here, was to map all of the laboratory test observations to LOINC codes. We were able to map 87% of the unique laboratory tests that cover 94% of the total number of laboratory tests results. Of the 13% of tests that we could not map, nearly 60% were due to test names whose real meaning could not be discerned and 29% represented tests that were not yet included in the LOINC table. These results suggest that LOINC codes cover most of laboratory tests used in critical care. We have delivered this work to the MIMIC-II researchers, who have included it in their standard MIMIC-II database release so that researchers who use this database in the future will not have to do this work. Published by Elsevier Inc.

Concussion Care Practices and Utilization of Evidence-Based Guidelines in the Evaluation and Management of Concussion: A Survey of New England Emergency Departments.

PubMed

Stern, Robert A; Seichepine, Daniel; Tschoe, Christine; Fritts, Nathan G; Alosco, Michael L; Berkowitz, Oren; Burke, Peter; Howland, Jonathan; Olshaker, Jonathan; Cantu, Robert C; Baugh, Christine M; Holsapple, James W

2017-02-15

Evidence-based clinical practice guidelines can facilitate proper evaluation and management of concussions in the emergency department (ED), often the initial and primary point of contact for concussion care. There is no universally adopted set of guidelines for concussion management, and extant evidence suggests that there may be variability in concussion care practices and limited application of clinical practice guidelines in the ED. This study surveyed EDs throughout New England to examine current practices of concussion care and utilization of evidence-based clinical practice guidelines in the evaluation and management of concussions. In 2013, a 32-item online survey was e-mailed to 149/168 EDs throughout New England (Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, Maine). Respondents included senior administrators asked to report on their EDs use of clinical practice guidelines, neuroimaging decision-making, and discharge instructions for concussion management. Of the 72/78 respondents included, 35% reported absence of clinical practice guidelines, and 57% reported inconsistency in the type of guidelines used. Practitioner preference guided neuroimaging decision-making for 57%. Although 94% provided written discharge instructions, there was inconsistency in the recommended time frame for follow-up care (13% provided no specific time frame), the referral specialist to be seen (25% did not recommend any specialist), and return to activity instructions were inconsistent. There is much variability in concussion care practices and application of evidence-based clinical practice guidelines in the evaluation and management of concussions in New England EDs. Knowledge translational efforts will be critical to improve concussion management in the ED setting.

[Visit-to-visit blood pressure variability: clinical and prognostic significance].

PubMed

Kotovskaia, Iu V; Troitskaia, E A; Kobalava, Zh D

2014-01-01

The phenomenon of variability of blood pressure (BP) was studied for a long time, but recently it has received increased attention, with the focus shifted from short-term BP variability, estimated at daily monitoring for clinical blood pressure variability from visit to visit, which can be regarded as one of the indicators quality control of blood pressure with prolonged treatment. In light of the recent years of clinical data from visit to visit BP variability seems a promising new target for antihypertensive therapy.

An assessment of the demographic and clinical correlates of the dimensions of alcohol use behaviour.

PubMed

Smith, Gillian W; Shevlin, Mark; Murphy, Jamie; Houston, James E

2010-01-01

To identify population-based clinical and demographic correlates of alcohol use dimensions. Using data from a population-based sample of Great Britain (n = 7849), structural equation modelling (SEM) was used to identify associations between demographic and clinical variables and two competing dimensional models of the Alcohol Use Disorders Identification Test (AUDIT). A two-factor SEM fit best. In this model, Factor 1, alcohol consumption, was associated with male sex, younger age, lower educational attainment, generalized anxiety disorder (GAD) and suicide attempts. Factor 2, alcohol-related problems, was associated with the demographic variables (to a lesser extent) and to a wider range of clinical variables, including depressive episode, GAD, mixed anxiety and depressive disorder, obsessive compulsive disorder, phobia, suicidal thoughts and suicide attempts. The one-factor SEM was associated with demographic and all assessed clinical correlates; however, this model did not fit the data well. Two main conclusions justify the two-factor approach to alcohol use classification. First, the model fit was considerably superior and, second, the dimensions of alcohol consumption and alcohol-related problems vary considerably in their associations with measures of demographic and clinical risk. A one-factor representation of alcohol use, for instance, would fail to recognize that measures of affective/anxiety disorders are more consistently related to alcohol-related problems than to alcohol consumption. It is suggested therefore that to fully understand the complexity of alcohol use behaviour and its associated risk, future research should acknowledge the basic underlying dimensional structure of the construct.

NF1 truncating mutations associated to aggressive clinical phenotype with elephantiasis neuromatosa and solid malignancies.

PubMed

Ponti, Giovanni; Martorana, Davide; Pellacani, Giovanni; Ruini, Cristel; Loschi, Pietro; Baccarani, Alessio; De Santis, Giorgio; Pollio, Annamaria; Neri, Tauro Maria; Mandel, Victor Desmond; Maiorana, Antonio; Maccio, Livia; Maccaferri, Monia; Tomasi, Aldo

2014-06-01

Von Recklinghausen disease is a syndrome characterized by a wide phenotypic variability giving rise to both, cutaneous and visceral benign and malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and plexiform neurofibromas. The latter can undergo malignant transformation and/or determine elephantiasis neuromatosa. Visceral tumors may include malignant peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas and abdominal neurofibromas. In the present study, the authors discuss the clinical and biomolecular characterization of a cohort of 20 families with a diagnosis of type 1 neurofibromatosis. Clinically, the cohort includes three probands with elephantiasis neuromatosa and a peculiarly high incidence of breast and gastrointestinal cancer. Among the 14 NF1 mutations documented, 10 encoding for a truncated protein have been associated to particularly aggressive clinical phenotypes including elephantiasis neuromatosa, malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal tumors. This effect on protein synthesis, rather than the type of NF1 mutation, is the key to the explanation of the genotype-phenotype correlations in the context of neurofibromatosis type 1. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Clinical audit of COPD patients requiring hospital admissions in Spain: AUDIPOC study.

PubMed

Pozo-Rodríguez, Francisco; López-Campos, Jose Luis; Alvarez-Martínez, Carlos J; Castro-Acosta, Ady; Agüero, Ramón; Hueto, Javier; Hernández-Hernández, Jesús; Barrón, Manuel; Abraira, Victor; Forte, Anabel; Sanchez Nieto, Juan Miguel; Lopez-Gabaldón, Encarnación; Cosío, Borja G; Agustí, Alvar

2012-01-01

AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines. The present study describes hospital resources, hospital factors related to case recruitment variability, patients' characteristics, and adherence to guidelines. An organisational database was completed by all participant hospitals recording resources and organisation. Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified. At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population. Audited patients were reassessed 90 days after admission for survival and readmission rates. A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death. Median inpatient mortality was 5% (across-hospital range 0-35%). Among discharged patients, 37% required readmission (0-62%) and 6.5% died (0-35%). The overall mortality rate was 11.6% (0-50%). Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment. Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles. The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes. The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement.

[Clinical-demographic factors associated with fear-avoidance in subjects with non-specific chronic low back pain in Primary Care: secondary analysis of intervention study].

PubMed

Díaz-Cerrillo, Juan Luis; Rondón-Ramos, Antonio; Clavero-Cano, Susana; Pérez-González, Rita; Martinez-Calderon, Javier; Luque-Suarez, Alejandro

2018-01-30

To describe some sociodemographics and clinical characteristics of subjects with Non-specific Chronic Low Back Pain (NCLBP) in Primary Care, as well as to investigate their association with Fear-Avoidance (FA). Cross-sectional. Secondary analysis of an intervention study. Basic Health Areas in Costa del Sol Health District (Málaga, Spain). An analysis was performed on 147 subjects with NCLBP from a previous intervention study database in Primary Care Physiotherapy (PCP). Characteristics: age 18-65; understanding of the Spanish language; absence of cognitive disorders, fibromyalgia or dorsolumbar surgery, and to be able to perform physical exercise. The main variable was FA level (FABQ and the FABQ-PA and FABQ-W) sub-scales. Clinical variables included: pain (NRPS-11), disability (RMQ), evolution, previous treatments and diagnostic imaging. The sociodemographic variables included: gender, age, educational level, and employment status. Just over half (51.7%) of the subjects had high FA on the FABQ-PA sub-scale. Sick leave (SL) [β=24.45 (P=.009 * ); β=13.03 (P=.016 * ); β=14.04 (P=.011 * ) for FABQ, FABQ-PA and FABQ-W, respectively]; primary studies level [β=15.09 (P=.01 * ); β=9.73 (P=.01 * ) for FABQ and FABQ-PA], and disability [β=1.45 (P<.001); β=0.61 (P<.001); β=0.68 (P<.001) for FABQ, FABQ-PA and FABQ-W, respectively] were associated with FA when they were modeled by multivariate regression. Some sociodemographic and clinical features of the NCLBP population are presented. Imaging tests (81.63%) and previous passive treatments (55.78%) could reflect problems of adherence to recommendations of CPGs. Sick leave, primary studies level, and disability were associated with FA. The findings should be interpreted in the light of possible limitations. Some suggestions for clinical practice are provided. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Predicting Fluid Responsiveness by Passive Leg Raising: A Systematic Review and Meta-Analysis of 23 Clinical Trials.

PubMed

Cherpanath, Thomas G V; Hirsch, Alexander; Geerts, Bart F; Lagrand, Wim K; Leeflang, Mariska M; Schultz, Marcus J; Groeneveld, A B Johan

2016-05-01

Passive leg raising creates a reversible increase in venous return allowing for the prediction of fluid responsiveness. However, the amount of venous return may vary in various clinical settings potentially affecting the diagnostic performance of passive leg raising. Therefore we performed a systematic meta-analysis determining the diagnostic performance of passive leg raising in different clinical settings with exploration of patient characteristics, measurement techniques, and outcome variables. PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and citation tracking of relevant articles. Clinical trials were selected when passive leg raising was performed in combination with a fluid challenge as gold standard to define fluid responders and non-responders. Trials were included if data were reported allowing the extraction of sensitivity, specificity, and area under the receiver operating characteristic curve. Twenty-three studies with a total of 1,013 patients and 1,034 fluid challenges were included. The analysis demonstrated a pooled sensitivity of 86% (95% CI, 79-92), pooled specificity of 92% (95% CI, 88-96), and a summary area under the receiver operating characteristic curve of 0.95 (95% CI, 0.92-0.98). Mode of ventilation, type of fluid used, passive leg raising starting position, and measurement technique did not affect the diagnostic performance of passive leg raising. The use of changes in pulse pressure on passive leg raising showed a lower diagnostic performance when compared with passive leg raising-induced changes in flow variables, such as cardiac output or its direct derivatives (sensitivity of 58% [95% CI, 44-70] and specificity of 83% [95% CI, 68-92] vs sensitivity of 85% [95% CI, 78-90] and specificity of 92% [95% CI, 87-94], respectively; p < 0.001). Passive leg raising retains a high diagnostic performance in various clinical settings and patient groups. The predictive value of a change in pulse pressure on passive leg raising is inferior to a passive leg raising-induced change in a flow variable.

The Impact of Clinical Information on the Assessment of Endoscopic Activity: Characteristics of the Ulcerative Colitis Endoscopic Index Of Severity [UCEIS].

PubMed

Travis, Simon P L; Schnell, Dan; Feagan, Brian G; Abreu, Maria T; Altman, Douglas G; Hanauer, Stephen B; Krzeski, Piotr; Lichtenstein, Gary R; Marteau, Philippe R; Mary, Jean-Yves; Reinisch, Walter; Sands, Bruce E; Schnell, Patrick; Yacyshyn, Bruce R; Colombel, Jean-Frédéric; Bernhardt, Christian A; Sandborn, William J

2015-08-01

To determine whether clinical information influences endoscopic scoring by central readers using the Ulcerative Colitis Endoscopic Index of Severity [UCEIS; comprising 'vascular pattern', 'bleeding', 'erosions and ulcers']. Forty central readers performed 28 evaluations, including 2 repeats, from a library of 44 video sigmoidoscopies stratified by Mayo Clinic Score. Following training, readers were randomised to scoring with ['unblinded', n = 20, including 4 control videos with misleading information] or without ['blinded', n 20] clinical information. A total of 21 virtual Central Reader Groups [CRGs], of three blinded readers, were created. Agreement criteria were pre-specified. Kappa [κ] statistics quantified intra- and inter-reader variability. Mean UCEIS scores did not differ between blinded and unblinded readers for any of the 40 main videos. UCEIS standard deviations [SD] were similar [median blinded 0.94, unblinded 0.93; p = 0.97]. Correlation between UCEIS and visual analogue scale [VAS] assessment of overall severity was high [r blinded = 0.90, unblinded = 0.93; p = 0.02]. Scores for control videos were similar [UCEIS: p ≥ 0.55; VAS: p ≥ 0.07]. Intra- [κ 0.47-0.74] and inter-reader [κ 0.40-0.53] variability for items and full UCEIS was 'moderate'-to-'substantial', with no significant differences except for intra-reader variability for erosions and ulcers [κ blinded: 0.47 vs unblinded: 0.74; p 0.047]. The SD of CRGs was lower than for individual central readers [0.54 vs 0.95; p < 0.001]. Correlation between blinded UCEIS and patient-reported symptoms was high [stool frequency: 0.76; rectal bleeding: 0.82; both: 0.81]. The UCEIS is minimally affected by knowledge of clinical details, strongly correlates with patient-reported symptoms, and is a suitable instrument for trials. CRGs performed better than individuals. © European Crohn’s and Colitis Organisation 2015.

Costs of HIV/AIDS outpatient services delivered through Zambian public health facilities.

PubMed

Bratt, John H; Torpey, Kwasi; Kabaso, Mushota; Gondwe, Yebo

2011-01-01

To present evidence on unit and total costs of outpatient HIV/AIDS services in ZPCT-supported facilities in Zambia; specifically, to measure unit costs of selected outpatient HIV/AIDS services, and to estimate total annual costs of antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) in Zambia. Cost data from 2008 were collected in 12 ZPCT-supported facilities (hospitals and health centres) in four provinces. Costs of all resources used to produce ART, PMTCT and CT visits were included, using the perspective of the provider. All shared costs were distributed to clinic visits using appropriate allocation variables. Estimates of annual costs of HIV/AIDS services were made using ZPCT and Ministry of Health data on numbers of persons receiving services in 2009. Unit costs of visits were driven by costs of drugs, laboratory tests and clinical labour, while variability in visit costs across facilities was explained mainly by differences in utilization. First-year costs of ART per client ranged from US$278 to US$523 depending on drug regimen and facility type; costs of a complete course of antenatal care (ANC) including PMTCT were approximately US$114. Annual costs of ART provided in ZPCT-supported facilities were estimated at US$14.7-$40.1 million depending on regimen, and annual costs of antenatal care including PMTCT were estimated at US$16 million. In Zambia as a whole, the respective estimates were US$41.0-114.2 million for ART and US$57.7 million for ANC including PMTCT. Consistent with the literature, total costs of services were dominated by drugs, laboratory tests and clinical labour. For each visit type, variability across facilities in total costs and cost components suggests that some potential exists to reduce costs through greater harmonization of care protocols and more intensive use of fixed resources. Improving facility-level information on the costs of resources used to produce services should be emphasized as an element of health systems strengthening. © 2010 Blackwell Publishing Ltd.

Kinematic measures of Arm-trunk movements during unilateral and bilateral reaching predict clinically important change in perceived arm use in daily activities after intensive stroke rehabilitation.

PubMed

Chen, Hao-ling; Lin, Keh-chung; Liing, Rong-jiuan; Wu, Ching-yi; Chen, Chia-ling

2015-09-21

Kinematic analysis has been used to objectively evaluate movement patterns, quality, and strategies during reaching tasks. However, no study has investigated whether kinematic variables during unilateral and bilateral reaching tasks predict a patient's perceived arm use during activities of daily living (ADL) after an intensive intervention. Therefore, this study investigated whether kinematic measures during unilateral and bilateral reaching tasks before an intervention can predict clinically meaningful improvement in perceived arm use during ADL after intensive poststroke rehabilitation. The study was a secondary analysis of 120 subjects with chronic stroke who received 90-120 min of intensive intervention every weekday for 3-4 weeks. Reaching kinematics during unilateral and bilateral tasks and the Motor Activity Log (MAL) were evaluated before and after the intervention. Kinematic variables explained 22 and 11 % of the variance in actual amount of use (AOU) and quality of movement (QOM), respectively, of MAL improvement during unilateral reaching tasks. Kinematic variables also explained 21 and 31 % of the variance in MAL-AOU and MAL-QOM, respectively, during bilateral reaching tasks. Selected kinematic variables, including endpoint variables, trunk involvement, and joint recruitment and interjoint coordination, were significant predictors for improvement in perceived arm use during ADL (P < 0.05). Arm-trunk kinematics may be used to predict clinically meaningful improvement in perceived arm use during ADL after intensive rehabilitation. Involvement of interjoint coordination and trunk control variables as predictors in bilateral reaching models indicates that a high level of motor control (i.e., multijoint coordination) and trunk stability may be important in obtaining treatment gains in arm use, especially for bilateral daily activities, in intensive rehabilitation after stroke.

The Association Between Internet Use and Ambulatory Care-Seeking Behaviors in Taiwan: A Cross-Sectional Study.

PubMed

Hsieh, Ronan Wenhan; Chen, Likwang; Chen, Tsung-Fu; Liang, Jyh-Chong; Lin, Tzu-Bin; Chen, Yen-Yuan; Tsai, Chin-Chung

2016-12-07

Compared with the traditional ways of gaining health-related information from newspapers, magazines, radio, and television, the Internet is inexpensive, accessible, and conveys diverse opinions. Several studies on how increasing Internet use affected outpatient clinic visits were inconclusive. The objective of this study was to examine the role of Internet use on ambulatory care-seeking behaviors as indicated by the number of outpatient clinic visits after adjusting for confounding variables. We conducted this study using a sample randomly selected from the general population in Taiwan. To handle the missing data, we built a multivariate logistic regression model for propensity score matching using age and sex as the independent variables. The questionnaires with no missing data were then included in a multivariate linear regression model for examining the association between Internet use and outpatient clinic visits. We included a sample of 293 participants who answered the questionnaire with no missing data in the multivariate linear regression model. We found that Internet use was significantly associated with more outpatient clinic visits (P=.04). The participants with chronic diseases tended to make more outpatient clinic visits (P<.01). The inconsistent quality of health-related information obtained from the Internet may be associated with patients' increasing need for interpreting and discussing the information with health care professionals, thus resulting in an increasing number of outpatient clinic visits. In addition, the media literacy of Web-based health-related information seekers may also affect their ambulatory care-seeking behaviors, such as outpatient clinic visits. ©Ronan Wenhan Hsieh, Likwang Chen, Tsung-Fu Chen, Jyh-Chong Liang, Tzu-Bin Lin, Yen-Yuan Chen, Chin-Chung Tsai. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 07.12.2016.

[Adrenal tumors. Principles of diagnostics and operative treatment].

PubMed

Gonsior, A; Pfeiffer, H; Führer, D; Liatsikos, E; Schwalenberg, T; Stolzenburg, J-U

2010-05-01

Adrenal masses are very heterogeneous and comprise benign or malignant tumors, unilateral or bilateral masses and variable endocrine activity. Because of these attributes adrenal gland masses are a clinical challenge. This article gives a summary of diagnostic steps and indications for adrenal surgery including perioperative management.

Return to preinjury sports participation following anterior cruciate ligament reconstruction: contributions of demographic, knee impairment, and self-report measures.

PubMed

Lentz, Trevor A; Zeppieri, Giorgio; Tillman, Susan M; Indelicato, Peter A; Moser, Michael W; George, Steven Z; Chmielewski, Terese L

2012-11-01

Cross-sectional cohort. (1) To examine differences in clinical variables (demographics, knee impairments, and self-report measures) between those who return to preinjury level of sports participation and those who do not at 1 year following anterior cruciate ligament reconstruction, (2) to determine the factors most strongly associated with return-to-sport status in a multivariate model, and (3) to explore the discriminatory value of clinical variables associated with return to sport at 1 year postsurgery. Demographic, physical impairment, and psychosocial factors individually prohibit return to preinjury levels of sports participation. However, it is unknown which combination of factors contributes to sports participation status. Ninety-four patients (60 men; mean age, 22.4 years) 1 year post-anterior cruciate ligament reconstruction were included. Clinical variables were collected and included demographics, knee impairment measures, and self-report questionnaire responses. Patients were divided into "yes return to sports" or "no return to sports" groups based on their answer to the question, "Have you returned to the same level of sports as before your injury?" Group differences in demographics, knee impairments, and self-report questionnaire responses were analyzed. Discriminant function analysis determined the strongest predictors of group classification. Receiver-operating-characteristic curves determined the discriminatory accuracy of the identified clinical variables. Fifty-two of 94 patients (55%) reported yes return to sports. Patients reporting return to preinjury levels of sports participation were more likely to have had less knee joint effusion, fewer episodes of knee instability, lower knee pain intensity, higher quadriceps peak torque-body weight ratio, higher score on the International Knee Documentation Committee Subjective Knee Evaluation Form, and lower levels of kinesiophobia. Knee joint effusion, episodes of knee instability, and score on the International Knee Documentation Committee Subjective Knee Evaluation Form were identified as the factors most strongly associated with self-reported return-to-sport status. The highest positive likelihood ratio for the yes-return-to-sports group classification (14.54) was achieved when patients met all of the following criteria: no knee effusion, no episodes of instability, and International Knee Documentation Committee Subjective Knee Evaluation Form score greater than 93. In multivariate analysis, the factors most strongly associated with return-to-sport status included only self-reported knee function, episodes of knee instability, and knee joint effusion.

Forms of work organization and associations with shoulder disorders: Results from a French working population.

PubMed

Bodin, Julie; Garlantézec, Ronan; Costet, Nathalie; Descatha, Alexis; Fouquet, Natacha; Caroly, Sandrine; Roquelaure, Yves

2017-03-01

The aim of this study was to identify forms of work organization in a French region and to study associations with the occurrence of symptomatic and clinically diagnosed shoulder disorders in workers. Workers were randomly included in this cross-sectional study from 2002 to 2005. Sixteen organizational variables were assessed by a self-administered questionnaire: i.e. shift work, job rotation, repetitiveness of tasks, paced work/automatic rate, work pace dependent on quantified targets, permanent controls or surveillance, colleagues' work and customer demand, and eight variables measuring decision latitude. Five forms of work organization were identified using hierarchical cluster analysis (HCA) of variables and HCA of workers: low decision latitude with pace constraints, medium decision latitude with pace constraints, low decision latitude with low pace constraints, high decision latitude with pace constraints and high decision latitude with low pace constraints. There were significant associations between forms of work organization and symptomatic and clinically-diagnosed shoulder disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dental occlusion and temporomandibular disorders.

PubMed

Stone, J Caitlin; Hannah, Andrew; Nagar, Nathan

2017-10-27

Data sourcesMedline, Scopus and Google Scholar.Study selectionTwo reviewers selected studies independently. English language clinical studies assessing the association between temporomandibular disorders (TMD) and features of dental occlusion were considered.Data extraction and synthesisStudy quality was assessed based on the Newcastle-Ottawa Scale (NOS) and a narrative synthesis was presented.ResultsIn all 25 studies (17 case-control, eight comparative) were included. Overall there was a high variability between occlusal features and TMD diagnosis. Findings were consistent with a lack of clinically relevant association between TMD and dental occlusion. Only two studies were associated with TMD in the majority (≥50%) of single variable analyses in patient populations. Only mediotrusive interferences are associated with TMD in the majority of multiple variable analyses.ConclusionsThe findings support the absence of a disease-specific association, there is no ground to hypothesise a major role for dental occlusion in the pathophysiology of TMDs. Dental clinicians are thus encouraged to move forward and abandon the old-fashioned gnathological paradig.

A Study to Identify Those Variables Which Contribute to the Utilization of Wellness Clinic Services by Active Duty Army Family Members

DTIC Science & Technology

1985-07-01

utilization of organizational assets. The marketing mix model consisting of the four key vari- ables of price, promotion, product, and place, is commonly...minimal marketing efforts may bring significant increases in useage. The author included some specific recommendations for marketing the Wellness Clinic. 12...care This five factor model indicates that the two major approa- ches to analyzing preventive health care consumer decisionmaking, marketing and health

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

PubMed Central

Vrana, Julie A.; Theis, Jason D.; Dasari, Surendra; Mereuta, Oana M.; Dispenzieri, Angela; Zeldenrust, Steven R.; Gertz, Morie A.; Kurtin, Paul J.; Grogg, Karen L.; Dogan, Ahmet

2014-01-01

Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. Here we describe the development and implementation of a clinical assay using mass spectrometry-based proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated the assay comparing amyloid-positive (n=43) and -negative (n=26) subcutaneous fat aspirates. The assay classified amyloidosis with 88% sensitivity and 96% specificity. We then implemented the assay as a clinical test, and analyzed 366 amyloid-positive subcutaneous fat aspirates in a 4-year period as part of routine clinical care. The assay had a sensitivity of 90%, and diverse amyloid types, including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A (%1), gelsolin (1%), and lysozyme (1%), were identified. Using bioinformatics, we identified a universal amyloid proteome signature, which has high sensitivity and specificity for amyloidosis similar to that of Congo red staining. We curated proteome databases which included variant proteins associated with systemic amyloidosis, and identified clonotypic immunoglobulin variable gene usage in immunoglobulin light chain amyloidosis, and the variant peptides in hereditary transthyretin amyloidosis. In conclusion, mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for the diagnosis and typing of systemic amyloidosis. The assay reveals the underlying pathogenesis by identifying variable gene usage in immunoglobulin light chains and the variant peptides in hereditary amyloidosis. PMID:24747948

[Study of the clinical phenotype of symptomatic chronic airways disease by hierarchical cluster analysis and two-step cluster analyses].

PubMed

Ning, P; Guo, Y F; Sun, T Y; Zhang, H S; Chai, D; Li, X M

2016-09-01

To study the distinct clinical phenotype of chronic airway diseases by hierarchical cluster analysis and two-step cluster analysis. A population sample of adult patients in Donghuamen community, Dongcheng district and Qinghe community, Haidian district, Beijing from April 2012 to January 2015, who had wheeze within the last 12 months, underwent detailed investigation, including a clinical questionnaire, pulmonary function tests, total serum IgE levels, blood eosinophil level and a peak flow diary. Nine variables were chosen as evaluating parameters, including pre-salbutamol forced expired volume in one second(FEV1)/forced vital capacity(FVC) ratio, pre-salbutamol FEV1, percentage of post-salbutamol change in FEV1, residual capacity, diffusing capacity of the lung for carbon monoxide/alveolar volume adjusted for haemoglobin level, peak expiratory flow(PEF) variability, serum IgE level, cumulative tobacco cigarette consumption (pack-years) and respiratory symptoms (cough and expectoration). Subjects' different clinical phenotype by hierarchical cluster analysis and two-step cluster analysis was identified. (1) Four clusters were identified by hierarchical cluster analysis. Cluster 1 was chronic bronchitis in smokers with normal pulmonary function. Cluster 2 was chronic bronchitis or mild chronic obstructive pulmonary disease (COPD) patients with mild airflow limitation. Cluster 3 included COPD patients with heavy smoking, poor quality of life and severe airflow limitation. Cluster 4 recognized atopic patients with mild airflow limitation, elevated serum IgE and clinical features of asthma. Significant differences were revealed regarding pre-salbutamol FEV1/FVC%, pre-salbutamol FEV1% pred, post-salbutamol change in FEV1%, maximal mid-expiratory flow curve(MMEF)% pred, carbon monoxide diffusing capacity per liter of alveolar(DLCO)/(VA)% pred, residual volume(RV)% pred, total serum IgE level, smoking history (pack-years), St.George's respiratory questionnaire(SGRQ) score, acute exacerbation in the past one year, PEF variability and allergic dermatitis (P<0.05). (2) Four clusters were also identified by two-step cluster analysis as followings, cluster 1, COPD patients with moderate to severe airflow limitation; cluster 2, asthma and COPD patients with heavy smoking, airflow limitation and increased airways reversibility; cluster 3, patients having less smoking and normal pulmonary function with wheezing but no chronic cough; cluster 4, chronic bronchitis patients with normal pulmonary function and chronic cough. Significant differences were revealed regarding gender distribution, respiratory symptoms, pre-salbutamol FEV1/FVC%, pre-salbutamol FEV1% pred, post-salbutamol change in FEV1%, MMEF% pred, DLCO/VA% pred, RV% pred, PEF variability, total serum IgE level, cumulative tobacco cigarette consumption (pack-years), and SGRQ score (P<0.05). By different cluster analyses, distinct clinical phenotypes of chronic airway diseases are identified. Thus, individualized treatments may guide doctors to provide based on different phenotypes.

Implementation of Departmental Quality Strategies Is Positively Associated with Clinical Practice: Results of a Multicenter Study in 73 Hospitals in 7 European Countries

PubMed Central

2015-01-01

Background Given the amount of time and resources invested in implementing quality programs in hospitals, few studies have investigated their clinical impact and what strategies could be recommended to enhance its effectiveness. Objective To assess variations in clinical practice and explore associations with hospital- and department-level quality management systems. Design Multicenter, multilevel cross-sectional study. Setting and Participants Seventy-three acute care hospitals with 276 departments managing acute myocardial infarction, deliveries, hip fracture, and stroke in seven countries. Intervention None. Measures Predictor variables included 3 hospital- and 4 department-level quality measures. Six measures were collected through direct observation by an external surveyor and one was assessed through a questionnaire completed by hospital quality managers. Dependent variables included 24 clinical practice indicators based on case note reviews covering the 4 conditions (acute myocardial infarction, deliveries, hip fracture and stroke). A directed acyclic graph was used to encode relationships between predictors, outcomes, and covariates and to guide the choice of covariates to control for confounding. Results and Limitations Data were provided on 9021 clinical records by 276 departments in 73 hospitals. There were substantial variations in compliance with the 24 clinical practice indicators. Weak associations were observed between hospital quality systems and 4 of the 24 indicators, but on analyzing department-level quality systems, strong associations were observed for 8 of the 11 indicators for acute myocardial infarction and stroke. Clinical indicators supported by higher levels of evidence were more frequently associated with quality systems and activities. Conclusions There are significant gaps between recommended standards of care and clinical practice in a large sample of hospitals. Implementation of department-level quality strategies was significantly associated with good clinical practice. Further research should aim to develop clinically relevant quality standards for hospital departments, which appear to be more effective than generic hospital-wide quality systems. PMID:26588842

Implementation of Departmental Quality Strategies Is Positively Associated with Clinical Practice: Results of a Multicenter Study in 73 Hospitals in 7 European Countries.

PubMed

Sunol, Rosa; Wagner, Cordula; Arah, Onyebuchi A; Kristensen, Solvejg; Pfaff, Holger; Klazinga, Niek; Thompson, Caroline A; Wang, Aolin; DerSarkissian, Maral; Bartels, Paul; Michel, Philippe; Groene, Oliver

2015-01-01

Given the amount of time and resources invested in implementing quality programs in hospitals, few studies have investigated their clinical impact and what strategies could be recommended to enhance its effectiveness. To assess variations in clinical practice and explore associations with hospital- and department-level quality management systems. Multicenter, multilevel cross-sectional study. Seventy-three acute care hospitals with 276 departments managing acute myocardial infarction, deliveries, hip fracture, and stroke in seven countries. None. Predictor variables included 3 hospital- and 4 department-level quality measures. Six measures were collected through direct observation by an external surveyor and one was assessed through a questionnaire completed by hospital quality managers. Dependent variables included 24 clinical practice indicators based on case note reviews covering the 4 conditions (acute myocardial infarction, deliveries, hip fracture and stroke). A directed acyclic graph was used to encode relationships between predictors, outcomes, and covariates and to guide the choice of covariates to control for confounding. Data were provided on 9021 clinical records by 276 departments in 73 hospitals. There were substantial variations in compliance with the 24 clinical practice indicators. Weak associations were observed between hospital quality systems and 4 of the 24 indicators, but on analyzing department-level quality systems, strong associations were observed for 8 of the 11 indicators for acute myocardial infarction and stroke. Clinical indicators supported by higher levels of evidence were more frequently associated with quality systems and activities. There are significant gaps between recommended standards of care and clinical practice in a large sample of hospitals. Implementation of department-level quality strategies was significantly associated with good clinical practice. Further research should aim to develop clinically relevant quality standards for hospital departments, which appear to be more effective than generic hospital-wide quality systems.

Prediction of remission of depression with clinical variables, neuropsychological performance, and serotonergic/dopaminergic gene polymorphisms.

PubMed

Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Asbun-Bojalil, Juan; Lira-Islas, Yuridia; Reyes-Ponce, Celia; Guàrdia-Olmos, Joan

2012-11-01

The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms on the prediction of depression remission after 12 weeks' treatment with fluoxetine. These variables have been studied as potential predictors of depression remission, but they present poor prognostic sensitivity and specificity by themselves. Seventy-two depressed patients were genotyped according to the aforementioned polymorphisms and were clinically and neuropsychologically assessed before a 12-week fluxetine treatment. Only the La allele of rs25531 polymorphism and the GG and AA forms of the val 108/158 Met polymorphism predict major depressive disorder remission after 12 weeks' treatment with fluoxetine. None of the clinical and neuropsychological variables studied predicted remission. Our results suggest that clinical and neuropsychological variables can initially predict early response to fluoxetine and mask the predictive role of genetic variables; but in remission, where clinical and neuropsychological symptoms associated with depression tend to disappear thanks to the treatment administered, the polymorphisms studied are the only variables in our model capable of predicting remission. However, placebo effects that are difficult to control require cautious interpretation of the results.

Therapeutic Drug Monitoring of Lacosamide in Norway: Focus on Pharmacokinetic Variability, Efficacy and Tolerability.

PubMed

Svendsen, Torleiv; Brodtkorb, Eylert; Baftiu, Arton; Burns, Margrete Larsen; Johannessen, Svein I; Johannessen Landmark, Cecilie

2017-07-01

Lacosamide (LCM) is a new antiepileptic drug (AED). Experience from therapeutic drug monitoring (TDM) in clinical practice is limited. The purpose of this study is to evaluate the pharmacokinetic variability of LCM in relation to efficacy and tolerability in patients with refractory epilepsy in a real-life setting. Variables included age, gender, daily doses and serum concentrations of LCM and other AEDs from the TDM-database at the National Center for Epilepsy in Norway. Clinical data regarding efficacy and tolerability were collected from medical records. The Norwegian Prescription Database (NorPD) was used to include population-based numbers of users. TDM-data from 344 patients were included. The median dose, serum concentration, and concentration/dose (C/D)-ratio of LCM was 350 (range 25-700) mg/day, 19.7 (range 8.1-56.2) µmol/L, and 0.06 (0.02-0.82) µmol/L/mg, respectively. Serum concentrations were reduced by 28% by concomitant use of enzyme inducers and increased by 30% in patients aged >65 years. Efficacy and tolerability were assessed in 227 patients: 29% had >50% seizure reduction (eight seizure free), 30% had no effect, and 44% reported adverse effects. In Norway, there were on average 500 patients per year using LCM in this period based on NorPD. The study demonstrated pharmacokinetic variability and use of TDM of LCM in Norway. Data were collected from multiple sources for improved pharmacovigilance. Serum concentrations were influenced by enzyme inducers and ageing, indicating the usefulness of TDM. Effect and tolerability were favorable within a suggested reference range of 10-40 µmol/L given drug-fasting conditions.

Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig(TM)) molecule that specifically and potently neutralizes both IL-1α and IL-1β.

PubMed

Lacy, Susan E; Wu, Chengbin; Ambrosi, Dominic J; Hsieh, Chung-Ming; Bose, Sahana; Miller, Renee; Conlon, Donna M; Tarcsa, Edit; Chari, Ravi; Ghayur, Tariq; Kamath, Rajesh V

2015-01-01

Interleukin-1 (IL-1) cytokines such as IL-1α, IL-1β, and IL-1Ra contribute to immune regulation and inflammatory processes by exerting a wide range of cellular responses, including expression of cytokines and chemokines, matrix metalloproteinases, and nitric oxide synthetase. IL-1α and IL-1β bind to IL-1R1 complexed to the IL-1 receptor accessory protein and induce similar physiological effects. Preclinical and clinical studies provide significant evidence for the role of IL-1 in the pathogenesis of osteoarthritis (OA), including cartilage degradation, bone sclerosis, and synovial proliferation. Here, we describe the generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig) of the IgG1/k subtype that specifically and potently neutralizes IL-1α and IL-1β. In ABT-981, the IL-1β variable domain resides in the outer domain of the DVD-Ig, whereas the IL-1α variable domain is located in the inner position. ABT-981 specifically binds to IL-1α and IL-1β, and is physically capable of binding 2 human IL-1α and 2 human IL-1β molecules simultaneously. Single-dose intravenous and subcutaneous pharmacokinetics studies indicate that ABT-981 has a half-life of 8.0 to 10.4 d in cynomolgus monkey and 10.0 to 20.3 d in rodents. ABT-981 exhibits suitable drug-like-properties including affinity, potency, specificity, half-life, and stability for evaluation in human clinical trials. ABT-981 offers an exciting new approach for the treatment of OA, potentially addressing both disease modification and symptom relief as a disease-modifying OA drug.

Technical aspects and inter-laboratory variability in native peptide profiling: the CE-MS experience.

