Variability of word discrimination scores in clinical practice and consequences on their sensitivity to hearing loss.

PubMed

Moulin, Annie; Bernard, André; Tordella, Laurent; Vergne, Judith; Gisbert, Annie; Martin, Christian; Richard, Céline

2017-05-01

Speech perception scores are widely used to assess patient's functional hearing, yet most linguistic material used in these audiometric tests dates to before the availability of large computerized linguistic databases. In an ENT clinic population of 120 patients with median hearing loss of 43-dB HL, we quantified the variability and the sensitivity of speech perception scores to hearing loss, measured using disyllabic word lists, as a function of both the number of ten-word lists and type of scoring used (word, syllables or phonemes). The mean word recognition scores varied significantly across lists from 54 to 68%. The median of the variability of the word recognition score ranged from 30% for one ten-word list down to 20% for three ten-word lists. Syllabic and phonemic scores showed much less variability with standard deviations decreasing by 1.15 with the use of syllabic scores and by 1.45 with phonemic scores. The sensitivity of each list to hearing loss and distortions varied significantly. There was an increase in the minimum effect size that could be seen for syllabic scores compared to word scores, with no significant further improvement with phonemic scores. The use of at least two ten-word lists, quoted in syllables rather than in whole words, contributed to a large decrease in variability and an increase in sensitivity to hearing loss. However, those results emphasize the need of using updated linguistic material for clinical speech score assessments.

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.

Combining clinical and angiographic variables for estimating risk of target lesion revascularization after drug eluting stent placement.

PubMed

Stolker, Joshua M; Cohen, David J; Kennedy, Kevin F; Pencina, Michael J; Arnold, Suzanne V; Kleiman, Neal S; Spertus, John A

Drug-eluting stents (DES) reduce restenosis but require prolonged antiplatelet therapy, when compared with bare metal stents. Ideally, the patient should be involved in this risk:benefit assessment prior to selecting DES, to maximize the benefits and cost-effectiveness of care, and to improve medication adherence. However, accurate estimation of restenosis risk may require angiographic factors identified at cardiac catheterization. In a large PCI registry, we used logistic regression to identify clinical and angiographic predictors of clinically-driven target lesion revascularization (TLR) over the first year after stent placement. Discrimination c-statistic and integrated discrimination improvement (IDI) were used to calculate the incremental utility of angiographic variables when added to clinical predictors. Of 8501 PCI patients, TLR occurred in 4.5%. After adjusting for DES use, clinical TLR predictors were younger age, female sex, diabetes, prior PCI, and prior bypass surgery (model c-statistic 0.630). Angiographic predictors were vein graft PCI, in-stent restenosis lesion, longer stent length, and smaller stent diameter (c-statistic 0.650). After adding angiographic factors to the clinical model, c-statistic improved to 0.680 and the average separation in TLR risk among patients with and without TLR improved by 1% (IDI=0.010, 95% CI 0.009-0.014), primarily driven by those experiencing TLR (from 5.9% to 6.9% absolute risk). Among unselected PCI patients, the incidence of clinically-indicated TLR is <5% at 1-year, and standard clinical variables only moderately discriminate who will and will not experience TLR. Angiographic variables significantly improve TLR risk assessment, suggesting that stent selection may be best performed after coronary anatomy has been delineated. Although several recent studies have challenged traditional expectations regarding the duration of dual antiplatelet therapy, current guidelines recommend at least 6 to 12months of treatment after implantation of a drug eluting stent, with a shorter course for bare metal stents. Stent selection ideally should involve input from the patient receiving these stents, but multiple studies have suggested that angiographic factors - obtained after the patient has received sedation during the diagnostic catheterization - are important predictors of repeat revascularization. In this analysis from a large registry of patients receiving coronary stents, angiographic characteristics were found to significantly improve risk assessment for target lesion revascularization, when added to clinical variables alone. Copyright © 2016 Elsevier Inc. All rights reserved.

Factors influencing the perceived quality of clinical supervision of occupational therapists in a large Australian state.

PubMed

Martin, Priya; Kumar, Saravana; Lizarondo, Lucylynn; Tyack, Zephanie

2016-10-01

Clinical supervision is important for effective health service delivery, professional development and practice. Despite its importance there is a lack of evidence regarding the factors that improve its quality. This study aimed to investigate the factors that influence the quality of clinical supervision of occupational therapists employed in a large public sector health service covering mental health, paediatrics, adult physical and other practice areas. A mixed method, sequential explanatory study design was used consisting of two phases. This article reports the quantitative phase (Phase One) which involved administration of the Manchester Clinical Supervision Scale (MCSS-26) to 207 occupational therapists. Frequency of supervision sessions, choice of supervisor and the type of supervision were found to be the predictor variables with a positive and significant influence on the quality of clinical supervision. Factors such as age, length of supervision and the area of practice were found to be the predictor variables with a negative and significant influence on the quality of clinical supervision. Factors that influence the perceived quality of clinical supervision among occupational therapists have been identified. High quality clinical supervision is an important component of clinical governance and has been shown to be beneficial to practitioners, patients and the organisation. Information on factors that make clinical supervision effective identified in this study can be added to existing supervision training and practices to improve the quality of clinical supervision. © 2016 Occupational Therapy Australia.

Optimization of large animal MI models; a systematic analysis of control groups from preclinical studies.

PubMed

Zwetsloot, P P; Kouwenberg, L H J A; Sena, E S; Eding, J E; den Ruijter, H M; Sluijter, J P G; Pasterkamp, G; Doevendans, P A; Hoefer, I E; Chamuleau, S A J; van Hout, G P J; Jansen Of Lorkeers, S J

2017-10-27

Large animal models are essential for the development of novel therapeutics for myocardial infarction. To optimize translation, we need to assess the effect of experimental design on disease outcome and model experimental design to resemble the clinical course of MI. The aim of this study is therefore to systematically investigate how experimental decisions affect outcome measurements in large animal MI models. We used control animal-data from two independent meta-analyses of large animal MI models. All variables of interest were pre-defined. We performed univariable and multivariable meta-regression to analyze whether these variables influenced infarct size and ejection fraction. Our analyses incorporated 246 relevant studies. Multivariable meta-regression revealed that infarct size and cardiac function were influenced independently by choice of species, sex, co-medication, occlusion type, occluded vessel, quantification method, ischemia duration and follow-up duration. We provide strong systematic evidence that commonly used endpoints significantly depend on study design and biological variation. This makes direct comparison of different study-results difficult and calls for standardized models. Researchers should take this into account when designing large animal studies to most closely mimic the clinical course of MI and enable translational success.

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.

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

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

A business planning model to identify new safety net clinic locations.

PubMed

Langabeer, James; Helton, Jeffrey; DelliFraine, Jami; Dotson, Ebbin; Watts, Carolyn; Love, Karen

2014-01-01

Community health clinics serving the poor and underserved are geographically expanding due to changes in U.S. health care policy. This paper describes the experience of a collaborative alliance of health care providers in a large metropolitan area who develop a conceptual and mathematical decision model to guide decisions on expanding its network of community health clinics. Community stakeholders participated in a collaborative process that defined constructs they deemed important in guiding decisions on the location of community health clinics. This collaboration also defined key variables within each construct. Scores for variables within each construct were then totaled and weighted into a community-specific optimal space planning equation. This analysis relied entirely on secondary data available from published sources. The model built from this collaboration revolved around the constructs of demand, sustainability, and competition. It used publicly available data defining variables within each construct to arrive at an optimal location that maximized demand and sustainability and minimized competition. This is a model that safety net clinic planners and community stakeholders can use to analyze demographic and utilization data to optimize capacity expansion to serve uninsured and Medicaid populations. Communities can use this innovative model to develop a locally relevant clinic location-planning framework.

Factor analysis in predominantly severe COPD: identification of disease heterogeneity by easily measurable characteristics.

PubMed

Postma, Dirkje S; Anzueto, Antonio R; Jenkins, Christine; Make, Barry J; Similowski, Thomas; Östlund, Ollie; Eriksson, Göran S; Calverley, Peter M

2013-12-01

The clinical and demographic variables defining the heterogeneity of chronic obstructive pulmonary disease (COPD) are unclear. A post-hoc analysis of five randomised studies in patients with a history of previous exacerbations examined the clinical and demographic characteristics describing moderate-to-very-severe COPD. Factor analysis was performed on all continuous baseline demographic and clinical data, without variable selection. Analyses were based on the full cohort and on stratifications by pack-years smoked, smoking status, gender, and comorbidities; patient exacerbation history was analysed in two of the five studies. 6162 COPD patients were evaluated (70% male; 40% current smokers; mean pre-bronchodilator forced expiratory volume in 1 s [FEV1] 35.2% predicted). Baseline clinical and demographic variables loaded differentially on six factors with minimal overlap, explaining 60.4% of the heterogeneity: 1) symptoms (cough, dyspnoea, sleep disturbance), health status, reliever use; 2) pre-bronchodilator FEV1, FEV1/forced vital capacity, morning peak expiratory flow (PEF), body mass index (BMI); 3) blood pressure; 4) age, months since first COPD symptoms; 5) PEF variability; 6) pulse, FEV1 reversibility. Most factors loaded similarly in stratified and exacerbation analyses. BMI loaded with reversibility in females, and with age and months since first COPD symptoms in ex-smokers. Exacerbations loaded to factor 6. Readily available data can explain ≈ 60% of COPD heterogeneity in a large dataset of predominantly severe COPD patients. Factors were robust over determinants of disease outcome; gender, smoking status, pack-years smoked, and comorbidities. The main factors were largely unchanged by adding exacerbations. Only BMI loaded to other factors. Copyright © 2013. Published by Elsevier Ltd.

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.

Exploring correlates of diabetes-related stress among adults with Type 1 diabetes in the T1D exchange clinic registry.

PubMed

Boden, Matthew Tyler; Gala, Sasha

2018-04-01

To explore relations between diabetes-related stress and multiple sociodemographic, diabetes health, other health, and treatment-related variables among a large sample of adults with Type 1 Diabetes (T1D). The sample consisted of 10,821 adults (over 18 years old) enrolled in the T1D Exchange Clinic Registry. The T1D Exchange clinic network consists of 67 diabetes clinical centers throughout the United States selected to broadly represent pediatric and adult patients with T1D. Variables were assessed through participant self-report and extraction of clinic chart data. Univariate and multiple linear regression (with simultaneous entry of all predictors) analyses were conducted. Robustly associated with increased diabetes-related stress across analyses were multiple sociodemographic (female [vs. male], native Hawaiian/other Pacific islander [vs. white/Caucasian], decreased age and diabetes duration), diabetes health (higher HbA1c), other health (lower general health, presence of major life stress and depression, less physical activity), and treatment related variables (use of injections/pen or combination injection/pen/pump [vs. pump], use of CGM, increased frequency of missing insulin doses and BG checking, decreased frequency of BG checking prior to bolus, receipt of mental health treatment). We replicated and extended research demonstrating that diabetes-related stress among people with T1D occurs at higher levels among those with particular sociodemographic characteristics and is associated with a range poorer diabetes health and other health variables, and multiple treatment-related variables. The strong incremental prediction of diabetes-related stress by multiple variables in our study suggests that a multi-variable, personalized approach may increase the effectiveness of treatments for diabetes-related stress. Published by Elsevier B.V.

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

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

Clinical supervision, emotional exhaustion, and turnover intention: A study of substance abuse treatment counselors in NIDA’s Clinical Trials Network

PubMed Central

Knudsen, Hannah K.; Ducharme, Lori J.; Roman, Paul M

2008-01-01

An intriguing hypothesis is that clinical supervision may protect against counselor turnover. This idea has been mentioned in recent discussions of the substance abuse treatment workforce. To test this hypothesis, we extend our previous research on emotional exhaustion and turnover intention among counselors by estimating the associations between clinical supervision and these variables in a large sample (n = 823). An exploratory analysis reveals that clinical supervision was negatively associated with emotional exhaustion and turnover intention. Given our previous findings that emotional exhaustion and turnover intention were associated with job autonomy, procedural justice, and distributive justice, we estimate a structural equation model to examine whether these variables mediated clinical supervision’s associations with emotional exhaustion and turnover intention. These data support the fully mediated model. We found the perceived quality of clinical supervision is strongly associated with counselors’ perceptions of job autonomy, procedural justice, and distributive justice, which are, in turn, associated with emotional exhaustion and turnover intention. These data offer support for the protective role of clinical supervision in substance abuse treatment counselors’ turnover and occupational wellbeing. PMID:18424048

Use of Portable Digital Devices to Analyze Autonomic Stress Response in Psychology Objective Structured Clinical Examination.

PubMed

Beltrán-Velasco, Ana Isabel; Bellido-Esteban, Alberto; Ruisoto-Palomera, Pablo; Clemente-Suárez, Vicente Javier

2018-01-12

The aim of the present study was to explore changes in the autonomic stress response of Psychology students in a Psychology Objective Structured Clinical Examination (OSCE) and their relationship with OSCE performance. Variables of autonomic modulation by the analysis of heart rate variability in temporal, frequency and non-linear domains, subjective perception of distress strait and academic performance were measured before and after the two different evaluations that composed the OSCE. A psychology objective structured clinical examination composed by two different evaluation scenarios produced a large anxiety anticipatory response, a habituation response in the first of the evaluation scenarios and a in the entire evaluation, and a no habituation response in the second evaluation scenario. Autonomic modulation parameters do not correlate with academic performance of students.

Automatic identification of variables in epidemiological datasets using logic regression.

PubMed

Lorenz, Matthias W; Abdi, Negin Ashtiani; Scheckenbach, Frank; Pflug, Anja; Bülbül, Alpaslan; Catapano, Alberico L; Agewall, Stefan; Ezhov, Marat; Bots, Michiel L; Kiechl, Stefan; Orth, Andreas

2017-04-13

For an individual participant data (IPD) meta-analysis, multiple datasets must be transformed in a consistent format, e.g. using uniform variable names. When large numbers of datasets have to be processed, this can be a time-consuming and error-prone task. Automated or semi-automated identification of variables can help to reduce the workload and improve the data quality. For semi-automation high sensitivity in the recognition of matching variables is particularly important, because it allows creating software which for a target variable presents a choice of source variables, from which a user can choose the matching one, with only low risk of having missed a correct source variable. For each variable in a set of target variables, a number of simple rules were manually created. With logic regression, an optimal Boolean combination of these rules was searched for every target variable, using a random subset of a large database of epidemiological and clinical cohort data (construction subset). In a second subset of this database (validation subset), this optimal combination rules were validated. In the construction sample, 41 target variables were allocated on average with a positive predictive value (PPV) of 34%, and a negative predictive value (NPV) of 95%. In the validation sample, PPV was 33%, whereas NPV remained at 94%. In the construction sample, PPV was 50% or less in 63% of all variables, in the validation sample in 71% of all variables. We demonstrated that the application of logic regression in a complex data management task in large epidemiological IPD meta-analyses is feasible. However, the performance of the algorithm is poor, which may require backup strategies.

Kinematic evaluation of the finger's interphalangeal joints coupling mechanism--variability, flexion-extension differences, triggers, locking swanneck deformities, anthropometric correlations.

PubMed

Leijnse, J N A L; Quesada, P M; Spoor, C W

2010-08-26

The human finger contains tendon/ligament mechanisms essential for proper control. One mechanism couples the movements of the interphalangeal joints when the (unloaded) finger is flexed with active deep flexor. This study's aim was to accurately determine in a large finger sample the kinematics and variability of the coupled interphalangeal joint motions, for potential clinical and finger model validation applications. The data could also be applied to humanoid robotic hands. Sixty-eight fingers were measured in seventeen hands in nine subjects. Fingers exhibited great joint mobility variability, with passive proximal interphalangeal hyperextension ranging from zero to almost fifty degrees. Increased measurement accuracy was obtained by using marker frames to amplify finger segment motions. Gravitational forces on the marker frames were not found to invalidate measurements. The recorded interphalangeal joint trajectories were highly consistent, demonstrating the underlying coupling mechanism. The increased accuracy and large sample size allowed for evaluation of detailed trajectory variability, systematic differences between flexion and extension trajectories, and three trigger types, distinct from flexor tendon triggers, involving initial flexion deficits in either proximal or distal interphalangeal joint. The experimental methods, data and analysis should advance insight into normal and pathological finger biomechanics (e.g., swanneck deformities), and could help improve clinical differential diagnostics of trigger finger causes. The marker frame measuring method may be useful to quantify interphalangeal joints trajectories in surgical/rehabilitative outcome studies. The data as a whole provide the most comprehensive collection of interphalangeal joint trajectories for clinical reference and model validation known to us to date. 2010 Elsevier Ltd. All rights reserved.

Exploring psychological mechanisms of clinical response to an internet-delivered psychological pain management program.

PubMed

Gandy, M; Karin, E; Jones, M P; McDonald, S; Sharpe, L; Titov, N; Dear, B F

2018-05-13

The evidence for Internet-delivered pain management programs for chronic pain is growing, but there is little empirical understanding of how they effect change. Understanding mechanisms of clinical response to these programs could inform their effective development and delivery. A large sample (n = 396) from a previous randomized controlled trial of a validated internet-delivered psychological pain management program, the Pain Course, was used to examine the influence of three potential psychological mechanisms (pain acceptance, pain self-efficacy, fear of movement/re-injury) on treatment-related change in disability, depression, anxiety and average pain. Analyses involved generalized estimating equation models for clinical outcomes that adjusted for co-occurring change in psychological variables. This was paired with cross-lagged analysis to assess for evidence of causality. Analyses involved two time points, pre-treatment and post-treatment. Changes in pain-acceptance were strongly associated with changes in three (depression, anxiety and average pain) of the four clinical outcomes. Changes in self-efficacy were also strongly associated with two (anxiety and average pain) clinical outcomes. These findings suggest that participants were unlikely to improve in these clinical outcomes without also experiencing increases in their pain self-efficacy and pain acceptance. However, there was no clear evidence from cross-lagged analyses to currently support these psychological variables as direct mechanisms of clinical improvements. There was only statistical evidence to suggest higher levels of self-efficacy moderated improvements in depression. The findings suggest that, while clinical improvements are closely associated with improvements in pain acceptance and self-efficacy, these psychological variables may not drive the treatment effects observed. This study employed robust statistical techniques to assess the psychological mechanisms of an established internet-delivered pain management program. While clinical improvements (e.g. depression, anxiety, pain) were closely associated with improvements in psychological variables (e.g. pain self-efficacy and pain acceptance), these variables do not appear to be treatment mechanisms. © 2018 European Pain Federation - EFIC®.

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

Sigma metrics used to assess analytical quality of clinical chemistry assays: importance of the allowable total error (TEa) target.

PubMed

Hens, Koen; Berth, Mario; Armbruster, Dave; Westgard, Sten

2014-07-01

Six Sigma metrics were used to assess the analytical quality of automated clinical chemistry and immunoassay tests in a large Belgian clinical laboratory and to explore the importance of the source used for estimation of the allowable total error. Clinical laboratories are continually challenged to maintain analytical quality. However, it is difficult to measure assay quality objectively and quantitatively. The Sigma metric is a single number that estimates quality based on the traditional parameters used in the clinical laboratory: allowable total error (TEa), precision and bias. In this study, Sigma metrics were calculated for 41 clinical chemistry assays for serum and urine on five ARCHITECT c16000 chemistry analyzers. Controls at two analyte concentrations were tested and Sigma metrics were calculated using three different TEa targets (Ricos biological variability, CLIA, and RiliBÄK). Sigma metrics varied with analyte concentration, the TEa target, and between/among analyzers. Sigma values identified those assays that are analytically robust and require minimal quality control rules and those that exhibit more variability and require more complex rules. The analyzer to analyzer variability was assessed on the basis of Sigma metrics. Six Sigma is a more efficient way to control quality, but the lack of TEa targets for many analytes and the sometimes inconsistent TEa targets from different sources are important variables for the interpretation and the application of Sigma metrics in a routine clinical laboratory. Sigma metrics are a valuable means of comparing the analytical quality of two or more analyzers to ensure the comparability of patient test results.

An analysis of variability in the manufacturing of dexosomes: implications for development of an autologous therapy.

PubMed

Patel, Sanjay; Mehta-Damani, Anita; Shu, Helen; Le Pecq, Jean-Bernard

2005-10-20

Dexosomes are nanometer-size vesicles released by dendritic-cells, possessing much of the cellular machinery required to stimulate an immune response (i.e. MHC Class I and II). The ability of patient-derived dexosomes loaded with tumor antigens to elicit anti-tumor activity is currently being evaluated in clinical trials. Unlike conventional biologics, where variability between lots of product arises mostly from the manufacturing process, an autologous product has inherent variability in the starting material due to heterogeneity in the human population. In an effort to assess the variability arising from the dexosome manufacturing process versus the human starting material, 144 dexosome preparations from normal donors (111) and cancer patients (33) from two Phase I clinical trials were analyzed. A large variability in the quantity of dexosomes (measured as the number of MHC Class II molecules) produced between individual lots was observed ( > 50-fold). An analysis of intra-lot variability shows that the manufacturing process introduces relatively little of this variability. To identify the source(s) of variability arising from the human starting material, distributions of the key parameters involved in dexosome production were established, and a model created. Computer simulations using this model were performed, and compared to the actual data observed. The main conclusion from these simulations is that the number of cells collected per individual and the productivity of these cells of are the principal sources of variability in the production of Class II. The approach described here can be extended to other autologous therapies in general to evaluate control of manufacturing processes. Moreover, this analysis of process variability is directly applicable to production at a commercial scale, since the large scale manufacture of autologous products entails an exact process replication rather than scale-up in volume, as is the case with traditional drugs or biologics. Copyright 2005 Wiley Periodicals, Inc.

Four hundred or more participants needed for stable contingency table estimates of clinical prediction rule performance.

PubMed

Kent, Peter; Boyle, Eleanor; Keating, Jennifer L; Albert, Hanne B; Hartvigsen, Jan

2017-02-01

To quantify variability in the results of statistical analyses based on contingency tables and discuss the implications for the choice of sample size for studies that derive clinical prediction rules. An analysis of three pre-existing sets of large cohort data (n = 4,062-8,674) was performed. In each data set, repeated random sampling of various sample sizes, from n = 100 up to n = 2,000, was performed 100 times at each sample size and the variability in estimates of sensitivity, specificity, positive and negative likelihood ratios, posttest probabilities, odds ratios, and risk/prevalence ratios for each sample size was calculated. There were very wide, and statistically significant, differences in estimates derived from contingency tables from the same data set when calculated in sample sizes below 400 people, and typically, this variability stabilized in samples of 400-600 people. Although estimates of prevalence also varied significantly in samples below 600 people, that relationship only explains a small component of the variability in these statistical parameters. To reduce sample-specific variability, contingency tables should consist of 400 participants or more when used to derive clinical prediction rules or test their performance. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Variability sensitivity of dynamic texture based recognition in clinical CT data

NASA Astrophysics Data System (ADS)

Kwitt, Roland; Razzaque, Sharif; Lowell, Jeffrey; Aylward, Stephen

2014-03-01

Dynamic texture recognition using a database of template models has recently shown promising results for the task of localizing anatomical structures in Ultrasound video. In order to understand its clinical value, it is imperative to study the sensitivity with respect to inter-patient variability as well as sensitivity to acquisition parameters such as Ultrasound probe angle. Fully addressing patient and acquisition variability issues, however, would require a large database of clinical Ultrasound from many patients, acquired in a multitude of controlled conditions, e.g., using a tracked transducer. Since such data is not readily attainable, we advocate an alternative evaluation strategy using abdominal CT data as a surrogate. In this paper, we describe how to replicate Ultrasound variabilities by extracting subvolumes from CT and interpreting the image material as an ordered sequence of video frames. Utilizing this technique, and based on a database of abdominal CT from 45 patients, we report recognition results on an organ (kidney) recognition task, where we try to discriminate kidney subvolumes/videos from a collection of randomly sampled negative instances. We demonstrate that (1) dynamic texture recognition is relatively insensitive to inter-patient variation while (2) viewing angle variability needs to be accounted for in the template database. Since naively extending the template database to counteract variability issues can lead to impractical database sizes, we propose an alternative strategy based on automated identification of a small set of representative models.

Hubness of strategic planning and sociality influences depressive mood and anxiety in College Population.

PubMed

Yun, Je-Yeon; Choi, Yoobin; Kwon, Yoonhee; Lee, Hwa Young; Choi, Soo-Hee; Jang, Joon Hwan

2017-12-19

Depressive mood and anxiety can reduce cognitive performance. Conversely, the presence of a biased cognitive tendency may serve as a trigger for depressive mood-anxiety. Previous studies have largely focused on group-wise correlations between clinical-neurocognitive variables. Using network analyses for intra-individual covariance, we sought to decipher the most influential clinical-neurocognitive hub in the differential severity of depressive-anxiety symptoms in a college population. Ninety college students were evaluated for depressive-anxiety symptoms, Minnesota multiphasic personality inventory-2(MMPI-2), and neuro-cognition. Weighted and undirected version of the intra-individual covariance networks, comprised of 18 clinical-neurocognitive variables satisfied small-worldness and modular organization in the sparsity range of K = 0.20-0.21. Furthermore, betweenness centrality of perseverative error for the Wisconsin card sorting test was reduced in more depressive individuals; higher anxiety was related to the increased betweenness centrality of MMPI-2 clinical scale 0(Si). Elevated edge-betweenness centrality of covariance between the MMPI-2 clinical scale 7(Pt) versus commission error of the continuous performance test predicted more anxiety higher than depressive mood. With intra-individual covariance network of clinical-neurocognitive variables, this study demonstrated critical drivers of depressive mood[attenuated influence of strategic planning] or anxiety[domination of social introversion/extroversion, in addition to the influence of compulsivity-impulsivity covariance as a shortcut component among various clinical-neurocognitive features].

Assessment of published models and prognostic variables in epithelial ovarian cancer at Mayo Clinic

PubMed Central

Hendrickson, Andrea Wahner; Hawthorne, Kieran M.; Goode, Ellen L.; Kalli, Kimberly R.; Goergen, Krista M.; Bakkum-Gamez, Jamie N.; Cliby, William A.; Keeney, Gary L.; Visscher, Dan W.; Tarabishy, Yaman; Oberg, Ann L.; Hartmann, Lynn C.; Maurer, Matthew J.

2015-01-01

Objectives Epithelial ovarian cancer (EOC) is an aggressive disease in which first line therapy consists of a surgical staging/debulking procedure and platinum based chemotherapy. There is significant interest in clinically applicable, easy to use prognostic tools to estimate risk of recurrence and overall survival. In this study we used a large prospectively collected cohort of women with EOC to validate currently published models and assess prognostic variables. Methods Women with invasive ovarian, peritoneal, or fallopian tube cancer diagnosed between 2000-2011 and prospectively enrolled into the Mayo Clinic Ovarian Cancer registry were identified. Demographics and known prognostic markers as well as epidemiologic exposure variables were abstracted from the medical record and collected via questionnaire. Six previously published models of overall and recurrence-free survival were assessed for external validity. In addition, predictors of outcome were assessed in our dataset. Results Previously published models validated with a range of c-statistics (0.587-0.827), though application of models containing variables not part of routine practice were somewhat limited by missing data; utilization of all applicable models and comparison of results is suggested. Examination of prognostic variables identified only the presence of ascites and ASA score to be independent predictors of prognosis in our dataset, albeit with marginal gain in prognostic information, after accounting for stage and debulking. Conclusions Existing prognostic models for newly diagnosed EOC showed acceptable calibration in our cohort for clinical application. However, modeling of prospective variables in our dataset reiterates that stage and debulking remain the most important predictors of prognosis in this setting. PMID:25620544

Improving prediction of recanalization in acute large-vessel occlusive stroke.

PubMed

Vanacker, P; Lambrou, D; Eskandari, A; Maeder, P; Meuli, R; Ntaios, G; Michel, P

2014-06-01

Recanalization in acute ischemic stroke with large-vessel occlusion is a potent indicator of good clinical outcome. To identify easily available clinical and radiologic variables predicting recanalization at various occlusion sites. All consecutive, acute stroke patients from the Acute STroke Registry and Analysis of Lausanne (2003-2011) who had a large-vessel occlusion on computed tomographic angiography (CTA) (< 12 h) were included. Recanalization status was assessed at 24 h (range: 12-48 h) with CTA, magnetic resonance angiography, or ultrasonography. Complete and partial recanalization (corresponding to the modified Treatment in Cerebral Ischemia scale 2-3) were grouped together. Patients were categorized according to occlusion site and treatment modality. Among 439 patients, 51% (224) showed complete or partial recanalization. In multivariate analysis, recanalization of any occlusion site was most strongly associated with endovascular treatment, including bridging therapy (odds ratio [OR] 7.1, 95% confidence interval [CI] 2.2-23.2), and less so with intravenous thrombolysis (OR 1.6, 95% CI 1.0-2.6) and recanalization treatments performed beyond guidelines (OR 2.6, 95% CI 1.2-5.7). Clot location (large vs. intermediate) and tandem pathology (the combination of intracranial occlusion and symptomatic extracranial stenosis) were other variables discriminating between recanalizers and non-recanalizers. For patients with intracranial occlusions, the variables significantly associated with recanalization after 24 h were: baseline National Institutes of Health Stroke Scale (NIHSS) (OR 1.04, 95% CI 1.02-1.1), Alberta Stroke Program Early CT Score (ASPECTS) on initial computed tomography (OR 1.2, 95% CI 1.1-1.3), and an altered level of consciousness (OR 0.2, 95% CI 0.1-0.5). Acute endovascular treatment is the single most important factor promoting recanalization in acute ischemic stroke. The presence of extracranial vessel stenosis or occlusion decreases recanalization rates. In patients with intracranial occlusions, higher NIHSS score and ASPECTS and normal vigilance facilitate recanalization. Clinical use of these predictors could influence recanalization strategies in individual patients. © 2014 International Society on Thrombosis and Haemostasis.

Between-Batch Pharmacokinetic Variability Inflates Type I Error Rate in Conventional Bioequivalence Trials: A Randomized Advair Diskus Clinical Trial.

PubMed

Burmeister Getz, E; Carroll, K J; Mielke, J; Benet, L Z; Jones, B

2017-03-01

We previously demonstrated pharmacokinetic differences among manufacturing batches of a US Food and Drug Administration (FDA)-approved dry powder inhalation product (Advair Diskus 100/50) large enough to establish between-batch bio-inequivalence. Here, we provide independent confirmation of pharmacokinetic bio-inequivalence among Advair Diskus 100/50 batches, and quantify residual and between-batch variance component magnitudes. These variance estimates are used to consider the type I error rate of the FDA's current two-way crossover design recommendation. When between-batch pharmacokinetic variability is substantial, the conventional two-way crossover design cannot accomplish the objectives of FDA's statistical bioequivalence test (i.e., cannot accurately estimate the test/reference ratio and associated confidence interval). The two-way crossover, which ignores between-batch pharmacokinetic variability, yields an artificially narrow confidence interval on the product comparison. The unavoidable consequence is type I error rate inflation, to ∼25%, when between-batch pharmacokinetic variability is nonzero. This risk of a false bioequivalence conclusion is substantially higher than asserted by regulators as acceptable consumer risk (5%). © 2016 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of The American Society for Clinical Pharmacology and Therapeutics.

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.

The inter-rater reliability of estimating the size of burns from various burn area chart drawings.

PubMed

Wachtel, T L; Berry, C C; Wachtel, E E; Frank, H A

2000-03-01

The accuracy and variability of burn size calculations using four Lund and Browder charts currently in clinical use and two Rule of Nine's diagrams were evaluated. The study showed that variability in estimation increased with burn size initially, plateaued in large burns and then decreased slightly in extensive burns. The Rule of Nine's technique often overestimates the burn size and is more variable, but can be performed somewhat faster than the Lund and Browder method. More burn experience leads to less variability in burn area chart drawing estimates. Irregularly shaped burns and burns on the trunk and thighs had greater variability than less irregularly shaped burns or burns on more defined anatomical parts of the body.

Patterns and Predictors of Tic Suppressibility in Youth With Tic Disorders

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-01-01

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

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.

Emotional intelligence, performance, and retention in clinical staff nurses.

PubMed

Codier, Estelle; Kamikawa, Cindy; Kooker, Barbara M; Shoultz, Jan

2009-01-01

Emotional intelligence has been correlated with performance, retention, and organizational commitment in professions other than nursing. A 2006 pilot study provided the first evidence of a correlation between emotional intelligence and performance in clinical staff nurses. A follow-up study was completed, the purpose of which was to explore emotional intelligence, performance level, organizational commitment, and retention. A convenience sample of 350 nurses in a large medical center in urban Hawaii participated in this study. This article reports the findings pertaining to the subset of 193 clinical staff nurses who responded. The Mayer-Salovey-Caruso Emotional Intelligence Test instrument was used to measure emotional intelligence abilities. Performance was defined as ranking on a clinical ladder. Commitment was scored on a Likert scale. The following variables measured retention: total years in nursing, years in current job, total years anticipated in current job, and total anticipated career length. Emotional intelligence scores in clinical staff nurses correlated positively with both performance level and retention variables. Clinical staff nurses with higher emotional intelligence scores demonstrated higher performance, had longer careers, and greater job retention.

Mechanisms of Disease and Clinical Features of Mutations of the Gene for Mitofusin 2: An Important Cause of Hereditary Peripheral Neuropathy with Striking Clinical Variability in Children and Adults

ERIC Educational Resources Information Center

Ouvrier, Robert; Grew, Simon

2010-01-01

Mitofusin 2, a large transmembrane GTPase located in the outer mitochondrial membrane, promotes membrane fusion and is involved in the maintenance of the morphology of axonal mitochondria. Mutations of the gene encoding mitofusin 2 ("MFN2") have recently been identified as the cause of approximately one-third of dominantly inherited cases of the…

[Personalized drug therapy-directed clinical pharmacology research based on genetic polymorphisms and pharmacokinetics analysis].

PubMed

Hayashi, Hideki

2013-01-01

In this decade, the field of pharmacogenomics (PGx), which is related to pharmacokinetics (PK) or pharmacodynamics (PD), has attracted much attention because it may provide a possible explanation for individual differences in the clinical efficacy of drugs. For the development of personalized drug therapy, it is important to accumulate evidence from PK/PD/PGx analysis in clinical trials. Warfarin (WF) is one of the most widely prescribed anticoagulants for the prevention and treatment of venous and arterial thromboembolism. However, large interindividual and interethnic differences have been observed in the WF dose required to elicit the anticoagulant effect. We investigated the factors influencing the WF maintenance dose in Japanese patients. Our study confirmed a large interindividual variability in the WF maintenance dose that was due to a VKORC1 1639 G>A polymorphism and differences in body weight, age, and serum albumin. In addition, we found that the CYP4F2 genotype affects the plasma concentration of menaquinone-4, and that this finding was correlated with the WF sensitivity index in Japanese pediatric patients. Methotrexate (MTX) is an antifolate that is widely used to treat rheumatoid arthritis (RA) and cancer. The response to low-dose MTX demonstrated wide interpatient variability; however, the contributing factors remain unclear. We found that the frequency of the RFC1 80A allele was higher in RA patients treated with MTX alone compared with patients who received biological disease-modifying antirheumatic drugs (bDMARDs). This finding may support the combined use of bDMARDs and MTX. Further large-scale prospective clinical trials are required to confirm these findings.

Clinical supervision, emotional exhaustion, and turnover intention: a study of substance abuse treatment counselors in the Clinical Trials Network of the National Institute on Drug Abuse.

PubMed

Knudsen, Hannah K; Ducharme, Lori J; Roman, Paul M

2008-12-01

An intriguing hypothesis is that clinical supervision may protect against counselor turnover. This idea has been mentioned in recent discussions of the substance abuse treatment workforce. To test this hypothesis, we extend our previous research on emotional exhaustion and turnover intention among counselors by estimating the associations between clinical supervision and these variables in a large sample (N = 823). An exploratory analysis reveals that clinical supervision was negatively associated with emotional exhaustion and turnover intention. Given our previous findings that emotional exhaustion and turnover intention were associated with job autonomy, procedural justice, and distributive justice, we estimate a structural equation model to examine whether these variables mediated clinical supervision's associations with emotional exhaustion and turnover intention. These data support the fully mediated model. We found that the perceived quality of clinical supervision is strongly associated with counselors' perceptions of job autonomy, procedural justice, and distributive justice, which are, in turn, associated with emotional exhaustion and turnover intention. These data offer support for the protective role of clinical supervision in substance abuse treatment counselors' turnover and occupational well-being.

Predictors of large esophageal varices in patients with cirrhosis.

PubMed

Chalasani, N; Imperiale, T F; Ismail, A; Sood, G; Carey, M; Wilcox, C M; Madichetty, H; Kwo, P Y; Boyer, T D

1999-11-01

Recent guidelines recommend that all cirrhotics undergo screening upper endoscopy to identify those patients at risk for bleeding from varices. However, this practice may not be cost effective as large esophageal varices are seen only in 9-36% of these patients. The aim of this study was to determine whether clinical variables were predictive of the presence of large esophageal varices. This is a retrospective analysis of cirrhotics who had a screening upper endoscopy during an evaluation for liver transplantation at three different centers and who had not previously bled from varices. A multivariate model was derived on the combined cohort using logistic regression. Three hundred forty-six patients were eligible for the study. The prevalence of large esophageal varices was 20%. On multivariate analysis, splenomegaly detected by computed tomographic scan (odds ratio: 4.3; 95% confidence interval: 1.6-11.5) or by physical examination (odds ratio: 2.0; 95% confidence interval: 1.1-3.8), and low platelet count were independent predictors of large esophageal varices. On the basis of these variables, cirrhotics were stratified into high- and low-risk groups for the presence of large esophageal varices. Patients with a platelet count of > or = 88,000/mm3 (median value) and no splenomegaly by physical examination had a risk of large esophageal varices of 7.2%. Those with splenomegaly or platelet count < 88,000/mm3 had a risk of large esophageal varices of 28% (p < 0.0001). Our data show that clinical predictors could be used to stratify cirrhotic patients for the risk of large esophageal varices and such stratification could be used to improve the cost effectiveness of screening endoscopy.

Posterior composite restoration update: focus on factors influencing form and function

PubMed Central

Bohaty, Brenda S; Ye, Qiang; Misra, Anil; Sene, Fabio; Spencer, Paulette

2013-01-01

Restoring posterior teeth with resin-based composite materials continues to gain popularity among clinicians, and the demand for such aesthetic restorations is increasing. Indeed, the most common aesthetic alternative to dental amalgam is resin composite. Moderate to large posterior composite restorations, however, have higher failure rates, more recurrent caries, and increased frequency of replacement. Investigators across the globe are researching new materials and techniques that will improve the clinical performance, handling characteristics, and mechanical and physical properties of composite resin restorative materials. Despite such attention, large to moderate posterior composite restorations continue to have a clinical lifetime that is approximately one-half that of the dental amalgam. While there are numerous recommendations regarding preparation design, restoration placement, and polymerization technique, current research indicates that restoration longevity depends on several variables that may be difficult for the dentist to control. These variables include the patient’s caries risk, tooth position, patient habits, number of restored surfaces, the quality of the tooth–restoration bond, and the ability of the restorative material to produce a sealed tooth–restoration interface. Although clinicians tend to focus on tooth form when evaluating the success and failure of posterior composite restorations, the emphasis must remain on advancing our understanding of the clinical variables that impact the formation of a durable seal at the restoration–tooth interface. This paper presents an update of existing technology and underscores the mechanisms that negatively impact the durability of posterior composite restorations in permanent teeth. PMID:23750102

Clinical Usefulness of Response Profiles to Rapidly Incremental Cardiopulmonary Exercise Testing

PubMed Central

Ramos, Roberta P.; Alencar, Maria Clara N.; Treptow, Erika; Arbex, Flávio; Ferreira, Eloara M. V.; Neder, J. Alberto

2013-01-01

The advent of microprocessed “metabolic carts” and rapidly incremental protocols greatly expanded the clinical applications of cardiopulmonary exercise testing (CPET). The response normalcy to CPET is more commonly appreciated at discrete time points, for example, at the estimated lactate threshold and at peak exercise. Analysis of the response profiles of cardiopulmonary responses at submaximal exercise and recovery, however, might show abnormal physiologic functioning which would not be otherwise unraveled. Although this approach has long been advocated as a key element of the investigational strategy, it remains largely neglected in practice. The purpose of this paper, therefore, is to highlight the usefulness of selected submaximal metabolic, ventilatory, and cardiovascular variables in different clinical scenarios and patient populations. Special care is taken to physiologically justify their use to answer pertinent clinical questions and to the technical aspects that should be observed to improve responses' reproducibility and reliability. The most recent evidence in favor of (and against) these variables for diagnosis, impairment evaluation, and prognosis in systemic diseases is also critically discussed. PMID:23766901

Stress-based animal models of depression: Do we actually know what we are doing?

PubMed

Yin, Xin; Guven, Nuri; Dietis, Nikolas

2016-12-01

Depression is one of the leading causes of disability and a significant health-concern worldwide. Much of our current understanding on the pathogenesis of depression and the pharmacology of antidepressant drugs is based on pre-clinical models. Three of the most popular stress-based rodent models are the forced swimming test, the chronic mild stress paradigm and the learned helplessness model. Despite their recognizable advantages and limitations, they are associated with an immense variability due to the high number of design parameters that define them. Only few studies have reported how minor modifications of these parameters affect the model phenotype. Thus, the existing variability in how these models are used has been a strong barrier for drug development as well as benchmark and evaluation of these pre-clinical models of depression. It also has been the source of confusing variability in the experimental outcomes between research groups using the same models. In this review, we summarize the known variability in the experimental protocols, identify the main and relevant parameters for each model and describe the variable values using characteristic examples. Our view of depression and our efforts to discover novel and effective antidepressants is largely based on our detailed knowledge of these testing paradigms, and requires a sound understanding around the importance of individual parameters to optimize and improve these pre-clinical models. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Associations between mood instability and emotional processing in a large cohort of bipolar patients.

PubMed

Bilderbeck, A C; Reed, Z E; McMahon, H C; Atkinson, L Z; Price, J; Geddes, J R; Goodwin, G M; Harmer, C J

2016-11-01

Aberrant emotional biases have been reported in bipolar disorder (BD), but results are inconsistent. Despite the clinical relevance of chronic mood variability in BD, there is no previous research investigating how the extent of symptom fluctuations in bipolar disorder might relate to emotional biases. This exploratory study investigated, in a large cohort of bipolar patients, whether instability in weekly mood episode symptoms and other clinical and demographic factors were related to emotional bias as measured in a simple laboratory task. Participants (N = 271, BDI = 206, BDII = 121) completed an 'emotional categorization and memory' task. Weekly self-reported symptoms of depression and mania were collected prospectively. In linear regression analyses, associations between cognitive bias and mood variability were explored together with the influence of demographic and clinical factors, including current medication. Greater accuracy in the classification of negative words relative to positive words was associated with greater instability in depressive symptoms. Furthermore, greater negative bias in free recall was associated with higher instability in manic symptoms. Participants diagnosed with BDII, compared with BDI, showed overall better word recognition and recall. Current antipsychotic use was associated with reduced instability in manic symptoms but this did not impact on emotional processing performance. Emotional processing biases in bipolar disorder are related to instability in mood. These findings prompt further investigation into the underpinnings as well as clinical significance of mood instability.

Designed experiment evaluation of key variables affecting the cutting performance of rotary instruments.

PubMed

Funkenbusch, Paul D; Rotella, Mario; Ercoli, Carlo

2015-04-01

Laboratory studies of tooth preparation are often performed under a limited range of conditions involving single values for all variables other than the 1 being tested. In contrast, in clinical settings not all variables can be tightly controlled. For example, a new dental rotary cutting instrument may be tested in the laboratory by making a specific cut with a fixed force, but in clinical practice, the instrument must make different cuts with individual dentists applying a range of different forces. Therefore, the broad applicability of laboratory results to diverse clinical conditions is uncertain and the comparison of effects across studies is difficult. The purpose of this study was to examine the effect of 9 process variables on dental cutting in a single experiment, allowing each variable to be robustly tested over a range of values for the other 8 and permitting a direct comparison of the relative importance of each on the cutting process. The effects of 9 key process variables on the efficiency of a simulated dental cutting operation were measured. A fractional factorial experiment was conducted by using a computer-controlled, dedicated testing apparatus to simulate dental cutting procedures and Macor blocks as the cutting substrate. Analysis of Variance (ANOVA) was used to judge the statistical significance (α=.05). Five variables consistently produced large, statistically significant effects (target applied load, cut length, starting rpm, diamond grit size, and cut type), while 4 variables produced relatively small, statistically insignificant effects (number of cooling ports, rotary cutting instrument diameter, disposability, and water flow rate). The control exerted by the dentist, simulated in this study by targeting a specific level of applied force, was the single most important factor affecting cutting efficiency. Cutting efficiency was also significantly affected by factors simulating patient/clinical circumstances as well as hardware choices. These results highlight the importance of local clinical conditions (procedure, dentist) in understanding dental cutting procedures and in designing adequate experimental methodologies for future studies. Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

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.

The Use of Multiple Correspondence Analysis to Explore Associations between Categories of Qualitative Variables in Healthy Ageing.

PubMed

Costa, Patrício Soares; Santos, Nadine Correia; Cunha, Pedro; Cotter, Jorge; Sousa, Nuno

2013-01-01

The main focus of this study was to illustrate the applicability of multiple correspondence analysis (MCA) in detecting and representing underlying structures in large datasets used to investigate cognitive ageing. Principal component analysis (PCA) was used to obtain main cognitive dimensions, and MCA was used to detect and explore relationships between cognitive, clinical, physical, and lifestyle variables. Two PCA dimensions were identified (general cognition/executive function and memory), and two MCA dimensions were retained. Poorer cognitive performance was associated with older age, less school years, unhealthier lifestyle indicators, and presence of pathology. The first MCA dimension indicated the clustering of general/executive function and lifestyle indicators and education, while the second association was between memory and clinical parameters and age. The clustering analysis with object scores method was used to identify groups sharing similar characteristics. The weaker cognitive clusters in terms of memory and executive function comprised individuals with characteristics contributing to a higher MCA dimensional mean score (age, less education, and presence of indicators of unhealthier lifestyle habits and/or clinical pathologies). MCA provided a powerful tool to explore complex ageing data, covering multiple and diverse variables, showing if a relationship exists and how variables are related, and offering statistical results that can be seen both analytically and visually.

Organizational technologies of chronic disease management programs in large rural multispecialty group practice systems.

PubMed

Gamm, Larry; Bolin, Jane Nelson; Kash, Bita A

2005-01-01

Four large rural multispecialty group practice systems employ a mix of organizational technologies to provide chronic disease management with measurable impacts on their patient populations and costs. Four technologies-administrative, clinical, information, and social-are proposed as key dimensions for examining disease management programs. The benefits of disease management are recognized by these systems despite marked variability in the organization of the programs. Committees spanning health plans and clinics in the 4 systems and electronic medical records and/or other disease management information systems are important coordinating mechanisms. Increased reliance on nurses for patient education and care coordination in all 4 systems reflects significant extension of clinical and social technologies in the management of patient care. The promise of disease management as offered by these systems and other auspices are considered.

Variability in clinical prevalence of PaV1 in Caribbean spiny lobsters occupying commercial casitas over a large bay in Mexico.

PubMed

Candia-Zulbarán, Rebeca I; Briones-Fourzán, Patricia; Negrete-Soto, Fernando; Barradas-Ortiz, Cecilia; Lozano-Álvarez, Enrique

2012-08-27

In Bahía de la Ascensión, Mexico, the fishery for spiny lobsters Panulirus argus is based on the extensive use of casitas, large artificial shelters that can harbor the full size range of these highly gregarious lobsters. The discovery of a pathogenic virus in these lobsters (Panulirus argus virus 1, or PaV1) has raised concern about its potential effects on casita-based fisheries. Because in Bahía de la Ascensión visibly infected lobsters represent an immediate loss of revenue, we examined variability in clinical prevalence of PaV1 (percentage of lobsters visibly infected) in thousands of lobsters sampled from the commercial catch at the onset of 3 consecutive fishing years, and from 530 casitas distributed over 3 zones within the bay during 2 fishing and 2 closed seasons. In the commercial catch (lobsters 67 to 147 mm carapace length [CL]), clinical prevalence of PaV1 was low and was not affected by year or sex. In lobsters (9.2 to 115.0 mm CL) that occupied casitas, clinical prevalence of PaV1 varied with sampling season and was always higher in juveniles than in subadults or adults, but was consistently lower in one zone relative to the other 2 zones. The average clinical prevalence of PaV1 in this bay was statistically similar to the average clinical prevalence reported in Cuba, where casitas are also used, and in Florida Bay, USA, where casitas are not used. To date, PaV1 has had no discernible impact on the lobster fishery in Bahía de la Ascensión, suggesting that clinical prevalence is not influenced by the use of casitas per se.

Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.

PubMed

Rakha, E A; Soria, D; Green, A R; Lemetre, C; Powe, D G; Nolan, C C; Garibaldi, J M; Ball, G; Ellis, I O

2014-04-02

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes. Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

NASA Astrophysics Data System (ADS)

Fatehullah, A.; Sharma, S.; Newton, I. P.; Langlands, A. J.; Lay, H.; Nelson, S. A.; McMahon, R. K.; McIlvenny, N.; Appleton, P. L.; Cochran, S.; Näthke, I. S.

2016-07-01

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.

Variability in objective and subjective measures affects baseline values in studies of patients with COPD

PubMed Central

Ha, Jae Wook; Couper, David J.; O’Neal, Wanda K.; Barr, R. Graham; Bleecker, Eugene R.; Carretta, Elizabeth E.; Cooper, Christopher B.; Doerschuk, Claire M.; Drummond, M Bradley; Han, MeiLan K.; Hansel, Nadia N.; Kim, Victor; Kleerup, Eric C.; Martinez, Fernando J.; Rennard, Stephen I.; Tashkin, Donald; Woodruff, Prescott G.; Paine, Robert; Curtis, Jeffrey L.; Kanner, Richard E.

2017-01-01

Rationale Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety. Objectives Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes. Methods Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same period. We utilized SPIROMICS participants (n = 98) that returned to their clinical center within 6 weeks of their baseline visit to repeat complete baseline assessments. Demographics, spirometry, questionnaires, complete blood cell counts (CBC), medical history, and emphysema status by computerized tomography (CT) imaging were obtained. Results Pulmonary function tests (PFTs) were highly repeatable (ICC’s >0.9) but the 6 minute walk (6MW) was less so (ICC = 0.79). Among questionnaires, the Saint George’s Respiratory Questionnaire (SGRQ) was most repeatable. Self-reported clinical features, such as exacerbation history, and features of chronic bronchitis, often produced kappa values <0.6. Reported age at starting smoking and average number of cigarettes smoked were modestly repeatable (kappa = 0.76 and 0.79). Complete blood counts (CBC) variables produced intraclass correlation coefficients (ICC) values between 0.6 and 0.8. Conclusions PFTs were highly repeatable, while subjective measures and subject recall were more variable. Analyses using features with poor repeatability could lead to misclassification and outcome errors. Hence, care should be taken when interpreting change in clinical features based on measures with low repeatability. Efforts to improve repeatability of key clinical features such as exacerbation history and chronic bronchitis are warranted. PMID:28934249

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.