PubMed

Mischak, Harald; Vlahou, Antonia; Ioannidis, John P A

2013-04-01

Mass spectrometry platforms have attracted a lot of interest in the last 2 decades as profiling tools for native peptides and proteins with clinical potential. However, limitations associated with reproducibility and analytical robustness, especially pronounced with the initial SELDI systems, hindered the application of such platforms in biomarker qualification and clinical implementation. The scope of this article is to give a short overview on data available on performance and on analytical robustness of the different platforms for peptide profiling. Using the CE-MS platform as a paradigm, data on analytical performance are described including reproducibility (short-term and intermediate repeatability), stability, interference, quantification capabilities (limits of detection), and inter-laboratory variability. We discuss these issues by using as an example our experience with the development of a 273-peptide marker for chronic kidney disease. Finally, we discuss pros and cons and means for improvement and emphasize the need to test in terms of comparative clinical performance and impact, different platforms that pass reasonably well analytical validation tests. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Organizational Correlates of Implementation of Colocation of Mental Health and Primary Care in the Veterans Health Administration

PubMed Central

Guerrero, Erick G.; Heslin, Kevin C.; Chang, Evelyn; Fenwick, Karissa; Yano, Elizabeth

2014-01-01

This study explored the role of organizational factors in the ability of Veterans Health Administration (VHA) clinics to implement colocated mental health care in primary care settings (PC-MH). The study used data from the VHA Clinical Practice Organizational Survey collected in 2007 from 225 clinic administrators across the United States. Clinic degree of implementation of PC-MH was the dependent variable, whereas independent variables included policies and procedures, organizational context, and leaders’ perceptions of barriers to change. Pearson bivariate correlations and multivariable linear regression were used to test hypotheses. Results show that depression care training for primary care providers and clinics’ flexibility and participation were both positively correlated with implementation of PC-MH. However, after accounting for other factors, regressions show that only training primary care providers in depression care was marginally associated with degree of implementation of PC-MH (p = 0.051). Given the importance of this topic for implementing integrated care as part of health care reform, these null findings underscore the need to improve theory and testing of more proximal measures of colocation in future work. PMID:25096986

Adapting Social Neuroscience Measures for Schizophrenia Clinical Trials, Part 3: Fathoming External Validity

PubMed Central

Olbert, Charles M.

2013-01-01

It is unknown whether measures adapted from social neuroscience linked to specific neural systems will demonstrate relationships to external variables. Four paradigms adapted from social neuroscience were administered to 173 clinically stable outpatients with schizophrenia to determine their relationships to functionally meaningful variables and to investigate their incremental validity beyond standard measures of social and nonsocial cognition. The 4 paradigms included 2 that assess perception of nonverbal social and action cues (basic biological motion and emotion in biological motion) and 2 that involve higher level inferences about self and others’ mental states (self- referential memory and empathic accuracy). Overall, social neuroscience paradigms showed significant relationships to functional capacity but weak relationships to community functioning; the paradigms also showed weak correlations to clinical symptoms. Evidence for incremental validity beyond standard measures of social and nonsocial cognition was mixed with additional predictive power shown for functional capacity but not community functioning. Of the newly adapted paradigms, the empathic accuracy task had the broadest external validity. These results underscore the difficulty of translating developments from neuroscience into clinically useful tasks with functional significance. PMID:24072806

Adapting social neuroscience measures for schizophrenia clinical trials, part 3: fathoming external validity.

PubMed

Olbert, Charles M; Penn, David L; Kern, Robert S; Lee, Junghee; Horan, William P; Reise, Steven P; Ochsner, Kevin N; Marder, Stephen R; Green, Michael F

2013-11-01

It is unknown whether measures adapted from social neuroscience linked to specific neural systems will demonstrate relationships to external variables. Four paradigms adapted from social neuroscience were administered to 173 clinically stable outpatients with schizophrenia to determine their relationships to functionally meaningful variables and to investigate their incremental validity beyond standard measures of social and nonsocial cognition. The 4 paradigms included 2 that assess perception of nonverbal social and action cues (basic biological motion and emotion in biological motion) and 2 that involve higher level inferences about self and others' mental states (self-referential memory and empathic accuracy). Overall, social neuroscience paradigms showed significant relationships to functional capacity but weak relationships to community functioning; the paradigms also showed weak correlations to clinical symptoms. Evidence for incremental validity beyond standard measures of social and nonsocial cognition was mixed with additional predictive power shown for functional capacity but not community functioning. Of the newly adapted paradigms, the empathic accuracy task had the broadest external validity. These results underscore the difficulty of translating developments from neuroscience into clinically useful tasks with functional significance.

Who is healthy? Aspects to consider when including healthy volunteers in QST--based studies-a consensus statement by the EUROPAIN and NEUROPAIN consortia.

PubMed

Gierthmühlen, Janne; Enax-Krumova, Elena K; Attal, Nadine; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B; Haanpää, Maija; Hansson, Per; Jensen, Troels S; Freynhagen, Rainer; Kennedy, Jeffrey D; Mainka, Tina; Rice, Andrew S C; Segerdahl, Märta; Sindrup, Søren H; Serra, Jordi; Tölle, Thomas; Treede, Rolf-Detlef; Baron, Ralf; Maier, Christoph

2015-11-01

Clinical and human experimental pain studies often include so-called "healthy" controls in investigations of sensory abnormalities, using quantitative sensory testing (QST) as an outcome measure. However, the criteria for what is considered "healthy" vary among the different studies and between study centers and investigators, partly explaining the high variability of the results. Therefore, several aspects should be considered during inclusion of healthy volunteers in QST-based trials to have homogenous groups of healthy controls with less variability between human experimental studies, so that results are less likely to be false negative or false positive because of subject-related factors. The EUROPAIN and NEUROPAIN consortia aimed to define factors influencing the variability in selection of healthy subjects in QST-based studies before the start of both projects and to give recommendations how to minimize it based on the current literature and expertise of the participants. The present suggestions for inclusion criteria of healthy volunteers into QST-based trials describe a 2-level approach including standardized questionnaires enabling the collection of relevant information on sociodemographic data, medical history, current health status, coping strategies in dealing with pain, and the motivation of the volunteer to participate in the study. These suggestions are believed to help researchers interpret their results in comparison with others and improve the quality of clinical studies including healthy volunteers as controls or in human experimental pain studies. They aim to reduce any confounding factors. Furthermore, the acquired information will allow post hoc analyses of variance for different potential influencing factors.

Factors Associated with Periodontal Disease in Pregnant Diabetic Women.

PubMed

Anwar, N; Zaman, N; Nimmi, N; Chowdhury, T A; Khan, M H

2016-04-01

There have been an association between systemic diseases and hormonal changes particularly diabetes which has been cited as a risk factor in the progression of periodontitis in pregnant women. The incidence and severity of periodontal diseases are increasing at a higher rate and a common condition in pregnant diabetic women among Bangladeshi population. This cross sectional study included 200 pregnant women who were selected from gynecological department and examined at the dental unit. The clinical parameters used were the Silness and Loe plaque index (PI), gingival scores and periodontal status and any relationship to socio demographic variables (age, occupation, level of education and urban or rural residence) and clinical variables (gestation period, previous pregnancy, type of diabetes and periodontal maintenance) were evaluated. The results showed that these clinical parameters increased concomitantly with an increase in the stage of pregnancy and in women with multiple pregnancies. Increased age, lower level of education, unemployment and patients residing in rural areas were associated with significantly higher gingival scores and periodontal measures. Women with increased age and multiple pregnancies usually have less interest to frequent periodontal maintenance showing a significant statistical relation between an increased age and changes in gingival and periodontal status; however no significant association was found between increased age and plaque index. It is concluded that gingival inflammatory symptoms are aggravated during pregnancy in diabetic women and are related to different clinical and demographic variables.

Increased prevalence of vegetarianism among women with eating pathology.

PubMed

Zuromski, Kelly L; Witte, Tracy K; Smith, April R; Goodwin, Natalie; Bodell, Lindsay P; Bartlett, Mary; Siegfried, Nicole

2015-12-01

Prior research has established a link between vegetarianism and disordered eating but has typically sampled vegetarians. This study examined prevalence of and variables related to vegetarianism in three samples with varying severity of eating pathology. Sample 1 consisted of female undergraduates who denied history of or current disordered eating (i.e., nonclinical; n=73), or engaged in disordered eating over past month (i.e., subclinical; n=136). Sample 2 included 69 female patients receiving residential treatment at an eating disorder center (i.e., clinical sample). Differences between groups were analyzed using Fisher's exact test. The prevalence of lifetime vegetarianism was lowest in the nonclinical group (6.80%) and highest in the clinical group (34.80%), with the subclinical group falling in between (17.60%). According to Fisher's exact test, all pairwise comparisons between groups were statistically significant (p's<.05). Regarding current vegetarian status, the clinical group was more likely (11.10%) than both other groups to self-identify as current vegetarians. Endorsement of vegetarianism was highest among females with severe eating pathology. Future research should use longitudinal data to examine the temporal relationship between these variables, or other underlying factors that may contribute to the co-occurrence of eating pathology and vegetarianism. Clinically, endorsement of vegetarianism may also be an important variable to consider in treatment disordered eating. Copyright © 2015 Elsevier Ltd. All rights reserved.

Application of lean methods improves surgical clinic experience.

PubMed

Waldhausen, John H T; Avansino, Jeffrey R; Libby, Arlene; Sawin, Robert S

2010-07-01

A quality visit in high volume surgery clinics is challenging. There is variability in numbers of patients seen and care provider behavior. Documentation, regulatory and compliance issues and computerization of patient care systems may decrease clinic efficiency and throughput. We tried to reduce variability and improve patient experience. Baseline data included: patients seen, time in exam rooms, and spent with providers, and patient satisfaction surveys. Two Rapid Process Improvement Workshops (RPIWs) were conducted to apply lean methods. 5S techniques helped standardize exam rooms. Similar data were collected at 30 days, 60 days, and 1 year. Satisfaction surveys were followed at 6 months and 1 year. Median pre-RPIW room time was 49 minutes. Post-RPIW times were 33 minutes at 30 days, 41 minutes at 60 days, and 42 minutes at 1 year. Face to face provider-patient time increased 30% to 61% at 30 days, 58% at 60 days, and 59% at 1 year. The median number of patients in a 4-hour clinic increased from 10 to 12. Satisfaction survey Problem Scores improved and were sustained. Lean methodology may be used to improve clinic efficiency as well as patient and staff's experience. Copyright 2010. Published by Elsevier Inc.

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.

Models Predictive of Metabolic Syndrome Components in Obese Pediatric Patients.

PubMed

Ortega-Cortes, Rosa; Trujillo, Xóchitl; Hurtado López, Erika Fabiola; López Beltrán, Ana Laura; Colunga Rodríguez, Cecilia; Barrera-de Leon, Juan Carlos; Tlacuilo-Parra, Alberto

2016-01-01

Components of metabolic syndrome (MetS) are complications caused by abdominal obesity and insulin resistance (IR). Diagnosis of MetS by clinical indicators could help to identify patients at risk of cardiovascular disease and type 2 diabetes. We undertook this study to propose predictive indicators of MetS in obese children and adolescents. A cross-sectional study was carried out. After obtaining informed consent and the registration of the study with an institutional research committee, 172 obese patients from an Obesity Clinic, aged 6-15 years, were included. Variables included were waist circumference (WC), glucose, high-density lipoprotein (HDL), triglycerides (TGL), blood pressure, insulin resistance (by homeostatic model assessment HOMA-index), acanthosis nigricans (AN), uric acid, serum glutamic oxaloacetic transaminase (GOT) and alanine transaminase, and hepatic sonogram. International standards for age and sex variables were used. Multivariate analysis was applied. Variables predicted components of MetS in children: HOMA-IR (insulin resistance by HOMA index) was increased by 2.4 in hepatic steatosis, by 0.6 for each unit of SUA (serum uric acid), and by 0.009 for every mg/dL of triglycerides. In adolescents, every cm of waist circumference increased systolic blood pressure by 0.6 mmHg, and each unit of SUA increased it by 2.9 mmHg. Serum uric acid and waist circumference are useful and accessible variables that can predict an increased risk of cardiovascular disease in obese pediatric patients. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Reward-related neural activity and structure predict future substance use in dysregulated youth.

PubMed

Bertocci, M A; Bebko, G; Versace, A; Iyengar, S; Bonar, L; Forbes, E E; Almeida, J R C; Perlman, S B; Schirda, C; Travis, M J; Gill, M K; Diwadkar, V A; Sunshine, J L; Holland, S K; Kowatch, R A; Birmaher, B; Axelson, D A; Frazier, T W; Arnold, L E; Fristad, M A; Youngstrom, E A; Horwitz, S M; Findling, R L; Phillips, M L

2017-06-01

Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth. LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables. Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%. These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.

Predictors and Moderators of Treatment Response in Childhood Anxiety Disorders: Results from the CAMS Trial

PubMed Central

Compton, Scott N.; Peris, Tara S.; Almirall, Daniel; Birmaher, Boris; Sherrill, Joel; Kendall, Phillip C.; March, John S.; Gosch, Elizabeth A.; Ginsburg, Golda S.; Rynn, Moira A.; Piacentini, John C.; McCracken, James T.; Keeton, Courtney P.; Suveg, Cynthia M.; Aschenbrand, Sasha G.; Sakolsky, Dara; Iyengar, Satish; Walkup, John T.; Albano, Anne Marie

2014-01-01

Objective To examine predictors and moderators of treatment outcomes among 488 youth ages 7-17 years (50% female; 74% ≤ 12 years) with DSM-IV diagnoses of separation anxiety disorder, social phobia, or generalized anxiety disorder who were randomly assigned to receive either cognitive behavior therapy (CBT), sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) in the Child/Adolescent Anxiety Multimodal Study (CAMS). Method Six classes of predictor and moderator variables (22 variables) were identified from the literature and examined using continuous (Pediatric Anxiety Ratings Scale; PARS) and categorical (Clinical Global Impression Scale-Improvement; CGI-I) outcome measures. Results Three baseline variables predicted better outcomes (independent of treatment condition) on the PARS, including low anxiety severity (as measured by parents and independent evaluators) and caregiver strain. No baseline variables were found to predict week 12 responder status (CGI-I). Participant's principal diagnosis moderated treatment outcomes, but only on the PARS. No baseline variables were found to moderate treatment outcomes on week 12 responder status (CGI-I). Discussion Overall, anxious children responded favorably to CAMS treatments. However, having more severe and impairing anxiety, greater caregiver strain, and a principal diagnosis of social phobia were associated with less favorable outcomes. Clinical implications of these findings are discussed. PMID:24417601

Elective neck dissection for primary oral cavity squamous cell carcinoma involving the tongue should include sublevel IIb.

PubMed

Maher, Nigel Gordon; Hoffman, Gary Russell

2014-11-01

The surgical clearance of sublevel IIb lymph nodes, facilitated by neck dissection, increases the risk of postoperative shoulder dysfunction. Our study purpose was to determine the value of including sublevel IIb in elective neck dissections for primary oral cavity squamous cell carcinoma (OCSCC). A retrospective cohort study based on a review of the pathology records accumulated by 1 head and neck surgeon was conducted for 71 patients with clinically node-negative, primary OCSCC treated from 2006 to June 2013. The predictor variables were the oral cavity subsite and tumor clinicopathologic characteristics (ie, perineural, perivascular, and perilymphatic invasion, tumor depth, and T stage). The primary outcome variable was the presence of sublevel IIb metastasis. The secondary outcome variables were the survival and tumor recurrence rates and metastases to any cervical level. Descriptive statistics were calculated for the categorical and continuous variables. A comparison of categorical variables was performed using Fisher's exact test; for continuous variables, t tests or the Mann-Whitney U test were used for 2 groups and analysis of variance or Kruskal-Wallis tests (with Bonferroni's correction) were used for more than 2 groups, depending on the distribution. Disease-specific survival (DSS) analyses were plotted for the predictor variables and patients with sublevel IIb metastasis. Competing risks models were created using the Fine and Gray method (SAS macro %PSHREG) to provide estimates of the crude and adjusted subhazard ratios for DSS for all variables. A total of 71 patients were included in the present study, of whom 69% were male. The greatest proportion of oral cavity subsites was from the tongue and floor of mouth. The overall frequency of sublevel IIb lymphatic metastases at neck dissection was 5.6% of the patient cohort. Sublevel IIb metastases occurred from the primary sites involving the tongue (n = 3) and retromolar trigone (n = 1). The incidence of perilymphatic and perivascular invasion was significantly associated with sublevel IIb lymphatic metastases (P < .02). Sublevel IIb is likely to be an important region to incorporate in elective neck dissections for primary OCSCC involving the tongue. More studies are needed, with greater numbers, to clarify the risk of metastasis to sublevel IIb from oral cavity subsites in primary OCSCC with clinically node-negative necks. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Prediction of Methotrexate Clinical Response in Portuguese Rheumatoid Arthritis Patients: Implication of MTHFR rs1801133 and ATIC rs4673993 Polymorphisms

PubMed Central

Lima, Aurea; Monteiro, Joaquim; Bernardes, Miguel; Sousa, Hugo; Azevedo, Rita; Seabra, Vitor; Medeiros, Rui

2014-01-01

Objective. Methotrexate (MTX), the most used drug in rheumatoid arthritis (RA) treatment, showing variability in clinical response, is often associated with genetic polymorphisms. This study aimed to elucidate the role of methylenetetrahydrofolate reductase (MTHFR) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase (ATIC) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese RA patients. Methods. Study included 233 RA patients treated with MTX for at least six months. MTHFR C677T and ATIC T675C polymorphisms were genotyped and clinicopathological variables were collected. Statistical analyses were performed and binary logistic regression method adjusted to possible confounding variables. Results. Multivariate analyses demonstrated that MTHFR 677TT (OR = 4.63; P = 0.013) and ATIC 675T carriers (OR = 5.16; P = 0.013) were associated with over 4-fold increased risk for nonresponse. For clinicopathological variables, noncurrent smokers (OR = 7.98; P = 0.001), patients positive to anti-cyclic citrullinated peptide (OR = 3.53; P = 0.004) and antinuclear antibodies (OR = 2.28; P = 0.045), with higher health assessment questionnaire score (OR = 2.42; P = 0.007), and nonsteroidal anti-inflammatory drug users (OR = 2.77; P = 0.018) were also associated with nonresponse. Contrarily, subcutaneous administration route (OR = 0.11; P < 0.001) was associated with response. Conclusion. Our study suggests that MTHFR C677T and ATIC T675C genotyping combined with clinicopathological data may help to identify patients whom will not benefit from MTX treatment and, therefore, assist clinicians in personalizing RA treatment. PMID:24967362

A predictive model for diagnosing bipolar disorder based on the clinical characteristics of major depressive episodes in Chinese population.

PubMed

Gan, Zhaoyu; Diao, Feici; Wei, Qinling; Wu, Xiaoli; Cheng, Minfeng; Guan, Nianhong; Zhang, Ming; Zhang, Jinbei

2011-11-01

A correct timely diagnosis of bipolar depression remains a big challenge for clinicians. This study aimed to develop a clinical characteristic based model to predict the diagnosis of bipolar disorder among patients with current major depressive episodes. A prospective study was carried out on 344 patients with current major depressive episodes, with 268 completing 1-year follow-up. Data were collected through structured interviews. Univariate binary logistic regression was conducted to select potential predictive variables among 19 initial variables, and then multivariate binary logistic regression was performed to analyze the combination of risk factors and build a predictive model. Receiver operating characteristic (ROC) curve was plotted. Of 19 initial variables, 13 variables were preliminarily selected, and then forward stepwise exercise produced a final model consisting of 6 variables: age at first onset, maximum duration of depressive episodes, somatalgia, hypersomnia, diurnal variation of mood, irritability. The correct prediction rate of this model was 78% (95%CI: 75%-86%) and the area under the ROC curve was 0.85 (95%CI: 0.80-0.90). The cut-off point for age at first onset was 28.5 years old, while the cut-off point for maximum duration of depressive episode was 7.5 months. The limitations of this study include small sample size, relatively short follow-up period and lack of treatment information. Our predictive models based on six clinical characteristics of major depressive episodes prove to be robust and can help differentiate bipolar depression from unipolar depression. Copyright © 2011 Elsevier B.V. All rights reserved.

Demographic, clinical, and quality of life variables related to embarrassment in veterans living with an intestinal stoma.

PubMed

Mitchell, Kimberly A; Rawl, Susan M; Schmidt, C Max; Grant, Marcia; Ko, Clifford Y; Baldwin, Carol M; Wendel, Christopher; Krouse, Robert S

2007-01-01

The study aims were to identify demographic, clinical, and quality of life variables related to embarrassment for people living with ostomies and to determine the experiences and/or feelings of veterans who were embarrassed by their ostomy. This was a cross-sectional, correlational study. A convenience sample of veterans (n = 239) living with ostomies from 3 VA medical centers was studied. The veterans were primarily Caucasian (84%), male (92%), and older (M = 69). The modified City of Hope Quality of Life-Ostomy questionnaire was used. Additionally, an open-ended question related to living with an ostomy was asked. The questionnaire packets were mailed to participants and self-administered. Approximately half of the participants (48%) rated their embarrassment as low, but 26% reported high embarrassment. Participants with high embarrassment were compared to those with low embarrassment on demographic, clinical, and quality of life variables. High embarrassment was associated with poorer total quality of life (P < .001) and poorer quality of life on the physical (P < .001), psychological (P < .001), social (P < .001), and spiritual (P < .001) subscales. Younger (P < .001) and unpartnered veterans (P < .001) were more likely to be highly embarrassed. Veterans with high embarrassment had higher anxiety (P < .001) and depression (P < .001), more difficulty with intimacy (P < .001), and felt more isolated (P < .001). Spiritual domain variables like hopefulness were associated with low embarrassment (P < .001). Sources of embarrassment included leakage, odor, and noise. Embarrassment may negatively impact a person's quality of life; therefore, the variables associated with high embarrassment should be recognized and addressed.

A statistically compiled test battery for feasible evaluation of knee function after rupture of the Anterior Cruciate Ligament - derived from long-term follow-up data.

PubMed

Schelin, Lina; Tengman, Eva; Ryden, Patrik; Häger, Charlotte

2017-01-01

Clinical test batteries for evaluation of knee function after injury to the Anterior Cruciate Ligament (ACL) should be valid and feasible, while reliably capturing the outcome of rehabilitation. There is currently a lack of consensus as to which of the many available assessment tools for knee function that should be included. The present aim was to use a statistical approach to investigate the contribution of frequently used tests to avoid redundancy, and filter them down to a proposed comprehensive and yet feasible test battery for long-term evaluation after ACL injury. In total 48 outcome variables related to knee function, all potentially relevant for a long-term follow-up, were included from a cross-sectional study where 70 ACL-injured (17-28 years post injury) individuals were compared to 33 controls. Cluster analysis and logistic regression were used to group variables and identify an optimal test battery, from which a summarized estimator of knee function representing various functional aspects was derived. As expected, several variables were strongly correlated, and the variables also fell into logical clusters with higher within-correlation (max ρ = 0.61) than between clusters (max ρ = 0.19). An extracted test battery with just four variables assessing one-leg balance, isokinetic knee extension strength and hop performance (one-leg hop, side hop) were mathematically combined to an estimator of knee function, which acceptably classified ACL-injured individuals and controls. This estimator, derived from objective measures, correlated significantly with self-reported function, e.g. Lysholm score (ρ = 0.66; p<0.001). The proposed test battery, based on a solid statistical approach, includes assessments which are all clinically feasible, while also covering complementary aspects of knee function. Similar test batteries could be determined for earlier phases of ACL rehabilitation or to enable longitudinal monitoring. Such developments, established on a well-grounded consensus of measurements, would facilitate comparisons of studies and enable evidence-based rehabilitation.

Transforming primary care in the New Orleans safety-net: the patient experience.

PubMed

Schmidt, Laura A; Rittenhouse, Diane R; Wu, Kevin J; Wiley, James A

2013-02-01

The patient-centered medical home (PCMH) is a key service delivery innovation in health reform. However, there are growing questions about whether the changes in clinics promoted by the PCMH model lead to improvements in the patient experience. To test the hypothesis that PCMH improvements in safety-net primary care clinics are associated with a more positive patient experience. Multilevel cross-sectional analysis of patients nested within the primary care clinics that serve them. Primary care clinic leaders and patients throughout the City of New Orleans health care safety-net. Dependent variables included patient ratings of accessibility, coordination, and confidence in the quality/safety of care. The key independent variable was a score measuring PCMH structural and process improvements at the clinic level. Approximately two thirds of patients in New Orleans gave positive ratings to their clinics on access and quality/safety, but only one third did for care coordination. In all but the largest clinics, patient experiences of care coordination were positively associated with the clinic's use of PCMH structural and process changes. Results for patient ratings of access and quality/safety were mixed. Among primary care clinics in the New Orleans safety-net, use of more PCMH improvements at the clinic level led to more positive patient rating of care coordination, but not of accessibility or confidence in quality/safety. Ongoing efforts to pilot, demonstrate, implement, and evaluate the PCMH should consider how the impact of medical practice transformation could vary across different aspects of the patient experience.

Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

PubMed

Pes, Giovanni Mario; Delitala, Alessandro Palmerio; Errigo, Alessandra; Delitala, Giuseppe; Dore, Maria Pina

2016-06-01

Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers) showed a faster beta-cells failure and PC-3 (characterized mostly by gender and high triglycerides) and PC-4 (high cholesterol) showed a slower beta-cells failure. PC-1 (including dislipidemia and other metabolic dysfunctions), showed a mild beta-cells failure. In conclusion variable clustering might be consistent with different pathogenic pathways and/or distinct immune mechanisms in LADA and could potentially help physicians improve the clinical management of these patients.

Allergen immunotherapy: exploring areas for further inquiry.

PubMed

Ramsey, Tam; Lai, Wanda; Svider, Peter F; Hojjat, Houmehr; Eloy, Jean Anderson; Folbe, Adam J

2017-12-01

Allergy-related illness impacts millions of individuals worldwide. Our objectives were to characterize current trends of clinical trials research relating to allergen immunotherapy and to describe the landscape of allergen immunotherapy in National Institutes of Health (NIH)-supported research inquiry. On ClinicalTrials.gov, the following terms were searched: allergen immunotherapy OR allergy immunotherapy. Variables, including completion status, dates, design, study population, funder, location, and allergen were recorded. The NIH Research Portfolio Online Reporting Tools (RePORTER) system was also used to gather relevant variables. A total of 372 clinical trials met inclusion criteria. The proportion of industry-funded clinical trials has declined over 15 years. There has been a slow decline in pollen allergy immunotherapy research, with an increase in both food and animal allergy immunotherapy research. Otolaryngologists comprised only 6.4% of clinical trials principal investigators (PIs). There was a total adjusted NIH funding of $74,986,125 for the 118 total funding years. Despite an immense interest in allergen immunotherapy, this analysis demonstrates that otolaryngologists represented a small proportion of PIs leading associated clinical trials and basic science inquiry. The proportion of trials with industry sponsorship has declined considerably in recent decades. These trends could help direct future resource allocation for allergen immunotherapy. © 2017 ARS-AAOA, LLC.

Clinical implications of single- versus multiple-site keloid disorder: a retrospective study in an Asian population.

PubMed

Park, Tae Hwan; Park, Ji Hae; Tirgan, Michael H; Halim, Ahmad Sukari; Chang, Choong Hyun

2015-02-01

There is strong evidence of genetic susceptibility in individuals with keloid disorder. The purpose of this cross-sectional study was to determine the clinical relevance of our proposed variables on the multiplicity of keloids by further investigating the presence of other keloids and a family history. This was a retrospective review, using institutional review board-approved questionnaires, of patients with keloids who were seen at Kangbuk Samsung Hospital between December 2002 and February 2010. Eight hundred sixty-eight patients were included in our study. Comparisons between the 2 groups were made using Mann-Whitney tests for continuous variables and χ2 tests for categorical variables. In our patient group, younger age of onset and the presence of family history were significantly associated with the occurrence of keloids at multiple sites. The locations of extra-auricular keloids, in order of frequency, included the shoulder; anterior chest, including the breasts; deltoid; trunk and pubic area; upper extremities; lower extremities; and other sites. As compared to secondary keloids, primary keloids were significantly associated with both a lower degree of recurrence and the presence of other keloids. The presence or absence of family history was significantly associated with the presence or absence of other keloids and primary or secondary keloids. Keloid disorder is one of the most frustrating problems in wound healing and advances in our understanding of the differences of occurrence at a single site versus multiple sites might help in understanding pathogenesis and improving treatment.

Research fellowship programs as a pathway for training independent clinical pharmacy scientists.

PubMed

Mueller, Eric W; Bishop, Jeffrey R; Kanaan, Abir O; Kiser, Tyree H; Phan, Hanna; Yang, Katherine Y

2015-03-01

The American College of Clinical Pharmacy (ACCP) Research Affairs Committee published a commentary in 2013 on training clinical pharmacy scientists in the context of changes in economic, professional, political, and research environments. The commentary centered on the opportunities for pharmacists in clinical/translational research including strategies for ACCP, colleges of pharmacy, and the profession to increase the number and impact of clinical pharmacy scientists. A postdoctoral fellowship is cited as a current training pathway, capable of producing independent and productive pharmacy researchers. However, a decline in the number of programs, decreased funding availability, and variability in fellowship program activities and research focus have brought into question the relevance of this research training pathway to meet demand and opportunities. In response to these points, this commentary examines the state of research fellowship training including the current ACCP research fellowship review process, the need for standardization of research fellowship programs, and strategies to strengthen and promote research fellowships as relevant researcher training pathways. © 2015 Pharmacotherapy Publications, Inc.

A Call to Standardize Preanalytic Data Elements for Biospecimens, Part II.

PubMed

Robb, James A; Bry, Lynn; Sluss, Patrick M; Wagar, Elizabeth A; Kennedy, Mary F

2015-09-01

Biospecimens must have appropriate clinical annotation (data) to ensure optimal quality for both patient care and research. Additional clinical preanalytic variables are the focus of this continuing study. To complete the identification of the essential preanalytic variables (data fields) that can, and in some instances should, be attached to every collected biospecimen by adding the additional specific variables for clinical chemistry and microbiology to our original 170 variables. The College of American Pathologists Diagnostic Intelligence and Health Information Technology Committee sponsored a second Biorepository Working Group to complete the list of preanalytic variables for annotating biospecimens. Members of the second Biorepository Working Group are experts in clinical pathology and microbiology. Additional preanalytic area-specific variables were identified and ranked along with definitions and potential negative impacts if the variable is not attached to the biospecimen. The draft manuscript was reviewed by additional national and international stakeholders. Four additional required preanalytic variables were identified specifically for clinical chemistry and microbiology biospecimens that can be used as a guide for site-specific implementation into patient care and research biorepository processes. In our collective experience, selecting which of the many preanalytic variables to attach to any specific set of biospecimens used for patient care and/or research is often difficult. The additional ranked list should be of practical benefit when selecting preanalytic variables for a given biospecimen collection.

Developing and validating a predictive model for stroke progression.

PubMed

Craig, L E; Wu, O; Gilmour, H; Barber, M; Langhorne, P

2011-01-01

Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Two patient cohorts were used for this study - the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p < 0.1) on univariate analysis were included in the multivariate model. Logistic regression was the technique employed using backward stepwise regression to drop the least significant variables (p > 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72-0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50-0.92)]. The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and calibration of the predictive model appear sufficiently high to provide accurate predictions. This study also offers some discussion around the validation of predictive models for wider use in clinical practice.

Factors associated with fear of falling in people with Parkinson’s disease

PubMed Central

2014-01-01

Background This study aimed to comprehensibly investigate potential contributing factors to fear of falling (FOF) among people with idiopathic Parkinson’s disease (PD). Methods The study included 104 people with PD. Mean (SD) age and PD-duration were 68 (9.4) and 5 (4.2) years, respectively, and the participants’ PD-symptoms were relatively mild. FOF (the dependent variable) was investigated with the Swedish version of the Falls Efficacy Scale, i.e. FES(S). The first multiple linear regression model replicated a previous study and independent variables targeted: walking difficulties in daily life; freezing of gait; dyskinesia; fatigue; need of help in daily activities; age; PD-duration; history of falls/near falls and pain. Model II included also the following clinically assessed variables: motor symptoms, cognitive functions, gait speed, dual-task difficulties and functional balance performance as well as reactive postural responses. Results Both regression models showed that the strongest contributing factor to FOF was walking difficulties, i.e. explaining 60% and 64% of the variance in FOF-scores, respectively. Other significant independent variables in both models were needing help from others in daily activities and fatigue. Functional balance was the only clinical variable contributing additional significant information to model I, increasing the explained variance from 66% to 73%. Conclusions The results imply that one should primarily target walking difficulties in daily life in order to reduce FOF in people mildly affected by PD. This finding applies even when considering a broad variety of aspects not previously considered in PD-studies targeting FOF. Functional balance performance, dependence in daily activities, and fatigue were also independently associated with FOF, but to a lesser extent. Longitudinal studies are warranted to gain an increased understanding of predictors of FOF in PD and who is at risk of developing a FOF. PMID:24456482

Hip fracture in the elderly: a re-analysis of the EPIDOS study with causal Bayesian networks.

PubMed

Caillet, Pascal; Klemm, Sarah; Ducher, Michel; Aussem, Alexandre; Schott, Anne-Marie

2015-01-01

Hip fractures commonly result in permanent disability, institutionalization or death in elderly. Existing hip-fracture predicting tools are underused in clinical practice, partly due to their lack of intuitive interpretation. By use of a graphical layer, Bayesian network models could increase the attractiveness of fracture prediction tools. Our aim was to study the potential contribution of a causal Bayesian network in this clinical setting. A logistic regression was performed as a standard control approach to check the robustness of the causal Bayesian network approach. EPIDOS is a multicenter study, conducted in an ambulatory care setting in five French cities between 1992 and 1996 and updated in 2010. The study included 7598 women aged 75 years or older, in which fractures were assessed quarterly during 4 years. A causal Bayesian network and a logistic regression were performed on EPIDOS data to describe major variables involved in hip fractures occurrences. Both models had similar association estimations and predictive performances. They detected gait speed and mineral bone density as variables the most involved in the fracture process. The causal Bayesian network showed that gait speed and bone mineral density were directly connected to fracture and seem to mediate the influence of all the other variables included in our model. The logistic regression approach detected multiple interactions involving psychotropic drug use, age and bone mineral density. Both approaches retrieved similar variables as predictors of hip fractures. However, Bayesian network highlighted the whole web of relation between the variables involved in the analysis, suggesting a possible mechanism leading to hip fracture. According to the latter results, intervention focusing concomitantly on gait speed and bone mineral density may be necessary for an optimal prevention of hip fracture occurrence in elderly people.

Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability.

PubMed

Szulc, P; Naylor, K; Hoyle, N R; Eastell, R; Leary, E T

2017-09-01

The National Bone Health Alliance (NBHA) recommends standardized sample handling and patient preparation for C-terminal telopeptide of type I collagen (CTX-I) and N-terminal propeptide of type I procollagen (PINP) measurements to reduce pre-analytical variability. Controllable and uncontrollable patient-related factors are reviewed to facilitate interpretation and minimize pre-analytical variability. The IOF and the International Federation of Clinical Chemistry (IFCC) Bone Marker Standards Working Group have identified PINP and CTX-I in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA Bone Turnover Marker Project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation. Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection. Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation. Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.

Perspectives on optimizing care of patients in multidisciplinary chronic kidney disease clinics.

PubMed

Collister, David; Russell, Randall; Verdon, Josee; Beaulieu, Monica; Levin, Adeera

2016-01-01

To summarize a jointly held symposium by the Canadian Society of Nephrology (CSN), the Canadian Association of Nephrology Administrators (CANA), and the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) entitled "Perspectives on Optimizing Care of Patients in Multidisciplinary Chronic Kidney Disease (CKD) Clinics" that was held on April 24, 2015, in Montreal, Quebec. The panel consisted of a variety of members from across Canada including a multidisciplinary CKD clinic patient (Randall Russell), nephrology fellow (Dr. David Collister), geriatrician (Dr. Josee Verdon), and nephrologists (Dr. Monica Beaulieu, Dr. Adeera Levin). The objectives of the symposium were (1) to gain an understanding of the goals of care for CKD patients, (2) to gain an appreciation of different perspectives regarding optimal care for patients with CKD, (3) to examine the components required for optimal care including education strategies, structures, and tools, and (4) to describe a framework and metrics for CKD care which respect patient and system needs. This article summarizes the key concepts discussed at the symposium from a patient and physician perspectives. Key messages include (1) understanding patient values and preferences is important as it provides a framework as to what to prioritize in multidisciplinary CKD clinic and provincial renal program models, (2) barriers to effective communication and education are common in the elderly, and adaptive strategies to limit their influence are critical to improve adherence and facilitate shared decision-making, (3) the use of standardized operating procedures (SOPs) improves efficiency and minimizes practice variability among health care practitioners, and (4) CKD scorecards with standardized system processes are useful in approaching variability as well as measuring and improving patient outcomes. The perspectives provided may not be applicable across centers given the differences in patient populations including age, ethnicity, culture, language, socioeconomic status, education, and multidisciplinary CKD clinic structure and function. Knowledge transmission by collaborative interprovincial and interprofessional networks may play a role in facilitating optimal CKD care. Validation of system and clinic models that improve outcomes is needed prior to disseminating these best practices.

Development of a clinical prediction rule for identifying women with tension-type headache who are likely to achieve short-term success with joint mobilization and muscle trigger point therapy.

PubMed

Fernández-de-las-Peñas, César; Cleland, Joshua A; Palomeque-del-Cerro, Luis; Caminero, Ana Belén; Guillem-Mesado, Amparo; Jiménez-García, Rodrigo

2011-02-01

To identify prognostic factors from the history and physical examination in women with tension-type headache (TTH) who are likely to experience self-perceived clinical improvement following a multimodal physical therapy session including joint mobilization and muscle trigger point (TrP) therapies. No definitive therapeutic intervention is available for TTH. It would be useful for clinicians to have a clinical prediction rule for selecting which TTH patients may experience improved outcomes following a multimodal physical therapy program. Women diagnosed with pure TTH by 3 experienced neurologists according to the International Headache Society criteria from different neurology departments were included. They underwent a standardized examination (neck mobility, pressure pain thresholds, total tenderness score, presence of muscle TrPs, Medical Outcomes Study 36-Item Short Form, the Neck Disability Index [NDI], the Beck Depression Inventory, and the Headache Disability Inventory) and then a multimodal physical therapy session including joint mobilization and TrP therapies. The treatment session included a 30-second grade III or IV central posterior-anterior nonthrust mobilization applied from T4 to T1 thoracic vertebrae, at C7-T1 cervico-thoracic junction and C1-C2 vertebrae for an overall intervention time of 5 minutes Different TrP techniques, particularly soft tissue stroke, pressure release, or muscle energy were applied to head and neck-shoulder muscles (temporalis, suboccipital, upper trapezius, splenius capitis, semispinalis capitis, sternocleidomastoid) to inactivate active muscle TrPs. Participants were classified as having achieved a successful outcome 1 week after the session based on their self-perceived recovery. Potential prognostic variables were entered into a stepwise logistic regression model to determine the most accurate set of variables for prediction of success. Data for 76 subjects were included in the analysis, of which 36 experienced a successful outcome (48%). Eight prognostic variables were retained in the regression model: mean age <44.5 years, presence of left sternocleidomastoid TrP, presence of suboccipital TrP, presence of left superior oblique muscle TrP, cervical rotation to the left > 69°, total tenderness score <20.5, NDI <18.5, referred pain area of right upper trapezius muscle TrP >42.23. The current clinical prediction rule may allow clinicians to make an a priori identification of women with TTH who are likely to experience short-term self-report improvement with a multimodal session including joint mobilizations and TrP therapies. Future studies are necessary to validate these findings. © 2010 American Headache Society.

Reporting the accuracy of biochemical measurements for epidemiologic and nutrition studies.

PubMed

McShane, L M; Clark, L C; Combs, G F; Turnbull, B W

1991-06-01

Procedures for reporting and monitoring the accuracy of biochemical measurements are presented. They are proposed as standard reporting procedures for laboratory assays for epidemiologic and clinical-nutrition studies. The recommended procedures require identification and estimation of all major sources of variability and explanations of laboratory quality control procedures employed. Variance-components techniques are used to model the total variability and calculate a maximum percent error that provides an easily understandable measure of laboratory precision accounting for all sources of variability. This avoids ambiguities encountered when reporting an SD that may taken into account only a few of the potential sources of variability. Other proposed uses of the total-variability model include estimating precision of laboratory methods for various replication schemes and developing effective quality control-checking schemes. These procedures are demonstrated with an example of the analysis of alpha-tocopherol in human plasma by using high-performance liquid chromatography.

Dysthymic Disorder and Double Depression: Prediction of 10-Year Course Trajectories and Outcomes

PubMed Central

Klein, Daniel N.; Shankman, Stewart A.; Rose, Suzanne

2008-01-01

We sought to identify baseline predictors of 10-year course trajectories and outcomes in patients with dysthymic disorder and double depression. Eighty-seven outpatients with early-onset (< 21 years) dysthymic disorder, with or without superimposed major depression, were assessed five times at 30-month intervals for 10 years. Baseline evaluations included semi-structured diagnostic interviews for Axis I and II psychopathology and childhood adversity. Direct interview and family history data were collected on first-degree relatives. Follow-up assessments included the Longitudinal Follow-up Evaluation and Hamilton Depression Rating Scale. Using mixed effects growth curve models, univariate predictors of depression severity and functional impairment at 10-year outcome included older age, less education, concurrent anxiety disorder, greater familial loading for chronic depression, a history of a poorer maternal relationship in childhood, and a history of childhood sexual abuse. In addition, longer duration of dysthymic disorder also predicted greater impairment 10 years later. Predictors of a poorer trajectory of depressive symptoms over time included ethnicity and personality disorders; predictors of a poorer trajectory of social functioning included familial loading of chronic depression and quality of the childhood maternal relationship. Thus, demographic, clinical, family history, and early adversity variables all contribute to predicting the long term trajectory and outcome of DD. These variables should be routinely assessed in clinical evaluations and can provide clinicians with valuable prognostic information. PMID:17466334

Dysthymic disorder and double depression: prediction of 10-year course trajectories and outcomes.

PubMed

Klein, Daniel N; Shankman, Stewart A; Rose, Suzanne

2008-04-01

We sought to identify baseline predictors of 10-year course trajectories and outcomes in patients with dysthymic disorder and double depression. Eighty-seven outpatients with early-onset (<21 years) dysthymic disorder, with or without superimposed major depression, were assessed five times at 30-month intervals for 10 years. Baseline evaluations included semi-structured diagnostic interviews for Axis I and II psychopathology and childhood adversity. Direct interview and family history data were collected on first-degree relatives. Follow-up assessments included the Longitudinal Follow-up Evaluation and Hamilton Depression Rating Scale. Using mixed effects growth curve models, univariate predictors of depression severity and functional impairment at 10-year outcome included older age, less education, concurrent anxiety disorder, greater familial loading for chronic depression, a history of a poorer maternal relationship in childhood, and a history of childhood sexual abuse. In addition, longer duration of dysthymic disorder also predicted greater impairment 10 years later. Predictors of a poorer trajectory of depressive symptoms over time included ethnicity and personality disorders; predictors of a poorer trajectory of social functioning included familial loading of chronic depression and quality of the childhood maternal relationship. Thus, demographic, clinical, family history, and early adversity variables all contribute to predicting the long-term trajectory and outcome of DD. These variables should be routinely assessed in clinical evaluations and can provide clinicians with valuable prognostic information.

An 80-year experience with optic nerve glioma cases at the Armed Forces Institute of Pathology: evolution from museum to molecular evaluation suggests possibe interventions in the cellular senescence and microglial pathways (an American Ophthalmological Society thesis).

PubMed

Cameron, J Douglas; Rodriguez, Fausto J; Rushing, Elisabeth; Horkayne-Szakaly, Iren; Eberhart, Charles

2014-01-01

To determine whether p16, a molecular marker of cellular senescence, and CD68, a microglial marker, are detectible in optic nerve glioma tissue stored for decades, thus providing potential targets for pharmacologic intervention. Cases were retrieved from the Armed Forces Institute of Pathology Registry of Ophthalmic Pathology. Clinical information was tabulated. In specimens with sufficient tissue, a tissue microarray was constructed to conduct molecular studies. Ninety-two cases were included: gender distribution was in a ratio of one male to 1.6 females, and age range was 2 months to 50 years (average age, 10.8 years). Neurofibromatosis type 1 was identified in 10 cases (10.8%). The majority presented with decreased vision and exophthalmos. Forty-eight cases were studied by a tissue microarray construction. Glial fibrillary acidic protein, a control for immunoreactivity, was positive in 46 cases (96%). Immunoreactivity for p16 protein was seen in 36 cases (75%) and CD68-positive cells in 34 (71%). Limitations include referral bias, limited clinical information, limited amount of tissue, and extended period of tissue preservation. Optic nerve glioma is a tumor of the visual axis in young individuals, which is generally indolent but with a variable clinical course. Traditional histopathologic techniques have not been reliably predictive of clinical course. This microarray contains tumors with representative demographic, clinical, and histologic characteristics for optic nerve glioma. Immunoreactivity for p16 protein and CD68 is positive in the majority. These findings suggest a possible explanation for the variable clinical course and identify therapeutic targets in the cell senescence and microglial pathways.

Intrinsic platelet reactivity before start with clopidogrel as predictor for on-clopidogrel platelet function and long-term clinical outcome.

PubMed

Hochholzer, Willibald; Valina, Christian M; Bömicke, Timo; Amann, Michael; Stratz, Christian; Nührenberg, Thomas; Trenk, Dietmar; Neumann, Franz-Josef

2015-07-01

High on-clopidogrel platelet reactivity is associated with worse clinical outcome. Previous data suggest that intrinsic platelet reactivity before initiation of clopidogrel contributes significantly to on-clopidogrel platelet reactivity. It is unknown whether intrinsic reactivity can sufficiently predict on-clopidogrel reactivity and therefore identify patients with insufficient response to clopidogrel before initiation of treatment and at risk for worse clinical outcome. This analysis included 765 consecutive patients undergoing elective coronary stent implantation. Platelet reactivity was assessed by light transmission aggregometry (5 µM ADP) before administration of clopidogrel 600mg and after intake of first maintenance dose of clopidogrel on day 1 following coronary stenting. Patients were followed for up to seven years. The combined primary endpoint was death of any cause or non-fatal myocardial infarction. Intrinsic and on-clopidogrel platelet reactivity were significant correlated (r=0.31; p < 0.001). Among all tested clinical and genetic factors including the cytochrome P450 2C19*2 polymorphism, intrinsic platelet reactivity was the strongest predictor for on-clopidogrel platelet reactivity. However, intrinsic platelet reactivity could only explain 8 % of variability of on-clopidogrel platelet function. Only on-treatment platelet reactivity was predictive for long-term clinical outcome (HR 1.47, 95 % CI 1.05-2.05; p = 0.02) whereas intrinsic platelet reactivity was not (HR 1.03, 95 % CI 0.74-1.43; p = 0.86). In conclusion, intrinsic platelet reactivity before initiation of clopidogrel is the strongest predictor of early on-clopidogrel platelet reactivity but can only explain a minor proportion of its variability and is not significantly associated with clinical outcome. Thus, baseline testing cannot substitute on-clopidogrel platelet function testing.

Concussion Care Practices and Utilization of Evidence-Based Guidelines in the Evaluation and Management of Concussion: A Survey of New England Emergency Departments

PubMed Central

Seichepine, Daniel; Tschoe, Christine; Fritts, Nathan G.; Alosco, Michael L.; Berkowitz, Oren; Burke, Peter; Howland, Jonathan; Olshaker, Jonathan; Cantu, Robert C.; Baugh, Christine M.; Holsapple, James W.

2017-01-01

Abstract Evidence-based clinical practice guidelines can facilitate proper evaluation and management of concussions in the emergency department (ED), often the initial and primary point of contact for concussion care. There is no universally adopted set of guidelines for concussion management, and extant evidence suggests that there may be variability in concussion care practices and limited application of clinical practice guidelines in the ED. This study surveyed EDs throughout New England to examine current practices of concussion care and utilization of evidence-based clinical practice guidelines in the evaluation and management of concussions. In 2013, a 32-item online survey was e-mailed to 149/168 EDs throughout New England (Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, Maine). Respondents included senior administrators asked to report on their EDs use of clinical practice guidelines, neuroimaging decision-making, and discharge instructions for concussion management. Of the 72/78 respondents included, 35% reported absence of clinical practice guidelines, and 57% reported inconsistency in the type of guidelines used. Practitioner preference guided neuroimaging decision-making for 57%. Although 94% provided written discharge instructions, there was inconsistency in the recommended time frame for follow-up care (13% provided no specific time frame), the referral specialist to be seen (25% did not recommend any specialist), and return to activity instructions were inconsistent. There is much variability in concussion care practices and application of evidence-based clinical practice guidelines in the evaluation and management of concussions in New England EDs. Knowledge translational efforts will be critical to improve concussion management in the ED setting. PMID:27112592

An official multi-society statement: the role of clinical research results in the practice of critical care medicine.

PubMed

Tonelli, Mark R; Curtis, J Randall; Guntupalli, Kalpalatha K; Rubenfeld, Gordon D; Arroliga, Alejandro C; Brochard, Laurent; Douglas, Ivor S; Gutterman, David D; Hall, Jesse R; Kavanagh, Brian P; Mancebo, Jordi; Misak, Cheryl J; Simpson, Steven Q; Slutsky, Arthur S; Suffredini, Anthony F; Thompson, B Taylor; Ware, Lorraine B; Wheeler, Arthur P; Levy, Mitchell M

2012-05-15

While the results of clinical research are clearly valuable in the care of critically ill patients, the limitations of such information and the role of other forms of medical knowledge for clinical decision making have not been carefully examined. The leadership of three large professional societies representing critical care practitioners convened a diverse group representing a wide variety of views regarding the role of clinical research results in clinical practice to develop a document to serve as a basis for agreement and a framework for ongoing discussion. Consensus was reached on several issues. While the results of rigorous clinical research are important in arriving at the best course of action for an individual critically ill patient, other forms of medical knowledge, including clinical experience and pathophysiologic reasoning, remain essential. No single source of knowledge is sufficient to guide clinical decisions, nor does one kind of knowledge always take precedence over others. Clinicians will find clinical research compelling for a variety of reasons that go beyond study design. While clinical practice guidelines and protocols based upon clinical research may improve care and decrease variability in practice, clinicians must be able to understand and articulate the rationale as to why a particular protocol or guideline is used or why an alternative approach is taken. Making this clinical reasoning explicit is necessary to understand practice variability. Understanding the strengths and weaknesses of different kinds of medical knowledge for clinical decision making and factors beyond study design that make clinical research compelling to clinicians can provide a framework for understanding the role of clinical research in practice.

Personalized treatment planning with a model of radiation therapy outcomes for use in multiobjective optimization of IMRT plans for prostate cancer.

PubMed

Smith, Wade P; Kim, Minsun; Holdsworth, Clay; Liao, Jay; Phillips, Mark H

2016-03-11

To build a new treatment planning approach that extends beyond radiation transport and IMRT optimization by modeling the radiation therapy process and prognostic indicators for more outcome-focused decision making. An in-house treatment planning system was modified to include multiobjective inverse planning, a probabilistic outcome model, and a multi-attribute decision aid. A genetic algorithm generated a set of plans embodying trade-offs between the separate objectives. An influence diagram network modeled the radiation therapy process of prostate cancer using expert opinion, results of clinical trials, and published research. A Markov model calculated a quality adjusted life expectancy (QALE), which was the endpoint for ranking plans. The Multiobjective Evolutionary Algorithm (MOEA) was designed to produce an approximation of the Pareto Front representing optimal tradeoffs for IMRT plans. Prognostic information from the dosimetrics of the plans, and from patient-specific clinical variables were combined by the influence diagram. QALEs were calculated for each plan for each set of patient characteristics. Sensitivity analyses were conducted to explore changes in outcomes for variations in patient characteristics and dosimetric variables. The model calculated life expectancies that were in agreement with an independent clinical study. The radiation therapy model proposed has integrated a number of different physical, biological and clinical models into a more comprehensive model. It illustrates a number of the critical aspects of treatment planning that can be improved and represents a more detailed description of the therapy process. A Markov model was implemented to provide a stronger connection between dosimetric variables and clinical outcomes and could provide a practical, quantitative method for making difficult clinical decisions.

Clinical impact of sepsis at admission to the ICU of a private hospital in Salvador, Brazil.

PubMed

Juncal, Verena Ribeiro; Britto Neto, Lelivaldo Antonio de; Camelier, Aquiles Assunção; Messeder, Octavio Henrique Coelho; Farias, Augusto Manoel de Carvalho

2011-01-01

To describe the clinical characteristics, laboratory data, and clinical outcomes of patients with and without sepsis admitted to the ICU of a private hospital in the city of Salvador, Brazil, and to identify clinical variables related to a worse prognosis in those with sepsis. This was a longitudinal study including all patients admitted to the general ICU of the Hospital Português, in the city of Salvador, Brazil, between June of 2008 and March of 2009. At ICU admission, two groups of patients were identified: with sepsis and without sepsis. Epidemiological, clinical and laboratory data were collected, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score was calculated. Of the 144 patients in the study, 29 (20.1%) had sepsis. Among the patients with sepsis, males accounted for 55.2%, the mean age was 73.1 ± 14.6 years, and the mean APACHE II score was 23.8 ± 9.1, compared with 36.3%, 68.7 ± 17.7 years, and 18.4 ± 9.5, respectively, among those without sepsis. There were significant associations between a diagnosis of sepsis and the following variables: APACHE II score; in-hospital mortality; ICU mortality; HR; mean arterial pressure; hematocrit level; white blood cell count; and antibiotic use. The use of life support measures and lower hematocrit levels were associated with a worse prognosis in the patients with sepsis. The patients diagnosed with sepsis presented worse clinical outcomes, probably due to their greater severity. Hematocrit level was the only variable that was a predictor of mortality risk in the patients with sepsis.

Intercenter Differences in Bronchopulmonary Dysplasia or Death Among Very Low Birth Weight Infants

PubMed Central

Walsh, Michele; Bobashev, Georgiy; Das, Abhik; Levine, Burton; Carlo, Waldemar A.; Higgins, Rosemary D.

2011-01-01

OBJECTIVES: To determine (1) the magnitude of clustering of bronchopulmonary dysplasia (36 weeks) or death (the outcome) across centers of the Eunice Kennedy Shriver National Institute of Child and Human Development National Research Network, (2) the infant-level variables associated with the outcome and estimate their clustering, and (3) the center-specific practices associated with the differences and build predictive models. METHODS: Data on neonates with a birth weight of <1250 g from the cluster-randomized benchmarking trial were used to determine the magnitude of clustering of the outcome according to alternating logistic regression by using pairwise odds ratio and predictive modeling. Clinical variables associated with the outcome were identified by using multivariate analysis. The magnitude of clustering was then evaluated after correction for infant-level variables. Predictive models were developed by using center-specific and infant-level variables for data from 2001 2004 and projected to 2006. RESULTS: In 2001–2004, clustering of bronchopulmonary dysplasia/death was significant (pairwise odds ratio: 1.3; P < .001) and increased in 2006 (pairwise odds ratio: 1.6; overall incidence: 52%; range across centers: 32%–74%); center rates were relatively stable over time. Variables that varied according to center and were associated with increased risk of outcome included lower body temperature at NICU admission, use of prophylactic indomethacin, specific drug therapy on day 1, and lack of endotracheal intubation. Center differences remained significant even after correction for clustered variables. CONCLUSION: Bronchopulmonary dysplasia/death rates demonstrated moderate clustering according to center. Clinical variables associated with the outcome were also clustered. Center differences after correction of clustered variables indicate presence of as-yet unmeasured center variables. PMID:21149431

Birth Control in Clinical Trials

PubMed Central

Stewart, J.; Beyer, B. K.; Chadwick, K.; De Schaepdrijver, L.; Desai, M.; Enright, B.; Foster, W.; Hui, J. Y.; Moffat, G. J.; Tornesi, B.; Van Malderen, K.; Wiesner, L.; Chen, C. L.

2015-01-01

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives. PMID:27042398

Clinical and psycho-social profile of child and adolescent mental health care users and services at an urban child mental health clinic in South Africa.

PubMed

Raman, N; Janse van Rensburg, A B

2013-09-01

National and international child and adolescent mental healthcare policy and action advocate that the health and well being of children should be increasingly given greater attention. The purpose of this study was to describe the demographic, socio economic and clinical profile of the users at the child and adolescent mental health clinic of the Rahima Moosa Mother and Child Hospital (RMMCH). A descriptive, retrospective clinical audit from users' clinical files was performed over a one-year period from January to December 2007. Descriptive statistical analyses of demographic and socio-economic variables were made and these variables were compared with the presenting clinical problems. Odds ratios were calculated for variables that showed a statistically significant association (p-value less than 0.05). A total of 303 users attended this clinic. Statistical comparisons between demographic data and disorders revealed that being male increased the likelihood of presenting with AHDH and disruptive behaviour disorders; being female increased the likelihood of being sexually abused. Race showed a significant association with parent-child relationship difficulties. Regarding socio-economic variables, the identity of the caregiver of the child influenced the risk of disruptive behaviour disorders, sexual abuse, neglect and academic problems. Where the child was placed was a risk factor for disruptive behaviour disorders, sexual abuse, neglect and academic problems. Whether the mother of a user was alive or deceased, was found to be related to ADHD and disruptive behaviour and whether the father of a user was alive or deceased, was found to be related to sexual abuse and academic problems. The education level of the caregiver showed a significant association with sexual abuse, neglect and academic problems; the marital status of the parent (widowed mother) showed a significant association with bereavement. Household income was associated with sexual abuse, neglect and academic problems. This study demonstrated the impact that socio-economic circumstances have on the prevalence of childhood disorders; hence the urgent need for government and social welfare departments to improve the socio-economic status of communities. There is a need to improve psychiatric services for the population served by this hospital, including more clinics in its catchment area, as well as child psychiatry training posts and extended social work services.

Physician control of needle and syringe during aspiration-injection procedures with the new reciprocating syringe.

PubMed

Sibbitt, Wilmer; Sibbitt, Randy R; Michael, Adrian A; Fu, Druce I; Draeger, Hilda T; Twining, Jon M; Bankhurst, Arthur D

2006-04-01

To evaluate physician control of needle and syringe during aspiration-injection syringe procedures by comparing the new reciprocating procedure syringe to a traditional conventional syringe. Twenty-six physicians were tested for their individual ability to control the reciprocating and conventional syringes in typical aspiration-injection procedures using a novel quantitative needle-based displacement procedure model. Subsequently, the physicians performed 48 clinical aspiration-injection (arthrocentesis) procedures on 32 subjects randomized to the reciprocating or conventional syringes. Clinical outcomes included procedure time, patient pain, and operator satisfaction. Multivariate modeling methods were used to determine the experimental variables in the syringe control model most predictive of clinical outcome measures. In the model system, the reciprocating syringe significantly improved physician control of the syringe and needle, with a 66% reduction in unintended forward penetration (p < 0.001) and a 68% reduction in unintended retraction (p < 0.001). In clinical arthrocentesis, improvements were also noted: 30% reduction in procedure time (p < 0.03), 57% reduction in patient pain (p < 0.001), and a 79% increase in physician satisfaction (p < 0.001). The variables in the experimental system--unintended forward penetration, unintended retraction, and operator satisfaction--independently predicted the outcomes of procedure time, patient pain, and physician satisfaction in the clinical study (p < or = 0.001). The reciprocating syringe reduces procedure time and patient pain and improves operator satisfaction with the procedure syringe. The reciprocating syringe improves physician performance in both the validated quantitative needle-based displacement model and in real aspiration-injection syringe procedures, including arthrocentesis.

Challenges in the Clinical Application of the American Society of Clinical Oncology Value Framework: A Medicare Cost-Benefit Analysis in Chronic Lymphocytic Leukemia.

PubMed

Seymour, Erlene K; Schiffer, Charles A; de Souza, Jonas A

2017-12-01

The ASCO Value Framework calculates the value of cancer therapies. Given costly novel therapeutics for chronic lymphocytic leukemia, we used the framework to compare net health benefit (NHB) and cost within Medicare of all regimens listed in the National Comprehensive Cancer Network (NCCN) guidelines. The current NCCN guidelines for chronic lymphocytic leukemia were reviewed. All referenced studies were screened, and only randomized controlled prospective trials were included. The revised ASCO Value Framework was used to calculate NHB. Medicare drug pricing was used to calculate the cost of therapies. Forty-nine studies were screened. The following observations were made: only 10 studies (20%) could be evaluated; when comparing regimens studied against the same control arm, ranking NHB scores were comparable to their preference in guidelines; NHB scores varied depending on which variables were used, and there were no clinically validated thresholds for low or high values; treatment-related deaths were not weighted in the toxicity scores; and six of the 10 studies used less potent control arms, ranked as the least-preferred NCCN-recommended regimens. The ASCO Value Framework is an important initial step to quantify value of therapies. Essential limitations include the lack of clinically relevant validated thresholds for NHB scores and lack of incorporation of grade 5 toxicities/treatment-related mortality into its methodology. To optimize its application for clinical practice, we urge investigators/sponsors to incorporate and report the required variables to calculate the NHB of regimens and encourage trials with stronger comparator arms to properly quantify the relative value of therapies.

Clinical Predictors of Attention and Executive Functioning Outcomes in Children After Perinatal Arterial Ischemic Stroke.

PubMed

Bosenbark, Danielle D; Krivitzky, Lauren; Ichord, Rebecca; Vossough, Arastoo; Bhatia, Aashim; Jastrzab, Laura E; Billinghurst, Lori

2017-04-01

Children with perinatal arterial ischemic stroke (PAIS) are at risk for later neurocognitive and behavioral deficits, yet the clinical predictors of these outcomes are understudied. We examined the influence of clinical and infarct characteristics on attention and executive functioning in children following PAIS. Forty children born at term (≥37 weeks' gestation) with PAIS (28 with neonatal arterial ischemic stroke and 12 with presumed PAIS) underwent a comprehensive neuropsychological battery at age three to 16 years (median age 7.2 years; 58% male) to assess attention and executive functioning. Parents also completed questionnaires regarding real-world functioning. Clinical variables including perinatal stroke subtype, infarct characteristics (location, laterality, and volume), and the presence of comorbid epilepsy were ascertained from the medical record. Presumed PAIS, larger infarct volume, and comorbid epilepsy negatively influenced the performance on attention and executive functioning measures. These clinical variables were also associated with greater functional problems on parent reports, including a higher frequency of attention-deficit/hyperactivity disorder symptoms and greater difficulties in some subdomains of executive functioning. Infarct location and laterality were not associated with performance measures or parental report of functioning. Although all children with PAIS are at risk for later deficits in attention and executive functioning, those with presumed PAIS, larger infarct size, and comorbid epilepsy appear to be the most vulnerable. As they approach and reach school age, these children should undergo neuropsychological assessment to ensure timely implementation of therapeutic interventions and behavioral strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Invited review: study design considerations for clinical research in veterinary radiology and radiation oncology.

PubMed

Scrivani, Peter V; Erb, Hollis N

2013-01-01

High quality clinical research is essential for advancing knowledge in the areas of veterinary radiology and radiation oncology. Types of clinical research studies may include experimental studies, method-comparison studies, and patient-based studies. Experimental studies explore issues relative to pathophysiology, patient safety, and treatment efficacy. Method-comparison studies evaluate agreement between techniques or between observers. Patient-based studies investigate naturally acquired disease and focus on questions asked in clinical practice that relate to individuals or populations (e.g., risk, accuracy, or prognosis). Careful preplanning and study design are essential in order to achieve valid results. A key point to planning studies is ensuring that the design is tailored to the study objectives. Good design includes a comprehensive literature review, asking suitable questions, selecting the proper sample population, collecting the appropriate data, performing the correct statistical analyses, and drawing conclusions supported by the available evidence. Most study designs are classified by whether they are experimental or observational, longitudinal or cross-sectional, and prospective or retrospective. Additional features (e.g., controlled, randomized, or blinded) may be described that address bias. Two related challenging aspects of study design are defining an important research question and selecting an appropriate sample population. The sample population should represent the target population as much as possible. Furthermore, when comparing groups, it is important that the groups are as alike to each other as possible except for the variables of interest. Medical images are well suited for clinical research because imaging signs are categorical or numerical variables that might be predictors or outcomes of diseases or treatments. © 2013 Veterinary Radiology & Ultrasound.

Variability in adherence to clinical practice guidelines and recommendations in COPD outpatients: a multi-level, cross-sectional analysis of the EPOCONSUL study.

PubMed

Calle Rubio, Myriam; López-Campos, José Luis; Soler-Cataluña, Juan J; Alcázar Navarrete, Bernardino; Soriano, Joan B; Rodríguez González-Moro, José Miguel; Fuentes Ferrer, Manuel E; Rodríguez Hermosa, Juan Luis

2017-12-02

Clinical audits have reported considerable variability in COPD medical care and frequent inconsistencies with recommendations. The objectives of this study were to identify factors associated with a better adherence to clinical practice guidelines and to explore determinants of this variability at the the hospital level. EPOCONSUL is a Spanish nationwide clinical audit that evaluates the outpatient management of COPD. Multilevel logistic regression with two levels was performed to assess the relationships between individual and disease-related factors, as well as hospital characteristics. A total of 4508 clinical records of COPD patients from 59 Spanish hospitals were evaluated. High variability was observed among hospitals in terms of medical care. Some of the patient's characteristics (airflow obstruction, degree of dyspnea, exacerbation risk, presence of comorbidities), the hospital factors (size and respiratory nurses available) and treatment at a specialized COPD outpatient clinic were identified as factors associated with a better adherence to recommendations, although this only explains a small proportion of the total variance. To be treated at a specialized COPD outpatient clinic and some intrinsic patient characteristics were factors associated with a better adherence to guideline recommendations, although these variables were only explaining part of the high variability observed among hospitals in terms of COPD medical care.

Validity and clinical utility of the DSM-5 severity specifier for bulimia nervosa: results from a multisite sample of patients who received evidence-based treatment.

PubMed

Dakanalis, Antonios; Bartoli, Francesco; Caslini, Manuela; Crocamo, Cristina; Zanetti, Maria Assunta; Riva, Giuseppe; Clerici, Massimo; Carrà, Giuseppe

2017-12-01

A new "severity specifier" for bulimia nervosa (BN), based on the frequency of inappropriate weight compensatory behaviours (IWCBs), was added to the DSM-5 as a means of documenting heterogeneity and variability in the severity of the disorder. Yet, evidence for its validity in clinical populations, including prognostic significance for treatment outcome, is currently lacking. Existing data from 281 treatment-seeking patients with DSM-5 BN, who received the best available treatment for their disorder (manual-based cognitive behavioural therapy; CBT) in an outpatient setting, were re-analysed to examine whether these patients subgrouped based on the DSM-5 severity levels would show meaningful and consistent differences on (a) a range of clinical variables assessed at pre-treatment and (b) post-treatment abstinence from IWCBs. Results highlight that the mild, moderate, severe, and extreme severity groups were statistically distinguishable on 22 variables assessed at pre-treatment regarding eating disorder pathological features, maintenance factors of BN, associated (current) and lifetime psychopathology, social maladjustment and illness-specific functional impairment, and abstinence outcome. Mood intolerance, a maintenance factor of BN but external to eating disorder pathological features (typically addressed within CBT), emerged as the primary clinical variable distinguishing the severity groups showing a differential treatment response. Overall, the findings speak to the concurrent and predictive validity of the new DSM-5 severity criterion for BN and are important because a common benchmark informing patients, clinicians, and researchers about severity of the disorder and allowing severity fluctuation and patient's progress to be tracked does not exist so far. Implications for future research are outlined.

Clinical Audit of COPD Patients Requiring Hospital Admissions in Spain: AUDIPOC Study

PubMed Central

Pozo-Rodríguez, Francisco; López-Campos, Jose Luis; Álvarez-Martínez, Carlos J.; Castro-Acosta, Ady; Agüero, Ramón; Hueto, Javier; Hernández-Hernández, Jesús; Barrón, Manuel; Abraira, Victor; Forte, Anabel; Sanchez Nieto, Juan Miguel; Lopez-Gabaldón, Encarnación; Cosío, Borja G.; Agustí, Alvar

2012-01-01

Backgrounds AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines. The present study describes hospital resources, hospital factors related to case recruitment variability, patients’ characteristics, and adherence to guidelines. Methodology/Principal Findings An organisational database was completed by all participant hospitals recording resources and organisation. Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified. At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population. Audited patients were reassessed 90 days after admission for survival and readmission rates. A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death. Median inpatient mortality was 5% (across-hospital range 0–35%). Among discharged patients, 37% required readmission (0–62%) and 6.5% died (0–35%). The overall mortality rate was 11.6% (0–50%). Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment. Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles. Conclusions/Significance The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes. The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement. PMID:22911875

Classification of Suicide Attempts through a Machine Learning Algorithm Based on Multiple Systemic Psychiatric Scales.

PubMed

Oh, Jihoon; Yun, Kyongsik; Hwang, Ji-Hyun; Chae, Jeong-Ho

2017-01-01

Classification and prediction of suicide attempts in high-risk groups is important for preventing suicide. The purpose of this study was to investigate whether the information from multiple clinical scales has classification power for identifying actual suicide attempts. Patients with depression and anxiety disorders ( N  = 573) were included, and each participant completed 31 self-report psychiatric scales and questionnaires about their history of suicide attempts. We then trained an artificial neural network classifier with 41 variables (31 psychiatric scales and 10 sociodemographic elements) and ranked the contribution of each variable for the classification of suicide attempts. To evaluate the clinical applicability of our model, we measured classification performance with top-ranked predictors. Our model had an overall accuracy of 93.7% in 1-month, 90.8% in 1-year, and 87.4% in lifetime suicide attempts detection. The area under the receiver operating characteristic curve (AUROC) was the highest for 1-month suicide attempts detection (0.93), followed by lifetime (0.89), and 1-year detection (0.87). Among all variables, the Emotion Regulation Questionnaire had the highest contribution, and the positive and negative characteristics of the scales similarly contributed to classification performance. Performance on suicide attempts classification was largely maintained when we only used the top five ranked variables for training (AUROC; 1-month, 0.75, 1-year, 0.85, lifetime suicide attempts detection, 0.87). Our findings indicate that information from self-report clinical scales can be useful for the classification of suicide attempts. Based on the reliable performance of the top five predictors alone, this machine learning approach could help clinicians identify high-risk patients in clinical settings.

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.

Work-associated irritable larynx syndrome.

PubMed

Anderson, Jennifer A

2015-04-01

The purpose of this study is to review the relevant literature concerning work-associated irritable larynx syndrome (WILS), a hyperkinetic laryngeal disorder associated with occupational irritant exposure. Clinical symptoms are variable and include dysphonia, cough, dyspnoea and globus pharyngeus. WILS is a clinical diagnosis and can be difficult to differentiate from asthma. Treatment options for WILS include medical and behavioural therapy. Laryngeal-centred upper airway symptoms secondary to airborne irritants have been documented in the literature under a variety of diagnostic labels, including WILS, vocal cord dysfunction (VCD), laryngeal hypersensitivity and laryngeal neuropathy and many others. The underlying pathophysiology is as yet poorly understood; however, the clinical scenario suggests a multifactorial nature to the disorder. More recent literature indicates that central neuronal plasticity, inflammatory processes and psychological factors are all likely contributors. Possible mechanisms for WILS include central neuronal network plasticity after noxious exposure and/or viral infection, inflammation (i.e. reflux disease) and intrinsic patient factors such a psychological state. Treatment is individualized and frequently includes one or more of the following: environmental changes in the workplace, GERD therapy, behavioural/speech therapy, psychotherapy counselling and neural modifiers.

Clinical predictors of resectability of pancreatic adenocarcinoma.

PubMed

Almadi, Majid A; Alharbi, Othman; Azzam, Nahla; Altayeb, Mohannad; Javed, Moammed; Alsaif, Faisal; Hassanain, Mazen; Alsharabi, Abdulsalam; Al-Saleh, Khalid; Aljebreen, Abdulrahman M

2013-01-01

Identifying patient-related factors as well as symptoms and signs that can predict pancreatic cancer at a resectable stage, which could be used in an attempt to identify patients at an early stage of pancreatic cancer that would be appropriate for surgical resection and those at an unresectable stage be sparred unnecessary surgery. A retrospective chart review was conducted at a major tertiary care, university hospital in Riyadh, Saudi Arabia. The study population included individuals who underwent a computed tomography and a pancreatic mass was reported as well as the endoscopic reporting database of endoscopic procedures where the indication was a pancreatic mass, between April 1996 and April 2012. Any patient with a histologically confirmed diagnosis of adenocarcinoma of the pancreas was included in the analysis. We included patients' demographic information (age, gender), height, weight, body mass index, historical data (smoking, comorbidities), symptoms (abdominal pain and its duration, anorexia and its duration, weight loss and its amount, and over what duration, vomiting, abdominal distention, itching and its duration, change in bowel movements, change in urine color), jaundice and its duration. Other variables were also collected including laboratory values, location of the mass, the investigation undertaken, and the stage of the tumor. A total of 61 patients were included, the mean age was 61.2 ± 1.51 years, 25 (41%) were females. The tumors were located in the head (83.6%), body (10.9%), tail (1.8%), and in multiple locations (3.6%) of the pancreas. Half of the patients (50%) had Stage IV, 16.7% stages IIB and III, and only 8.3% were stages IB and IIA. On univariable analysis a lower hemoglobin level predicted resectability odds ratio 0.65 (95% confidence interval, 0.42-0.98), whereas on multivariable regression none of the variables included in the model could predict resectability of pancreatic cancer. A CA 19-9 cutoff level of 166 ng/mL had a sensitivity of 89%, specificity of 75%, positive likelihood ratio of 3.6, and a negative likelihood ratio of 0.15 for resectability of pancreatic adenocarcinoma. This study describes the clinical characteristics of patients with pancreatic adenocarcinoma in Saudi Arabia. None of the clinical or laboratory variables that were included in our study could independently predict resectability of pancreatic adenocarcinoma. Further studies are warranted to validate these results.

SU-G-IeP4-13: PET Image Noise Variability and Its Consequences for Quantifying Tumor Hypoxia

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

Kueng, R; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario; Manser, P

Purpose: The values in a PET image which represent activity concentrations of a radioactive tracer are influenced by a large number of parameters including patient conditions as well as image acquisition and reconstruction. This work investigates noise characteristics in PET images for various image acquisition and image reconstruction parameters. Methods: Different phantoms with homogeneous activity distributions were scanned using several acquisition parameters and reconstructed with numerous sets of reconstruction parameters. Images from six PET scanners from different vendors were analyzed and compared with respect to quantitative noise characteristics. Local noise metrics, which give rise to a threshold value defining themore » metric of hypoxic fraction, as well as global noise measures in terms of noise power spectra (NPS) were computed. In addition to variability due to different reconstruction parameters, spatial variability of activity distribution and its noise metrics were investigated. Patient data from clinical trials were mapped onto phantom scans to explore the impact of the scanner’s intrinsic noise variability on quantitative clinical analysis. Results: Local noise metrics showed substantial variability up to an order of magnitude for different reconstruction parameters. Investigations of corresponding NPS revealed reconstruction dependent structural noise characteristics. For the acquisition parameters, noise metrics were guided by Poisson statistics. Large spatial non-uniformity of the noise was observed in both axial and radial direction of a PET image. In addition, activity concentrations in PET images of homogeneous phantom scans showed intriguing spatial fluctuations for most scanners. The clinical metric of the hypoxic fraction was shown to be considerably influenced by the PET scanner’s spatial noise characteristics. Conclusion: We showed that a hypoxic fraction metric based on noise characteristics requires careful consideration of the various dependencies in order to justify its quantitative validity. This work may result in recommendations for harmonizing QA of PET imaging for multi-institutional clinical trials.« less

A retrospective clinical study of cervical restorations: longevity and failure-prognostic variables.