Service and Education: The Association Between Workload, Patient Complexity, and Teaching on Internal Medicine Inpatient Services.

PubMed

Ratcliffe, Temple A; Crabtree, Meghan A; Palmer, Raymond F; Pugh, Jacqueline A; Lanham, Holly J; Leykum, Luci K

2018-04-01

Attending rounds remain the primary venue for formal teaching and learning at academic medical centers. Little is known about the effect of increasing clinical demands on teaching during attending rounds. To explore the relationships among teaching time, teaching topics, clinical workload, and patient complexity variables. Observational study of medicine teaching teams from September 2008 through August 2014. Teams at two large teaching hospitals associated with a single medical school were observed for periods of 2 to 4 weeks. Twelve medicine teaching teams consisting of one attending, one second- or third-year resident, two to three interns, and two to three medical students. The study examined relationships between patient complexity (comorbidities, complications) and clinical workload variables (census, turnover) with educational measures. Teams were clustered based on clinical workload and patient complexity. Educational measures of interest were time spent teaching and number of teaching topics. Data were analyzed both at the daily observation level and across a given patient's admission. We observed 12 teams, 1994 discussions (approximately 373 h of rounds) of 563 patients over 244 observation days. Teams clustered into three groups: low patient complexity/high clinical workload, average patient complexity/low clinical workload, and high patient complexity/high clinical workload. Modest associations for team, patient complexity, and clinical workload variables were noted with total time spent teaching (9.1% of the variance in time spent teaching during a patient's admission; F[8,549] = 6.90, p < 0.001) and number of teaching topics (16% of the variance in the total number of teaching topics during a patient's admission; F[8,548] = 14.18, p < 0.001). Clinical workload and patient complexity characteristics among teams were only modestly associated with total teaching time and teaching topics.

Effects of sources of variability on sample sizes required for RCTs, applied to trials of lipid-altering therapies on carotid artery intima-media thickness.

PubMed

Gould, A Lawrence; Koglin, Joerg; Bain, Raymond P; Pinto, Cathy-Anne; Mitchel, Yale B; Pasternak, Richard C; Sapre, Aditi

2009-08-01

Studies measuring progression of carotid artery intima-media thickness (cIMT) have been used to estimate the effect of lipid-modifying therapies cardiovascular event risk. The likelihood that future cIMT clinical trials will detect a true treatment effect is estimated by leveraging results from prior studies. The present analyses assess the impact of between- and within-study variability based on currently published data from prior clinical studies on the likelihood that ongoing or future cIMT trials will detect the true treatment effect of lipid-modifying therapies. Published data from six contemporary cIMT studies (ASAP, ARBITER 2, RADIANCE 1, RADIANCE 2, ENHANCE, and METEOR) including data from a total of 3563 patients were examined. Bayesian and frequentist methods were used to assess the impact of between study variability on the likelihood of detecting true treatment effects on 1-year cIMT progression/regression and to provide a sample size estimate that would specifically compensate for the effect of between-study variability. In addition to the well-described within-study variability, there is considerable between-study variability associated with the measurement of annualized change in cIMT. Accounting for the additional between-study variability decreases the power for existing study designs. In order to account for the added between-study variability, it is likely that future cIMT studies would require a large increase in sample size in order to provide substantial probability (> or =90%) to have 90% power of detecting a true treatment effect.Limitation Analyses are based on study level data. Future meta-analyses incorporating patient-level data would be useful for confirmation. Due to substantial within- and between-study variability in the measure of 1-year change of cIMT, as well as uncertainty about progression rates in contemporary populations, future study designs evaluating the effect of new lipid-modifying therapies on atherosclerotic disease progression are likely to be challenged by large sample sizes in order to demonstrate a true treatment effect.

Planning performance in schizophrenia patients: a meta-analysis of the influence of task difficulty and clinical and sociodemographic variables.

PubMed

Knapp, F; Viechtbauer, W; Leonhart, R; Nitschke, K; Kaller, C P

2017-08-01

Despite a large body of research on planning performance in adult schizophrenia patients, results of individual studies are equivocal, suggesting either no, moderate or severe planning deficits. This meta-analysis therefore aimed to quantify planning deficits in schizophrenia and to examine potential sources of the heterogeneity seen in the literature. The meta-analysis comprised outcomes of planning accuracy of 1377 schizophrenia patients and 1477 healthy controls from 31 different studies which assessed planning performance using tower tasks such as the Tower of London, the Tower of Hanoi and the Stockings of Cambridge. A meta-regression analysis was applied to assess the influence of potential moderator variables (i.e. sociodemographic and clinical variables as well as task difficulty). The findings indeed demonstrated a planning deficit in schizophrenia patients (mean effect size: ; 95% confidence interval 0.56-0.78) that was moderated by task difficulty in terms of the minimum number of moves required for a solution. The results did not reveal any significant relationship between the extent of planning deficits and sociodemographic or clinical variables. The current results provide first meta-analytic evidence for the commonly assumed impairments of planning performance in schizophrenia. Deficits are more likely to become manifest in problem items with higher demands on planning ahead, which may at least partly explain the heterogeneity of previous findings. As only a small fraction of studies reported coherent information on sample characteristics, future meta-analyses would benefit from more systematic reports on those variables.

Update on the therapy of Behçet disease

PubMed Central

Saleh, Zeinab

2014-01-01

Behçet disease is a chronic inflammatory systemic disorder, characterized by a relapsing and remitting course. It manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. The main histopathological finding is a widespread vasculitis of the arteries and veins of any size. The cause of this disease is presumed to be multifactorial involving infectious triggers, genetic predisposition, and dysregulation of the immune system. As the clinical expression of Behçet disease is heterogeneous, pharmacological therapy is variable and depends largely on the severity of the disease and organ involvement. Treatment of Behçet disease continues to be based largely on anecdotal case reports, case series, and a few randomized clinical trials. PMID:24790727

Sci-Sat AM: Radiation Dosimetry and Practical Therapy Solutions - 12: Suitability of plan class specific reference fields for estimating dosimeter correction factors for small clinical CyberKnife fields

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

Vandervoort, Eric; Christiansen, Eric; Belec, Jaso

Purpose: The purpose of this work is to investigate the utility of plan class specific reference (PCSR) fields for predicting dosimeter response within isocentric and non-isocentric composite clinical fields using the smallest fields employed by the CyberKnife radiosurgery system. Methods: Monte Carlo dosimeter response correction factors (CFs) were calculated for a plastic scintillator and microchamber dosimeter in 21 clinical fields and 9 candidate plan-class PCSR fields which employ the 5, 7.5 and 10 mm diameter collimators. Measurements were performed in 5 PCSR fields to confirm the predicted relative response of detectors in the same field. Results: Ratios of corrected measuredmore » dose in the PCSR fields agree to within 1% of unity. Calculated CFs for isocentric fields agree within 1.5% of those for PCSR fields. Large and variable microchamber CFs are required for non-isocentric fields, with differences as high as 5% between different clinical fields in the same plan class and 4% within the same field depending on the point of measurement. Non-isocentric PCSR fields constructed to have relatively homogenous dose over a region larger than the detector have very different ion chamber CFs from clinical fields. The plastic scintillator detector has much more consistent response within each plan class but still require 3–4% corrections in some fields. Conclusions: While the PCSR field concept is useful for small isocentric fields, this approach may not be appropriate for non-isocentric clinical fields which exhibit large and variable ion chamber CFs which differ significantly from CFs for homogenous field PCSRs.« less

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

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.

Longitudinal multiple imputation approaches for body mass index or other variables with very low individual-level variability: the mibmi command in Stata.

PubMed

Kontopantelis, Evangelos; Parisi, Rosa; Springate, David A; Reeves, David

2017-01-13

In modern health care systems, the computerization of all aspects of clinical care has led to the development of large data repositories. For example, in the UK, large primary care databases hold millions of electronic medical records, with detailed information on diagnoses, treatments, outcomes and consultations. Careful analyses of these observational datasets of routinely collected data can complement evidence from clinical trials or even answer research questions that cannot been addressed in an experimental setting. However, 'missingness' is a common problem for routinely collected data, especially for biological parameters over time. Absence of complete data for the whole of a individual's study period is a potential bias risk and standard complete-case approaches may lead to biased estimates. However, the structure of the data values makes standard cross-sectional multiple-imputation approaches unsuitable. In this paper we propose and evaluate mibmi, a new command for cleaning and imputing longitudinal body mass index data. The regression-based data cleaning aspects of the algorithm can be useful when researchers analyze messy longitudinal data. Although the multiple imputation algorithm is computationally expensive, it performed similarly or even better to existing alternatives, when interpolating observations. The mibmi algorithm can be a useful tool for analyzing longitudinal body mass index data, or other longitudinal data with very low individual-level variability.

The Depression Anxiety Stress Scales (DASS): normative data and latent structure in a large non-clinical sample.

PubMed

Crawford, John R; Henry, Julie D

2003-06-01

To provide UK normative data for the Depression Anxiety and Stress Scale (DASS) and test its convergent, discriminant and construct validity. Cross-sectional, correlational and confirmatory factor analysis (CFA). The DASS was administered to a non-clinical sample, broadly representative of the general adult UK population (N = 1,771) in terms of demographic variables. Competing models of the latent structure of the DASS were derived from theoretical and empirical sources and evaluated using confirmatory factor analysis. Correlational analysis was used to determine the influence of demographic variables on DASS scores. The convergent and discriminant validity of the measure was examined through correlating the measure with two other measures of depression and anxiety (the HADS and the sAD), and a measure of positive and negative affectivity (the PANAS). The best fitting model (CFI =.93) of the latent structure of the DASS consisted of three correlated factors corresponding to the depression, anxiety and stress scales with correlated error permitted between items comprising the DASS subscales. Demographic variables had only very modest influences on DASS scores. The reliability of the DASS was excellent, and the measure possessed adequate convergent and discriminant validity Conclusions: The DASS is a reliable and valid measure of the constructs it was intended to assess. The utility of this measure for UK clinicians is enhanced by the provision of large sample normative data.

An Introduction to Recursive Partitioning: Rationale, Application, and Characteristics of Classification and Regression Trees, Bagging, and Random Forests

ERIC Educational Resources Information Center

Strobl, Carolin; Malley, James; Tutz, Gerhard

2009-01-01

Recursive partitioning methods have become popular and widely used tools for nonparametric regression and classification in many scientific fields. Especially random forests, which can deal with large numbers of predictor variables even in the presence of complex interactions, have been applied successfully in genetics, clinical medicine, and…

The Behavioural Phenotype of Cornelia de Lange Syndrome: A Study of 56 Individuals

ERIC Educational Resources Information Center

Basile, Emanuele; Villa, L.; Selicorni, A.; Molteni, M.

2007-01-01

Background: Few studies have investigated functional and behavioural variables of Cornelia de Lange Syndrome (CdLS) in a large sample of individuals. The aim of this study is to provide greater insight into the clinical, behavioural and cognitive characteristics that are associated with CdLS. Methods: In total, 56 individuals with CdLS…

Ratio index variables or ANCOVA? Fisher's cats revisited.

PubMed

Tu, Yu-Kang; Law, Graham R; Ellison, George T H; Gilthorpe, Mark S

2010-01-01

Over 60 years ago Ronald Fisher demonstrated a number of potential pitfalls with statistical analyses using ratio variables. Nonetheless, these pitfalls are largely overlooked in contemporary clinical and epidemiological research, which routinely uses ratio variables in statistical analyses. This article aims to demonstrate how very different findings can be generated as a result of less than perfect correlations among the data used to generate ratio variables. These imperfect correlations result from measurement error and random biological variation. While the former can often be reduced by improvements in measurement, random biological variation is difficult to estimate and eliminate in observational studies. Moreover, wherever the underlying biological relationships among epidemiological variables are unclear, and hence the choice of statistical model is also unclear, the different findings generated by different analytical strategies can lead to contradictory conclusions. Caution is therefore required when interpreting analyses of ratio variables whenever the underlying biological relationships among the variables involved are unspecified or unclear. (c) 2009 John Wiley & Sons, Ltd.

Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.

PubMed

Cobb, J; Cule, E; Moncrieffe, H; Hinks, A; Ursu, S; Patrick, F; Kassoumeri, L; Flynn, E; Bulatović, M; Wulffraat, N; van Zelst, B; de Jonge, R; Bohm, M; Dolezalova, P; Hirani, S; Newman, S; Whitworth, P; Southwood, T R; De Iorio, M; Wedderburn, L R; Thomson, W

2014-08-01

Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.

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.

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.

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.

TU-AB-BRA-04: Quantitative Radiomics: Sensitivity of PET Textural Features to Image Acquisition and Reconstruction Parameters Implies the Need for Standards

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

Nyflot, MJ; Yang, F; Byrd, D

Purpose: Despite increased use of heterogeneity metrics for PET imaging, standards for metrics such as textural features have yet to be developed. We evaluated the quantitative variability caused by image acquisition and reconstruction parameters on PET textural features. Methods: PET images of the NEMA IQ phantom were simulated with realistic image acquisition noise. 35 features based on intensity histograms (IH), co-occurrence matrices (COM), neighborhood-difference matrices (NDM), and zone-size matrices (ZSM) were evaluated within lesions (13, 17, 22, 28, 33 mm diameter). Variability in metrics across 50 independent images was evaluated as percent difference from mean for three phantom girths (850,more » 1030, 1200 mm) and two OSEM reconstructions (2 iterations, 28 subsets, 5 mm FWHM filtration vs 6 iterations, 28 subsets, 8.6 mm FWHM filtration). Also, patient sample size to detect a clinical effect of 30% with Bonferroni-corrected α=0.001 and 95% power was estimated. Results: As a class, NDM features demonstrated greatest sensitivity in means (5–50% difference for medium girth and reconstruction comparisons and 10–100% for large girth comparisons). Some IH features (standard deviation, energy, entropy) had variability below 10% for all sensitivity studies, while others (kurtosis, skewness) had variability above 30%. COM and ZSM features had complex sensitivities; correlation, energy, entropy (COM) and zone percentage, short-zone emphasis, zone-size non-uniformity (ZSM) had variability less than 5% while other metrics had differences up to 30%. Trends were similar for sample size estimation; for example, coarseness, contrast, and strength required 12, 38, and 52 patients to detect a 30% effect for the small girth case but 38, 88, and 128 patients in the large girth case. Conclusion: The sensitivity of PET textural features to image acquisition and reconstruction parameters is large and feature-dependent. Standards are needed to ensure that prospective trials which incorporate textural features are properly designed to detect clinical endpoints. Supported by NIH grants R01 CA169072, U01 CA148131, NCI Contract (SAIC-Frederick) 24XS036-004, and a research contract from GE Healthcare.« less

Echocardiography parameters of clinically normal adult captive chimpanzees (Pan troglodytes).

PubMed

Sleeper, Meg M; Drobatz, Ken; Lee, D Richard; Lammey, Michael L

2014-04-15

To generate reference ranges for echocardiographic variables in clinically normal adult chimpanzees (Pan troglodytes). Retrospective cohort study. 88 clinically normal adult chimpanzees. Echocardiographic data obtained between 2002 and 2011 from chimpanzees at the Alamogordo Primate Facility were reviewed (263 echocardiograms obtained from 158 individuals). Data from clinically normal individuals (33 females and 55 males) were analyzed. Basic cardiac parameters measured in all individuals included aortic root diameter and left atrial diameter in the short and long axis during diastole. Left ventricular measurements included left ventricular internal diameter in systole and diastole and diastolic septal and posterior wall thickness. The E point to septal separation was also measured. Spectral Doppler measurements included the peak flow velocity of the pulmonary artery and aorta and diastolic transmitral flow. The presence of arrhythmias was also noted. Standard echocardiographic findings for a large group of adult female and male chimpanzees were obtained. Female and male chimpanzees were grouped by age in 10-year blocks, and echocardiographic findings were analyzed statistically by 10-year block. In male chimpanzees, cardiac arrhythmias were noted to increase with age. Cardiovascular disease is an important cause of morbidity and death in captive chimpanzees; however, basic echocardiographic measurements from a large cohort of clinically normal animals have not previously been reported. The number of animals in the present study was insufficient to generate reference ranges; however, data from a large cohort of clinically normal animals are presented. This information will be useful for veterinarians working in clinical and research settings with this species.

Thomsen or Becker myotonia? A novel autosomal recessive nonsense mutation in the CLCN1 gene associated with a mild phenotype.

PubMed

Gurgel-Giannetti, Juliana; Senkevics, Adriano S; Zilbersztajn-Gotlieb, Dinorah; Yamamoto, Lydia U; Muniz, Viviane P; Pavanello, Rita C M; Oliveira, Acary B; Zatz, Mayana; Vainzof, Mariz

2012-02-01

We describe a large Brazilian consanguineous kindred with 3 clinically affected patients with a Thomsen myotonia phenotype. They carry a novel homozygous nonsense mutation in the CLCN1 gene (K248X). None of the 6 heterozygote carriers show any sign of myotonia on clinical evaluation or electromyography. These findings confirm the autosomal recessive inheritance of the novel mutation in this family, as well as the occurrence of phenotypic variability in the autosomal recessive forms of myotonia. Copyright © 2011 Wiley Periodicals, Inc.

ASTRAL-R score predicts non-recanalisation after intravenous thrombolysis in acute ischaemic stroke.

PubMed

Vanacker, Peter; Heldner, Mirjam R; Seiffge, David; Mueller, Hubertus; Eskandari, Ashraf; Traenka, Christopher; Ntaios, George; Mosimann, Pascal J; Sztajzel, Roman; Mendes Pereira, Vitor; Cras, Patrick; Engelter, Stefan; Lyrer, Philippe; Fischer, Urs; Lambrou, Dimitris; Arnold, Marcel; Michel, Patrik

2015-05-01

Intravenous thrombolysis (IVT) as treatment in acute ischaemic strokes may be insufficient to achieve recanalisation in certain patients. Predicting probability of non-recanalisation after IVT may have the potential to influence patient selection to more aggressive management strategies. We aimed at deriving and internally validating a predictive score for post-thrombolytic non-recanalisation, using clinical and radiological variables. In thrombolysis registries from four Swiss academic stroke centres (Lausanne, Bern, Basel and Geneva), patients were selected with large arterial occlusion on acute imaging and with repeated arterial assessment at 24 hours. Based on a logistic regression analysis, an integer-based score for each covariate of the fitted multivariate model was generated. Performance of integer-based predictive model was assessed by bootstrapping available data and cross validation (delete-d method). In 599 thrombolysed strokes, five variables were identified as independent predictors of absence of recanalisation: Acute glucose > 7 mmol/l (A), significant extracranial vessel STenosis (ST), decreased Range of visual fields (R), large Arterial occlusion (A) and decreased Level of consciousness (L). All variables were weighted 1, except for (L) which obtained 2 points based on β-coefficients on the logistic scale. ASTRAL-R scores 0, 3 and 6 corresponded to non-recanalisation probabilities of 18, 44 and 74 % respectively. Predictive ability showed AUC of 0.66 (95 %CI, 0.61-0.70) when using bootstrap and 0.66 (0.63-0.68) when using delete-d cross validation. In conclusion, the 5-item ASTRAL-R score moderately predicts non-recanalisation at 24 hours in thrombolysed ischaemic strokes. If its performance can be confirmed by external validation and its clinical usefulness can be proven, the score may influence patient selection for more aggressive revascularisation strategies in routine clinical practice.

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.

In vivo short-term precision of hip structure analysis variables in comparison with bone mineral density using paired dual-energy X-ray absorptiometry scans from multi-center clinical trials.

PubMed

Khoo, Benjamin C C; Beck, Thomas J; Qiao, Qi-Hong; Parakh, Pallav; Semanick, Lisa; Prince, Richard L; Singer, Kevin P; Price, Roger I

2005-07-01

Hip structural analysis (HSA) is a technique for extracting strength-related structural dimensions of bone cross-sections from two-dimensional hip scan images acquired by dual energy X-ray absorptiometry (DXA) scanners. Heretofore the precision of the method has not been thoroughly tested in the clinical setting. Using paired scans from two large clinical trials involving a range of different DXA machines, this study reports the first precision analysis of HSA variables, in comparison with that of conventional bone mineral density (BMD) on the same scans. A key HSA variable, section modulus (Z), biomechanically indicative of bone strength during bending, had a short-term precision percentage coefficient of variation (CV%) in the femoral neck of 3.4-10.1%, depending on the manufacturer or model of the DXA equipment. Cross-sectional area (CSA), a determinant of bone strength during axial loading and closely aligned with conventional DXA bone mineral content, had a range of CV% from 2.8% to 7.9%. Poorer precision was associated with inadequate inclusion of the femoral shaft or femoral head in the DXA-scanned hip region. Precision of HSA-derived BMD varied between 2.4% and 6.4%. Precision of DXA manufacturer-derived BMD varied between 1.9% and 3.4%, arising from the larger analysis region of interest (ROI). The precision of HSA variables was not generally dependent on magnitude, subject height, weight, or conventional femoral neck densitometric variables. The generally poorer precision of key HSA variables in comparison with conventional DXA-derived BMD highlights the critical roles played by correct limb repositioning and choice of an adequate and appropriately positioned ROI.

Multivariate evaluation of the cutting performance of rotary instruments with electric and air-turbine handpieces.

PubMed

Funkenbusch, Paul D; Rotella, Mario; Chochlidakis, Konstantinos; Ercoli, Carlo

2016-10-01

Laboratory studies of tooth preparation often involve single values for all variables other than the one being tested. In contrast, in clinical settings, not all variables can be adequately controlled. For example, a new dental rotary cutting instrument may be tested in the laboratory by making a specific cut with a fixed force, but, in clinical practice, the instrument must make different cuts with individual dentists applying different forces. Therefore, the broad applicability of laboratory results to diverse clinical conditions is uncertain and the comparison of effects across studies difficult. The purpose of this in vitro study was to examine the effects of 9 process variables on the dental cutting of rotary cutting instruments used with an electric handpiece and compare them with those of a previous study that used an air-turbine handpiece. The effects of 9 key process variables on the efficiency of a simulated dental cutting operation were measured. A fractional factorial experiment was conducted by using an electric handpiece in a computer-controlled, dedicated testing apparatus to simulate dental cutting procedures with Macor blocks as the cutting substrate. Analysis of variance (ANOVA) was used to assess the statistical significance (α=.05). Four variables (targeted applied load, cut length, diamond grit size, and cut type) consistently produced large, statistically significant effects, whereas 5 variables (rotation per minute, number of cooling ports, rotary cutting instrument diameter, disposability, and water flow rate) produced relatively small, statistically insignificant effects. These results are generally similar to those previously found for an air-turbine handpiece. Regardless of whether an electric or air-turbine handpiece was used, the control exerted by the dentist, simulated in this study by targeting a specific level of applied force, was the single most important factor affecting cutting efficiency. Cutting efficiency was also significantly affected by factors simulating patient/clinical circumstances and hardware choices. These results highlight the greater importance of local clinical conditions (procedure, dentist) in understanding dental cutting as opposed to other hardware-related factors. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Intestinal nodular lymphoid hyperplasia and extraintestinal lymphoma--a rare association.

PubMed

Monsanto, P; Lérias, C; Almeida, N; Lopes, S; Cabral, J E; Figueiredo, P; Silva, M; Julião, M; Gouveia, H; Sofia, C

2012-06-01

Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of innumerable small discrete nodules involving a variable segment of the gastrointestinal tract. The association between nodular lymphoid hyperplasia and other benign and malignant diseases has been clearly described, with an increased risk of gastrointestinal tumours, namely gastrointestinal lymphoma. However, the association with extraintestinal lymphoma seems extremely rare. The authors present a clinical case of a patient with nodular lymphoid hyperplasia of the small and large intestine that subsequently developed an extraintestinal lymphoma (diffuse large B-cell lymphoma).

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.

Gingival recession and associated factors in a homogeneous Mexican adult male population: A cross-sectional study

PubMed Central

Minaya-Sánchez, Mirna; Medina-Solís, Carlo E.; Vallejos-Sánchez, Ana A.; Marquez-Corona, Maria L.; Pontigo-Loyola, América P.; Islas-Granillo, Horacio; Maupomé, Gerardo

2012-01-01

Background: Diverse variables are implicated in the pathogenesis of gingival recession; more detailed knowledge about the relationship between the clinical presentation of gingival recession and assorted risk indicators may lead to improved patient monitoring, early intervention, and subsequent prevention. The objective was to evaluate clinically gingival recession in a homogeneous Mexican adult male population and to determine the strength of association with related factors. Method: A cross-sectional study was carried out in a largely homogeneous group in terms of ethnic background, socioeconomic status, gender, occupation, and medical/dental insurance, in Campeche, Mexico. Periodontal examinations were undertaken to determine diverse clinical dental variables. All periodontal clinical examinations were assessed using the Florida Probe System, a dental chair and one examiner. Questionnaires were used to collect diverse risk indicators. Statistical analyses were undertaken with negative binomial regression models. Results: The mean number of sites with gingival recession per subject was 6.73±5.81; the prevalence was 87.6%. In the negative binomial regression model we observed that for (i) each year of age, and (ii) each percentage unit of increase in sites with plaque, and (iii) with suppuration, mean sites with gingival recession increased 2.9%, 1.0% and 13.0%, respectively. Having a spouse was associated with gingival recession. Conclusions: We observed association between gingival recession, and sociodemographic and clinical parameters. Patients need to be educated about risk indicators for gingival recession as well as the preventive maneuvers that may be implemented to minimize its occurrence. The potential of improved oral self-care to prevent a largely benign condition such as gingival recession is important, given the associated disorders that may ensue root exposure, such as root caries and root hypersensitivity. Key words:Oral health, periodontal health, gingival recession, adults, Mexico. PMID:22549678

A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies

PubMed Central

Jobard, Elodie; Trédan, Olivier; Postoly, Déborah; André, Fabrice; Martin, Anne-Laure; Elena-Herrmann, Bénédicte; Boyault, Sandrine

2016-01-01

The recent thriving development of biobanks and associated high-throughput phenotyping studies requires the elaboration of large-scale approaches for monitoring biological sample quality and compliance with standard protocols. We present a metabolomic investigation of human blood samples that delineates pitfalls and guidelines for the collection, storage and handling procedures for serum and plasma. A series of eight pre-processing technical parameters is systematically investigated along variable ranges commonly encountered across clinical studies. While metabolic fingerprints, as assessed by nuclear magnetic resonance, are not significantly affected by altered centrifugation parameters or delays between sample pre-processing (blood centrifugation) and storage, our metabolomic investigation highlights that both the delay and storage temperature between blood draw and centrifugation are the primary parameters impacting serum and plasma metabolic profiles. Storing the blood drawn at 4 °C is shown to be a reliable routine to confine variability associated with idle time prior to sample pre-processing. Based on their fine sensitivity to pre-analytical parameters and protocol variations, metabolic fingerprints could be exploited as valuable ways to determine compliance with standard procedures and quality assessment of blood samples within large multi-omic clinical and translational cohort studies. PMID:27929400

Validation of the Carotid Intima-Media Thickness Variability: Can Manual Segmentations Be Trusted as Ground Truth?

PubMed

Meiburger, Kristen M; Molinari, Filippo; Wong, Justin; Aguilar, Luis; Gallo, Diego; Steinman, David A; Morbiducci, Umberto

2016-07-01

The common carotid artery intima-media thickness (IMT) is widely accepted and used as an indicator of atherosclerosis. Recent studies, however, have found that the irregularity of the IMT along the carotid artery wall has a stronger correlation with atherosclerosis than the IMT itself. We set out to validate IMT variability (IMTV), a parameter defined to assess IMT irregularities along the wall. In particular, we analyzed whether or not manual segmentations of the lumen-intima and media-adventitia can be considered reliable in calculation of the IMTV parameter. To do this, we used a total of 60 simulated ultrasound images with a priori IMT and IMTV values. The images, simulated using the Fast And Mechanistic Ultrasound Simulation software, presented five different morphologies, four nominal IMT values and three different levels of variability along the carotid artery wall (no variability, small variability and large variability). Three experts traced the lumen-intima (LI) and media-adventitia (MA) profiles, and two automated algorithms were employed to obtain the LI and MA profiles. One expert also re-traced the LI and MA profiles to test intra-reader variability. The average IMTV measurements of the profiles used to simulate the longitudinal B-mode images were 0.002 ± 0.002, 0.149 ± 0.035 and 0.286 ± 0.068 mm for the cases of no variability, small variability and large variability, respectively. The IMTV measurements of one of the automated algorithms were statistically similar (p > 0.05, Wilcoxon signed rank) when considering small and large variability, but non-significant when considering no variability (p < 0.05, Wilcoxon signed rank). The second automated algorithm resulted in statistically similar values in the small variability case. Two readers' manual tracings, however, produced IMTV measurements with a statistically significant difference considering all three variability levels, whereas the third reader found a statistically significant difference in both the no variability and large variability cases. Moreover, the error range between the reader and automatic IMTV values was approximately 0.15 mm, which is on the same order of small IMTV values, indicating that manual and automatic IMTV readings should be not used interchangeably in clinical practice. On the basis of our findings, we conclude that expert manual tracings should not be considered reliable in IMTV measurement and, therefore, should not be trusted as ground truth. On the other hand, our automated algorithm was found to be more reliable, indicating how automated techniques could therefore foster analysis of the carotid artery intima-media thickness irregularity. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Using network projections to explore co-incidence and context in large clinical datasets: Application to homelessness among U.S. Veterans.

PubMed

Pettey, Warren B P; Toth, Damon J A; Redd, Andrew; Carter, Marjorie E; Samore, Matthew H; Gundlapalli, Adi V

2016-06-01

Network projections of data can provide an efficient format for data exploration of co-incidence in large clinical datasets. We present and explore the utility of a network projection approach to finding patterns in health care data that could be exploited to prevent homelessness among U.S. Veterans. We divided Veteran ICD-9-CM (ICD9) data into two time periods (0-59 and 60-364days prior to the first evidence of homelessness) and then used Pajek social network analysis software to visualize these data as three different networks. A multi-relational network simultaneously displayed the magnitude of ties between the most frequent ICD9 pairings. A new association network visualized ICD9 pairings that greatly increased or decreased. A signed, subtraction network visualized the presence, absence, and magnitude difference between ICD9 associations by time period. A cohort of 9468 U.S. Veterans was identified as having administrative evidence of homelessness and visits in both time periods. They were seen in 222,599 outpatient visits that generated 484,339 ICD9 codes (average of 11.4 (range 1-23) visits and 2.2 (range 1-60) ICD9 codes per visit). Using the three network projection methods, we were able to show distinct differences in the pattern of co-morbidities in the two time periods. In the more distant time period preceding homelessness, the network was dominated by routine health maintenance visits and physical ailment diagnoses. In the 59days immediately prior to the homelessness identification, alcohol related diagnoses along with economic circumstances such as unemployment, legal circumstances, along with housing instability were noted. Network visualizations of large clinical datasets traditionally treated as tabular and difficult to manipulate reveal rich, previously hidden connections between data variables related to homelessness. A key feature is the ability to visualize changes in variables with temporality and in proximity to the event of interest. These visualizations lend support to cognitive tasks such as exploration of large clinical datasets as a prelude to hypothesis generation. Published by Elsevier Inc.

Big Data Toolsets to Pharmacometrics: Application of Machine Learning for Time-to-Event Analysis.

PubMed

Gong, Xiajing; Hu, Meng; Zhao, Liang

2018-05-01

Additional value can be potentially created by applying big data tools to address pharmacometric problems. The performances of machine learning (ML) methods and the Cox regression model were evaluated based on simulated time-to-event data synthesized under various preset scenarios, i.e., with linear vs. nonlinear and dependent vs. independent predictors in the proportional hazard function, or with high-dimensional data featured by a large number of predictor variables. Our results showed that ML-based methods outperformed the Cox model in prediction performance as assessed by concordance index and in identifying the preset influential variables for high-dimensional data. The prediction performances of ML-based methods are also less sensitive to data size and censoring rates than the Cox regression model. In conclusion, ML-based methods provide a powerful tool for time-to-event analysis, with a built-in capacity for high-dimensional data and better performance when the predictor variables assume nonlinear relationships in the hazard function. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

[Impact analysis of shuxuetong injection on abnormal changes of ALT based on generalized boosted models propensity score weighting].

PubMed

Yang, Wei; Yi, Dan-Hui; Xie, Yan-Ming; Yang, Wei; Dai, Yi; Zhi, Ying-Jie; Zhuang, Yan; Yang, Hu

2013-09-01

To estimate treatment effects of Shuxuetong injection on abnormal changes on ALT index, that is, to explore whether the Shuxuetong injection harms liver function in clinical settings and to provide clinical guidance for its safe application. Clinical information of traditional Chinese medicine (TCM) injections is gathered from hospital information system (HIS) of eighteen general hospitals. This is a retrospective cohort study, using abnormal changes in ALT index as an outcome. A large number of confounding biases are taken into account through the generalized boosted models (GBM) and multiple logistic regression model (MLRM) to estimate the treatment effects of Shuxuetong injections on abnormal changes in ALT index and to explore possible influencing factors. The advantages and process of application of GBM has been demonstrated with examples which eliminate the biases from most confounding variables between groups. This serves to modify the estimation of treatment effects of Shuxuetong injection on ALT index making the results more reliable. Based on large scale clinical observational data from HIS database, significant effects of Shuxuetong injection on abnormal changes in ALT have not been found.

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

[Personalization in the medicine of the future : Opportunities and risks].

PubMed

Malek, N P

2017-07-01

Personalized medicine is not a new concept. The renaissance of the term is due to the enormous progress in gene sequencing technology and functional imaging, as well as the development of targeted therapies. Application of these technologies in clinical medicine will necessitate infrastructural as well as organizational and educational changes in the healthcare system. An important change required already in the short-term is the introduction of centralized structures, preferably in university clinics, which adopt these innovations and incorporate them into clinical care. Simultaneously, the collation and use of large quantities of relevant data from highly variable sources must be successfully mastered, in order to pave the way for disruptive technologies such as artificial intelligence.

Osteogenesis imperfecta in childhood: treatment strategies.

PubMed

Engelbert, R H; Pruijs, H E; Beemer, F A; Helders, P J

1998-12-01

Osteogenesis imperfecta (OI) is a skeletal disorder of remarkable clinical variability characterized by bone fragility, osteopenia, variable degrees of short stature, and progressive skeletal deformities. Additional clinical manifestations such as blue sclerae, dentinogenesis imperfecta, joint laxity, and maturity onset deafness are described in the literature. OI occurs in about 1 in 20,000 births and is caused by quantitative and qualitative defects in the synthesis of collagen I. Depending on the severity of the disease, a large impact on motor development, range of joint motion, muscle strength, and functional ability may occur. Treatment strategies should primarily focus on the improvement of functional ability and the adoption of compensatory strategies, rather than merely improving range of joint motion and muscle strength. Surgical treatment of the extremities may be indicated to stabilize the long bones to optimize functional ability and walking capacity. Surgical treatment of the spine may be indicated in patients with progressive spinal deformity and in those with symptomatic basilar impression.

Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 Genotypes and Warfarin Dosing

PubMed Central

Johnson, JA; Gong, L; Whirl-Carrillo, M; Gage, BF; Scott, SA; Stein, CM; Anderson, JL; Kimmel, SE; Lee, MTM; Pirmohamed, M; Wadelius, M; Klein, TE; Altman, RB

2011-01-01

Warfarin is a widely used anticoagulant with a narrow therapeutic index and large interpatient variability in the dose required to achieve target anticoagulation. Common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K–epoxide reductase complex (VKORC1) enzymes, in addition to known nongenetic factors, account for ~50% of warfarin dose variability. The purpose of this article is to assist in the interpretation and use of CYP2C9 and VKORC1 geno-type data for estimating therapeutic warfarin dose to achieve an INR of 2–3, should genotype results be available to the clinician. The Clinical Pharmacogenetics Implementation Consortium (CPIC) of the National Institutes of Health Pharmacogenomics Research Network develops peer-reviewed gene–drug guidelines that are published and updated periodically on http://www.pharmgkb.org based on new developments in the field.1 PMID:21900891

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

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.

Individualized prediction of lung-function decline in chronic obstructive pulmonary disease

PubMed Central

Zafari, Zafar; Sin, Don D.; Postma, Dirkje S.; Löfdahl, Claes-Göran; Vonk, Judith; Bryan, Stirling; Lam, Stephen; Tammemagi, C. Martin; Khakban, Rahman; Man, S.F. Paul; Tashkin, Donald; Wise, Robert A.; Connett, John E.; McManus, Bruce; Ng, Raymond; Hollander, Zsuszanna; Sadatsafavi, Mohsen

2016-01-01

Background: The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV1) in current smokers with mild-to-moderate COPD. Methods: Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV1 values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations. Results: We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV1 2.75 L) to create the individualized prediction equations. There was significant between-individual variability in the rate of FEV1 decline, with the interval for the annual rate of decline that contained 95% of individuals being −124 to −15 mL/yr for smokers and −83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets. Interpretation: A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD. Trial registration: Lung Health Study — ClinicalTrials.gov, no. NCT00000568; Pan-Canadian Early Detection of Lung Cancer Study — ClinicalTrials.gov, no. NCT00751660 PMID:27486205

Dolichoectatic aneurysms of the vertebrobasilar system: clinical and radiographic factors that predict poor outcomes.

PubMed

Xu, David S; Levitt, Michael R; Kalani, M Yashar S; Rangel-Castilla, Leonardo; Mulholland, Celene B; Abecassis, Isaac J; Morton, Ryan P; Nerva, John D; Siddiqui, Adnan H; Levy, Elad I; Spetzler, Robert F; Albuquerque, Felipe C; McDougall, Cameron G

2018-02-01

OBJECTIVE Fusiform dolichoectatic vertebrobasilar aneurysms are rare, challenging lesions. The natural history of these lesions and medium- and long-term patient outcomes are poorly understood. The authors sought to evaluate patient prognosis after diagnosis of fusiform dolichoectatic vertebrobasilar aneurysms and to identify clinical and radiographic predictors of neurological deterioration. METHODS The authors reviewed multiple, prospectively maintained, single-provider databases at 3 large-volume cerebrovascular centers to obtain data on patients with unruptured, fusiform, basilar artery dolichoectatic aneurysms diagnosed between January 1, 2000, and January 1, 2015. RESULTS A total of 50 patients (33 men, 17 women) were identified; mean clinical follow-up was 50.1 months and mean radiographic follow-up was 32.4 months. At last follow-up, 42% (n = 21) of aneurysms had progressed and 44% (n = 22) of patients had deterioration of their modified Rankin Scale scores. When patients were dichotomized into 2 groups- those who worsened and those who did not-univariate analysis showed 5 variables to be statistically significantly different: sex (p = 0.007), radiographic brainstem compression (p = 0.03), clinical posterior fossa compression (p < 0.001), aneurysmal growth on subsequent imaging (p = 0.001), and surgical therapy (p = 0.006). A binary logistic regression was then created to evaluate these variables. The only variable found to be a statistically significant predictor of clinical worsening was clinical symptoms of posterior fossa compression at presentation (p = 0.01). CONCLUSIONS Fusiform dolichoectatic vertebrobasilar aneurysms carry a poor prognosis, with approximately one-half of the patients deteriorating or experiencing progression of their aneurysm within 5 years. Despite being high risk, intervention-when carefully timed (before neurological decline)-may be beneficial in select patients.

PROGNOSTIC SIGNIFICANCE OF CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR CHARACTERISTICS OF MEDULLOBLASTOMAS IN THE PROSPECTIVE HIT2000 MULTICENTER CLINICAL TRIAL COHORT

PubMed Central

Pietsch, Torsten; Schmidt, Rene; Remke, Marc; Korshunov, Andrey; Hovestadt, Volker; Jones, David TW; Felsberg, Jörg; Kaulich, Kerstin; Goschzik, Tobias; Kool, Marcel; Northcott, Paul A.; von Hoff, Katja; von Bueren, André O.; Friedrich, Carsten; Skladny, Heyko; Fleischhack, Gudrun; Taylor, Michael D.; Cremer, Friedrich; Lichter, Peter; Faldum, Andreas; Reifenberger, Guido; Rutkowski, Stefan; Pfister, Stefan M.

2014-01-01

BACKGROUND: This study aimed to prospectively evaluate clinical, histopathological and molecular variables for outcome prediction in medulloblastoma patients. METHODS: Patients from the HIT2000 cooperative clinical trial were prospectively enrolled based on the availability of sufficient tumor material and complete clinical information. This revealed a cohort of 184 patients (median age 7.6 years), which was randomly split at a 2:1 ratio into a training (n = 127), and a validation (n = 57) dataset. All samples were subjected to thorough histopathological investigation, CTNNB1 mutation analysis, quantitative PCR, MLPA and FISH analyses for cytogenetic variables, and methylome analysis. RESULTS: By univariable analysis, clinical factors (M-stage), histopathological variables (large cell component, endothelial proliferation, synaptophysin pattern), and molecular features (chromosome 6q status, MYC amplification, TOP2A copy-number, subgrouping) were found to be prognostic. Molecular consensus subgrouping (WNT, SHH, Group 3, Group 4) was validated as an independent feature to stratify patients into different risk groups. When comparing methods for the identification of WNT-driven medulloblastoma, this study identified CTNNB1 sequencing and methylation profiling to most reliably identify these patients. After removing patients with particularly favorable (CTNNB1 mutation, extensive nodularity) or unfavorable (MYC amplification) markers, a risk score for the remaining “intermediate molecular risk” population dependent on age, M-stage, pattern of synaptophysin expression, and MYCN copy-number status was identified and validated, with speckled synaptophysin expression indicating worse outcome. CONCLUSIONS: Methylation subgrouping and CTNNB1 mutation status represent robust tools for the risk-stratification of medulloblastoma. A simple clinico-pathological risk score for “intermediate molecular risk” patients was identified, which deserves further validation. SECONDARY CATEGORY: Pediatrics.

Lateral hip pain: findings from magnetic resonance imaging and clinical examination.

PubMed

Woodley, Stephanie J; Nicholson, Helen D; Livingstone, Vicki; Doyle, Terence C; Meikle, Grant R; Macintosh, Janet E; Mercer, Susan R

2008-06-01

Prospective cross-sectional study. To examine the radiological and physical therapy diagnoses of lateral hip pain (LHP), and determine the validity of selected clinical variables for predicting gluteal tendon pathology. LHP is frequently encountered by clinicians. Further investigation is required to establish the specific pathologies implicated in the cause of LHP, and which clinical tests are useful in the assessment of this problem. Forty patients with unilateral LHP underwent a physical therapy examination followed by magnetic resonance imaging (MRI) studies. Three radiologists analyzed the images of both hips for signs of pathology. Interobserver reliability of the image analyses, the agreement between the physical therapy and radiological diagnoses, and the validity of the clinical tests were examined. Gluteus medius tendon pathology, bursitis, osteoarthritis and gluteal muscle atrophy (predominantly affecting gluteus minimus) were all implicated in the imaging report of LHP. While prevalent in symptomatic hips, abnormalities were also identified in asymptomatic hips, particularly relating to the diagnosis of bursitis. The strength of agreement between radiologists was variable and little agreement existed between the physical therapy and radiological diagnoses of pathology. Nine of the 26 clinical variables examined in relation to gluteal tendon pathology had likelihood ratios above 2.0 or below 0.5, but the associated 95% confidence intervals were large. The diagnosis of LHP is challenging and our results highlight some problems associated with the use of MRI as a diagnostic reference standard. This factor, together with the imprecise point estimates of the likelihood ratios, means that no firm conclusions can be made regarding the diagnostic utility of the clinical tests used in the assessment of gluteal tendon pathology.

Attention-deficit/hyperactivity disorder and phonological working memory: Methodological variability affects clinical and experimental performance metrics.

PubMed

Tarle, Stephanie J; Alderson, R Matt; Patros, Connor H G; Lea, Sarah E; Hudec, Kristen L; Arrington, Elaine F

2017-05-01

Despite promising findings in extant research that suggest impaired working memory (WM) serves as a central neurocognitive deficit or candidate endophenotype of attention-deficit/hyperactivity disorder (ADHD), findings from translational research have been relatively underwhelming. This study aimed to explicate previous equivocal findings by systematically examining the effect of methodological variability on WM performance estimates across experimental and clinical WM measures. Age-matched boys (ages 8-12 years) with (n = 20) and without (n = 20) ADHD completed 1 experimental (phonological) and 2 clinical (digit span, letter-number sequencing) WM measures. The use of partial scoring procedures, administration of greater trial numbers, and high central executive demands yielded moderate-to-large between-groups effect sizes. Moreover, the combination of these best-case procedures, compared to worst-case procedures (i.e., absolute scoring, administration of few trials, use of discontinue rules, and low central executive demands), resulted in a 12.5% increase in correct group classification. Collectively, these findings explain inconsistent ADHD-related WM deficits in previous reports, and highlight the need for revised clinical measures that utilize best-case procedures. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Combining censored and uncensored data in a U-statistic: design and sample size implications for cell therapy research.

PubMed

Moyé, Lemuel A; Lai, Dejian; Jing, Kaiyan; Baraniuk, Mary Sarah; Kwak, Minjung; Penn, Marc S; Wu, Colon O

2011-01-01

The assumptions that anchor large clinical trials are rooted in smaller, Phase II studies. In addition to specifying the target population, intervention delivery, and patient follow-up duration, physician-scientists who design these Phase II studies must select the appropriate response variables (endpoints). However, endpoint measures can be problematic. If the endpoint assesses the change in a continuous measure over time, then the occurrence of an intervening significant clinical event (SCE), such as death, can preclude the follow-up measurement. Finally, the ideal continuous endpoint measurement may be contraindicated in a fraction of the study patients, a change that requires a less precise substitution in this subset of participants.A score function that is based on the U-statistic can address these issues of 1) intercurrent SCE's and 2) response variable ascertainments that use different measurements of different precision. The scoring statistic is easy to apply, clinically relevant, and provides flexibility for the investigators' prospective design decisions. Sample size and power formulations for this statistic are provided as functions of clinical event rates and effect size estimates that are easy for investigators to identify and discuss. Examples are provided from current cardiovascular cell therapy research.

Bimodal Programming: A Survey of Current Clinical Practice.

PubMed

Siburt, Hannah W; Holmes, Alice E

2015-06-01

The purpose of this study was to determine the current clinical practice in approaches to bimodal programming in the United States. To be specific, if clinicians are recommending bimodal stimulation, who programs the hearing aid in the bimodal condition, and what method is used for programming the hearing aid? An 11-question online survey was created and sent via email to a comprehensive list of cochlear implant programming centers in the United States. The survey was sent to 360 recipients. Respondents in this study represented a diverse group of clinical settings (response rate: 26%). Results indicate little agreement about who programs the hearing aids, when they are programmed, and how they are programmed in the bimodal condition. Analysis of small versus large implant centers indicated small centers are less likely to add a device to the contralateral ear. Although a growing number of cochlear implant recipients choose to wear a hearing aid on the contralateral ear, there is inconsistency in the current clinical approach to bimodal programming. These survey results provide evidence of large variability in the current bimodal programming practices and indicate a need for more structured clinical recommendations and programming approaches.

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.

Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

PubMed Central

Grande, Michele; Milito, Giovanni; Attinà, Grazia Maria; Cadeddu, Federica; Muzi, Marco Gallinella; Nigro, Casimiro; Rulli, Francesco; Farinon, Attilio Maria

2008-01-01

Background The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data. Methods Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable. Results On survival analysis we found that depth of tumour invasion (P < 0.001; F-ratio 2.11), type of operation (P < 0.001; F-ratio 3.51) and CT scanning (P < 0.001; F-ratio 5.21) were predictors of survival. Considering the degree of mural invasion as independent variable, on univariate analysis, we observed that mucorrhea, anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour. Conclusion The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted. PMID:18778464

Pharmacogenetics and outcome with antipsychotic drugs.

PubMed

Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

2014-12-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

Pharmacogenetics and outcome with antipsychotic drugs

PubMed Central

Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.

2014-01-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959

The National Clinical Trials Network: Conducting Successful Clinical Trials of New Therapies for Rare Cancers

PubMed Central

Schott, Anne F.; Welch, John J.; Verschraegen, Claire F.; Kurzrock, Razelle

2015-01-01

Rare cancers account for 27% of neoplasms diagnosed each year, and 25% of cancer-related deaths in the United States. However, rare cancers show some of the highest response rates to targeted therapies, probably due to identification of oncogenic drivers with little inter-patient variability. Although the low incidence of rare cancers make large scale randomized trials involving single histologies difficult to perform, drugs have been successfully developed in rare cancers utilizing clinical trial designs that combine microscopic anatomies. Such trials are being pursued within the National Clinical Trials Network (NCTN), which possesses unique qualifications to perform widespread molecular screening of tumors for patient enrollment onto therapeutic clinical trials. When larger clinical trials are needed to determine optimum treatment strategies in rare cancers, the NCTN's broad reach in North America and internationally, and ability to partner with both US-based and international research organizations, can make these challenging studies feasible. PMID:26433554

Three-dimensional study of pelvic asymmetry on anatomical specimens and its clinical perspectives.

PubMed

Boulay, Christophe; Tardieu, Christine; Bénaim, Charles; Hecquet, Jérome; Marty, Catherine; Prat-Pradal, Dominique; Legaye, Jean; Duval-Beaupère, Ginette; Pélissier, Jacques

2006-01-01

The aim of this study was to assess pelvic asymmetry (i.e. to determine whether the right iliac bone and the right part of the sacrum are mirror images of the left), both quantitatively and qualitatively, using three-dimensional measurements. Pelvic symmetry was described osteologically using a common reference coordinate system for a large sample of pelvises. Landmarks were established on 12 anatomical specimens with an electromagnetic Fastrak system. Seventy-one paired variables were tested with a paired t-test and a non-parametric test (Wilcoxon). A Pearson correlation matrix between the right and left values of the same variable was applied exclusively to values that were significantly asymmetric in order to calculate a dimensionless asymmetry index, ABGi, for each variable. Fifteen variables were significantly asymmetric and correlated with the right vs. left sides for the following anatomical regions: sacrum, iliac blades, iliac width, acetabulum and the superior lunate surface of the acetabulum. ABGi values above a threshold of +/- 4.8% were considered significantly asymmetric in seven variables of the pelvic area. Total asymmetry involving the right and the left pelvis seems to follow a spiral path in the pelvis; in the upper part, the iliac blades rotate clockwise, and in the lower part, the pubic symphysis rotates anticlockwise. Thus, pelvic asymmetry may be evaluated in clinical examinations by measuring iliac crest orientation.