PubMed

Namgung, C; Rho, Y J; Jin, B H; Lim, B S; Cho, B H

2013-01-01

The aim of this retrospective clinical study was to compare the longevity of cervical restorations between resin composite (RC) and glass ionomer (GI) and to investigate variables predictive of their outcome. The clinical performance of the two restorative materials in function was compared using the ratings of the modified United States Public Health Service (USPHS) criteria. A total of 479 cervical restorations were included in the study. Ninety-one already-replaced restorations were reviewed from dental records. The other 388 restorations still in function were evaluated according to the modified USPHS criteria by two investigators. Longevity and prognostic variables were analyzed with the Kaplan-Meier survival analysis and multivariate Cox proportional hazard model. The clinical performances of the two materials were evaluated according to the ratings of the USPHS criteria and compared using the Pearson chi-square test and Fisher exact test. The longevity was not significantly different between RC and GI (median survival time, 10.4 ± 0.7 and 11.5 ± 1.1 years, respectively). The main reasons for failure were loss of retention (82.2%) and secondary caries (17.8%). The longevity of cervical restoration was significantly influenced by tooth group and operator group (Wald test, p<0.05), while material, gender, presence or absence of systemic diseases, arch, and reason for treatment did not affect the longevity. Contrary to the longevity, the clinical performance of RC was superior to GI in the criteria of retention, marginal discoloration, and marginal adaptation, but similar in secondary caries, wear, and postoperative sensitivity.

Population Pharmacokinetics of Intravenous Methotrexate in Patients with Hematological Malignancies: Utilization of Routine Clinical Monitoring Parameters.

PubMed

Nader, Ahmed; Zahran, Noran; Alshammaa, Aya; Altaweel, Heba; Kassem, Nancy; Wilby, Kyle John

2017-04-01

Clinical response to methotrexate in cancer is variable and depends on several factors including serum drug exposure. This study aimed to develop a population pharmacokinetic model describing methotrexate disposition in cancer patients using retrospective chart review data available from routine clinical practice. A retrospective review of medical records was conducted for cancer patients in Qatar. Relevant data (methotrexate dosing/concentrations from multiple occasions, patient history, and laboratory values) were extracted and analyzed using NONMEM VII ® . A population pharmacokinetic model was developed and used to estimate inter-individual and inter-occasion variability terms on methotrexate pharmacokinetic parameters, as well as patient factors affecting methotrexate pharmacokinetics. Methotrexate disposition was described by a two-compartment model with clearance (CL) of 15.7 L/h and central volume of distribution (V c ) of 79.2 L. Patient weight and hematocrit levels were significant covariates on methotrexate V c and CL, respectively. Methotrexate CL changed by 50 % with changes in hematocrit levels from 23 to 50 %. Inter-occasion variability in methotrexate CL was estimated for patients administered the drug on multiple occasions (48 and 31 % for 2nd and 3rd visits, respectively). Therapeutic drug monitoring data collected during routine clinical practice can provide a useful tool for understanding factors affecting methotrexate pharmacokinetics. Patient weight and hematocrit levels may play a clinically important role in determining methotrexate serum exposure and dosing requirements. Future prospective studies are needed to validate results of the developed model and evaluate its usefulness to predict methotrexate exposure and optimize dosing regimens.

The impact of temperament and character inventory personality traits on long-term outcome of Roux-en-Y gastric bypass.

PubMed

Gordon, Pedro Caldana; Sallet, José Afonso; Sallet, Paulo Clemente

2014-10-01

A significant proportion of patients who undergo bariatric surgery fail to achieve enduring weight loss. Previous studies suggest that psychosocial variables affect postoperative outcome, although this subject is still considered unclear. The purpose of this study is to further investigate the impact of psychosocial variables on Roux-en-Y gastric bypass (RYGB) outcomes over long-term follow-up. Individuals eligible for bariatric surgery were evaluated using validated psychopathological scales and the Temperament and Character Inventory in a specialized clinic for bariatric treatment. Adult patients who had RYGB were selected for the study. Percent of excess weight loss (%EWL) was measured after surgery at 6 months, 1 year, 2 years, and on the last clinical observation. This study included 333 subjects who had RYGB. Before surgery, mean age was 35.4 years (±9.5) and mean BMI was 43.3 kg/m(2) (±4.8). Higher baseline age and BMI were associated with lower %EWL across endpoints, although this association diminished over time. Follow up at 2 years and on the last clinical observation demonstrated that lower scores on the persistence personality variable and lower body dissatisfaction before surgery predicted lower %EWL. Psychosocial variables and personality traits assessed during preoperative evaluation significantly predicted weight loss after bariatric surgery. Greater impact was observed in long-term follow-up at 2 years. These findings provide guidance in identifying patients at risk for worse outcomes and designing interventions to improve long-term weight loss.

The Analytic Information Warehouse (AIW): a Platform for Analytics using Electronic Health Record Data

PubMed Central

Post, Andrew R.; Kurc, Tahsin; Cholleti, Sharath; Gao, Jingjing; Lin, Xia; Bornstein, William; Cantrell, Dedra; Levine, David; Hohmann, Sam; Saltz, Joel H.

2013-01-01

Objective To create an analytics platform for specifying and detecting clinical phenotypes and other derived variables in electronic health record (EHR) data for quality improvement investigations. Materials and Methods We have developed an architecture for an Analytic Information Warehouse (AIW). It supports transforming data represented in different physical schemas into a common data model, specifying derived variables in terms of the common model to enable their reuse, computing derived variables while enforcing invariants and ensuring correctness and consistency of data transformations, long-term curation of derived data, and export of derived data into standard analysis tools. It includes software that implements these features and a computing environment that enables secure high-performance access to and processing of large datasets extracted from EHRs. Results We have implemented and deployed the architecture in production locally. The software is available as open source. We have used it as part of hospital operations in a project to reduce rates of hospital readmission within 30 days. The project examined the association of over 100 derived variables representing disease and co-morbidity phenotypes with readmissions in five years of data from our institution’s clinical data warehouse and the UHC Clinical Database (CDB). The CDB contains administrative data from over 200 hospitals that are in academic medical centers or affiliated with such centers. Discussion and Conclusion A widely available platform for managing and detecting phenotypes in EHR data could accelerate the use of such data in quality improvement and comparative effectiveness studies. PMID:23402960

On assessing the quality of physicians' clinical judgment: the search for outcome variables.

PubMed

Wainer, Howard; Mee, Janet

2004-12-01

A primary question that must be resolved in the development of tasks to assess the quality of physicians' clinical judgment is, "What is the outcome variable?" One natural choice would seem to be the correctness of the clinical decision. In this article, we use data on the diagnosis of urinary tract infections among young girls to illustrate why, in many clinical situations, this is not a useful variable. We propose instead a judgment weighted by the relative costs of an error. This variable has the disadvantage of requiring expert judgment for scoring, but the advantage of measuring the construct of interest.

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

PubMed

Chess, Laura E; Gagnier, Joel J

2016-02-17

Clinical heterogeneity can be defined as differences in participant characteristics, types or timing of outcome measurements and intervention characteristics. Clinical heterogeneity in systematic reviews has the possibility to significantly affect statistical heterogeneity leading to inaccurate conclusions and misled decision making. The aim of this study is to identify to what extent investigators are assessing clinical heterogeneity in both Cochrane and non-Cochrane systematic reviews. The most recent 100 systematic reviews from the top five journals in medicine-JAMA, Archives of Internal Medicine, British Medical Journal, The Lancet, and PLOS Medicine-and the 100 most recently published and/or updated systematic reviews from Cochrane were collected. Various defined items of clinical heterogeneity were extracted from the included reviews. Investigators used chi-squared tests, logarithmic modeling and linear regressions to determine if the presence of such items served as a predictor for clinical heterogeneity when comparing Cochrane to non-Cochrane reviews. Extracted variables include number of studies, number of participants, presence of quantitative synthesis, exploration of clinical heterogeneity, heterogeneous characteristics explored, basis and methods used for investigating clinical heterogeneity, plotting/visual aids, author contact, inferences from clinical heterogeneity investigation, reporting assessment, and the presence of a priori or post-hoc analysis. A total of 317 systematic reviews were considered, of which 199 were in the final analysis. A total of 81% of Cochrane reviews and 90% of non-Cochrane reviews explored characteristics that are considered aspects of clinical heterogeneity and also described the methods they planned to use to investigate the influence of those characteristics. Only 1% of non-Cochrane reviews and 8% of Cochrane reviews explored the clinical characteristics they initially chose as potential for clinical heterogeneity. Very few studies mentioned clinician training, compliance, brand, co-interventions, dose route, ethnicity, prognostic markers and psychosocial variables as covariates to investigate as potentially clinically heterogeneous. Addressing aspects of clinical heterogeneity was not different between Cochrane and non-Cochrane reviews. The ability to quantify and compare the clinical differences of trials within a meta-analysis is crucial to determining its applicability and use in clinical practice. Despite Cochrane Collaboration emphasis on methodology, the proportion of reviews that assess clinical heterogeneity is less than those of non-Cochrane reviews. Our assessment reveals that there is room for improvement in assessing clinical heterogeneity in both Cochrane and non-Cochrane reviews.

Personalizing medicine with clinical pharmacogenetics

PubMed Central

Scott, Stuart A.

2012-01-01

Clinical genetic testing has grown substantially over the past 30 years as the causative mutations for Mendelian diseases have been identified, particularly aided in part by the recent advances in molecular-based technologies. Importantly, the adoption of new tests and testing strategies (e.g., diagnostic confirmation, prenatal testing, and population-based carrier screening) has often been met with caution and careful consideration before clinical implementation, which facilitates the appropriate use of new genetic tests. Although the field of pharmacogenetics was established in the 1950s, clinical testing for constitutional pharmacogenetic variants implicated in interindividual drug response variability has only recently become available to help clinicians guide pharmacotherapy, in part due to US Food and Drug Administration-mediated product insert revisions that include pharmacogenetic information for selected drugs. However, despite pharmacogenetic associations with adverse outcomes, physician uptake of clinical pharmacogenetic testing has been slow. Compared with testing for Mendelian diseases, pharmacogenetic testing for certain indications can have a lower positive predictive value, which is one reason for underutilization. A number of other barriers remain with implementing clinical pharmacogenetics, including clinical utility, professional education, and regulatory and reimbursement issues, among others. This review presents some of the current opportunities and challenges with implementing clinical pharmacogenetic testing. PMID:22095251

Factors affecting Korean nursing student empowerment in clinical practice.

PubMed

Ahn, Yang-Heui; Choi, Jihea

2015-12-01

Understanding the phenomenon of nursing student empowerment in clinical practice is important. Investigating the cognition of empowerment and identifying predictors are necessary to enhance nursing student empowerment in clinical practice. To identify empowerment predictors for Korean nursing students in clinical practice based on studies by Bradbury-Jones et al. and Spreitzer. A cross-sectional design was used for this study. This study was performed in three nursing colleges in Korea, all of which had similar baccalaureate nursing curricula. Three hundred seven junior or senior nursing students completed a survey designed to measure factors that were hypothesized to influence nursing student empowerment in clinical practice. Data were collected from November to December 2011. Study variables included self-esteem, clinical decision making, being valued as a learner, satisfaction regarding practice with a team member, perception on professor/instructor/clinical preceptor attitude, and total number of clinical practice fields. Data were analyzed using stepwise multiple regression analyses. All of the hypothesized study variables were significantly correlated to nursing student empowerment. Stepwise multiple regression analysis revealed that clinical decision making in nursing (t=7.59, p<0.001), being valued as a learner (t=6.24, p<0.001), self-esteem (t=3.62, p<0.001), and total number of clinical practice fields (t=2.06, p=0.040). The explanatory power of these predictors was 35% (F=40.71, p<0.001). Enhancing nursing student empowerment in clinical practice will be possible by using educational strategies to improve nursing student clinical decision making. Simultaneously, attitudes of nurse educators are also important to ensure that nursing students are treated as valued learners and to increase student self-esteem in clinical practice. Finally, diverse clinical practice field environments should be considered to enhance experience. Copyright © 2015 Elsevier Ltd. All rights reserved.

Predicting cognitive function from clinical measures of physical function and health status in older adults.

PubMed

Bolandzadeh, Niousha; Kording, Konrad; Salowitz, Nicole; Davis, Jennifer C; Hsu, Liang; Chan, Alison; Sharma, Devika; Blohm, Gunnar; Liu-Ambrose, Teresa

2015-01-01

Current research suggests that the neuropathology of dementia-including brain changes leading to memory impairment and cognitive decline-is evident years before the onset of this disease. Older adults with cognitive decline have reduced functional independence and quality of life, and are at greater risk for developing dementia. Therefore, identifying biomarkers that can be easily assessed within the clinical setting and predict cognitive decline is important. Early recognition of cognitive decline could promote timely implementation of preventive strategies. We included 89 community-dwelling adults aged 70 years and older in our study, and collected 32 measures of physical function, health status and cognitive function at baseline. We utilized an L1-L2 regularized regression model (elastic net) to identify which of the 32 baseline measures were strongly predictive of cognitive function after one year. We built three linear regression models: 1) based on baseline cognitive function, 2) based on variables consistently selected in every cross-validation loop, and 3) a full model based on all the 32 variables. Each of these models was carefully tested with nested cross-validation. Our model with the six variables consistently selected in every cross-validation loop had a mean squared prediction error of 7.47. This number was smaller than that of the full model (115.33) and the model with baseline cognitive function (7.98). Our model explained 47% of the variance in cognitive function after one year. We built a parsimonious model based on a selected set of six physical function and health status measures strongly predictive of cognitive function after one year. In addition to reducing the complexity of the model without changing the model significantly, our model with the top variables improved the mean prediction error and R-squared. These six physical function and health status measures can be easily implemented in a clinical setting.

24-Hour Blood Pressure Variability Assessed by Average Real Variability: A Systematic Review and Meta-Analysis.

PubMed

Mena, Luis J; Felix, Vanessa G; Melgarejo, Jesus D; Maestre, Gladys E

2017-10-19

Although 24-hour blood pressure (BP) variability (BPV) is predictive of cardiovascular outcomes independent of absolute BP levels, it is not regularly assessed in clinical practice. One possible limitation to routine BPV assessment is the lack of standardized methods for accurately estimating 24-hour BPV. We conducted a systematic review to assess the predictive power of reported BPV indexes to address appropriate quantification of 24-hour BPV, including the average real variability (ARV) index. Studies chosen for review were those that presented data for 24-hour BPV in adults from meta-analysis, longitudinal or cross-sectional design, and examined BPV in terms of the following issues: (1) methods used to calculate and evaluate ARV; (2) assessment of 24-hour BPV determined using noninvasive ambulatory BP monitoring; (3) multivariate analysis adjusted for covariates, including some measure of BP; (4) association of 24-hour BPV with subclinical organ damage; and (5) the predictive value of 24-hour BPV on target organ damage and rate of cardiovascular events. Of the 19 assessed studies, 17 reported significant associations between high ARV and the presence and progression of subclinical organ damage, as well as the incidence of hard end points, such as cardiovascular events. In all these cases, ARV remained a significant independent predictor ( P <0.05) after adjustment for BP and other clinical factors. In addition, increased ARV in systolic BP was associated with risk of all cardiovascular events (hazard ratio, 1.18; 95% confidence interval, 1.09-1.27). Only 2 cross-sectional studies did not find that high ARV was a significant risk factor. Current evidence suggests that ARV index adds significant prognostic information to 24-hour ambulatory BP monitoring and is a useful approach for studying the clinical value of BPV. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Microcephaly, ectodermal dysplasia, multiple skeletal anomalies and distinctive facial appearance: delineation of cerebro-dermato-osseous-dysplasia.

PubMed

Castori, Marco; Pascolini, Giulia; Parisi, Valentina; Sana, Maria Elena; Novelli, Antonio; Nürnberg, Peter; Iascone, Maria; Grammatico, Paola

2015-04-01

In 1980, a novel multiple malformation syndrome has been described in a 17-year-old woman with micro- and turricephaly, intellectual disability, distinctive facial appearance, congenital atrichia, and multiple skeletal anomalies mainly affecting the limbs. Four further sporadic patients and a couple of affected sibs are also reported with a broad clinical variability. Here, we describe a 4-year-old girl strikingly resembling the original report. Phenotype comparison identified a recurrent pattern of multisystem features involving the central nervous system, and skin and bones in five sporadic patients (including ours), while the two sibs and a further sporadic case show significant phenotypic divergence. Marked clinical variability within the same entity versus syndrome splitting is discussed and the term "cerebro-dermato-osseous dysplasia" is introduced to define this condition. © 2015 Wiley Periodicals, Inc.

Treatment of peri-implantitis: clinical outcome of chloramine as an adjunctive to non-surgical therapy, a randomized clinical trial.

PubMed

Roos-Jansåker, Ann-Marie; Almhöjd, Ulrica S; Jansson, Henrik

2017-01-01

To evaluate the adjunctive clinical effects of a chloramine to non-surgical treatment of peri-implantitis. Eighteen individuals diagnosed with peri-implantitis (clinical signs of inflammation and progressive bone loss) on at least two implants were included. Clinical variables; plaque accumulation (Pl), probing depth (PD), clinical attachment level (CAL) and bleeding on probing (BoP), were recorded at baseline and at 3-month follow-up. Primary clinical efficacy variable was the change in the number of sites with BoP. The implants were randomized into two different treatment groups: test and control. Both implants received supra- and submucosal debridement by ultrasonic instrumentation supplemented with hand instruments. The implants assigned to the test group first received local applications of a chloramine gel (Perisolv ™ ; RLS Global AB, Gothenburg, Sweden) followed by mechanical instrumentation. The oral hygiene was checked at 6 weeks. After 3 months, implants of both groups showed statistically significant reduction (P < 0.001) in the number of BoP-positive sites compared with baseline. The reduction of BoP-positive sites in the test group changed from 0.97 (SD ± 0.12) to 0.38 (SD ± 0.46), and in the control group from 0.97 (SD ± 0.12) to 0.31 (SD ± 0.42). Between-group comparisons revealed no statistically significant differences at baseline and after 3 months, for BoP or any of the other variables. In the present randomized clinical trial of peri-implantitis therapy; non-surgical mechanical debridement with adjunctive use of a chloramine is equally effective in the reduction of mucosal inflammation as conventional non-surgical mechanical debridement up to 3 months. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Data Linkage from Clinical to Study Databases via an R Data Warehouse User Interface. Experiences from a Large Clinical Follow-up Study.

PubMed

Kaspar, Mathias; Ertl, Maximilian; Fette, Georg; Dietrich, Georg; Toepfer, Martin; Angermann, Christiane; Störk, Stefan; Puppe, Frank

2016-08-05

Data that needs to be documented for clinical studies has often been acquired and documented in clinical routine. Usually this data is manually transferred to Case Report Forms (CRF) and/or directly into an electronic data capture (EDC) system. To enhance the documentation process of a large clinical follow-up study targeting patients admitted for acutely decompensated heart failure by accessing the data created during routine and study visits from a hospital information system (HIS) and by transferring it via a data warehouse (DWH) into the study's EDC system. This project is based on the clinical DWH developed at the University of Würzburg. The DWH was extended by several new data domains including data created by the study team itself. An R user interface was developed for the DWH that allows to access its source data in all its detail, to transform data as comprehensively as possible by R into study-specific variables and to support the creation of data and catalog tables. A data flow was established that starts with labeling patients as study patients within the HIS and proceeds with updating the DWH with this label and further data domains at a daily rate. Several study-specific variables were defined using the implemented R user interface of the DWH. This system was then used to export these variables as data tables ready for import into our EDC system. The data tables were then used to initialize the first 296 patients within the EDC system by pseudonym, visit and data values. Afterwards, these records were filled with clinical data on heart failure, vital parameters and time spent on selected wards. This solution focuses on the comprehensive access and transformation of data for a DWH-EDC system linkage. Using this system in a large clinical study has demonstrated the feasibility of this approach for a study with a complex visit schedule.

Exploring the interaction of patient activation and message design variables: message frame and presentation mode influence on the walking behavior of patients with type 2 diabetes.

PubMed

Ledford, Christy J W

2012-10-01

Examining interpersonal (physician-patient) communication strategies for promoting walking exercise to patients with type 2 diabetes assigned to primary care clinics, the study evaluated two message design variables--frame and presentation mode--as influencers of communication and adoption success. The single-site, four-week, prospective intervention study followed a 2×3 factorial, non-equivalent comparison group quasi-experimental design. Results showed frame was significantly related to steps walked; however, when including patient activation as an interaction, frame was non-significant. The model including patient activation interactions, however, detected significant mode effects on behavior. Results provide evidence that statistics are most effectively used with activated patients.

Perceived Causal Relations: Novel Methodology for Assessing Client Attributions about Causal Associations between Variables Including Symptoms and Functional Impairment

ERIC Educational Resources Information Center

Frewen, Paul A.; Allen, Samantha L.; Lanius, Ruth A.; Neufeld, Richard W. J.

2012-01-01

Researchers have argued that the investigation of causal interrelationships between symptoms may help explain the high comorbidity rate between certain psychiatric disorders. Clients' own attributions concerning the causal interrelationships linking the co-occurrence of their symptoms represent data that may inform their clinical case…

Pursuit of Muscularity in Adolescent Boys: Relations among Biopsychosocial Variables and Clinical Outcomes

ERIC Educational Resources Information Center

Cafri, Guy; van den Berg, Patricia; Thompson, J. Kevin

2006-01-01

Adolescent boys (n = 269) were assessed for levels of several risky behaviors related to the pursuit of muscularity, including substance use (anabolic steroids, prohormones, and ephedrine) dieting to gain weight, and symptoms of muscle dysmorphia (MD). The association between these behaviors and a variety of putative biological, psychological, and…

Professional ethics: beyond the clinical competency.

PubMed

Vanaki, Zohreh; Memarian, Robabeh

2009-01-01

Assessment of clinical competency in professional roles especially in crucial situations can improve the nursing profession. This qualitative research was conducted to determine the process of acquiring clinical competency by nurses in its cultural context and within the health care delivery system in Iran. This study, using grounded theory methodology, took place in universities and hospitals in Tehran. Nurses (36) included nurse managers, tutors, practitioners, and members of the Iranian Nursing Organization. Simultaneous data collection and analysis took place using participant semistructured interviews. Three categories emerged: (a) personal characteristics such as philanthropy, strong conscience, being attentive, accepting responsibility, being committed to and respecting self and others; (b) care environment including appropriate management systems, in-service training provision, employment laws, and control mechanisms, suitable and adequate equipment; and (c) provision of productive work practices including love of the profession, critical thinking, nursing knowledge, and professional expertise. Professional ethics has emerged as the core variable that embodies concepts such as commitment, responsibility, and accountability. Professional ethics guarantees clinical competency and leads to the application of specialized knowledge and skill by nurses. The results can be used to form the basis of guiding the process of acquiring clinical competency by nurses using a systematic process.

Clinical dysphagia risk predictors after prolonged orotracheal intubation

PubMed Central

de Medeiros, Gisele Chagas; Sassi, Fernanda Chiarion; Mangilli, Laura Davison; Zilberstein, Bruno; de Andrade, Claudia Regina Furquim

2014-01-01

OBJECTIVES: To elucidate independent risk factors for dysphagia after prolonged orotracheal intubation. METHODS: The participants were 148 consecutive patients who underwent clinical bedside swallowing assessments from September 2009 to September 2011. All patients had received prolonged orotracheal intubations and were admitted to one of several intensive care units of a large Brazilian school hospital. The correlations between the conducted water swallow test results and dysphagia risk levels were analyzed for statistical significance. RESULTS: Of the 148 patients included in the study, 91 were male and 57 were female (mean age, 53.64 years). The univariate analysis results indicated that specific variables, including extraoral loss, multiple swallows, cervical auscultation, vocal quality, cough, choking, and other signs, were possible significant high-risk indicators of dysphagia onset. The multivariate analysis results indicated that cervical auscultation and coughing were independent predictive variables for high dysphagia risk. CONCLUSIONS: Patients displaying extraoral loss, multiple swallows, cervical auscultation, vocal quality, cough, choking and other signs should benefit from early swallowing evaluations. Additionally, early post-extubation dysfunction recognition is paramount in reducing the morbidity rate in this high-risk population. PMID:24473554

Inductive creation of an annotation schema for manually indexing clinical conditions from emergency department reports

PubMed Central

Chapman, Wendy W.; Dowling, John N.

2006-01-01

Evaluating automated indexing applications requires comparing automatically indexed terms against manual reference standard annotations. However, there are no standard guidelines for determining which words from a textual document to include in manual annotations, and the vague task can result in substantial variation among manual indexers. We applied grounded theory to emergency department reports to create an annotation schema representing syntactic and semantic variables that could be annotated when indexing clinical conditions. We describe the annotation schema, which includes variables representing medical concepts (e.g., symptom, demographics), linguistic form (e.g., noun, adjective), and modifier types (e.g., anatomic location, severity). We measured the schema’s quality and found: (1) the schema was comprehensive enough to be applied to 20 unseen reports without changes to the schema; (2) agreement between author annotators applying the schema was high, with an F measure of 93%; and (3) an error analysis showed that the authors made complementary errors when applying the schema, demonstrating that the schema incorporates both linguistic and medical expertise. PMID:16230050

The role of insurance claims databases in drug therapy outcomes research.

PubMed

Lewis, N J; Patwell, J T; Briesacher, B A

1993-11-01

The use of insurance claims databases in drug therapy outcomes research holds great promise as a cost-effective alternative to post-marketing clinical trials. Claims databases uniquely capture information about episodes of care across healthcare services and settings. They also facilitate the examination of drug therapy effects on cohorts of patients and specific patient subpopulations. However, there are limitations to the use of insurance claims databases including incomplete diagnostic and provider identification data. The characteristics of the population included in the insurance plan, the plan benefit design, and the variables of the database itself can influence the research results. Given the current concerns regarding the completeness of insurance claims databases, and the validity of their data, outcomes research usually requires original data to validate claims data or to obtain additional information. Improvements to claims databases such as standardisation of claims information reporting, addition of pertinent clinical and economic variables, and inclusion of information relative to patient severity of illness, quality of life, and satisfaction with provided care will enhance the benefit of such databases for outcomes research.

Clinical dysphagia risk predictors after prolonged orotracheal intubation.

PubMed

Medeiros, Gisele Chagas de; Sassi, Fernanda Chiarion; Mangilli, Laura Davison; Zilberstein, Bruno; Andrade, Claudia Regina Furquim de

2014-01-01

To elucidate independent risk factors for dysphagia after prolonged orotracheal intubation. The participants were 148 consecutive patients who underwent clinical bedside swallowing assessments from September 2009 to September 2011. All patients had received prolonged orotracheal intubations and were admitted to one of several intensive care units of a large Brazilian school hospital. The correlations between the conducted water swallow test results and dysphagia risk levels were analyzed for statistical significance. Of the 148 patients included in the study, 91 were male and 57 were female (mean age, 53.64 years). The univariate analysis results indicated that specific variables, including extraoral loss, multiple swallows, cervical auscultation, vocal quality, cough, choking, and other signs, were possible significant high-risk indicators of dysphagia onset. The multivariate analysis results indicated that cervical auscultation and coughing were independent predictive variables for high dysphagia risk. Patients displaying extraoral loss, multiple swallows, cervical auscultation, vocal quality, cough, choking and other signs should benefit from early swallowing evaluations. Additionally, early post-extubation dysfunction recognition is paramount in reducing the morbidity rate in this high-risk population.

LEPROSY NEPHROPATHY: A REVIEW OF CLINICAL AND HISTOPATHOLOGICAL FEATURES

PubMed Central

da Silva, Geraldo Bezerra; Daher, Elizabeth De Francesco; Pires, Roberto da Justa; Pereira, Eanes Delgado Barros; Meneses, Gdayllon Cavalcante; Araújo, Sônia Maria Holanda Almeida; Barros, Elvino José Guardão

2015-01-01

Leprosy is a chronic disease caused by Mycobacterium leprae, highly incapacitating, and with systemic involvement in some cases. Renal involvement has been reported in all forms of the disease, and it is more frequent in multibacillary forms. The clinical presentation is variable and is determined by the host immunologic system reaction to the bacilli. During the course of the disease there are the so called reactional states, in which the immune system reacts against the bacilli, exacerbating the clinical manifestations. Different renal lesions have been described in leprosy, including acute and chronic glomerulonephritis, interstitial nephritis, secondary amyloidosis and pyelonephritis. The exact mechanism that leads to glomerulonephritis in leprosy is not completely understood. Leprosy treatment includes rifampicin, dapsone and clofazimine. Prednisone and non-steroidal anti-inflammatory drugs may be used to control acute immunological episodes. PMID:25651321

Individual Differences in Pain: Understanding the Mosaic that Makes Pain Personal

PubMed Central

Fillingim, Roger B.

2016-01-01

The experience of pain is characterized by tremendous inter-individual variability. Multiple biological and psychosocial variables contribute to these individual differences in pain, including demographic variables, genetic factors, and psychosocial processes. For example, sex, age and ethnic group differences in the prevalence of chronic pain conditions have been widely reported. Moreover, these demographic factors have been associated with responses to experimentally-induced pain. Similarly, both genetic and psychosocial factors contribute to clinical and experimental pain responses. Importantly, these different biopsychosocial influences interact with each other in complex ways to sculpt the experience of pain. Some genetic associations with pain have been found to vary across sex and ethnic group. Moreover, genetic factors also interact with psychosocial factors, including stress and pain catastrophizing, to influence pain. The individual and combined influences of these biological and psychosocial variables results in a unique mosaic of factors that contributes pain in each individual. Understanding these mosaics is critically important in order to provide optimal pain treatment, and future research to further elucidate the nature of these biopsychosocial interactions is needed in order to provide more informed and personalized pain care. PMID:27902569

The clinical spectrum of Erdheim-Chester disease: an observational cohort study

PubMed Central

O’Brien, Kevin J.; Xi, Liqiang; Malayeri, Ashkan A.; Gardner, Pamela J.; Alvarado Enriquez, Jhonell R.; Shah, Nikeith; Gochuico, Bernadette R.; Raffeld, Mark; Gahl, William A.

2017-01-01

Erdheim-Chester disease (ECD) is a rare, potentially fatal multiorgan myeloid neoplasm occurring mainly in adults. The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a−, and frequently S100−. The purpose of this report is to describe the clinical and molecular variability of ECD. Between 2011 and 2015, 60 consecutive ECD patients (45 males, 15 females) were prospectively evaluated at the National Institutes of Health Clinical Center. Comprehensive imaging and laboratory studies were performed, and tissues were examined for BRAF V600E and MAPK pathway mutations. Mean age at first manifestations of ECD was 46 years; a diagnosis was established, on average, 4.2 years after initial presentation. Bone was the most common tissue affected, with osteosclerosis in 95% of patients. Other manifestations observed in one-third to two-thirds of patients included cardiac mass and periaortic involvement, diabetes insipidus, retro-orbital infiltration, retroperitoneal, lung, central nervous system, skin, and xanthelasma, affecting patients in variable ways. Methods of detection included imaging studies of various modalities. Mutation in BRAF V600E was detected in 51% of 57 biopsy specimens. One patient had an ARAF D228V mutation, and 1 patient had an activating ALK fusion. Treatments included interferon α, imatinib, anakinra, cladribine, vemurafenib, and dabrafenib with trametinib; 11 patients received no therapy. The diagnosis of ECD is elusive because of the rarity and varied presentations of the disorder. Identification of BRAF and other MAPK pathway mutations in biopsy specimens improves ECD diagnosis, allows for development of targeted treatments, and demonstrates that ECD is a neoplastic disorder. This study was registered at www.clinicaltrials.gov as #NCT01417520. PMID:28553668

Medication possession ratio predicts antiretroviral regimens persistence in Peru.

PubMed

Salinas, Jorge L; Alave, Jorge L; Westfall, Andrew O; Paz, Jorge; Moran, Fiorella; Carbajal-Gonzalez, Danny; Callacondo, David; Avalos, Odalie; Rodriguez, Martin; Gotuzzo, Eduardo; Echevarria, Juan; Willig, James H

2013-01-01

In developing nations, the use of operational parameters (OPs) in the prediction of clinical care represents a missed opportunity to enhance the care process. We modeled the impact of multiple measurements of antiretroviral treatment (ART) adherence on antiretroviral treatment outcomes in Peru. Retrospective cohort study including ART naïve, non-pregnant, adults initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010). Three OPs were defined: 1) Medication possession ratio (MPR): days with antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory constancy (LMC): proportion of 6 months intervals with ≥1 viral load or CD4 reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with ≥1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one per OP) were fit for (1) time of first-line ART persistence and (2) time to second-line virologic failure. All models were adjusted for socio-demographic, clinical and laboratory variables. 856 patients were included in first-line persistence analyses, median age was 35.6 years [29.4-42.9] and most were male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66; 95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with prolonged time on first-line therapies. Among 79 individuals included in time to second-line virologic failure analyses, MPR was the only OP independently associated with prolonged time to second-line virologic failure (per 10% increase 0.88; 0.77-0.99). The capture and utilization of program level parameters such as MPR can provide valuable insight into patient-level treatment outcomes.

Fear of GI symptoms has an important impact on quality of life in patients with moderate-to-severe IBS.

PubMed

Lackner, Jeffrey M; Gudleski, Gregory D; Ma, Chang-Xing; Dewanwala, Akriti; Naliboff, Bruce

2014-11-01

Because irritable bowel syndrome (IBS) is a functional medical condition for which there is no curative therapy, treatment goals emphasize relieving gastrointestinal (GI) symptoms and optimizing the quality of life (QOL). This study sought to characterize the magnitude of the associations between QOL impairment, fear of IBS symptoms, and confounding variables. Subjects included 234 Rome III-diagnosed IBS patients (mean age, 41 years, 79%, female) without comorbid organic GI disease who were referred to two specialty care clinics of an National Institutes of Health trial for IBS. Subjects completed a testing battery that included the IBS-specific QOL (IBS-QOL), SF-12 (generic QOL), the UCLA GI Symptom Severity Scale, the Visceral Sensitivity Index, Trait Anxiety Inventory, and Brief Symptom Inventory. Multiple linear regression was used to develop a model for predicting QOL. Data supported an overall model that included sociodemographic, clinical (e.g., current severity of GI symptoms), and psychosocial (e.g., fear of GI symptoms, distress, neuroticism) variables, accounting for 48.7% of the variance in IBS-QOL (F=15.1, P <0.01). GI symptom fear was the most robust predictor of IBS-QOL (β=-0.45 P <0.01), accounting for 14.4% of the total variance. Patients' fear that GI symptoms have aversive consequences, is a predictor of QOL impairment that cannot be fully explained by the severity of their GI symptoms, overall emotional well-being, neurotic personality style, or other clinical features of IBS. An understanding of the unique impact that GI symptom fears have on QOL can inform treatment planning and help gastroenterologists to better manage more severe IBS patients seen in tertiary care clinics.

[CARDIOREABILITATION PECULIARITIES AND CORRECTION OF VIOLATIONS OF SISTOLIC, DIASOLIC FUNCTION AND HEART RATE VARIABILITY IN PATIENTS WITH ACUTE CORONARY SYNDROME AND CORONARY ARTERY REVASCULARIZATION].

PubMed

Shved, M; Tsuglevych, L; Kyrychok, I; Levytska, L; Boiko, T; Kitsak, Ya

2017-04-01

In patients with acute coronary syndrome (ACS) who underwent coronary arteries revascularization, violations of hemodynamics, metabolism and heart rate variability often develop in the postoperative period, therefore, the goal of the study was to establish the features of disturbances and the effectiveness of correction of left ventricular systolic and diastolic dysfunction and heart rate variability in stages of cardiorehabilitation in patients with acute coronary syndrome who underwent coronary arteries revascularization. The experimental group included 40 patients with ACS in the postoperative period who underwent balloon angioplasty and stenting of the coronary arteries (25 patients with ST-segment elevation ACS and 15 patients without ST-segment elevation ACS). The age of examined patients was 37 to 74 years, an average of 52.6±6.7 years. The control group consisted of 20 patients, comparable in age and clinico-laboratory manifestations of ACS, who underwent drug treatment with direct anticoagulants, double antiplatelet therapy, β-blockers, ACE inhibitors and statins. Clinical efficacy of cardiorespiratory process in patients of both groups was assessed by the dynamics of general clinical symptoms and parameters of natriuretic propeptide, systolic and diastolic function of the left ventricle and heart rate variability. In the initial state, clinical and laboratory-instrumental signs of myocardial ischemia disappear in patients with ACS undergoing surgical revascularization of the coronary arteries, but clinical and subclinical manifestations of heart failure were diagnosed. The use of the accelerated program of cardiac rehabilitation already during the first month of studies leads to a decreasement of the signs of systolic and diastolic dysfunction, the level of NT-proBNP and improve in the variability of the heart rhythm wich significantly improves the life quality of patients with ACS. To monitor the effectiveness and safety of cardiac rehabilitation in patients with ACS who underwent coronary arteries revascularization, in addition to the generally accepted methods (determination of heart rate, blood pressure, a 6-minute test), it is advisable to diagnose the subclinical stage of heart failure by determining the level of NT-proBNP, Doppler echocardiogram, parameters of the left ventricular systolic and diastolic function and heart rate variability.

A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer: Reducing the interobserver variability in multicentre clinical studies.

PubMed

Schimek-Jasch, Tanja; Troost, Esther G C; Rücker, Gerta; Prokic, Vesna; Avlar, Melanie; Duncker-Rohr, Viola; Mix, Michael; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula

2015-06-01

Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study results.

Rationale and Design of the Registry for Stones of the Kidney and Ureter (ReSKU): A Prospective Observational Registry to Study the Natural History of Urolithiasis Patients.