Three-dimensional study of pelvic asymmetry on anatomical specimens and its clinical perspectives

PubMed Central

Boulay, Christophe; Tardieu, Christine; Bénaim, Charles; Hecquet, Jérome; Marty, Catherine; Prat-Pradal, Dominique; Legaye, Jean; Duval-Beaupère, Ginette; Pélissier, Jacques

2006-01-01

The aim of this study was to assess pelvic asymmetry (i.e. to determine whether the right iliac bone and the right part of the sacrum are mirror images of the left), both quantitatively and qualitatively, using three-dimensional measurements. Pelvic symmetry was described osteologically using a common reference coordinate system for a large sample of pelvises. Landmarks were established on 12 anatomical specimens with an electromagnetic Fastrak system. Seventy-one paired variables were tested with a paired t-test and a non-parametric test (Wilcoxon). A Pearson correlation matrix between the right and left values of the same variable was applied exclusively to values that were significantly asymmetric in order to calculate a dimensionless asymmetry index, ABGi, for each variable. Fifteen variables were significantly asymmetric and correlated with the right vs. left sides for the following anatomical regions: sacrum, iliac blades, iliac width, acetabulum and the superior lunate surface of the acetabulum. ABGi values above a threshold of ± 4.8% were considered significantly asymmetric in seven variables of the pelvic area. Total asymmetry involving the right and the left pelvis seems to follow a spiral path in the pelvis; in the upper part, the iliac blades rotate clockwise, and in the lower part, the pubic symphysis rotates anticlockwise. Thus, pelvic asymmetry may be evaluated in clinical examinations by measuring iliac crest orientation. PMID:16420376

The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer

NASA Astrophysics Data System (ADS)

Tilly, N.; Johansson, J.; Isacsson, U.; Medin, J.; Blomquist, E.; Grusell, E.; Glimelius, B.

2005-06-01

Currently, most clinical range-modulated proton beams are assumed to have a fixed overall relative biological effectiveness (RBE) of 1.1. However, it is well known that the RBE increases with depth in the spread-out Bragg peak (SOBP) and becomes about 10% higher than mid-SOBP RBE at 2 mm from the distal edge (Paganetti 2003 Technol. Cancer Res. Treat. 2 413-26) and can reach values of 1.3-1.4 in vitro at the distal edge (Robertson et al 1975 Cancer 35 1664-77, Courdi et al 1994 Br. J. Radiol. 67 800-4). We present a fast method for applying a variable RBE correction with linear energy transfer (LET) dependent tissue-specific parameters based on the αref/βref ratios suitable for implementation in a treatment planning system. The influence of applying this variable RBE correction on a clinical multiple beam proton dose plan is presented here. The treatment plan is evaluated by RBE weighted dose volume histograms (DVHs) and the calculation of tumour control probability (TCP) and normal tissue complication probability (NTCP) values. The variable RBE correction yields DVHs for the clinical target volumes (CTVs), a primary advanced hypopharynx cancer and subclinical disease in the lymph nodes, that are slightly higher than those achieved by multiplying the absorbed dose with RBE = 1.1. Although, more importantly, the RBE weighted DVH for an organ at risk, the spinal cord is considerably increased for the variable RBE. As the spinal cord in this particular case is located 8 mm behind the planning target volume (PTV) and hence receives only low total doses, the NTCP values are zero in spite of the significant increase in the RBE weighted DVHs for the variable RBE. However, high NTCP values for the non-target normal tissue were obtained when applying the variable RBE correction. As RBE variations tend to be smaller for in vivo systems, this study—based on in vitro data since human tissue RBE values are scarce and have large uncertainties—can be interpreted as showing the upper limits of the possible effects of utilizing a variable RBE correction. In conclusion, the results obtained here still indicate a significant difference in introducing a variable RBE compared to applying a generic RBE of 1.1, suggesting it is worth considering such a correction in clinical proton therapy planning, especially when risk organs are located immediately behind the target volume.

VARIABLE SELECTION FOR QUALITATIVE INTERACTIONS IN PERSONALIZED MEDICINE WHILE CONTROLLING THE FAMILY-WISE ERROR RATE

PubMed Central

Gunter, Lacey; Zhu, Ji; Murphy, Susan

2012-01-01

For many years, subset analysis has been a popular topic for the biostatistics and clinical trials literature. In more recent years, the discussion has focused on finding subsets of genomes which play a role in the effect of treatment, often referred to as stratified or personalized medicine. Though highly sought after, methods for detecting subsets with altering treatment effects are limited and lacking in power. In this article we discuss variable selection for qualitative interactions with the aim to discover these critical patient subsets. We propose a new technique designed specifically to find these interaction variables among a large set of variables while still controlling for the number of false discoveries. We compare this new method against standard qualitative interaction tests using simulations and give an example of its use on data from a randomized controlled trial for the treatment of depression. PMID:22023676

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

Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers.

PubMed

Clementz, Brett A; Sweeney, John A; Hamm, Jordan P; Ivleva, Elena I; Ethridge, Lauren E; Pearlson, Godfrey D; Keshavan, Matcheri S; Tamminga, Carol A

2016-04-01

Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations. A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected. Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders. These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard.

Atypical Fibroxanthoma Revisited.

PubMed

Mentzel, Thomas; Requena, Luis; Brenn, Thomas

2017-06-01

Atypical fibroxanthoma (AFX) represents a rare mesenchymal neoplasm arising predominantly in the head and neck area of elderly patients. Clinically, the neoplasm is characterized by a rapid and exophytic growth with frequent ulceration of the epidermis. Histopathologically, AFX represents a well-circumscribed, dermal-based neoplasm composed of a variable admixture of large histiocytoid cells, enlarged spindled and epithelioid tumor cells, and multinucleated tumor giant cells with bizarre and pleomorphic nuclei. If strict diagnostic criteria are applied, the clinical behavior of AFX is benign in most cases, and complete excision represents the treatment of choice. Copyright © 2017 Elsevier Inc. All rights reserved.

Boxing-related head injuries.

PubMed

Jayarao, Mayur; Chin, Lawrence S; Cantu, Robert C

2010-10-01

Fatalities in boxing are most often due to traumatic brain injury that occurs in the ring. In the past 30 years, significant improvements in ringside and medical equipment, safety, and regulations have resulted in a dramatic reduction in the fatality rate. Nonetheless, the rate of boxing-related head injuries, particularly concussions, remains unknown, due in large part to its variability in clinical presentation. Furthermore, the significance of repeat concussions sustained when boxing is just now being understood. In this article, we identify the clinical manifestations, pathophysiology, and management of boxing-related head injuries, and discuss preventive strategies to reduce head injuries sustained by boxers.

The prognostic impact of clinical and CT parameters in patients with pontine hemorrhage.

PubMed

Dziewas, Rainer; Kremer, Marion; Lüdemann, Peter; Nabavi, Darius G; Dräger, Bianca; Ringelstein, Bernd

2003-01-01

In patients with pontine hemorrhage (PH), an accurate prognostic assessment is critical for establishing a reasonable therapeutic approach. The initial clinical symptoms and computed tomography (CT) features were analyzed with multivariate regression analysis in 39 consecutive patients with PH. PHs were classified into three types: (1) large paramedian, (2) basal or basotegmental and (3) lateral tegmental, and the hematomas' diameters were measured. The patients' outcome was evaluated. Twenty-seven patients (69%) died and 12 (31%) survived for more than 1 year after PH. The symptom most predictive of death was coma on admission. The large paramedian type of PH predicted a poor prognosis, whereas the lateral tegmental type was associated with a favorable outcome. The transverse hematoma diameter was also related to outcome, with the threshold value found to be 20 mm. We conclude that PH outcome can be estimated best by combining the CT parameters 'large paramedian PH' and 'transverse diameter >/=20 mm' with the clinical variable 'coma on admission'. Survival is unlikely if all 3 features are present, whereas survival may be expected if only 1 or none of these features is found. Copyright 2003 S. Karger AG, Basel

Big biomedical data and cardiovascular disease research: opportunities and challenges.

PubMed

Denaxas, Spiros C; Morley, Katherine I

2015-07-01

Electronic health records (EHRs), data generated and collected during normal clinical care, are increasingly being linked and used for translational cardiovascular disease research. Electronic health record data can be structured (e.g. coded diagnoses) or unstructured (e.g. clinical notes) and increasingly encapsulate medical imaging, genomic and patient-generated information. Large-scale EHR linkages enable researchers to conduct high-resolution observational and interventional clinical research at an unprecedented scale. A significant amount of preparatory work and research, however, is required to identify, obtain, and transform raw EHR data into research-ready variables that can be statistically analysed. This study critically reviews the opportunities and challenges that EHR data present in the field of cardiovascular disease clinical research and provides a series of recommendations for advancing and facilitating EHR research.

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.

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.

Validity and Usefulness of `Wearable Blood Pressure Sensing' for Detection of Inappropriate Short-Term Blood Pressure Variability in the Elderly

NASA Astrophysics Data System (ADS)

Iijima, Katsuya; Kameyama, Yumi; Akishita, Masahiro; Ouchi, Yasuyoshi; Yanagimoto, Shintaro; Imai, Yasushi; Yahagi, Naoki; Lopez, Guillaume; Shuzo, Masaki; Yamada, Ichiro

An increase in short-term blood pressure (BP) variability is a characteristic feature in the elderly. It makes the management of hemodynamics more difficult, because it is frequently seen disturbed baro-reflex function and increased arterial stiffness, leading to isolated systolic hypertension. Large BP variability aggravates hypertensive target organ damage and is an independent risk factor for the cardiovascular (CV) events in elderly hypertensive patients. Therefore, appropriate control in BP is indispensable to manage lifestyle-related diseases and to prevent subsequent CV events. In addition, accumulating recent reports show that excessive BP variability is also associated with a decline in cognitive function and fall in the elderly. In the clinical settings, we usually evaluate their health condition, mainly with single point BP measurement using cuff inflation. However, unfortunately we are not able to find the close changes in BP by the traditional way. Here, we can show our advantageous approach of continuous BP monitoring using newly developing device `wearable BP sensing' without a cuff stress in the elderly. The new device could reflect systolic BP and its detailed changes, in consistent with cuff-based BP measurement. Our new challenge suggests new possibility of its clinical application with high accuracy.

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

Correlates and responsiveness to change of measures of skin and musculoskeletal disease in early diffuse systemic sclerosis.

PubMed

Wiese, Alexandra B; Berrocal, Veronica J; Furst, Daniel E; Seibold, James R; Merkel, Peter A; Mayes, Maureen D; Khanna, Dinesh

2014-11-01

Skin and musculoskeletal involvement are frequently present early in diffuse cutaneous systemic sclerosis (dcSSc). The current study examined the correlates for skin and musculoskeletal measures in a 1-year longitudinal observational study. Patients with dcSSc were recruited at 4 US centers and enrolled in a 1-year study. Prespecified and standardized measures included physician and patient assessments of skin involvement, modified Rodnan skin score (MRSS), durometer score, Health Assessment Questionnaire disability index, serum creatine phosphokinase, tender joint counts, and presence/absence of tendon friction rubs, small joint contractures, and large joint contractures. Additionally, physician and patient global health assessments and health-related quality of life assessments were recorded. Correlations were computed among the baseline global assessments, skin variables, and musculoskeletal variables. Using the followup physician and patient anchors, effect sizes were calculated. A total of 200 patients were studied: 75% were women, mean ± SD age was 50.0 ± 11.9 years, and mean ± SD disease duration from first non-Raynaud's phenomenon symptom was 1.6 ± 1.4 years. Physician global health assessment had large correlations with MRSS (r = 0.60) and physician-reported skin involvement visual analog scale in the last month (r = 0.74), whereas patient global assessment had large correlations with MRSS, the Short Form 36 health survey physical component scale, skin interference, and skin involvement in the last month (r = 0.37-0.72). Four of 9 skin variables had moderate to large effect sizes (0.51-1.09). Physician and patient global assessments have larger correlations with skin measures compared to musculoskeletal measures. From a clinical trial perspective, skin variables were more responsive to change than musculoskeletal variables over a 1-year period, although both provide complementary information. Copyright © 2014 by the American College of Rheumatology.

Correlates and Responsiveness to Change of Measures of Skin and Musculoskeletal Disease in Early Diffuse Systemic Sclerosis

PubMed Central

Wiese, Alexandra B.; Berrocal, Veronica J.; Furst, Daniel E.; Seibold, James R.; Merkel, Peter A.; Mayes, Maureen D.; Khanna, Dinesh

2015-01-01

Objective Skin and musculoskeletal involvement are frequently present early in diffuse cutaneous systemic sclerosis (dcSSc). The current study examined the correlates for skin and musculoskeletal measures in a 1-year longitudinal observational study. Methods Patients with dcSSc were recruited at 4 US centers and enrolled in a 1-year study. Prespecified and standardized measures included physician and patient assessments of skin involvement, modified Rodnan skin score (MRSS), durometer score, Health Assessment Questionnaire disability index, serum creatine phosphokinase, tender joint counts, and presence/absence of tendon friction rubs, small joint contractures, and large joint contractures. Additionally, physician and patient global health assessments and health-related quality of life assessments were recorded. Correlations were computed among the baseline global assessments, skin variables, and musculoskeletal variables. Using the followup physician and patient anchors, effect sizes were calculated. Results A total of 200 patients were studied: 75% were women, mean ± SD age was 50.0 ± 11.9 years, and mean ± SD disease duration from first non–Raynaud’s phenomenon symptom was 1.6 ± 1.4 years. Physician global health assessment had large correlations with MRSS (r = 0.60) and physician-reported skin involvement visual analog scale in the last month (r = 0.74), whereas patient global assessment had large correlations with MRSS, the Short Form 36 health survey physical component scale, skin interference, and skin involvement in the last month (r = 0.37–0.72). Four of 9 skin variables had moderate to large effect sizes (0.51–1.09). Conclusion Physician and patient global assessments have larger correlations with skin measures compared to musculoskeletal measures. From a clinical trial perspective, skin variables were more responsive to change than musculoskeletal variables over a 1-year period, although both provide complementary information. PMID:24692361

Imaging mass spectrometry data reduction: automated feature identification and extraction.

PubMed

McDonnell, Liam A; van Remoortere, Alexandra; de Velde, Nico; van Zeijl, René J M; Deelder, André M

2010-12-01

Imaging MS now enables the parallel analysis of hundreds of biomolecules, spanning multiple molecular classes, which allows tissues to be described by their molecular content and distribution. When combined with advanced data analysis routines, tissues can be analyzed and classified based solely on their molecular content. Such molecular histology techniques have been used to distinguish regions with differential molecular signatures that could not be distinguished using established histologic tools. However, its potential to provide an independent, complementary analysis of clinical tissues has been limited by the very large file sizes and large number of discrete variables associated with imaging MS experiments. Here we demonstrate data reduction tools, based on automated feature identification and extraction, for peptide, protein, and lipid imaging MS, using multiple imaging MS technologies, that reduce data loads and the number of variables by >100×, and that highlight highly-localized features that can be missed using standard data analysis strategies. It is then demonstrated how these capabilities enable multivariate analysis on large imaging MS datasets spanning multiple tissues. Copyright © 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

Reliability and validity of a novel Kinect-based software program for measuring posture, balance and side-bending.

PubMed

Grooten, Wilhelmus Johannes Andreas; Sandberg, Lisa; Ressman, John; Diamantoglou, Nicolas; Johansson, Elin; Rasmussen-Barr, Eva

2018-01-08

Clinical examinations are subjective and often show a low validity and reliability. Objective and highly reliable quantitative assessments are available in laboratory settings using 3D motion analysis, but these systems are too expensive to use for simple clinical examinations. Qinematic™ is an interactive movement analyses system based on the Kinect camera and is an easy-to-use clinical measurement system for assessing posture, balance and side-bending. The aim of the study was to test the test-retest the reliability and construct validity of Qinematic™ in a healthy population, and to calculate the minimal clinical differences for the variables of interest. A further aim was to identify the discriminative validity of Qinematic™ in people with low-back pain (LBP). We performed a test-retest reliability study (n = 37) with around 1 week between the occasions, a construct validity study (n = 30) in which Qinematic™ was tested against a 3D motion capture system, and a discriminative validity study, in which a group of people with LBP (n = 20) was compared to healthy controls (n = 17). We tested a large range of psychometric properties of 18 variables in three sections: posture (head and pelvic position, weight distribution), balance (sway area and velocity in single- and double-leg stance), and side-bending. The majority of the variables in the posture and balance sections, showed poor/fair reliability (ICC < 0.4) and poor/fair validity (Spearman <0.4), with significant differences between occasions, between Qinematic™ and the 3D-motion capture system. In the clinical study, Qinematic™ did not differ between people with LPB and healthy for these variables. For one variable, side-bending to the left, there was excellent reliability (ICC =0.898), excellent validity (r = 0.943), and Qinematic™ could differentiate between LPB and healthy individuals (p = 0.012). This paper shows that a novel software program (Qinematic™) based on the Kinect camera for measuring balance, posture and side-bending has poor psychometric properties, indicating that the variables on balance and posture should not be used for monitoring individual changes over time or in research. Future research on the dynamic tasks of Qinematic™ is warranted.

Variability of creatinine measurements in clinical laboratories: results from the CRIC study.

PubMed

Joffe, Marshall; Hsu, Chi-yuan; Feldman, Harold I; Weir, Matthew; Landis, J R; Hamm, L Lee

2010-01-01

Estimating equations using serum creatinine (SCr) are often used to assess glomerular filtration rate (GFR). Such creatinine (Cr)-based formulae may produce biased estimates of GFR when using Cr measurements that have not been calibrated to reference laboratories. In this paper, we sought to examine the degree of this variation in Cr assays in several laboratories associated with academic medical centers affiliated with the Chronic Renal Insufficiency Cohort (CRIC) Study; to consider how best to correct for this variation, and to quantify the impact of such corrections on eligibility for participation in CRIC. Variability of Cr is of particular concern in the conduct of CRIC, a large multicenter study of subjects with chronic renal disease, because eligibility for the study depends on Cr-based assessment of GFR. A library of 5 large volume plasma specimens from apheresis patients was assembled, representing levels of plasma Cr from 0.8 to 2.4 mg/dl. Samples from this library were used for measurement of Cr at each of the 14 CRIC laboratories repetitively over time. We used graphical displays and linear regression methods to examine the variability in Cr, and used linear regression to develop calibration equations. We also examined the impact of the various calibration equations on the proportion of subjects screened as potential participants who were actually eligible for the study. There was substantial variability in Cr assays across laboratories and over time. We developed calibration equations for each laboratory; these equations varied substantially among laboratories and somewhat over time in some laboratories. The laboratory site contributed the most to variability (51% of the variance unexplained by the specimen) and variation with time accounted for another 15%. In some laboratories, calibration equations resulted in differences in eligibility for CRIC of as much as 20%. The substantial variability in SCr assays across laboratories necessitates calibration of SCr measures to a common standard. Failing to do so may substantially affect study eligibility and clinical interpretations when they are determined by Cr-based estimates of GFR. 2010 S. Karger AG, Basel.

Seasonal Variations in Mortality, Clinical, and Laboratory Parameters in Hemodialysis Patients: A 5-Year Cohort Study

PubMed Central

Usvyat, Len A.; Carter, Mary; Thijssen, Stephan; Kooman, Jeroen P.; van der Sande, Frank M.; Zabetakis, Paul; Balter, Paul; Levin, Nathan W.; Kotanko, Peter

2012-01-01

Summary Background and objectives Mortality varies seasonally in the general population, but it is unknown whether this phenomenon is also present in hemodialysis patients with known higher background mortality and emphasis on cardiovascular causes of death. This study aimed to assess seasonal variations in mortality, in relation to clinical and laboratory variables in a large cohort of chronic hemodialysis patients over a 5-year period. Design, setting, participants, & measurements This study included 15,056 patients of 51 Renal Research Institute clinics from six states of varying climates in the United States. Seasonal differences were assessed by chi-squared tests and univariate and multivariate cosinor analyses. Results Mortality, both all-cause and cardiovascular, was significantly higher during winter compared with other seasons (14.2 deaths per 100 patient-years in winter, 13.1 in spring, 12.3 in autumn, and 11.9 in summer). The increase in mortality in winter was more pronounced in younger patients, as well as in whites and in men. Seasonal variations were similar across climatologically different regions. Seasonal variations were also observed in neutrophil/lymphocyte ratio and serum calcium, potassium, and platelet values. Differences in mortality disappeared when adjusted for seasonally variable clinical parameters. Conclusions In a large cohort of dialysis patients, significant seasonal variations in overall and cardiovascular mortality were observed, which were consistent over different climatic regions. Other physiologic and laboratory parameters were also seasonally different. Results showed that mortality differences were related to seasonality of physiologic and laboratory parameters. Seasonal variations should be taken into account when designing and interpreting longitudinal studies in dialysis patients. PMID:22096041

X-linked juvenile retinoschisis (XLRS): a review of genotype-phenotype relationships.

PubMed

Kim, David Y; Mukai, Shizuo

2013-01-01

X-linked juvenile retinoschisis (XLRS) is one of the most common genetic causes of juvenile progressive retinal-vitreal degeneration in males. To date, more than 196 different mutations of the RS1 gene have been associated with XLRS. The mutation spectrum is large and the phenotype variable. This review will focus on the clinical features of XLRS and examine the relationship between phenotype and genotype.

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

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.

Assessment of large copy number variants in patients with apparently isolated congenital left-sided cardiac lesions reveals clinically relevant genomic events.

PubMed

Hanchard, Neil A; Umana, Luis A; D'Alessandro, Lisa; Azamian, Mahshid; Poopola, Mojisola; Morris, Shaine A; Fernbach, Susan; Lalani, Seema R; Towbin, Jeffrey A; Zender, Gloria A; Fitzgerald-Butt, Sara; Garg, Vidu; Bowman, Jessica; Zapata, Gladys; Hernandez, Patricia; Arrington, Cammon B; Furthner, Dieter; Prakash, Siddharth K; Bowles, Neil E; McBride, Kim L; Belmont, John W

2017-08-01

Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data were used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families. CNVs were molecularly confirmed and the medical records of individual carriers reviewed. The gene content of novel CNVs was then compared with public CNV data from CHD patients. Large CNVs (>1 MB) were observed in 33 probands (∼3%). Six of these were de novo and 14 were not observed in the only available parent sample. Associated cardiac phenotypes spanned a broad spectrum without clear predilection. Candidate CNVs were largely non-recurrent, associated with heterozygous loss of copy number, and overlapped known CHD genomic regions. Novel CNV regions were enriched for cardiac development genes, including seven that have not been previously associated with human CHD. CNV analysis can be a clinically useful and molecularly informative tool in LSLs without obvious extra-cardiac defects, and may identify a clinically relevant genomic disorder in a small but important proportion of these individuals. © 2017 Wiley Periodicals, Inc.

Rationale, design and objectives of ARegPKD, a European ARPKD registry study.

PubMed

Ebner, Kathrin; Feldkoetter, Markus; Ariceta, Gema; Bergmann, Carsten; Buettner, Reinhard; Doyon, Anke; Duzova, Ali; Goebel, Heike; Haffner, Dieter; Hero, Barbara; Hoppe, Bernd; Illig, Thomas; Jankauskiene, Augustina; Klopp, Norman; König, Jens; Litwin, Mieczyslaw; Mekahli, Djalila; Ranchin, Bruno; Sander, Anja; Testa, Sara; Weber, Lutz Thorsten; Wicher, Dorota; Yuzbasioglu, Ayse; Zerres, Klaus; Dötsch, Jörg; Schaefer, Franz; Liebau, Max Christoph

2015-02-18

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but frequently severe disorder that is typically characterized by cystic kidneys and congenital hepatic fibrosis but displays pronounced phenotypic heterogeneity. ARPKD is among the most important causes for pediatric end stage renal disease and a leading reason for liver-, kidney- or combined liver kidney transplantation in childhood. The underlying pathophysiology, the mechanisms resulting in the observed clinical heterogeneity and the long-term clinical evolution of patients remain poorly understood. Current treatment approaches continue to be largely symptomatic and opinion-based even in most-advanced medical centers. While large clinical trials for the frequent and mostly adult onset autosomal dominant polycystic kidney diseases have recently been conducted, therapeutic initiatives for ARPKD are facing the challenge of small and clinically variable cohorts for which reliable end points are hard to establish. ARegPKD is an international, mostly European, observational study to deeply phenotype ARPKD patients in a pro- and retrospective fashion. This registry study is conducted with the support of the German Society for Pediatric Nephrology (GPN) and the European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients (ESCAPE Network). ARegPKD clinically characterizes long-term ARPKD courses by a web-based approach that uses detailed basic data questionnaires in combination with yearly follow-up visits. Clinical data collection is accompanied by associated biobanking and reference histology, thus setting roots for future translational research. The novel registry study ARegPKD aims to characterize miscellaneous subcohorts and to compare the applied treatment options in a large cohort of deeply characterized patients. ARegPKD will thus provide evidence base for clinical treatment decisions and contribute to the pathophysiological understanding of this severe inherited disorder.

Clopidogrel and warfarin pharmacogenetic tests: what is the evidence for use in clinical practice?

PubMed Central

Shahin, Mohamed H.A.; Johnson, Julie A.

2013-01-01

Purpose of review To review the most promising genetic markers associated with the variability in the safety or efficacy of warfarin and clopidogrel and highlight the verification and validation initiatives for translating clopidogrel and warfarin pharmacogenetic tests to clinical practice. Recent findings Rapid advances in pharmacogenetics, continuous decrease in genotyping cost, development of point-of-care devices and the newly established clinical genotyping programs at several institutions hold the promise of individualizing clopidogrel and warfarin based on genotype. Guidelines have been established to assist clinicians in prescribing clopidogrel or warfarin dose based on genotype. However, the clinical utility of clopidogrel and warfarin is still limited. Accordingly, large randomized clinical trials are underway to define the role of clopidogrel and warfarin pharmacogenetics in clinical practice. Summary Pharmacogenetics has offered compelling evidence toward the individualization of clopidogrel and warfarin therapies. The rapid advances in technology make the clinical implementation of clopidogrel and warfarin pharmacogenetics possible. The clinical genotyping programs and the ongoing clinical trials will help in overcoming some of the barriers facing the clinical implementation of clopidogrel and warfarin pharmacogenetics. PMID:23478884

Integrated care in rural health: Seeking sustainability.

PubMed

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

2017-06-01

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

Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers

PubMed Central

Clementz, Brett A.; Sweeney, John A.; Hamm, Jordan P.; Ivleva, Elena I.; Ethridge, Lauren E.; Pearlson, Godfrey D.; Keshavan, Matcheri S.; Tamminga, Carol A.

2017-01-01

Objective Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations. Method A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected. Results Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders. Conclusions These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard. PMID:26651391

Predicting recovery of voluntary upper extremity movement in subacute stroke patients with severe upper extremity paresis.

PubMed

Koh, Chia-Lin; Pan, Shin-Liang; Jeng, Jiann-Shing; Chen, Bang-Bin; Wang, Yen-Ho; Hsueh, I-Ping; Hsieh, Ching-Lin

2015-01-01

Prediction of voluntary upper extremity (UE) movement recovery is largely unknown in patients with little voluntary UE movement at admission. The present study aimed to investigate (1) the extent and variation of voluntary UE movement recovery, and (2) the best predictive model of the recovery of voluntary UE movement by clinical variables in patients with severe UE paresis. Prospective cohort study. 140 (out of 590) stroke patients with severe UE paresis completed all assessments. Voluntary UE movement was assessed using the UE subscale of the Stroke Rehabilitation Assessment of Movement (STREAM-UE). Two outcome measures, STREAM-UE scores at discharge (DC(STREAM-UE)) and changes between admission and discharge (Δ(STREAM-UE)), were investigated to represent the final states and improvement of the recovery of voluntary UE movement. Stepwise regression analyses were used to investigate 19 clinical variables and to find the best predictive models of the two outcome measures. The participants showed wide variation in both DC(STREAM-UE) and Δ(STREAM-UE). 3.6% of the participants almost fully recovered at discharge (DC(STREAM-UE) > 15). A large improvement (Δ(STREAM-UE) >= 10) occurred in 16.4% of the participants, while 32.9% of the participants did not have any improvement. The four predictors for the DC(STREAM-UE) (R(2) = 35.0%) were 'baseline STREAM-UE score', 'hemorrhagic stroke', 'baseline National Institutes of Health Stroke Scale (NIHSS) score', and 'cortical lesion excluding primary motor cortex'. The three predictors for the Δ(STREAM-UE) (R(2) = 22.0%) were 'hemorrhagic stroke', 'baseline NIHSS score', and 'cortical lesion excluding primary motor cortex'. Recovery of voluntary UE movement varied widely in patients with severe UE paresis after stroke. The predictive power of clinical variables was poor. Both results indicate the complex nature of voluntary UE movement recovery in patients with severe UE paresis after stroke.

Bias Field Inconsistency Correction of Motion-Scattered Multislice MRI for Improved 3D Image Reconstruction

PubMed Central

Kim, Kio; Habas, Piotr A.; Rajagopalan, Vidya; Scott, Julia A.; Corbett-Detig, James M.; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

2012-01-01

A common solution to clinical MR imaging in the presence of large anatomical motion is to use fast multi-slice 2D studies to reduce slice acquisition time and provide clinically usable slice data. Recently, techniques have been developed which retrospectively correct large scale 3D motion between individual slices allowing the formation of a geometrically correct 3D volume from the multiple slice stacks. One challenge, however, in the final reconstruction process is the possibility of varying intensity bias in the slice data, typically due to the motion of the anatomy relative to imaging coils. As a result, slices which cover the same region of anatomy at different times may exhibit different sensitivity. This bias field inconsistency can induce artifacts in the final 3D reconstruction that can impact both clinical interpretation of key tissue boundaries and the automated analysis of the data. Here we describe a framework to estimate and correct the bias field inconsistency in each slice collectively across all motion corrupted image slices. Experiments using synthetic and clinical data show that the proposed method reduces intensity variability in tissues and improves the distinction between key tissue types. PMID:21511561

Bias field inconsistency correction of motion-scattered multislice MRI for improved 3D image reconstruction.

PubMed

Kim, Kio; Habas, Piotr A; Rajagopalan, Vidya; Scott, Julia A; Corbett-Detig, James M; Rousseau, Francois; Barkovich, A James; Glenn, Orit A; Studholme, Colin

2011-09-01

A common solution to clinical MR imaging in the presence of large anatomical motion is to use fast multislice 2D studies to reduce slice acquisition time and provide clinically usable slice data. Recently, techniques have been developed which retrospectively correct large scale 3D motion between individual slices allowing the formation of a geometrically correct 3D volume from the multiple slice stacks. One challenge, however, in the final reconstruction process is the possibility of varying intensity bias in the slice data, typically due to the motion of the anatomy relative to imaging coils. As a result, slices which cover the same region of anatomy at different times may exhibit different sensitivity. This bias field inconsistency can induce artifacts in the final 3D reconstruction that can impact both clinical interpretation of key tissue boundaries and the automated analysis of the data. Here we describe a framework to estimate and correct the bias field inconsistency in each slice collectively across all motion corrupted image slices. Experiments using synthetic and clinical data show that the proposed method reduces intensity variability in tissues and improves the distinction between key tissue types.

Prevalence, Clinical Characteristics, and Management of Functional Constipation at Pediatric Gastroenterology Clinics

PubMed Central

Chang, Soo Hee; Park, Kie Young; Kang, Sung Kil; Kang, Ki Soo; Na, So Young; Yang, Hye Ran; Uhm, Ji Hyun

2013-01-01

The purpose of this study was to investigate the prevalence, clinical characteristics, and management of functional constipation at pediatric gastroenterology clinics. A prospective survey using the Rome III criteria was distributed to a group of parents of children with a constipation history and its control group in May 2008. The mean prevalence of constipation was 6.4%, which was similar to those in other countries. Statistically significant variables for children without constipation were that more children had a body mass index of below the 10th percentile even though they received more mother's care and ate balanced meals compared to the constipation group. Meanwhile, the constipation group frequently showed a history of constipation in infancy, picky-eating, lack of exercise, and retentive posturing. When analyzed with the Rome III criteria, the children showed greater than 60% rate of hard stools, painful stools, a history of large fecal mass in rectum, and its disappearance of constipation symptoms after passing a large stool. Our study found different approaches amongst pediatric gastroenterologists like rectal examinations, disimpaction, or drug treatment. Several factors addressed in our study can provide better guidelines for clinicians treating constipation and its future research. PMID:24015043

Prevalence, clinical characteristics, and management of functional constipation at pediatric gastroenterology clinics.

PubMed

Chang, Soo Hee; Park, Kie Young; Kang, Sung Kil; Kang, Ki Soo; Na, So Young; Yang, Hye Ran; Uhm, Ji Hyun; Ryoo, Eell

2013-09-01

The purpose of this study was to investigate the prevalence, clinical characteristics, and management of functional constipation at pediatric gastroenterology clinics. A prospective survey using the Rome III criteria was distributed to a group of parents of children with a constipation history and its control group in May 2008. The mean prevalence of constipation was 6.4%, which was similar to those in other countries. Statistically significant variables for children without constipation were that more children had a body mass index of below the 10th percentile even though they received more mother's care and ate balanced meals compared to the constipation group. Meanwhile, the constipation group frequently showed a history of constipation in infancy, picky-eating, lack of exercise, and retentive posturing. When analyzed with the Rome III criteria, the children showed greater than 60% rate of hard stools, painful stools, a history of large fecal mass in rectum, and its disappearance of constipation symptoms after passing a large stool. Our study found different approaches amongst pediatric gastroenterologists like rectal examinations, disimpaction, or drug treatment. Several factors addressed in our study can provide better guidelines for clinicians treating constipation and its future research.

Variability in sublingual microvessel density and flow measurements in healthy volunteers.

PubMed

Hubble, Sheena M A; Kyte, Hayley L; Gooding, Kim; Shore, Angela C

2009-02-01

As sublingual microvascular indices are increasingly heralded as new resuscitation end-points, better population data are required to power clinical studies. This paper describes improved methods to quantify sublingual microvessel flow and density in images obtained by sidestream dark field (SDF) technology in healthy volunteers, including vessels under 10 microm in diameter. Measurements of sublingual capillary density and flow were obtained by recording three 15-second images in 20 healthy volunteers over three days. Two independent observers quantified capillary density by using two methods: total vessel length (mm/mm2) and counting (number/mm). Both intraoral and temporal variabilities within subject and observer reproducibilities were determined by using coefficients of variability and reproducibility indices. For small (1-10 microm), medium (11-20 microm), and large (21-50 microm) diameter, mean vessel density with standard deviations (SDs) in volunteers was 21.3(+/- 4.9), 5.2 (+/- 1.2), and 2.7 (+/- 0.9) mm/mm2, respectively. Also, 94.0 +/- 1.4% of small vessels, 94.5 +/- 1.4% of medium vessels, and 94.5+/- 4.0% of large vessels had continuous perfusion. Within subjects, the means of all measurements over three days varied less than 13, 22, and 35% in small, medium, and large vessels, respectively. Interobserver reproducibility was good, especially for capillary (1-10 microm) density and flow measurements. Our methods of microvessel flow and density quantification have low observer variability and confirm the stability of microcirculatory measurements over time. These results facilitate the development of SDF-acquired sublingual microvascular indices as feasible microperfusion markers in shock resuscitation.

Influence of family history of major depression, bipolar disorder, and suicide on clinical features in patients with major depression and bipolar disorder.

PubMed

Serretti, Alessandro; Chiesa, Alberto; Calati, Raffaella; Linotte, Sylvie; Sentissi, Othman; Papageorgiou, Konstantinos; Kasper, Siegfried; Zohar, Joseph; De Ronchi, Diana; Mendlewicz, Julien; Amital, Daniela; Montgomery, Stuart; Souery, Daniel

2013-03-01

The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide-considered both separately and together-on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed.

Alcohol- and light-induced electro-oculographic responses: variability and clinical utility.

PubMed

Marmor, Michael F; Wu, Kathy H C

2005-01-01

The alcohol-induced electro-oculographic (EOG) response has been proposed by Arden as an indicator of retinal pigment epithelial (RPE) integrity. We have evaluated the consistency of the alcohol-EOG with respect to clinical applicability and compared this response to the ISCEV-standard EOG. We recorded, in a group of normal subjects (n=29, 14 men with mean age 42+/-11 years and 15 women with mean age 36+/-13 years), the alcohol response to a single oral dose of ethanol at 160 mg/kg (as 40 proof vodka, drunk in 15 s after 12 h of fasting), followed by an ISCEV-standard EOG 90 min after alcohol administration. Blood alcohol levels were monitored at regular intervals with a breath analyzer. We found a wide range of amplitudes in both light and alcohol responses among participants, from minimal to large values. Subjects had a wide range of blood alcohol concentrations from 0.02 to 0.10%; near the time of the response peak, but there was no relationship between alcohol levels and peak/baseline ratios. In addition, there was no relationship between alcohol peak/baseline ratio and the Arden ratio. Neither the alcohol nor the light response parameters showed any relationship with age or gender. Some of the inter-individual variability in the EOG response to alcohol may reflect variable absorption of oral alcohol. The alcohol-induced EOG has too broad a range of responses to be useful clinically for the one-time evaluation of individual patients. We have similar concerns regarding clinical applications of the standard light-induced EOG.

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.

[Cost at the first level of care].

PubMed

Villarreal-Ríos, E; Montalvo-Almaguer, G; Salinas-Martínez, M; Guzmán-Padilla, J E; Tovar-Castillo, N H; Garza-Elizondo, M E

1996-01-01

To estimate the unit cost of 15 causes of demand for primary care per health clinic in an institutional (social security) health care system, and to determine the average cost at the state level. The cost of 80% of clinic visits was estimated in 35 of 40 clinics in the social security health care system in the state of Nuevo Leon, Mexico. The methodology for fixed costs consisted of: departmentalization, inputs, cost, weights and construction of matrices. Variable costs were estimated for standard patients by type of health care sought and with the consensus of experts; the sum of fixed and variable costs gave the unit cost. A computerized model was employed for data processing. A large variation in unit cost was observed between health clinics studied for all causes of demand, in both metropolitan and non-metropolitan areas. Prenatal care ($92.26) and diarrhea ($93.76) were the least expensive while diabetes ($240.42) and hypertension ($312.54) were the most expensive. Non-metropolitan costs were higher than metropolitan costs (p < 0.05); controlling for number of physician's offices showed that this was determined by medical units with only one physician's office. Knowledge of unit costs is a tool that, when used by medical administrators, allows adequate health care planning and efficient allocation of health resources.

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.

Do team processes really have an effect on clinical performance? A systematic literature review.

PubMed

Schmutz, J; Manser, T

2013-04-01

There is a growing literature on the relationship between team processes and clinical performance. The purpose of this review is to summarize these articles and examine the impact of team process behaviours on clinical performance. We conducted a literature search in five major databases. Inclusion criteria were: English peer-reviewed papers published between January 2001 and May 2012, which showed or tried to show (i) a statistical relationship of a team process variable and clinical performance or (ii) an improvement of a performance variable through a team process intervention. Study quality was assessed using predefined quality indicators. For every study, we calculated the relevant effect sizes. We included 28 studies in the review, seven of which were intervention studies. Every study reported at least one significant relationship between team processes or an intervention and performance. Also, some non-significant effects were reported. Most of the reported effect sizes were large or medium. The study quality ranged from medium to high. The studies are highly diverse regarding the specific team process behaviours investigated and also regarding the methods used. However, they suggest that team process behaviours do influence clinical performance and that training results in increased performance. Future research should rely on existing theoretical frameworks, valid, and reliable methods to assess processes such as teamwork or coordination and focus on the development of adequate tools to assess process performance, linking them with outcomes in the clinical setting.

Quantitative topographic differentiation of the neonatal EEG.

PubMed

Paul, Karel; Krajca, Vladimír; Roth, Zdenek; Melichar, Jan; Petránek, Svojmil

2006-09-01

To test the discriminatory topographic potential of a new method of the automatic EEG analysis in neonates. A quantitative description of the neonatal EEG can contribute to the objective assessment of the functional state of the brain, and may improve the precision of diagnosing cerebral dysfunctions manifested by 'disorganization', 'dysrhythmia' or 'dysmaturity'. 21 healthy, full-term newborns were examined polygraphically during sleep (EEG-8 referential derivations, respiration, ECG, EOG, EMG). From each EEG record, two 5-min samples (one from the middle of quiet sleep, the other from the middle of active sleep) were subject to subsequent automatic analysis and were described by 13 variables: spectral features and features describing shape and variability of the signal. The data from individual infants were averaged and the number of variables was reduced by factor analysis. All factors identified by factor analysis were statistically significantly influenced by the location of derivation. A large number of statistically significant differences were also established when comparing the effects of individual derivations on each of the 13 measured variables. Both spectral features and features describing shape and variability of the signal are largely accountable for the topographic differentiation of the neonatal EEG. The presented method of the automatic EEG analysis is capable to assess the topographic characteristics of the neonatal EEG, and it is adequately sensitive and describes the neonatal electroencephalogram with sufficient precision. The discriminatory capability of the used method represents a promise for their application in the clinical practice.

Anatomic variants in Dandy-Walker complex.

PubMed

Jurcă, Maria Claudia; Kozma, Kinga; Petcheşi, CodruŢa Diana; Bembea, Marius; Pop, Ovidiu Laurean; MuŢiu, Gabriela; Coroi, Mihaela Cristiana; Jurcă, Alexandru Daniel; Dobjanschi, Luciana

2017-01-01

Dandy-Walker complex (DWC) is a malformative association of the central nervous system. DWC includes four different types: Dandy-Walker malformation (vermis agenesis or hypoplasia, cystic dilatation of the fourth ventricle and a large posterior fossa); Dandy-Walker variant (vermis hypoplasia, cystic dilatation of the fourth ventricle, normal posterior fossa); mega cysterna magna (large posterior fossa, normal vermis and fourth ventricle) and posterior fossa arachnoid cyst. We present and discuss four cases with different morphological and clinical forms of the Dandy-Walker complex. In all four cases, diagnosis was reached by incorporation of clinical (macrocephaly, seizures) and imaging [X-ray, computed tomography (CT), magnetic resonance imaging (MRI)] data. Two patients were diagnosed with Dandy-Walker complex, one patient was diagnosed with Dandy-Walker variant in a rare association with neurofibromatosis and one patient was diagnosed with a posterior fossa arachnoid cyst associated with left-sided Claude Bernard-Horner syndrome, congenital heart disease (coarctation of the aorta, mitral stenosis) and gastroesophageal reflux. In all forms of DWC, the clinical, radiological and functional manifestations are variable and require adequate diagnostic and therapeutic measures.

Site-Specific Expression of Polycomb-Group Genes Encoding the HPC-HPH/PRC1 Complex in Clinically Defined Primary Nodal and Cutaneous Large B-Cell Lymphomas

PubMed Central

Raaphorst, Frank M.; Vermeer, Maarten; Fieret, Elly; Blokzijl, Tjasso; Dukers, Danny; Sewalt, Richard G.A.B.; Otte, Arie P.; Willemze, Rein; Meijer, Chris J.L.M.

2004-01-01

Polycomb-group (PcG) genes preserve cell identity by gene silencing, and contribute to regulation of lymphopoiesis and malignant transformation. We show that primary nodal large B-cell lymphomas (LBCLs), and secondary cutaneous deposits from such lymphomas, abnormally express the BMI-1, RING1, and HPH1 PcG genes in cycling neoplastic cells. By contrast, tumor cells in primary cutaneous LBCLs lacked BMI-1 expression, whereas RING1 was variably detected. Lack of BMI-1 expression was characteristic for primary cutaneous LBCLs, because other primary extranodal LBCLs originating from brain, testes, and stomach were BMI-1-positive. Expression of HPH1 was rarely detected in primary cutaneous LBCLs of the head or trunk and abundant in primary cutaneous LBCLs of the legs, which fits well with its earlier recognition as a distinct clinical pathological entity with different clinical behavior. We conclude that clinically defined subclasses of primary LBCLs display site-specific abnormal expression patterns of PcG genes of the HPC-HPH/PRC1 PcG complex. Some of these patterns (such as the expression profile of BMI-1) may be diagnostically relevant. We propose that distinct expression profiles of PcG genes results in abnormal formation of HPC-HPH/PRC1 PcG complexes, and that this contributes to lymphomagenesis and different clinical behavior of clinically defined LBCLs. PMID:14742259

A Paradox-based data collection and management system for multi-center randomized clinical trials.

PubMed

Abdellatif, Mazen; Reda, Domenic J

2004-02-01

We have developed a Paradox-based data collection and management system for large-scale multi-site randomized clinical trials. The system runs under Windows operating system and integrates Symantec pcAnywhere32 telecommunications software for data transmission and remote control sessions, PKZIP utility for the compression/decompression of transmitted data, and Stat/Transfer for exporting the centralized Paradox database for analyses. We initially developed this system for VA Cooperative Study #399 'The Effect of Antiarrhythmic Therapy in Maintaining Stability of Sinus Rhythm in Atrial Fibrillation', which collects over 1000 variables on 706 patients at 20 sites. Patient intake for this 5-year study began in March of 1998. We have also developed an enhanced version of this system, which is being used in the NIH-funded 'Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)' that collects over 1200 variables on 1588 patients at 13 sites. Patient intake for this 4-year study began in October of 2000.

Faster PET reconstruction with a stochastic primal-dual hybrid gradient method

NASA Astrophysics Data System (ADS)

Ehrhardt, Matthias J.; Markiewicz, Pawel; Chambolle, Antonin; Richtárik, Peter; Schott, Jonathan; Schönlieb, Carola-Bibiane

2017-08-01

Image reconstruction in positron emission tomography (PET) is computationally challenging due to Poisson noise, constraints and potentially non-smooth priors-let alone the sheer size of the problem. An algorithm that can cope well with the first three of the aforementioned challenges is the primal-dual hybrid gradient algorithm (PDHG) studied by Chambolle and Pock in 2011. However, PDHG updates all variables in parallel and is therefore computationally demanding on the large problem sizes encountered with modern PET scanners where the number of dual variables easily exceeds 100 million. In this work, we numerically study the usage of SPDHG-a stochastic extension of PDHG-but is still guaranteed to converge to a solution of the deterministic optimization problem with similar rates as PDHG. Numerical results on a clinical data set show that by introducing randomization into PDHG, similar results as the deterministic algorithm can be achieved using only around 10 % of operator evaluations. Thus, making significant progress towards the feasibility of sophisticated mathematical models in a clinical setting.

Assessment of variability in cerebral vasculature for neuro-anatomical surgery planning in rodent brain

NASA Astrophysics Data System (ADS)

Rangarajan, J. R.; Van Kuyck, K.; Himmelreich, U.; Nuttin, B.; Maes, F.; Suetens, P.

2011-03-01

Clinical and pre-clinical studies show that deep brain stimulation (DBS) of targeted brain regions by neurosurgical techniques ameliorate psychiatric disorder such as anorexia nervosa. Neurosurgical interventions in preclinical rodent brain are mostly accomplished manually with a 2D atlas. Considering both the large number of animals subjected to stereotactic surgical experiments and the associated imaging cost, feasibility of sophisticated pre-operative imaging based surgical path planning and/or robotic guidance is limited. Here, we spatially normalize vasculature information and assess the intra-strain variability in cerebral vasculature for a neurosurgery planning. By co-registering and subsequently building a probabilistic vasculature template in a standard space, we evaluate the risk of a user defined electrode trajectory damaging a blood vessel on its path. The use of such a method may not only be confined to DBS therapy in small animals, but also could be readily applicable to a wide range of stereotactic small animal surgeries like targeted injection of contrast agents and cell labeling applications.

Ultrasound imaging transducer motion during clinical maneuvers: respiration, active straight leg raise test and abdominal drawing in.

PubMed

Whittaker, Jackie L; Warner, Martin B; Stokes, Maria J

2010-08-01

Clinical use of ultrasound imaging by physiotherapists is increasing; however, the clinical setting may be problematic due to variability inherent in the environment. As transducer motion interferes with accurate measurement, this study aimed to measure handheld transducer motion, relative to the pelvis, during a clinical simulation involving typical maneuvers employed in a physiotherapy assessment of the lumbopelvic region. Transducer motion about three axes and through one plane was measured (Vicon, Oxford, UK) on 12 participants during three clinical maneuvers at four abdominal imaging sites. Data were grouped and means used to determine discrepancies in transducer and pelvic motion for each imaging site/maneuver combination. None of the conditions produced large transducer motions relative to the pelvis and all findings were within previously established guidelines for acceptable amounts of transducer motion. These findings suggest that an ultrasound transducer can be held relatively stationary in a clinical setting, for the maneuvers tested. Copyright 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Sex Differences in Cannabis Use Disorder Diagnosis Involved Hospitalizations in the United States

PubMed Central

Zhu, He; Wu, Li-Tzy

2017-01-01

Objectives: The study examined sex differences in trend and clinical characteristics of cannabis use disorder (CUD) diagnosis involved hospitalizations among adult patients. Methods: We analyzed hospitalization data from the 2007–2011 Nationwide Inpatient Samples for patients aged 18–64 years (N = 15,114,930). Descriptive statistics were used to characterize demographic variables and to compare the proportions of CUD diagnosis and comorbid patterns between male and female hospitalizations. Logistic regressions were performed to examine the association of sex and other demographic variables with CUD diagnosis. Results: During the study period, 3.3% of male and 1.5% of female hospitalizations had any-listed CUD diagnoses, and both sexes presented an upward trend in the number, rate, and proportion of CUD diagnosis. Among hospitalizations for patients aged 18–25 years, about 1 in 10 males and 1 in 20 females included a CUD diagnosis, and this proportion decreased with age strata. Mental disorders accounted for the highest proportion of CUD involved inpatient hospitalizations, and female CUD involved hospitalizations included a higher proportion of mental disorders that required hospitalized care compared with male hospitalizations (41% vs 36%). In each sex group, younger age, black race, lower household income, large metropolitan residence, non-private insurance, substance use diagnosis, and mental disorders were associated with elevated odds of having CUD diagnosis. Conclusion: The large sample of clinical hospitalization data suggest an increased trend in CUD diagnosis and sex differences in several comorbidities with CUD-involved hospital admissions. Prevention and treatment for CUD should consider sex differences in clinical comorbidities. PMID:28700366

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.

Heart rate variability and turbulence in hyperthyroidism before, during, and after treatment.

PubMed

Osman, Faizel; Franklyn, Jayne A; Daykin, Jacqueline; Chowdhary, Saqib; Holder, Roger L; Sheppard, Michael C; Gammage, Michael D

2004-08-15

Patients with subclinical and treated overt hyperthyroidism have an excess vascular mortality rate. Several symptoms and signs in overt hyperthyroidism suggest abnormality of cardiac autonomic function that may account in part for this excess mortality rate, but few studies have examined cardiac autonomic function in untreated and treated hyperthyroidism. We assessed heart rate turbulence (HRT) and time-domain parameters of heart rate variability in a large, unselected cohort of patients with overt hyperthyroidism referred to our thyroid clinic (n = 259) and compared findings with a group of normal subjects with euthyroidism (n = 440). These measures were also evaluated during antithyroid therapy (when serum-free thyroxine and triiodothyronine concentrations returned to normal but thyrotropin remained suppressed (i.e., subclinical hyperthyroidism, n = 110) and when subjects were rendered clinically and biochemically euthyroid (normal serum thyrotropin, free thyroxine and triiodothyronine concentrations, n = 219). We found that overall measures of heart rate variability and those specific for cardiac vagal modulation were attenuated in patients with overt hyperthyroidism compared with normal subjects; measurements of overall heart rate variability remained low in those with low levels of serum thyrotropin but returned to normal in patients with biochemical euthyroidism. Measurements of HRT (onset and slope) were also decreased in patients with overt hyperthyroidism, but HRT slope returned to normal values with antithyroid treatment. This study is the first to evaluate HRT in overt and treated hyperthyroidism.

Deciphering Sources of Variability in Clinical Pathology.

PubMed

Tripathi, Niraj K; Everds, Nancy E; Schultze, A Eric; Irizarry, Armando R; Hall, Robert L; Provencher, Anne; Aulbach, Adam

2017-01-01

The objectives of this session were to explore causes of variability in clinical pathology data due to preanalytical and analytical variables as well as study design and other procedures that occur in toxicity testing studies. The presenters highlighted challenges associated with such variability in differentiating test article-related effects from the effects of experimental procedures and its impact on overall data interpretation. These presentations focused on preanalytical and analytical variables and study design-related factors and their influence on clinical pathology data, and the importance of various factors that influence data interpretation including statistical analysis and reference intervals. Overall, these presentations touched upon potential effect of many variables on clinical pathology parameters, including animal physiology, sample collection process, specimen handling and analysis, study design, and some discussion points on how to manage those variables to ensure accurate interpretation of clinical pathology data in toxicity studies. This article is a brief synopsis of presentations given in a session entitled "Deciphering Sources of Variability in Clinical Pathology-It's Not Just about the Numbers" that occurred at the 35th Annual Symposium of the Society of Toxicologic Pathology in San Diego, California.

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

PubMed Central

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

2010-01-01

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

Epicardial fat thickness: distribution and association with diabetes mellitus, hypertension and the metabolic syndrome in the ELSA-Brasil study.

PubMed

Graeff, Daniela Bertol; Foppa, Murilo; Pires, Julio Cesar Gall; Vigo, Alvaro; Schmidt, Maria Ines; Lotufo, Paulo Andrade; Mill, Jose Geraldo; Duncan, Bruce Bartholow

2016-04-01

Epicardial fat thickness (EFT) has emerged as a marker of cardiometabolic risk, but its clinical use warrants proper knowledge of its distribution and associations in populations. We aimed to describe the distribution of EFT, its demographic correlates and independent associations with diabetes, hypertension and metabolic syndrome (MS) in free-living Brazilian adults. From the baseline echocardiography of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)-a cohort study of civil servants aged 35-74 years-EFT was measured from a randomly selected sample of 998 participants as the mean of two paraesternal windows obtained at end systole (EFTsyst) and end diastole (EFTdiast). From the 421 individuals free of diabetes, hypertension and MS, we defined EFT reference values and the EFTsyst 75th percentile cut-off. Median EFTsyst was 1.5 (IQR 0-2.6) mm; a large proportion (84 %) had EFTdiast = 0. EFT was higher in women and lower in blacks, and increased with age and BMI. Although EFT was higher in those with diabetes, hypertension, and MS, EFT associations were reduced when adjusted for age, sex and ethnicity, and were non-significant after adjusting for obesity measures. In conclusion, the amount of EFT in this large multiethnic population is smaller than reported in other populations. EFT reference values varied across demographic and clinical variables, EFT associations with cardiometabolic variables being largely explained by age, sex, ethnicity and central obesity. Although EFT can help identify individuals at increased cardiometabolic risk, it will likely have a limited additional role compared to current risk stratification strategies.

Orientation program for hospital-based nurse practitioners.

PubMed

Bahouth, Mona N; Esposito-Herr, Mary Beth

2009-01-01

The transition from student to practicing clinician is often a challenging and difficult period for many nurse practitioners. Newly graduated nurse practitioners commonly describe feelings of inadequacy in assuming clinical responsibilities, lack of support by team members, unclear expectations for the orientation period, and role isolation. This article describes the formal nurse practitioner orientation program implemented at the University of Maryland Medical Center, a large urban academic medical center, to facilitate the transition of new nurse practitioners into the workforce. This comprehensive program incorporates streamlined administrative activities, baseline didactic and simulation-based critical care education, ongoing and focused peer support, access to formalized resources, and individualized clinical preceptor programs. This formalized orientation program has proven to be one of the key variables to successful integration of nurse practitioners into our acute care clinical teams.

Dietary interventions in overweight and obese pregnant women: a systematic review of the content, delivery, and outcomes of randomized controlled trials.

PubMed

Flynn, Angela C; Dalrymple, Kathryn; Barr, Suzanne; Poston, Lucilla; Goff, Louise M; Rogozińska, Ewelina; van Poppel, Mireille N M; Rayanagoudar, Girish; Yeo, SeonAe; Barakat Carballo, Ruben; Perales, Maria; Bogaerts, Annick; Cecatti, Jose G; Dodd, Jodie; Owens, Julie; Devlieger, Roland; Teede, Helena; Haakstad, Lene; Motahari-Tabari, Narges; Tonstad, Serena; Luoto, Riitta; Guelfi, Kym; Petrella, Elisabetta; Phelan, Suzanne; Scudeller, Tânia T; Hauner, Hans; Renault, Kristina; Sagedal, Linda Reme; Stafne, Signe N; Vinter, Christina; Astrup, Arne; Geiker, Nina R W; McAuliffe, Fionnuala M; Mol, Ben W; Thangaratinam, Shakila

2016-05-01

Interventions targeting maternal obesity are a healthcare and public health priority. The objective of this review was to evaluate the adequacy and effectiveness of the methodological designs implemented in dietary intervention trials for obesity in pregnancy. A systematic review of the literature, consistent with PRISMA guidelines, was performed as part of the International Weight Management in Pregnancy collaboration. Thirteen randomized controlled trials, which aimed to modify diet and physical activity in overweight and obese pregnant women, were identified. There was significant variability in the content, delivery, and dietary assessment methods of the dietary interventions examined. A number of studies demonstrated improved dietary behavior in response to diet and/or lifestyle interventions. Nine studies reduced gestational weight gain. This review reveals large methodological variability in dietary interventions to control gestational weight gain and improve clinical outcomes in overweight and obese pregnant women. This lack of consensus limits the ability to develop clinical guidelines and apply the evidence in clinical practice. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

A national survey of pain clinics within the United Kingdom and Ireland focusing on the multidisciplinary team and the incorporation of the extended nursing role.

PubMed

Kailainathan, Pungavi; Humble, Stephen; Dawson, Helen; Cameron, Fiona; Gokani, Shyam; Lidder, Gursimren

2018-02-01

Inconsistencies in the availability and quality of pain service provision have been noted nationally, as have lengthy waiting times for appointments and lack of awareness of the Pain Clinic role. The 2013 NHS England report stated that specialist pain services must offer multispecialty and multidisciplinary pain clinics. This national survey of multidisciplinary pain service provision in the United Kingdom and Ireland provides a snapshot of pain service provision in order to review and highlight what variations exist in multidisciplinary team (MDT) provision and working patterns. A common perception among clinicians is that financial pressures have led to alternate ways of staff utilisation with variable degrees of success. The survey included 143 pain clinics, focusing principally on MDT working patterns, MDT composition and adoption of the extended role. The results identified that the majority of Pain Clinics utilise the MDT approach. However, provision of critical components such as regular MDT meetings is highly variable as is the composition of the MDT itself and also working patterns of the individual clinicians. The survey reports the successful use of the extended roles for specialist nurses in follow up clinics. In contrast, the survey highlights that a large proportion of clinicians surveyed have reservations about both the effectiveness and the safety of utilising specialist nurses in the extended role to see new referrals of complex pain patients to pain clinics. This survey underlines the essential requirement for incorporation of greater MDT working locally and nationally and allocation of appropriate resources to facilitate this.

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.

Variables selection methods in near-infrared spectroscopy.

PubMed

Xiaobo, Zou; Jiewen, Zhao; Povey, Malcolm J W; Holmes, Mel; Hanpin, Mao

2010-05-14

Near-infrared (NIR) spectroscopy has increasingly been adopted as an analytical tool in various fields, such as the petrochemical, pharmaceutical, environmental, clinical, agricultural, food and biomedical sectors during the past 15 years. A NIR spectrum of a sample is typically measured by modern scanning instruments at hundreds of equally spaced wavelengths. The large number of spectral variables in most data sets encountered in NIR spectral chemometrics often renders the prediction of a dependent variable unreliable. Recently, considerable effort has been directed towards developing and evaluating different procedures that objectively identify variables which contribute useful information and/or eliminate variables containing mostly noise. This review focuses on the variable selection methods in NIR spectroscopy. Selection methods include some classical approaches, such as manual approach (knowledge based selection), "Univariate" and "Sequential" selection methods; sophisticated methods such as successive projections algorithm (SPA) and uninformative variable elimination (UVE), elaborate search-based strategies such as simulated annealing (SA), artificial neural networks (ANN) and genetic algorithms (GAs) and interval base algorithms such as interval partial least squares (iPLS), windows PLS and iterative PLS. Wavelength selection with B-spline, Kalman filtering, Fisher's weights and Bayesian are also mentioned. Finally, the websites of some variable selection software and toolboxes for non-commercial use are given. Copyright 2010 Elsevier B.V. All rights reserved.

Significance of Large Vessel Intracranial Occlusion Causing Acute Ischemic Stroke and TIA

PubMed Central

Smith, Wade S.; Lev, Michael H.; English, Joey D.; Camargo, Erica C.; Chou, Maggie; Johnston, S. Claiborne; Gonzalez, Gilberto; Schaefer, Pamela W.; Dillon, William P.; Koroshetz, Walter J.; Furie, Karen L.

2009-01-01

Background: Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries- likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data has been reported on a cohort of unselected stroke and TIA patients, the clinical impact of LVO has been difficult to quantify. Methods: The STOP-Stroke Study is a prospective imaging-based study of stroke outcomes performed at two academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multi-modality CT/CTA were approached for consent for collection of clinical data and 6 month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin scores (mRS) were collected and combined with blinded interpretation of the CTA data. The odds ratio (OR) of each variable including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality was calculated using univariate and multivariate logistic regression. Results: Over a 33 month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as TIA. Among stroke patients, 267 (46%) had LVO accounting for the stroke and 13 (13%) of TIA patients had LVO accounting for TIA symptoms. LVO predicted six-month mortality (OR 4.5; 95% CI 2.7-7.3; p<0.001). Six-month good outcome (mRS≤ 2) was negatively predicted by LVO (0.33; 0.24-0.45; p<0.001). Based on multivariate analysis, the presence of basilar and internal carotid terminus occlusions, in addition to NIHSS and age, independently predicted outcome. Conclusion: Large vessel intracranial occlusion accounted for nearly half of acute ischemic strokes in unselected patients presenting to academic medical centers. In addition to age and baseline stroke severity, occlusion of either the basilar or internal carotid terminus segment is an independent predictor of outcome at 6 months. PMID:19834014

[Clinical and pathogenetic aspects of the chronic occupational intoxication with fluorine compounds in modern reality].

PubMed

Roslaia, N A; Likhacheva, E I; Oranskiĭ, I E; Odinokaia, V A; Plotko, É G; Zhovtiak, E P; Fedorov, A A; Riabko, E V

2012-01-01

Multi-year follow-up of 358 workers of aluminum pot rooms, including 165 individuals suffering from fluorosis, has shown significant changes in the clinical picture of the chronic occupational fluorine intoxication, developed under modern conditions of production, at lower concentrations of fluorine compounds in the air of working area. In this connection, the pathology of the musculoskeletal system plays the dominating role in this clinical picture and has the large variability of combinations of the individual sections destructions of the bone tissue. The main criterion to establish the phase of the disease is still the number and severity of the signs of this destruction. The visceral pathology in contemporary production circumstances is registered with less frequency and loses a number of the previously described clinical manifestations, however, is still of some importance to identify the early signs of the disease and to prevent the dental fluorosis on time.

Delinquency prevention through training parents in family management

PubMed Central

Bank, Lew; Patterson, Gerald R.; Reid, John B.

1987-01-01

Nearly two decades of clinical research at the Oregon Social Learning Center (OSLC) have helped to shape a theory of antisocial behavior in boys. Models depicting the theory are presented and discussed. In addition, family management variables such as “discipline,” “monitoring,” “positive parenting,” and “problem solving” are described as used in clinical applications. Total aversive behavior (TAB), based on home observations, and parent daily report (PDR), based on telephone interviews, are examined as outcome indicators for a variety of studies investigating the efficacy of the OSLC social interactional therapy. Several recent reports of treatment for adjudicated adolescents and their families are included; law violations are the dependent measures in those studies. Examples of the interface between clinical work and theory at OSLC are presented. Questions of generalization of the clinical methodology to large urban populations, and access to parents who most need to learn the parenting techniques are noted. PMID:22477963

Neuropsychiatric disorders in persons with severe traumatic brain injury: prevalence, phenomenology, and relationship with demographic, clinical, and functional features.

PubMed

Ciurli, Paola; Formisano, Rita; Bivona, Umberto; Cantagallo, Anna; Angelelli, Paola

2011-01-01

To characterize neuropsychiatric symptoms in a large group of individuals with severe traumatic brain injury (TBI) and to correlate these symptoms with demographic, clinical, and functional features. The Neuropsychiatric Inventory (NPI), a frequently used scale to assess behavioral, emotional, and motivational disorders in persons with neurological diseases, was administered to a sample of 120 persons with severe TBI. Controls were 77 healthy subjects. A wide range of neuropsychiatric symptoms was found in the population with severe TBI: apathy (42%), irritability (37%), dysphoria/depressed mood (29%), disinhibition (28%), eating disturbances (27%), and agitation (24%). A clear relationship was also found with other demographic and clinical variables. Neuropsychiatric disorders constitute an important part of the comorbidity in populations with severe TBI. Our study emphasizes the importance of integrating an overall assessment of cognitive disturbances with a specific neuropsychiatric evaluation to improve clinical understanding and treatment of persons with TBI.

A tool for prediction of risk of rehospitalisation and mortality in the hospitalised elderly: secondary analysis of clinical trial data

PubMed Central

Alassaad, Anna; Melhus, Håkan; Hammarlund-Udenaes, Margareta; Bertilsson, Maria; Gillespie, Ulrika; Sundström, Johan

2015-01-01

Objectives To construct and internally validate a risk score, the ‘80+ score’, for revisits to hospital and mortality for older patients, incorporating aspects of pharmacotherapy. Our secondary aim was to compare the discriminatory ability of the score with that of three validated tools for measuring inappropriate prescribing: Screening Tool of Older Person's Prescriptions (STOPP), Screening Tool to Alert doctors to Right Treatment (START) and Medication Appropriateness Index (MAI). Setting Two acute internal medicine wards at Uppsala University hospital. Patient data were used from a randomised controlled trial investigating the effects of a comprehensive clinical pharmacist intervention. Participants Data from 368 patients, aged 80 years and older, admitted to one of the study wards. Primary outcome measure Time to rehospitalisation or death during the year after discharge from hospital. Candidate variables were selected among a large number of clinical and drug-specific variables. After a selection process, a score for risk estimation was constructed. The 80+ score was internally validated, and the discriminatory ability of the score and of STOPP, START and MAI was assessed using C-statistics. Results Seven variables were selected. Impaired renal function, pulmonary disease, malignant disease, living in a nursing home, being prescribed an opioid or being prescribed a drug for peptic ulcer or gastroesophageal reflux disease were associated with an increased risk, while being prescribed an antidepressant drug (tricyclic antidepressants not included) was linked to a lower risk of the outcome. These variables made up the components of the 80+ score. The C-statistics were 0.71 (80+), 0.57 (STOPP), 0.54 (START) and 0.63 (MAI). Conclusions We developed and internally validated a score for prediction of risk of rehospitalisation and mortality in hospitalised older people. The score discriminated risk better than available tools for inappropriate prescribing. Pending external validation, this score can aid in clinical identification of high-risk patients and targeting of interventions. PMID:25694461

Respiratory function of children in homes insulated with urea formaldehyde foam insulation.

PubMed Central

Norman, G R; Pengelly, L D; Kerigan, A T; Goldsmith, C H

1986-01-01

A study was carried out to assess the respiratory function of children living in homes insulated with urea formaldehyde foam insulation (UFFI). A large data base on the effect of environmental variables on the respiratory function of 3500 children in the Hamilton, Ont., area had been collected from 1978 to 1980. From this data base 29 children who lived in UFFI-insulated homes were identified, and each was matched with 2 controls according to nine variables that had been shown to be strongly predictive of respiratory function. Reported respiratory symptoms and results of pulmonary function testing in the year immediately following installation of UFFI were examined. No significant differences in any variable were found between the subjects and controls. A power calculation indicated that the study had adequate power to detect clinically important changes. The authors conclude that there was no evidence of respiratory problems resulting from UFFI in the sample studied. PMID:3697859

Post-marketing survey on clinical response to interferon beta in relapsing multiple sclerosis: the Roman experience.

PubMed

Pozzilli, C; Prosperini, L; Sbardella, E; De Giglio, L; Onesti, E; Tomassini, V

2005-12-01

Safety, tolerability and efficacy profiles of interferon beta (IFNbeta) therapy in relapsing multiple sclerosis (MS) has been widely verified both in trial settings and in daily clinical practice. However, for a variable percentage of treated patients, it remains only partially effective. In this study, we reported the post-marketing experience of the efficacy of IFNbeta therapy for a large cohort of MS patients regularly attending the MS Outpatient Clinic of "La Sapienza University" in Rome. In this cohort we also sought clinical and paraclinical variables responsible for the clinical course of MS during IFNbeta therapy. Patients that received treatment with one of the IFNbeta formulations for at least 1 year were included. Clinical outcomes (i. e., relapses and disability score) were monitored throughout the entire study period. Magnetic resonance imaging (MRI) scans were performed twice for each subject: at baseline and after 1 year of therapy. The occurrence of more than one relapse during the study period or a sustained disability progression in the Expanded Disability Status Scale (EDSS) score were considered as criteria for the definition of suboptimal clinical response to IFNbeta therapy. During IFNbeta therapy (number of patients 242, mean length of treatment 4.3+/-2.3 years) a reduction in the annualised relapse rate of 59% (p<0.001) was observed. Eighty-six patients (35%) fulfilled the criterion for defining "suboptimal responder" on the basis of relapses, and 69 (28.5%) did the same on the basis of EDSS sustained progression. Twenty-seven (11.1%) patients showed both an EDSS progression and two or more relapses. The presence of T1-enhancing lesions and new T2 hyperintense lesions on the scan performed after the first year of therapy were the best MRI features associated with both the occurrence of relapses during the treatment period (OR for enhancing lesions and relapses 3.6; OR for new T2 lesion and relapses 2.8). The present post-marketing experience confirms the efficacy of IFNbeta in modifying the natural course of MS and encourages the use of paraclinical variables measuring subclinical disease activity as surrogate markers to monitor the clinical course of MS during IFNbeta therapy.

LabVIEW: a software system for data acquisition, data analysis, and instrument control.

PubMed

Kalkman, C J

1995-01-01

Computer-based data acquisition systems play an important role in clinical monitoring and in the development of new monitoring tools. LabVIEW (National Instruments, Austin, TX) is a data acquisition and programming environment that allows flexible acquisition and processing of analog and digital data. The main feature that distinguishes LabVIEW from other data acquisition programs is its highly modular graphical programming language, "G," and a large library of mathematical and statistical functions. The advantage of graphical programming is that the code is flexible, reusable, and self-documenting. Subroutines can be saved in a library and reused without modification in other programs. This dramatically reduces development time and enables researchers to develop or modify their own programs. LabVIEW uses a large amount of processing power and computer memory, thus requiring a powerful computer. A large-screen monitor is desirable when developing larger applications. LabVIEW is excellently suited for testing new monitoring paradigms, analysis algorithms, or user interfaces. The typical LabVIEW user is the researcher who wants to develop a new monitoring technique, a set of new (derived) variables by integrating signals from several existing patient monitors, closed-loop control of a physiological variable, or a physiological simulator.

Evaluation of machine learning algorithms for improved risk assessment for Down's syndrome.

PubMed

Koivu, Aki; Korpimäki, Teemu; Kivelä, Petri; Pahikkala, Tapio; Sairanen, Mikko

2018-05-04

Prenatal screening generates a great amount of data that is used for predicting risk of various disorders. Prenatal risk assessment is based on multiple clinical variables and overall performance is defined by how well the risk algorithm is optimized for the population in question. This article evaluates machine learning algorithms to improve performance of first trimester screening of Down syndrome. Machine learning algorithms pose an adaptive alternative to develop better risk assessment models using the existing clinical variables. Two real-world data sets were used to experiment with multiple classification algorithms. Implemented models were tested with a third, real-world, data set and performance was compared to a predicate method, a commercial risk assessment software. Best performing deep neural network model gave an area under the curve of 0.96 and detection rate of 78% with 1% false positive rate with the test data. Support vector machine model gave area under the curve of 0.95 and detection rate of 61% with 1% false positive rate with the same test data. When compared with the predicate method, the best support vector machine model was slightly inferior, but an optimized deep neural network model was able to give higher detection rates with same false positive rate or similar detection rate but with markedly lower false positive rate. This finding could further improve the first trimester screening for Down syndrome, by using existing clinical variables and a large training data derived from a specific population. Copyright © 2018 Elsevier Ltd. All rights reserved.

Head Circumference and Height in Autism

PubMed Central

Lainhart, Janet E.; Bigler, Erin D.; Bocian, Maureen; Coon, Hilary; Dinh, Elena; Dawson, Geraldine; Deutsch, Curtis K.; Dunn, Michelle; Estes, Annette; Tager-Flusberg, Helen; Folstein, Susan; Hepburn, Susan; Hyman, Susan; McMahon, William; Minshew, Nancy; Munson, Jeff; Osann, Kathy; Ozonoff, Sally; Rodier, Patricia; Rogers, Sally; Sigman, Marian; Spence, M. Anne; Stodgell, Christopher J.; Volkmar, Fred

2016-01-01

Data from 10 sites of the NICHD/NIDCD Collaborative Programs of Excellence in Autism were combined to study the distribution of head circumference and relationship to demographic and clinical variables. Three hundred thirty-eight probands with autism-spectrum disorder (ASD) including 208 probands with autism were studied along with 147 parents, 149 siblings, and typically developing controls. ASDs were diagnosed, and head circumference and clinical variables measured in a standardized manner across all sites. All subjects with autism met ADI-R, ADOS-G, DSM-IV, and ICD-10 criteria. The results show the distribution of standardized head circumference in autism is normal in shape, and the mean, variance, and rate of macrocephaly but not microcephaly are increased. Head circumference tends to be large relative to height in autism. No site, gender, age, SES, verbal, or non-verbal IQ effects were present in the autism sample. In addition to autism itself, standardized height and average parental head circumference were the most important factors predicting head circumference in individuals with autism. Mean standardized head circumference and rates of macrocephaly were similar in probands with autism and their parents. Increased head circumference was associated with a higher (more severe) ADI-R social algorithm score. Macrocephaly is associated with delayed onset of language. Although mean head circumference and rates of macrocephaly are increased in autism, a high degree of variability is present, underscoring the complex clinical heterogeneity of the disorder. The wide distribution of head circumference in autism has major implications for genetic, neuroimaging, and other neurobiological research. PMID:17022081

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

PubMed

Karsten, Schober; Stephanie, Savino; Vedat, Yildiz

2017-11-10

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

Scrub typhus in South India: clinical and laboratory manifestations, genetic variability, and outcome.

PubMed

Varghese, George M; Janardhanan, Jeshina; Trowbridge, Paul; Peter, John V; Prakash, John A J; Sathyendra, Sowmya; Thomas, Kurien; David, Thambu S; Kavitha, M L; Abraham, Ooriapadickal C; Mathai, Dilip

2013-11-01

This study sought to document the clinical and laboratory manifestations, genetic variability, and outcomes of scrub typhus, an often severe infection caused by Orientia tsutsugamushi, in South India. Patients admitted to a large teaching hospital with IgM ELISA-confirmed scrub typhus were evaluated. Clinical examination with a thorough search for an eschar, laboratory testing, chest X-ray, and outcome were documented and analyzed. Additionally, a 410-bp region of the 56-kDa type-specific antigen gene of O. tsutsugamushi was sequenced and compared with isolates from other regions of Asia. Most of the 154 patients evaluated presented with fever and non-specific symptoms. An eschar was found in 86 (55%) patients. Mild hepatic involvement was seen in most, with other organ involvement including respiratory, cardiovascular, and renal. Multi-organ dysfunction was noted in 59 (38.3%), and the fatality rate was 7.8%. Hypotension requiring vasoactive agents was found to be an independent predictor of mortality (p<0.001). The phylogeny of 26 samples showed 17 (65%) clustering with the Kato-like group and eight (31%) with the Karp-like group. The presentation of scrub typhus can be variable, often non-specific, but with potentially severe multi-organ dysfunction. Prompt recognition is key to specific treatment and good outcomes. Further study of the circulating strains is essential for the development of a successful vaccine and sensitive point-of-care testing. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Clinical audit of COPD in outpatient respiratory clinics in Spain: the EPOCONSUL study

PubMed Central

Calle Rubio, Myriam; Alcázar Navarrete, Bernardino; Soriano, Joan B; Soler-Cataluña, Juan J; Rodríguez González-Moro, José Miguel; Fuentes Ferrer, Manuel E; López-Campos, José Luis

2017-01-01

Background Chronic obstructive pulmonary disease (COPD) outpatients account for a large burden of usual care by respirologists. EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics. We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines. Methodology This is an observational study with prospective recruitment (May 2014–May 2015) of patients with a COPD diagnosis as seen in outpatient respiratory clinics. The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent. Results A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated. Of the 5,726 patients selected, 4,508 (78.7%) were eligible. Overall, 12.1% of COPD patients did not fulfill a diagnostic spirometry criteria. Considerable variability existed in the available resources and work organization of the hospitals, although the majority were university hospitals with respiratory inpatient units. There was insufficient implementation of clinical guidelines in preventive and educational matters. In contrast, quantitative evaluation of dyspnea grade (81.9%) and exacerbation history (70.9%) were more frequently performed. Only 12.4% had COPD severity calculated according to the Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) index. Phenotype characteristics according to Spanish National Guideline for COPD were determined in 46.3% of the audited patients, and the risk evaluation according to Global initiative for chronic Obstructive Lung Disease was estimated only in 21.9%. Conclusion The EPOCONSUL study reports the current situation of medical care for COPD patients in outpatient clinics in Spain, revealing its variability, strengths, and weaknesses. This information has to be accounted for by health managers to define corrective strategies and maximize good clinical practice. PMID:28182155

Clinical audit of COPD in outpatient respiratory clinics in Spain: the EPOCONSUL study.

PubMed

Calle Rubio, Myriam; Alcázar Navarrete, Bernardino; Soriano, Joan B; Soler-Cataluña, Juan J; Rodríguez González-Moro, José Miguel; Fuentes Ferrer, Manuel E; López-Campos, José Luis

2017-01-01

Chronic obstructive pulmonary disease (COPD) outpatients account for a large burden of usual care by respirologists. EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics. We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines. This is an observational study with prospective recruitment (May 2014-May 2015) of patients with a COPD diagnosis as seen in outpatient respiratory clinics. The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent. A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated. Of the 5,726 patients selected, 4,508 (78.7%) were eligible. Overall, 12.1% of COPD patients did not fulfill a diagnostic spirometry criteria. Considerable variability existed in the available resources and work organization of the hospitals, although the majority were university hospitals with respiratory inpatient units. There was insufficient implementation of clinical guidelines in preventive and educational matters. In contrast, quantitative evaluation of dyspnea grade (81.9%) and exacerbation history (70.9%) were more frequently performed. Only 12.4% had COPD severity calculated according to the Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) index. Phenotype characteristics according to Spanish National Guideline for COPD were determined in 46.3% of the audited patients, and the risk evaluation according to Global initiative for chronic Obstructive Lung Disease was estimated only in 21.9%. The EPOCONSUL study reports the current situation of medical care for COPD patients in outpatient clinics in Spain, revealing its variability, strengths, and weaknesses. This information has to be accounted for by health managers to define corrective strategies and maximize good clinical practice.

Photon migration through fetal head in utero using continuous wave, near infrared spectroscopy: clinical and experimental model studies

NASA Astrophysics Data System (ADS)

Ramanujam, Nirmala; Vishnoi, Gargi; Hielscher, Andreas H.; Rode, Martha; Forouzan, Iraj; Chance, Britton

2000-04-01

Near infrared (NIR) measurements were made from the maternal abdomen (clinical studies) and laboratory tissue phantoms (experimental studies) to gain insight into photon migration through the fetal head in utero. Specifically, a continuous wave spectrometer was modified and employed to make NIR measurements at 760 and 850 nm, at a large (10 cm) and small (2.5/4 cm) source-detector separation, simultaneously, on the maternal abdomen, directly above the fetal head. A total of 19 patients were evaluated, whose average gestational age and fetal head depth, were 37 weeks +/- 3 and 2.25 cm +/- 0.7, respectively. At the large source-detector separation, the photons are expected to migrate through both the underlying maternal and fetal tissues before being detected at the surface, while at the short source-detector separation, the photons are expected to migrate primarily through the superficial maternal tissues before being detected. Second, similar NIR measurements were made on laboratory tissue phantoms, with variable optical properties and physical geometries. The variable optical properties were obtained using different concentrations of India ink and Intralipid in water, while the variable physical geometries were realized by employing glass containers of different shapes and sizes. Third, the NIR measurements, which were made on the laboratory tissue phantoms, were compared to the NIR measurements made on the maternal abdomen to determine which tissue phantom best simulates the photon migration path through the fetal head in utero. The results of the comparison were used to provide insight into the optical properties and physical geometry of the maternal and fetal tissues in the photon migration path.

Gait Deviation Index, Gait Profile Score and Gait Variable Score in children with spastic cerebral palsy: Intra-rater reliability and agreement across two repeated sessions.

PubMed

Rasmussen, Helle Mätzke; Nielsen, Dennis Brandborg; Pedersen, Niels Wisbech; Overgaard, Søren; Holsgaard-Larsen, Anders

2015-07-01

The Gait Deviation Index (GDI) and Gait Profile Score (GPS) are the most used summary measures of gait in children with cerebral palsy (CP). However, the reliability and agreement of these indices have not been investigated, limiting their clinimetric quality for research and clinical practice. The aim of this study was to investigate the intra-rater reliability and agreement of summary measures of gait (GDI; GPS; and the Gait Variable Score (GVS) derived from the GPS). The intra-rater reliability and agreement were investigated across two repeated sessions in 18 children aged 5-12 years diagnosed with spastic CP. No systematic bias was observed between the sessions and no heteroscedasticity was observed in Bland-Altman plots. For the GDI and GPS, excellent reliability with intraclass correlation coefficient (ICC) values of 0.8-0.9 was found, while the GVS was found to have fair to good reliability with ICCs of 0.4-0.7. The agreement for the GDI and the logarithmically transformed GPS, in terms of the standard error of measurement as a percentage of the grand mean (SEM%) varied from 4.1 to 6.7%, whilst the smallest detectable change in percent (SDC%) ranged from 11.3 to 18.5%. For the logarithmically transformed GVS, we found a fair to large variation in SEM% from 7 to 29% and in SDC% from 18 to 81%. The GDI and GPS demonstrated excellent reliability and acceptable agreement proving that they can both be used in research and clinical practice. However, the observed large variability for some of the GVS requires cautious consideration when selecting outcome measures. Copyright © 2015 Elsevier B.V. All rights reserved.

Proposed clinical pathway for nonoperative management of high-grade pediatric pancreatic injuries based on a multicenter analysis: A pediatric trauma society collaborative.

PubMed

Naik-Mathuria, Bindi J; Rosenfeld, Eric H; Gosain, Ankush; Burd, Randall; Falcone, Richard A; Thakkar, Rajan; Gaines, Barbara; Mooney, David; Escobar, Mauricio; Jafri, Mubeen; Stallion, Anthony; Klinkner, Denise B; Russell, Robert; Campbell, Brendan; Burke, Rita V; Upperman, Jeffrey; Juang, David; St Peter, Shawn; Fenton, Stephon J; Beaudin, Marianne; Wills, Hale; Vogel, Adam; Polites, Stephanie; Pattyn, Adam; Leeper, Christine; Veras, Laura V; Maizlin, Ilan; Thaker, Shefali; Smith, Alexis; Waddell, Megan; Drews, Joseph; Gilmore, James; Armstrong, Lindsey; Sandler, Alexis; Moody, Suzanne; Behrens, Brandon; Carmant, Laurence

2017-10-01

Guidelines for nonoperative management (NOM) of high-grade pancreatic injuries in children have not been established, and wide practice variability exists. The purpose of this study was to evaluate common clinical strategies across multiple pediatric trauma centers to develop a consensus-based standard clinical pathway. A multicenter, retrospective review was conducted of children with high-grade (American Association of Surgeons for Trauma grade III-V) pancreatic injuries treated with NOM between 2010 and 2015. Data were collected on demographics, clinical management, and outcomes. Eighty-six patients were treated at 20 pediatric trauma centers. Median age was 9 years (range, 1-18 years). The majority (73%) of injuries were American Association of Surgeons for Trauma grade III, 24% were grade IV, and 3% were grade V. Median time from injury to presentation was 12 hours and median ISS was 16 (range, 4-66). All patients had computed tomography scan and serum pancreatic enzyme levels at presentation, but serial enzyme level monitoring was variable. Pancreatic enzyme levels did not correlate with injury grade or pseudocyst development. Parenteral nutrition was used in 68% and jejunal feeds in 31%. 3Endoscopic retrograde cholangiopancreatogram was obtained in 25%. An organized peripancreatic fluid collection present for at least 7 days after injury was identified in 59% (42 of 71). Initial management of these included: observation 64%, percutaneous drain 24%, and endoscopic drainage 10% and needle aspiration 2%. Clear liquids were started at a median of 6 days (IQR, 3-13 days) and regular diet at a median of 8 days (IQR 4-20 days). Median hospitalization length was 13 days (IQR, 7-24 days). Injury grade did not account for prolonged time to initiating oral diet or hospital length; indicating that the variability in these outcomes was largely due to different surgeon preferences. High-grade pancreatic injuries in children are rare and significant variability exists in NOM strategies, which may affect outcomes and effective resource utilization. A standard clinical pathway is proposed. Therapeutic/care management, level V (case series).

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

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

The role of Epstein-Barr virus in systemic lupus erythematosus.

PubMed

McClain, M T; Harley, J B; James, J A

2001-10-01

Systemic lupus erythematosus (SLE) is a devastating autoimmune disease with no known cure. Lupus patients suffer from a myriad of clinical symptoms which variably include arthritis, pleuritis, pericarditis, vasculitis, and nephritis. The underlying mechanisms behind these clinical findings and the etiologic events preceding and causing disease onset, however, remain largely unknown. For many years, investigators have suspected that Epstein-Barr virus might somehow be involved in the etiology and/or pathogenesis of systemic lupus. Numerous studies have examined this possibility from various angles and have arrived at different conclusions. This work reviews these historical papers in the context of new results and presents a hypothetical role for this virus as an etiological environmental trigger for SLE.

Optimal auxiliary-covariate-based two-phase sampling design for semiparametric efficient estimation of a mean or mean difference, with application to clinical trials.

PubMed

Gilbert, Peter B; Yu, Xuesong; Rotnitzky, Andrea

2014-03-15

To address the objective in a clinical trial to estimate the mean or mean difference of an expensive endpoint Y, one approach employs a two-phase sampling design, wherein inexpensive auxiliary variables W predictive of Y are measured in everyone, Y is measured in a random sample, and the semiparametric efficient estimator is applied. This approach is made efficient by specifying the phase two selection probabilities as optimal functions of the auxiliary variables and measurement costs. While this approach is familiar to survey samplers, it apparently has seldom been used in clinical trials, and several novel results practicable for clinical trials are developed. We perform simulations to identify settings where the optimal approach significantly improves efficiency compared to approaches in current practice. We provide proofs and R code. The optimality results are developed to design an HIV vaccine trial, with objective to compare the mean 'importance-weighted' breadth (Y) of the T-cell response between randomized vaccine groups. The trial collects an auxiliary response (W) highly predictive of Y and measures Y in the optimal subset. We show that the optimal design-estimation approach can confer anywhere between absent and large efficiency gain (up to 24 % in the examples) compared to the approach with the same efficient estimator but simple random sampling, where greater variability in the cost-standardized conditional variance of Y given W yields greater efficiency gains. Accurate estimation of E[Y | W] is important for realizing the efficiency gain, which is aided by an ample phase two sample and by using a robust fitting method. Copyright © 2013 John Wiley & Sons, Ltd.

Optimal Auxiliary-Covariate Based Two-Phase Sampling Design for Semiparametric Efficient Estimation of a Mean or Mean Difference, with Application to Clinical Trials

PubMed Central

Gilbert, Peter B.; Yu, Xuesong; Rotnitzky, Andrea

2014-01-01

To address the objective in a clinical trial to estimate the mean or mean difference of an expensive endpoint Y, one approach employs a two-phase sampling design, wherein inexpensive auxiliary variables W predictive of Y are measured in everyone, Y is measured in a random sample, and the semi-parametric efficient estimator is applied. This approach is made efficient by specifying the phase-two selection probabilities as optimal functions of the auxiliary variables and measurement costs. While this approach is familiar to survey samplers, it apparently has seldom been used in clinical trials, and several novel results practicable for clinical trials are developed. Simulations are performed to identify settings where the optimal approach significantly improves efficiency compared to approaches in current practice. Proofs and R code are provided. The optimality results are developed to design an HIV vaccine trial, with objective to compare the mean “importance-weighted” breadth (Y) of the T cell response between randomized vaccine groups. The trial collects an auxiliary response (W) highly predictive of Y, and measures Y in the optimal subset. We show that the optimal design-estimation approach can confer anywhere between absent and large efficiency gain (up to 24% in the examples) compared to the approach with the same efficient estimator but simple random sampling, where greater variability in the cost-standardized conditional variance of Y given W yields greater efficiency gains. Accurate estimation of E[Y∣W] is important for realizing the efficiency gain, which is aided by an ample phase-two sample and by using a robust fitting method. PMID:24123289

Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project

PubMed Central

Kim, Youn H.; Tavallaee, Mahkam; Sundram, Uma; Salva, Katrin A.; Wood, Gary S.; Li, Shufeng; Rozati, Sima; Nagpal, Seema; Krathen, Michael; Reddy, Sunil; Hoppe, Richard T.; Nguyen-Lin, Annie; Weng, Wen-Kai; Armstrong, Randall; Pulitzer, Melissa; Advani, Ranjana H.; Horwitz, Steven M.

2015-01-01

Purpose In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. Patients and Methods In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. Results Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event. Conclusion Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin. PMID:26195720

Characterization and genetic variability of feed-borne and clinical animal/human Aspergillus fumigatus strains using molecular markers.

PubMed

Pena, Gabriela A; Coelho, Irene; Reynoso, María M; Soleiro, Carla; Cavaglieri, Lilia R

2015-09-01

Aspergillus fumigatus, the major etiological agent of human and animal aspergillosis, is a toxigenic fungus largely regarded as a single species by macroscopic and microscopic features. However, molecular studies have demonstrated that several morphologically identified A. fumigatus strains might be genetically distinct. This work was aimed to apply PCR-restriction length fragment polymorphisms (PCR-RFLP) and random amplification of polymorphic DNA (RAPD) molecular markers to characterize a set of feed-borne and clinical A. fumigatus sensu lato strains isolated from Argentina and Brazil and to determine and compare their genetic variability. All A. fumigatus strains had the same band profile and those typical of A. fumigatus sensu stricto positive controls by PCR-RFLP. Moreover, all Argentinian and Brazilian strains typified by RAPD showed similar band patterns to each other and to A. fumigatus sensu stricto reference strains regardless of their isolation source (animal feeds or human/animal clinical cases) and geographic origin. Genetic similarity coefficients ranged from 0.61 to 1.00, but almost all isolates showed 78% of genetic similarly suggesting that genetic variability was found at intraspecific level. Finally, benA sequencing confirmed its identification as A. fumigatus sensu stricto species. These results suggest that A. fumigatus sensu stricto is a predominant species into Aspergillus section Fumigati found in animal environments as well as in human/animal clinical cases, while other species may be rarely isolated. The strains involved in human and animal aspergillosis could come from the environment where this fungus is frequently found. Rural workers and animals would be constantly exposed. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A marketing clinical doctorate programs.

PubMed

Montoya, Isaac D; Kimball, Olive M

2007-01-01

Over the past decade, clinical doctorate programs in health disciplines have proliferated amid both support and controversy among educators, professional organizations, practitioners, administrators, and third-party payers. Supporters argue that the explosion of new knowledge and increasing sophistication of technology have created a need for advanced practice models to enhance patient care and safety and to reduce costs. Critics argue that necessary technological advances can be incorporated into existing programs and believe that clinical doctorates will increase health care costs, not reduce them. Despite the controversy, many health disciplines have advanced the clinical doctorate (the most recent is the doctor of nursing practice in 2004), with some professions mandating the doctorate as the entry-level degree (i.e., psychology, pharmacy, audiology, and so on). One aspect of the introduction of clinical doctoral degrees has been largely overlooked, and that is the marketing aspect. Because of marketing considerations, some clinical doctorates have been more successfully implemented and accepted than others. Marketing is composed of variables commonly known as "the four P's of marketing": product, price, promotion, and place. This report explores these four P's within the context of clinical doctorates in the health disciplines.

How do intake clinicians use patient characteristics to select treatment for patients with personality disorders?

PubMed

van Manen, Janine; Kamphuis, Jan Henk; Visbach, Geny; Ziegler, Uli; Gerritsen, Ad; Van Rossum, Bert; Rijnierse, Piet; Timman, Reinier; Verheul, Roel

2008-11-01

Treatment selection in clinical practice is a poorly understood, often largely implicit decision process, perhaps especially for patients with personality disorders. This study, therefore, investigated how intake clinicians use information about patient characteristics to select psychotherapeutic treatment for patients with personality disorder. A structured interview with a forced-choice format was administered to 27 experienced intake clinicians working in five specialist mental health care institutes in the Netherlands. Substantial consensus was evident among intake clinicians. The results revealed that none of the presented patient characteristics were deemed relevant for the selection of the suitable treatment setting. The appropriate duration and intensity are selected using severity or personal strength variables. The theoretical orientation is selected using personal strength variables.

Psychobiologic correlates of treatment response in schizophrenia.

PubMed

Lieberman, J A; Alvir, J M; Koreen, A; Geisler, S; Chakos, M; Sheitman, B; Woerner, M

1996-03-01

In studies conducted on largely treatment naive patients in their first episode of psychosis, we have found that treatment outcome is quite good and that most patients recover or at least achieve a substantial degree of symptom remission. However, over the course of their illness and in the context of subsequent psychotic episodes, they may experience some decrease in their treatment response from illness progression. In addition, the heterogeneity of treatment outcome is associated with specific clinical (gender, primary negative symptoms of the deficit state, duration of psychosis) and biological variables (pHVA, ventricular volume). It is unclear whether these variables represent aspects of discrete subtypes of schizophrenia or dimensional measures of pathology within the broad context of a unitary disease entity.

Prevalence and correlates of cannabis use in an outpatient VA posttraumatic stress disorder clinic.

PubMed

Gentes, Emily L; Schry, Amie R; Hicks, Terrell A; Clancy, Carolina P; Collie, Claire F; Kirby, Angela C; Dennis, Michelle F; Hertzberg, Michael A; Beckham, Jean C; Calhoun, Patrick S

2016-05-01

Recent research has documented high rates of comorbidity between cannabis use disorders and posttraumatic stress disorder (PTSD) in veterans. However, despite possible links between PTSD and cannabis use, relatively little is known about cannabis use in veterans who present for PTSD treatment, particularly among samples not diagnosed with a substance use disorder. This study examined the prevalence of cannabis use and the psychological and functional correlates of cannabis use among a large sample of veterans seeking treatment at a Veterans Affairs (VA) PTSD specialty clinic. Male veterans (N = 719) who presented at a VA specialty outpatient PTSD clinic completed measures of demographic variables, combat exposure, alcohol, cannabis and other drug use, and PTSD and depressive symptoms. The associations among demographic, psychological, and functional variables were estimated using logistic regressions. Overall, 14.6% of participants reported using cannabis in the past 6 months. After controlling for age, race, service era, and combat exposure, past 6-month cannabis use was associated with unmarried status, use of tobacco products, other drug use, hazardous alcohol use, PTSD severity, depressive symptom severity, and suicidality. The present findings show that cannabis use is quite prevalent among veterans seeking PTSD specialty treatment and is associated with poorer mental health and use of other substances. It may be possible to identify and treat individuals who use cannabis in specialty clinics (e.g., PTSD clinics) where they are likely to present for treatment of associated mental health issues. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

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

A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis

PubMed Central

Lucarelli, Marco; Bruno, Sabina Maria; Pierandrei, Silvia; Ferraguti, Giampiero; Stamato, Antonella; Narzi, Fabiana; Amato, Annalisa; Cimino, Giuseppe; Bertasi, Serenella; Quattrucci, Serena; Strom, Roberto

2015-01-01

Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype–phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype–phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype–phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway. PMID:25910067

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.

Normative data for a battery of free recall, cued recall and recognition tests in the elderly Italian population.

PubMed

Coluccia, Emanuele; Gamboz, Nadia; Brandimonte, Maria A

2011-12-01

The present study aimed to provide normative data on a large sample of the elderly Italian population (N = 464; range of age = 49-94; range of education = 3-25) on both the word and the picture versions of a battery of free recall, cued recall, and recognition tests of memory. Results from multiple regression analyses showed that both age and education were significant predictors of performance. Therefore, norms were calculated taking into account these demographic variables. The availability of normative data based on a large sample will allow a more reliable use of the battery for clinical assessment in Italian-speaking dementia population.

[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.

Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.

PubMed

Keogh, Ruth; Frost, Chris; Owen, Gail; Daniel, Rhian M; Langbehn, Doug R; Leavitt, Blair; Durr, Alexandra; Roos, Raymund A C; Landwehrmeyer, G Bernhard; Reilmann, Ralf; Borowsky, Beth; Stout, Julie; Craufurd, David; Tabrizi, Sarah J

2016-01-11

 Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.

Neuroactive steroids and PTSD treatment.

PubMed

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

2017-05-10

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

Outcome Measures Used in Clinical Trials for Behçet Syndrome: A Systematic Review

PubMed Central

Hatemi, Gulen; Merkel, Peter A.; Hamuryudan, Vedat; Boers, Maarten; Direskeneli, Haner; Aydin, Sibel Z.; Yazici, Hasan

2015-01-01

Behçet syndrome (BS) is a multisystem vasculitis that is most active during young adulthood, causing serious disability and significant impairment in quality of life. Differences in the disease course, severity, and organ involvement between patients, depending on the age at presentation and sex, makes it impossible to determine a single management strategy. The diversity and variability in the outcome measures used in clinical trials in BS makes it difficult to compare the results or inform physicians about the best management strategy for individual patients. There is a large unmet need to determine or develop validated outcome measures for use in clinical trials in BS that are acceptable to researchers and regulatory agencies. We conducted a systematic review to describe the outcomes and outcome measures that have been used in clinical trials in BS. This review revealed the diversity and variability in the outcomes and outcome measures and the lack of standard definitions for most outcomes and rarity of validated outcome tools for disease assessment in BS. This systematic literature review will identify domains and candidate instruments for use in a Delphi exercise, the next step in the development of a core set of outcome measures that are properly validated and widely accepted by the collaboration of researchers from many different regions of the world and from different specialties, including rheumatology, ophthalmology, dermatology, gastroenterology, and neurology. PMID:24488418

Clinically Identified Postpartum Depression in Asian American Mothers

PubMed Central

Goyal, Deepika; Wang, Elsie J.; Shen, Jeremy; Wong, Eric C.; Palaniappan, Latha P.

2015-01-01

Objective To identify the clinical diagnosis rate of postpartum depression (PPD) in Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) compared to non-Hispanic Whites. Design Cross-sectional study using electronic health records (EHR). Setting A large, outpatient, multiservice clinic in Northern California. Participants A diverse clinical population of non-Hispanic White (N = 4582), Asian Indian (N = 1264), Chinese (N = 1160), Filipino (N = 347), Japanese (N = 124), Korean (N = 183), and Vietnamese (N = 147) mothers. Methods Cases of PPD were identified from EHRs using physician diagnosis codes, medication usage, and age standardized for comparison. The relationship between PPD and other demographic variables (race/ethnicity, maternal age, delivery type, marital status, and infant gender) were examined in a multivariate logistic regression model. Results The PPD diagnosis rate for all Asian American mothers in aggregate was significantly lower than the diagnosis rate in non-Hispanic White mothers. Moreover, of the six Asian American subgroups, PPD diagnosis rates for Asian Indian, Chinese, and Filipino mothers were significantly lower than non-Hispanic White mothers. In multivariate analyses, race/ethnicity, age, and cesarean were significant predictors of PPD. Conclusion In this insured population, PPD diagnosis rates were lower among Asian Americans, with variability in rates across the individual Asian American subgroups. It is unclear whether these lower rates are due to underreporting, underdiagnosis, or underutilization of mental health care in this setting. PMID:22536783

Clinically identified postpartum depression in Asian American mothers.

PubMed

Goyal, Deepika; Wang, Elsie J; Shen, Jeremy; Wong, Eric C; Palaniappan, Latha P

2012-01-01

To identify the clinical diagnosis rate of postpartum depression (PPD) in Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) compared to non-Hispanic Whites. Cross-sectional study using electronic health records (EHR). A large, outpatient, multiservice clinic in Northern California. A diverse clinical population of non-Hispanic White (N = 4582), Asian Indian (N = 1264), Chinese (N = 1160), Filipino (N = 347), Japanese (N = 124), Korean (N = 183), and Vietnamese (N = 147) mothers. Cases of PPD were identified from EHRs using physician diagnosis codes, medication usage, and age standardized for comparison. The relationship between PPD and other demographic variables (race/ethnicity, maternal age, delivery type, marital status, and infant gender) were examined in a multivariate logistic regression model. The PPD diagnosis rate for all Asian American mothers in aggregate was significantly lower than the diagnosis rate in non-Hispanic White mothers. Moreover, of the six Asian American subgroups, PPD diagnosis rates for Asian Indian, Chinese, and Filipino mothers were significantly lower than non-Hispanic White mothers. In multivariate analyses, race/ethnicity, age, and cesarean were significant predictors of PPD. In this insured population, PPD diagnosis rates were lower among Asian Americans, with variability in rates across the individual Asian American subgroups. It is unclear whether these lower rates are due to underreporting, underdiagnosis, or underutilization of mental health care in this setting. © 2012 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Outcome measures used in clinical trials for Behçet syndrome: a systematic review.

PubMed

Hatemi, Gulen; Merkel, Peter A; Hamuryudan, Vedat; Boers, Maarten; Direskeneli, Haner; Aydin, Sibel Z; Yazici, Hasan

2014-03-01

Behçet syndrome (BS) is a multisystem vasculitis that is most active during young adulthood, causing serious disability and significant impairment in quality of life. Differences in the disease course, severity, and organ involvement between patients, depending on the age at presentation and sex, makes it impossible to determine a single management strategy. The diversity and variability in the outcome measures used in clinical trials in BS makes it difficult to compare the results or inform physicians about the best management strategy for individual patients. There is a large unmet need to determine or develop validated outcome measures for use in clinical trials in BS that are acceptable to researchers and regulatory agencies. We conducted a systematic review to describe the outcomes and outcome measures that have been used in clinical trials in BS. This review revealed the diversity and variability in the outcomes and outcome measures and the lack of standard definitions for most outcomes and rarity of validated outcome tools for disease assessment in BS. This systematic literature review will identify domains and candidate instruments for use in a Delphi exercise, the next step in the development of a core set of outcome measures that are properly validated and widely accepted by the collaboration of researchers from many different regions of the world and from different specialties, including rheumatology, ophthalmology, dermatology, gastroenterology, and neurology.