PubMed

Chang, Helena C; Tzou, David T; Usawachintachit, Manint; Duty, Brian D; Hsi, Ryan S; Harper, Jonathan D; Sorensen, Mathew D; Stoller, Marshall L; Sur, Roger L; Chi, Thomas

2016-12-01

Registry-based clinical research in nephrolithiasis is critical to advancing quality in urinary stone disease management and ultimately reducing stone recurrence. A need exists to develop Health Insurance Portability and Accountability Act (HIPAA)-compliant registries that comprise integrated electronic health record (EHR) data using prospectively defined variables. An EHR-based standardized patient database-the Registry for Stones of the Kidney and Ureter (ReSKU™)-was developed, and herein we describe our implementation outcomes. Interviews with academic and community endourologists in the United States, Canada, China, and Japan identified demographic, intraoperative, and perioperative variables to populate our registry. Variables were incorporated into a HIPAA-compliant Research Electronic Data Capture database linked to text prompts and registration data within the Epic EHR platform. Specific data collection instruments supporting New patient, Surgery, Postoperative, and Follow-up clinical encounters were created within Epic to facilitate automated data extraction into ReSKU. The number of variables within each instrument includes the following: New patient-60, Surgery-80, Postoperative-64, and Follow-up-64. With manual data entry, the mean times to complete each of the clinic-based instruments were (minutes) as follows: New patient-12.06 ± 2.30, Postoperative-7.18 ± 1.02, and Follow-up-8.10 ± 0.58. These times were significantly reduced with the use of ReSKU structured clinic note templates to the following: New patient-4.09 ± 1.73, Postoperative-1.41 ± 0.41, and Follow-up-0.79 ± 0.38. With automated data extraction from Epic, manual entry is obviated. ReSKU is a longitudinal prospective nephrolithiasis registry that integrates EHR data, lowering the barriers to performing high quality clinical research and quality outcome assessments in urinary stone disease.

Rationale and Design of the Registry for Stones of the Kidney and Ureter (ReSKU): A Prospective Observational Registry to Study the Natural History of Urolithiasis Patients

PubMed Central

Chang, Helena C.; Tzou, David T.; Usawachintachit, Manint; Duty, Brian D.; Hsi, Ryan S.; Harper, Jonathan D.; Sorensen, Mathew D.; Stoller, Marshall L.; Sur, Roger L.

2016-01-01

Abstract Objectives: Registry-based clinical research in nephrolithiasis is critical to advancing quality in urinary stone disease management and ultimately reducing stone recurrence. A need exists to develop Health Insurance Portability and Accountability Act (HIPAA)-compliant registries that comprise integrated electronic health record (EHR) data using prospectively defined variables. An EHR-based standardized patient database—the Registry for Stones of the Kidney and Ureter (ReSKU™)—was developed, and herein we describe our implementation outcomes. Materials and Methods: Interviews with academic and community endourologists in the United States, Canada, China, and Japan identified demographic, intraoperative, and perioperative variables to populate our registry. Variables were incorporated into a HIPAA-compliant Research Electronic Data Capture database linked to text prompts and registration data within the Epic EHR platform. Specific data collection instruments supporting New patient, Surgery, Postoperative, and Follow-up clinical encounters were created within Epic to facilitate automated data extraction into ReSKU. Results: The number of variables within each instrument includes the following: New patient—60, Surgery—80, Postoperative—64, and Follow-up—64. With manual data entry, the mean times to complete each of the clinic-based instruments were (minutes) as follows: New patient—12.06 ± 2.30, Postoperative—7.18 ± 1.02, and Follow-up—8.10 ± 0.58. These times were significantly reduced with the use of ReSKU structured clinic note templates to the following: New patient—4.09 ± 1.73, Postoperative—1.41 ± 0.41, and Follow-up—0.79 ± 0.38. With automated data extraction from Epic, manual entry is obviated. Conclusions: ReSKU is a longitudinal prospective nephrolithiasis registry that integrates EHR data, lowering the barriers to performing high quality clinical research and quality outcome assessments in urinary stone disease. PMID:27758162

Clinical process in an integrative psychotherapy for self-wounds.

PubMed

Wolfe, Barry E

2013-09-01

In this article, I will briefly describe the clinical process of an integrative psychotherapy for the healing of self-wounds, including its intended interventions and the variability of their application and outcome. Four specific strategies will be considered, including (a) the role of empathy throughout the course of therapy; (b) exposure therapy as a paradigmatic treatment for the treatment of feared thoughts, behavior, and emotions; (c) focusing and other experiential interventions for eliciting self-wounds; and (d) modification and healing of self-wounds with an individualized array of psychodynamic, experiential, and cognitive-behavioral strategies. In addition, we will briefly consider the impact of transference and countertransference on the trajectory of therapy. 2013 APA, all rights reserved

Health-related quality of life in multiple sclerosis: role of cognitive appraisals of self, illness and treatment.

PubMed

Wilski, Maciej; Tasiemski, Tomasz

2016-07-01

Health-related quality of life (HRQoL) is considered an important measure of treatment and rehabilitation outcomes in multiple sclerosis (MS) patients. In this study, we used multivariate regression analysis to examine the role of cognitive appraisals, adjusted for clinical, socioeconomic and demographic variables, as correlates of HRQoL in MS. The cross-sectional study included 257 MS patients, who completed Multiple Sclerosis Impact Scale, Generalized Self-Efficacy Scale, Rosenberg Self-Esteem Scale, Brief Illness Perception Questionnaire, Treatment Beliefs Scale, Actually Received Support Scale (a part of Berlin Social Support Scale) and Socioeconomic Resources Scale. Demographic and clinical characteristics of the participants were collected with a self-report survey. Correlation and regression analyses were conducted to determine associations between the variables. Five variables, illness identity (β = 0.29, p ≤ 0.001), self-esteem (β = -0.22, p ≤ 0.001), general self-efficacy (β = -0.21, p ≤ 0.001), disability subgroup "EDSS" (β = 0.14, p = 0.006) and age (β = 0.12, p = 0.012), were significant correlates of HRQoL in MS. These variables explained 46 % of variance in the dependent variable. Moreover, we identified correlates of physical and psychological dimensions of HRQoL. Cognitive appraisals, such as general self-efficacy, self-esteem and illness perception, are more salient correlates of HRQoL than social support, socioeconomic resources and clinical characteristics, such as type and duration of MS. Therefore, interventions aimed at cognitive appraisals may also improve HRQoL of MS patients.

Associations between weather conditions and clinical symptoms in patients with hip osteoarthritis: a 2-year cohort study.

PubMed

Dorleijn, Desirée M J; Luijsterburg, Pim A J; Burdorf, Alex; Rozendaal, Rianne M; Verhaar, Jan A N; Bos, Pieter K; Bierma-Zeinstra, Sita M A

2014-04-01

The goal of this study was to assess whether there is an association between ambient weather conditions and patients' clinical symptoms in patients with hip osteoarthritis (OA). The design was a cohort study with a 2-year follow-up and 3-monthly measurements and prospectively collected data on weather variables. The study population consisted of 222 primary care patients with hip OA. Weather variables included temperature, wind speed, total amount of sun hours, precipitation, barometric pressure, and relative humidity. The primary outcomes were severity of hip pain and hip disability as measured with the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) pain and function subscales. Associations between hip pain and hip disability and the weather variables were assessed using crude and multivariate adjusted linear mixed-model analysis for repeated measurements. On the day of questionnaire completion, mean relative humidity was associated with WOMAC pain (estimate 0.1; 95% confidence interval=0.0-0.2; P=.02). Relative humidity contributed < or = 1% to the explained within-patient variance and between-patient variance of the WOMAC pain score. Mean barometric pressure was associated with WOMAC function (estimate 0.1; 95% confidence interval=0.0-0.1; P=.02). Barometric pressure contributed < or = 1% to the explained within-patient variance and between-patient variance of the WOMAC function score. The other weather variables were not associated with the WOMAC pain or function score. Our results support the general opinion of OA patients that barometric pressure and relative humidity influence perceived OA symptoms. However, the contribution of these weather variables (< or = 1%) to the severity of OA symptoms is not considered to be clinically relevant. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Systematic review of the neural basis of social cognition in patients with mood disorders

PubMed Central

Cusi, Andrée M.; Nazarov, Anthony; Holshausen, Katherine; MacQueen, Glenda M.; McKinnon, Margaret C.

2012-01-01

Background This review integrates neuroimaging studies of 2 domains of social cognition — emotion comprehension and theory of mind (ToM) — in patients with major depressive disorder and bipolar disorder. The influence of key clinical and method variables on patterns of neural activation during social cognitive processing is also examined. Methods Studies were identified using PsycINFO and PubMed (January 1967 to May 2011). The search terms were “fMRI,” “emotion comprehension,” “emotion perception,” “affect comprehension,” “affect perception,” “facial expression,” “prosody,” “theory of mind,” “mentalizing” and “empathy” in combination with “major depressive disorder,” “bipolar disorder,” “major depression,” “unipolar depression,” “clinical depression” and “mania.” Results Taken together, neuroimaging studies of social cognition in patients with mood disorders reveal enhanced activation in limbic and emotion-related structures and attenuated activity within frontal regions associated with emotion regulation and higher cognitive functions. These results reveal an overall lack of inhibition by higher-order cognitive structures on limbic and emotion-related structures during social cognitive processing in patients with mood disorders. Critically, key variables, including illness burden, symptom severity, comorbidity, medication status and cognitive load may moderate this pattern of neural activation. Limitations Studies that did not include control tasks or a comparator group were included in this review. Conclusion Further work is needed to examine the contribution of key moderator variables and to further elucidate the neural networks underlying altered social cognition in patients with mood disorders. The neural networks underlying higher-order social cognitive processes, including empathy, remain unexplored in patients with mood disorders. PMID:22297065

Variable methodological quality and use found in systematic reviews referenced in STEMI clinical practice guidelines.

PubMed

Scott, Jared; Howard, Benjamin; Sinnett, Philip; Schiesel, Michael; Baker, Jana; Henderson, Patrick; Vassar, Matt

2017-12-01

The objective of this study was to assess the methodological quality and clarity of reporting of the systematic reviews (SRs) supporting clinical practice guideline (CPG) recommendations in the management of ST-elevation myocardial infarction (STEMI) across international CPGs. We searched 13 guideline clearinghouses including the National Guideline Clearinghouse and Guidelines International Network (GIN). To meet inclusion criteria CPGs must be pertinent to the management of STEMI, endorsed by a governing body or national organization, and written in English. We retrieved SRs from the reference sections using a combination of keywords and hand searching. Two investigators scored eligible SRs using AMSTAR and PRISMA. We included four CPGs. We extracted 71 unique SRs. These SRs received AMSTAR scores ranging from 1 (low) to 9 (high) on an 11-point scale. All CPGs consistently underperformed in areas including disclosure of funding sources, risk of bias, and publication bias according to AMSTAR. PRISMA checklist completeness ranged from 44% to 96%. The PRISMA scores indicated that SRs did not provide a full search strategy, study protocol and registration, assessment of publication bias or report funding sources. Only one SR was referenced in all four CPGs. All CPGs omitted a large subset of available SRs cited by other guidelines. Our study demonstrates the variable quality of SRs used to establish recommendations within guidelines included in our sample. Although guideline developers have acknowledged this variability, it remains a significant finding that needs to be addressed further. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Copyright © 2017 Elsevier Inc. All rights reserved.

Big data in sleep medicine: prospects and pitfalls in phenotyping

PubMed Central

Bianchi, Matt T; Russo, Kathryn; Gabbidon, Harriett; Smith, Tiaundra; Goparaju, Balaji; Westover, M Brandon

2017-01-01

Clinical polysomnography (PSG) databases are a rich resource in the era of “big data” analytics. We explore the uses and potential pitfalls of clinical data mining of PSG using statistical principles and analysis of clinical data from our sleep center. We performed retrospective analysis of self-reported and objective PSG data from adults who underwent overnight PSG (diagnostic tests, n=1835). Self-reported symptoms overlapped markedly between the two most common categories, insomnia and sleep apnea, with the majority reporting symptoms of both disorders. Standard clinical metrics routinely reported on objective data were analyzed for basic properties (missing values, distributions), pairwise correlations, and descriptive phenotyping. Of 41 continuous variables, including clinical and PSG derived, none passed testing for normality. Objective findings of sleep apnea and periodic limb movements were common, with 51% having an apnea–hypopnea index (AHI) >5 per hour and 25% having a leg movement index >15 per hour. Different visualization methods are shown for common variables to explore population distributions. Phenotyping methods based on clinical databases are discussed for sleep architecture, sleep apnea, and insomnia. Inferential pitfalls are discussed using the current dataset and case examples from the literature. The increasing availability of clinical databases for large-scale analytics holds important promise in sleep medicine, especially as it becomes increasingly important to demonstrate the utility of clinical testing methods in management of sleep disorders. Awareness of the strengths, as well as caution regarding the limitations, will maximize the productive use of big data analytics in sleep medicine. PMID:28243157

Evaluation of the DSM-5 Severity Indicator for Bulimia Nervosa

PubMed Central

Grilo, Carlos M.; Ivezaj, Valentina; White, Marney A.

2015-01-01

This study examined the DSM-5 severity criterion for bulimia nervosa (BN) based on the frequency of inappropriate weight compensatory behaviors. 199 community volunteers classified with BN were categorized using DSM-5 severity levels and compared on demographic and clinical variables. 77 (39%) participants were categorized as mild, 68 (34%) as moderate, 32 (16%) as severe, and 22 (11%) as extreme. The severity groups did not differ significantly in demographic variables or body mass index. Shape and Weight concerns did not differ significantly across severity groups. Binge eating differed with the extreme group having higher frequency than the severe, moderate, and mild groups, which did not differ from each other. Restraint differed with the extreme group having significantly higher levels than the mild group. Eating concerns differed with the extreme group having higher levels than moderate and mild groups. Depression differed with the extreme group having higher levels than severe, moderate, and mild groups, which did not differ from each other. Findings from this non-clinical group provide new, albeit modest, support for DSM-5 severity rating for BN based on frequency of inappropriate weight compensatory behaviors. Statistical findings indicate that differences in collateral clinical variables associated with the DSM-5 severity ratings reflect small effect sizes. Further research is needed with treatment-seeking patient groups with BN to establish the validity of the DSM-5 severity specifier and should include broader clinical and functional validators. PMID:25744910

Evaluation of the DSM-5 severity indicator for bulimia nervosa.

PubMed

Grilo, Carlos M; Ivezaj, Valentina; White, Marney A

2015-04-01

This study examined the DSM-5 severity criterion for bulimia nervosa (BN) based on the frequency of inappropriate weight compensatory behaviors. 199 community volunteers classified with BN were categorized using DSM-5 severity levels and compared on demographic and clinical variables. 77 (39%) participants were categorized as mild, 68 (34%) as moderate, 32 (16%) as severe, and 22 (11%) as extreme. The severity groups did not differ significantly in demographic variables or body mass index. Shape and Weight concerns did not differ significantly across severity groups. Binge eating differed with the extreme group having significantly higher frequency than the severe, moderate, and mild groups, which did not differ from each other. Restraint differed with the extreme group having significantly higher levels than the mild group. Eating concerns differed with the extreme group having significantly higher levels than moderate and mild groups. Depression differed with the extreme group having significantly higher levels than severe, moderate, and mild groups, which did not differ from each other. Findings from this non-clinical group provide new, albeit modest, support for DSM-5 severity rating for BN based on frequency of inappropriate weight compensatory behaviors. Statistical findings indicate that differences in collateral clinical variables associated with the DSM-5 severity ratings reflect small effect sizes. Further research is needed with treatment-seeking patient groups with BN to establish the validity of the DSM-5 severity specifier and should include broader clinical and functional validators. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical associations of white matter damage in cART-treated HIV-positive children in South Africa.

PubMed

Hoare, Jacqueline; Fouche, Jean-Paul; Phillips, Nicole; Joska, John A; Donald, Kirsten A; Thomas, Kevin; Stein, Dan J

2015-04-01

A range of factors contributes to white matter damage in vertically infected HIV-positive children. These may include combination antiretroviral treatment (cART) regimen, sociodemographic factors, nutritional-hematological status, HIV-relevant clinical variables, and cognitive functioning. We explored associations between a number of these factors and diffusion tensor imaging (DTI) measures in 50 cART-treated children aged 6 to 15 years. Fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD), and axial diffusion (AD) were derived from 48 cerebral white matter regions. Significant associations between a number of the clinical variables and white matter integrity were found. Decreased FA, a measure of neuronal damage, was associated with being on second-line cART, low hemoglobin, and younger age. Children with increased MD, a measure of neuronal damage, were younger, had reduced albumin and hemoglobin, and increased viral load. Decreased AD, a measure of axonal damage, was associated with increased viral load and total protein, decreased albumin and hemoglobin, younger age, poorer fronto-striatal cognition, and being on second-line cART. Increased RD, a measure of myelin loss, was associated with younger age, low current CD4 count, low albumin and hemoglobin, and higher viral load and total protein. The current findings underline the possible association of first-line treatment failure with white matter brain dysfunction in pediatric neuroHIV and the importance of examining the effects of HIV disease in the context of treatable clinical variables such as anemia and nutritional status.

HLA-G expression in gastric carcinoma: clinicopathological correlations and prognostic impact.

PubMed

Murdaca, Giuseppe; Calamaro, Paola; Lantieri, Francesca; Pigozzi, Simona; Mastracci, Luca; Grillo, Federica; Magnani, Ottavia; Ceppa, Paola; Puppo, Francesco; Fiocca, Roberto

2018-05-29

To analyze expression of human leukocyte antigen-G (HLA-G) in gastric adenocarcinoma and correlate its expression with histological and clinical variables. A continuous series of 94 unselected patients with gastric adenocarcinoma (stage I to III) were selected. All histological and clinical variables were collected including the intensity of intra- and peri-tumor lymphocytic infiltration. HLA-G expression was investigated using immunohistochemistry. All histological samples analyzed for HLA-G expression were taken from the primary gastric lesion and included non-neoplastic mucosa. Evaluation of HLA-G expression was performed on the transition zone between tumor and non-neoplastic mucosa, and the invasive front of the tumor and assessment was performed as follows: percentage of positive (strong expression vs weak) cells. A variable amount of HLA-G-positive tumor cells was found in 24 out of 94 cases (25.5%). No significant correlation was found between HLA-G expression and other clinicopathological variables (sex, age, stage, grade, histotype). The overall median survival was worse in patients with HLA-G-positive adenocarcinoma (24.3 months, CI 95% 7.7-41.0) compared to those with HLA-G-negative tumors (66.3 months, CI 95% 53.0-79.7; p < 0.0001). Two- and 5-year survival rates of HLA-G-negative patients were 88 and 44%, respectively, while were 42 and 11% in those HLA-G-positive. This trend was observed in all stages but was more marked in stage III. HLA-G expression is associated with poor survival in stage III gastric cancer patients and represents a possible immunoescape mechanism of cancer cells.

Prevalence and associated risk factors of latent tuberculosis infection in a Spanish prison.

PubMed

López de Goicoechea-Saiz, M E; Sternberg, F; Portilla-Sogorb, J

2018-01-01

To determine the prevalence of latent tuberculosis infection (LTI) in a Spanish prison, analyze the main sociodemographic and clinical variables associated with this condition and estimate the percentage of individuals with LTI who have received chemoprophylactic treatment. Cross-sectional study including inmates hosted in the Madrid VI Prison on 16/07/2016. Exclusion criteria: history of tuberculosis; non-updated tuberculin test according to the Tuberculosis Prevention and Control Program in Prisons protocol. Information of the variables was collected from SANIT and SIP programs, and by checking the clinical records of inmates. Description of the participant population and comparison between the frequency of distribution of the independent variables in LTI present and absent groups were performed, the last calculating the p value with Ji2 and Mann-Whitney U tests. Bivariate and multivariate analysis have been carried out with a logistic regression model. 936 individuals have been included. The prevalence of LTI in prison is 54.6%. This condition has been linked to the sociodemographic variables age, sex and nationality of origin, being age the one that has shown the strongest association. Among the other factors analyzed, only HCV infection behaves as a predictor of LTI. 30.3% of the individuals with LTI have completed or are receiving chemoprophylactic treatment in the moment of the study. LTI prevalence is high in the Spanish current prison population. The results of the study emphasize the relevance of the LTI screening in the prison setting, specially among high risk groups, and point out the need of a greater effort in the indication and completion of the chemoprophylactic treatment.

Heart rate variability measurement and clinical depression in acute coronary syndrome patients: narrative review of recent literature

PubMed Central

Harris, Patricia RE; Sommargren, Claire E; Stein, Phyllis K; Fung, Gordon L; Drew, Barbara J

2014-01-01

Aim We aimed to explore links between heart rate variability (HRV) and clinical depression in patients with acute coronary syndrome (ACS), through a review of recent clinical research literature. Background Patients with ACS are at risk for both cardiac autonomic dysfunction and clinical depression. Both conditions can negatively impact the ability to recover from an acute physiological insult, such as unstable angina or myocardial infarction, increasing the risk for adverse cardiovascular outcomes. HRV is recognized as a reflection of autonomic function. Methods A narrative review was undertaken to evaluate state-of-the-art clinical research, using the PubMed database, January 2013. The search terms “heart rate variability” and “depression” were used in conjunction with “acute coronary syndrome”, “unstable angina”, or “myocardial infarction” to find clinical studies published within the past 10 years related to HRV and clinical depression, in patients with an ACS episode. Studies were included if HRV measurement and depression screening were undertaken during an ACS hospitalization or within 2 months of hospital discharge. Results Nine clinical studies met the inclusion criteria. The studies’ results indicate that there may be a relationship between abnormal HRV and clinical depression when assessed early after an ACS event, offering the possibility that these risk factors play a modest role in patient outcomes. Conclusion While a definitive conclusion about the relevance of HRV and clinical depression measurement in ACS patients would be premature, the literature suggests that these measures may provide additional information in risk assessment. Potential avenues for further research are proposed. PMID:25071372

Bootstrap investigation of the stability of a Cox regression model.

PubMed

Altman, D G; Andersen, P K

1989-07-01

We describe a bootstrap investigation of the stability of a Cox proportional hazards regression model resulting from the analysis of a clinical trial of azathioprine versus placebo in patients with primary biliary cirrhosis. We have considered stability to refer both to the choice of variables included in the model and, more importantly, to the predictive ability of the model. In stepwise Cox regression analyses of 100 bootstrap samples using 17 candidate variables, the most frequently selected variables were those selected in the original analysis, and no other important variable was identified. Thus there was no reason to doubt the model obtained in the original analysis. For each patient in the trial, bootstrap confidence intervals were constructed for the estimated probability of surviving two years. It is shown graphically that these intervals are markedly wider than those obtained from the original model.

Implementation and evaluation of a clinical pathway for TRAM breast reconstruction.

PubMed

Hwang, T G; Wilkins, E G; Lowery, J C; Gentile, J

2000-02-01

Among strategies recently proposed to reduce practice variation, promote quality, and control costs in health care delivery, the concept of the clinical pathway has received considerable attention. Because transverse rectus abdominis musculocutaneous (TRAM) breast reconstruction is a common and often costly intervention, this institution sought to evaluate cost and quality outcomes of a clinical pathways program for this procedure. The TRAM reconstruction clinical pathway was implemented in April of 1996 to standardize postoperative care in this patient population. Outcomes of consecutive pathway cases for the first 14 months of the program were assessed in a retrospective cohort design, by using all nonpathway TRAM cases from the 18 months immediately before pathway implementation as controls. Outcomes assessed included length of hospital stay, postoperative complications, total postoperative charges, and total postoperative costs in relative value units. Data on these dependent variables were collected from hospital charts and billing records. The effects of pathway implementation on the outcomes of interest were analyzed by using analysis of covariance to control for potential confounding by other independent variables, including surgical site (unilateral versus bilateral reconstructions), technique (pedicle versus free TRAMs), timing (immediate versus delayed reconstructions), and patient age. Finally, a comparison of variances in the outcomes of interest between the two groups was analyzed by using an Ftest. For all statistical tests, p values of < or = 0.05 were considered significant. Twenty-nine patients were treated in the TRAM pathway group, whereas the control population included 40 nonpathway patients. After implementation of the TRAM pathway, length of stay decreased from 6.0 to 5.2 days; total postoperative charges were reduced from $8587 to $7744; and total postoperative relative value unit utilization declined from 1686 to 1104. Analysis of covariance showed that the decreases in length of hospital stay and relative value units in the TRAM pathway were statistically significant (p = 0.05 and p = 0.007, respectively). By contrast, no significant increase in complications was observed after pathway implementation. Variability in the TRAM pathway group, as measured by SD, decreased significantly for both length of hospital stay (p = 0.039) and relative value units (p = 0.023). Implementation of the TRAM reconstruction clinical pathway resulted in significant declines in length of hospital stay and total costs. These decreases in resource utilization had no significant effect on postoperative complication rates. Although additional research is needed to further assess the impact of clinical pathways, this approach offers considerable promise for improving the cost-effectiveness of health care.

Clinical phenotype of ASD-associated DYRK1A haploinsufficiency.

PubMed

Earl, Rachel K; Turner, Tychele N; Mefford, Heather C; Hudac, Caitlin M; Gerdts, Jennifer; Eichler, Evan E; Bernier, Raphael A

2017-01-01

DYRK1A is a gene recurrently disrupted in 0.1-0.5% of the ASD population. A growing number of case reports with DYRK1A haploinsufficiency exhibit common phenotypic features including microcephaly, intellectual disability, speech delay, and facial dysmorphisms. Phenotypic information from previously published DYRK1A cases ( n  = 51) and participants in an ongoing study at the University of Washington (UW, n  = 10) were compiled. Frequencies of recurrent phenotypic features in this population were compared to features observed in a large sample with idiopathic ASD from the Simons Simplex Collection ( n  = 1981). UW DYRK1A cases were further characterized quantitatively and compared to a randomly subsampled set of idiopathic ASD cases matched on age and gender ( n  = 10) and to cases with an ASD-associated disruptive mutation to CHD8 ( n  = 12). Contribution of familial genetic background to clinical heterogeneity was assessed by comparing head circumference, IQ, and ASD-related symptoms of UW DYRK1A cases to their unaffected parents. DYRK1A haploinsufficiency results in a common phenotypic profile including intellectual disability, speech and motor difficulties, microcephaly, feeding difficulties, and vision abnormalities. Eighty-nine percent of DYRK1A cases ascertained for ASD presented with a constellation of five or more of these symptoms. When compared quantitatively, DYRK1A cases presented with significantly lower IQ and adaptive functioning compared to idiopathic cases and significantly smaller head size compared to both idiopathic and CHD8 cases. Phenotypic variability in parental head circumference, IQ, and ASD-related symptoms corresponded to observed variability in affected child phenotype. Results confirm a core clinical phenotype for DYRK1A disruptions, with a combination of features that is distinct from idiopathic ASD. Cases with DYRK1A mutations are also distinguishable from disruptive mutations to CHD8 by head size. Measurable, quantitative characterization of DYRK1A haploinsufficiency illuminates clinical variability, which may be, in part, due to familial genetic background.

Toward the International Classification of Functioning, Disability and Health (ICF) Rehabilitation Set: A Minimal Generic Set of Domains for Rehabilitation as a Health Strategy.

PubMed

Prodinger, Birgit; Cieza, Alarcos; Oberhauser, Cornelia; Bickenbach, Jerome; Üstün, Tevfik Bedirhan; Chatterji, Somnath; Stucki, Gerold

2016-06-01

To develop a comprehensive set of the International Classification of Functioning, Disability and Health (ICF) categories as a minimal standard for reporting and assessing functioning and disability in clinical populations along the continuum of care. The specific aims were to specify the domains of functioning recommended for an ICF Rehabilitation Set and to identify a minimal set of environmental factors (EFs) to be used alongside the ICF Rehabilitation Set when describing disability across individuals and populations with various health conditions. Secondary analysis of existing data sets using regression methods (Random Forests and Group Lasso regression) and expert consultations. Along the continuum of care, including acute, early postacute, and long-term and community rehabilitation settings. Persons (N=9863) with various health conditions participated in primary studies. The number of respondents for whom the dependent variable data were available and used in this analysis was 9264. Not applicable. For regression analyses, self-reported general health was used as a dependent variable. The ICF categories from the functioning component and the EF component were used as independent variables for the development of the ICF Rehabilitation Set and the minimal set of EFs, respectively. Thirty ICF categories to be complemented with 12 EFs were identified as relevant to the identified ICF sets. The ICF Rehabilitation Set constitutes of 9 ICF categories from the component body functions and 21 from the component activities and participation. The minimal set of EFs contains 12 categories spanning all chapters of the EF component of the ICF. The identified sets proposed serve as minimal generic sets of aspects of functioning in clinical populations for reporting data within and across heath conditions, time, clinical settings including rehabilitation, and countries. These sets present a reference framework for harmonizing existing information on disability across general and clinical populations. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Rationale, objectives, and design of the EUTrigTreat clinical study: a prospective observational study for arrhythmia risk stratification and assessment of interrelationships among repolarization markers and genotype

PubMed Central

Seegers, Joachim; Vos, Marc A.; Flevari, Panagiota; Willems, Rik; Sohns, Christian; Vollmann, Dirk; Lüthje, Lars; Kremastinos, Dimitrios T.; Floré, Vincent; Meine, Mathias; Tuinenburg, Anton; Myles, Rachel C.; Simon, Dirk; Brockmöller, Jürgen; Friede, Tim; Hasenfuß, Gerd; Lehnart, Stephan E.; Zabel, Markus

2012-01-01

Aims The EUTrigTreat clinical study has been designed as a prospective multicentre observational study and aims to (i) risk stratify patients with an implantable cardioverter defibrillator (ICD) for mortality and shock risk using multiple novel and established risk markers, (ii) explore a link between repolarization biomarkers and genetics of ion (Ca2+, Na+, K+) metabolism, (iii) compare the results of invasive and non-invasive electrophysiological (EP) testing, (iv) assess changes of non-invasive risk stratification tests over time, and (v) associate arrythmogenomic risk through 19 candidate genes. Methods and results Patients with clinical ICD indication are eligible for the trial. Upon inclusion, patients will undergo non-invasive risk stratification, including beat-to-beat variability of repolarization (BVR), T-wave alternans, T-wave morphology variables, ambient arrhythmias from Holter, heart rate variability, and heart rate turbulence. Non-invasive or invasive programmed electrical stimulation will assess inducibility of ventricular arrhythmias, with the latter including recordings of monophasic action potentials and assessment of restitution properties. Established candidate genes are screened for variants. The primary endpoint is all-cause mortality, while one of the secondary endpoints is ICD shock risk. A mean follow-up of 3.3 years is anticipated. Non-invasive testing will be repeated annually during follow-up. It has been calculated that 700 patients are required to identify risk predictors of the primary endpoint, with a possible increase to 1000 patients based on interim risk analysis. Conclusion The EUTrigTreat clinical study aims to overcome current shortcomings in sudden cardiac death risk stratification and to answer several related research questions. The initial patient recruitment is expected to be completed in July 2012, and follow-up is expected to end in September 2014. Clinicaltrials.gov identifier: NCT01209494. PMID:22117037

What variables can influence clinical reasoning?

PubMed

Ashoorion, Vahid; Liaghatdar, Mohammad Javad; Adibi, Peyman

2012-12-01

Clinical reasoning is one of the most important competencies that a physician should achieve. Many medical schools and licensing bodies try to predict it based on some general measures such as critical thinking, personality, and emotional intelligence. This study aimed at providing a model to design the relationship between the constructs. Sixty-nine medical students participated in this study. A battery test devised that consist four parts: Clinical reasoning measures, personality NEO inventory, Bar-On EQ inventory, and California critical thinking questionnaire. All participants completed the tests. Correlation and multiple regression analysis consumed for data analysis. There is low to moderate correlations between clinical reasoning and other variables. Emotional intelligence is the only variable that contributes clinical reasoning construct (r=0.17-0.34) (R(2) chnage = 0.46, P Value = 0.000). Although, clinical reasoning can be considered as a kind of thinking, no significant correlation detected between it and other constructs. Emotional intelligence (and its subscales) is the only variable that can be used for clinical reasoning prediction.

Phenotypic variability in monozygotic twins with neurofibromatosis 2

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

Baser, M.E.; Ragge, N.K.; Riccardi, V.M.

Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on chromosome 22q12 cause a clinically variable autosomal dominant syndrome characterized by bilateral vestibular schwannomas (VSs), other nervous system tumors, and early onset lenticular cataracts. We studied three pairs of monozygotic (MZ) twins with NF2, all with bilateral VSs, to separate genetic from nongenetic causes of clinical variability. The evaluation included gadolinium-enhanced high-resolution magnetic resonance imaging of the head and spine, neuro-ophthalmic examination with slit lamp, physical examination, and zygosity testing with microsatellite markers. Each MZ pair was concordant for general phenotypic subtype (mild or severe) and often for the affectedmore » organ systems. However, the MZ pairs were discordant for some features of disease presentation or progression. For example, all three pairs were discordant for presence or type of associated cranial tumors. We hypothesize that phenotypic differences between NF2 MZ twins are at least partly due to stochastic processes, such as the loss of the second NF2 allele or alleles of other genes. 42 refs., 1 tab.« less

A multi-segment foot model based on anatomically registered technical coordinate systems: method repeatability in pediatric feet.

PubMed

Saraswat, Prabhav; MacWilliams, Bruce A; Davis, Roy B

2012-04-01

Several multi-segment foot models to measure the motion of intrinsic joints of the foot have been reported. Use of these models in clinical decision making is limited due to lack of rigorous validation including inter-clinician, and inter-lab variability measures. A model with thoroughly quantified variability may significantly improve the confidence in the results of such foot models. This study proposes a new clinical foot model with the underlying strategy of using separate anatomic and technical marker configurations and coordinate systems. Anatomical landmark and coordinate system identification is determined during a static subject calibration. Technical markers are located at optimal sites for dynamic motion tracking. The model is comprised of the tibia and three foot segments (hindfoot, forefoot and hallux) and inter-segmental joint angles are computed in three planes. Data collection was carried out on pediatric subjects at two sites (Site 1: n=10 subjects by two clinicians and Site 2: five subjects by one clinician). A plaster mold method was used to quantify static intra-clinician and inter-clinician marker placement variability by allowing direct comparisons of marker data between sessions for each subject. Intra-clinician and inter-clinician joint angle variability were less than 4°. For dynamic walking kinematics, intra-clinician, inter-clinician and inter-laboratory variability were less than 6° for the ankle and forefoot, but slightly higher for the hallux. Inter-trial variability accounted for 2-4° of the total dynamic variability. Results indicate the proposed foot model reduces the effects of marker placement variability on computed foot kinematics during walking compared to similar measures in previous models. Copyright © 2011 Elsevier B.V. All rights reserved.

Formant Frequencies and Bandwidths in Relation to Clinical Variables in an Obstructive Sleep Apnea Population.

PubMed

Montero Benavides, Ana; Blanco Murillo, José Luis; Fernández Pozo, Rubén; Espinoza Cuadros, Fernando; Torre Toledano, Doroteo; Alcázar-Ramírez, José D; Hernández Gómez, Luis A

2016-01-01

We investigated whether differences in formants and their bandwidths, previously reported comparing small sample population of healthy individuals and patients with obstructive sleep apnea (OSA), are detected on a larger population representative of a clinical practice scenario. We examine possible indirect or mediated effects of clinical variables, which may shed some light on the connection between speech and OSA. In a retrospective study, 241 male subjects suspected to suffer from OSA were examined. The apnea-hypopnea index (AHI) was obtained for every subject using overnight polysomnography. Furthermore, the clinical variables usually reported as predictors of OSA, body mass index (BMI), cervical perimeter, height, weight, and age, were collected. Voice samples of sustained phonations of the vowels /a/, /e/, /i/, /o/, and /u/ were recorded. Formant frequencies F1, F2, and F3 and bandwidths BW1, BW2, and BW3 of the sustained vowels were determined using spectrographic analysis. Correlations among AHI, clinical parameters, and formants and bandwidths were determined. Correlations between AHI and clinical variables were stronger than those between AHI and voice features. AHI only correlates poorly with BW2 of /a/ and BW3 of /e/. A number of further weak but significant correlations have been detected between voice and clinical variables. Most of them were for height and age, with two higher values for age and F2 of /o/ and F2 of /u/. Only few very weak correlations were detected between voice and BMI, weight and cervical perimeter, wich are the clinical variables more correlated with AHI. No significant correlations were detected between AHI and formant frequencies and bandwidths. Correlations between voice and other clinical factors characterizing OSA are weak but highlight the importance of considering indirect or mediated effects of such clinical variables in any research on speech and OSA. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Clinical Databases for Chest Physicians.

PubMed

Courtwright, Andrew M; Gabriel, Peter E

2018-04-01

A clinical database is a repository of patient medical and sociodemographic information focused on one or more specific health condition or exposure. Although clinical databases may be used for research purposes, their primary goal is to collect and track patient data for quality improvement, quality assurance, and/or actual clinical management. This article aims to provide an introduction and practical advice on the development of small-scale clinical databases for chest physicians and practice groups. Through example projects, we discuss the pros and cons of available technical platforms, including Microsoft Excel and Access, relational database management systems such as Oracle and PostgreSQL, and Research Electronic Data Capture. We consider approaches to deciding the base unit of data collection, creating consensus around variable definitions, and structuring routine clinical care to complement database aims. We conclude with an overview of regulatory and security considerations for clinical databases. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Predictors of persistent pain after total knee arthroplasty: a systematic review and meta-analysis.

PubMed

Lewis, G N; Rice, D A; McNair, P J; Kluger, M

2015-04-01

Several studies have identified clinical, psychosocial, patient characteristic, and perioperative variables that are associated with persistent postsurgical pain; however, the relative effect of these variables has yet to be quantified. The aim of the study was to provide a systematic review and meta-analysis of predictor variables associated with persistent pain after total knee arthroplasty (TKA). Included studies were required to measure predictor variables prior to or at the time of surgery, include a pain outcome measure at least 3 months post-TKA, and include a statistical analysis of the effect of the predictor variable(s) on the outcome measure. Counts were undertaken of the number of times each predictor was analysed and the number of times it was found to have a significant relationship with persistent pain. Separate meta-analyses were performed to determine the effect size of each predictor on persistent pain. Outcomes from studies implementing uni- and multivariable statistical models were analysed separately. Thirty-two studies involving almost 30 000 patients were included in the review. Preoperative pain was the predictor that most commonly demonstrated a significant relationship with persistent pain across uni- and multivariable analyses. In the meta-analyses of data from univariate models, the largest effect sizes were found for: other pain sites, catastrophizing, and depression. For data from multivariate models, significant effects were evident for: catastrophizing, preoperative pain, mental health, and comorbidities. Catastrophizing, mental health, preoperative knee pain, and pain at other sites are the strongest independent predictors of persistent pain after TKA. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

HIV-associated anal dysplasia: experience from a multiethnic-HIV clinic in Hawaii.