Novel mutation in TSPAN12 leads to autosomal recessive inheritance of congenital vitreoretinal disease with intra-familial phenotypic variability.

PubMed

Gal, Moran; Levanon, Erez Y; Hujeirat, Yasir; Khayat, Morad; Pe'er, Jacob; Shalev, Stavit

2014-12-01

Developmental malformations of the vitreoretinal vasculature are a heterogeneous group of conditions with various modes of inheritance, and include familial exudative vitreoretinopathy (FEVR), persistent fetal vasculature (PFV), and Norrie disease. We investigated a large consanguineous kindred with multiple affected individuals exhibiting variable phenotypes of abnormal vitreoretinal vasculature, consistent with the three above-mentioned conditions and compatible with autosomal recessive inheritance. Exome sequencing identified a novel c.542G > T (p.C181F) apparently mutation in the TSPAN12 gene that segregated with the ocular disease in the family. The TSPAN12 gene was previously reported to cause dominant and recessive FEVR, but has not yet been associated with other vitreoretinal manifestations. The intra-familial clinical variability caused by a single mutation in the TSPAN12 gene underscores the complicated phenotype-genotype correlation of mutations in this gene, and suggests that there are additional genetic and environmental factors involved in the complex process of ocular vascularization during embryonic development. Our study supports considering PFV, FEVR, and Norrie disease a spectrum of disorders, with clinical and genetic overlap, caused by mutations in distinct genes acting in the Norrin/β-catenin signaling pathway. © 2014 Wiley Periodicals, Inc.

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].

The value of magnetic resonance imaging as a biomarker for amyotrophic lateral sclerosis: a systematic review.

PubMed

Grolez, G; Moreau, C; Danel-Brunaud, V; Delmaire, C; Lopes, R; Pradat, P F; El Mendili, M M; Defebvre, L; Devos, D

2016-08-27

Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease that mainly affects the motor system. A number of potentially neuroprotective and neurorestorative disease-modifying drugs are currently in clinical development. At present, the evaluation of a drug's clinical efficacy in ALS is based on the ALS Functional Rating Scale Revised, motor tests and survival. However, these endpoints are general, variable and late-stage measures of the ALS disease process and thus require the long-term assessment of large cohorts. Hence, there is a need for more sensitive radiological biomarkers. Various sequences for magnetic resonance imaging (MRI) of the brain and spinal cord have may have value as surrogate biomarkers for use in future clinical trials. Here, we review the MRI findings in ALS, their clinical correlations, and their limitations and potential role as biomarkers. The PubMed database was screened to identify studies using MRI in ALS. We included general MRI studies with a control group and an ALS group and longitudinal studies even if a control group was lacking. A total of 116 studies were analysed with MRI data and clinical correlations. The most disease-sensitive MRI patterns are in motor regions but the brain is more broadly affected. Despite the existing MRI biomarkers, there is a need for large cohorts with long term MRI and clinical follow-up. MRI assessment could be improved by standardized MRI protocols with multicentre studies.

Array-Based Comparative Genomic Hybridization Analysis Reveals Chromosomal Copy Number Aberrations Associated with Clinical Outcome in Canine Diffuse Large B-Cell Lymphoma

PubMed Central

Bresolin, Silvia; Marconato, Laura; Comazzi, Stefano; Te Kronnie, Geertruy; Aresu, Luca

2014-01-01

Canine Diffuse Large B-cell Lymphoma (cDLBCL) is an aggressive cancer with variable clinical response. Despite recent attempts by gene expression profiling to identify the dog as a potential animal model for human DLBCL, this tumor remains biologically heterogeneous with no prognostic biomarkers to predict prognosis. The aim of this work was to identify copy number aberrations (CNAs) by high-resolution array comparative genomic hybridization (aCGH) in 12 dogs with newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end of therapy and at relapse were also assessed. In primary DLBCLs, 90 different genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains in chr13 were significantly correlated with clinical stage. In addition, specific regions of gains and losses were significantly associated to duration of remission. In primary DLBCLs, individual variability was found, however 14 recurrent CNAs (>30%) were identified. Losses involving IGK, IGL and IGH were always found, and gains along the length of chr13 and chr31 were often observed (>41%). In these segments, MYC, LDHB, HSF1, KIT and PDGFRα are annotated. At the end of therapy, dogs in remission showed four new CNAs, whereas three new CNAs were observed in dogs at relapse compared with the previous profiles. One ex novo CNA, involving TCR, was present in dogs in remission after therapy, possibly induced by the autologous vaccine. Overall, aCGH identified small CNAs associated with outcome, which, along with future expression studies, may reveal target genes relevant to cDLBCL. PMID:25372838

Implications of comorbidity for genetic studies of bipolar disorder: P300 and eye tracking as biological markers for illness.

PubMed

Blackwood, D H; Sharp, C W; Walker, M T; Doody, G A; Glabus, M F; Muir, W J

1996-06-01

In large families with affective illness, identification of a biological variable is needed that reflects brain dysfunction at an earlier point than symptom development. Eye movement disorder, a possible vulnerability marker in schizophrenia, is less clearly associated with affective illness, although a subgroup of affective disorders shows smooth-pursuit eye movement disorder. The auditory P300 event-related potential may be a useful marker for risk to schizophrenia, but a role in bipolar illness is less certain. The distribution of these two biological variables and their association with symptoms in two multiply affected bipolar families is described. In a single, five-generation family identified for linkage studies through two bipolar I (BPI) probands, 128 members (including 20 spouses) were interviewed. The 108 related individuals had diagnoses of BPI (7), bipolar II (2), cyclothymia (3), or major depressive disorder (19). Eight others had generalised anxiety (1), minor depression (5), intermittent depression (1), or alcoholism (1). Sixty-nine subjects had no psychiatric diagnosis. P300 latency (81) and eye tracking (71) were recorded from a subgroup of relatives within the pedigree. Eye tracking was abnormal in 11 of 71 relatives (15.5%) and was bimodally distributed. In these 11 relatives, clinical diagnoses included minor depression (1), alcoholism (1) and generalised anxiety disorder (1). P300 latency was normally distributed and did not differ from controls. In a second family in which five of seven siblings have BPI illness, P300 latency and eye movement disorder were found in affected relatives and in some unaffected offspring. In these large families, clinical diagnoses of general anxiety, alcoholism and minor depression, when associated with eye tracking abnormality, may be considered alternative clinical manifestations of the same trait that in other relatives is expressed as bipolar illness.

Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma.

PubMed

Reddy, Anupama; Zhang, Jenny; Davis, Nicholas S; Moffitt, Andrea B; Love, Cassandra L; Waldrop, Alexander; Leppa, Sirpa; Pasanen, Annika; Meriranta, Leo; Karjalainen-Lindsberg, Marja-Liisa; Nørgaard, Peter; Pedersen, Mette; Gang, Anne O; Høgdall, Estrid; Heavican, Tayla B; Lone, Waseem; Iqbal, Javeed; Qin, Qiu; Li, Guojie; Kim, So Young; Healy, Jane; Richards, Kristy L; Fedoriw, Yuri; Bernal-Mizrachi, Leon; Koff, Jean L; Staton, Ashley D; Flowers, Christopher R; Paltiel, Ora; Goldschmidt, Neta; Calaminici, Maria; Clear, Andrew; Gribben, John; Nguyen, Evelyn; Czader, Magdalena B; Ondrejka, Sarah L; Collie, Angela; Hsi, Eric D; Tse, Eric; Au-Yeung, Rex K H; Kwong, Yok-Lam; Srivastava, Gopesh; Choi, William W L; Evens, Andrew M; Pilichowska, Monika; Sengar, Manju; Reddy, Nishitha; Li, Shaoying; Chadburn, Amy; Gordon, Leo I; Jaffe, Elaine S; Levy, Shawn; Rempel, Rachel; Tzeng, Tiffany; Happ, Lanie E; Dave, Tushar; Rajagopalan, Deepthi; Datta, Jyotishka; Dunson, David B; Dave, Sandeep S

2017-10-05

Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed an integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of 1,001 DLBCL patients to comprehensively define the landscape of 150 genetic drivers of the disease. We characterized the functional impact of these genes using an unbiased CRISPR screen of DLBCL cell lines to define oncogenes that promote cell growth. A prognostic model comprising these genetic alterations outperformed current established methods: cell of origin, the International Prognostic Index comprising clinical variables, and dual MYC and BCL2 expression. These results comprehensively define the genetic drivers and their functional roles in DLBCL to identify new therapeutic opportunities in the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Menstrual versus clinical estimate of gestational age dating in the United States: temporal trends and variability in indices of perinatal outcomes.

PubMed

Ananth, Cande V

2007-09-01

Accurate estimation of gestational age early in pregnancy is paramount for obstetric care decisions and for determining fetal growth and other conditions that may necessitate timing the iatrogenic intervention or delivery. We sought to examine temporal changes in the distributions of two measures of gestational age, namely, those based on menstrual dating and a clinical estimate. We further sought to evaluate relative comparisons and variability in indices of perinatal outcomes. We utilised the Natality data files in the US, 1990-2002 comprising women that delivered a singleton livebirth between 22 and 44 weeks gestation (n = 42 689 603). Changes were shown in the distributions of gestational age based on menstrual vs. clinical estimate between 1990 and 2002, as well as changes in the proportions of preterm (<37, <32 and <28 weeks) and post-term (>or=42 weeks) birth, and small- (SGA; <10th percentile) and large-for-gestational-age (LGA; birthweight >90th percentile) births. While the absolute rates of preterm birth <37 weeks, SGA and LGA births were lower based on the clinical estimate of gestational age relative to that based on menstrual dating, the increases in preterm birth rate between 1990 and 2002 were fairly similar between the two measures of gestational dating. However, the decline in post-term births was larger, based on the clinical estimate (-73.8%), than on the menstrual estimate (-36.6%) between 1990 and 2002. While the clinical estimate of gestational age appears to provide a reasonably good approximation to the menstrual estimate, disregarding the clinical estimate of gestational age may ignore the advantages of gestational age assessment in modern obstetrics.

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.

MUC1 and MUC4: Switching the Emphasis from Large to Small

PubMed Central

Carraway, Kermit L.

2011-01-01

Summation The MUC1 and MUC4 membrane mucins are each composed of a large alpha (α) and a small beta (β) subunit. The α subunits are fully exposed at the cell surface and contain variable numbers of repeated amino acid sequences that are heavily glycosylated. In contrast, the β subunits are much smaller and are anchored within the cell membrane, with their amino-terminal portions exposed at the cell surface and their carboxy-terminal tails facing the cytosol. Studies over the last several years are challenging the long-held belief that α subunits play the predominant role in cancer by conferring cellular properties that allow tumor cells to evade immune recognition and destruction. Indeed, the β subunits of MUC1 and MUC4 have emerged as oncogenes, as they engage signaling pathways responsible for tumor initiation and progression. Thus, a switch in the emphasis from the large α to the small β subunits offers attractive possibilities for successful clinical application. Such a focus shift is further supported by the absence of allelic polymorphism and variable glycosylation in the β subunit as well as by the presence of the β subunit in most MUC1 and MUC4 isoforms expressed by tumors. MUC1α, also known as CA15.3, is a Food and Drug Administration-approved serum biomarker for breast cancer, but its use is no longer recommended by the American Society of Clinical Oncology. However, comparison of β subunit expression in normal and malignant breast tissues may offer a novel approach to the exploitation of membrane mucins as biomarkers, as MUC1β-induced gene signatures with prognostic and predictive values in breast cancer have been reported. Preclinical studies with peptides that interfere with MUC1β oncogenic functions also look promising. PMID:21728842

The gait standard deviation, a single measure of kinematic variability.

PubMed

Sangeux, Morgan; Passmore, Elyse; Graham, H Kerr; Tirosh, Oren

2016-05-01

Measurement of gait kinematic variability provides relevant clinical information in certain conditions affecting the neuromotor control of movement. In this article, we present a measure of overall gait kinematic variability, GaitSD, based on combination of waveforms' standard deviation. The waveform standard deviation is the common numerator in established indices of variability such as Kadaba's coefficient of multiple correlation or Winter's waveform coefficient of variation. Gait data were collected on typically developing children aged 6-17 years. Large number of strides was captured for each child, average 45 (SD: 11) for kinematics and 19 (SD: 5) for kinetics. We used a bootstrap procedure to determine the precision of GaitSD as a function of the number of strides processed. We compared the within-subject, stride-to-stride, variability with the, between-subject, variability of the normative pattern. Finally, we investigated the correlation between age and gait kinematic, kinetic and spatio-temporal variability. In typically developing children, the relative precision of GaitSD was 10% as soon as 6 strides were captured. As a comparison, spatio-temporal parameters required 30 strides to reach the same relative precision. The ratio stride-to-stride divided by normative pattern variability was smaller in kinematic variables (the smallest for pelvic tilt, 28%) than in kinetic and spatio-temporal variables (the largest for normalised stride length, 95%). GaitSD had a strong, negative correlation with age. We show that gait consistency may stabilise only at, or after, skeletal maturity. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Light-sheet microscopy for slide-free non-destructive pathology of large clinical specimens

PubMed Central

Glaser, Adam K.; Reder, Nicholas P.; Chen, Ye; McCarty, Erin F.; Yin, Chengbo; Wei, Linpeng; Wang, Yu; True, Lawrence D.; Liu, Jonathan T.C.

2017-01-01

For the 1.7 million patients per year in the U.S. who receive a new cancer diagnosis, treatment decisions are largely made after a histopathology exam. Unfortunately, the gold standard of slide-based microscopic pathology suffers from high inter-observer variability and limited prognostic value due to sampling limitations and the inability to visualize tissue structures and molecular targets in their native 3D context. Here, we show that an open-top light-sheet microscope optimized for non-destructive slide-free pathology of clinical specimens enables the rapid imaging of intact tissues at high resolution over large 2D and 3D fields of view, with the same level of detail as traditional pathology. We demonstrate the utility of this technology for various applications: wide-area surface microscopy to triage surgical specimens (with ~200 μm surface irregularities), rapid intraoperative assessment of tumour-margin surfaces (12.5 sec/cm2), and volumetric assessment of optically cleared core–needle biopsies (1 mm in diameter, 2 cm in length). Light-sheet microscopy can be a versatile tool for both rapid surface microscopy and deep volumetric microscopy of human specimens. PMID:29750130

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.

Computational methods using genome-wide association studies to predict radiotherapy complications and to identify correlative molecular processes

NASA Astrophysics Data System (ADS)

Oh, Jung Hun; Kerns, Sarah; Ostrer, Harry; Powell, Simon N.; Rosenstein, Barry; Deasy, Joseph O.

2017-02-01

The biological cause of clinically observed variability of normal tissue damage following radiotherapy is poorly understood. We hypothesized that machine/statistical learning methods using single nucleotide polymorphism (SNP)-based genome-wide association studies (GWAS) would identify groups of patients of differing complication risk, and furthermore could be used to identify key biological sources of variability. We developed a novel learning algorithm, called pre-conditioned random forest regression (PRFR), to construct polygenic risk models using hundreds of SNPs, thereby capturing genomic features that confer small differential risk. Predictive models were trained and validated on a cohort of 368 prostate cancer patients for two post-radiotherapy clinical endpoints: late rectal bleeding and erectile dysfunction. The proposed method results in better predictive performance compared with existing computational methods. Gene ontology enrichment analysis and protein-protein interaction network analysis are used to identify key biological processes and proteins that were plausible based on other published studies. In conclusion, we confirm that novel machine learning methods can produce large predictive models (hundreds of SNPs), yielding clinically useful risk stratification models, as well as identifying important underlying biological processes in the radiation damage and tissue repair process. The methods are generally applicable to GWAS data and are not specific to radiotherapy endpoints.

Quantitative radiomics: impact of stochastic effects on textural feature analysis implies the need for standards

PubMed Central

Nyflot, Matthew J.; Yang, Fei; Byrd, Darrin; Bowen, Stephen R.; Sandison, George A.; Kinahan, Paul E.

2015-01-01

Abstract. Image heterogeneity metrics such as textural features are an active area of research for evaluating clinical outcomes with positron emission tomography (PET) imaging and other modalities. However, the effects of stochastic image acquisition noise on these metrics are poorly understood. We performed a simulation study by generating 50 statistically independent PET images of the NEMA IQ phantom with realistic noise and resolution properties. Heterogeneity metrics based on gray-level intensity histograms, co-occurrence matrices, neighborhood difference matrices, and zone size matrices were evaluated within regions of interest surrounding the lesions. The impact of stochastic variability was evaluated with percent difference from the mean of the 50 realizations, coefficient of variation and estimated sample size for clinical trials. Additionally, sensitivity studies were performed to simulate the effects of patient size and image reconstruction method on the quantitative performance of these metrics. Complex trends in variability were revealed as a function of textural feature, lesion size, patient size, and reconstruction parameters. In conclusion, the sensitivity of PET textural features to normal stochastic image variation and imaging parameters can be large and is feature-dependent. Standards are needed to ensure that prospective studies that incorporate textural features are properly designed to measure true effects that may impact clinical outcomes. PMID:26251842

Quantitative radiomics: impact of stochastic effects on textural feature analysis implies the need for standards.

PubMed

Nyflot, Matthew J; Yang, Fei; Byrd, Darrin; Bowen, Stephen R; Sandison, George A; Kinahan, Paul E

2015-10-01

Image heterogeneity metrics such as textural features are an active area of research for evaluating clinical outcomes with positron emission tomography (PET) imaging and other modalities. However, the effects of stochastic image acquisition noise on these metrics are poorly understood. We performed a simulation study by generating 50 statistically independent PET images of the NEMA IQ phantom with realistic noise and resolution properties. Heterogeneity metrics based on gray-level intensity histograms, co-occurrence matrices, neighborhood difference matrices, and zone size matrices were evaluated within regions of interest surrounding the lesions. The impact of stochastic variability was evaluated with percent difference from the mean of the 50 realizations, coefficient of variation and estimated sample size for clinical trials. Additionally, sensitivity studies were performed to simulate the effects of patient size and image reconstruction method on the quantitative performance of these metrics. Complex trends in variability were revealed as a function of textural feature, lesion size, patient size, and reconstruction parameters. In conclusion, the sensitivity of PET textural features to normal stochastic image variation and imaging parameters can be large and is feature-dependent. Standards are needed to ensure that prospective studies that incorporate textural features are properly designed to measure true effects that may impact clinical outcomes.

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

Memory bias for threatening information in anxiety and anxiety disorders: a meta-analytic review.

PubMed

Mitte, Kristin

2008-11-01

Although some theories suggest that anxious individuals selectively remember threatening stimuli, findings remain contradictory despite a considerable amount of research. A quantitative integration of 165 studies with 9,046 participants (clinical and nonclinical samples) examined whether a memory bias exists and which moderator variables influence its magnitude. Implicit memory bias was investigated in lexical decision/stimulus identification and word-stem completion paradigms; explicit memory bias was investigated in recognition and recall paradigms. Overall, effect sizes showed no significant impact of anxiety on implicit memory and recognition. Analyses indicated a memory bias for recall, whose magnitude depended on experimental study procedures like the encoding procedure or retention interval. Anxiety influenced recollection of previous experiences; anxious individuals favored threat-related information. Across all paradigms, clinical status was not significantly linked to effect sizes, indicating no qualitative difference in information processing between anxiety patients and high-anxious persons. The large discrepancy between study effects in recall and recognition indicates that future research is needed to identify moderator variables for avoidant and preferred remembering.

Variations in clinicopathologic characteristics of thyroid cancer among racial ethnic groups: analysis of a large public city hospital and the SEER database.

PubMed

Moo-Young, Tricia A; Panergo, Jessel; Wang, Chih E; Patel, Subhash; Duh, Hong Yan; Winchester, David J; Prinz, Richard A; Fogelfeld, Leon

2013-11-01

Clinicopathologic variables influence the treatment and prognosis of patients with thyroid cancer. A retrospective analysis of public hospital thyroid cancer database and the Surveillance, Epidemiology and End Results 17 database was conducted. Demographic, clinical, and pathologic data were compared across ethnic groups. Within the public hospital database, Hispanics versus non-Hispanic whites were younger and had more lymph node involvement (34% vs 17%, P < .001). Median tumor size was not statistically different across ethnic groups. Similar findings were demonstrated within the Surveillance, Epidemiology and End Results database. African Americans aged <45 years had the largest tumors but were least likely to have lymph node involvement. Asians had the most stage IV disease despite having no differences in tumor size, lymph node involvement, and capsular invasion. There is considerable variability in the clinical presentation of thyroid cancer across ethnic groups. Such disparities persist within an equal-access health care system. These findings suggest that factors beyond socioeconomics may contribute to such differences. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

A Legionella pneumophila collagen-like protein encoded by a gene with a variable number of tandem repeats is involved in the adherence and invasion of host cells.

PubMed

Vandersmissen, Liesbeth; De Buck, Emmy; Saels, Veerle; Coil, David A; Anné, Jozef

2010-05-01

Legionella pneumophila is a Gram-negative, facultative intracellular pathogen and the causative agent of Legionnaires' disease, a severe pneumonia in humans. Analysis of the Legionella sequenced genomes revealed a gene with a variable number of tandem repeats (VNTRs), whose number varies between strains. We examined the strain distribution of this gene among a collection of 108 clinical, environmental and hot spring serotype I strains. Twelve variants were identified, but no correlation was observed between the number of repeat units and clinical and environmental strains. The encoded protein contains the C-terminal consensus motif of outer membrane proteins and has a large region of collagen-like repeats that is encoded by the VNTR region. We have therefore annotated this protein Lcl for Legionella collagen-like protein. Lcl was shown to contribute to the adherence and invasion of host cells and it was demonstrated that the number of repeat units present in lcl had an influence on these adhesion characteristics.

[Big data in imaging].

PubMed

Sewerin, Philipp; Ostendorf, Benedikt; Hueber, Axel J; Kleyer, Arnd

2018-04-01

Until now, most major medical advancements have been achieved through hypothesis-driven research within the scope of clinical trials. However, due to a multitude of variables, only a certain number of research questions could be addressed during a single study, thus rendering these studies expensive and time consuming. Big data acquisition enables a new data-based approach in which large volumes of data can be used to investigate all variables, thus opening new horizons. Due to universal digitalization of the data as well as ever-improving hard- and software solutions, imaging would appear to be predestined for such analyses. Several small studies have already demonstrated that automated analysis algorithms and artificial intelligence can identify pathologies with high precision. Such automated systems would also seem well suited for rheumatology imaging, since a method for individualized risk stratification has long been sought for these patients. However, despite all the promising options, the heterogeneity of the data and highly complex regulations covering data protection in Germany would still render a big data solution for imaging difficult today. Overcoming these boundaries is challenging, but the enormous potential advances in clinical management and science render pursuit of this goal worthwhile.

Empirical Support for DSM-IV Schizoaffective Disorder: Clinical and Cognitive Validators from a Large Patient Sample

PubMed Central

DeRosse, Pamela; Burdick, Katherine E.; Lencz, Todd; Siris, Samuel G.; Malhotra, Anil K.

2013-01-01

Objective The diagnosis of schizoaffective disorder has long maintained an uncertain status in psychiatric nosology. Studies comparing clinical and biological features of patients with schizoaffective disorder to patients with related disorders [e.g., schizophrenia and bipolar disorder] can provide an evidence base for judging the validity of the diagnostic category. However, because most prior studies of schizoaffective disorder have only evaluated differences between groups at a static timepoint, it is unclear how these disorders may be related when the entire illness course is taken into consideration. Methods We ascertained a large cohort [N = 993] of psychiatric patients with a range of psychotic diagnoses including schizophrenia with no history of major affective episodes [SZ−; N = 371], schizophrenia with a superimposed mood syndrome [SZ+; N = 224], schizoaffective disorder [SAD; N = 129] and bipolar I disorder with psychotic features [BPD+; N = 269]. Using cross-sectional data we designed key clinical and neurocognitive dependent measures that allowed us to test longitudinal hypotheses about the differences between these diagnostic entities. Results Large differences between diagnostic groups on several demographic and clinical variables were observed. Most notably, groups differed on a putative measure of cognitive decline. Specifically, the SAD group demonstrated significantly greater post-onset cognitive decline compared to the BP+ group, with the SZ− and SZ+ group both exhibiting levels of decline intermediate to BPD+ and SAD. Conclusions These results suggest that schizoaffective disorder may possess distinct features. Contrary to earlier formulations, schizoaffective disorder may be a more severe form of illness. PMID:23737946

Empirical support for DSM-IV schizoaffective disorder: clinical and cognitive validators from a large patient sample.

PubMed

DeRosse, Pamela; Burdick, Katherine E; Lencz, Todd; Siris, Samuel G; Malhotra, Anil K

2013-01-01

The diagnosis of schizoaffective disorder has long maintained an uncertain status in psychiatric nosology. Studies comparing clinical and biological features of patients with schizoaffective disorder to patients with related disorders [e.g., schizophrenia and bipolar disorder] can provide an evidence base for judging the validity of the diagnostic category. However, because most prior studies of schizoaffective disorder have only evaluated differences between groups at a static timepoint, it is unclear how these disorders may be related when the entire illness course is taken into consideration. We ascertained a large cohort [N = 993] of psychiatric patients with a range of psychotic diagnoses including schizophrenia with no history of major affective episodes [SZ-; N = 371], schizophrenia with a superimposed mood syndrome [SZ+; N = 224], schizoaffective disorder [SAD; N = 129] and bipolar I disorder with psychotic features [BPD+; N = 269]. Using cross-sectional data we designed key clinical and neurocognitive dependent measures that allowed us to test longitudinal hypotheses about the differences between these diagnostic entities. Large differences between diagnostic groups on several demographic and clinical variables were observed. Most notably, groups differed on a putative measure of cognitive decline. Specifically, the SAD group demonstrated significantly greater post-onset cognitive decline compared to the BP+ group, with the SZ- and SZ+ group both exhibiting levels of decline intermediate to BPD+ and SAD. These results suggest that schizoaffective disorder may possess distinct features. Contrary to earlier formulations, schizoaffective disorder may be a more severe form of illness.

High interindividual variability in dose-dependent reduction in speed of movement after exposing C. elegans to shock waves

PubMed Central

Angstman, Nicholas B.; Kiessling, Maren C.; Frank, Hans-Georg; Schmitz, Christoph

2015-01-01

In blast-related mild traumatic brain injury (br-mTBI) little is known about the connections between initial trauma and expression of individual clinical symptoms. Partly due to limitations of current in vitro and in vivo models of br-mTBI, reliable prediction of individual short- and long-term symptoms based on known blast input has not yet been possible. Here we demonstrate a dose-dependent effect of shock wave exposure on C. elegans using shock waves that share physical characteristics with those hypothesized to induce br-mTBI in humans. Increased exposure to shock waves resulted in decreased mean speed of movement while increasing the proportion of worms rendered paralyzed. Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods. Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions. Reduction of cavitation by exposing worms to shock waves in polyvinyl alcohol resulted in reduced effect, implicating primary blast effects as damaging components in shock wave induced trauma. Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures. Taken together, these data indicate that reliable prediction of individual clinical symptoms based on known blast input as well as drawing conclusions on blast input from individual clinical symptoms is not feasible in br-mTBI. PMID:25705183

The geometrical precision of virtual bone models derived from clinical computed tomography data for forensic anthropology.

PubMed

Colman, Kerri L; Dobbe, Johannes G G; Stull, Kyra E; Ruijter, Jan M; Oostra, Roelof-Jan; van Rijn, Rick R; van der Merwe, Alie E; de Boer, Hans H; Streekstra, Geert J

2017-07-01

Almost all European countries lack contemporary skeletal collections for the development and validation of forensic anthropological methods. Furthermore, legal, ethical and practical considerations hinder the development of skeletal collections. A virtual skeletal database derived from clinical computed tomography (CT) scans provides a potential solution. However, clinical CT scans are typically generated with varying settings. This study investigates the effects of image segmentation and varying imaging conditions on the precision of virtual modelled pelves. An adult human cadaver was scanned using varying imaging conditions, such as scanner type and standard patient scanning protocol, slice thickness and exposure level. The pelvis was segmented from the various CT images resulting in virtually modelled pelves. The precision of the virtual modelling was determined per polygon mesh point. The fraction of mesh points resulting in point-to-point distance variations of 2 mm or less (95% confidence interval (CI)) was reported. Colour mapping was used to visualise modelling variability. At almost all (>97%) locations across the pelvis, the point-to-point distance variation is less than 2 mm (CI = 95%). In >91% of the locations, the point-to-point distance variation was less than 1 mm (CI = 95%). This indicates that the geometric variability of the virtual pelvis as a result of segmentation and imaging conditions rarely exceeds the generally accepted linear error of 2 mm. Colour mapping shows that areas with large variability are predominantly joint surfaces. Therefore, results indicate that segmented bone elements from patient-derived CT scans are a sufficiently precise source for creating a virtual skeletal database.

Head circumference and height in autism: a study by the Collaborative Program of Excellence in Autism.

PubMed

Lainhart, Janet E; Bigler, Erin D; Bocian, Maureen; Coon, Hilary; Dinh, Elena; Dawson, Geraldine; Deutsch, Curtis K; Dunn, Michelle; Estes, Annette; Tager-Flusberg, Helen; Folstein, Susan; Hepburn, Susan; Hyman, Susan; McMahon, William; Minshew, Nancy; Munson, Jeff; Osann, Kathy; Ozonoff, Sally; Rodier, Patricia; Rogers, Sally; Sigman, Marian; Spence, M Anne; Stodgell, Christopher J; Volkmar, Fred

2006-11-01

Data from 10 sites of the NICHD/NIDCD Collaborative Programs of Excellence in Autism were combined to study the distribution of head circumference and relationship to demographic and clinical variables. Three hundred thirty-eight probands with autism-spectrum disorder (ASD) including 208 probands with autism were studied along with 147 parents, 149 siblings, and typically developing controls. ASDs were diagnosed, and head circumference and clinical variables measured in a standardized manner across all sites. All subjects with autism met ADI-R, ADOS-G, DSM-IV, and ICD-10 criteria. The results show the distribution of standardized head circumference in autism is normal in shape, and the mean, variance, and rate of macrocephaly but not microcephaly are increased. Head circumference tends to be large relative to height in autism. No site, gender, age, SES, verbal, or non-verbal IQ effects were present in the autism sample. In addition to autism itself, standardized height and average parental head circumference were the most important factors predicting head circumference in individuals with autism. Mean standardized head circumference and rates of macrocephaly were similar in probands with autism and their parents. Increased head circumference was associated with a higher (more severe) ADI-R social algorithm score. Macrocephaly is associated with delayed onset of language. Although mean head circumference and rates of macrocephaly are increased in autism, a high degree of variability is present, underscoring the complex clinical heterogeneity of the disorder. The wide distribution of head circumference in autism has major implications for genetic, neuroimaging, and other neurobiological research.

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.

Efficacy of periodontal plastic surgery procedures in the treatment of localized facial gingival recessions. A systematic review.

PubMed

Cairo, Francesco; Nieri, Michele; Pagliaro, Umberto

2014-04-01

The aim of this Systematic Review (SR) was to assess the clinical efficacy of periodontal plastic surgery procedures in the treatment of localized gingival recessions (Rec) with or without inter-dental clinical attachment loss (iCAL). Electronic and hand searches were performed to identify randomized clinical trials (RCTs) on treatment of single gingival recessions with at least 6 months of follow-up. Primary outcome variable was complete root coverage (CRC). Secondary outcome variables were recession reduction (RecRed) and keratinized tissue (KT) gain. To evaluate treatment effect, Odds Ratios were combined for dichotomous data and mean differences in continuous data using a random-effect model. Fifty-one RCTs (53 articles) with a total of 1574 treated patients (1744 recessions) were included in this SR. Finally, 30 groups of comparisons were identified and a total of 80 meta-analyses were performed. Coronally Advanced Flap (CAF) was associated with higher probability of CRC and higher amount of RecRed than Semilunar Coronal Positioned Flap (SCPF). The combination CAF plus Connective Tissue Graft (CAF+CTG) or CAF plus Enamel Matrix Derivative (CAF+EMD) was more effective than CAF alone in terms of CRC and RecRed. The combination CAF plus Collagen Matrix (CAF+CM) achieved higher RecRed than CAF alone. In addition, CAF+CTG achieved CRC more frequently than CAF+EMD, SCPF, Free Gingival Graft (FGG) and Laterally Positioned Flap (LPS). CAF+CTG was also associated with higher RecRed than Barrier Membranes (CAF+GTR), CAF+EMD and CAF+CM. GTR was not able to improve the clinical efficacy of CAF. Studies adding Acellular Dermal Matrix (ADM) under CAF showed a large heterogeneity and not significant benefits compared with CAF alone. Multiple combinations, using more than a single graft/biomaterial under the flap, usually provide similar or less benefits than simpler, control procedures in term of root coverage outcomes. CAF procedures alone or with CTG, EMD are supported by large evidence in modern periodontal plastic surgery. CAF+CTG achieved the best clinical outcomes in single gingival recessions with or without iCAL. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Variable phenotypic expression and onset in MYH14 distal hereditary motor neuropathy phenotype in a large, multigenerational North American family.

PubMed

Iyadurai, Stanley; Arnold, W David; Kissel, John T; Ruhno, Corey; Mcgovern, Vicki L; Snyder, Pamela J; Prior, Thomas W; Roggenbuck, Jennifer; Burghes, Arthur H; Kolb, Stephen J

2017-08-01

Distal hereditary motor neuropathy (dHMN) causes distal-predominant weakness without prominent sensory loss. Myosin heavy chain disorders most commonly result in distal myopathy and cardiomyopathy with or without hearing loss, but a complex phenotype with dHMN, myopathy, hoarseness, and hearing loss was reported in a Korean family with a c.2822G>T mutation in MYH14. In this study we report phenotypic features in a North American family with the c.2822G>T in MYH14. Clinical and molecular characterization was performed in a large, 6-generation, Caucasian family with MYH14 dHMN. A total of 11 affected and 7 unaffected individuals were evaluated and showed varying age of onset and severity of weakness. Genotypic concordance was confirmed with molecular analysis. Electrophysiological studies demonstrated distal motor axonal degeneration without myopathy in all affected subjects tested. Mutation of MYH14 can result in a range of neuromuscular phenotypes that includes a dHMN and hearing loss phenotype with variable age of onset. Muscle Nerve 56: 341-345, 2017. © 2016 Wiley Periodicals, Inc.

Sacro-anterior haemangiopericytoma: a case report

PubMed Central

Ge, Xiu-Hong; Liu, Shuai-Shuai; Shan, Hu-Sheng; Wang, Zhi-Min; Li, Qian-Wen

2014-01-01

Haemangiopericytoma (HPC) is a rare vascular tumor with borderline malignancy, considerable histological variability, and unpredictable clinical and biological behavior. HPC can present a diagnostic challenge because of its indeterminate clinical, radiological, and pathological features. HPC generally presents in adulthood and is equally frequent in both sexes. HPC can arise in any site in the body as a slowly growing and painless mass. The precise cell type origin of HPC is uncertain. One third of HPCs occur in the head and neck areas. Exceptional cases of hemangioblastoma arising outside the head and neck areas have been reported, but little is known about their clinicopathologic and immunohistochemical features. This study reports on a case of a large sacro-anterior HPC in a 65-year-old male. PMID:25009757

Optical phantoms with variable properties and geometries for diffuse and fluorescence optical spectroscopy

NASA Astrophysics Data System (ADS)

Leh, Barbara; Siebert, Rainer; Hamzeh, Hussein; Menard, Laurent; Duval, Marie-Alix; Charon, Yves; Abi Haidar, Darine

2012-10-01

Growing interest in optical instruments for biomedical applications has increased the use of optically calibrated phantoms. Often associated with tissue modeling, phantoms allow the characterization of optical devices for clinical purposes. Fluorescent gel phantoms have been developed, mimicking optical properties of healthy and tumorous brain tissues. Specific geometries of dedicated molds offer multiple-layer phantoms with variable thicknesses and monolayer phantoms with cylindrical inclusions at various depths and diameters. Organic chromophores are added to allow fluorescence spectroscopy. These phantoms are designed to be used with 405 nm as the excitation wavelength. This wavelength is then adapted to excite large endogenous molecules. The benefits of these phantoms in understanding fluorescence tissue analysis are then demonstrated. In particular, detectability aspects as a function of geometrical and optical parameters are presented and discussed.

[Variability in the in-hospital management of acute myocardial infarction in Spain. IBERICA Study (Investigación, Búsqueda Específica y Registro de Isquemia Coronaria Aguda)].

PubMed

Fiol, M; Cabadés, A; Sala, J; Marrugat, J; Elosua, R; Vega, G; José Tormo Díaz, M; Segura, A; Aldasoro, E; Moreno-Iribas, C; Muñiz, J; Hurtado de Saracho, I; García, J

2001-04-01

Introduction and objective. Although some in-hospital studies have described the management of acute myocardial infarction (MI) patients in Spain, none has been able to guarantee the exhaustiveness of patient registry. This study sought to determine the clinical characteristics and in-hospital management of patients with MI in eight Spanish population registries.Methods. The IBERICA study is a population-based MI registry carried out in the 25 to 74 year-old population, in eight Spanish regions in 1997. A standardized methodology was used to register and investigate all MI arriving alive to a hospital. Clinical characteristics, cardiovascular risk factors prevalence, pharmacological treatment, invasive and non-invasive procedures performed and complications at 28 days of evolution were recorded. A descriptive analysis was performed and the variation coefficient (VC) was calculated.Results. In 1997, 4,041 MI patients were registered, 79.9% were men with a mean age of 61.1 years. Although 10.9% (95% CI: 9.9-11.9%) were not admitted to the coronary care unit, a large variability existed among different areas (VC = 53%). There was a high variability in the utilization and performance of non-invasive and invasive procedures among regions, as well as in the use of pharmacological treatment. Only the use of antiaggregants (91.5%) and thrombolytic therapy (41.8%) showed a low variability (VC < 10%). Twenty-eight day mortality was 16.2% (95% CI: 15.1-17.4%) with a high variability being observed among the different regions (VC = 20.6%).Conclusion. Patient characteristics vary among the different Spanish regions. The differences in management and prognosis suggest a lack of equality in the health care provided to MI patients in the different regions in Spain.

Bleeding complications and mortality in warfarin-treated VTE patients, dependence of INR variability and iTTR.

PubMed

Sandén, Per; Renlund, Henrik; Svensson, Peter J; Själander, Anders

2017-01-05

High quality of warfarin treatment is important to prevent recurrence of venous thromboembolism (VTE) without bleeding complications. The aim of this study was to examine the effect of individual time in therapeutic range (iTTR) and International Normalised Ratio (INR) variability on bleeding risk and mortality in a large cohort of well-managed patients with warfarin due to VTE. A cohort of 16612 patients corresponding to 19502 treatment periods with warfarin due to VTE between January 1, 2006 and December 31, 2011 was retrieved from the Swedish national quality register AuriculA and matched with the Swedish National Patient Register for bleeding complications and background characteristics and the Cause of death register for occurrence and date of death. The rate of bleeding was 1.79 (confidence interval (CI) 95 % 1.66-1.93) per 100 treatment years among all patients. Those with poor warfarin treatment quality had a higher rate of clinically relevant bleeding, both when measured as iTTR below 70 %, 2.91 (CI 95 % 2.61-3.21) or as INR variability over the mean value 0.85, 2.61 (CI 95 % 2.36-2.86). Among those with both high INR variability and low iTTR the risk of clinically relevant bleeding was clearly increased hazard ratio (HR) 3.47 (CI 95 % 2.89-4.17). A similar result was found for all-cause mortality with a HR of 3.67 (CI 95 % 3.02-4.47). Both a low iTTR and a high INR variability increase the risk of bleeding complications or mortality. When combining the two treatment quality indicators patients at particular high risk of bleeding or death can be identified.

Casting wider nets for anxiety and depression: disability-driven cross-diagnostic subtypes in a large cohort.

PubMed

Wanders, R B K; van Loo, H M; Vermunt, J K; Meijer, R R; Hartman, C A; Schoevers, R A; Wardenaar, K J; de Jonge, P

2016-12-01

In search of empirical classifications of depression and anxiety, most subtyping studies focus solely on symptoms and do so within a single disorder. This study aimed to identify and validate cross-diagnostic subtypes by simultaneously considering symptoms of depression and anxiety, and disability measures. A large cohort of adults (Lifelines, n = 73 403) had a full assessment of 16 symptoms of mood and anxiety disorders, and measurement of physical, social and occupational disability. The best-fitting subtyping model was identified by comparing different hybrid mixture models with and without disability covariates on fit criteria in an independent test sample. The best model's classes were compared across a range of external variables. The best-fitting Mixed Measurement Item Response Theory model with disability covariates identified five classes. Accounting for disability improved differentiation between people reporting isolated non-specific symptoms ['Somatic' (13.0%), and 'Worried' (14.0%)] and psychopathological symptoms ['Subclinical' (8.8%), and 'Clinical' (3.3%)]. Classes showed distinct associations with clinically relevant external variables [e.g. somatization: odds ratio (OR) 8.1-12.3, and chronic stress: OR 3.7-4.4]. The Subclinical class reported symptomatology at subthreshold levels while experiencing disability. No pure depression or anxiety, but only mixed classes were found. An empirical classification model, incorporating both symptoms and disability identified clearly distinct cross-diagnostic subtypes, indicating that diagnostic nets should be cast wider than current phenomenology-based categorical systems.

Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis.

PubMed

Mota, Pedro; Reddy, Venkat; Isenberg, David

2017-07-01

Rituximab-based B-cell depletion (BCD) therapy is effective in refractory rheumatoid arthritis (RA) and although used to treat patients with refractory systemic lupus erythematosus (SLE) in routine clinical practice, rituximab failed to meet the primary endpoints in two large randomised controlled trials (RCTs) of non-renal (EXPLORER) and renal (LUNAR) SLE. Areas covered: We review how BCD could be improved to achieve better clinical responses in RA and SLE. Insights into the variability in clinical response to BCD in RA and SLE may help develop new therapeutic strategies. To this end, a literature search was performed using the following terms: rheumatoid arthritis, systemic erythematosus lupus, rituximab and B-cell depletion. Expert commentary: Poor trial design may have, at least partly, contributed to the apparent lack of response to BCD in the two RCTs of patients with SLE. Enhanced B-cell depletion and/or sequential therapy with belimumab may improve clinical response at least in some patients with SLE.

Cardiac Cachexia: Perspectives for Prevention and Treatment.

PubMed

Okoshi, Marina Politi; Capalbo, Rafael Verardino; Romeiro, Fernando G; Okoshi, Katashi

2017-01-01

Cachexia is a prevalent pathological condition associated with chronic heart failure. Its occurrence predicts increased morbidity and mortality independent of important clinical variables such as age, ventricular function, or heart failure functional class. The clinical consequences of cachexia are dependent on both weight loss and systemic inflammation, which accompany cachexia development. Skeletal muscle wasting is an important component of cachexia; it often precedes cachexia development and predicts poor outcome in heart failure. Cachexia clinically affects several organs and systems. It is a multifactorial condition where underlying pathophysiological mechanisms are not completely understood making it difficult to develop specific prevention and treatment therapies. Preventive strategies have largely focused on muscle mass preservation. Different treatment options have been described, mostly in small clinical studies or experimental settings. These include nutritional support, neurohormonal blockade, reducing intestinal bacterial translocation, anemia and iron deficiency treatment, appetite stimulants, immunomodulatory agents, anabolic hormones, and physical exercise regimens. Currently, nonpharmacological therapy such as nutritional support and physical exercise are considered central to cachexia prevention and treatment.

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.

Eating disorders and major depression: role of anger and personality.

PubMed

Giovanni, Abbate-Daga; Carla, Gramaglia; Enrica, Marzola; Federico, Amianto; Maria, Zuccolin; Secondo, Fassino

2011-01-01

This study aimed to evaluate comorbidity for MD in a large ED sample and both personality and anger as clinical characteristics of patients with ED and MD. We assessed 838 ED patients with psychiatric evaluations and psychometric questionnaires: Temperament and Character Inventory, Eating Disorder Inventory-2, Beck Depression Inventory, and State-Trait Anger Expression Inventory. 19.5% of ED patients were found to suffer from comorbid MD and 48.7% reported clinically significant depressive symptomatology: patients with Anorexia Binge-Purging and Bulimia Nervosa were more likely to be diagnosed with MD. Irritable mood was found in the 73% of patients with MD. High Harm Avoidance (HA) and low Self-Directedness (SD) predicted MD independently of severity of the ED symptomatology, several clinical variables, and ED diagnosis. Assessing both personality and depressive symptoms could be useful to provide effective treatments. Longitudinal studies are needed to investigate the pathogenetic role of HA and SD for ED and MD.

Use of near-infrared spectroscopy (NIRS) in cerebral tissue oxygenation monitoring in neonates.

PubMed

Gumulak, Rene; Lucanova, Lucia Casnocha; Zibolen, Mirko

2017-06-01

Near-infrared spectroscopy (NIRS) is a technology capable of non-invasive, continuous measuring of regional tissue oxygen saturation (StO 2 ). StO 2 represents a state of hemodynamic stability, which is influenced by many factors. Extensive research has been done in the field of measuring StO 2 of various organs. The current clinical availability of several NIRS-based devices reflects an important development in prevention, detection and correction of discrepancy in oxygen delivery to the brain and vital organs. Managing cerebral ischemia remains a significant issue in the neonatal intensive care units (NICU). Cerebral tissue oxygenation (cStO 2 ) and cerebral fractional tissue extraction (cFTOE) are reported in a large number of clinical studies. This review provides a summary of the concept of function, current variability of NIRS-based devices used in neonatology, clinical applications in continuous cStO 2 monitoring, limitations, disadvantages, and the potential of current technology.

The Relationship between Grandiose and Vulnerable (Hypersensitive) Narcissism

PubMed Central

Jauk, Emanuel; Weigle, Elena; Lehmann, Konrad; Benedek, Mathias; Neubauer, Aljoscha C.

2017-01-01

Narcissistic grandiosity is characterized by overt expressions of feelings of superiority and entitlement, while narcissistic vulnerability reflects hypersensitivity and introversive self-absorbedness. Clinical evidence suggests that grandiosity is accompanied by vulnerable aspects, pointing to a common foundation. Subclinical personality research, however, views grandiose and vulnerable narcissism as independent traits. Grandiose narcissism displays substantial correlation with extraversion, while vulnerable narcissism correlates highly with introversion. We investigated if (1) controlling for intro-/extraversion might reveal a “common core” of grandiose and vulnerable narcissism, and if (2) the correlation between both aspects might be higher at higher levels of narcissism. Latent variable structural equation modeling and segmented regression analysis confirmed these hypotheses in a large non-clinical sample (N = 1,006). Interindividual differences in intro-/extraversion mask the common core of grandiose and vulnerable narcissism. The association between both aspects increases at high levels (upper 10%) of grandiose narcissism, which suggests a possible transition to clinically relevant (pathological) narcissism. PMID:28955288

Illness severity and self-efficacy as course predictors of DSM-IV alcohol dependence in a multisite clinical sample.

PubMed

Langenbucher, J; Sulesund, D; Chung, T; Morgenstern, J

1996-01-01

Illness severity and self-efficacy are two constructs of growing interest as predictors of clinical response in alcoholism. Using alternative measures of illness severity (DSM-IV symptom count, Alcohol Dependence Scale, and Addiction Severity Index) and self-efficacy (brief version of the Situational Confidence Questionnaire) rigorously controlled for theoretically important background variables, we studied their unique contribution to multiple indices of relapse, relapse latency, and use of alternative coping behaviors in a large, heterogeneous clinical sample. The Alcohol Dependence Scale contributed to the prediction of 4 of 5 relapse indicators. The SCQ failed to predict relapse behavior or its precursor, coping response. The findings emphasize the predictive validity of severity of dependence as a course specifier and underline the need for more sensitive and externally valid measures of cognitive processes such as self-efficacy for application in future studies of posttreatment behavior.

Clinical features of body dysmorphic disorder in adolescents and adults

PubMed Central

Phillips, Katharine A.; Didie, Elizabeth R.; Menard, William; Pagano, Maria E.; Fay, Christina; Weisberg, Risa B.

2006-01-01

Body dysmorphic disorder (BDD) usually begins during adolescence, but its clinical features have received little investigation in this age group. Two hundred individuals with BDD (36 adolescents; 164 adults) completed interviewer-administered and self-report measures. Adolescents were preoccupied with numerous aspects of their appearance, most often their skin, hair, and stomach. Among the adolescents, 94.3% reported moderate, severe, or extreme distress due to BDD, 80.6% had a history of suicidal ideation, and 44.4% had attempted suicide. Adolescents experienced high rates and levels of impairment in school, work, and other aspects of psychosocial functioning. Adolescents and adults were comparable on most variables, although adolescents had significantly more delusional BDD beliefs and a higher lifetime rate of suicide attempts. Thus, adolescents with BDD have high levels of distress and rates of functional impairment, suicidal ideation, and suicide attempts. BDD’s clinical features in adolescents appear largely similar to those in adults. PMID:16499973

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.

Vocal fold pseudocyst: results of 46 cases undergoing a uniform treatment algorithm.

PubMed

Estes, Christine; Sulica, Lucian

2014-05-01

To describe treatment results and identify predictors of the need for surgical intervention in patients with vocal fold pseudocyst. Retrospective cohort study with longitudinal followup via survey. Clinical records were reviewed for demographic information, VHI-10 score, and degree of severity of dysphonia. Videostroboscopic examinations were evaluated for presence of vocal fold pseudocyst, along with additional clinical variables, including laterality, reactive lesion, paresis, varix, and hemorrhage. Follow-up surveys were sent to all participants to evaluate current VHI-10 score and degree of vocal limitation. Results were analyzed to determine predictors of surgery and recurrence of pathology. Forty-six patients (41F:5M) with pseudocyst (40 unilateral: 6 bilateral) were reviewed. Twenty-three (50%) had reactive lesions, nineteen (41%) had paresis by clinical criteria, 10 (22%) had varices, and 6 (13%) had hemorrhage on examination. All underwent initial behavioral management (2-12 sessions of voice therapy; mean of 8 sessions). Seventeen (37%) eventually required surgical intervention. No demographic or clinical variables proved predictive of surgical intervention. Follow-up surveys were completed by 63% of patients, and 79% agreed with the statement that they were not professionally limited by their voices. This experience supports behavioral management as an initial intervention in patients with pseudocyst, sufficient by itself to restore vocal function in approximately two out of three patients. Neither initial severity nor any of the studied clinical findings predicted the need for surgery. The large majority of patients with pseudocyst are able to be treated effectively without impact in their professional function. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Decomposition of Near-Infrared Spectroscopy Signals Using Oblique Subspace Projections: Applications in Brain Hemodynamic Monitoring.

PubMed

Caicedo, Alexander; Varon, Carolina; Hunyadi, Borbala; Papademetriou, Maria; Tachtsidis, Ilias; Van Huffel, Sabine

2016-01-01

Clinical data is comprised by a large number of synchronously collected biomedical signals that are measured at different locations. Deciphering the interrelationships of these signals can yield important information about their dependence providing some useful clinical diagnostic data. For instance, by computing the coupling between Near-Infrared Spectroscopy signals (NIRS) and systemic variables the status of the hemodynamic regulation mechanisms can be assessed. In this paper we introduce an algorithm for the decomposition of NIRS signals into additive components. The algorithm, SIgnal DEcomposition base on Obliques Subspace Projections (SIDE-ObSP), assumes that the measured NIRS signal is a linear combination of the systemic measurements, following the linear regression model y = Ax + ϵ . SIDE-ObSP decomposes the output such that, each component in the decomposition represents the sole linear influence of one corresponding regressor variable. This decomposition scheme aims at providing a better understanding of the relation between NIRS and systemic variables, and to provide a framework for the clinical interpretation of regression algorithms, thereby, facilitating their introduction into clinical practice. SIDE-ObSP combines oblique subspace projections (ObSP) with the structure of a mean average system in order to define adequate signal subspaces. To guarantee smoothness in the estimated regression parameters, as observed in normal physiological processes, we impose a Tikhonov regularization using a matrix differential operator. We evaluate the performance of SIDE-ObSP by using a synthetic dataset, and present two case studies in the field of cerebral hemodynamics monitoring using NIRS. In addition, we compare the performance of this method with other system identification techniques. In the first case study data from 20 neonates during the first 3 days of life was used, here SIDE-ObSP decoupled the influence of changes in arterial oxygen saturation from the NIRS measurements, facilitating the use of NIRS as a surrogate measure for cerebral blood flow (CBF). The second case study used data from a 3-years old infant under Extra Corporeal Membrane Oxygenation (ECMO), here SIDE-ObSP decomposed cerebral/peripheral tissue oxygenation, as a sum of the partial contributions from different systemic variables, facilitating the comparison between the effects of each systemic variable on the cerebral/peripheral hemodynamics.

Autosomal dominant polycystic kidney disease in a family with mosaicism and hypomorphic allele.

PubMed

Reiterová, Jana; Štekrová, Jitka; Merta, Miroslav; Kotlas, Jaroslav; Elišáková, Veronika; Lněnička, Petr; Korabečná, Marie; Kohoutová, Milada; Tesař, Vladimír

2013-03-15

Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability of ADPKD highlights a role for genetic background. Here we report a case of ADPKD family initially appearing unlinked to the PKD1 or PKD2 loci and the influence of mosaicism and hypomorphic allele on the variability of the clinical course of the disease. A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation. On the other hand, her grandson had a severe clinical course (end stage renal disease at the age of 45) in spite of the early treatment of mild hypertension. There was found by mutational analysis of PKD genes that the severe clinical course was caused by PKD1 gene frameshifting mutation inherited from his father and mildly affected grandmother in combination with inherited hypomorphic PKD1 allele with described missense mutation (p.Thr2250Met) from his clinically healthy mother. The sister with two cysts and with PKD1 hypomorphic allele became the kidney donor to her severely affected brother. We present the first case of ADPKD with the influence of mosaicism and hypomorphic allele of the PKD1 gene on clinical course of ADPKD in one family. Moreover, this report illustrates the role of molecular genetic testing in assessing young related kidney donors for patients with ADPKD.

Stent Retriever Thrombectomy in Different Thrombus Locations of Anterior Cerebral Circulation

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

Protto, Sara; Sillanpää, Niko, E-mail: niko.sillanpaa@pshp.fi; Pienimäki, Juha-Pekka

BackgroundMechanical thrombectomy (MT) is a safe and efficient treatment for acute ischemic stroke in patients with proximal anterior occlusion and large penumbra. We evaluated the technical and clinical success of MT in relation to the location of the occlusion (internal carotid artery, M1 and M2 segments of the middle cerebral artery).MethodsWe prospectively reviewed 130 patients of whom 105 met the inclusion criteria. Baseline clinical, procedural and imaging variables, technical outcome (TICI, thrombolysis in cerebral infarction), 24 h imaging outcome and three-month clinical outcome (mRS, modified Rankin Scale) were recorded. Differences between the groups were studied with statistical tests according to themore » type of the variable.ResultsThere were 37, 46 and 22 patients in the internal carotid artery (ICA), M1 and M2 groups, respectively. TICI 2b or 3 was achieved in 92 cases (88 %) with a non-significant trend towards a better recanalization outcome in the ICA and M1 groups. Overall, 57 of the 105 patients (55 %) experienced favorable clinical outcome (mRS ≤ 2) with no significant differences between the groups. Excellent outcome (mRS ≤ 1) was seen in 40 patients (39 %) and there proportionally more patients with excellent outcome in the ICA and M1 groups (ICA: 44 %, M1: 41 %, M2: 23 % of patients, p = 0.22).ConclusionsThere were no statistically significant differences in the technical or clinical outcomes between the different sites of occlusion (ICA, M1 or M2). There was a non-significant trend towards achieving excellent clinical outcome (3-month mRS ≤ 1) more often and better recanalization results in the two more proximal locations.« less

Different disease subtypes with distinct clinical expression in familial Mediterranean fever: results of a cluster analysis.

PubMed

Akar, Servet; Solmaz, Dilek; Kasifoglu, Timucin; Bilge, Sule Yasar; Sari, Ismail; Gumus, Zeynep Zehra; Tunca, Mehmet

2016-02-01

The aim of this study was to evaluate whether there are clinical subgroups that may have different prognoses among FMF patients. The cumulative clinical features of a large group of FMF patients [1168 patients, 593 (50.8%) male, mean age 35.3 years (s.d. 12.4)] were studied. To analyse our data and identify groups of FMF patients with similar clinical characteristics, a two-step cluster analysis using log-likelihood distance measures was performed. For clustering the FMF patients, we evaluated the following variables: gender, current age, age at symptom onset, age at diagnosis, presence of major clinical features, variables related with therapy and family history for FMF, renal failure and carriage of M694V. Three distinct groups of FMF patients were identified. Cluster 1 was characterized by a high prevalence of arthritis, pleuritis, erysipelas-like erythema (ELE) and febrile myalgia. The dosage of colchicine and the frequency of amyloidosis were lower in cluster 1. Patients in cluster 2 had an earlier age of disease onset and diagnosis. M694V carriage and amyloidosis prevalence were the highest in cluster 2. This group of patients was using the highest dose of colchicine. Patients in cluster 3 had the lowest prevalence of arthritis, ELE and febrile myalgia. The frequencies of M694V carriage and amyloidosis were lower in cluster 3 than the overall FMF patients. Non-response to colchicine was also slightly lower in cluster 3. Patients with FMF can be clustered into distinct patterns of clinical and genetic manifestations and these patterns may have different prognostic significance. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cluster Analysis to Identify Possible Subgroups in Tinnitus Patients.

PubMed

van den Berge, Minke J C; Free, Rolien H; Arnold, Rosemarie; de Kleine, Emile; Hofman, Rutger; van Dijk, J Marc C; van Dijk, Pim

2017-01-01

In tinnitus treatment, there is a tendency to shift from a "one size fits all" to a more individual, patient-tailored approach. Insight in the heterogeneity of the tinnitus spectrum might improve the management of tinnitus patients in terms of choice of treatment and identification of patients with severe mental distress. The goal of this study was to identify subgroups in a large group of tinnitus patients. Data were collected from patients with severe tinnitus complaints visiting our tertiary referral tinnitus care group at the University Medical Center Groningen. Patient-reported and physician-reported variables were collected during their visit to our clinic. Cluster analyses were used to characterize subgroups. For the selection of the right variables to enter in the cluster analysis, two approaches were used: (1) variable reduction with principle component analysis and (2) variable selection based on expert opinion. Various variables of 1,783 tinnitus patients were included in the analyses. Cluster analysis (1) included 976 patients and resulted in a four-cluster solution. The effect of external influences was the most discriminative between the groups, or clusters, of patients. The "silhouette measure" of the cluster outcome was low (0.2), indicating a "no substantial" cluster structure. Cluster analysis (2) included 761 patients and resulted in a three-cluster solution, comparable to the first analysis. Again, a "no substantial" cluster structure was found (0.2). Two cluster analyses on a large database of tinnitus patients revealed that clusters of patients are mostly formed by a different response of external influences on their disease. However, both cluster outcomes based on this dataset showed a poor stability, suggesting that our tinnitus population comprises a continuum rather than a number of clearly defined subgroups.

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.

Systematic evaluation of a targeted gene capture sequencing panel for molecular diagnosis of retinitis pigmentosa.

PubMed

Huang, Hui; Chen, Yanhua; Chen, Huishuang; Ma, Yuanyuan; Chiang, Pei-Wen; Zhong, Jing; Liu, Xuyang; Asan; Wu, Jing; Su, Yan; Li, Xin; Deng, Jianlian; Huang, Yingping; Zhang, Xinxin; Li, Yang; Fan, Ning; Wang, Ying; Tang, Lihui; Shen, Jinting; Chen, Meiyan; Zhang, Xiuqing; Te, Deng; Banerjee, Santasree; Liu, Hui; Qi, Ming; Yi, Xin

2018-01-01

Inherited eye diseases are major causes of vision loss in both children and adults. Inherited eye diseases are characterized by clinical variability and pronounced genetic heterogeneity. Genetic testing may provide an accurate diagnosis for ophthalmic genetic disorders and allow gene therapy for specific diseases. A targeted gene capture panel was designed to capture exons of 283 inherited eye disease genes including 58 known causative retinitis pigmentosa (RP) genes. 180 samples were tested with this panel, 68 were previously tested by Sanger sequencing. Systematic evaluation of our method and comprehensive molecular diagnosis were carried on 99 RP patients. 96.85% targeted regions were covered by at least 20 folds, the accuracy of variants detection was 99.994%. In 4 of the 68 samples previously tested by Sanger sequencing, mutations of other diseases not consisting with the clinical diagnosis were detected by next-generation sequencing (NGS) not Sanger. Among the 99 RP patients, 64 (64.6%) were detected with pathogenic mutations, while in 3 patients, it was inconsistent between molecular diagnosis and their initial clinical diagnosis. After revisiting, one patient's clinical diagnosis was reclassified. In addition, 3 patients were found carrying large deletions. We have systematically evaluated our method and compared it with Sanger sequencing, and have identified a large number of novel mutations in a cohort of 99 RP patients. The results showed a sufficient accuracy of our method and suggested the importance of molecular diagnosis in clinical diagnosis.

Systematic evaluation of a targeted gene capture sequencing panel for molecular diagnosis of retinitis pigmentosa

PubMed Central

Ma, Yuanyuan; Chiang, Pei-Wen; Zhong, Jing; Liu, Xuyang; Asan; Wu, Jing; Su, Yan; Li, Xin; Deng, Jianlian; Huang, Yingping; Zhang, Xinxin; Li, Yang; Fan, Ning; Wang, Ying; Tang, Lihui; Shen, Jinting; Chen, Meiyan; Zhang, Xiuqing; Te, Deng; Banerjee, Santasree; Liu, Hui; Qi, Ming; Yi, Xin

2018-01-01

Background Inherited eye diseases are major causes of vision loss in both children and adults. Inherited eye diseases are characterized by clinical variability and pronounced genetic heterogeneity. Genetic testing may provide an accurate diagnosis for ophthalmic genetic disorders and allow gene therapy for specific diseases. Methods A targeted gene capture panel was designed to capture exons of 283 inherited eye disease genes including 58 known causative retinitis pigmentosa (RP) genes. 180 samples were tested with this panel, 68 were previously tested by Sanger sequencing. Systematic evaluation of our method and comprehensive molecular diagnosis were carried on 99 RP patients. Results 96.85% targeted regions were covered by at least 20 folds, the accuracy of variants detection was 99.994%. In 4 of the 68 samples previously tested by Sanger sequencing, mutations of other diseases not consisting with the clinical diagnosis were detected by next-generation sequencing (NGS) not Sanger. Among the 99 RP patients, 64 (64.6%) were detected with pathogenic mutations, while in 3 patients, it was inconsistent between molecular diagnosis and their initial clinical diagnosis. After revisiting, one patient’s clinical diagnosis was reclassified. In addition, 3 patients were found carrying large deletions. Conclusions We have systematically evaluated our method and compared it with Sanger sequencing, and have identified a large number of novel mutations in a cohort of 99 RP patients. The results showed a sufficient accuracy of our method and suggested the importance of molecular diagnosis in clinical diagnosis. PMID:29641573

Review and classification of variability analysis techniques with clinical applications.

PubMed

Bravi, Andrea; Longtin, André; Seely, Andrew J E

2011-10-10

Analysis of patterns of variation of time-series, termed variability analysis, represents a rapidly evolving discipline with increasing applications in different fields of science. In medicine and in particular critical care, efforts have focussed on evaluating the clinical utility of variability. However, the growth and complexity of techniques applicable to this field have made interpretation and understanding of variability more challenging. Our objective is to provide an updated review of variability analysis techniques suitable for clinical applications. We review more than 70 variability techniques, providing for each technique a brief description of the underlying theory and assumptions, together with a summary of clinical applications. We propose a revised classification for the domains of variability techniques, which include statistical, geometric, energetic, informational, and invariant. We discuss the process of calculation, often necessitating a mathematical transform of the time-series. Our aims are to summarize a broad literature, promote a shared vocabulary that would improve the exchange of ideas, and the analyses of the results between different studies. We conclude with challenges for the evolving science of variability analysis.

Review and classification of variability analysis techniques with clinical applications

PubMed Central

2011-01-01

Analysis of patterns of variation of time-series, termed variability analysis, represents a rapidly evolving discipline with increasing applications in different fields of science. In medicine and in particular critical care, efforts have focussed on evaluating the clinical utility of variability. However, the growth and complexity of techniques applicable to this field have made interpretation and understanding of variability more challenging. Our objective is to provide an updated review of variability analysis techniques suitable for clinical applications. We review more than 70 variability techniques, providing for each technique a brief description of the underlying theory and assumptions, together with a summary of clinical applications. We propose a revised classification for the domains of variability techniques, which include statistical, geometric, energetic, informational, and invariant. We discuss the process of calculation, often necessitating a mathematical transform of the time-series. Our aims are to summarize a broad literature, promote a shared vocabulary that would improve the exchange of ideas, and the analyses of the results between different studies. We conclude with challenges for the evolving science of variability analysis. PMID:21985357

A three-dimensional comparison of a morphometric and conventional cephalometric midsagittal planes for craniofacial asymmetry.

PubMed

Damstra, Janalt; Fourie, Zacharias; De Wit, Marnix; Ren, Yijin

2012-02-01

Morphometric methods are used in biology to study object symmetry in living organisms and to determine the true plane of symmetry. The aim of this study was to determine if there are clinical differences between three-dimensional (3D) cephalometric midsagittal planes used to describe craniofacial asymmetry and a true symmetry plane derived from a morphometric method based on visible facial features. The sample consisted of 14 dry skulls (9 symmetric and 5 asymmetric) with metallic markers which were imaged with cone-beam computed tomography. An error study and statistical analysis were performed to validate the morphometric method. The morphometric and conventional cephalometric planes were constructed and compared. The 3D cephalometric planes constructed as perpendiculars to the Frankfort horizontal plane resembled the morphometric plane the most in both the symmetric and asymmetric groups with mean differences of less than 1.00 mm for most variables. However, the standard deviations were often large and clinically significant for these variables. There were clinically relevant differences (>1.00 mm) between the different 3D cephalometric midsagittal planes and the true plane of symmetry determined by the visible facial features. The difference between 3D cephalometric midsagittal planes and the true plane of symmetry determined by the visible facial features were clinically relevant. Care has to be taken using cephalometric midsagittal planes for diagnosis and treatment planning of craniofacial asymmetry as they might differ from the true plane of symmetry as determined by morphometrics.

Calcium supplementation improves clinical outcome in intensive care unit patients: a propensity score matched analysis of a large clinical database MIMIC-II.

PubMed

Zhang, Zhongheng; Chen, Kun; Ni, Hongying

2015-01-01

Observational studies have linked hypocalcemia with adverse clinical outcome in critically ill patients. However, calcium supplementation has never been formally investigated for its beneficial effect in critically ill patients. To investigate whether calcium supplementation can improve 28-day survival in adult critically ill patients. Secondary analysis of a large clinical database consisting over 30,000 critical ill patients was performed. Multivariable analysis was performed to examine the independent association of calcium supplementation and 28-day morality. Furthermore, propensity score matching technique was employed to investigate the role of calcium supplementation in improving survival. none. Primary outcome was the 28-day mortality. 90-day mortality was used as secondary outcome. A total of 32,551 adult patients, including 28,062 survivors and 4489 non-survivors (28-day mortality rate: 13.8 %) were included. Calcium supplementation was independently associated with improved 28-day mortality after adjusting for confounding variables (hazard ratio: 0.51; 95 % CI 0.47-0.56). Propensity score matching was performed and the after-matching cohort showed well balanced covariates. The results showed that calcium supplementation was associated with improved 28- and 90-day mortality (p < 0.05 for both Log-rank test). In adult critically ill patients, calcium supplementation during their ICU stay improved 28-day survival. This finding supports the use of calcium supplementation in critically ill patients.

Wearable sensor-based objective assessment of motor symptoms in Parkinson's disease.

PubMed

Ossig, Christiana; Antonini, Angelo; Buhmann, Carsten; Classen, Joseph; Csoti, Ilona; Falkenburger, Björn; Schwarz, Michael; Winkler, Jürgen; Storch, Alexander

2016-01-01

Effective management and development of new treatment strategies of motor symptoms in Parkinson's disease (PD) largely depend on clinical rating instruments like the Unified PD rating scale (UPDRS) and the modified abnormal involuntary movement scale (mAIMS). Regarding inter-rater variability and continuous monitoring, clinical rating scales have various limitations. Patient-administered questionnaires such as the PD home diary to assess motor stages and fluctuations in late-stage PD are frequently used in clinical routine and as clinical trial endpoints, but diary/questionnaire are tiring, and recall bias impacts on data quality, particularly in patients with cognitive dysfunction or depression. Consequently, there is a strong need for continuous and objective monitoring of motor symptoms in PD for improving therapeutic regimen and for usage in clinical trials. Recent advances in battery technology, movement sensors such as gyroscopes, accelerometers and information technology boosted the field of objective measurement of movement in everyday life and medicine using wearable sensors allowing continuous (long-term) monitoring. This systematic review summarizes the current wearable sensor-based devices to objectively assess the various motor symptoms of PD.

Automated array-based genomic profiling in chronic lymphocytic leukemia: Development of a clinical tool and discovery of recurrent genomic alterations

PubMed Central

Schwaenen, Carsten; Nessling, Michelle; Wessendorf, Swen; Salvi, Tatjana; Wrobel, Gunnar; Radlwimmer, Bernhard; Kestler, Hans A.; Haslinger, Christian; Stilgenbauer, Stephan; Döhner, Hartmut; Bentz, Martin; Lichter, Peter

2004-01-01

B cell chronic lymphocytic leukemia (B-CLL) is characterized by a highly variable clinical course. Recurrent chromosomal imbalances provide significant prognostic markers. Risk-adapted therapy based on genomic alterations has become an option that is currently being tested in clinical trials. To supply a robust tool for such large scale studies, we developed a comprehensive DNA microarray dedicated to the automated analysis of recurrent genomic imbalances in B-CLL by array-based comparative genomic hybridization (matrix–CGH). Validation of this chip in a series of 106 B-CLL cases revealed a high specificity and sensitivity that fulfils the criteria for application in clinical oncology. This chip is immediately applicable within clinical B-CLL treatment trials that evaluate whether B-CLL cases with distinct chromosomal abnormalities should be treated with chemotherapy of different intensities and/or stem cell transplantation. Through the control set of DNA fragments equally distributed over the genome, recurrent genomic imbalances were discovered: trisomy of chromosome 19 and gain of the MYCN oncogene correlating with an elevation of MYCN mRNA expression. PMID:14730057

Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA.

PubMed

Smith, Wade S; Lev, Michael H; English, Joey D; Camargo, Erica C; Chou, Maggie; Johnston, S Claiborne; Gonzalez, Gilberto; Schaefer, Pamela W; Dillon, William P; Koroshetz, Walter J; Furie, Karen L

2009-12-01

Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries-likely portends a worse prognosis than stroke unassociated with LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify. The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression. Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3; P<0.001). Six-month good outcome (modified Rankin Scale score

[Renal elastography].

PubMed

Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

2016-04-01

Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Childhood trauma is not a confounder of the overlap between autistic and schizotypal traits: A study in a non-clinical adult sample.

PubMed

Gong, Jing-Bo; Wang, Ya; Lui, Simon S Y; Cheung, Eric F C; Chan, Raymond C K

2017-11-01

Childhood trauma has been shown to be a robust risk factor for mental disorders, and may exacerbate schizotypal traits or contribute to autistic trait severity. However, little is known whether childhood trauma confounds the overlap between schizotypal traits and autistic traits. This study examined whether childhood trauma acts as a confounding variable in the overlap between autistic and schizotypal traits in a large non-clinical adult sample. A total of 2469 participants completed the Autism Spectrum Quotient (AQ), the Schizotypal Personality Questionnaire (SPQ), and the Childhood Trauma Questionnaire-Short Form. Correlation analysis showed that the majority of associations between AQ variables and SPQ variables were significant (p < 0.05). In the multiple regression models predicting scores on the AQ total, scores on the three SPQ subscales were significant predictors(Ps < 0.05). Scores on the Positive schizotypy and Negative schizotypy subscales were significant predictors in the multiple regression model predicting scores on the AQ Social Skill, AQ Attention Switching, AQ Attention to Detail, AQ Communication, and AQ Imagination subscales. The association between autistic and schizotypal traits could not be explained by shared variance in terms of exposure to childhood trauma. The findings point to important overlaps in the conceptualization of ASD and SSD, independent of childhood trauma. Copyright © 2017 Elsevier B.V. All rights reserved.

A systematic literature search to identify performance measure outcomes used in clinical studies of racehorses.

PubMed

Wylie, C E; Newton, J R

2018-05-01

Racing performance is often used as a measurable outcome variable in research studies investigating clinical diagnoses or interventions. However, the use of many different performance measures largely precludes conduct of meaningful comparative studies and, to date, those being used have not been collated. To systematically review the veterinary scientific literature for the use of racing performance as a measurable outcome variable in clinical studies of racehorses, collate and identify those most popular, and identify their advantages and disadvantages. Systematic literature search. The search criteria "((racing AND performance) AND (horses OR equidae))" were adapted for both MEDLINE and CAB Abstracts databases. Data were collected in standardised recording forms for binary, categorical and quantitative measures, and the use of performance indices. In total, 217 studies that described racing performance were identified, contributing 117 different performance measures. No one performance measure was used in all studies, despite 90.3% using more than one variable. Data regarding race starts and earnings were used most commonly, with 88.0% and 54.4% of studies including at least one measure of starts and earnings, respectively. Seventeen variables were used 10 times or more, with the top five comprising: 'return to racing', 'number of starts', 'days to first start', 'earnings per period of time' and 'earnings per start'. The search strategies may not have identified all relevant papers, introducing bias to the review. Performance indices have been developed to improve assessment of interventions; however, they are not widely adopted in the scientific literature. Use of the two most commonly identified measures, whether the horse returned to racing and number of starts over a defined period of time, would best facilitate future systematic reviews and meta-analyses in advance of the development of a gold-standard measure of race performance outcome. © 2017 EVJ Ltd.

Validation of a Cochlear Implant Patient-Specific Model of the Voltage Distribution in a Clinical Setting

PubMed Central

Nogueira, Waldo; Schurzig, Daniel; Büchner, Andreas; Penninger, Richard T.; Würfel, Waldemar

2016-01-01

Cochlear Implants (CIs) are medical implantable devices that can restore the sense of hearing in people with profound hearing loss. Clinical trials assessing speech intelligibility in CI users have found large intersubject variability. One possibility to explain the variability is the individual differences in the interface created between electrodes of the CI and the auditory nerve. In order to understand the variability, models of the voltage distribution of the electrically stimulated cochlea may be useful. With this purpose in mind, we developed a parametric model that can be adapted to each CI user based on landmarks from individual cone beam computed tomography (CBCT) scans of the cochlea before and after implantation. The conductivity values of each cochlea compartment as well as the weighting factors of different grounding modes have also been parameterized. Simulations were performed modeling the cochlea and electrode positions of 12 CI users. Three models were compared with different levels of detail: a homogeneous model (HM), a non-patient-specific model (NPSM), and a patient-specific model (PSM). The model simulations were compared with voltage distribution measurements obtained from the backward telemetry of the 12 CI users. Results show that the PSM produces the lowest error when predicting individual voltage distributions. Given a patient-specific geometry and electrode positions, we show an example on how to optimize the parameters of the model and how to couple it to an auditory nerve model. The model here presented may help to understand speech performance variability and support the development of new sound coding strategies for CIs. PMID:27933290

The influence of cultural variables on treatment retention and engagement in a sample of Mexican American adolescent males with substance use disorders.

PubMed

Burrow-Sánchez, Jason J; Meyers, Kimberly; Corrales, Carolina; Ortiz-Jensen, Cynthia

2015-12-01

Adolescent substance abuse is a serious public health concern, and in response to this problem, a number of effective treatment approaches have been developed. Despite this, retaining and engaging adolescents in treatment are 2 major challenges continuously faced by practitioners and clinical researchers. Low retention and engagement rates are especially salient for ethnic minority adolescents because they are at high risk for underutilization of substance abuse treatment compared to their White peers. Latino adolescents, in particular, are part of the fastest growing ethnic minority group in the United States and experience high rates of substance use disorders. Heretofore, the empirical examination of cultural factors that influence treatment retention and engagement has been lacking in the literature. The goal of this study was to investigate the influence of the cultural variables ethnic identity, familism, and acculturation on the retention and engagement of Latino adolescents participating in substance abuse treatment. This study used data collected from a sample of Latino adolescent males (N = 96), predominantly of Mexican descent, and largely recruited from the juvenile justice system. Analysis was conducted using generalized regression models for count variables. Results indicated that higher levels of exploration, a subfactor of ethnic identity, and familism were predictive of attendance and engagement. In contrast, higher levels of Anglo orientation, a subfactor of acculturation, were predictive of lower treatment attendance and engagement. Clinical implications for the variables of ethnic identity, acculturation, and familism as well as suggestions for future research are discussed. (c) 2016 APA, all rights reserved).

Contemporary Animal Models For Human Gene Therapy Applications.

PubMed

Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Nelson, Everette Jacob Remington

2015-01-01

Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.

Variable mechanical ventilation

PubMed Central

Fontela, Paula Caitano; Prestes, Renata Bernardy; Forgiarini Jr., Luiz Alberto; Friedman, Gilberto

2017-01-01

Objective To review the literature on the use of variable mechanical ventilation and the main outcomes of this technique. Methods Search, selection, and analysis of all original articles on variable ventilation, without restriction on the period of publication and language, available in the electronic databases LILACS, MEDLINE®, and PubMed, by searching the terms "variable ventilation" OR "noisy ventilation" OR "biologically variable ventilation". Results A total of 36 studies were selected. Of these, 24 were original studies, including 21 experimental studies and three clinical studies. Conclusion Several experimental studies reported the beneficial effects of distinct variable ventilation strategies on lung function using different models of lung injury and healthy lungs. Variable ventilation seems to be a viable strategy for improving gas exchange and respiratory mechanics and preventing lung injury associated with mechanical ventilation. However, further clinical studies are necessary to assess the potential of variable ventilation strategies for the clinical improvement of patients undergoing mechanical ventilation. PMID:28444076

SU-E-J-262: Variability in Texture Analysis of Gynecological Tumors in the Context of An 18F-FDG PET Adaptive Protocol

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

Nawrocki, J; Chino, J; Das, S

Purpose: This study examines the effect on texture analysis due to variable reconstruction of PET images in the context of an adaptive FDG PET protocol for node positive gynecologic cancer patients. By measuring variability in texture features from baseline and intra-treatment PET-CT, we can isolate unreliable texture features due to large variation. Methods: A subset of seven patients with node positive gynecological cancers visible on PET was selected for this study. Prescribed dose varied between 45–50.4Gy, with a 55–70Gy boost to the PET positive nodes. A baseline and intratreatment (between 30–36Gy) PET-CT were obtained on a Siemens Biograph mCT. Eachmore » clinical PET image set was reconstructed 6 times using a TrueX+TOF algorithm with varying iterations and Gaussian filter. Baseline and intra-treatment primary GTVs were segmented using PET Edge (MIM Software Inc., Cleveland, OH), a semi-automatic gradient-based algorithm, on the clinical PET and transferred to the other reconstructed sets. Using an in-house MATLAB program, four 3D texture matrices describing relationships between voxel intensities in the GTV were generated: co-occurrence, run length, size zone, and neighborhood difference. From these, 39 textural features characterizing texture were calculated in addition to SUV histogram features. The percent variability among parameters was first calculated. Each reconstructed texture feature from baseline and intra-treatment per patient was normalized to the clinical baseline scan and compared using the Wilcoxon signed-rank test in order to isolate variations due to reconstruction parameters. Results: For the baseline scans, 13 texture features showed a mean range greater than 10%. For the intra scans, 28 texture features showed a mean range greater than 10%. Comparing baseline to intra scans, 25 texture features showed p <0.05. Conclusion: Variability due to different reconstruction parameters increased with treatment, however, the majority of texture features showed significant changes during treatment independent of reconstruction effects.« less

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.

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.

High variability in baseline urinary free cortisol values in patients with Cushing's disease.

PubMed

Petersenn, S; Newell-Price, J; Findling, J W; Gu, F; Maldonado, M; Sen, K; Salgado, L R; Colao, A; Biller, B M K

2014-02-01

Twenty-four-hour urinary free cortisol (UFC) sampling is commonly used to evaluate Cushing's syndrome. Because there are few data on UFC variability in patients with active Cushing's disease, we analysed baseline UFC in a large patient cohort with moderate-to-severe Cushing's disease and assessed whether variability correlates with hypercortisolism severity. These data will help clinicians establish the minimum number of UFC samples required to obtain reliable data. Observational study (enrolment phase of Phase III study). Patients (n = 152) with persistent/recurrent or de novo Cushing's disease and mean UFC (mUFC) ≥1·5×ULN (normal: 30-145 nmol/24 h) were included. Mean UFC level was calculated from four 24-h urine samples collected over 2 weeks. Over 600 24-h UFC samples were analysed. The mUFC levels of samples 1 and 2 and samples 3 and 4 were 1000 nmol/24 h (SD 1872) and 940 nmol/24 h (SD 2148), respectively; intrapatient coefficient of variation (CV) was 38% for mUFC. The intrapatient CV using all four samples was 52% (95% CI: 48-56). The intrapatient CV was 51% (95% CI: 44-58) for samples 1 and 2, 49% (95% CI: 43-56) for samples 3 and 4 and 54% (95% CI: 49-59) for samples 1, 2 and 3. Variability in mUFC increased as UFC levels increased. There were no correlations between UFC and clinical features of hypercortisolism. There is intrapatient variability of approximately 50% in 24-h UFC measurements, which is relevant to targets set to estimate any treatment effect. Analysing more than two 24-h collection periods in individual patients does not result in a relevant decrease in variability. Interestingly, UFC levels did not correlate with hypercortisolism severity. © 2013 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

[Assessment of the correlation between histological degeneration and radiological and clinical parameters in a series of patients who underwent lumbar disc herniation surgery].

PubMed

Munarriz, Pablo M; Paredes, Igor; Alén, José F; Castaño-Leon, Ana M; Cepeda, Santiago; Hernandez-Lain, Aurelio; Lagares, Alfonso

The use of histological degeneration scores in surgically-treated herniated lumbar discs is not common in clinical practice and its use has been primarily restricted to research. The objective of this study is to evaluate if there is an association between a higher grade of histological degeneration when compared with clinical or radiological parameters. Retrospective consecutive analysis of 122 patients who underwent single-segment lumbar disc herniation surgery. Clinical information was available on all patients, while the histological study and preoperative magnetic resonance imaging were also retrieved for 75 patients. Clinical variables included age, duration of symptoms, neurological deficits, or affected deep tendon reflex. The preoperative magnetic resonance imaging was evaluated using Modic and Pfirrmann scores for the affected segment by 2 independent observers. Histological degeneration was evaluated using Weiler's score; the presence of inflammatory infiltrates and neovascularization, not included in the score, were also studied. Correlation and chi-square tests were used to assess the association between histological variables and clinical or radiological variables. Interobserver agreement was also evaluated for the MRI variables using weighted kappa. No statistically significant correlation was found between histological variables (histological degeneration score, inflammatory infiltrates or neovascularization) and clinical or radiological variables. Interobserver agreement for radiological scores resulted in a kappa of 0.79 for the Pfirrmann scale and 0.65 for the Modic scale, both statistically significant. In our series of patients, we could not demonstrate any correlation between the degree of histological degeneration or the presence of inflammatory infiltrates when compared with radiological degeneration scales or clinical variables such as the patient's age or duration of symptoms. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

Linking crop yield anomalies to large-scale atmospheric circulation in Europe.

PubMed

Ceglar, Andrej; Turco, Marco; Toreti, Andrea; Doblas-Reyes, Francisco J

2017-06-15

Understanding the effects of climate variability and extremes on crop growth and development represents a necessary step to assess the resilience of agricultural systems to changing climate conditions. This study investigates the links between the large-scale atmospheric circulation and crop yields in Europe, providing the basis to develop seasonal crop yield forecasting and thus enabling a more effective and dynamic adaptation to climate variability and change. Four dominant modes of large-scale atmospheric variability have been used: North Atlantic Oscillation, Eastern Atlantic, Scandinavian and Eastern Atlantic-Western Russia patterns. Large-scale atmospheric circulation explains on average 43% of inter-annual winter wheat yield variability, ranging between 20% and 70% across countries. As for grain maize, the average explained variability is 38%, ranging between 20% and 58%. Spatially, the skill of the developed statistical models strongly depends on the large-scale atmospheric variability impact on weather at the regional level, especially during the most sensitive growth stages of flowering and grain filling. Our results also suggest that preceding atmospheric conditions might provide an important source of predictability especially for maize yields in south-eastern Europe. Since the seasonal predictability of large-scale atmospheric patterns is generally higher than the one of surface weather variables (e.g. precipitation) in Europe, seasonal crop yield prediction could benefit from the integration of derived statistical models exploiting the dynamical seasonal forecast of large-scale atmospheric circulation.

Neurocognitive Functioning in Patients with 22q11.2 Deletion Syndrome: A Meta-Analytic Review.

PubMed

Moberg, Paul J; Richman, Mara J; Roalf, David R; Morse, Chelsea L; Graefe, Anna C; Brennan, Laura; Vickers, Kayci; Tsering, Wangchen; Kamath, Vidyulata; Turetsky, Bruce I; Gur, Ruben C; Gur, Raquel E

2018-06-19

The 22q11.2 deletion syndrome (22q11.2DS) is a known risk factor for development of schizophrenia and is characterized by a complex neuropsychological profile. To date, a quantitative meta-analysis examining cognitive functioning in 22q11.2DS has not been conducted. A systematic review of cross-sectional studies comparing neuropsychological performance of individuals with 22q11.2DS with age-matched healthy typically developing and sibling comparison subjects was carried out. Potential moderators were analyzed. Analyses included 43 articles (282 effects) that met inclusion criteria. Very large and heterogeneous effects were seen for global cognition (d = - 1.21) and in specific neuropsychological domains (intellectual functioning, achievement, and executive function; d range = - 0.51 to - 2.43). Moderator analysis revealed a significant role for type of healthy comparison group used (typically developing or siblings), demographics (age, sex) and clinical factors (externalizing behavior). Results revealed significant differences between pediatric and adult samples, with isolated analysis within the pediatric sample yielding large effects in several neuropsychological domains (intellectual functioning, achievement, visual memory; d range = - 0.56 to - 2.50). Large cognitive deficits in intellectual functioning and specific neuropsychological variables in individuals with 22q11.2DS represent a robust finding, but these deficits are influenced by several factors, including type of comparison group utilized, age, sex, and clinical status. These findings highlight the clinical relevance of characterizing cognitive functioning in 22q11.2DS and the importance of considering demographic and clinical moderators in future analyses.

Regulatory scientific advice in drug development: does company size make a difference?

PubMed Central

Putzeist, Michelle; Gispen-De Wied, Christine C.; Hoes, Arno W.; Leufkens, Hubert G.

2010-01-01

Purpose To assess whether the content of Scientific Advice (SA) questions addressed to a national drug regulatory agency is associated with company size. This may help to increase understanding about the knowledge, strategic, and regulatory gaps companies face during drug development. Methodology A cross-sectional analysis was performed of SA provided by the Dutch Medicines Evaluation Board (MEB) in 2006–2008. Definition of company size was based on ranking by total revenues (Scrip’s Pharmaceutical Company League Tables 2008). The content of each SA question was scored according to predefined domains (quality, nonclinical, clinical, regulatory, and product information), their subdomains (e.g., efficacy), and a selection of additional content variables (e.g., endpoints, choice of active comparator). Results In total, 201 SA documents including 1,087 questions could be identified. Small, medium-sized, and large companies asked for SA 110 (54.7%), 40 (19.9%), and 51 (25.4%) times, respectively. Clinical questions were asked most often (65.9%), mainly including efficacy (33.2%) and safety questions (24.0%). The most frequent topics were overall efficacy and safety strategy. Small companies asked quality and nonclinical questions more often (P < 0.001) and clinical questions less frequently than large companies (P = 0.004). Small companies asked significantly more clinical questions about pharmacokinetics, including bioequivalence, than medium-sized and large companies (P < 0.001). Conclusion The array of topics addressed in SA provides an interesting outlook on what industry considers to be still unresolved in drug development and worthwhile to discuss with regulators. Company size is associated with the content of SA questions. MEB advice accommodates both innovative and noninnovative drug development. PMID:21049297

Regulatory scientific advice in drug development: does company size make a difference?

PubMed

Putzeist, Michelle; Mantel-Teeuwisse, Aukje K; Gispen-De Wied, Christine C; Hoes, Arno W; Leufkens, Hubert G

2011-02-01

To assess whether the content of Scientific Advice (SA) questions addressed to a national drug regulatory agency is associated with company size. This may help to increase understanding about the knowledge, strategic, and regulatory gaps companies face during drug development. A cross-sectional analysis was performed of SA provided by the Dutch Medicines Evaluation Board (MEB) in 2006-2008. Definition of company size was based on ranking by total revenues (Scrip's Pharmaceutical Company League Tables 2008). The content of each SA question was scored according to predefined domains (quality, nonclinical, clinical, regulatory, and product information), their subdomains (e.g., efficacy), and a selection of additional content variables (e.g., endpoints, choice of active comparator). In total, 201 SA documents including 1,087 questions could be identified. Small, medium-sized, and large companies asked for SA 110 (54.7%), 40 (19.9%), and 51 (25.4%) times, respectively. Clinical questions were asked most often (65.9%), mainly including efficacy (33.2%) and safety questions (24.0%). The most frequent topics were overall efficacy and safety strategy. Small companies asked quality and nonclinical questions more often (P < 0.001) and clinical questions less frequently than large companies (P = 0.004). Small companies asked significantly more clinical questions about pharmacokinetics, including bioequivalence, than medium-sized and large companies (P < 0.001). The array of topics addressed in SA provides an interesting outlook on what industry considers to be still unresolved in drug development and worthwhile to discuss with regulators. Company size is associated with the content of SA questions. MEB advice accommodates both innovative and noninnovative drug development.

A psychometric investigation of gender differences and common processes across Borderline and Antisocial Personality Disorders

PubMed Central

Chun, Seokjoon; Harris, Alexa; Carrion, Margely; Rojas, Elizabeth; Stark, Stephen; Lejuez, Carl; Lechner, William V.; Bornovalova, Marina A.

2016-01-01

The comorbidity between Borderline Personality Disorder (BPD) and Antisocial Personality Disorder (ASPD) is well-established, and the two disorders share many similarities. However, there are also differences across disorders: most notably, BPD is diagnosed more frequently in females and ASPD in males. We investigated if a) comorbidity between BPD and ASPD is attributable to two discrete disorders or the expression of common underlying processes, and b) if the model of comorbidity is true across sex. Using a clinical sample of 1400 drug users in residential substance abuse treatment, we tested three competing models to explore whether the comorbidity of ASPD and BPD should be represented by a single common factor, two correlated factors, or a bifactor structure involving a general and disorder-specific factors. Next, we tested whether our resulting model was meaningful by examining its relationship with criterion variables previously reported to be associated with BPD and ASPD. The bifactor model provided the best fit and was invariant across sex. Overall, the general factor of the bifactor model significantly accounted for a large percentage of the variance in criterion variables, whereas the BPD and AAB specific factors added little to the models. The association of the general and specific factor with all criterion variables was equal for males and females. Our results suggest common underlying vulnerability accounts for both the comorbidity between BPD and AAB (across sex), and this common vulnerability drives the association with other psychopathology and maladaptive behavior. This in turn has implications for diagnostic classification systems and treatment. General scientific summary This study found that, for both males and females, borderline and antisocial personality disorders show a large degree of overlap, and little uniqueness. The commonality between BPD and ASPD mainly accounted for associations with criterion variables. This suggests that BPD and ASPD show a large common core that accounts for their comorbidity. PMID:27808543

Ethical dilemmas of a large national multi-centre study in Australia: time for some consistency.

PubMed

Driscoll, Andrea; Currey, Judy; Worrall-Carter, Linda; Stewart, Simon

2008-08-01

To examine the impact and obstacles that individual Institutional Research Ethics Committee (IRECs) had on a large-scale national multi-centre clinical audit called the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study. Multi-centre research is commonplace in the health care system. However, IRECs continue to fail to differentiate between research and quality audit projects. The National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes study used an investigator-developed questionnaire concerning a clinical audit for heart failure programmes throughout Australia. Ethical guidelines developed by the National governing body of health and medical research in Australia classified the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study as a low risk clinical audit not requiring ethical approval by IREC. Fifteen of 27 IRECs stipulated that the research proposal undergo full ethical review. None of the IRECs acknowledged: national quality assurance guidelines and recommendations nor ethics approval from other IRECs. Twelve of the 15 IRECs used different ethics application forms. Variability in the type of amendments was prolific. Lack of uniformity in ethical review processes resulted in a six- to eight-month delay in commencing the national study. Development of a national ethics application form with full ethical review by the first IREC and compulsory expedited review by subsequent IRECs would resolve issues raised in this paper. IRECs must change their ethics approval processes to one that enhances facilitation of multi-centre research which is now normative process for health services. The findings of this study highlight inconsistent ethical requirements between different IRECs. Also highlighted are the obstacles and delays that IRECs create when undertaking multi-centre clinical audits. However, in our clinical practice it is vital that clinical audits are undertaken for evaluation purposes. The findings of this study raise awareness of inconsistent ethical processes and highlight the need for expedient ethical review for clinical audits.

A network of epigenetic modifiers and DNA repair genes controls tissue-specific copy number alteration preference.

PubMed

Cramer, Dina; Serrano, Luis; Schaefer, Martin H

2016-11-10

Copy number alterations (CNAs) in cancer patients show a large variability in their number, length and position, but the sources of this variability are not known. CNA number and length are linked to patient survival, suggesting clinical relevance. We have identified genes that tend to be mutated in samples that have few or many CNAs, which we term CONIM genes (COpy Number Instability Modulators). CONIM proteins cluster into a densely connected subnetwork of physical interactions and many of them are epigenetic modifiers. Therefore, we investigated how the epigenome of the tissue-of-origin influences the position of CNA breakpoints and the properties of the resulting CNAs. We found that the presence of heterochromatin in the tissue-of-origin contributes to the recurrence and length of CNAs in the respective cancer type.

Dose requirements of alfentanil to eliminate autonomic responses during rapid-sequence induction with thiopental 4 mg/kg and rocuronium 0.6 mg/kg.

PubMed

Abou-Arab, Mohammad H; Rostrup, Morten; Heier, Tom

2016-12-01

Opioids are integral part of anesthesia induction, but information on optimal dosing is limited. We aimed to determine doses of alfentanil needed to eliminate increases in 5 autonomic response variables (plasma concentrations of epinephrine, norepinephrine and vasopressin, arterial blood pressure [ABP], and heart rate) during rapid-sequence induction of anesthesia with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. Prospective, randomized, observer-blinded, interventional clinical study. Large academic institution. Eighty-four healthy patients, aged 18 to 55 years, received 1 of 7 assessor-blinded doses of alfentanil (0, 10, 20, 30, 40, 50, and 60 μg/kg) together with thiopental 4 mg/kg and rocuronium 0.6 mg/kg, administered in rapid succession (15 seconds). Laryngoscopy was initiated 40 seconds after rocuronium, and tracheal intubation was concluded within 15 seconds thereafter. An indwelling radial artery catheter was used for hemodynamic monitoring and blood sampling. Relationships between alfentanil dose and response variables were tested with linear regression, and the influence of covariates (sex, body weight, and age) was determined. Alfentanil dose needed to prevent increases in ABP >10% above baseline with 95% probability was estimated with logistic regression. Significant relationships were determined between alfentanil dose and response variables. Clinically interesting influence of covariates was not found. Alfentanil 55 μg/kg was needed to prevent increases in ABP postintubation >10% above baseline with 95% probability. One individual needed a bolus of vasopressor postintubation. Optimal control of autonomic responses during rapid-sequence induction was achieved with clinically relevant doses of alfentanil in healthy patients anesthetized with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. Copyright © 2016 Elsevier Inc. All rights reserved.

Phenotype variability in a large Spanish family with Alport syndrome associated with novel mutations in COL4A3 gene.

PubMed

Cervera-Acedo, C; Coloma, A; Huarte-Loza, E; Sierra-Carpio, M; Domínguez-Garrido, E

2017-10-31

Alport syndrome is an inherited renal disorder characterized by glomerular basement membrane lesions with hematuria, proteinuria and frequent hearing defects and ocular abnormalities. The disease is associated with mutations in genes encoding α3, α4, or α5 chains of type IV collagen, namely COL4A3 and COL4A4 in chromosome 2 and COL4A5 in chromosome X. In contrast to the well-known X-linked and autosomal recessive phenotypes, there is very little information about the autosomal dominant. In view of the wide spectrum of phenotypes, an exact diagnosis is sometimes difficult to achieve. We investigated a Spanish family with variable phenotype of autosomal dominant Alport syndrome using clinical, histological, and genetic analysis. Mutational analysis of COL4A3 and COL4A4 genes showed a novel heterozygous mutation (c. 998G > A; p.G333E) in exon 18 of the COL4A3 gene. Among relatives carrying the novel mutation, the clinical phenotype was variable. Two additional COL4A3 mutations were found, a Pro-Leu substitution in exon 48 (p.P1461L) and a Ser-Cys substitution in exon 49 (p.S1492C), non-pathogenics alone. Carriers of p.G333E and p.P1461L or p.S1492C mutations in COL4A3 gene appear to be more severely affected than carriers of only p.G333E mutation, and the clinical findings has an earlier onset. In this way, we could speculate on a synergistic effect of compound heterozygosity that could explain the different phenotype observed in this family.

Syncope Best Practices: A Syncope Clinical Practice Guideline to Improve Quality.

PubMed

Phelps, Heather M; Sachdeva, Ritu; Mahle, William T; McCracken, Courtney E; Kelleman, Michael; McConnell, Michael; Fischbach, Peter S; Cardis, Brian M; Campbell, Robert M; Oster, Matthew E

2016-05-01

To determine whether implementation of a standardized clinical practice guideline (CPG) for the evaluation of syncope would decrease practice variability and resource utilization. A retrospective review of medical records of patients presenting to our practice for outpatient evaluation of syncope before and after implementation of the CPG. The guideline included elements of history, physical exam, electrocardiogram, and "red flags" for further testing. Outpatient pediatric cardiology offices of a large pediatric cardiology practice. All new patients between 3 and 21 years old, who presented to cardiology clinic with a chief complaint of syncope. The CPG for the evaluation of pediatric syncope was presented to the providers. Resource utilization was determined by the tests ordered by individual physicians before and after initiation of the CPG. Patient final diagnoses were recorded and the medical records were subsequently reviewed to determine if any patients, who presented again to the system, were ultimately diagnosed with cardiac disease. Of the 1496 patients with an initial visit for syncope, there was no significant difference in the diagnosis of cardiac disease before or after initiation of the CPG: (0.6% vs. 0.4%, P = .55). Electrocardiography provides the highest yield in the evaluation of pediatric syncope. Despite high compliance (86.9%), there were no overall changes in costs ($346.31 vs. $348.53, P = .85) or in resource utilization. There was, however, a decrease in the variability of ordering of echocardiograms among physicians, particularly among those at the extremes of utilization. Although the CPG did not decrease already low costs, it did decrease the wide variability in echo utilization. Evaluation beyond detailed history, physical exam, and electrocardiography provides no additional benefit in the evaluations of pediatric patients presenting with syncope. © 2015 Wiley Periodicals, Inc.

Quality requirements for veterinary hematology analyzers in small animals-a survey about veterinary experts' requirements and objective evaluation of analyzer performance based on a meta-analysis of method validation studies: bench top hematology analyzer.

PubMed

Cook, Andrea M; Moritz, Andreas; Freeman, Kathleen P; Bauer, Natali

2016-09-01

Scarce information exists about quality requirements and objective evaluation of performance of large veterinary bench top hematology analyzers. The study was aimed at comparing the observed total error (TEobs ) derived from meta-analysis of published method validation data to the total allowable error (TEa ) for veterinary hematology variables in small animals based on experts' opinions. Ideally, TEobs should be < TEa . An online survey was sent to veterinary experts in clinical pathology and small animal internal medicine for providing the maximal allowable deviation from a given result for each variable. Percent of TEa = (allowable median deviation/clinical threshold) * 100%. Second, TEobs for 3 laser-based bench top hematology analyzers (ADVIA 2120; Sysmex XT2000iV, and CellDyn 3500) was calculated based on method validation studies published between 2005 and 2013 (n = 4). The percent TEobs = 2 * CV (%) + bias (%). The CV was derived from published studies except for the ADVIA 2120 (internal data), and bias was estimated from the regression equation. A total of 41 veterinary experts (19 diplomates, 8 residents, 10 postgraduate students, 4 anonymous specialists) responded. The proposed range of TEa was wide, but generally ≤ 20%. The TEobs was < TEa for all variables and analyzers except for canine and feline HGB (high bias, low CV) and platelet counts (high bias, high CV). Overall, veterinary bench top analyzers fulfilled experts' requirements except for HGB due to method-related bias, and platelet counts due to known preanalytic/analytic issues. © 2016 American Society for Veterinary Clinical Pathology.

High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a prospective multicentre study.