PubMed

Payam, Ahoora; Shiramizu, Bruce; Shikuma, Cecilia; Milne, Cris; Terada, Kevin; Kajioka, Eric; Ka'opua, Lana Sue; Cassel, Kevin; Chow, Dominic

2011-01-01

To assess the proportion as well as predictors of anal dysplasia in HIV-infected Asian/Pacific Islanders. This was a retrospective chart review evaluating the proportion of anal dysplasia among a multiethnic population from an ambulatory university-based HIV clinic in Hawaii. Demographic, clinical, and virologic parameters were examined with respect to abnormal anal Pap smear. Variables included: Pap smear results (outcome variable), cytology results, age, self-reported ethnicity, CD4/ nadir CD4 counts, HIV viral load, antiretroviral therapy use, Hepatitis B and C co-infections, history of sexually transmitted diseases, personal history of cancer, tobacco use, alcohol use, intravenous drug abuse, family history of cancer, and history of genital/anal warts. There were no significant differences in rates of abnormal Pap smear among the ethnic groups. Abnormal Pap smears were associated with history of genital warts (7% normal vs. 18% abnormal, p=.01) and alcohol consumption (16% vs. 27%, p=.05). Hepatitis B infection and current anti-retroviral therapy (ART) were associated with normal Pap cytology (9.7% vs. 0%, p=.03) and (96.8% vs. 86.5%, p=.05) respectively. No differences in the proportion of abnormal Pap smears were seen among ethnic groups followed within an ambulatory HIV clinic.

Improving clinical outcomes for naltrexone as a management of problem alcohol use

PubMed Central

Hulse, Gary K

2013-01-01

Despite being a relatively effective and safe treatment, the clinical management of alcohol abuse/dependence by oral naltrexone can be compromised due to the patient's non-compliance with daily use of this medication. Over the past decade an increasing body of research has suggested that the use of sustained release depot naltrexone preparations can overcome this issue and deliver improved clinical outcomes. However, at the same time, research findings from diverse areas of pharmacogenetics, neurobiology and behavioural psychology have also been converging to identify variables including genetic markers, patient psychosocial characteristics and drug use history differences, or clusters of these variables that play a major role in mediating the response of alcohol abuse/dependent persons to treatment by naltrexone. While this article does not attempt to review all available data pertaining to an individual alcohol dependent patient's response to treatment by naltrexone, it does identify relevant research areas and highlights the importance of data arising from them. The characterization of clinical markers, to identify those patients who are most likely to benefit from naltrexone and to tailor a more individual naltrexone treatment, will ultimately provide significant benefit to both patients and clinicians by optimizing treatment outcome. PMID:22946873

Achilles Tendinopathy: Current Concepts about the Basic Science and Clinical Treatments

PubMed Central

Li, Hong-Yun

2016-01-01

Achilles tendinopathy is one of the most frequently ankle and foot overuse injuries, which is a clinical syndrome characterized by the combination of pain, swelling, and impaired performance. The two main categories of Achilles tendinopathy are classified according to anatomical location and broadly include insertional and noninsertional tendinopathy. The etiology of Achilles tendinopathy is multifactorial including both intrinsic and extrinsic factors. Failed healing response and degenerative changes were found in the tendon. The failed healing response includes three different and continuous stages (reactive tendinopathy, tendon disrepair, and degenerative tendinopathy). The histological studies have demonstrated an increased number of tenocytes and concentration of glycosaminoglycans in the ground substance, disorganization and fragmentation of the collagen, and neovascularization. There are variable conservative and surgical treatment options for Achilles tendinopathy. However, there has not been a gold standard of these treatments because of the controversial clinical results between various studies. In the future, new level I researches will be needed to prove the effect of these treatment options. PMID:27885357

Cancer-related anorexia/cachexia syndrome and oxidative stress: an innovative approach beyond current treatment.

PubMed

Mantovani, Giovanni; Madeddu, Clelia; Macciò, Antonio; Gramignano, Giulia; Lusso, Maria Rita; Massa, Elena; Astara, Giorgio; Serpe, Roberto

2004-10-01

Cancer-related anorexia/cachexia syndrome and oxidative stress play a key role in the progression and outcome of neoplastic disease. On the basis of our previously published studies and clinical experience, we have developed an innovative approach consisting of diet with high polyphenol content (400 mg), p.o. pharmaconutritional support enriched with n - 3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) 2 cans (237 mL each) per day, medroxiprogesterone acetate 500 mg/d, antioxidant treatment with alpha-lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400 mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d, and selective cyclooxygenase-2 inhibitor Celecoxib 200 mg/d. The treatment is administered for 16 weeks. The following variables are evaluated: (a) clinical variables (stage and Eastern Cooperative Oncology Group performance status); (b) nutritional variables (lean body mass, appetite, and resting energy expenditure); (c) laboratory variables (serum levels of proinflammatory cytokines, C-reactive protein, and leptin and blood levels of reactive oxygen species and antioxidant enzymes); and (d) quality of life variables (European Organization for Research and Treatment of Cancer QLQ-C30, EQ-5Dindex, and EQ-5DVAS). A phase II nonrandomized study has been designed to enroll 40 patients with advanced cancer at different sites with symptoms of cancer-related anorexia/cachexia syndrome and oxidative stress. As of January 2004, 28 patients have been enrolled: 25 patients were evaluable and 14 of them have completed the treatment (20 patients have completed 2 months of treatment). As for clinical response, five patients improved, three patients remained unchanged, and six patients worsened. The Eastern Cooperative Oncology Group performance status (grade) 1 remained unchanged. As for nutritional/functional variables, the lean body mass increased significantly at 2 and 4 months. As for laboratory variables, reactive oxygen species decreased significantly and proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha decreased significantly. As for quality of life, it comprehensively improved after treatment. The treatment has been shown to be effective for clinical response, increase of lean body mass, decrease of reactive oxygen species and proinflammatory cytokines, and improvement of quality of life. The treatment has been shown to be safe with good compliance of patients. The study is in progress (14 further patients will be included).

Public funding of pharmaceuticals in The Netherlands: investigating the effect of evidence, process and context on CVZ decision-making.

PubMed

Cerri, Karin H; Knapp, Martin; Fernandez, Jose-Luis

2014-09-01

The College Voor Zorgverzekeringen (CVZ) provides guidance to the Dutch healthcare system on funding and use of new pharmaceutical technologies. This study examined the impact of evidence, process and context factors on CVZ decisions in 2004-2009. A data set of CVZ decisions pertaining to pharmaceutical technologies was created, including 29 variables extracted from published information. A three-category outcome variable was used, defined as the decision to 'recommend', 'restrict' or 'not recommend' a technology. Technologies included in list 1A/1B or on the expensive drug list were considered recommended; those included in list 2 or for which patient co-payment is required were considered restricted; technologies not included on any reimbursement list were classified as 'not recommended'. Using multinomial logistic regression, the relative contribution of explanatory variables on CVZ decisions was assessed. In all, 244 technology appraisals (256 technologies) were analysed, with 51%, of technologies recommended, 33% restricted and 16% not recommended by CVZ for funding. The multinomial model showed significant associations (p ≤ 0.10) between CVZ outcome and several variables, including: (1) use of an active comparator and demonstration of statistical superiority of the primary endpoint in clinical trials, (2) pharmaceutical budget impact associated with introduction of the technology, (3) therapeutic indication and (4) prevalence of the target population. Results confirm the value of a comprehensive and multivariate approach to understanding CVZ decision-making.

Institutional Profile: University of Chicago Center for Personalized Therapeutics: research, education and implementation science.

PubMed

Dolan, M Eileen; Maitland, Michael L; O'Donnell, Peter H; Nakamura, Yusuke; Cox, Nancy J; Ratain, Mark J

2013-09-01

Pharmacogenomics is aimed at advancing our knowledge of the genetic basis of variable drug response. The Center for Personalized Therapeutics within the University of Chicago comprises basic, translational and clinical research as well as education including undergraduate, graduate, medical students, clinical/postdoctoral fellows and faculty. The Committee on Clinical Pharmacology and Pharmacogenomics is the educational arm of the Center aimed at training clinical and postdoctoral fellows in translational pharmacology and pharmacogenomics. Research runs the gamut from basic discovery and functional studies to pharmacogenomic implementation studies to evaluate physician adoption of genetic medicine. The mission of the Center is to facilitate research, education and implementation of pharmacogenomics to realize the true potential of personalized medicine and improve the lives of patients.

Hand assessment in older adults with musculoskeletal hand problems: a reliability study.

PubMed

Myers, Helen L; Thomas, Elaine; Hay, Elaine M; Dziedzic, Krysia S

2011-01-07

Musculoskeletal hand pain is common in the general population. This study aims to investigate the inter- and intra-observer reliability of two trained observers conducting a simple clinical interview and physical examination for hand problems in older adults. The reliability of applying the American College of Rheumatology (ACR) criteria for hand osteoarthritis to community-dwelling older adults will also be investigated. Fifty-five participants aged 50 years and over with a current self-reported hand problem and registered with one general practice were recruited from a previous health questionnaire study. Participants underwent a standardised, structured clinical interview and physical examination by two independent trained observers and again by one of these observers a month later. Agreement beyond chance was summarised using Kappa statistics and intra-class correlation coefficients. Median values for inter- and intra-observer reliability for clinical interview questions were found to be "substantial" and "moderate" respectively [median agreement beyond chance (Kappa) was 0.75 (range: -0.03, 0.93) for inter-observer ratings and 0.57 (range: -0.02, 1.00) for intra-observer ratings]. Inter- and intra-observer reliability for physical examination items was variable, with good reliability observed for some items, such as grip and pinch strength, and poor reliability observed for others, notably assessment of altered sensation, pain on resisted movement and judgements based on observation and palpation of individual features at single joints, such as bony enlargement, nodes and swelling. Moderate agreement was observed both between and within observers when applying the ACR criteria for hand osteoarthritis. Standardised, structured clinical interview is reliable for taking a history in community-dwelling older adults with self reported hand problems. Agreement between and within observers for physical examination items is variable. Low Kappa values may have resulted, in part, from a low prevalence of clinical signs and symptoms in the study participants. The decision to use clinical interview and hand assessment variables in clinical practice or further research in primary care should include consideration of clinical applicability and training alongside reliability. Further investigation is required to determine the relationship between these clinical questions and assessments and the clinical course of hand pain and hand problems in community-dwelling older adults.

Urinary Tract Infection Antibiotic Trial Study Design: A Systematic Review.

PubMed

Basmaci, Romain; Vazouras, Konstantinos; Bielicki, Julia; Folgori, Laura; Hsia, Yingfen; Zaoutis, Theoklis; Sharland, Mike

2017-12-01

Urinary tract infections (UTIs) represent common bacterial infections in children. No guidance on the conduct of pediatric febrile UTI clinical trials (CTs) exist. To assess the criteria used for patient selection and the efficacy end points in febrile pediatric UTI CTs. Medline, Embase, Cochrane central databases, and clinicaltrials.gov were searched between January 1, 1990, and November 24, 2016. We combined Medical Subject Headings terms and free-text terms for "urinary tract infections" and "therapeutics" and "clinical trials" in children (0-18 years), identifying 3086 articles. Two independent reviewers assessed study quality and performed data extraction. We included 40 CTs in which a total of 4381 cases of pediatric UTIs were investigated. Positive urine culture results and fever were the most common inclusion criteria (93% and 78%, respectively). Urine sampling method, pyuria, and colony thresholds were highly variable. Clinical and microbiological end points were assessed in 88% and 93% of the studies, respectively. Timing for end point assessment was highly variable, and only 3 studies (17%) out of the 18 performed after the Food and Drug Administration 1998 guidance publication assessed primary and secondary end points consistently with this guidance. Our limitations included a mixed population of healthy children and children with an underlying condition. In 6 trials, researchers studied a subgroup of patients with afebrile UTI. We observed a wide variability in the microbiological inclusion criteria and the timing for end point assessment. The available guidance for adults appear not to be used by pediatricians and do not seem applicable to the childhood UTI. A harmonized design for pediatric UTIs CT is necessary. Copyright © 2017 by the American Academy of Pediatrics.

Diagnostic accuracy and receiver-operating characteristics curve analysis in surgical research and decision making.

PubMed

Søreide, Kjetil; Kørner, Hartwig; Søreide, Jon Arne

2011-01-01

In surgical research, the ability to correctly classify one type of condition or specific outcome from another is of great importance for variables influencing clinical decision making. Receiver-operating characteristic (ROC) curve analysis is a useful tool in assessing the diagnostic accuracy of any variable with a continuous spectrum of results. In order to rule a disease state in or out with a given test, the test results are usually binary, with arbitrarily chosen cut-offs for defining disease versus health, or for grading of disease severity. In the postgenomic era, the translation from bench-to-bedside of biomarkers in various tissues and body fluids requires appropriate tools for analysis. In contrast to predetermining a cut-off value to define disease, the advantages of applying ROC analysis include the ability to test diagnostic accuracy across the entire range of variable scores and test outcomes. In addition, ROC analysis can easily examine visual and statistical comparisons across tests or scores. ROC is also favored because it is thought to be independent from the prevalence of the condition under investigation. ROC analysis is used in various surgical settings and across disciplines, including cancer research, biomarker assessment, imaging evaluation, and assessment of risk scores.With appropriate use, ROC curves may help identify the most appropriate cutoff value for clinical and surgical decision making and avoid confounding effects seen with subjective ratings. ROC curve results should always be put in perspective, because a good classifier does not guarantee the expected clinical outcome. In this review, we discuss the fundamental roles, suggested presentation, potential biases, and interpretation of ROC analysis in surgical research.

Music and metronome cues produce different effects on gait spatiotemporal measures but not gait variability in healthy older adults.

PubMed

Wittwer, Joanne E; Webster, Kate E; Hill, Keith

2013-02-01

Rhythmic auditory cues including music and metronome beats have been used, sometimes interchangeably, to improve disordered gait arising from a range of clinical conditions. There has been limited investigation into whether there are optimal cue types. Different cue types have produced inconsistent effects across groups which differed in both age and clinical condition. The possible effect of normal ageing on response to different cue types has not been reported for gait. The aim of this study was to determine the effects of both rhythmic music and metronome cues on gait spatiotemporal measures (including variability) in healthy older people. Twelve women and seven men (>65 years) walked on an instrumented walkway at comfortable pace and then in time to each of rhythmic music and metronome cues at comfortable pace stepping frequency. Music but not metronome cues produced a significant increase in group mean gait velocity of 4.6 cm/s, due mostly to a significant increase in group mean stride length of 3.1cm. Both cue types produced a significant but small increase in cadence of 1 step/min. Mean spatio-temporal variability was low at baseline and did not increase with either cue type suggesting cues did not disrupt gait timing. Study findings suggest music and metronome cues may not be used interchangeably and cue type as well as frequency should be considered when evaluating effects of rhythmic auditory cueing on gait. Further work is required to determine whether optimal cue types and frequencies to improve walking in different clinical groups can be identified. Copyright © 2012 Elsevier B.V. All rights reserved.

Convergent, discriminant, and criterion validity of DSM-5 traits.

PubMed

Yalch, Matthew M; Hopwood, Christopher J

2016-10-01

Section III of the Diagnostic and Statistical Manual of Mental Disorders (5th edi.; DSM-5; American Psychiatric Association, 2013) contains a system for diagnosing personality disorder based in part on assessing 25 maladaptive traits. Initial research suggests that this aspect of the system improves the validity and clinical utility of the Section II Model. The Computer Adaptive Test of Personality Disorder (CAT-PD; Simms et al., 2011) contains many similar traits as the DSM-5, as well as several additional traits seemingly not covered in the DSM-5. In this study we evaluate the convergent and discriminant validity between the DSM-5 traits, as assessed by the Personality Inventory for DSM-5 (PID-5; Krueger et al., 2012), and CAT-PD in an undergraduate sample, and test whether traits included in the CAT-PD but not the DSM-5 provide incremental validity in association with clinically relevant criterion variables. Results supported the convergent and discriminant validity of the PID-5 and CAT-PD scales in their assessment of 23 out of 25 DSM-5 traits. DSM-5 traits were consistently associated with 11 criterion variables, despite our having intentionally selected clinically relevant criterion constructs not directly assessed by DSM-5 traits. However, the additional CAT-PD traits provided incremental information above and beyond the DSM-5 traits for all criterion variables examined. These findings support the validity of pathological trait models in general and the DSM-5 and CAT-PD models in particular, while also suggesting that the CAT-PD may include additional traits for consideration in future iterations of the DSM-5 system. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Longitudinal assessment of excessive daytime sleepiness in early Parkinson's disease.

PubMed

Amara, Amy W; Chahine, Lama M; Caspell-Garcia, Chelsea; Long, Jeffrey D; Coffey, Christopher; Högl, Birgit; Videnovic, Aleksandar; Iranzo, Alex; Mayer, Geert; Foldvary-Schaefer, Nancy; Postuma, Ron; Oertel, Wolfgang; Lasch, Shirley; Marek, Ken; Simuni, Tanya

2017-08-01

Excessive daytime sleepiness (EDS) is common and disabling in Parkinson's disease (PD). Predictors of EDS are unclear, and data on biological correlates of EDS in PD are limited. We investigated clinical, imaging and biological variables associated with longitudinal changes in sleepiness in early PD. The Parkinson's Progression Markers Initiative is a prospective cohort study evaluating progression markers in participants with PD who are unmedicated at baseline (n=423) and healthy controls (HC; n=196). EDS was measured with the Epworth Sleepiness Scale (ESS). Clinical, biological and imaging variables were assessed for associations with EDS for up to 3 years. A machine learning approach (random survival forests) was used to investigate baseline predictors of incident EDS. ESS increased in PD from baseline to year 3 (mean±SD 5.8±3.5 to 7.55±4.6, p<0.0001), with no change in HC. Longitudinally, EDS in PD was associated with non-tremor dominant phenotype, autonomic dysfunction, depression, anxiety and probable behaviour disorder, but not cognitive dysfunction or motor severity. Dopaminergic therapy was associated with EDS at years 2 and 3, as dose increased. EDS was also associated with presynaptic dopaminergic dysfunction, whereas biofluid markers at year 1 showed no significant associations with EDS. A predictive index for EDS was generated, which included seven baseline characteristics, including non-motor symptoms and cerebrospinal fluid phosphorylated-tau/total-tau ratio. In early PD, EDS increases significantly over time and is associated with several clinical variables. The influence of dopaminergic therapy on EDS is dose dependent. Further longitudinal analyses will better characterise associations with imaging and biomarkers. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The real world cost and health resource utilization associated to manic episodes: The MANACOR study.

PubMed

Hidalgo-Mazzei, Diego; Undurraga, Juan; Reinares, María; Bonnín, Caterina del Mar; Sáez, Cristina; Mur, María; Nieto, Evaristo; Vieta, Eduard

2015-01-01

Bipolar disorder is a relapsing-remitting condition affecting approximately 1-2% of the population. Even when the treatments available are effective, relapses are still very frequent. Therefore, the burden and cost associated to every new episode of the disorder have relevant implications in public health. The main objective of this study was to estimate the associated health resource consumption and direct costs of manic episodes in a real world clinical setting, taking into consideration clinical variables. Bipolar I disorder patients who recently presented an acute manic episode based on DSM-IV criteria were consecutively included. Sociodemographic variables were retrospectively collected and during the 6 following months clinical variables were prospectively assessed (YMRS,HDRS-17,FAST and CGI-BP-M). The health resource consumption and associate cost were estimated based on hospitalization days, pharmacological treatment, emergency department and outpatient consultations. One hundred sixty-nine patients patients from 4 different university hospitals in Catalonia (Spain) were included. The mean direct cost of the manic episodes was €4,771. The 77% (€3,651) was attributable to hospitalization costs while 14% (€684) was related to pharmacological treatment, 8% (€386) to outpatient visits and only 1% (€50) to emergency room visits. The hospitalization days were the main cost driver. An initial FAST score>41 significantly predicted a higher direct cost. Our results show the high cost and burden associated with BD and the need to design more cost-efficient strategies in the prevention and management of manic relapses in order to avoid hospital admissions. Poor baseline functioning predicted high costs, indicating the importance of functional assessment in bipolar disorder. Copyright © 2014 SEP y SEPB. Published by Elsevier España. All rights reserved.

The importance of histopathological and clinical variables in predicting the evolution of colon cancer.

PubMed

Diculescu, Mircea; Iacob, Răzvan; Iacob, Speranţa; Croitoru, Adina; Becheanu, Gabriel; Popeneciu, Valentin

2002-09-01

It has been a consensus that prognostic factors should always be taken into account before planning treatment in colorectal cancer. A 5 year prospective study was conducted, in order to assess the importance of several histopathological and clinical prognostic variables in the prediction of evolution in colon cancer. Some of the factors included in the analysis are still subject to dispute by different authors. 46 of 53 screened patients qualified to enter the study and underwent a potentially curative resection of the tumor, followed, when necessary, by adjuvant chemotherapy. Univariate and multivariate analyses were carried out in order to identify independent prognostic indicators. The endpoint of the study was considered the recurrence of the tumor or the detection of metastases. 65.2% of the patients had a good evolution during the follow up period. Multivariate survival analysis performed by Cox proportional hazard model identified 3 independent prognostic factors: Dukes stage (p = 0.00002), the grade of differentiation (p = 0.0009) and the weight loss index, representing the weight loss of the patient divided by the number of months when it was actually lost (p = 0.02). Age under 40 years, sex, microscopic aspect of the tumor, tumor location, anemia degree were not identified by our analysis as having prognostic importance. Histopathological factors continue to be the most valuable source of information regarding the possible evolution of patients with colorectal cancer. Individual clinical symptoms or biological parameters such as erytrocyte sedimentation rate or hemoglobin level are of little or no prognostic value. More research is required relating to the impact of a performance status index (which could include also weight loss index) as another reliable prognostic variable.

Measure of functional independence dominates discharge outcome prediction after inpatient rehabilitation for stroke.

PubMed

Brown, Allen W; Therneau, Terry M; Schultz, Billie A; Niewczyk, Paulette M; Granger, Carl V

2015-04-01

Identifying clinical data acquired at inpatient rehabilitation admission for stroke that accurately predict key outcomes at discharge could inform the development of customized plans of care to achieve favorable outcomes. The purpose of this analysis was to use a large comprehensive national data set to consider a wide range of clinical elements known at admission to identify those that predict key outcomes at rehabilitation discharge. Sample data were obtained from the Uniform Data System for Medical Rehabilitation data set with the diagnosis of stroke for the years 2005 through 2007. This data set includes demographic, administrative, and medical variables collected at admission and discharge and uses the FIM (functional independence measure) instrument to assess functional independence. Primary outcomes of interest were functional independence measure gain, length of stay, and discharge to home. The sample included 148,367 people (75% white; mean age, 70.6±13.1 years; 97% with ischemic stroke) admitted to inpatient rehabilitation a mean of 8.2±12 days after symptom onset. The total functional independence measure score, the functional independence measure motor subscore, and the case-mix group were equally the strongest predictors for any of the primary outcomes. The most clinically relevant 3-variable model used the functional independence measure motor subscore, age, and walking distance at admission (r(2)=0.107). No important additional effect for any other variable was detected when added to this model. This analysis shows that a measure of functional independence in motor performance and age at rehabilitation hospital admission for stroke are predominant predictors of outcome at discharge in a uniquely large US national data set. © 2015 American Heart Association, Inc.

Cystic fibrosis: a clinical view.

PubMed

Castellani, Carlo; Assael, Baroukh M

2017-01-01

Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude. Classical treatment includes pancreatic enzyme replacement, respiratory physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant proportion of patients with severe symptoms still requires lung or, less frequently, liver transplantation. The great number of mutations and their diverse effects on the CFTR protein account only partially for CF clinical variability, and modifier genes have a role in modulating the clinical expression of the disease. Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder. Research is focusing on new drugs restoring CFTR function, some already available and with good clinical impact, others showing promising preliminary results that need to be confirmed in phase III clinical trials.

Psychosocial predictors of four health-promoting behaviors for cancer prevention using the stage of change of Transtheoretical Model.

PubMed

Choi, Jean H; Chung, Kyong-Mee; Park, Keeho

2013-10-01

The present study aimed to examine whether demographic as well as psychosocial variables related to the five stages of change of the Transtheoretical Model can predict non-clinical adults' cancer preventive and health-promoting behaviors. This study specifically focused on cancer, one of the major chronic diseases, which is a serious threat of national health. A total of 1530 adults participated in the study and completed questionnaires. Collected data were analyzed by using multinominal logistic regression. The significant predictors of later stages varied among the types of health-promoting behaviors. Certain cancer preventive health-promoting behaviors such as well-balanced diet and exercise were significantly associated with psychosocial variables including cancer prevention-related self-efficacy, personality traits, psychosocial stress, and social support. On the other hand, smoking cessation and moderate or abstinence from drinking were more likely to be predicted by demographic variables including sex and age. The present study found that in addition to self-efficacy-a relatively well-studied psychological variable-other personality traits and psychological factors including introversion, neuroticism, psychosocial stress, and social support also significantly predicted later stages of change with respect to cancer preventive health-promoting behaviors. The implications of this study are also discussed. Copyright © 2013 John Wiley & Sons, Ltd.

Phenotypic variability in patients with ADA2 deficiency due to identical homozygous R169Q mutations.

PubMed

Van Montfrans, Joris M; Hartman, Esther A R; Braun, Kees P J; Hennekam, Eric A M; Hak, Elisabeth A; Nederkoorn, Paul J; Westendorp, Willeke F; Bredius, Robbert G M; Kollen, Wouter J W; Schölvinck, Elisabeth H; Legger, G Elizabeth; Meyts, Isabelle; Liston, Adrian; Lichtenbelt, Klaske D; Giltay, Jacques C; Van Haaften, Gijs; De Vries Simons, Gaby M; Leavis, Helen; Sanders, Cornelis J G; Bierings, Marc B; Nierkens, Stefan; Van Gijn, Marielle E

2016-05-01

To determine the genotype-phenotype association in patients with adenosine deaminase-2 (ADA2) deficiency due to identical homozygous R169Q mutations inCECR1 METHODS: We present a case series of nine ADA2-deficient patients with an identical homozygous R169Q mutation. Clinical and diagnostic data were collected and available MRI studies were reviewed. We performed genealogy and haplotype analyses and measured serum ADA2 activity. ADA2 activity values were correlated to clinical symptoms. Age of presentation differed widely between the nine presented patients (range: 0 months to 8 years). The main clinical manifestations were (hepato)splenomegaly (8/9), skin involvement (8/9) and neurological involvement (8/9, of whom 6 encountered stroke). Considerable variation was seen in type, frequency and intensity of other symptoms, which included aplastic anaemia, acute myeloid leukaemia and cutaneous ulcers. Common laboratory abnormalities included cytopenias and hypogammaglobulinaemia. ADA2 enzyme activity in patients was significantly decreased compared with healthy controls. ADA2 activity levels tended to be lower in patients with stroke compared with patients without stroke. Genealogical studies did not identify a common ancestor; however, based on allele frequency, a North-West European founder effect can be noted. Three patients underwent haematopoietic cell transplantation, after which ADA2 activity was restored and clinical symptoms resolved. This case series revealed large phenotypic variability in patients with ADA2 deficiency though they were homozygous for the same R169Q mutation inCECR1 Disease modifiers, including epigenetic and environmental factors, thus seem important in determining the phenotype. Furthermore, haematopoietic cell transplantation appears promising for those patients with a severe clinical phenotype. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Using intraindividual variability to detect malingering in cognitive performance.

PubMed

Strauss, E; Hultsch, D F; Hunter, M; Slick, D J; Patry, B; Levy-Bencheton, J

1999-11-01

The utility of measures for detecting malingering was evaluated using a simulation design in which half the participants were encouraged to do their best and half were asked to feign head injury. Particular attention was focused on the utility of repeated assessment (intraindividual variability) in discriminating the groups. Participants were tested on three occasions on measures commonly used to detect malingering including a specific symptom validity test (SVT). The results indicated that multiple measures of malingering obtained in single assessment (occasion one) discriminated the groups effectively. In addition, however, intraindividual variability in performance, particularly of indicators from the SVT, provided unique information beyond level of performance. The results suggest that response inconsistency across testing sessions may be a clinically useful measure for the detection of malingering.

Quantitative PET/CT scanner performance characterization based upon the society of nuclear medicine and molecular imaging clinical trials network oncology clinical simulator phantom.

PubMed

Sunderland, John J; Christian, Paul E

2015-01-01

The Clinical Trials Network (CTN) of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) operates a PET/CT phantom imaging program using the CTN's oncology clinical simulator phantom, designed to validate scanners at sites that wish to participate in oncology clinical trials. Since its inception in 2008, the CTN has collected 406 well-characterized phantom datasets from 237 scanners at 170 imaging sites covering the spectrum of commercially available PET/CT systems. The combined and collated phantom data describe a global profile of quantitative performance and variability of PET/CT data used in both clinical practice and clinical trials. Individual sites filled and imaged the CTN oncology PET phantom according to detailed instructions. Standard clinical reconstructions were requested and submitted. The phantom itself contains uniform regions suitable for scanner calibration assessment, lung fields, and 6 hot spheric lesions with diameters ranging from 7 to 20 mm at a 4:1 contrast ratio with primary background. The CTN Phantom Imaging Core evaluated the quality of the phantom fill and imaging and measured background standardized uptake values to assess scanner calibration and maximum standardized uptake values of all 6 lesions to review quantitative performance. Scanner make-and-model-specific measurements were pooled and then subdivided by reconstruction to create scanner-specific quantitative profiles. Different makes and models of scanners predictably demonstrated different quantitative performance profiles including, in some cases, small calibration bias. Differences in site-specific reconstruction parameters increased the quantitative variability among similar scanners, with postreconstruction smoothing filters being the most influential parameter. Quantitative assessment of this intrascanner variability over this large collection of phantom data gives, for the first time, estimates of reconstruction variance introduced into trials from allowing trial sites to use their preferred reconstruction methodologies. Predictably, time-of-flight-enabled scanners exhibited less size-based partial-volume bias than non-time-of-flight scanners. The CTN scanner validation experience over the past 5 y has generated a rich, well-curated phantom dataset from which PET/CT make-and-model and reconstruction-dependent quantitative behaviors were characterized for the purposes of understanding and estimating scanner-based variances in clinical trials. These results should make it possible to identify and recommend make-and-model-specific reconstruction strategies to minimize measurement variability in cancer clinical trials. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Statistics 101 for Radiologists.

PubMed

Anvari, Arash; Halpern, Elkan F; Samir, Anthony E

2015-10-01

Diagnostic tests have wide clinical applications, including screening, diagnosis, measuring treatment effect, and determining prognosis. Interpreting diagnostic test results requires an understanding of key statistical concepts used to evaluate test efficacy. This review explains descriptive statistics and discusses probability, including mutually exclusive and independent events and conditional probability. In the inferential statistics section, a statistical perspective on study design is provided, together with an explanation of how to select appropriate statistical tests. Key concepts in recruiting study samples are discussed, including representativeness and random sampling. Variable types are defined, including predictor, outcome, and covariate variables, and the relationship of these variables to one another. In the hypothesis testing section, we explain how to determine if observed differences between groups are likely to be due to chance. We explain type I and II errors, statistical significance, and study power, followed by an explanation of effect sizes and how confidence intervals can be used to generalize observed effect sizes to the larger population. Statistical tests are explained in four categories: t tests and analysis of variance, proportion analysis tests, nonparametric tests, and regression techniques. We discuss sensitivity, specificity, accuracy, receiver operating characteristic analysis, and likelihood ratios. Measures of reliability and agreement, including κ statistics, intraclass correlation coefficients, and Bland-Altman graphs and analysis, are introduced. © RSNA, 2015.

Cost analysis of public health influenza vaccine clinics in Ontario.

PubMed

Mercer, Nicola J

2009-01-01

Public health in Ontario delivers, promotes and provides each fall the universal influenza immunization program. This paper addresses the question of whether Ontario public health agencies are able to provide the influenza immunization program within the Ministry of Health fiscal funding envelope of $5 per dose. Actual program delivery data from the 2006 influenza season of Wellington-Dufferin-Guelph Public Health (WDGPH) were used to create a model template for influenza clinics capturing all variable costs. Promotional and administrative costs were separated from clinic costs. Maximum staff workloads were estimated. Vaccine clinics were delivered by public health staff in accordance with standard vaccine administration practices. The most significant economic variables for influenza clinics are labour costs and number of vaccines given per nurse per hour. The cost of facility rental was the only other significant cost driver. The ability of influenza clinics to break even depended on the ability to manage these cost drivers. At WDGPH, weekday flu clinics required the number of vaccines per nurse per hour to exceed 15, and for weekend flu clinics this number was greater than 21. We estimate that 20 vaccines per hour is at the limit of a safe workload over several hours. Managing cost then depends on minimizing hourly labour costs. The results of this analysis suggest that by managing the labour costs along with planning the volume of patients and avoiding expensive facilities, flu clinics can just break even. However, any increased costs, including negotiated wage increases or the move to safety needles, with a fixed revenue of $5.00 per dose will negate this conclusion.

Etiology and management of spontaneous haemothorax

PubMed Central

Panagiotopoulos, Nikolaos; Pararajasingham, Jonathan; Gvinianidze, Lasha; Iqbal, Yassir; Lawrence, David R.

2015-01-01

Spontaneous haemothorax (SH) is a subcategory of haemothorax that involves the accumulation of blood within the pleural space in the abscence of trauma or other causes. The clinical presentation is variable and includes a rapid progression of symptoms of chest pain and dyspnea that can be life threatening when hemodynamic instability and hypovolemic shock occurs. Despite haemothorax, SH is much less common with data limited to case reports and case series. A literature review has been performed to identify and summarise all potentials causes leading to this clinical entity. PMID:25922734

Antiplatelet Drugs

PubMed Central

Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

2012-01-01

The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

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.

Optimization of the decision-making process for the selection of therapeutics to undergo clinical testing for spinal cord injury in the North American Clinical Trials Network.

PubMed

Guest, James; Harrop, James S; Aarabi, Bizhan; Grossman, Robert G; Fawcett, James W; Fehlings, Michael G; Tator, Charles H

2012-09-01

The North American Clinical Trials Network (NACTN) includes 9 clinical centers funded by the US Department of Defense and the Christopher Reeve Paralysis Foundation. Its purpose is to accelerate clinical testing of promising therapeutics in spinal cord injury (SCI) through the development of a robust interactive infrastructure. This structure includes key committees that serve to provide longitudinal guidance to the Network. These committees include the Executive, Data Management, and Neurological Outcome Assessments Committees, and the Therapeutic Selection Committee (TSC), which is the subject of this manuscript. The NACTN brings unique elements to the SCI field. The Network's stability is not restricted to a single clinical trial. Network members have diverse expertise and include experts in clinical care, clinical trial design and methodology, pharmacology, preclinical and clinical research, and advanced rehabilitation techniques. Frequent systematic communication is assigned a high value, as is democratic process, fairness and efficiency of decision making, and resource allocation. This article focuses on how decision making occurs within the TSC to rank alternative therapeutics according to 2 main variables: quality of the preclinical data set, and fit with the Network's aims and capabilities. This selection process is important because if the Network's resources are committed to a therapeutic, alternatives cannot be pursued. A proposed methodology includes a multicriteria decision analysis that uses a Multi-Attribute Global Inference of Quality matrix to quantify the process. To rank therapeutics, the TSC uses a series of consensus steps designed to reduce individual and group bias and limit subjectivity. Given the difficulties encountered by industry in completing clinical trials in SCI, stable collaborative not-for-profit consortia, such as the NACTN, may be essential to clinical progress in SCI. The evolution of the NACTN also offers substantial opportunity to refine decision making and group dynamics. Making the best possible decisions concerning therapeutics selection for trial testing is a cornerstone of the Network's function.

Cost-effectiveness of different strategies for selecting and treating individuals at increased risk of osteoporosis or osteopenia: a systematic review.

PubMed

Müller, Dirk; Pulm, Jannis; Gandjour, Afschin

2012-01-01

To compare cost-effectiveness modeling analyses of strategies to prevent osteoporotic and osteopenic fractures either based on fixed thresholds using bone mineral density or based on variable thresholds including bone mineral density and clinical risk factors. A systematic review was performed by using the MEDLINE database and reference lists from previous reviews. On the basis of predefined inclusion/exclusion criteria, we identified relevant studies published since January 2006. Articles included for the review were assessed for their methodological quality and results. The literature search resulted in 24 analyses, 14 of them using a fixed-threshold approach and 10 using a variable-threshold approach. On average, 70% of the criteria for methodological quality were fulfilled, but almost half of the analyses did not include medication adherence in the base case. The results of variable-threshold strategies were more homogeneous and showed more favorable incremental cost-effectiveness ratios compared with those based on a fixed threshold with bone mineral density. For analyses with fixed thresholds, incremental cost-effectiveness ratios varied from €80,000 per quality-adjusted life-year in women aged 55 years to cost saving in women aged 80 years. For analyses with variable thresholds, the range was €47,000 to cost savings. Risk assessment using variable thresholds appears to be more cost-effective than selecting high-risk individuals by fixed thresholds. Although the overall quality of the studies was fairly good, future economic analyses should further improve their methods, particularly in terms of including more fracture types, incorporating medication adherence, and including or discussing unrelated costs during added life-years. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

A population-based study of demographical variables and ability to perform activities of daily living in adults with osteogenesis imperfecta.

PubMed

Wekre, Lena Lande; Frøslie, Kathrine Frey; Haugen, Lena; Falch, Jan A

2010-01-01

To describe demographical variables, and to study functional ability to perform activities of daily life in adults with osteogenesis imperfecta (OI). Population-based study. Ninety-seven patients aged 25 years and older, 41 men and 56 women, were included. For the demographical variables, comparison was made to a matched control-group (475 persons) from the Norwegian general population. Structured interviews concerning social conditions, employment and educational issues and clinical examination were performed. The Sunnaas Activities of Daily Living (ADL) Index was used to assess the ability to perform ADL. The prevalence of clinical manifestations according to Sillence was in accordance with other studies. Demographical variables showed that most adults with OI are married and have children. They had a higher educational level than the control group, but the employment rate was significantly lower. However, the rate of employed men was similar in both groups. Adult persons with OI achieved a high score when tested for ADL. Adults with OI are well educated compared with the general population, and most of them are employed. High scores when tested for ADL indicate that most of them are able to live their lives independently, even though there are some differences according to the severity of the disorder.