PubMed

van der Stoep, M Y Eileen C; Bertaina, Alice; Ten Brink, Marloes H; Bredius, Robbert G; Smiers, Frans J; Wanders, Dominique C M; Moes, Dirk Jan A R; Locatelli, Franco; Guchelaar, Henk-Jan; Zwaveling, Juliëtte; Lankester, Arjan C

2017-12-01

Treosulfan-based conditioning is increasingly employed in paediatric haematopoietic stem cell transplantation (HSCT). Data on treosulfan pharmacokinetics in children are scarce, and the relationship between treosulfan exposure, toxicity and clinical outcome is unresolved. In this multicentre prospective observational study, we studied treosulfan pharmacokinetics and the drug's relationship with regimen-related toxicity and early clinical outcome in 77 paediatric patients. Treosulfan dose was 30 g/m 2 , administered over 3 consecutive days in infants <1 year old (n = 12) and 42 g/m 2 in children ≥1 year old (n = 65). Mean day 1 treosulfan exposure was 1744 ± 795 mg*h/l (10 g/m 2 ) and 1561 ± 511 mg*h/l (14 g/m 2 ), with an inter-individual variability of 56 and 33% in the respective groups. High treosulfan exposure (>1650 mg*h/l) was associated with an increased risk of mucosal [Odds ratio (OR) 4·40; 95% confidence interval (CI) 1·19-16·28, P = 0·026] and skin toxicity (OR 4·51; 95% CI 1·07-18·93, P = 0·040). No correlation was found between treosulfan exposure and the early clinical outcome parameters: engraftment, acute graft-versus-host disease and donor chimerism. Our study provides the first evidence in a large cohort of paediatric patients of high variability in treosulfan pharmacokinetics and an association between treosulfan exposure and early toxicity. Ongoing studies will reveal whether treosulfan exposure is related to long-term disease-specific outcome and late treatment-related toxicity. © 2017 John Wiley & Sons Ltd.

Prevalence of suicide attempt and clinical characteristics of suicide attempters with obsessive-compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).

PubMed

Dell'Osso, Bernardo; Benatti, Beatrice; Arici, Chiara; Palazzo, Carlotta; Altamura, A Carlo; Hollander, Eric; Fineberg, Naomi; Stein, Dan J; Nicolini, Humberto; Lanzagorta, Nuria; Marazziti, Donatella; Pallanti, Stefano; van Ameringen, Michael; Lochner, Christine; Karamustafalioglu, Oguz; Hranov, Luchezar; Figee, Martijn; Drummond, Lynne; Rodriguez, Carolyn I; Grant, John; Denys, Damiaan; Menchon, Jose M; Zohar, Joseph

2018-02-01

Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients. A total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearson's chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable. 14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables. Our international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.

Multiple endocrine neoplasia type 1: analysis of germline MEN1 mutations in the Italian multicenter MEN1 patient database.

PubMed

Marini, Francesca; Giusti, Francesca; Fossi, Caterina; Cioppi, Federica; Cianferotti, Luisella; Masi, Laura; Boaretto, Francesca; Zovato, Stefania; Cetani, Filomena; Colao, Annamaria; Davì, Maria Vittoria; Faggiano, Antongiulio; Fanciulli, Giuseppe; Ferolla, Piero; Ferone, Diego; Loli, Paola; Mantero, Franco; Marcocci, Claudio; Opocher, Giuseppe; Beck-Peccoz, Paolo; Persani, Luca; Scillitani, Alfredo; Guizzardi, Fabiana; Spada, Anna; Tomassetti, Paola; Tonelli, Francesco; Brandi, Maria Luisa

2018-03-01

Multiple endocrine neoplasia type 1 (MEN1) is caused by germline inactivating mutations of the MEN1 gene. Currently, no direct genotype-phenotype correlation is identified. We aim to analyze MEN1 mutation site and features, and possible correlations between the mutation type and/or the affected menin functional domain and clinical presentation in patients from the Italian multicenter MEN1 database, one of the largest worldwide MEN1 mutation series published to date. The study included the analysis of MEN1 mutation profile in 410 MEN1 patients [370 familial cases from 123 different pedigrees (48 still asymptomatic at the time of this study) and 40 single cases]. We identified 99 different mutations: 41 frameshift [small intra-exon deletions (28) or insertions (13)], 13 nonsense, 26 missense and 11 splicing site mutations, 4 in-frame small deletions, and 4 intragenic large deletions spanning more than one exon. One family had two different inactivating MEN1 mutations on the same allele. Gastro-entero-pancreatic tumors resulted more frequent in patients with a nonsense mutation, and thoracic neuroendocrine tumors in individuals bearing a splicing-site mutation. Our data regarding mutation type frequency and distribution are in accordance with previously published data: MEN1 mutations are scattered through the entire coding region, and truncating mutations are the most common in MEN1 syndrome. A specific direct correlation between MEN1 genotype and clinical phenotype was not found in all our families, and wide intra-familial clinical variability and variable disease penetrance were both confirmed, suggesting a role for modifying, still undetermined, factors, explaining the variable MEN1 tumorigenesis.

Incentives and Barriers That Influence Clinical Computerization in Hong Kong: A Population-based Physician Survey

PubMed Central

Leung, Gabriel M.; Yu, Philip L. H.; Wong, Irene O. L.; Johnston, Janice M.; Tin, Keith Y. K.

2003-01-01

Objective: Given the slow adoption of medical informatics in Hong Kong and Asia, we sought to understand the contributory barriers and potential incentives associated with information technology implementation. Design and Measurements: A representative sample of 949 doctors (response rate = 77.0%) was asked through a postal survey to rank a list of nine barriers associated with clinical computerization according to self-perceived importance. They ranked seven incentives or catalysts that may influence computerization. We generated mean rank scores and used multidimensional preference analysis to explore key explanatory dimensions of these variables. A hierarchical cluster analysis was performed to identify homogenous subgroups of respondents. We further determined the relationships between the sets of barriers and incentives/catalysts collectively using canonical correlation. Results: Time costs, lack of technical support and large capital investments were the biggest barriers to computerization, whereas improved office efficiency and better-quality care were ranked highest as potential incentives to computerize. Cost vs. noncost, physician-related vs. patient-related, and monetary vs. nonmonetary factors were the key dimensions explaining the barrier variables. Similarly, within-practice vs external and “push” vs “pull” factors accounted for the incentive variables. Four clusters were identified for barriers and three for incentives/catalysts. Canonical correlation revealed that respondents who were concerned with the costs of computerization also perceived financial incentives and government regulation to be important incentives/catalysts toward computerization. Those who found the potential interference with communication important also believed that the promise of improved care from computerization to be a significant incentive. Conclusion: This study provided evidence regarding common barriers associated with clinical computerization. Our findings also identified possible incentive strategies that may be employed to accelerate uptake of computer systems. PMID:12595409

A novel and simple test of gait adaptability predicts gold standard measures of functional mobility in stroke survivors.

PubMed

Hollands, K L; Pelton, T A; van der Veen, S; Alharbi, S; Hollands, M A

2016-01-01

Although there is evidence that stroke survivors have reduced gait adaptability, the underlying mechanisms and the relationship to functional recovery are largely unknown. We explored the relationships between walking adaptability and clinical measures of balance, motor recovery and functional ability in stroke survivors. Stroke survivors (n=42) stepped to targets, on a 6m walkway, placed to elicit step lengthening, shortening and narrowing on paretic and non-paretic sides. The number of targets missed during six walks and target stepping speed was recorded. Fugl-Meyer (FM), Berg Balance Scale (BBS), self-selected walking speed (SWWS) and single support (SS) and step length (SL) symmetry (using GaitRite when not walking to targets) were also assessed. Stepwise multiple-linear regression was used to model the relationships between: total targets missed, number missed with paretic and non-paretic legs, target stepping speed, and each clinical measure. Regression revealed a significant model for each outcome variable that included only one independent variable. Targets missed by the paretic limb, was a significant predictor of FM (F(1,40)=6.54, p=0.014,). Speed of target stepping was a significant predictor of each of BBS (F(1,40)=26.36, p<0.0001), SSWS (F(1,40)=37.00, p<0.0001). No variables were significant predictors of SL or SS asymmetry. Speed of target stepping was significantly predictive of BBS and SSWS and paretic targets missed predicted FM, suggesting that fast target stepping requires good balance and accurate stepping demands good paretic leg function. The relationships between these parameters indicate gait adaptability is a clinically meaningful target for measurement and treatment of functionally adaptive walking ability in stroke survivors. Copyright © 2015 Elsevier B.V. All rights reserved.

Joseph Adams (1756-1818).

PubMed

Emery, A E

1989-02-01

Joseph Adams was eclectic in his interests and wrote on a variety of medical subjects. His last book published in 1814 was on hereditary disease and based on a lifetime's careful clinical observations. In it he distinguished between what would now be defined as dominant and recessive disorders; defined the term congenital; emphasised the role of inbreeding in producing clustering of certain inherited disorders; introduced concepts now known as founder effect, incomplete penetrance, and variable age at onset; emphasised the importance of environmental factors in precipitating disease in certain genetic disorders; and, finally, recommended the establishment of registers for the purpose of preventing genetic disease. But because he proposed no scientific explanation for these various ideas, they were largely ignored by his contemporaries. Nevertheless, it would seem right to regard Joseph Adams as perhaps the first clinical geneticist.

Parent and Teacher Concordance of Child Outcomes for Youth with Autism Spectrum Disorder

PubMed Central

Suhrheinrich, Jessica; Rieth, Sarah R.; Stahmer, Aubyn C.

2017-01-01

Cross-informant ratings of are considered gold standard for child behavioral assessment. To date, little work has examined informant ratings of adaptive functioning for youth with autism spectrum disorder (ASD). In a large, diverse sample of youth with ASD, this study evaluated parent–teacher concordance of ratings of adaptive functioning and ASD-specific symptomatology across time. The impact of child clinical characteristics on concordance was also examined. Participants included 246 children, their caregivers and teachers. Parent–teacher concordance was variable but generally consistent across time. Concordance was significantly impacted by autism severity and child cognitive abilities. Findings inform the broader concordance literature and support the need to consider child clinical factors when assessing child functioning in samples of children with ASD. PMID:29164440

Clinical prediction and the idea of a population.

PubMed

Armstrong, David

2017-04-01

Using an analysis of the British Medical Journal over the past 170 years, this article describes how changes in the idea of a population have informed new technologies of medical prediction. These approaches have largely replaced older ideas of clinical prognosis based on understanding the natural histories of the underlying pathologies. The 19 th -century idea of a population, which provided a denominator for medical events such as births and deaths, was constrained in its predictive power by its method of enumerating individual bodies. During the 20 th century, populations were increasingly constructed through inferential techniques based on patient groups and samples seen to possess variable characteristics. The emergence of these new virtual populations created the conditions for the emergence of predictive algorithms that are used to foretell our medical futures.

Tailored cognitive-behavioural therapy and exercise training improves the physical fitness of patients with fibromyalgia.

PubMed

van Koulil, S; van Lankveld, W; Kraaimaat, F W; van Helmond, T; Vedder, A; van Hoorn, H; Donders, A R T; Wirken, L; Cats, H; van Riel, P L C M; Evers, A W M

2011-12-01

Patients with fibromyalgia have diminished levels of physical fitness, which may lead to functional disability and exacerbating complaints. Multidisciplinary treatment comprising cognitive-behavioural therapy (CBT) and exercise training has been shown to be effective in improving physical fitness. However, due to the high drop-out rates and large variability in patients' functioning, it was proposed that a tailored treatment approach might yield more promising treatment outcomes. High-risk fibromyalgia patients were randomly assigned to a waiting list control group (WLC) or a treatment condition (TC), with the treatment consisting of 16 twice-weekly sessions of CBT and exercise training tailored to the patient's cognitive-behavioural pattern. Physical fitness was assessed with two physical tests before and 3 months after treatment and at corresponding intervals in the WLC. Treatment effects were evaluated using linear mixed models. The level of physical fitness had improved significantly in the TC compared with the WLC. Attrition rates were low, effect sizes large and reliable change indices indicated a clinically relevant improvement among the TC. A tailored multidisciplinary treatment approach for fibromyalgia consisting of CBT and exercise training is well tolerated, yields clinically relevant changes, and appears a promising approach to improve patients' physical fitness. ClinicalTrials.gov ID NCT00268606.

Newborn screening of metabolic disorders: recent progress and future developments.

PubMed

Rinaldo, Piero; Lim, James S; Tortorelli, Silvia; Gavrilov, Dimitar; Matern, Dietrich

2008-01-01

Tandem mass spectrometry has been the main driver behind a significant expansion in newborn screening programs. The ability to detect more than 40 conditions by a single test underscores the need to better understand the clinical and laboratory characteristics of the conditions being tested, and the complexity of pattern recognition and differential diagnoses of one or more elevated markers. The panel of conditions recommended by the American College of Medical Genetics, including 20 primary conditions and 22 secondary targets that are detectable by tandem mass spectrometry has been adopted as the standard of care in the vast majority of US states. The evolution of newborn screening is far from being idle as a large number of infectious, genetic, and metabolic conditions are currently under investigation at variable stages of test development and clinical validation. In the US, a formal process with oversight by the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children has been established for nomination and evidence-based review of new candidate conditions. If approved, these conditions could be added to the uniform panel and consequently pave the way to large scale implementation.

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.

Clinical practice patterns in the assessment and management of low testosterone in men: an international survey of endocrinologists.

PubMed

Grossmann, Mathis; Anawalt, Bradley D; Wu, Frederick C W

2015-02-01

To document current practices in the approach to low testosterone in older men. Given that recommendations are based on low-level evidence, we hypothesized that there would be a wide variability in clinical practice patterns. Members of all major endocrine and andrological societies were invited to participate in a Web-based survey of the diagnostic work-up and management of a hypothetical index case of a 61-year old overweight man presenting with symptoms suggestive of androgen deficiency, without evidence of hypothalamic-pituitary-gonadal (HPT) axis disease. Nine hundred and forty-three respondents (91·2% adult endocrinologists) from Northern America (63·7%), Europe (12·7%), Oceania (8·2%), Latin America and Caribbean (7·6%), and the Middle East, Asia, or Africa (7·8%) completed the survey. Response rates among participating societies ranged from 4·1-20·0%. There was a wide variability in clinical practice patterns, especially regarding biochemical diagnosis of androgen deficiency, exclusion of HPT axis pathology, and monitoring for prostate cancer. In a man with suggestive symptoms, 42·4% of participants would offer testosterone treatment below a serum total testosterone of 10·4 nmol/l (300 ng/dl). A total of 46·0% of participants were, over the last five years, 'less inclined' to prescribe testosterone to men with nonspecific symptoms and borderline testosterone levels, compared to 'no change' (29·3%) or 'more inclined' (24·7%), P < 0·001. This large-scale international survey shows a wide variability in the management of lowered testosterone in older men, with deviations from current clinical practice guidelines, and a temporal trend towards increasing reluctance to prescribe testosterone to men without classical hypogonadism. These findings highlight the need for better evidence to guide clinicians regarding testosterone therapy. © 2014 John Wiley & Sons Ltd.

Predictors of hydrocephalus as a complication of non-traumatic subarachnoid hemorrhage: a retrospective observational cohort study in 107 patients.

PubMed

Vinas Rios, Juan Manuel; Sanchez-Aguilar, Martin; Kretschmer, Thomas; Heinen, Christian; Medina Govea, Fatima Azucena; Jose Juan, Sanchez-Rodriguez; Schmidt, Thomas

2018-01-01

The predictors of shunt dependency such as amount of subarachnoid blood, acute hydrocephalus (HC), mode of aneurysm repair, clinical grade at admission and cerebro spinal fluid (CSF) drainage in excess of 1500 ml during the 1st week after the subarachnoid hemorrhage (SAH) have been identified as predictors of shunt dependency. Therefore our main objective is to identify predictors of CSF shunt dependency following non-traumatic subarachnoid hemorrhage. We performed a retrospective study including patients from January 1st 2012 to September 30th 2014 between 16 and 89 years old and had a non-traumatic subarachnoid hemorrhage in cranial computed tomography (CCT). We excluded patients with the following characteristics: Patients who died 3 days after admittance, lesions in brainstem, previous surgical treatment in another clinic, traumatic brain injury, pregnancy and disability prior to SAH.We performed a descriptive and comparative analysis as well as a logistic regression with the variables that showed a significant difference ( p  < 0.05). Hence we identified the variables concerning HC after non traumatic SAH and its correlation. One hundred and seven clinical files of patients with non-traumatic SAH were analyzed. Twenty one (48%) later underwent shunt treatment. Shunt patients had significantly clinical and corroborated with doppler ultrasonography vasospasmus ( p  = 0.015), OR = 5.2. The amount of subarachnoidal blood according to modified Fisher grade was ( p  = 0.008) OR = 10.9. Endovascularly treated patients were less often shunted as compared with those undergoing surgical aneurysm repair ( p  = 0.004). Vasospasmus and a large amount of ventricular blood seem to be a predictor concerning hydrocephalus after non-traumatic SAH. Hence according to our results the presence of these two variables could alert the treating physician in the decision whether an early shunt implantation < 7 days after SAH should be necessary.

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

PubMed Central

Galipeau, Jacques; Nooka, Ajay K.

2013-01-01

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

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.

Measuring the degree of integrated tuberculosis and HIV service delivery in Cape Town, South Africa.

PubMed

Uyei, Jennifer; Coetzee, David; Macinko, James; Weinberg, Sharon L; Guttmacher, Sally

2014-01-01

To address the considerable tuberculosis (TB)/HIV co-infected population in Cape Town, a number of clinics have made an effort of varying degrees to integrate TB and HIV services. This article describes the development of a theory-based survey instrument designed to quantify the extent to which services were integrated in 33 clinics and presents the results of the survey. Using principal factor analysis, eight factors were extracted and used to make comparisons across three types of clinics: co-located TB and antiretroviral therapy (ART) services, clinics with TB services only and clinics with ART only. Clinics with co-located services scored highest on measures related to integrated TB/ART service delivery compared to clinics with single services, but within group variability was high indicating that co-location of TB and ART services is a necessary but insufficient condition for integrated service delivery. In addition, we found almost all clinics with only TB services in our sample had highly integrated pre-ART services, suggesting that integration of these services across a large number of clinics is feasible and acceptable to clinic staff. TB clinics with highly integrated pre-ART services appear to be efficient sites for introducing ART given that co-infected patients are already engaged in care, and may potentially facilitate earlier access to treatment and minimize loss to follow-up.

The Challenges of Measuring Glycemic Variability

PubMed Central

Rodbard, David

2012-01-01

This commentary reviews several of the challenges encountered when attempting to quantify glycemic variability and correlate it with risk of diabetes complications. These challenges include (1) immaturity of the field, including problems of data accuracy, precision, reliability, cost, and availability; (2) larger relative error in the estimates of glycemic variability than in the estimates of the mean glucose; (3) high correlation between glycemic variability and mean glucose level; (4) multiplicity of measures; (5) correlation of the multiple measures; (6) duplication or reinvention of methods; (7) confusion of measures of glycemic variability with measures of quality of glycemic control; (8) the problem of multiple comparisons when assessing relationships among multiple measures of variability and multiple clinical end points; and (9) differing needs for routine clinical practice and clinical research applications. PMID:22768904

SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

PubMed

Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

2017-08-01

There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

Prevalence and correlates of cognitive impairment in kidney transplant recipients.

PubMed

Gupta, Aditi; Mahnken, Jonathan D; Johnson, David K; Thomas, Tashra S; Subramaniam, Dipti; Polshak, Tyler; Gani, Imran; John Chen, G; Burns, Jeffrey M; Sarnak, Mark J

2017-05-12

There is a high prevalence of cognitive impairment in dialysis patients. The prevalence of cognitive impairment after kidney transplantation is unknown. Study Design: Cross-sectional study. Single center study of prevalent kidney transplant recipients from a transplant clinic in a large academic center. Assessment of cognition using the Montreal Cognitive Assessment (MoCA). Demographic and clinical variables associated with cognitive impairment were also examined. Outcomes and Measurements: a) Prevalence of cognitive impairment defined by a MoCA score of <26. b) Multivariable linear and logistic regression to examine the association of demographic and clinical factors with cognitive impairment. Data from 226 patients were analyzed. Mean (SD) age was 54 (13.4) years, 73% were white, 60% were male, 37% had diabetes, 58% had an education level of college or above, and the mean (SD) time since kidney transplant was 3.4 (4.1) years. The prevalence of cognitive impairment was 58.0%. Multivariable linear regression demonstrated that older age, male gender and absence of diabetes were associated with lower MoCA scores (p < 0.01 for all). Estimated glomerular filtration rate (eGFR) was not associated with level of cognition. The logistic regression analysis confirmed the association of older age with cognitive impairment. Cognitive impairment is common in prevalent kidney transplant recipients, at a younger age compared to general population, and is associated with certain demographic variables, but not level of eGFR.

Simplified methods of determining treatment retention in Malawi: ART cohort reports vs. pharmacy stock cards.

PubMed

Chan, A K; Singogo, E; Changamire, R; Ratsma, Y E C; Tassie, J-M; Harries, A D

2012-06-21

Rapid scale-up of antiretroviral therapy (ART) has challenged the health system in Malawi to monitor large numbers of patients effectively. To compare two methods of determining retention on treatment: quarterly ART clinic data aggregation vs. pharmacy stock cards. Between October 2010 and March 2011, data on ART outcomes were extracted from monitoring tools at five facilities. Pharmacy data on ART consumption were extracted. Workload for each method was observed and timed. We used intraclass correlation and Bland-Altman plots to compare the agreeability of both methods to determine treatment retention. There is wide variability between ART clinic cohort data and pharmacy data to determine treatment retention due to divergence in data at sites with large numbers of patients. However, there is a non-significant trend towards agreeability between the two methods (intraclass correlation coefficient > 0.9; P > 0.05). Pharmacy stock card monitoring is more time-efficient than quarterly ART data aggregation (81 min vs. 573 min). In low-resource settings, pharmacy records could be used to improve drug forecasting and estimate ART retention in a more time-efficient manner than quarterly data aggregation; however, a necessary precondition would be capacity building around pharmacy data management, particularly for large-sized cohorts.

Reproducibility of 3D kinematics and surface electromyography measurements of mastication.

PubMed

Remijn, Lianne; Groen, Brenda E; Speyer, Renée; van Limbeek, Jacques; Nijhuis-van der Sanden, Maria W G

2016-03-01

The aim of this study was to determine the measurement reproducibility for a procedure evaluating the mastication process and to estimate the smallest detectable differences of 3D kinematic and surface electromyography (sEMG) variables. Kinematics of mandible movements and sEMG activity of the masticatory muscles were obtained over two sessions with four conditions: two food textures (biscuit and bread) of two sizes (small and large). Twelve healthy adults (mean age 29.1 years) completed the study. The second to the fifth chewing cycle of 5 bites were used for analyses. The reproducibility per outcome variable was calculated with an intraclass correlation coefficient (ICC) and a Bland-Altman analysis was applied to determine the standard error of measurement relative error of measurement and smallest detectable differences of all variables. ICCs ranged from 0.71 to 0.98 for all outcome variables. The outcome variables consisted of four bite and fourteen chewing cycle variables. The relative standard error of measurement of the bite variables was up to 17.3% for 'time-to-swallow', 'time-to-transport' and 'number of chewing cycles', but ranged from 31.5% to 57.0% for 'change of chewing side'. The relative standard error of measurement ranged from 4.1% to 24.7% for chewing cycle variables and was smaller for kinematic variables than sEMG variables. In general, measurements obtained with 3D kinematics and sEMG are reproducible techniques to assess the mastication process. The duration of the chewing cycle and frequency of chewing were the best reproducible measurements. Change of chewing side could not be reproduced. The published measurement error and smallest detectable differences will aid the interpretation of the results of future clinical studies using the same study variables. Copyright © 2015 Elsevier Inc. All rights reserved.

Pitfalls of mapping a large Turkish consanguineous family with vertical monilethrix inheritance.

PubMed

Celep, F; Uzumcu, A; Sonmez, F M; Uyguner, O; Balci, Y Isik; Bahadir, S; Karaguzel, A

2009-01-01

Monilethrix, a rare autosomal dominant disease characterized by hair fragility and follicular hyperkeratosis, is caused by mutations in three type II hair cortex keratins. The human keratin family comprises 54 members, 28 type I and 26 type II. The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. In our study, Monilethrix was diagnosed on the basis of clinical characteristics and microscopic examination in a family with 11 affected members. Haplotype analysis was performed by three Simple Tandem Repeat markers (STR) and KRT86 gene was sequenced for the identification of the disease causing mutation. In the results of this, autosomal dominant mutation (E402K) in exon 7 of KRT86 gene was identified as a cause of Moniltherix in the large family from Turkey.

Clinical characteristics and molecular epidemiology of Enterovirus infection in infants <3 months in a referral paediatric hospital of Barcelona.

PubMed

Rodà, Diana; Pérez-Martínez, Esther; Cabrerizo, María; Trallero, Gloria; Martínez-Planas, Aina; Luaces, Carles; García-García, Juan-José; Muñoz-Almagro, Carmen; Launes, Cristian

2015-11-01

Enterovirus (EV) infection is common in infants, but the information with regard to the molecular epidemiology and the associations between types and clinical variables is very scarce. This study includes 195 children <3 months old with fever, attended from March 2010 to December 2012 in an emergency department of a tertiary paediatric hospital in whom EV infection was confirmed by real-time PCR in blood and/or cerebrospinal fluid. Clinical and epidemiological data was prospectively collected. In 152 (77.9 %) patients, EVs could be typed. The most common type was Echovirus-5 (E5; 32, 21.1 %), followed by Echovirus-11 (E11; 18, 11.8 %), Echovirus-21 and Echovirus-25 (E21, E25; 11 each one, 7.2 %) and Coxsackievirus-B4 (CVB4; 6, 6.6 %). The majority of types appeared in spring, but E5 and E25 were found mainly during summer (p < 0.01). E21 was associated with high-grade fever (p < 0.01); E5 with exanthema (p = 0.03) and CVB4 tended to cause meningitis more often than the other types (p = 0.07). The most common EV types were Echovirus-5 and Echovirus-11. Some significant associations between types and epidemiologic and clinical findings were observed. What is Known-What is New • Enteroviruses cause a normally benign illness in young infants, except in some cases. • The molecular epidemiology of Enterovirus infection is not well known in European countries. • This study describes a large number of infants with Enterovirus infection and shows the seasonality of different types, and their associations with epidemiologic and clinical variables.

Predictors of motivation for abstinence at the end of outpatient substance abuse treatment

PubMed Central

Laudet, Alexandre B.; Stanick, Virginia

2010-01-01

Commitment to abstinence, a motivational construct, is a strong predictor of reductions in drug and alcohol use. Level of commitment to abstinence at treatment end predicts sustained abstinence, a requirement for recovery. This study sought to identify predictors of commitment to abstinence at treatment end to guide clinical practice and to inform the conceptualization of motivational constructs. Polysubstance users (N = 250) recruited at the start of outpatient treatment were re-interviewed at the end of services. Based on the extant literature, potential predictors were during treatment measures of substance use and related cognitions, psychological functioning, recovery supports, stress, quality of life satisfaction, and treatment experiences. In multivariate analyses, perceived harm of future drug use, abstinence self-efficacy, quality of life satisfaction, and number of network members in 12-step recovery contributed 26.6% of the variance explained in the dependent variable, a total of 49.6% when combined with the control variables (demographics and baseline level of the outcome). Gender subgroup analyses yielded largely similar results. Clinical implications of findings for maximizing commitment to abstinence when clients leave treatment are discussed as are future research directions. PMID:20185267

Bioinformatics and variability in drug response: a protein structural perspective

PubMed Central

Lahti, Jennifer L.; Tang, Grace W.; Capriotti, Emidio; Liu, Tianyun; Altman, Russ B.

2012-01-01

Marketed drugs frequently perform worse in clinical practice than in the clinical trials on which their approval is based. Many therapeutic compounds are ineffective for a large subpopulation of patients to whom they are prescribed; worse, a significant fraction of patients experience adverse effects more severe than anticipated. The unacceptable risk–benefit profile for many drugs mandates a paradigm shift towards personalized medicine. However, prior to adoption of patient-specific approaches, it is useful to understand the molecular details underlying variable drug response among diverse patient populations. Over the past decade, progress in structural genomics led to an explosion of available three-dimensional structures of drug target proteins while efforts in pharmacogenetics offered insights into polymorphisms correlated with differential therapeutic outcomes. Together these advances provide the opportunity to examine how altered protein structures arising from genetic differences affect protein–drug interactions and, ultimately, drug response. In this review, we first summarize structural characteristics of protein targets and common mechanisms of drug interactions. Next, we describe the impact of coding mutations on protein structures and drug response. Finally, we highlight tools for analysing protein structures and protein–drug interactions and discuss their application for understanding altered drug responses associated with protein structural variants. PMID:22552919

Implementation of a laboratory quality assurance program: the Louisville experience.

PubMed

Metz, Michael J; Abdel-Azim, Tamer; Miller, Cynthia J; Lin, Wei-Shao; ZandiNejad, Amirali; Oliveira, Gustavo M; Morton, Dean

2014-02-01

Remakes, or the refabrication of dental prostheses, can occur as a result of inherent inaccuracies in both clinical and laboratory procedures. Because dental schools manage large numbers of predoctoral dental students with limited familiarity and expertise as related to clinical prosthodontic techniques, it is likely these schools will experience an elevated incidence of laboratory remakes and their ramifications. The University of Louisville School of Dentistry, not unlike other dental schools, has experienced remakes associated with both fixed and removable prosthodontic procedures. Limitations in faculty standardization and variable enforcement of established preclinical protocols have been identified as variables associated with the high percentage of remakes documented. The purpose of this study was to introduce the implementation of a new multidepartmental quality assurance program designed to increase consistency and quality in both information provided to commercial dental laboratories and the prostheses returned. The program has shown to be advantageous in terms of cost-effectiveness and treatment outcomes. A statistically significant decrease in remake percentages has been recorded from inception of this program in December 2010 until December 2012. Furthermore, this program has resulted in more consistent communication between the dental school and commercial dental laboratories, among faculty members, and between faculty and students.

Ilaprazole for the treatment of gastro-esophageal reflux.

PubMed

Savarino, Edoardo; Ottonello, Andrea; Martinucci, Irene; Dulbecco, Pietro; Savarino, Vincenzo

2016-10-01

Despite the undoubted benefit of proton pump inhibitors (PPIs), they have several shortcomings, such as a slow onset of action and a remarkable inter-individual variability, that limit the complete success of these drugs. Recently, a new PPI, ilaprazole, has been developed and used in GERD patients. The present review provides an update on the following points: current knowledge of GERD mechanisms; limitations of actual therapies; pharmacokinetic profile and metabolism of ilaprazole; initial studies on the therapeutic efficacy of ilaprazole in GERD. Compared with all other approved PPIs, ilaprazole has shown an extended plasma half-life, a metabolism not significantly influenced by CYP2C19 genetic polymorphism and similar safety. This characteristics account for a low inter-individual variability, particularly in Asian populations, a higher suppression of gastric acid secretion, a more rapid acid control and consequent quicker symptom relief and a better effect on nocturnal acidity. However, clinical investigations assessing the efficacy of ilaprazole in the management of GERD are lacking and therefore the potential improvements achievable with ilaprazole in the current standard of care for acid-suppressing treatment must be confirmed in large and randomly controlled clinical trials enrolling patients with both erosive and non-erosive reflux disease.

Subchondral drilling for articular cartilage repair: a systematic review of translational research.

PubMed

Gao, Liang; Goebel, Lars K H; Orth, Patrick; Cucchiarini, Magali; Madry, Henning

2018-05-03

Articular cartilage defects may initiate osteoarthritis. Subchondral drilling, a widely applied clinical technique to treat small cartilage defects, does not yield cartilage regeneration. Various translational studies aiming to improve the outcome of drilling have been performed, however, a robust systematic analysis of its translational evidence has been still lacking. Here, we performed a systematic review of the outcome of subchondral drilling for knee cartilage repair in translational animal models. A total of 12 relevant publications studying 198 animals were identified, detailed study characteristics were extracted, and methodological quality and risk of bias were analyzed. Subchondral drilling was superior to defects untreated or treated with abrasion arthroplasty for cartilage repair in multiple translational models. Considerable subchondral bone changes were observed, including subchondral bone cysts and intralesional osteophytes. Furthermore, extensive alterations of the subchondral bone microarchitecture appeared in a temporal pattern in small and large animal models, together with specific topographic aspects of repair. Moreover, variable technical aspects directly affected the outcomes of osteochondral repair. The data from this systematic review indicate that subchondral drilling yields improved short-term structural articular cartilage repair compared with spontaneous repair in multiple small and large animal models. These results have important implications for future investigations aimed at an enhanced translation into clinical settings for the treatment of cartilage defects, highlighting the importance of considering specific aspects of modifiable variables such as improvements in the design and reporting of preclinical studies, together with the need to better understand the underlying mechanisms of cartilage repair following subchondral drilling. © 2018. Published by The Company of Biologists Ltd.

Limited Documentation and Treatment Quality of Glycemic Inpatient Care in Relation to Structural Deficits of Heterogeneous Insulin Charts at a Large University Hospital.

PubMed

Kopanz, Julia; Lichtenegger, Katharina M; Sendlhofer, Gerald; Semlitsch, Barbara; Cuder, Gerald; Pak, Andreas; Pieber, Thomas R; Tax, Christa; Brunner, Gernot; Plank, Johannes

2018-02-09

Insulin charts represent a key component in the inpatient glycemic management process. The aim was to evaluate the quality of structure, documentation, and treatment of diabetic inpatient care to design a new standardized insulin chart for a large university hospital setting. Historically grown blank insulin charts in use at 39 general wards were collected and evaluated for quality structure features. Documentation and treatment quality were evaluated in a consecutive snapshot audit of filled-in charts. The primary end point was the percentage of charts with any medication error. Overall, 20 different blank insulin charts with variable designs and significant structural deficits were identified. A medication error occurred in 55% of the 102 audited filled-in insulin charts, consisting of prescription and management errors in 48% and 16%, respectively. Charts of insulin-treated patients had more medication errors relative to patients treated with oral medication (P < 0.01). Chart design did support neither clinical authorization of individual insulin prescription (10%), nor insulin administration confirmed by nurses' signature (25%), nor treatment of hypoglycemia (0%), which resulted in a reduced documentation and treatment quality in clinical practice 7%, 30%, 25%, respectively. A multitude of charts with variable design characteristics and structural deficits were in use across the inpatient wards. More than half of the inpatients had a chart displaying a medication error. Lack of structure quality features of the charts had an impact on documentation and treatment quality. Based on identified deficits and international standards, a new insulin chart was developed to overcome these quality hurdles.

Differences in clinical and biological characteristics and prevalence of chronic complications related to aging in patients with type 2 diabetes.

PubMed

Basanta-Alario, María Luisa; Ferri, Jordi; Civera, Miguel; Martínez-Hervás, Sergio; Ascaso, Juan Francisco; Real, José Tomás

2016-02-01

Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease that increases with age. Because of this, and due to its chronic complications, T2DM causes high human, social, and financial costs. In addition, the elderly population with T2DM has a marked clinical heterogeneity. Therefore, our main objective was to analyze the relationship of age with the clinical and biological manifestations of the disease and the prevalence of chronic complications in patients with T2DM. A cross-sectional study of a large population with T2DM (n=405) randomly selected from a Diabetes Unit and 2 health care centers (60%). The clinical, anthropometric, and biochemical variables of the subjects were collected using standard methods to assess the effect of age on the clinical and biochemical phenotype of patients with T2DM. We have noted that patients with T2DM > 70 years old have a clinical and biochemical phenotype different from younger subjects (<60 years) including longer times since diabetes onset, higher diastolic blood pressure levels, and lower body mass index (BMI) values. As regards to biological variables, these patients have lower triglyceride levels, impaired kidney function, and lower HbA1c values. Prevalence of metabolic syndrome is lower in patients with T2DM > 70 years of age. Age was inversely related to parameters associated to metabolic syndrome (BMI, waist circumference, blood pressure, and triglyceride levels). We have defined the clinical and biochemical profile of patients with T2DM > 70 years attending health care centers. In addition, the prevalence of stroke, kidney disease, and distal symmetrical polyneuropathy is higher in patients with T2DM >70 years as compared to younger patients (<60 years). Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Anodal transcranial direct current stimulation of the left dorsolateral prefrontal cortex enhances emotion recognition in depressed patients and controls.

PubMed

Brennan, Sean; McLoughlin, Declan M; O'Connell, Redmond; Bogue, John; O'Connor, Stephanie; McHugh, Caroline; Glennon, Mark

2017-05-01

Transcranial direct current stimulation (tDCS) can enhance a range of neuropsychological functions but its efficacy in addressing clinically significant emotion recognition deficits associated with depression is largely untested. A randomized crossover placebo controlled study was used to investigate the effects of tDCS over the left dorsolateral prefrontal cortex (L-DLPFC) on a range of neuropsychological variables associated with depression as well as neural activity in the associated brain region. A series of computerized tests was administered to clinical (n = 17) and control groups (n = 20) during sham and anodal (1.5 mA) stimulation. Anodal tDCS led to a significant main effect for overall emotion recognition (p = .02), with a significant improvement in the control group (p = .04). Recognition of disgust was significantly greater in the clinical group (p = .01). Recognition of anger was significantly improved for the clinical group (p = .04) during anodal stimulation. Differences between groups for each of the six emotions at varying levels of expression found that at 40% during anodal stimulation, happy recognition significantly improved for the clinical group (p = .01). Anger recognition at 80% during anodal stimulation significantly improved for the clinical group (p = .02). These improvements were observed in the absence of any change in psychomotor speed or trail making ability during anodal stimulation. Working memory significantly improved during anodal stimulation for the clinical group but not for controls (p = .03). The tentative findings of this study indicate that tDCS can have a neuromodulatory effect on a range of neuropsychological variables. However, it is clear that there was a wide variation in responses to tDCS and that individual difference and different approaches to testing and stimulation have a significant impact on final outcomes. Nonetheless, tDCS remains a promising tool for future neuropsychological research.

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

Depressive Symptoms, Anatomical Region, and Clinical Outcomes for Patients Seeking Outpatient Physical Therapy for Musculoskeletal Pain

PubMed Central

Coronado, Rogelio A.; Beneciuk, Jason M.; Valencia, Carolina; Werneke, Mark W.; Hart, Dennis L.

2011-01-01

Background Clinical guidelines advocate the routine identification of depressive symptoms for patients with pain in the lumbar or cervical spine, but not for other anatomical regions. Objective The purpose of this study was to investigate the prevalence and impact of depressive symptoms for patients with musculoskeletal pain across different anatomical regions. Design This was a prospective, associational study. Methods Demographic, clinical, depressive symptom (Symptom Checklist 90–Revised), and outcome data were collected by self-report from a convenience sample of 8,304 patients. Frequency of severe depressive symptoms was assessed by chi-square analysis for demographic and clinical variables. An analysis of variance examined the influence of depressive symptoms and anatomical region on intake pain intensity and functional status. Separate hierarchical multiple regression models by anatomical region examined the influence of depressive symptoms on clinical outcomes. Results Prevalence of severe depression was higher in women, in industrial and pain clinics, and in patients who reported chronic pain or prior surgery. Lower prevalence rates were found in patients older than 65 years and those who had upper- or lower-extremity pain. Depressive symptoms had a moderate to large effect on pain ratings (Cohen d=0.55–0.87) and a small to large effect on functional status (Cohen d=0.28–0.95). In multivariate analysis, depressive symptoms contributed additional variance to pain intensity and functional status for all anatomical locations, except for discharge values for the cervical region. Conclusions Rates of depressive symptoms varied slightly based on anatomical region of musculoskeletal pain. Depressive symptoms had a consistent detrimental influence on outcomes, except on discharge scores for the cervical anatomical region. Expanding screening recommendations for depressive symptoms to include more anatomical regions may be indicated in physical therapy settings. PMID:21233305

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

PubMed

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

2017-02-01

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

Exploring the Potential of Predictive Analytics and Big Data in Emergency Care.

PubMed

Janke, Alexander T; Overbeek, Daniel L; Kocher, Keith E; Levy, Phillip D

2016-02-01

Clinical research often focuses on resource-intensive causal inference, whereas the potential of predictive analytics with constantly increasing big data sources remains largely unexplored. Basic prediction, divorced from causal inference, is much easier with big data. Emergency care may benefit from this simpler application of big data. Historically, predictive analytics have played an important role in emergency care as simple heuristics for risk stratification. These tools generally follow a standard approach: parsimonious criteria, easy computability, and independent validation with distinct populations. Simplicity in a prediction tool is valuable, but technological advances make it no longer a necessity. Emergency care could benefit from clinical predictions built using data science tools with abundant potential input variables available in electronic medical records. Patients' risks could be stratified more precisely with large pools of data and lower resource requirements for comparing each clinical encounter to those that came before it, benefiting clinical decisionmaking and health systems operations. The largest value of predictive analytics comes early in the clinical encounter, in which diagnostic and prognostic uncertainty are high and resource-committing decisions need to be made. We propose an agenda for widening the application of predictive analytics in emergency care. Throughout, we express cautious optimism because there are myriad challenges related to database infrastructure, practitioner uptake, and patient acceptance. The quality of routinely compiled clinical data will remain an important limitation. Complementing big data sources with prospective data may be necessary if predictive analytics are to achieve their full potential to improve care quality in the emergency department. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Disclosure Control using Partially Synthetic Data for Large-Scale Health Surveys, with Applications to CanCORS

PubMed Central

Loong, Bronwyn; Zaslavsky, Alan M.; He, Yulei; Harrington, David P.

2013-01-01

Statistical agencies have begun to partially synthesize public-use data for major surveys to protect the confidentiality of respondents’ identities and sensitive attributes, by replacing high disclosure risk and sensitive variables with multiple imputations. To date, there are few applications of synthetic data techniques to large-scale healthcare survey data. Here, we describe partial synthesis of survey data collected by CanCORS, a comprehensive observational study of the experiences, treatments, and outcomes of patients with lung or colorectal cancer in the United States. We review inferential methods for partially synthetic data, and discuss selection of high disclosure risk variables for synthesis, specification of imputation models, and identification disclosure risk assessment. We evaluate data utility by replicating published analyses and comparing results using original and synthetic data, and discuss practical issues in preserving inferential conclusions. We found that important subgroup relationships must be included in the synthetic data imputation model, to preserve the data utility of the observed data for a given analysis procedure. We conclude that synthetic CanCORS data are suited best for preliminary data analyses purposes. These methods address the requirement to share data in clinical research without compromising confidentiality. PMID:23670983

eFAST for Pneumothorax: Real-Life Application in an Urban Level 1 Center by Trauma Team Members.

PubMed

Maximus, Steven; Figueroa, Cesar; Whealon, Matthew; Pham, Jacqueline; Kuncir, Eric; Barrios, Cristobal

2018-02-01

The focused assessment with sonography for trauma (FAST) examination has become the standard of care for rapid evaluation of trauma patients. Extended FAST (eFAST) is the use of ultrasonography for the detection of pneumothorax (PTX). The exact sensitivity and specificity of eFAST detecting traumatic PTX during practical "real-life" application is yet to be investigated. This is a retrospective review of all trauma patients with a diagnosis of PTX, who were treated at a large level 1 urban trauma center from March 2013 through July 2014. Charts were reviewed for results of imaging, which included eFAST, chest X-ray, and CT scan. The requirement of tube thoracostomy and mechanism of injury were also analyzed. A total of 369 patients with a diagnosis of PTX were identified. A total of 69 patients were excluded, as eFAST was either not performed or not documented, leaving 300 patients identified with PTX. A total of 113 patients had clinically significant PTX (37.6%), requiring immediate tube thoracostomy placement. eFAST yielded a positive diagnosis of PTX in 19 patients (16.8%), and all were clinically significant, requiring tube thoracostomy. Chest X-ray detected clinically significant PTX in 105 patients (92.9%). The literature on the utility of eFAST for PTX in trauma is variable. Our data show that although specific for clinically significant traumatic PTX, it has poor sensitivity when performed by clinicians with variable levels of ultrasound training. We conclude that CT is still the gold standard in detecting PTX, and clinicians performing eFAST should have adequate training.

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

Effect of intensive oral hygiene regimen during pregnancy on periodontal health, cytokine levels, and pregnancy outcomes: a pilot study.

PubMed

Kaur, Maninder; Geisinger, Maria L; Geurs, Nicolaas C; Griffin, Russell; Vassilopoulos, Philip J; Vermeulen, Lisa; Haigh, Sandra; Reddy, Michael S

2014-12-01

Data are limited on the potential effect of intensive oral hygiene regimens and periodontal therapy during pregnancy on periodontal health, gingival crevicular fluid (GCF) and serum cytokines, and pregnancy outcomes. A clinical trial was conducted on 120 community-dwelling, 16- to 35-year-old pregnant women at 16 to 24 weeks of gestation. Each participant presented with clinical evidence of generalized, moderate-to-severe gingivitis. Oral hygiene products were provided, together with instructions for an intensive daily regimen of hygiene practices. Non-surgical therapy was provided at baseline. Oral examinations were completed at baseline and again at 4 and 8 weeks. In addition, samples of blood and GCF were collected at baseline and week 8. Mean changes in clinical variables and GCF and serum cytokine levels (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α) between baseline and week 8 were calculated using paired t test. Pregnancy outcomes were recorded at parturition. RESULTS indicated a statistically significant reduction in all clinical variables (P <0.0001) and decreased levels of TNF-α (P = 0.0076) and IL-1β (P = 0.0098) in GCF during the study period. The rate of preterm births (<37 weeks of gestation) was 6.7% (P = 0.113) and low birth weight (<2,500 g) was 10.2% (P = 1.00). Among the population studied, intensive instructions and non-surgical periodontal therapy provided during 8 weeks at early pregnancy resulted in decreased gingival inflammation and a generalized improvement in periodontal health. Large-scale, randomized, controlled studies are needed to substantiate these findings.

Factors associated with survival of epiploic foramen entrapment colic: a multicentre, international study.

PubMed

Archer, D C; Pinchbeck, G L; Proudman, C J

2011-08-01

Epiploic foramen entrapment (EFE) has been associated with reduced post operative survival compared to other types of colic but specific factors associated with reduced long-term survival of these cases have not been evaluated in a large number of horses using survival analysis. To describe post operative survival of EFE cases and to identify factors associated with long-term survival. A prospective, multicentre, international study was conducted using clinical data and long-term follow-up information for 126 horses diagnosed with EFE during exploratory laparotomy at 15 clinics in the UK, Ireland and USA. Descriptive data were generated and survival analysis performed to identify factors associated with reduced post operative survival. For the EFE cohort that recovered following anaesthesia, survival to hospital discharge was 78.5%. Survival to 1 and 2 years post operatively was 50.6 and 34.3%, respectively. The median survival time of EFE cases undergoing surgery was 397 days. Increased packed cell volume (PCV) and increased length of small intestine (SI) resected were significantly associated with increased likelihood of mortality when multivariable analysis of pre- and intraoperative variables were analysed. When all pre-, intra- and post operative variables were analysed separately, only horses that developed post operative ileus (POI) were shown to be at increased likelihood of mortality. Increased PCV, increased length of SI resected and POI are all associated with increased likelihood of mortality of EFE cases. This emphasises the importance of early diagnosis and treatment and the need for improved strategies in the management of POI in order to reduce post operative mortality in these cases. The present study provides evidence-based information to clinicians and owners of horses undergoing surgery for EFE about long-term survival. These results are applicable to university and large private clinics over a wide geographical area. © 2011 EVJ Ltd.

Anesthesia and Databases: Pediatric Cardiac Disease as a Role Model.

PubMed

Vener, David F; Pasquali, Sara K; Mossad, Emad B

2017-02-01

Large data sets have now become ubiquitous in clinical medicine; they are particularly useful in high-acuity, low-volume conditions such as congenital heart disease where data must be collected from many centers. These data fall into 2 categories: administrative data arising from hospital admissions and charges and clinical data relating to specific diseases or procedures. In congenital cardiac diseases, there are now over a dozen of these data sets or registries focusing on various elements of patient care. Using probabilistic statistic matching, it is possible to marry administrative and clinical data post hoc using common elements to determine valuable information about care patterns, outcomes, and costs. These data sets can also be used in a collaborative fashion between institutions to drive quality improvement (QI). Because these data may include protected health information (PHI), care must be taken to adhere to federal guidelines on their use. A fundamental principle of large data management is the use of a common language and definition (nomenclature) to be effective. In addition, research derived from these information sources must be appropriately balanced to ensure that risk adjustments for preoperative and surgical factors are taken into consideration during the analysis. Care of patients with cardiac disease both in the United States and abroad consistently shows wide variability in mortality, morbidity, and costs, and there has been a tremendous amount of discussion about the benefits of regionalization of care based on center volume and outcome measurements. In the absence of regionalization, collaborative learning techniques have consistently been shown to minimize this variability and improve care at all centers, but before changes can be made it is necessary to accurately measure accurately current patient outcomes. Outcomes measurement generally falls under hospital-based QI initiatives, but more detailed analysis and research require Institutional Review Board and administrative oversight. Cardiac anesthesia providers for these patients have partnered with the Society of Thoracic Surgeons Congenital Heart surgeons to include anesthesia elements to help in this process.

How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study

PubMed Central

Chu, Hongling; Zeng, Lin; Fetters, Micheal D; Li, Nan; Tao, Liyuan; Shi, Yanyan; Zhang, Hua; Wang, Xiaoxiao; Li, Fengwei; Zhao, Yiming

2017-01-01

Objectives Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research. Setting The setting for this research was a major academic institution in Beijing, China. Participants The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts. Methods Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research. Results Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly. Conclusion These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive planning procedures such as those used by expert clinical researchers. PMID:28928184

How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study.

PubMed

Chu, Hongling; Zeng, Lin; Fetters, Micheal D; Li, Nan; Tao, Liyuan; Shi, Yanyan; Zhang, Hua; Wang, Xiaoxiao; Li, Fengwei; Zhao, Yiming

2017-09-18

Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research. The setting for this research was a major academic institution in Beijing, China. The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts. Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research. Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly. These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive planning procedures such as those used by expert clinical researchers. © 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.

An 'Observational Large Ensemble' to compare observed and modeled temperature trend uncertainty due to internal variability.

NASA Astrophysics Data System (ADS)

Poppick, A. N.; McKinnon, K. A.; Dunn-Sigouin, E.; Deser, C.

2017-12-01

Initial condition climate model ensembles suggest that regional temperature trends can be highly variable on decadal timescales due to characteristics of internal climate variability. Accounting for trend uncertainty due to internal variability is therefore necessary to contextualize recent observed temperature changes. However, while the variability of trends in a climate model ensemble can be evaluated directly (as the spread across ensemble members), internal variability simulated by a climate model may be inconsistent with observations. Observation-based methods for assessing the role of internal variability on trend uncertainty are therefore required. Here, we use a statistical resampling approach to assess trend uncertainty due to internal variability in historical 50-year (1966-2015) winter near-surface air temperature trends over North America. We compare this estimate of trend uncertainty to simulated trend variability in the NCAR CESM1 Large Ensemble (LENS), finding that uncertainty in wintertime temperature trends over North America due to internal variability is largely overestimated by CESM1, on average by a factor of 32%. Our observation-based resampling approach is combined with the forced signal from LENS to produce an 'Observational Large Ensemble' (OLENS). The members of OLENS indicate a range of spatially coherent fields of temperature trends resulting from different sequences of internal variability consistent with observations. The smaller trend variability in OLENS suggests that uncertainty in the historical climate change signal in observations due to internal variability is less than suggested by LENS.

Ectodermal dysplasias: a new clinical-genetic classification

PubMed Central

Priolo, M.; Lagana, C.