Performance on a computerized shopping task significantly predicts real world functioning in persons diagnosed with bipolar disorder.

PubMed

Laloyaux, Julien; Pellegrini, Nadia; Mourad, Haitham; Bertrand, Hervé; Domken, Marc-André; Van der Linden, Martial; Larøi, Frank

2013-12-15

Persons diagnosed with bipolar disorder often suffer from cognitive impairments. However, little is known concerning how these cognitive deficits impact their real world functioning. We developed a computerized real-life activity task, where participants are required to shop for a list of grocery store items. Twenty one individuals diagnosed with bipolar disorder and 21 matched healthy controls were administered the computerized shopping task. Moreover, the patient group was assessed with a battery of cognitive tests and clinical scales. Performance on the shopping task significantly differentiated patients and healthy controls for two variables: Total time to complete the shopping task and Mean time spent to consult the shopping list. Moreover, in the patient group, performance on these variables from the shopping task correlated significantly with cognitive functioning (i.e. processing speed, verbal episodic memory, planning, cognitive flexibility, and inhibition) and with clinical variables including duration of illness and real world functioning. Finally, variables from the shopping task were found to significantly explain 41% of real world functioning of patients diagnosed with bipolar disorder. These findings suggest that the shopping task provides a good indication of real world functioning and cognitive functioning of persons diagnosed with bipolar disorder. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine.

PubMed

El Rouby, Nihal; Lima, John J; Johnson, Julie A

2018-04-01

Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism. Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy. Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.

Flexibility and variability in lexicon usage among Yoruba-speaking Nigerian outpatients with schizophrenia: a controlled study.

PubMed

Adewuya, Abiola O; Adewuya, Abiodun O

2008-01-01

The studies on language dysfunction in schizophrenia are few, inconclusive and have all been done in the western culture. There may be cross-cultural and cross-lingual differences in problems with speeches of patients with schizophrenia. This study aims to examine the flexibility or variability in the use of words among a group of Nigerian patients with schizophrenia compared with healthy controls. The spoken samples of 48 outpatients with schizophrenia and 48 matched controls were assessed using the mean segmental type-token ratio (MSTTR). The sociodemographic and clinical variables of the patients with schizophrenia were also compared with their MSTTR scores. The MSTTR score for the patients with schizophrenia was significantly lower compared with that of healthy controls (p < 0.001). The factors independently associated with a lower MSTTR in patients with schizophrenia include younger age at onset of illness, presence of negative formal thought disorder and simple or hebephrenic subtype of schizophrenia. The problem with flexibility and variability in lexicon usage among patients with schizophrenia is a cross-cultural phenomenon. The MSTTR may have value in predicting clinical judgements of thought disorder or in identifying deviant language. These may have broad potentials for application in longitudinal and pathogenetic studies of schizophrenia. (c) 2008 S. Karger AG, Basel.

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

PubMed Central

El Rouby, Nihal; Lima, John J.; Johnson, Julie A.

2018-01-01

ABSTRACT Introduction: Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism. Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy. Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs. PMID:29620484

Manchester Clinical Placement Index (MCPI). Conditions for Medical Students' Learning in Hospital and Community Placements

ERIC Educational Resources Information Center

Dornan, Tim; Muijtjens, Arno; Graham, Jennifer; Scherpbier, Albert; Boshuizen, Henny

2012-01-01

The drive to quality-manage medical education has created a need for valid measurement instruments. Validity evidence includes the theoretical and contextual origin of items, choice of response processes, internal structure, and interrelationship of a measure's variables. This research set out to explore the validity and potential utility of an…

Factors Associated with Sexual Behavior Problems in Young Sexually Abused Children.

ERIC Educational Resources Information Center

Hall, Darlene Kordich; Mathews, Fred; Pearce, John

1998-01-01

Analysis of data from the clinical records of 100 sexually abused boys and girls, ages 3-7 years, identified five variables predictive of sexual behavior problems, including sexual arousal of the child during the abuse, perpetrator's use of sadism, a history of physical and emotional abuse, and who the child blames for the abuse. (DB)

Gender Differences in the Clinical Presentation of PTSD and Its Concomitants in Survivors of Interpersonal Assault

ERIC Educational Resources Information Center

Galovski, Tara E.; Mott, Juliette; Young-Xu, Yinong; Resick, Patricia A.

2011-01-01

This study compares a sample of PTSD-positive, female survivors of interpersonal assault (n = 162) to a sample of similarly traumatized male counterparts (n = 45) on a number of variables, including PTSD-symptom severity, depressive symptoms, anger, guilt, and health-related concerns. Results indicate that male and female interpersonal assault…

Subtypes in 22q11.2 Deletion Syndrome Associated with Behaviour and Neurofacial Morphology

ERIC Educational Resources Information Center

Sinderberry, Brooke; Brown, Scott; Hammond, Peter; Stevens, Angela F.; Schall, Ulrich; Murphy, Declan G. M.; Murphy, Kieran C.; Campbell, Linda E.

2013-01-01

22q11.2 deletion syndrome (22q11DS) has a complex phenotype with more than 180 characteristics, including cardiac anomalies, cleft palate, intellectual disabilities, a typical facial morphology, and mental health problems. However, the variable phenotype makes it difficult to predict clinical outcome, such as the high prevalence of psychosis among…

Lateral and Anterior Thalamic Lesions Impair Independent Memory Systems

ERIC Educational Resources Information Center

Mitchell, Anna S.; Dalrymple-Alford, John C.

2006-01-01

Damage to the medial region of the thalamus, both in clinical cases (e.g., patients with infarcts or the Korsakoff's syndrome) and animal lesion models, is associated with variable amnesic deficits. Some studies suggest that many of these memory deficits rely on the presence of lateral thalamic lesions (LT) that include the intralaminar nuclei,…

Birth Control in Clinical Trials: Industry Survey of Current Use Practices, Governance, and Monitoring.

PubMed

Stewart, J; Breslin, W J; Beyer, B K; Chadwick, K; De Schaepdrijver, L; Desai, M; Enright, B; Foster, W; Hui, J Y; Moffat, G J; Tornesi, B; Van Malderen, K; Wiesner, L; Chen, C L

2016-03-01

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives.

The preanalytic phase in veterinary clinical pathology.

PubMed

Braun, Jean-Pierre; Bourgès-Abella, Nathalie; Geffré, Anne; Concordet, Didier; Trumel, Cathy

2015-03-01

This article presents the general causes of preanalytic variability with a few examples showing specialists and practitioners that special and improved care should be given to this too often neglected phase. The preanalytic phase of clinical pathology includes all the steps from specimen collection to analysis. It is the phase where most laboratory errors occur in human, and probably also in veterinary clinical pathology. Numerous causes may affect the validity of the results, including technical factors, such as the choice of anticoagulant, the blood vessel sampled, and the duration and conditions of specimen handling. While the latter factors can be defined, influence of biologic and physiologic factors such as feeding and fasting, stress, and biologic and endocrine rhythms can often not be controlled. Nevertheless, as many factors as possible should at least be documented. The importance of the preanalytic phase is often not given the necessary attention, although the validity of the results and consequent clinical decision making and medical management of animal patients would likely be improved if the quality of specimens submitted to the laboratory was optimized. © 2014 American Society for Veterinary Clinical Pathology.

Clinical and neurocognitive course in early-onset psychosis: a longitudinal study of adolescents with schizophrenia-spectrum disorders*

PubMed Central

Wozniak, Jeffrey R.; Block, Erin E.; White, Tonya; Jensen, Jonathan B.; Schulz, S. Charles

2017-01-01

Aim Adolescents with psychotic disorders show deficits in IQ, attention, learning and memory, executive functioning, and processing speed that are related to important clinical variables including negative symptoms, adaptive functioning and academics. Previous studies have reported relatively consistent deficits with varying relationships to illness status and symptoms. The goals of this study were to examine these relationships in a larger sample at baseline, and also to examine the longitudinal course of these deficits in a smaller subset of adolescents. Method Thirty-six subjects, aged 10 to 17 years, were included at baseline. All had Diagnostic and Statistical Manual-Fourth Edition diagnoses of schizophrenia, schizoaffective disorder, schizophreniform disorder and psychosis – not otherwise specified, as determined by Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children structured interviews. Patients were administered a neuropsychological battery, and Positive and Negative Syndrome Scale ratings were completed at baseline and again at 1 year (n = 14). Most participants were inpatients at baseline, and 13 of 14were on atypical antipsychotic medication during both sessions. Results At baseline, the patients demonstrated impairments in working memory, processing speed, executive function and verbal learning. No significant cognitive change was detected at 1-year follow-up. In contrast, clinical symptoms were variable across 1 year, with an improvement in positive symptoms at 1 year. No relationships between clinical and cognitive symptoms were observed, with the exception of baseline IQ predicting negative symptoms at 1 year. Conclusions Young patients with schizophrenia-spectrum disorders displayed neurocognitive impairments at baseline. Despite measurable fluctuations in clinical symptoms over the year, no significant changes were measured in cognition. Lower IQ at baseline was predictive of more negative symptoms at 1 year. PMID:21352150

Emergency Department Referrals for Adolescent Urgent Psychiatric Consultation: Comparison of Clinical Characteristics of Repeat-presentations and Single-presentation.

PubMed

Roberts, Nasreen; Nesdole, Robert; Hu, Tina

2018-01-01

a) to examine the demographic and clinical characteristics of repeat-presentations to an adolescent urgent psychiatric clinic, and b) to compare them with single-time presentation. This 18-month retrospective study compared repeat-presenters to age and gender matched single-time presenters. Demographic variables included age gender and ethnicity. Clinical variables included reason for referral, family history, diagnosis, recommendations and compliance. Data were analyzed using descriptive statistics, McNemar's Chi-square tests for matched pairs, and conditional logistic regression. Of 624 assessments 24% (N=151) were repeat-presentations. Compared with single-presentation, repeat-presentation group had a higher proportion of Aboriginal youth (X2 (1) = 108.28 p < 0.01), a higher proportion in special educational placement (X2 (1) = 6.82, p < 0.01), a higher proportion with a family history of anxiety disorders (X2 (1) = 10.62, p = 0.01) and substance use disorder (X2 (1) = 18.99, p < 0.01). Conditional logistic regression results suggested that repeat-presentation group had higher odds of past hospital admission (OR: 3.50, p < 0.01) higher odds of family history of mood disorders (OR: 4.86, p < 0.01) and of antisocial disorders (OR: 4.97, p = 0.02), and lower odds of recommendation compliance (OR: 0.10, p < 0.01). Repeat-presentations for urgent psychiatric consultation constitute a quarter of referrals to the urgent psychiatric clinic. Identifying and addressing factors that contribute to repeat-presentations may, assist in improving treatment compliance by ensuring focused interventions and service delivery for these youth. In turn, this will improve access to the limited urgent services for other youth.

Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type.

PubMed

Grolimund, Eva; Kutz, Alexander; Marlowe, Robert J; Vögeli, Alaadin; Alan, Murat; Christ-Crain, Mirjam; Thomann, Robert; Falconnier, Claudine; Hoess, Claus; Henzen, Christoph; Zimmerli, Werner; Mueller, Beat; Schuetz, Philipp

2015-06-01

Long-term outcome prediction in COPD is challenging. We conducted a prospective 5-7-year follow-up study in patients with COPD to determine the association of exacerbation type, discharge levels of inflammatory biomarkers including procalctionin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and plasma proadrenomedullin (ProADM), alone or combined with demographic/clinical characteristics, with long-term all-cause mortality in the COPD setting. The analyzed cohort comprised 469 patients with index hospitalization for pneumonic (n = 252) or non-pneumonic (n = 217) COPD exacerbation. Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/primary care physicians. We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve (AUC). After a median [25th-75th percentile] 6.1 [5.6-6.5] years, mortality was 55% (95%CI 50%-59%). Discharge ProADM concentration was strongly associated with 5-7-year non-survival: adjusted hazard ratio (HR)/10-fold increase (95%CI) 10.4 (6.2-17.7). Weaker associations were found for PCT and no significant associations were found for CRP or WBC. Combining ProADM with demographic/clinical variables including age, smoking status, BMI, New York Heart Association dyspnea class, exacerbation type, and comorbidities significantly improved long-term predictive accuracy over that of the demographic/clinical model alone: AUC (95%CI) 0.745 (0.701-0.789) versus 0.727 (0.681-0.772), (p) = .043. In patients hospitalized for COPD exacerbation, discharge ProADM levels appeared to accurately predict 5-7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/clinical mortality risk assessment.

Evaluation of a Serum Lung Cancer Biomarker Panel.

PubMed

Mazzone, Peter J; Wang, Xiao-Feng; Han, Xiaozhen; Choi, Humberto; Seeley, Meredith; Scherer, Richard; Doseeva, Victoria

2018-01-01

A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results.

Evaluation of a Serum Lung Cancer Biomarker Panel

PubMed Central

Mazzone, Peter J; Wang, Xiao-Feng; Han, Xiaozhen; Choi, Humberto; Seeley, Meredith; Scherer, Richard; Doseeva, Victoria

2018-01-01

Background: A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. Methods: The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. Results: The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. Conclusions: This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results. PMID:29371783

Carbohydrates and insulin resistance in clinical nutrition: Recommendations from the ESPEN expert group.

PubMed

Barazzoni, R; Deutz, N E P; Biolo, G; Bischoff, S; Boirie, Y; Cederholm, T; Cuerda, C; Delzenne, N; Leon Sanz, M; Ljungqvist, O; Muscaritoli, M; Pichard, C; Preiser, J C; Sbraccia, P; Singer, P; Tappy, L; Thorens, B; Van Gossum, A; Vettor, R; Calder, P C

2017-04-01

Growing evidence underscores the important role of glycemic control in health and recovery from illness. Carbohydrate ingestion in the diet or administration in nutritional support is mandatory, but carbohydrate intake can adversely affect major body organs and tissues if resulting plasma glucose becomes too high, too low, or highly variable. Plasma glucose control is especially important for patients with conditions such as diabetes or metabolic stress resulting from critical illness or surgery. These patients are particularly in need of glycemic management to help lessen glycemic variability and its negative health consequences when nutritional support is administered. Here we report on recent findings and emerging trends in the field based on an ESPEN workshop held in Venice, Italy, 8-9 November 2015. Evidence was discussed on pathophysiology, clinical impact, and nutritional recommendations for carbohydrate utilization and management in nutritional support. The main conclusions were: a) excess glucose and fructose availability may exacerbate metabolic complications in skeletal muscle, adipose tissue, and liver and can result in negative clinical impact; b) low-glycemic index and high-fiber diets, including specialty products for nutritional support, may provide metabolic and clinical benefits in individuals with obesity, insulin resistance, and diabetes; c) in acute conditions such as surgery and critical illness, insulin resistance and elevated circulating glucose levels have a negative impact on patient outcomes and should be prevented through nutritional and/or pharmacological intervention. In such acute settings, efforts should be implemented towards defining optimal plasma glucose targets, avoiding excessive plasma glucose variability, and optimizing glucose control relative to nutritional support. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Clinical picture and risk prediction of short-term mortality in cardiogenic shock.

PubMed

Harjola, Veli-Pekka; Lassus, Johan; Sionis, Alessandro; Køber, Lars; Tarvasmäki, Tuukka; Spinar, Jindrich; Parissis, John; Banaszewski, Marek; Silva-Cardoso, Jose; Carubelli, Valentina; Di Somma, Salvatore; Tolppanen, Heli; Zeymer, Uwe; Thiele, Holger; Nieminen, Markku S; Mebazaa, Alexandre

2015-05-01

The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality. The CardShock study was a multicentre, prospective, observational study conducted between 2010 and 2012. Patients with either acute coronary syndrome (ACS) or non-ACS aetiologies were enrolled within 6 h from detection of cardiogenic shock defined as severe hypotension with clinical signs of hypoperfusion and/or serum lactate >2 mmol/L despite fluid resuscitation (n = 219, mean age 67, 74% men). Data on clinical presentation, management, and biochemical variables were compared between different aetiologies of shock. Systolic blood pressure was on average 78 mmHg (standard deviation 14 mmHg) and mean arterial pressure 57 (11) mmHg. The most common cause (81%) was ACS (68% ST-elevation myocardial infarction and 8% mechanical complications); 94% underwent coronary angiography, of which 89% PCI. Main non-ACS aetiologies were severe chronic heart failure and valvular causes. In-hospital mortality was 37% (n = 80). ACS aetiology, age, previous myocardial infarction, prior coronary artery bypass, confusion, low LVEF, and blood lactate levels were independently associated with increased mortality. The CardShock risk Score including these variables and estimated glomerular filtration rate predicted in-hospital mortality well (area under the curve 0.85). Although most commonly due to ACS, other causes account for one-fifth of cases with shock. ACS is independently associated with in-hospital mortality. The CardShock risk Score, consisting of seven common variables, easily stratifies risk of short-term mortality. It might facilitate early decision-making in intensive care or guide patient selection in clinical trials. NCT01374867. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Use of Subjective Global Assessment, Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 to evaluate the nutritional status of non-critically ill patients on parenteral nutrition.

PubMed

Badia-Tahull, M B; Cobo-Sacristán, S; Leiva-Badosa, E; Miquel-Zurita, M E; Méndez-Cabalerio, N; Jódar-Masanés, R; Llop-Talaverón, J

2014-02-01

To evaluate the nutritional status of non-critically ill digestive surgery patients at the moment of parenteral nutrition initiation using three different nutritional test tools and to study their correlation. To study the association between the tests and the clinical and laboratory parameters used in the follow-up of PN treatment. Prospective study over 4 months. Anthropometric and clinical variables were recorded. Results of Subjective Global Assessment; Patient-Generated Subjective Global Assessment; and Nutritional Risk Screening 2002 were compared applying kappa test. Relationship between the clinical and laboratory parameters with Subjective Global Assessment was studied by multinominal regression and with the other two tests by multiple linear regression models. Age and sex were included as adjustment variables. Malnutrition in 45 studied patients varied from 51% to 57%. Subjective Global Assessment correlated well with Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 (κ = 0531 p = 0.000). The test with the greatest correlation with the clinical and analytical variables was the Nutritional Risk Screening 2002. Worse nutritional state in this test was associated with worse results in albumin (B = -0.087; CI = -0.169/-0.005], prealbumin (B = -0.005; CI = [-0.011/-0.001]), C-reactive protein (B = 0.006;CI = [0.001/ 0.011]) and leukocytes (B = 0.134; CI = [0.031/0.237]) at the en of parenteral nutrition treatment. Half of the digestive surgery patients were at malnutritional risk at the moment of initiating parenteral nutrition. Nutritional Risk Screening 2002 was the test with best association with the parameters used in the clinical follow-up of parenteral nutrition treated patients. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

A clinical return-to-work rule for patients with back pain.

PubMed

Dionne, Clermont E; Bourbonnais, Renée; Frémont, Pierre; Rossignol, Michel; Stock, Susan R; Larocque, Isabelle

2005-06-07

Tools for early identification of workers with back pain who are at high risk of adverse occupational outcome would help concentrate clinical attention on the patients who need it most, while helping reduce unnecessary interventions (and costs) among the others. This study was conducted to develop and validate clinical rules to predict the 2-year work disability status of people consulting for nonspecific back pain in primary care settings. This was a 2-year prospective cohort study conducted in 7 primary care settings in the Quebec City area. The study enrolled 1007 workers (participation, 68.4% of potential participants expected to be eligible) aged 18-64 years who consulted for nonspecific back pain associated with at least 1 day's absence from work. The majority (86%) completed 5 telephone interviews documenting a large array of variables. Clinical information was abstracted from the medical files. The outcome measure was "return to work in good health" at 2 years, a variable that combined patients' occupational status, functional limitations and recurrences of work absence. Predictive models of 2-year outcome were developed with a recursive partitioning approach on a 40% random sample of our study subjects, then validated on the rest. The best predictive model included 7 baseline variables (patient's recovery expectations, radiating pain, previous back surgery, pain intensity, frequent change of position because of back pain, irritability and bad temper, and difficulty sleeping) and was particularly efficient at identifying patients with no adverse occupational outcome (negative predictive value 78%- 94%). A clinical prediction rule accurately identified a large proportion of workers with back pain consulting in a primary care setting who were at a low risk of an adverse occupational outcome.

A clinical return-to-work rule for patients with back pain

PubMed Central

Dionne, Clermont E.; Bourbonnais, Renée; Frémont, Pierre; Rossignol, Michel; Stock, Susan R.; Larocque, Isabelle

2005-01-01

Background Tools for early identification of workers with back pain who are at high risk of adverse occupational outcome would help concentrate clinical attention on the patients who need it most, while helping reduce unnecessary interventions (and costs) among the others. This study was conducted to develop and validate clinical rules to predict the 2-year work disability status of people consulting for nonspecific back pain in primary care settings. Methods This was a 2-year prospective cohort study conducted in 7 primary care settings in the Quebec City area. The study enrolled 1007 workers (participation, 68.4% of potential participants expected to be eligible) aged 18–64 years who consulted for nonspecific back pain associated with at least 1 day's absence from work. The majority (86%) completed 5 telephone interviews documenting a large array of variables. Clinical information was abstracted from the medical files. The outcome measure was “return to work in good health” at 2 years, a variable that combined patients' occupational status, functional limitations and recurrences of work absence. Predictive models of 2-year outcome were developed with a recursive partitioning approach on a 40% random sample of our study subjects, then validated on the rest. Results The best predictive model included 7 baseline variables (patient's recovery expectations, radiating pain, previous back surgery, pain intensity, frequent change of position because of back pain, irritability and bad temper, and difficulty sleeping) and was particularly efficient at identifying patients with no adverse occupational outcome (negative predictive value 78%– 94%). Interpretation A clinical prediction rule accurately identified a large proportion of workers with back pain consulting in a primary care setting who were at a low risk of an adverse occupational outcome. PMID:15939915

Heterogeneity of Prognostic Studies of 24-Hour Blood Pressure Variability: Systematic Review and Meta-Analysis

PubMed Central

Taylor, Kathryn S.; Heneghan, Carl J.; Stevens, Richard J.; Adams, Emily C.; Nunan, David; Ward, Alison

2015-01-01

In addition to mean blood pressure, blood pressure variability is hypothesized to have important prognostic value in evaluating cardiovascular risk. We aimed to assess the prognostic value of blood pressure variability within 24 hours. Using MEDLINE, EMBASE and Cochrane Library to April 2013, we conducted a systematic review of prospective studies of adults, with at least one year follow-up and any day, night or 24-hour blood pressure variability measure as a predictor of one or more of the following outcomes: all-cause mortality, cardiovascular mortality, all cardiovascular events, stroke and coronary heart disease. We examined how blood pressure variability is defined and how its prognostic use is reported. We analysed relative risks adjusted for covariates including the appropriate mean blood pressure and considered the potential for meta-analysis. Our analysis of methods included 24 studies and analysis of predictions included 16 studies. There were 36 different measures of blood pressure variability and 13 definitions of night- and day-time periods. Median follow-up was 5.5 years (interquartile range 4.2–7.0). Comparing measures of dispersion, coefficient of variation was less well researched than standard deviation. Night dipping based on percentage change was the most researched measure and the only measure for which data could be meaningfully pooled. Night dipping or lower night-time blood pressure was associated with lower risk of cardiovascular events. The interpretation and use in clinical practice of 24-hour blood pressure variability, as an important prognostic indicator of cardiovascular events, is hampered by insufficient evidence and divergent methodologies. We recommend greater standardisation of methods. PMID:25984791

Method and apparatus for assessing cardiovascular risk

NASA Technical Reports Server (NTRS)

Albrecht, Paul (Inventor); Bigger, J. Thomas (Inventor); Cohen, Richard J. (Inventor)

1998-01-01

The method for assessing risk of an adverse clinical event includes detecting a physiologic signal in the subject and determining from the physiologic signal a sequence of intervals corresponding to time intervals between heart beats. The long-time structure of fluctuations in the intervals over a time period of more than fifteen minutes is analyzed to assess risk of an adverse clinical event. In a preferred embodiment, the physiologic signal is an electrocardiogram and the time period is at least fifteen minutes. A preferred method for analyzing the long-time structure variability in the intervals includes computing the power spectrum and fitting the power spectrum to a power law dependence on frequency over a selected frequency range such as 10.sup.-4 to 10.sup.-2 Hz. Characteristics of the long-time structure fluctuations in the intervals is used to assess risk of an adverse clinical event.

Metacognitive factors that impact student nurse use of point of care technology in clinical settings.

PubMed

Kuiper, RuthAnne

2010-01-01

The utility of personal digital assistants (PDA) as a point of care resource in health care practice and education presents new challenges for nursing faculty. While there is a plethora of PDA resources available, little is known about the variables that effect student learning and technology adoption. In this study nursing students used PDA software programs which included a drug guide, medical dictionary, laboratory manual and nursing diagnosis manual during acute care clinical experiences. Analysis of student journals comparative reflective statements about the PDA as an adjunct to other available resources in clinical practice are presented. The benefits of having a PDA included readily available data, validation of thinking processes, and facilitation of care plan re-evaluation. Students reported increased frequency of use and independence. Significant correlations between user perceptions and computer self-efficacy suggested greater confidence in abilities with technology resulting in increased self-awareness and achievement of learning outcomes.

Three-factor model of premorbid adjustment in a sample with chronic schizophrenia and first-episode psychosis.

PubMed

Barajas, Ana; Usall, Judith; Baños, Iris; Dolz, Montserrat; Villalta-Gil, Victoria; Vilaplana, Miriam; Autonell, Jaume; Sánchez, Bernardo; Cervilla, Jorge A; Foix, Alexandrina; Obiols, Jordi E; Haro, Josep Maria; Ochoa, Susana

2013-12-01

The dimensionality of premorbid adjustment (PA) has been a debated issue, with attempts to determine whether PA is a unitary construct or composed of several independent domains characterized by a differential deterioration pattern and specific outcome correlates. This study examines the factorial structure of PA, as well as, the course and correlates of its domains. Retrospective study of 84 adult patients experiencing first-episode psychosis (FEP) (n=33) and individuals with schizophrenia (SCH) (n=51). All patients were evaluated with a comprehensive battery of instruments including clinical, functioning and neuropsychological variables. A principal component analysis accompanied by a varimax rotation method was used to examine the factor structure of the PAS-S scale. Paired t tests and Wilcoxon rank tests were used to assess the changes in PAS domains over time. Bivariate correlation analyses were performed to analyse the relationship between PAS factors and clinical, social and cognitive variables. PA was better explained by three factors (71.65% of the variance): Academic PA, Social PA and Socio-sexual PA. The academic domain showed higher scores of PA from childhood. Social and clinical variables were more strongly related to Social PA and Socio-sexual PA domains, and the Academic PA domain was exclusively associated with cognitive variables. This study supports previous evidence, emphasizing the validity of dividing PA into its sub-components. A differential deterioration pattern and specific correlates were observed in each PA domains, suggesting that impairments in each PA domain might predispose individuals to develop different expressions of psychotic dimensions. © 2013.

Post-exposure prophylaxis against rabies at two newly designated intradermal rabies vaccination clinics in Kerala, India.

PubMed

J, Teena M; Mathew, T; S, Anish T; M, Sujina C; Philip, R R

2012-01-01

The two-site intradermal rabies vaccination (IDRV) regimen was recently introduced in Kerala. We aimed to determine factors associated with exposure of category III severity among patients seeking prophylaxis against rabies at IDRV clinics. This hospital-based, cross-sectional study was done at two clinics in Thiruvananthapuram district, Kerala. Data were collected using a semi-structured questionnaire by direct interview and 320 patients were included. Bivariate analysis of quantitative variables was done using t-test and that of qualitative variables using chi-square test. The mean (standard deviation) age of patients was 32.4 (19.6) years. Among the 320 cases, 202 (63.1%) had category III exposure. Lower extremities were the most frequent site of exposure (146, 45.6%). The most frequent mode of exposure was being bitten by an animal (214, 66.9%), often a dog. Residence in rural areas, exposure to dogs and wounds on the extremities had a significant association with severity of exposure. Animal exposures were more among people from rural areas. About two-thirds of exposures which necessitated post-exposure prophylaxis were category III. Copyright 2012, NMJI.

[Prenatal care in public and private health services: a population-based survey in Rio Grande, Rio Grande do Sul State, Brazil].

PubMed

Cesar, Juraci A; Sutil, Andréa T; Santos, Gabriela B dos; Cunha, Carolina F; Mendoza-Sassi, Raúl A

2012-11-01

This study aimed to evaluate public and private prenatal care for women in Rio Grande, Rio Grande do Sul State, Brazil. Women who gave birth at the two local maternity hospitals from January 1 to December 31, 2010, answered a standardized questionnaire. The interview sites in the public sector were primary health care units with and without the Family Health Strategy (FHS) and outpatient clinics; the private sector included clinics operated by health plans and private physicians' offices. The chi-square test was used to compare proportions. The response rate was 97.2% (2,395 out of 2,464). Among the 23 target variables and indicators, seven showed a clear advantage for mothers who had received prenatal care under the FHS and six for health plan clinics and private offices. Four variables showed virtually universal coverage at all five study sites. Prenatal care showed better coverage for pregnant women treated in the private sector. Pregnant women treated under the FHS showed similar coverage to that in the private sector.

Heart rate variability.

PubMed

Cygankiewicz, Iwona; Zareba, Wojciech

2013-01-01

Heart rate variability (HRV) provides indirect insight into autonomic nervous system tone, and has a well-established role as a marker of cardiovascular risk. Recent decades brought an increasing interest in HRV assessment as a diagnostic tool in detection of autonomic impairment, and prediction of prognosis in several neurological disorders. Both bedside analysis of simple markers of HRV, as well as more sophisticated HRV analyses including time, frequency domain and nonlinear analysis have been proven to detect early autonomic involvement in several neurological disorders. Furthermore, altered HRV parameters were shown to be related with cardiovascular risk, including sudden cardiac risk, in patients with neurological diseases. This chapter aims to review clinical and prognostic application of HRV analysis in diabetes, stroke, multiple sclerosis, muscular dystrophies, Parkinson's disease and epilepsy. © 2013 Elsevier B.V. All rights reserved.

The Impact of General Medical Conditions in Obsessive-Compulsive Disorder

PubMed Central

Aguglia, Andrea; Signorelli, Maria Salvina; Albert, Umberto; Maina, Giuseppe

2018-01-01

Objective The co-occurrence of general medical conditions (GMCs) and major psychiatric disorders is well documented. The aim of this study was to assess the prevalence of GMCs in patients with a primary diagnosis of obsessive-compulsive disorder (OCD) and, secondly, to investigate which clinical variables are associated with the presence of a GMC. Methods Subjects with a primary diagnosis of OCD were included. Socio-demographic and clinical characteristics were collected. GMCs were classified using the ICD-10 and grouped according to the Cumulative Illness Rating Scale (CIRS) in: cardiac, vascular, hematopoietic, respiratory, ear/nose/throat, upper and lower gastrointestinal, hepatic, renal, genitourinary, musculoskeletal, neurologic, endocrine/metabolic. The association between the presence of GMCs and demographic/clinical variables of OCD was investigated. Results A total of 162 patients with OCD were included. 78 (48.1%) patients had at least one comorbid GMC. Most frequent GMCs were endocrine/metabolic diseases (25.9%), followed by upper/lower gastrointestinal (20.5%) and cardio-vascular diseases (13.6%). The presence of a GMC was significantly associated with female gender, older age, duration of untreated illness (DUI), and absence of physical activity. Conclusion Patients with OCD have high rates of comorbid GMCs. A longer DUI is associated with having at least one GMCs; this might be due to the long-lasting adoption of unhealthy lifestyles, not counterbalanced by appropriate treatment and psychoeducation. PMID:29475243

Outcomes of patients in clinical trials with ST-segment elevation myocardial infarction among countries with different gross national incomes.

PubMed

Orlandini, Andrés; Díaz, Rafael; Wojdyla, Daniel; Pieper, Karen; Van de Werf, Frans; Granger, Christopher B; Harrington, Robert A; Boersma, Eric; Califf, Robert M; Armstrong, Paul; White, Harvey; Simes, John; Paolasso, Ernesto

2006-03-01

To evaluate whether there is an association between 30-day mortality in patients with ST-segment elevation myocardial infarction (STEMI) included in clinical trials and country gross national income (GNI). A retrospective analysis of the databases of five randomized trials including 50 310 patients with STEMI (COBALT 7169, GIK-2 2931, HERO-2 17,089, ASSENT-2 17,005, and ASSENT-3 6116 patients) from 53 countries was performed. Countries were divided into three groups according to their GNI based on the World Bank data: low (less than 2900 US dollars), medium (between 2900 US dollars and 9000 US dollars), and high GNI (more than 9000 US dollars per capita). Baseline characteristics, in-hospital management variables, and 30-day outcomes were evaluated. A previously defined logistic regression model was used to adjust for differences in baseline characteristics and to predict mortality. The observed mortality was higher than the predicted mortality in the low (12.1 vs. 11.8%) and in the medium income groups (9.4 vs. 7.9%), whereas it was lower in the high income group (4.9 vs. 5.6%). An inverse relationship between mortality and GNI was observed in STEMI clinical trials. Most of the variability in mortality can be explained by differences in baseline characteristics; however, after adjustment, lower income countries have higher mortality than the expected.

An unusual clinical severity of 16p11.2 deletion syndrome caused by unmasked recessive mutation of CLN3.

PubMed

Pebrel-Richard, Céline; Debost-Legrand, Anne; Eymard-Pierre, Eléonore; Greze, Victoria; Kemeny, Stéphan; Gay-Bellile, Mathilde; Gouas, Laetitia; Tchirkov, Andreï; Vago, Philippe; Goumy, Carole; Francannet, Christine

2014-03-01

With the introduction of array comparative genomic hybridization (aCGH) techniques in the diagnostic setting of patients with developmental delay and congenital malformations, many new microdeletion syndromes have been recognized. One of these recently recognized microdeletion syndromes is the 16p11.2 deletion syndrome, associated with variable clinical outcomes including developmental delay, autism spectrum disorder, epilepsy, and obesity, but also apparently normal phenotype. We report on a 16-year-old patient with developmental delay, exhibiting retinis pigmentosa with progressive visual failure from the age of 9 years, ataxia, and peripheral neuropathy. Chromosomal microarray analysis identified a 1.7-Mb 16p11.2 deletion encompassing the 593-kb common deletion (∼29.5 to ∼30.1 Mb; Hg18) and the 220-kb distal deletion (∼28.74 to ∼28.95 Mb; Hg18) that partially included the CLN3 gene. As the patient's clinical findings were different from usual 16p11.2 microdeletion phenotypes and showed some features reminiscent of juvenile neuronal ceroid-lipofuscinosis (JNCL, Batten disease, OMIM 204200), we suspected and confirmed a mutation of the remaining CLN3 allele. This case further illustrates that unmasking of hemizygous recessive mutations by chromosomal deletion represents one explanation for the phenotypic variability observed in chromosomal deletion disorders.

An unusual clinical severity of 16p11.2 deletion syndrome caused by unmasked recessive mutation of CLN3

PubMed Central

Pebrel-Richard, Céline; Debost-Legrand, Anne; Eymard-Pierre, Eléonore; Greze, Victoria; Kemeny, Stéphan; Gay-Bellile, Mathilde; Gouas, Laetitia; Tchirkov, Andreï; Vago, Philippe; Goumy, Carole; Francannet, Christine

2014-01-01

With the introduction of array comparative genomic hybridization (aCGH) techniques in the diagnostic setting of patients with developmental delay and congenital malformations, many new microdeletion syndromes have been recognized. One of these recently recognized microdeletion syndromes is the 16p11.2 deletion syndrome, associated with variable clinical outcomes including developmental delay, autism spectrum disorder, epilepsy, and obesity, but also apparently normal phenotype. We report on a 16-year-old patient with developmental delay, exhibiting retinis pigmentosa with progressive visual failure from the age of 9 years, ataxia, and peripheral neuropathy. Chromosomal microarray analysis identified a 1.7-Mb 16p11.2 deletion encompassing the 593-kb common deletion (∼29.5 to ∼30.1 Mb; Hg18) and the 220-kb distal deletion (∼28.74 to ∼28.95 Mb; Hg18) that partially included the CLN3 gene. As the patient's clinical findings were different from usual 16p11.2 microdeletion phenotypes and showed some features reminiscent of juvenile neuronal ceroid-lipofuscinosis (JNCL, Batten disease, OMIM 204200), we suspected and confirmed a mutation of the remaining CLN3 allele. This case further illustrates that unmasking of hemizygous recessive mutations by chromosomal deletion represents one explanation for the phenotypic variability observed in chromosomal deletion disorders. PMID:23860047

A statistically compiled test battery for feasible evaluation of knee function after rupture of the Anterior Cruciate Ligament – derived from long-term follow-up data

PubMed Central

2017-01-01

Purpose Clinical test batteries for evaluation of knee function after injury to the Anterior Cruciate Ligament (ACL) should be valid and feasible, while reliably capturing the outcome of rehabilitation. There is currently a lack of consensus as to which of the many available assessment tools for knee function that should be included. The present aim was to use a statistical approach to investigate the contribution of frequently used tests to avoid redundancy, and filter them down to a proposed comprehensive and yet feasible test battery for long-term evaluation after ACL injury. Methods In total 48 outcome variables related to knee function, all potentially relevant for a long-term follow-up, were included from a cross-sectional study where 70 ACL-injured (17–28 years post injury) individuals were compared to 33 controls. Cluster analysis and logistic regression were used to group variables and identify an optimal test battery, from which a summarized estimator of knee function representing various functional aspects was derived. Results As expected, several variables were strongly correlated, and the variables also fell into logical clusters with higher within-correlation (max ρ = 0.61) than between clusters (max ρ = 0.19). An extracted test battery with just four variables assessing one-leg balance, isokinetic knee extension strength and hop performance (one-leg hop, side hop) were mathematically combined to an estimator of knee function, which acceptably classified ACL-injured individuals and controls. This estimator, derived from objective measures, correlated significantly with self-reported function, e.g. Lysholm score (ρ = 0.66; p<0.001). Conclusions The proposed test battery, based on a solid statistical approach, includes assessments which are all clinically feasible, while also covering complementary aspects of knee function. Similar test batteries could be determined for earlier phases of ACL rehabilitation or to enable longitudinal monitoring. Such developments, established on a well-grounded consensus of measurements, would facilitate comparisons of studies and enable evidence-based rehabilitation. PMID:28459885

Predicting clinical decline in progressive agrammatic aphasia and apraxia of speech.

PubMed

Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R; Clark, Heather M; Strand, Edythe A; Machulda, Mary M; Spychalla, Anthony J; Senjem, Matthew L; Jack, Clifford R; Josephs, Keith A

2017-11-28

To determine whether baseline clinical and MRI features predict rate of clinical decline in patients with progressive apraxia of speech (AOS). Thirty-four patients with progressive AOS, with AOS either in isolation or in the presence of agrammatic aphasia, were followed up longitudinally for up to 4 visits, with clinical testing and MRI at each visit. Linear mixed-effects regression models including all visits (n = 94) were used to assess baseline clinical and MRI variables that predict rate of worsening of aphasia, motor speech, parkinsonism, and behavior. Clinical predictors included baseline severity and AOS type. MRI predictors included baseline frontal, premotor, motor, and striatal gray matter volumes. More severe parkinsonism at baseline was associated with faster rate of decline in parkinsonism. Patients with predominant sound distortions (AOS type 1) showed faster rates of decline in aphasia and motor speech, while patients with segmented speech (AOS type 2) showed faster rates of decline in parkinsonism. On MRI, we observed trends for fastest rates of decline in aphasia in patients with relatively small left, but preserved right, Broca area and precentral cortex. Bilateral reductions in lateral premotor cortex were associated with faster rates of decline of behavior. No associations were observed between volumes and decline in motor speech or parkinsonism. Rate of decline of each of the 4 clinical features assessed was associated with different baseline clinical and regional MRI predictors. Our findings could help improve prognostic estimates for these patients. © 2017 American Academy of Neurology.

Personalized health care and health information technology policy: an exploratory analysis.

PubMed

Wald, Jonathan S; Shapiro, Michael

2013-01-01

Personalized healthcare (PHC) is envisioned to enhance clinical practice decision-making using new genome-driven knowledge that tailors diagnosis, treatment, and prevention to the individual patient. In 2012, we conducted a focused environmental scan and informal interviews with fifteen experts to anticipate how PHC might impact health Information Technology (IT) policy in the United States. Findings indicatedthat PHC has a variable impact on current clinical practice, creates complex questions for providers, patients, and policy-makers, and will require a robust health IT infrastructure with advanced data architecture, clinical decision support, provider workflow tools, and re-use of clinical data for research. A number of health IT challenge areas were identified, along with five policy areas including: interoperable clinical decision support, standards for patient values and preferences, patient engagement, data transparency, and robust privacy and security.

Designing healthcare information technology to catalyse change in clinical care.

PubMed

Lester, William T; Zai, Adrian H; Grant, Richard W; Chueh, Henry C

2008-01-01

The gap between best practice and actual patient care continues to be a pervasive problem in our healthcare system. Efforts to improve on this knowledge-performance gap have included computerised disease management programs designed to improve guideline adherence. However, current computerised reminder and decision support interventions directed at changing physician behaviour have had only a limited and variable effect on clinical outcomes. Further, immediate pay-for-performance financial pressures on institutions have created an environment where disease management systems are often created under duress, appended to existing clinical systems and poorly integrated into the existing workflow, potentially limiting their real-world effectiveness. The authors present a review of disease management as well as a conceptual framework to guide the development of more effective health information technology (HIT) tools for translating clinical information into clinical action.

Cardiopulmonary measurements in dogs undergoing gastropexy without gastrectomy for correction of gastric dilatation-volvulus.

PubMed

Wagner, A E; Dunlop, C I; Chapman, P L

1999-08-15

To measure cardiopulmonary variables, including cardiac index, in dogs with naturally acquired gastric dilatation-volvulus (GDV). Prospective clinical study. 6 dogs with GDV. In addition to typical medical and surgical management of GDV, the dorsal metatarsal and pulmonary arteries and right atrium of the dogs were catheterized to obtain cardiopulmonary measurements before and during anesthesia and surgery. All dogs underwent gastropexy but none required gastrectomy. Mean cardiac index and mean arterial blood pressure for this small population of dogs with GDV were not significantly different from those reported for clinically normal awake or anesthetized dogs. Dogs with naturally acquired GDV without gastric necrosis may not have the classic characteristics, including decreased cardiac index and hypotension, of hypovolemic circulatory shock.

Bias, Confounding, and Interaction: Lions and Tigers, and Bears, Oh My!

PubMed

Vetter, Thomas R; Mascha, Edward J

2017-09-01

Epidemiologists seek to make a valid inference about the causal effect between an exposure and a disease in a specific population, using representative sample data from a specific population. Clinical researchers likewise seek to make a valid inference about the association between an intervention and outcome(s) in a specific population, based upon their randomly collected, representative sample data. Both do so by using the available data about the sample variable to make a valid estimate about its corresponding or underlying, but unknown population parameter. Random error in an experiment can be due to the natural, periodic fluctuation or variation in the accuracy or precision of virtually any data sampling technique or health measurement tool or scale. In a clinical research study, random error can be due to not only innate human variability but also purely chance. Systematic error in an experiment arises from an innate flaw in the data sampling technique or measurement instrument. In the clinical research setting, systematic error is more commonly referred to as systematic bias. The most commonly encountered types of bias in anesthesia, perioperative, critical care, and pain medicine research include recall bias, observational bias (Hawthorne effect), attrition bias, misclassification or informational bias, and selection bias. A confounding variable is a factor associated with both the exposure of interest and the outcome of interest. A confounding variable (confounding factor or confounder) is a variable that correlates (positively or negatively) with both the exposure and outcome. Confounding is typically not an issue in a randomized trial because the randomized groups are sufficiently balanced on all potential confounding variables, both observed and nonobserved. However, confounding can be a major problem with any observational (nonrandomized) study. Ignoring confounding in an observational study will often result in a "distorted" or incorrect estimate of the association or treatment effect. Interaction among variables, also known as effect modification, exists when the effect of 1 explanatory variable on the outcome depends on the particular level or value of another explanatory variable. Bias and confounding are common potential explanations for statistically significant associations between exposure and outcome when the true relationship is noncausal. Understanding interactions is vital to proper interpretation of treatment effects. These complex concepts should be consistently and appropriately considered whenever one is not only designing but also analyzing and interpreting data from a randomized trial or observational study.

What variables can influence clinical reasoning?

PubMed Central

Ashoorion, Vahid; Liaghatdar, Mohammad Javad; Adibi, Peyman

2012-01-01

Background: Clinical reasoning is one of the most important competencies that a physician should achieve. Many medical schools and licensing bodies try to predict it based on some general measures such as critical thinking, personality, and emotional intelligence. This study aimed at providing a model to design the relationship between the constructs. Materials and Methods: Sixty-nine medical students participated in this study. A battery test devised that consist four parts: Clinical reasoning measures, personality NEO inventory, Bar-On EQ inventory, and California critical thinking questionnaire. All participants completed the tests. Correlation and multiple regression analysis consumed for data analysis. Results: There is low to moderate correlations between clinical reasoning and other variables. Emotional intelligence is the only variable that contributes clinical reasoning construct (r=0.17-0.34) (R2 chnage = 0.46, P Value = 0.000). Conclusion: Although, clinical reasoning can be considered as a kind of thinking, no significant correlation detected between it and other constructs. Emotional intelligence (and its subscales) is the only variable that can be used for clinical reasoning prediction. PMID:23853636

Cystic kidneys in fetal Walker-Warburg syndrome with POMT2 mutation: Intrafamilial phenotypic variability in four siblings and review of literature.

PubMed

Nabhan, Marwa M; ElKhateeb, Nour; Braun, Daniela A; Eun, Sungho; Saleem, Sahar N; YungGee, Heon; Hildebrandt, Friedhelm; Soliman, Neveen A

2017-10-01

Walker-Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy secondary to α-dystroglycanopathy with muscle, brain, and eye abnormalities often leading to death in the first weeks of life. It is transmitted in an autosomal recessive pattern, and has been linked to at least 15 different genes; including protein O-mannosyltransferase 1 (POMT1), protein O-mannosyltransferase 2 (POMT2), protein O-mannose beta-1,2-N acetylglucosaminyltransferase (POMGNT1), fukutin (FKTN), isoprenoid synthase domain-containing protein (ISPD), and other genes. We report on a consanguineous family with four consecutive siblings affected by this condition with lethal outcome in three (still birth), and termination of the fourth pregnancy based on antenatal MRI identification of brain and kidney anomalies that heralded proper and deep clinical phenotyping. The diagnosis of WWS was suggested based on the unique collective phenotype comprising brain anomalies in the form of lissencephaly, subcortical/subependymal heterotopia, and cerebellar hypoplasia shared by all four siblings; microphthalmia in one sibling; and large cystic kidneys in the fetus and another sibling. Other unshared neurological abnormalities included hydrocephalus and Dandy-Walker malformation. Whole exome sequencing of the fetus revealed a highly conserved missense mutation in POMT2 that is known to cause WWS with brain and eye anomalies.In conclusion, the heterogeneous clinical presentation in the four affected conceptions with POMT2 mutation expands the current clinical spectrum of POMT2-associated WWS to include large cystic kidneys; and confirms intra-familial variability in terms of brain, kidney, and eye anomalies. © 2017 Wiley Periodicals, Inc.

Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose volume outcome relationships

NASA Astrophysics Data System (ADS)

El Naqa, I.; Suneja, G.; Lindsay, P. E.; Hope, A. J.; Alaly, J. R.; Vicic, M.; Bradley, J. D.; Apte, A.; Deasy, J. O.

2006-11-01

Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial.

PubMed

Williams, T E; Chalder, T; Sharpe, M; White, P D

2017-06-01

Chronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome. We used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients. Latent class analysis was then used to empirically define subgroups. The most statistically significant and clinically recognizable model comprised five subgroups. The largest, 'core' subgroup (33% of participants), had relatively low scores across all domains and good self-efficacy. A further three subgroups were defined by: the presence of mood disorders (21%); the presence of features of other functional somatic syndromes (such as fibromyalgia or irritable bowel syndrome) (21%); or by many symptoms - a group which combined features of both of the above (14%). The smallest 'avoidant-inactive' subgroup was characterized by physical inactivity, belief that symptoms were entirely physical in nature, and fear that they indicated harm (11%). Differences in the severity of fatigue and disability provided some discriminative validation of the subgroups. In addition to providing further evidence for the heterogeneity of chronic fatigue syndrome, the subgroups identified may aid future research into the important aetiological factors of specific subtypes of chronic fatigue syndrome and the development of more personalized treatment approaches.

[Characterization of patients with skeletal genetic diseases in a Colombian referral center].

PubMed

Velasco, Harvy Mauricio; Buelvas, Lina Patricia

2017-06-01

Short height in Colombia has an estimated prevalence of 10%. The 2009 Nosology and Classification of Skeletal Genetic Diseases described 456 clinical conditions using biochemical, molecular and radiological criteria for diagnosis. To analyze demographic, epidemiological and clinical variables in a group of patients with skeletal genetic diseases referred to the Instituto de Ortopedia Infantil Roosevelt. Patients referred between 2008 and 2014 were analyzed filtering 167 diagnoses of the International Classification of Diseases, 10th revision (ICD 10), related to skeletal genetic diseases. Demographic, epidemiological and clinical variables were explored using descriptive statistics. An intervention score was generated contemplating different combinations of treatments. An inferential statistical analysis using Student's t test was performed on such variables. The most frequent reason for consultation was suspicion of a genetic skeletal disorder. The types of treatments considered included support, surgical, pharmacological and orthotics, and it was established that genetic skeletal disorders were associated with higher intervention scores while tall and short height showed a lower score. Most referred patients were classified with genetic bone diseases, short stature and other monogenic genetic diseases. Significant differences were found between the age at symptoms onset and the age of diagnosis. Diversity was found in the therapeutic approach among different groups of pathologies. Patients with tall and short height showed lower intervention scores, which may warn on the need to reassess the therapeutic requirements of these groups.

Implementing clinical guidelines for chronic obstructive pulmonary disease: barriers and solutions

PubMed Central

Overington, Jeff D.; Huang, Yao C.; Abramson, Michael J.; Brown, Juliet L.; Goddard, John R.; Bowman, Rayleen V.; Fong, Kwun M.

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a complex chronic lung disease characterised by progressive fixed airflow limitation and acute exacerbations that frequently require hospitalisation. Evidence-based clinical guidelines for the diagnosis and management of COPD are now widely available. However, the uptake of these COPD guidelines in clinical practice is highly variable, as is the case for many other chronic disease guidelines. Studies have identified many barriers to implementation of COPD and other guidelines, including factors such as lack of familiarity with guidelines amongst clinicians and inadequate implementation programs. Several methods for enhancing adherence to clinical practice guidelines have been evaluated, including distribution methods, professional education sessions, electronic health records (EHR), point of care reminders and computer decision support systems (CDSS). Results of these studies are mixed to date, and the most effective ways to implement clinical practice guidelines remain unclear. Given the significant resources dedicated to evidence-based medicine, effective dissemination and implementation of best practice at the patient level is an important final step in the process of guideline development. Future efforts should focus on identifying optimal methods for translating the evidence into everyday clinical practice to ensure that patients receive the best care. PMID:25478199

Big Data in Designing Clinical Trials: Opportunities and Challenges

PubMed Central

Mayo, Charles S.; Matuszak, Martha M.; Schipper, Matthew J.; Jolly, Shruti; Hayman, James A.; Ten Haken, Randall K.

2017-01-01

Emergence of big data analytics resource systems (BDARSs) as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs) have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials. PMID:28913177

Big Data in Designing Clinical Trials: Opportunities and Challenges.

PubMed

Mayo, Charles S; Matuszak, Martha M; Schipper, Matthew J; Jolly, Shruti; Hayman, James A; Ten Haken, Randall K

2017-01-01

Emergence of big data analytics resource systems (BDARSs) as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs) have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials.

Datamining approaches for modeling tumor control probability.

PubMed

Naqa, Issam El; Deasy, Joseph O; Mu, Yi; Huang, Ellen; Hope, Andrew J; Lindsay, Patricia E; Apte, Aditya; Alaly, James; Bradley, Jeffrey D

2010-11-01

Tumor control probability (TCP) to radiotherapy is determined by complex interactions between tumor biology, tumor microenvironment, radiation dosimetry, and patient-related variables. The complexity of these heterogeneous variable interactions constitutes a challenge for building predictive models for routine clinical practice. We describe a datamining framework that can unravel the higher order relationships among dosimetric dose-volume prognostic variables, interrogate various radiobiological processes, and generalize to unseen data before when applied prospectively. Several datamining approaches are discussed that include dose-volume metrics, equivalent uniform dose, mechanistic Poisson model, and model building methods using statistical regression and machine learning techniques. Institutional datasets of non-small cell lung cancer (NSCLC) patients are used to demonstrate these methods. The performance of the different methods was evaluated using bivariate Spearman rank correlations (rs). Over-fitting was controlled via resampling methods. Using a dataset of 56 patients with primary NCSLC tumors and 23 candidate variables, we estimated GTV volume and V75 to be the best model parameters for predicting TCP using statistical resampling and a logistic model. Using these variables, the support vector machine (SVM) kernel method provided superior performance for TCP prediction with an rs=0.68 on leave-one-out testing compared to logistic regression (rs=0.4), Poisson-based TCP (rs=0.33), and cell kill equivalent uniform dose model (rs=0.17). The prediction of treatment response can be improved by utilizing datamining approaches, which are able to unravel important non-linear complex interactions among model variables and have the capacity to predict on unseen data for prospective clinical applications.

A Prospective Follow-Up of Adipocytokines in Cohort Patients With Gout: Association With Metabolic Syndrome But Not With Clinical Inflammatory Findings: Strobe-Compliant Article.

PubMed

García-Méndez, Sergio; Rivera-Bahena, Carolina Bustos; Montiel-Hernández, José Luis; Xibillé-Friedmann, Daniel; Álvarez-Hernández, Everardo; Peláez-Ballestas, Ingris; Burgos-Vargas, Rubén; Vázquez-Mellado, Janitzia

2015-07-01

The aim of this study was to determine the levels of leptin (Lep) and adiponectin (AdipoQ) in patients with gout and its relationship with joint inflammatory data and/or with metabolic syndrome (MetS) variables, during 1 year follow-up.Forty-one patients (40 males) with gout diagnosis, attending for the first time to a rheumatology department, were included. Evaluations were performed baseline, at 6 and 12 months. Variables included the following: demographic, clinical and laboratory data related to gout and associated diseases. Lep and AdipoQ determinations by the ELISA method were performed in frozen serum from each visit. The pharmacological and no-pharmacological treatment for gout and associated diseases was individualized for each patient according to published guidelines. Statistical analysis included Mann-Whitney U test, Fisher test, x, ANOVA, Cochran Q, Pearson and Spearman correlation tests, as well as linear regression.In the baseline evaluation, 29.2% had MetS (hypertriglyceridemia 66%, hypertension 44% and obesity 37%); patients with MetS had higher C reactive protein (CRP) levels [34.1 ± 28.6 vs. 12.2 ± 11.2 mg/dL, P = 0.033]. Although not significant, also had higher Lep and lower AdipoQ levels (3.2 ± 3.0 vs. 1.9 ± 1.2 ng/mL, P = 0.142 and 40.5 ± 26.8 vs. 38.0 ± 24.9 ng/mL, P = 0.877, respectively). During follow-up, our patients had significant improvement in serum uric acid (sUA) levels and variables evaluating pain and joint swelling (P ≤ 0.05). Metabolic abnormalities tended to persist or even worsen during the monitoring period: significant increase in total cholesterol (P = 0.004), tendency to higher triglycerides (P = 0.883) and slight improvement in glycaemia (P = 0.052). Lep values increased significantly during follow-up (P = 0.001) while AdipoQ levels diminished slightly (P = 0.317). Neither Lep nor AdipoQ values showed important correlation (r > 0.5) with metabolic variables or joint swelling.This study suggests that in patients with gout, concentrations of Lep and AdipoQ are more in line with the metabolic state than with clinical disease activity.

Developing and Validating a Predictive Model for Stroke Progression

PubMed Central

Craig, L.E.; Wu, O.; Gilmour, H.; Barber, M.; Langhorne, P.

2011-01-01

Background Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Methods Two patient cohorts were used for this study – the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p < 0.1) on univariate analysis were included in the multivariate model. Logistic regression was the technique employed using backward stepwise regression to drop the least significant variables (p > 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Results Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72–0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50–0.92)]. Conclusion The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and calibration of the predictive model appear sufficiently high to provide accurate predictions. This study also offers some discussion around the validation of predictive models for wider use in clinical practice. PMID:22566988

Efficacy of Platelet-Rich Fibrin After Mandibular Third Molar Extraction: A Systematic Review and Meta-Analysis.

PubMed

Al-Hamed, Faez Saleh; Tawfik, Mohamed Abdel-Monem; Abdelfadil, Ehab; Al-Saleh, Mohammed A Q

2017-06-01

To assess the effect of platelet-rich fibrin (PRF) on the healing process of the alveolar socket after surgical extraction of the mandibular third molars. PubMed, the Cochrane Central Register of Controlled Trials, Scopus, and relevant journals were searched using a combination of specific keywords ("platelet-rich fibrin," "oral surgery," and "third molar"). The final search was conducted on November 2, 2015. Randomized controlled clinical trials, as well as controlled clinical trials, aimed at comparing the effect of PRF versus natural healing after extraction of mandibular third molars were included. Five randomized controlled trials and one controlled clinical trial were included. There were 335 extractions (168 with PRF and 167 controls) in 183 participants. Considerable heterogeneity in study characteristics, outcome variables, and estimated scales was observed. Positive results were generally recorded for pain, trismus, swelling, periodontal pocket depth, soft tissue healing, and incidence of localized osteitis, but not in all studies. However, no meta-analysis could be conducted for such variables because of the different measurement scales used. The qualitative and meta-analysis results showed no significant improvement in bone healing with PRF-treated sockets compared with the naturally healing sockets. Within the limitations of the available evidence, PRF seems to have no beneficial role in bone healing after extraction of the mandibular third molars. Future standardized randomized controlled clinical trials are required to estimate the effect of PRF on socket regeneration. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Refractory chronic migraine: is drug withdrawal necessary before starting a therapy with onabotulinum toxin type A?

PubMed

Butera, Calogera; Colombo, Bruno; Bianchi, Francesca; Cursi, Marco; Messina, Roberta; Amadio, Stefano; Guerriero, Roberta; Comi, Giancarlo; Del Carro, Ubaldo

2016-10-01

Onabotulinum toxin A (BT-A) is now one of the authorized prophylaxis treatments for chronic migraine (CM) thanks to previous clinical trials, which usually required a pharmacologic washout as a precondition for demonstrating its efficacy. Aim of our study was to assess the efficacy in daily clinical practice of BT-A injections in refractory CM patients, regardless of medication overuse without any standardized withdrawal protocol and without stopping the ongoing prophylaxis treatment as well. We treated 44 refractory CM patients (37 females and 7 males) trimonthly without any modification in symptomatic, or prophylactic drug therapy. Main efficacy variables included number of headache, or migraine days and episodes, total cumulative headache hours, MIDAS and HIT-6 scores; all items were assessed at baseline and at the 12-, 24-, and 36-week follow-up. All variables showed a statistically significant improvement at week 36. In general, more than 50 % of patients had a good clinical outcome (including all improved patients, either partial or full responder) and that the percentage of drug abuser patients significantly decreased from 75 to 50 %, thanks to a spontaneous reduction of the symptomatic drug intake. Adverse events were uncommon and did not require treatment discontinuation. Onabotulinum toxin A treatment in refractory CM patients with unsatisfactory prophylactic drug treatments and pharmacological abuse is effective in improving clinical outcome and quality of life. This result may be achieved through a flexible pharmacologic approach tailored to each patient's needs; moreover, the patient himself can be often expected to reduce drug consumption spontaneously.

Sporadic and familial glut1ds Italian patients: A wide clinical variability.

PubMed

De Giorgis, Valentina; Teutonico, Federica; Cereda, Cristina; Balottin, Umberto; Bianchi, Marika; Giordano, Lucio; Olivotto, Sara; Ragona, Francesca; Tagliabue, Anna; Zorzi, Giovanna; Nardocci, Nardo; Veggiotti, Pierangelo

2015-01-01

GLUT1 deficiency syndrome is a treatable neurological disorder characterized by developmental delay, movement disorders and epilepsy. It is caused by mutations in the SLC2A1 gene inherited as an autosomal dominant trait with complete penetrance, even if most detected SCL2A1 mutations are de novo. Our aim is to present a wide series of Italian patients to highlight the differences among subjects with de novo mutations and those with familial transmission. We present clinical and genetic features in a series of 22 GLUT1DS Italian patients. Our patients were classified in two different groups: familial cases including GLUT1DS patients with genetically confirmed affected relatives and sporadic cases with detection of SLC2A1 de novo mutation. We found remarkable differences in the severity of the clinical picture regarding the type of genetic inheritance (sporadic versus familial): sporadic patients were characterized by an earlier epilepsy-onset and higher degree of intellectual disability. No significant differences were found in terms of type of movement disorder, whilst Paroxysmal Exertion-induced Dyskinesia (PED) is confirmed to be the most characteristic movement disorder type in GLUT1DS. In familial cases the clinical manifestation of the disease was particularly variable and heterogeneous, also including asymptomatic patients or those with minimal-symptoms. The finding of a "mild" phenotype in familial GLUT1DS gives rise to several questions: the real incidence of the disease, treatment option with ketogenic diet in adult patients and genetic counseling. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Higher body mass index is associated with plantar fasciopathy/'plantar fasciitis': systematic review and meta-analysis of various clinical and imaging risk factors.

PubMed

van Leeuwen, K D B; Rogers, J; Winzenberg, T; van Middelkoop, M

2016-08-01

What (risk) factors are associated with plantar fasciopathy (PF)? Systematic review with meta-analyses. Patients with PF. All factors described in prospective, case-control or cross-sectional observational studies. 51 included studies (1 prospective, 46 case-control and 4 cross-sectional studies) evaluated a total of 104 variables. Pooling was possible for 12 variables. Higher body mass index (BMI) (BMI>27, OR 3.7 (95% CI 2.93 to 5.62)) in patients with PF was the only significant clinical association, and its effect was the strongest in the non-athletic subgroup. In people with PF compared to controls, pooled imaging data demonstrated a significantly thicker, hypoechogenic plantar fascia with increased vascular signal and perifascial fluid collection. In addition, people with PF were more likely to have a thicker loaded and unloaded heel fat pat, and bone findings, including a subcalcaneal spur and increased Tc-99 uptake. No significant difference was found in the extension of the first metatarsophalangeal joint. We found a consistent clinical association between higher BMI and plantar fasciopathy. This association may differ between athletic and non-athletic subgroups. While consistent evidence supports a range of bone and soft tissue abnormalities, there is lack of evidence for the dogma of clinical and mechanical measures of foot and ankle function. Clinicians can use this information in shared decision-making. 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/

Performance of Male and Female C57BL/6J Mice on Motor and Cognitive Tasks Commonly Used in Pre-Clinical Traumatic Brain Injury Research

PubMed Central

Tucker, Laura B.; Fu, Amanda H.

2016-01-01

Abstract To date, clinical trials have failed to find an effective therapy for victims of traumatic brain injury (TBI) who live with motor, cognitive, and psychiatric complaints. Pre-clinical investigators are now encouraged to include male and female subjects in all translational research, which is of particular interest in the field of neurotrauma given that circulating female hormones (progesterone and estrogen) have been demonstrated to exert neuroprotective effects. To determine whether behavior of male and female C57BL6/J mice is differentially impaired by TBI, male and cycling female mice were injured by controlled cortical impact and tested for several weeks with functional assessments commonly employed in pre-clinical research. We found that cognitive and motor impairments post-TBI, as measured by the Morris water maze (MWM) and rotarod, respectively, were largely equivalent in male and female animals. However, spatial working memory, assessed by the y-maze, was poorer in female mice. Female mice were generally more active, as evidenced by greater distance traveled in the first exposure to the open field, greater distance in the y-maze, and faster swimming speeds in the MWM. Statistical analysis showed that variability in all behavioral data was no greater in cycling female mice than it was in male mice. These data all suggest that with careful selection of tests, procedures, and measurements, both sexes can be included in translational TBI research without concern for effect of hormones on functional impairments or behavioral variability. PMID:25951234

Predictors of Time to Union After Operative Fixation of Closed Ankle Fractures.

PubMed

Matson, Andrew P; Hamid, Kamran S; Adams, Samuel B

2017-08-01

Ankle fractures are common and represent a significant burden to society. We aim to report the rate of union as determined by clinical and radiographic data, and to identify factors that predict time to union. A cohort of 112 consecutive patients with isolated, closed, operative malleolar ankle fractures treated with open reduction and internal fixation was retrospectively reviewed for time to clinical union. Clinical union was defined based on radiographic and clinical parameters, and delayed union was defined by time to union >12 weeks. Injury characteristics, patient factors and treatment variables were recorded, and statistical techniques employed included the Chi-square test, the Student's T-test, and multivariate linear regression modeling. Forty-two (37.5%) of patients who achieved union did so in less than 12 weeks, and 69 (61.6%) of these patients demonstrated delayed union at a mean of 16.7 weeks (range, 12.1-26.7 weeks), and the remaining patient required revision surgery. Factors associated with higher rates of delayed union or increased time to union included tobacco use, bimalleolar fixation, and high energy mechanism (all p<0.05). In regression analysis, statistically significant negative predictors of time to union were BMI, dislocation of the tibiotalar joint, external fixation for initial stabilization and delay of definitive management (all p<0.05). Patient characteristics, injury factors and treatment variables are predictive of time to union following open reduction and internal fixation of closed ankle fractures. These findings should assist with patient counseling, and help guide the provider when considering adjunctive therapies that promote bone healing. Prognostic, Level IV: Case series.

Gingival Retraction Methods: A Systematic Review.

PubMed

Tabassum, Sadia; Adnan, Samira; Khan, Farhan Raza

2017-12-01

The aim of this systematic review was to assess the gingival retraction methods in terms of the amount of gingival retraction achieved and changes observed in various clinical parameters: gingival index (GI), plaque index (PI), probing depth (PD), and attachment loss (AL). Data sources included three major databases, PubMed, CINAHL plus (Ebsco), and Cochrane, along with hand search. Search was made using the key terms in different permutations of gingival retraction* AND displacement method* OR technique* OR agents OR material* OR medicament*. The initial search results yielded 145 articles which were narrowed down to 10 articles using a strict eligibility criteria of including clinical trials or experimental studies on gingival retraction methods with the amount of tooth structure gained and assessment of clinical parameters as the outcomes conducted on human permanent teeth only. Gingival retraction was measured in 6/10 studies whereas the clinical parameters were assessed in 5/10 studies. The total number of teeth assessed in the 10 included studies was 400. The most common method used for gingival retraction was chemomechanical. The results were heterogeneous with regards to the outcome variables. No method seemed to be significantly superior to the other in terms of gingival retraction achieved. Clinical parameters were not significantly affected by the gingival retraction method. © 2016 by the American College of Prosthodontists.

An Investigation of the Facilitative and Inhibitory Variables Impacting Breast Health Practices in Low-Socioeconomic Status Black Women of African American and Caribbean Descent

DTIC Science & Technology

2003-10-01

Honestly, it’~> been a very difficult tim~p here ... pancreatic cancer is a bumpy ride of lingering pain and suffering. I hope every day that my time...TELEPHONE NUMBER (include area code) 14. ABSTRACT Black women of low-socioeconomic status (SES) demonstrate a high incidence of breast cancer ...mortality associated with late-state diagnosis. Breast cancer screening, including mammography, breast self-examination, and clinical breast

Analysis of cardiovascular oscillations: A new approach to the early prediction of pre-eclampsia

NASA Astrophysics Data System (ADS)

Malberg, H.; Bauernschmitt, R.; Voss, A.; Walther, T.; Faber, R.; Stepan, H.; Wessel, N.

2007-03-01

Pre-eclampsia (PE) is a serious disorder with high morbidity and mortality occurring during pregnancy; 3%-5% of all pregnant women are affected. Early prediction is still insufficient in clinical practice. Although most pre-eclamptic patients show pathological uterine perfusion in the second trimester, this parameter has a positive predictive accuracy of only 30%, which makes it unsuitable for early, reliable prediction. The study is based on the hypothesis that alterations in cardiovascular regulatory behavior can be used to predict PE. Ninety-six pregnant women in whom Doppler investigation detected perfusion disorders of the uterine arteries were included in the study. Twenty-four of these pregnant women developed PE after the 30th week of gestation. During pregnancy, additional several noninvasive continuous blood pressure recordings were made over 30 min under resting conditions by means of a finger cuff. The time series extracted of systolic as well as diastolic beat-to-beat pressures and the heart rate were studied by variability and coupling analysis to find predictive factors preceding genesis of the disease. In the period between the 18th and 26th weeks of pregnancy, three special variability and baroreflex parameters were able to predict PE several weeks before clinical manifestation. Discriminant function analysis of these parameters was able to predict PE with a sensitivity and specificity of 87.5% and a positive predictive value of 70%. The combined clinical assessment of uterine perfusion and cardiovascular variability demonstrates the best current prediction several weeks before clinical manifestation of PE.

Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature.

PubMed

Dell'Isola, A; Allan, R; Smith, S L; Marreiros, S S P; Steultjens, M

2016-10-12

Knee Osteoarthritis (KOA) is a heterogeneous pathology characterized by a complex and multifactorial nature. It has been hypothesised that these differences are due to the existence of underlying phenotypes representing different mechanisms of the disease. The aim of this study is to identify the current evidence for the existence of groups of variables which point towards the existence of distinct clinical phenotypes in the KOA population. A systematic literature search in PubMed was conducted. Only original articles were selected if they aimed to identify phenotypes of patients aged 18 years or older with KOA. The methodological quality of the studies was independently assessed by two reviewers and qualitative synthesis of the evidence was performed. Strong evidence for existence of specific phenotypes was considered present if the phenotype was supported by at least two high-quality studies. A total of 24 studies were included. Through qualitative synthesis of evidence, six main sets of variables proposing the existence of six phenotypes were identified: 1) chronic pain in which central mechanisms (e.g. central sensitisation) are prominent; 2) inflammatory (high levels of inflammatory biomarkers); 3) metabolic syndrome (high prevalence of obesity, diabetes and other metabolic disturbances); 4) Bone and cartilage metabolism (alteration in local tissue metabolism); 5) mechanical overload characterised primarily by varus malalignment and medial compartment disease; and 6) minimal joint disease characterised as minor clinical symptoms with slow progression over time. This study identified six distinct groups of variables which should be explored in attempts to better define clinical phenotypes in the KOA population.

Association between family history of mood disorders and clinical characteristics of bipolar disorder: results from the Brazilian bipolar research network.

PubMed

Berutti, Mariangeles; Nery, Fabiano G; Sato, Rodrigo; Scippa, Angela; Kapczinski, Flavio; Lafer, Beny

2014-06-01

To compare clinical characteristics of bipolar disorder (BD) in patients with and without a family history of mood disorders (FHMD) in a large sample from the Brazilian Research Network of Bipolar Disorders. Four-hundred eighty-eight DSM-IV BD patients participating in the Brazilian Research Network of Bipolar Disorders were included. Participants were divided between those with FHMD (n=230) and without FHMD (n=258). We compared these two groups on demographic and clinical variables and performed a logistic regression to identify which variables were most strongly associated with positive family history of mood disorders. BD patients with FHMD presented with significantly higher lifetime prevalence of any anxiety disorder, obsessive-compulsive disorder, social phobia, substance abuse, and were more likely to present history of suicide attempts, family history of suicide attempts and suicide, and more psychiatric hospitalizations than BD patients without FHMD. Logistic regression showed that the variables most strongly associated with a positive FHMD were any comorbid anxiety disorder, comorbid substance abuse, and family history of suicide. Cross-sectional study and verification of FHMD by indirect information. BD patients with FHMD differ from BD patients without FHMD in rates of comorbid anxiety disorder and substance abuse, number of hospitalizations and suicide attempts. As FHMD is routinely assessed in clinical practice, these findings may help to identify patients at risk for particular manifestations of BD and may point to a common, genetically determined neurobiological substrate that increases the risk of conditions such as comorbidities and suicidality in BD patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Gingival recession: prevalence and risk indicators among young greek adults.

PubMed

Chrysanthakopoulos, Nikolaos A

2014-07-01

The aim of the current research was to assess the prevalence of gingival recession and to investigate possible associations among this condition, periodontal and epidemiological variables in a sample of young Greek adults in a general dental practice. A total of 1,430 young adults was examined clinically and interviewed regarding several periodontal and epidemiological variables. Collected data included demographic variables, oral hygiene habits and smoking status. Clinical examination included the recording of dental plaque, supragingival calculus presence, gingival status and buccal gingival recession. Multivariate logistic regression analysis model was performed to access the possible association between gingival recession and several periodontal and epidemiological variables as potential risk factors. The overall prevalence of gingival recession was 63.9%. The statistical analysis indicated that higher educational level [OR= 2.12, 95% CI= 0.53-8.51], cigarette smoking [OR= 1.97, 95% CI= 1.48-7.91], frequent tooth brushing [OR= 0.98, 95% CI= 0.56-1.96], presence of oral piercing [OR= 0.92, 95% CI= 0.38-1.58], presence of gingival inflammation [OR= 4.54, 95% CI= 1.68-7.16], presence of dental plaque [OR= 1.67, 95% CI= 0.68-2.83] and presence of supragingival calculus [OR=1.34, 95% CI= 0.59-1.88], were the most important associated factors of gingival recession. The observations of the current research supported the results from previous authors that several periodontal factors, educational level and smoking were significantly associated with the presence of gingival recession, while presence of oral piercing was a new factor that was found to be associated with gingival recession. Key words:Gingival recession, prevalence, risk factors, young adults.

Gingival recession: prevalence and risk indicators among young greek adults

PubMed Central

2014-01-01

Objectives: The aim of the current research was to assess the prevalence of gingival recession and to investigate possible associations among this condition, periodontal and epidemiological variables in a sample of young Greek adults in a general dental practice. Material and Methods: A total of 1,430 young adults was examined clinically and interviewed regarding several periodontal and epidemiological variables. Collected data included demographic variables, oral hygiene habits and smoking status. Clinical examination included the recording of dental plaque, supragingival calculus presence, gingival status and buccal gingival recession. Multivariate logistic regression analysis model was performed to access the possible association between gingival recession and several periodontal and epidemiological variables as potential risk factors. Results: The overall prevalence of gingival recession was 63.9%. The statistical analysis indicated that higher educational level [OR= 2.12, 95% CI= 0.53-8.51], cigarette smoking [OR= 1.97, 95% CI= 1.48-7.91], frequent tooth brushing [OR= 0.98, 95% CI= 0.56-1.96], presence of oral piercing [OR= 0.92, 95% CI= 0.38-1.58], presence of gingival inflammation [OR= 4.54, 95% CI= 1.68-7.16], presence of dental plaque [OR= 1.67, 95% CI= 0.68-2.83] and presence of supragingival calculus [OR=1.34, 95% CI= 0.59-1.88], were the most important associated factors of gingival recession. Conclusions: The observations of the current research supported the results from previous authors that several periodontal factors, educational level and smoking were significantly associated with the presence of gingival recession, while presence of oral piercing was a new factor that was found to be associated with gingival recession. Key words:Gingival recession, prevalence, risk factors, young adults. PMID:25136424