2001-01-01

The ectodermal dysplasias (EDs) are a large and complex nosological group of diseases, first described by Thurnam in 1848. In the last 10 years more than 170 different pathological clinical conditions have been recognised and defined as EDs, all sharing in common anomalies of the hair, teeth, nails, and sweat glands. Many are associated with anomalies in other organs and systems and, in some conditions, with mental retardation.
The anomalies affecting the epidermis and epidermal appendages are extremely variable and clinical overlap is present among the majority of EDs. Most EDs are defined by particular clinical signs (for example, eyelid adhesion in AEC syndrome, ectrodactyly in EEC). To date, few causative genes have been identified for these diseases.
We recently reviewed genes known to be responsible for EDs in light of their molecular and biological function and proposed a new approach to EDs, integrating both molecular-genetic data and corresponding clinical findings. Based on our previous report, we now propose a clinical-genetic classification of EDs, expand it to other entities in which no causative genes have been identified based on the phenotype, and speculate on possible candidate genes suggested by associated "non-ectodermal" features.


Keywords: ectodermal dysplasia; clinical-functional correlation; epithelial-mesenchymal interaction; ectodermal structural proteins PMID:11546825

[Comparative study of two treatment methods for acute periodontal abscess].

PubMed

Jin, Dong-mei; Wang, Wei-qian

2012-10-01

The aim of this short-term study was to compare the clinical efficacy of 2 different methods to treat acute periodontal abscesses. After patient selection, 100 cases of acute periodontal abscess were randomly divided into two groups. The experimental group was treated by supra- and subgingival scaling, while the control group was treated by incision and drainage. A clinical examination was carried out to record the following variables: subjective clinical variables including pain, edema, redness and swelling; objective clinical variables including gingival index(GI), bleeding index(BI), probing depth(PD),suppuration, lymphadenopathy and tooth mobility. The data was analyzed with SPSS 19.0 software package. RESULES: Subjective clinical variables demonstrated statistically significant improvements with both methods from the first day after treatment and lasted for at least 30 days(P<0.05), but the results of experimental group showed much better than the control group 1 day and 7 days after treatment. 30 days after treatment, there was no significant difference between the two groups in pain and swelling improvement(P>0.05), but the experimental group showed more improvement in edema and redness than the control group(P<0.05).On improving objective variables, the experimental group showed significant improvement in GI,BI,PD and suppuration 1 day after treatment(P<0.05).After 7 days, all objective clinical variables in the experimental group improved significantly(P<0.05) in the control group, there were significant improvements in GI,suppuration,lymphadenopathy and tooth mobility(P<0.05) but the four variables of the experimental group showed more improvement than the control group(P<0.05).After 30 days, all objective clinical variables improved significantly in both groups as compared to baseline, but in the experimental group, improvements were more significant regarding to GI,BI,PD,suppuration and tooth mobility(P<0.05). The method of supra- and subgingival scaling was rapid and effective in treatment of acute periodontal abscesses.

Large variable conductance heat pipe. Transverse header

NASA Technical Reports Server (NTRS)

Edelstein, F.

1975-01-01

The characteristics of gas-loaded, variable conductance heat pipes (VCHP) are discussed. The difficulties involved in developing a large VCHP header are analyzed. The construction of the large capacity VCHP is described. A research project to eliminate some of the problems involved in large capacity VCHP operation is explained.

Appending Limited Clinical Data to an Administrative Database for Acute Myocardial Infarction Patients: The Impact on the Assessment of Hospital Quality.

PubMed

Hannan, Edward L; Samadashvili, Zaza; Cozzens, Kimberly; Jacobs, Alice K; Venditti, Ferdinand J; Holmes, David R; Berger, Peter B; Stamato, Nicholas J; Hughes, Suzanne; Walford, Gary

2016-05-01

Hospitals' risk-standardized mortality rates and outlier status (significantly higher/lower rates) are reported by the Centers for Medicare and Medicaid Services (CMS) for acute myocardial infarction (AMI) patients using Medicare claims data. New York now has AMI claims data with blood pressure and heart rate added. The objective of this study was to see whether the appended database yields different hospital assessments than standard claims data. New York State clinically appended claims data for AMI were used to create 2 different risk models based on CMS methods: 1 with and 1 without the added clinical data. Model discrimination was compared, and differences between the models in hospital outlier status and tertile status were examined. Mean arterial pressure and heart rate were both significant predictors of mortality in the clinically appended model. The C statistic for the model with the clinical variables added was significantly higher (0.803 vs. 0.773, P<0.001). The model without clinical variables identified 10 low outliers and all of them were percutaneous coronary intervention hospitals. When clinical variables were included in the model, only 6 of those 10 hospitals were low outliers, but there were 2 new low outliers. The model without clinical variables had only 3 high outliers, and the model with clinical variables included identified 2 new high outliers. Appending even a small number of clinical data elements to administrative data resulted in a difference in the assessment of hospital mortality outliers for AMI. The strategy of adding limited but important clinical data elements to administrative datasets should be considered when evaluating hospital quality for procedures and other medical conditions.

Toward a unified theory of childhood trauma and psychosis: A comprehensive review of epidemiological, clinical, neuropsychological and biological findings.

PubMed

Misiak, Błażej; Krefft, Maja; Bielawski, Tomasz; Moustafa, Ahmed A; Sąsiadek, Maria M; Frydecka, Dorota

2017-04-01

There is a growing body of research focused on the relationship between childhood trauma and the risk of developing psychosis. Numerous studies, including many large-scale population-based studies, controlling for possible mediating variables, provide persuasive evidence of a dose-response association and are indicative of a causal relationship. Existing evidence supports the specificity model, showing differential associations between particular adversities and clinical symptoms, with cumulative adversity causing less favorable clinical and functional outcomes in psychotic patients. To date, several psychological and biological models have been proposed to search for underlying developmental trajectories leading to the onset of psychosis, influencing psychopathological manifestation and negative functional outcomes due to a history of childhood trauma. In this article, we provide a unified review on the relationship between childhood trauma and psychosis by integrating results of epidemiological, clinical, neuropsychological and biological studies. The question whether psychosis with a positive history of childhood trauma should be considered as a new psychotic phenotype, requiring specific therapeutic interventions, warrants further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

The state of ophthalmology medical student education in the United States and Canada, 2012 through 2013.

PubMed

Shah, Manjool; Knoch, Daniel; Waxman, Evan

2014-06-01

To characterize the state of ophthalmology medical student education in the United States and Canada. Survey of United States and Canadian medical schools. One hundred thirty-five Association of University Professors of Ophthalmology (AUPO) member institutions were surveyed, along with 30 osteopathic medical schools in the United States and 40 non-AUPO-affiliated allopathic medical schools in the United States. A survey characterizing preclinical, clinical, and extracurricular exposures to ophthalmology was used. Response rate, presence of, and types of preclinical and clinical exposures. Response rates to the survey were lower from non-AUPO institutions. Preclinical exposures largely consisted of basic lectures and examination skills, and most responding institutions had some sort of required preclinical ophthalmology experience. Clinical exposures were more variable, with an overall rate of required clinical rotations diminishing. There continues to be a gradual erosion of the role of ophthalmic medical education in the standard medical school curriculum. Clearly, there is room for improvement across all types of medical educational institutions. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A single center study: Aβ42/p-Tau181 CSF ratio to discriminate AD from FTD in clinical setting.

PubMed

Vergallo, Andrea; Carlesi, Cecilia; Pagni, Cristina; Giorgi, Filippo Sean; Baldacci, Filippo; Petrozzi, Lucia; Ceravolo, Roberto; Tognoni, Gloria; Siciliano, Gabriele; Bonuccelli, Ubaldo

2017-10-01

Abnormal levels of beta amyloid (Aβ42) and tau protein concentrations in the cerebral spinal fluid (CSF) have been largely described in Alzheimer's disease (AD). Thus, CSF analysis of these biomarkers has been incorporated in recent AD diagnostic criteria, and it is increasingly performed for neurodegenerative dementia diagnostic workout in clinical setting. Nevertheless, the precise biomarkers CSF features in neurodegenerative dementia, either AD or Frontotemporal dementia (FTD), are still not fully clear today. This is mainly due to lack of CSF clear cutoff values due to a well-known intersite (but even intrasite) variability of CSF procedures, ranging from collection to analysis. Applying CSF biomarker ratios, rather than their single values could represent a useful tool, especially for the differential diagnosis of different forms of dementia. We explored clinical values of six CSF ratios (by combining Aβ42 and tau) in order to better discriminate between AD and FTD; we identified Aβ42/p-Tau 181 ratio as a potential good candidate for helping differentiating AD from FTD in the clinical practice.

Blocking monocyte transmigration in in vitro system by an anti-CD99 human antibody in single chain fragment variable (scFv) format. Efficient large scale purification of biological active scFv from inclusion bodies in E. coli expression system

PubMed Central

Moricoli, Diego; Muller, William A.; Carbonella, Damiano Cosimo; Balducci, Maria Cristina; Dominici, Sabrina; Fiori, Valentina; Watson, Richard; Weber, Evan; Cianfriglia, Maurizio; Scotlandi, Katia; Magnani, Mauro

2015-01-01

Migration of leukocytes into a site of inflammation involves several steps mediated by various families of adhesion molecules. CD99 play a significant role in transendothelial migration (TEM) of leukocytes. Inhibition of TEM by specific monoclonal antibody (mAb) can provide a potent therapeutic approach to treating inflammatory conditions. However, the therapeutic utilization of whole IgG can lead to an inappropriate activation of Fc receptor-expressing cells inducing serious adverse side effects due to cytokine release. In this regard, specific recombinant antibody in single chain variable fragments (scFvs) originated by phage library may offer a solution by affecting TEM function in a safe clinical context. However, this consideration requires large scale production of functional scFv antibodies under GMP conditions and hence, the absence of toxic reagents utilized for the solubilization and refolding steps of inclusion bodies that may discourage industrial application of these antibody fragments. In order to apply the scFv anti-CD99 named C7A in a clinical setting we herein describe an efficient and large scale production of the antibody fragments expressed in E.coli as insoluble protein avoiding gel filtration chromatography approach, and laborious refolding step pre- and post-purification. Using differential salt elution which is a simple, reproducible and effective procedure we are able to separate scFv in monomer format from aggregates. The purified scFv antibody C7A exhibits inhibitory activity comparable to an antagonistic conventional mAb, thus providing an excellent agent for blocking CD99 signalling. Thanks to the original purification protocol that can be extended to other scFvs that are expressed as inclusion bodies in bacterial systems, the scFv anti-CD99 C7A herein described represents the first step towards the construction of new antibody therapeutic. PMID:24798881

A tonic heat test stimulus yields a larger and more reliable conditioned pain modulation effect compared to a phasic heat test stimulus

PubMed Central

Lie, Marie Udnesseter; Matre, Dagfinn; Hansson, Per; Stubhaug, Audun; Zwart, John-Anker; Nilsen, Kristian Bernhard

2017-01-01

Abstract Introduction: The interest in conditioned pain modulation (CPM) as a clinical tool for measuring endogenously induced analgesia is increasing. There is, however, large variation in the CPM methodology, hindering comparison of results across studies. Research comparing different CPM protocols is needed in order to obtain a standardized test paradigm. Objectives: The aim of the study was to assess whether a protocol with phasic heat stimuli as test-stimulus is preferable to a protocol with tonic heat stimulus as test-stimulus. Methods: In this experimental crossover study, we compared 2 CPM protocols with different test-stimulus; one with tonic test-stimulus (constant heat stimulus of 120-second duration) and one with phasic test-stimuli (3 heat stimulations of 5 seconds duration separated by 10 seconds). Conditioning stimulus was a 7°C water bath in parallel with the test-stimulus. Twenty-four healthy volunteers were assessed on 2 occasions with minimum 1 week apart. Differences in the magnitude and test–retest reliability of the CPM effect in the 2 protocols were investigated with repeated-measures analysis of variance and by relative and absolute reliability indices. Results: The protocol with tonic test-stimulus induced a significantly larger CPM effect compared to the protocol with phasic test-stimuli (P < 0.001). Fair and good relative reliability was found with the phasic and tonic test-stimuli, respectively. Absolute reliability indices showed large intraindividual variability from session to session in both protocols. Conclusion: The present study shows that a CPM protocol with a tonic test-stimulus is preferable to a protocol with phasic test-stimuli. However, we emphasize that one should be cautious to use the CPM effect as biomarker or in clinical decision making on an individual level due to large intraindividual variability. PMID:29392240

Framing of feedback impacts student's satisfaction, self-efficacy and performance.

PubMed

van de Ridder, J M Monica; Peters, Claudia M M; Stokking, Karel M; de Ru, J Alexander; Ten Cate, Olle Th J

2015-08-01

Feedback is considered important to acquire clinical skills. Research evidence shows that feedback does not always improve learning and its effects may be small. In many studies, a variety of variables involved in feedback provision may mask either one of their effects. E.g., there is reason to believe that the way oral feedback is framed may affect its effect if other variables are held constant. In a randomised controlled trial we investigated the effect of positively and negatively framed feedback messages on satisfaction, self-efficacy, and performance. A single blind randomised controlled between-subject design was used, with framing of the feedback message (positively-negatively) as independent variable and examination of hearing abilities as the task. First year medical students' (n = 59) satisfaction, self-efficacy, and performance were the dependent variables and were measured both directly after the intervention and after a 2 weeks delay. Students in the positively framed feedback condition were significantly more satisfied and showed significantly higher self-efficacy measured directly after the performance. Effect sizes found were large, i.e., partial η (2) = 0.43 and η (2) = 0.32 respectively. They showed a better performance throughout the whole study. Significant performance differences were found both at the initial performance and when measured 2 weeks after the intervention: effects were of medium size, respectively r = -.31 and r = -.32. Over time in both conditions performance and self-efficacy decreased. Framing the feedback message in either a positive or negative manner affects students' satisfaction and self-efficacy directly after the intervention be it that these effects seem to fade out over time. Performance may be enhanced by positive framing, but additional studies need to confirm this. We recommend using a positive frame when giving feedback on clinical skills.

Population pharmacodynamic modelling of midazolam induced sedation in terminally ill adult patients

PubMed Central

de Winter, Brenda C. M.; Masman, Anniek D.; van Dijk, Monique; Baar, Frans P. M.; Tibboel, Dick; Koch, Birgit C. P.; van Gelder, Teun; Mathot, Ron A. A.

2017-01-01

Aims Midazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. A previous pharmacokinetic (PK) study showed that variability between patients could be partly explained by renal function and inflammatory status. The goal of this study was to combine this PK information with pharmacodynamic (PD) data, to evaluate the variability in response to midazolam and to find clinically relevant covariates that may predict PD response. Method A population PD analysis using nonlinear mixed effect models was performed with data from 43 terminally ill patients. PK profiles were predicted by a previously described PK model and depth of sedation was measured using the Ramsay sedation score. Patient and disease characteristics were evaluated as possible covariates. The final model was evaluated using a visual predictive check. Results The effect of midazolam on the sedation level was best described by a differential odds model including a baseline probability, Emax model and interindividual variability on the overall effect. The EC50 value was 68.7 μg l–1 for a Ramsay score of 3–5 and 117.1 μg l–1 for a Ramsay score of 6. Comedication with haloperidol was the only significant covariate. The visual predictive check of the final model showed good model predictability. Conclusion We were able to describe the clinical response to midazolam accurately. As expected, there was large variability in response to midazolam. The use of haloperidol was associated with a lower probability of sedation. This may be a result of confounding by indication, as haloperidol was used to treat delirium, and deliria has been linked to a more difficult sedation procedure. PMID:28960387

Cost-effectiveness analysis using data from multinational trials: The use of bivariate hierarchical modelling

PubMed Central

Manca, Andrea; Lambert, Paul C; Sculpher, Mark; Rice, Nigel

2008-01-01

Healthcare cost-effectiveness analysis (CEA) often uses individual patient data (IPD) from multinational randomised controlled trials. Although designed to account for between-patient sampling variability in the clinical and economic data, standard analytical approaches to CEA ignore the presence of between-location variability in the study results. This is a restrictive limitation given that countries often differ in factors that could affect the results of CEAs, such as the availability of healthcare resources, their unit costs, clinical practice, and patient case-mix. We advocate the use of Bayesian bivariate hierarchical modelling to analyse multinational cost-effectiveness data. This analytical framework explicitly recognises that patient-level costs and outcomes are nested within countries. Using real life data, we illustrate how the proposed methods can be applied to obtain (a) more appropriate estimates of overall cost-effectiveness and associated measure of sampling uncertainty compared to standard CEA; and (b) country-specific cost-effectiveness estimates which can be used to assess the between-location variability of the study results, while controlling for differences in country-specific and patient-specific characteristics. It is demonstrated that results from standard CEA using IPD from multinational trials display a large degree of variability across the 17 countries included in the analysis, producing potentially misleading results. In contrast, ‘shrinkage estimates’ obtained from the modelling approach proposed here facilitate the appropriate quantification of country-specific cost-effectiveness estimates, while weighting the results based on the level of information available within each country. We suggest that the methods presented here represent a general framework for the analysis of economic data collected from different locations. PMID:17641141

Upper body kinematics in patients with cerebellar ataxia.

PubMed

Conte, Carmela; Pierelli, Francesco; Casali, Carlo; Ranavolo, Alberto; Draicchio, Francesco; Martino, Giovanni; Harfoush, Mahmoud; Padua, Luca; Coppola, Gianluca; Sandrini, Giorgio; Serrao, Mariano

2014-12-01

Although abnormal oscillations of the trunk are a common clinical feature in patients with cerebellar ataxia, the kinematic behaviour of the upper body in ataxic patients has yet to be investigated in quantitative studies. In this study, an optoelectronic motion analysis system was used to measure the ranges of motion (ROMs) of the head and trunk segments in the sagittal, frontal and yaw planes in 16 patients with degenerative cerebellar ataxia during gait at self-selected speed. The data obtained were compared with those collected in a gender-, age- and gait speed-matched sample of healthy subjects and correlated with gait variables (time-distance means and coefficients of variation) and clinical variables (disease onset, duration and severity). The results showed significantly larger head and/or trunk ROMs in ataxic patients compared with controls in all three spatial planes, and significant correlations between trunk ROMs and disease duration and severity (in sagittal and frontal planes) and time-distance parameters (in the yaw plane), and between both head and trunk ROMs and swing phase duration variability (in the sagittal plane). Furthermore, the ataxic patients showed a flexed posture of both the head and the trunk during walking. In conclusion, our study revealed abnormal motor behaviour of the upper body in ataxic patients, mainly resulting in a flexed posture and larger oscillations of the head and trunk. The results of the correlation analyses suggest that the longer and more severe the disease, the larger the upper body oscillations and that large trunk oscillations may explain some aspects of gait variability. These results suggest the need of specific rehabilitation treatments or the use of elastic orthoses that may be particularly useful to reduce trunk oscillations and improve dynamic stability.

Cancer family caregiver depression: are religion-related variables important?

PubMed

Williams, Anna-Leila; Dixon, Jane; Feinn, Richard; McCorkle, Ruth

2015-07-01

Prevalence estimates for clinical depression among cancer family caregivers (CFC) range upwards to 39%. Research inconsistently reports risk for CFC depressive symptoms when evaluating age, gender, ethnicity, or length of time as caregiver. The discrepant findings, coupled with emerging literature indicating religiosity may mitigate depression in some populations, led us to investigate religion-related variables to help predict CFC depressive symptoms. We conducted a cross-sectional study of 150 CFC. Explanatory variables included age, gender, spousal status, length of time as caregiver, attendance at religious services, and prayer. The outcome variable was the Center for Epidemiological Studies Depression Scale score. Compared with large national and state datasets, our sample has lower representation of individuals with no religious affiliation (10.7% vs. 16.1% national, p = 0.07 and 23.0% state, p = 0.001), higher rate of attendance at religious services (81.3% vs. 67.2% national, p < 0.001 and 30.0% state, p < 0.001), and higher rate of prayer (65.3% vs. 42.9% national, p < 0.001; no state data available). In unadjusted and adjusted models, prayer is not significantly associated with caregiver depressive symptoms or clinically significant depressive symptomology. Attendance at religious services is associated with depressive symptoms (p = 0.004) with an inversely linear trend (p = 0.002). The significant inverse association between attendance at religious services and depressive symptoms, despite no association between prayer and depressive symptoms, indicates that social or other factors may accompany attendance at religious services and contribute to the association. Clinicians can consider supporting a CFC's attendance at religious services as a potential preventive measure for depressive symptoms. Copyright © 2014 John Wiley & Sons, Ltd.

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.

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.

Effects of Ensemble Configuration on Estimates of Regional Climate Uncertainties

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

Goldenson, N.; Mauger, G.; Leung, L. R.

Internal variability in the climate system can contribute substantial uncertainty in climate projections, particularly at regional scales. Internal variability can be quantified using large ensembles of simulations that are identical but for perturbed initial conditions. Here we compare methods for quantifying internal variability. Our study region spans the west coast of North America, which is strongly influenced by El Niño and other large-scale dynamics through their contribution to large-scale internal variability. Using a statistical framework to simultaneously account for multiple sources of uncertainty, we find that internal variability can be quantified consistently using a large ensemble or an ensemble ofmore » opportunity that includes small ensembles from multiple models and climate scenarios. The latter also produce estimates of uncertainty due to model differences. We conclude that projection uncertainties are best assessed using small single-model ensembles from as many model-scenario pairings as computationally feasible, which has implications for ensemble design in large modeling efforts.« less

Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome

PubMed Central

Willemsen, Marjolein H; Fernandez, Bridget A; Bacino, Carlos A; Gerkes, Erica; de Brouwer, Arjan PM; Pfundt, Rolph; Sikkema-Raddatz, Birgit; Scherer, Stephen W; Marshall, Christian R; Potocki, Lorraine; van Bokhoven, Hans; Kleefstra, Tjitske

2010-01-01

The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes. PMID:19920853

Weak ventral striatal responses to monetary outcomes predict an unwillingness to resist cigarette smoking.

PubMed

Wilson, Stephen J; Delgado, Mauricio R; McKee, Sherry A; Grigson, Patricia S; MacLean, R Ross; Nichols, Travis T; Henry, Shannon L

2014-12-01

As a group, cigarette smokers exhibit blunted subjective, behavioral, and neurobiological responses to nondrug incentives and rewards, relative to nonsmokers. Findings from recent studies suggest, however, that there are large individual differences in the devaluation of nondrug rewards among smokers. Moreover, this variability appears to have significant clinical implications, since reduced sensitivity to nondrug rewards is associated with poorer smoking cessation outcomes. Currently, little is known about the neurobiological mechanisms that underlie these individual differences in the responsiveness to nondrug rewards. Here, we tested the hypothesis that individual variability in reward devaluation among smokers is linked to the functioning of the striatum. Specifically, functional magnetic resonance imaging was used to examine variability in the neural response to monetary outcomes in nicotine-deprived smokers anticipating an opportunity to smoke-circumstances found to heighten the devaluation of nondrug rewards by smokers in prior work. We also investigated whether individual differences in reward-related brain activity in those expecting to have access to cigarettes were associated with the degree to which the same individuals subsequently were willing to resist smoking in order to earn additional money. Our key finding was that deprived smokers who exhibited the weakest response to rewards (i.e., monetary gains) in the ventral striatum were least willing to refrain from smoking for monetary reinforcement. These results provide evidence that outcome-related signals in the ventral striatum serve as a marker for clinically meaningful individual differences in reward-motivated behavior among nicotine-deprived smokers.

Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance

PubMed Central

Noetzli, Muriel; Guidi, Monia; Ebbing, Karsten; Eyer, Stephan; Wilhelm, Laurence; Michon, Agnès; Thomazic, Valérie; Stancu, Ioana; Alnawaqil, Abdel-Messieh; Bula, Christophe; Zumbach, Serge; Gaillard, Michel; Giannakopoulos, Panteleimon; von Gunten, Armin; Csajka, Chantal; Eap, Chin B

2014-01-01

Aims A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. Methods A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. Results The average donepezil clearance was 7.3 l h−1 with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. Conclusion The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment. PMID:24433464

Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.

PubMed

Noetzli, Muriel; Guidi, Monia; Ebbing, Karsten; Eyer, Stephan; Wilhelm, Laurence; Michon, Agnès; Thomazic, Valérie; Stancu, Ioana; Alnawaqil, Abdel-Messieh; Bula, Christophe; Zumbach, Serge; Gaillard, Michel; Giannakopoulos, Panteleimon; von Gunten, Armin; Csajka, Chantal; Eap, Chin B

2014-07-01

A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. The average donepezil clearance was 7.3 l h(-1) with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment. © 2014 The British Pharmacological Society.

Why Summary Comorbidity Measures Such As the Charlson Comorbidity Index and Elixhauser Score Work.

PubMed

Austin, Steven R; Wong, Yu-Ning; Uzzo, Robert G; Beck, J Robert; Egleston, Brian L

2015-09-01

Comorbidity adjustment is an important component of health services research and clinical prognosis. When adjusting for comorbidities in statistical models, researchers can include comorbidities individually or through the use of summary measures such as the Charlson Comorbidity Index or Elixhauser score. We examined the conditions under which individual versus summary measures are most appropriate. We provide an analytic proof of the utility of comorbidity summary measures when used in place of individual comorbidities. We compared the use of the Charlson and Elixhauser scores versus individual comorbidities in prognostic models using a SEER-Medicare data example. We examined the ability of summary comorbidity measures to adjust for confounding using simulations. We devised a mathematical proof that found that the comorbidity summary measures are appropriate prognostic or adjustment mechanisms in survival analyses. Once one knows the comorbidity score, no other information about the comorbidity variables used to create the score is generally needed. Our data example and simulations largely confirmed this finding. Summary comorbidity measures, such as the Charlson Comorbidity Index and Elixhauser scores, are commonly used for clinical prognosis and comorbidity adjustment. We have provided a theoretical justification that validates the use of such scores under many conditions. Our simulations generally confirm the utility of the summary comorbidity measures as substitutes for use of the individual comorbidity variables in health services research. One caveat is that a summary measure may only be as good as the variables used to create it.

Natural trophic variability in a large, oligotrophic, near-pristine lake

USGS Publications Warehouse

Young, Talia; Jensen, Olaf P.; Weidel, Brian C.; Chandra, Sudeep

2015-01-01

Conclusions drawn from stable isotope data can be limited by an incomplete understanding of natural isotopic variability over time and space. We quantified spatial and temporal variability in fish carbon and nitrogen stable isotopes in Lake Hövsgöl, Mongolia, a large, remote, oligotrophic lake with an unusually species-poor fish community. The fish community demonstrated a high degree of trophic level overlap. Variability in δ13C was inversely related to littoral-benthic dependence, with pelagic species demonstrating more δ13C variability than littoral-benthic species. A mixed effects model suggested that space (sampling location) had a greater impact than time (collection year) on both δ13C and δ15N variability. The observed variability in Lake Hövsgöl was generally greater than isotopic variability documented in other large, oligotrophic lakes, similar to isotopic shifts attributed to introduced species, and less than isotopic shifts attributed to anthropogenic chemical changes such as eutrophication. This work complements studies on isotopic variability and changes in other lakes around the world.

Population PKPD modelling of the long-term hypoglycaemic effect of gliclazide given as a once-a-day modified release (MR) formulation

PubMed Central

Frey, N; Laveille, C; Paraire, M; Francillard, M; Holford, N H G; Jochemsen, Roeline

2003-01-01

Aims To study the relationship between the pharmacokinetics (PK) of gliclazide and its long-term pharmacodynamic (PD) effect in a large population of Type 2 diabetic patients and to identify factors predicting intersubject variability. Methods A PKPD database of 634 Type 2 diabetic patients with a total of 5258 fasting plasma glucose (FPG) samples was built up from the data collected during the clinical development of a modified release formulation of gliclazide (gliclazide MR). The PKPD analysis used a nonlinear mixed effect modelling approach. A mixture model was used to identify patients with a FPG response to treatment. In patients identified as responders, the decrease in FPG was related to gliclazide exposure (AUC) by an Emax relationship. An effect compartment was used to describe the link between PK and PD. A linear disease-progression model was used to assess the glycaemic deterioration observable over several months of treatment. Simulations were performed to evaluate the predictive performance of the PKPD model and to illustrate the time course of the antidiabetic effect of gliclazide MR. Results Disease state was found to be the main explanatory factor for intersubject variability in response to gliclazide. The percentage of responders to gliclazide, used as monotherapy, increased inversely to the number of classes of antidiabetic agents received prior to entry in the studies. In responders, the initial dose (30 mg) of the gliclazide MR dosing regimen induced half of the maximum hypoglycaemic effect. The equilibration half-life between the PK and PD steady states was 3 weeks (intersubject variability of 84%). The rate of disease progression was 0.84 mmol l−1 year−1 (intersubject variability 143%). The PKPD model adequately predicted the FPG profiles of 234 patients who received the current formulation of gliclazide. Simulation of a 1-year parallel dose ranging clinical trial illustrated the influence of dose, time and type of previous antidiabetic treatment on the percentage of patients with clinically significant improvement of blood glucose control. Conclusions This population PKPD analysis has characterized the relationship between the exposure to gliclazide and its long-term hypoglycaemic effect, and has established that the intersubject variability in response is mostly related to disease state. These results underline the clinical interest of quickly increasing the dose of gliclazide MR according to the response to treatment in order to achieve effective blood glucose control. PMID:12580986

The impact of productivity-based incentives on faculty salary-based compensation.

PubMed

Miller, Ronald D; Cohen, Neal H

2005-07-01

In industry and academic anesthesia departments, incentives and bonus payments based on productivity are accounting for an increasing proportion of a total compensation. When incentives are primarily based on clinical productivity, the impact on the distribution of total compensation to the faculty is not known. We compared a pure salary-based compensation methodology based entirely on academic rank to salary plus incentives and/or clinical productivity compensation (i.e., billable hours). The change in compensation methodology resulted in two major findings. First, the productivity-based compensation resulted in a large increase in the variability of total compensation among faculty, especially at the Assistant Professor rank. Second, the mean difference in total compensation between Assistant and Full Professors decreased. The authors conclude that this particular incentive plan, primarily directed toward clinical productivity, dramatically changed the distribution of total compensation in favor of junior faculty. Although not analytically investigated, the potential impact of these changes on faculty morale and distribution of faculty activities is discussed.

Eating Disorders and Major Depression: Role of Anger and Personality

PubMed Central

Giovanni, Abbate-Daga; Carla, Gramaglia; Enrica, Marzola; Federico, Amianto; Maria, Zuccolin; Secondo, Fassino

2011-01-01

This study aimed to evaluate comorbidity for MD in a large ED sample and both personality and anger as clinical characteristics of patients with ED and MD. We assessed 838 ED patients with psychiatric evaluations and psychometric questionnaires: Temperament and Character Inventory, Eating Disorder Inventory-2, Beck Depression Inventory, and State-Trait Anger Expression Inventory. 19.5% of ED patients were found to suffer from comorbid MD and 48.7% reported clinically significant depressive symptomatology: patients with Anorexia Binge-Purging and Bulimia Nervosa were more likely to be diagnosed with MD. Irritable mood was found in the 73% of patients with MD. High Harm Avoidance (HA) and low Self-Directedness (SD) predicted MD independently of severity of the ED symptomatology, several clinical variables, and ED diagnosis. Assessing both personality and depressive symptoms could be useful to provide effective treatments. Longitudinal studies are needed to investigate the pathogenetic role of HA and SD for ED and MD. PMID:21977317

Application of machine learning algorithms for clinical predictive modeling: a data-mining approach in SCT.

PubMed

Shouval, R; Bondi, O; Mishan, H; Shimoni, A; Unger, R; Nagler, A

2014-03-01

Data collected from hematopoietic SCT (HSCT) centers are becoming more abundant and complex owing to the formation of organized registries and incorporation of biological data. Typically, conventional statistical methods are used for the development of outcome prediction models and risk scores. However, these analyses carry inherent properties limiting their ability to cope with large data sets with multiple variables and samples. Machine learning (ML), a field stemming from artificial intelligence, is part of a wider approach for data analysis termed data mining (DM). It enables prediction in complex data scenarios, familiar to practitioners and researchers. Technological and commercial applications are all around us, gradually entering clinical research. In the following review, we would like to expose hematologists and stem cell transplanters to the concepts, clinical applications, strengths and limitations of such methods and discuss current research in HSCT. The aim of this review is to encourage utilization of the ML and DM techniques in the field of HSCT, including prediction of transplantation outcome and donor selection.

Tularaemia: clinical aspects in Europe.

PubMed

Maurin, Max; Gyuranecz, Miklós

2016-01-01

Tularaemia is a zoonotic disease caused by Francisella tularensis, a Gram-negative, facultative intracellular bacterium. Typically, human and animal infections are caused by F tularensis subspecies tularensis (type A) strains mainly in Canada and USA, and F tularensis subspecies holarctica (type B) strains throughout the northern hemisphere, including Europe. In the past, the epidemiological, clinical, therapeutic, and prognostic aspects of tularaemia reported in the English medical literature were mainly those that had been reported in the USA, where the disease was first described. Tularaemia has markedly changed in the past decade, and a large number of studies have provided novel data for the disease characteristics in Europe. In this Review we aim to emphasise the specific and variable aspects of tularaemia in different European countries. In particular, two natural lifecycles of F tularensis have been described in this continent, although not fully characterised, which are associated with different modes of transmission, clinical features, and public health burdens of tularaemia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Abdominal aortic aneurysm events in the women's health initiative: cohort study.

PubMed

Lederle, Frank A; Larson, Joseph C; Margolis, Karen L; Allison, Matthew A; Freiberg, Matthew S; Cochrane, Barbara B; Graettinger, William F; Curb, J David

2008-10-14

To assess the association between potential risk factors and subsequent clinically important abdominal aortic aneurysm events (repairs and ruptures) in women. Large prospective observational cohort study with mean follow-up of 7.8 years. 40 clinical centres across the United States. 161 808 postmenopausal women aged 50-79 enrolled in the women's health initiative. Association of self reported or measured baseline variables with confirmed abdominal aortic aneurysm events assessed with multiple logistic regression. Events occurred in 184 women and were strongly associated with age and smoking. Ever smoking, current smoking, and amount smoked all contributed independent risk. Diabetes showed a negative association (odds ratio 0.29, 95% confidence interval 0.13, 0.68), as did postmenopausal hormone therapy. Positive associations were also seen for height, hypertension, cholesterol lowering treatment, and coronary and peripheral artery disease. Our findings confirm the strong positive associations of clinically important abdominal aortic aneurysm with age and smoking in women and the negative association with diabetes previously reported in men.

Wechsler Adult Intelligence Scale-IV Dyads for Estimating Global Intelligence.

PubMed

Girard, Todd A; Axelrod, Bradley N; Patel, Ronak; Crawford, John R

2015-08-01

All possible two-subtest combinations of the core Wechsler Adult Intelligence Scale-IV (WAIS-IV) subtests were evaluated as possible viable short forms for estimating full-scale IQ (FSIQ). Validity of the dyads was evaluated relative to FSIQ in a large clinical sample (N = 482) referred for neuropsychological assessment. Sample validity measures included correlations, mean discrepancies, and levels of agreement between dyad estimates and FSIQ scores. In addition, reliability and validity coefficients were derived from WAIS-IV standardization data. The Coding + Information dyad had the strongest combination of reliability and validity data. However, several other dyads yielded comparable psychometric performance, albeit with some variability in their particular strengths. We also observed heterogeneity between validity coefficients from the clinical and standardization-based estimates for several dyads. Thus, readers are encouraged to also consider the individual psychometric attributes, their clinical or research goals, and client or sample characteristics when selecting among the dyadic short forms. © The Author(s) 2014.

Prediction complements explanation in understanding the developing brain.

PubMed

Rosenberg, Monica D; Casey, B J; Holmes, Avram J

2018-02-21

A central aim of human neuroscience is understanding the neurobiology of cognition and behavior. Although we have made significant progress towards this goal, reliance on group-level studies of the developed adult brain has limited our ability to explain population variability and developmental changes in neural circuitry and behavior. In this review, we suggest that predictive modeling, a method for predicting individual differences in behavior from brain features, can complement descriptive approaches and provide new ways to account for this variability. Highlighting the outsized scientific and clinical benefits of prediction in developmental populations including adolescence, we show that predictive brain-based models are already providing new insights on adolescent-specific risk-related behaviors. Together with large-scale developmental neuroimaging datasets and complementary analytic approaches, predictive modeling affords us the opportunity and obligation to identify novel treatment targets and individually tailor the course of interventions for developmental psychopathologies that impact so many young people today.

Genetic variability in environmental isolates of Legionella pneumophila from Comunidad Valenciana (Spain).

PubMed

Coscollá, Mireia; Gosalbes, María José; Catalán, Vicente; González-Candelas, Fernando

2006-06-01

Legionella pneumophila is associated to recurrent outbreaks in several Comunidad Valenciana (Spain) localities, especially in Alcoi, where social and climatic conditions seem to provide an excellent environment for bacterial growth. We have analysed the nucleotide sequences of three loci from 25 environmental isolates from Alcoi and nearby locations sampled over 3 years. The analysis of these isolates has revealed a substantial level of genetic variation, with consistent patterns of variability across loci, and comparable to that found in a large, European-wide sampling of clinical isolates. Among the tree loci studied, fliC showed the highest level of nucleotide diversity. The analysis of isolates sampled in different years revealed a clear differentiation, with samples from 2001 being significantly distinct from those obtained in 2002 and 2003. Furthermore, although linkage disequilibrium measures indicate a clonal nature for population structure in this sample, the presence of some recombination events cannot be ruled out.

Essential Oil Composition of Phagnalon sordidum (L.) from Corsica, Chemical Variability and Antimicrobial Activity.

PubMed

Brunel, Marion; Vitrac, Caroline; Costa, Jean; Mzali, Fatima; Vitrac, Xavier; Muselli, Alain

2016-03-01

The chemical composition of Phagnalon sordidum (L.) essential oil was investigated for the first time using gas chromatography and chromatography/mass spectrometry. Seventy-six compounds, which accounted for 87.9% of the total amount, were identified in a collective essential oil of P. sordidum from Corsica. The main essential oil components were (E)-β-caryophyllene (14.4%), β-pinene (11.0%), thymol (9.0%), and hexadecanoic acid (5.3%). The chemical compositions of essential oils from 19 Corsican locations were investigated. The study of the chemical variability using statistical analysis allowed identifying direct correlation between the three populations of P. sordidum widespread in Corsica and the essential oil compositions they produce. The in vitro antimicrobial activity of P. sordidum essential oil was evaluated and it exhibited a notable activity on a large panel of clinically significant microorganisms. © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Relative body weight as a factor in the decision to abort.

PubMed

Thelen, T H; Alumbaugh, R V

1983-06-01

Abortion referral data of 692 pregnant women visiting a large urban planned parenthood clinic were analyzed to determine whether relative weight, as measured by an adiposity index, as well as other variables, were associated with a decision to terminate or not terminate a pregnancy. Relative weight, length of pregnancy, education, age, ethnicity, and marital status were found to be associated with the decision to abort. While most of these variables were previously shown to have been related to the decision to terminate or not terminate a pregnancy, a relationship between relative weight and abortion has not previously been reported. In the analyses of all the women in this study and of a subsample consisting only of those in the early stages of their pregnancies, increased relative weight was associated with a decrease in the likelihood of pregnancy termination. Possible reasons for this relationship and the evolutionary implications are discussed.

Phenotypic variability of the cat eye syndrome. Case report and review of the literature.

PubMed

Rosias, P R; Sijstermans, J M; Theunissen, P M; Pulles-Heintzberger, C F; De Die-Smulders, C E; Engelen, J J; Van Der Meer, S B

2001-01-01

We present a male infant with preauricular skin tags and pits, downslanting palpebral fissures, hypertelorism, ectopic anus, hypospadias, and hypoplastic left heart syndrome. The clinical features in our patient show phenotypic overlap with the cat eye syndrome, as illustrated by the review of 105 reported cases. Cytogenetic analysis revealed a supernumerary marker chromosome, which was identified by microdissection and fluorescence in situ hybridization as an isodicentric chromosome 22(pter --> q11.2::q11.2 --> pter). It was proved with probes specific for the cat eye syndrome critical region that this region was present in quadruplicate in the propositus. We conclude that CES is characterized by large phenotypic variability, ranging from near normal to severe malformations, as reflected in the neurodevelopmental outcome. Preauricular skin tags and/or pits are the most consistent features, and suggest the presence of a supernumerary bisatellited marker chromosome 22 derived from duplication of the CES critical region.

Chronic cerebro-spinal venous insufficiency (CCSVI) and multiple sclerosis.

PubMed

Ghezzi, A; Comi, G; Federico, A

2011-02-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS caused by the interplay of genetic and environmental factors. In the last years, it has been suggested that an abnormal venous drainage due to stenosis or malformation of the internal jugular and/or azygous veins may play a major pathogenetic role in MS. This abnormality called chronic cerebro-spinal venous insufficiency (CCSVI) could result in increased permeability of blood brain barrier, local iron deposition and secondary multifocal inflammation. In the present paper, literature data in favour and against this hypothesis are reported. A great variability of CCSVI has been found in both MS patients (ranging from 0 to 100%) and in control subjects (from 0 to 23%). This large variability is explained by methodological aspects, problems in assessing CCSVI, and differences among clinical series. It is urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS.

Variability of human pluripotent stem cell lines.

PubMed

Ortmann, Daniel; Vallier, Ludovic

2017-10-01

Human pluripotent stem cells derived from embryos (human Embryonic Stem Cells or hESCs) or generated by direct reprogramming of somatic cells (human Induced Pluripotent Stem Cells or hiPSCs) can proliferate almost indefinitely in vitro while maintaining the capacity to differentiate into a broad diversity of cell types. These two properties (self-renewal and pluripotency) confers human pluripotent stem cells a unique interest for clinical applications since they could allow the production of infinite quantities of cells for disease modelling, drug screening and cell based therapy. However, recent studies have clearly established that human pluripotent stem cell lines can display variable capacity to differentiate into specific lineages. Consequently, the development of universal protocols of differentiation which could work efficiently with any human pluripotent cell line is complicated substantially. As a consequence, each protocol needs to be adapted to every cell line thereby limiting large scale applications and precluding personalised therapies. Here, we summarise our knowledge concerning the origin of this variability and describe potential solutions currently available to bypass this major challenge. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of large-scale, long-term optical surveys on pulsating star research

NASA Astrophysics Data System (ADS)

Soszyński, Igor

2017-09-01

The era of large-scale photometric variability surveys began a quarter of a century ago, when three microlensing projects - EROS, MACHO, and OGLE - started their operation. These surveys initiated a revolution in the field of variable stars and in the next years they inspired many new observational projects. Large-scale optical surveys multiplied the number of variable stars known in the Universe. The huge, homogeneous and complete catalogs of pulsating stars, such as Cepheids, RR Lyrae stars, or long-period variables, offer an unprecedented opportunity to calibrate and test the accuracy of various distance indicators, to trace the three-dimensional structure of the Milky Way and other galaxies, to discover exotic types of intrinsically variable stars, or to study previously unknown features and behaviors of pulsators. We present historical and recent findings on various types of pulsating stars obtained from the optical large-scale surveys, with particular emphasis on the OGLE project which currently offers the largest photometric database among surveys for stellar variability.

Ocular myasthenia gravis: A review

PubMed Central

Nair, Akshay Gopinathan; Patil-Chhablani, Preeti; Venkatramani, Devendra V; Gandhi, Rashmin Anilkumar

2014-01-01

Myasthenia gravis (MG) is a disease that affects the neuro-muscular junction resulting in classical symptoms of variable muscle weakness and fatigability. It is called the great masquerader owing to its varied clinical presentations. Very often, a patient of MG may present to the ophthalmologist given that a large proportion of patients with systemic myasthenia have ocular involvement either at presentation or during the later course of the disease. The treatment of ocular MG involves both the neurologist and ophthalmologist. Thus, the aim of this review was to highlight the current diagnosis, investigations, and treatment of ocular MG. PMID:25449931

Metabolic effects of large-volume liposuction for obese healthy women: a meta-analysis of fasting insulin levels.

PubMed

Boriani, Filippo; Villani, Riccardo; Morselli, Paolo Giovanni

2014-10-01

Obesity is increasingly frequent in our society and is associated closely with metabolic disorders. As some studies have suggested, removal of fat tissue through liposuction and dermolipectomies may be of some benefit in the improvement of metabolic indices. This article aimed to review the published literature on this topic and to evaluate metabolic variations meta-analytically after liposuction, dermolipectomy, or both. Through a literature search with the PubMed/Medline database, 14 studies were identified. All articles were analyzed, and several metabolic variables were chosen in the attempt to meta-analyze the effect of adipose tissue removal through the various studies. All statistical calculations were performed with Review Manager (RevMan), version 5.0. Several cardiovascular and metabolic variables are described as prone to variations after body-contouring procedures when a significant amount of adipose tissue has been excised. Four of the studies included in the analysis reported improvements in all the parameters examined. Seven articles showed improvement in some variables and no improvement in others, whereas three studies showed no beneficial variation in any of the considered indicators after body-contouring procedures. Fasting plasma insulin was identified as the only variable for which a meta-analysis of five included studies was possible. The meta-analysis showed a statistically significant reduction in fasting plasma insulin resulting from large-volume liposuction in obese healthy women. Many beneficial metabolic effects resulting from dermolipectomy and liposuction procedures are described in the literature. In particular, fasting plasma insulin and thus insulin sensitivity seem to be positively influenced. Further research, including prospective clinical studies, is necessary for better exploration of the effects that body-contouring plastic surgery procedures have on metabolic parameters.

Search and retrieval of medical images for improved diagnosis of neurodegenerative diseases

NASA Astrophysics Data System (ADS)

Ekin, Ahmet; Jasinschi, Radu; Turan, Erman; Engbers, Rene; van der Grond, Jeroen; van Buchem, Mark A.

2007-01-01

In the medical world, the accuracy of diagnosis is mainly affected by either lack of sufficient understanding of some diseases or the inter-, and/or intra-observer variability of the diagnoses. The former requires understanding the progress of diseases at much earlier stages, extraction of important information from ever growing amounts of data, and finally finding correlations with certain features and complications that will illuminate the disease progression. The latter (inter-, and intra- observer variability) is caused by the differences in the experience levels of different medical experts (inter-observer variability) or by mental and physical tiredness of one expert (intra-observer variability). We believe that the use of large databases can help improve the current status of disease understanding and decision making. By comparing large number of patients, some of the otherwise hidden relations can be revealed that results in better understanding, patients with similar complications can be found, the diagnosis and treatment can be compared so that the medical expert can make a better diagnosis. To this effect, this paper introduces a search and retrieval system for brain MR databases and shows that brain iron accumulation shape provides additional information to the shape-insensitive features, such as the total brain iron load, that are commonly used in the clinics. We propose to use Kendall's correlation value to automatically compare various returns to a query. We also describe a fully automated and fast brain MR image analysis system to detect degenerative iron accumulation in brain, as it is the case in Alzheimer's and Parkinson's. The system is composed of several novel image processing algorithms and has been extensively tested in Leiden University Medical Center over so far more than 600 patients.

Zoom‐in comparative genomic hybridisation arrays for the characterisation of variable breakpoint contiguous gene syndromes

PubMed Central

Johnston, Jennifer J; Walker, Robert L; Davis, Sean; Facio, Flavia; Turner, Joyce T; Bick, David P; Daentl, Donna L; Ellison, Jay W; Meltzer, Paul S; Biesecker, Leslie G

2007-01-01

Contiguous gene syndromes cause disorders via haploinsufficiency for adjacent genes. Some contiguous gene syndromes (CGS) have stereotypical breakpoints, but others have variable breakpoints. In CGS that have variable breakpoints, the extent of the deletions may be correlated with severity. The Greig cephalopolysyndactyly contiguous gene syndrome (GCPS‐CGS) is a multiple malformation syndrome caused by haploinsufficiency of GLI3 and adjacent genes. In addition, non‐CGS GCPS can be caused by deletions or duplications in GLI3. Although fluorescence in situ hybridisation (FISH) can identify large deletion mutations in patients with GCPS or GCPS‐CGS, it is not practical for identification of small intragenic deletions or insertions, and it is difficult to accurately characterise the extent of the large deletions using this technique. We have designed a custom comparative genomic hybridisation (CGH) array that allows identification of deletions and duplications at kilobase resolution in the vicinity of GLI3. The array averages one probe every 730 bp for a total of about 14 000 probes over 10 Mb. We have analysed 16 individuals with known or suspected deletions or duplications. In 15 of 16 individuals (14 deletions and 1 duplication), the array confirmed the prior results. In the remaining patient, the normal CGH array result was correct, and the prior assessment was a false positive quantitative polymerase chain reaction result. We conclude that high‐density CGH array analysis is more sensitive than FISH analysis for detecting deletions and provides clinically useful results on the extent of the deletion. We suggest that high‐density CGH array analysis should replace FISH analysis for assessment of deletions and duplications in patients with contiguous gene syndromes caused by variable deletions. PMID:17098889

Hereditary motor and sensory neuropathy type VI with optic atrophy.

PubMed

Voo, Irene; Allf, Bryan E; Udar, Nitin; Silva-Garcia, Rosamaria; Vance, Jeffrey; Small, Kent W

2003-10-01

To present the detailed clinical findings of a large family with hereditary motor and sensory neuropathy type VI (HMSN VI), a syndrome featuring optic atrophy. Observational case series. A detailed history was obtained and physical examination was made of the extended family of the proband for evidence of neurologic dysfunction. The OPA1 gene was screened for mutations by direct DNA sequencing. Twelve of 97 family members examined are affected with signs of HMSN VI. Three other members have either optic atrophy or peripheral neuropathy, thus allowing an appreciation of the full clinical spectrum of disease. No mutations were found in the OPA1 gene. This family demonstrates the variable expressivity of this disorder as well as incomplete penetrance. This is the largest known family with HMSN VI. No association was found with changes in the OPA1 gene.

Application of person-centered analytic methodology in longitudinal research: exemplars from the Women's Health Initiative Clinical Trial data.

PubMed

Zaslavsky, Oleg; Cochrane, Barbara B; Herting, Jerald R; Thompson, Hilaire J; Woods, Nancy F; Lacroix, Andrea

2014-02-01

Despite the variety of available analytic methods, longitudinal research in nursing has been dominated by use of a variable-centered analytic approach. The purpose of this article is to present the utility of person-centered methodology using a large cohort of American women 65 and older enrolled in the Women's Health Initiative Clinical Trial (N = 19,891). Four distinct trajectories of energy/fatigue scores were identified. Levels of fatigue were closely linked to age, socio-demographic factors, comorbidities, health behaviors, and poor sleep quality. These findings were consistent regardless of the methodological framework. Finally, we demonstrated that energy/fatigue levels predicted future hospitalization in non-disabled elderly. Person-centered methods provide unique opportunities to explore and statistically model the effects of longitudinal heterogeneity within a population. © 2013 Wiley Periodicals, Inc.

Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon

PubMed Central

Verhoef, Talitha I; Redekop, William K; Daly, Ann K; van Schie, Rianne M F; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse

2014-01-01

Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose–response and a small therapeutic window, treatment with coumarin derivatives is challenging. Certain polymorphisms in CYP2C9 and VKORC1 are associated with lower dose requirements and a higher risk of bleeding. In this review we describe the use of different coumarin derivatives, pharmacokinetic characteristics of these drugs and differences amongst the coumarins. We also describe the current clinical challenges and the role of pharmacogenetic factors. These genetic factors are used to develop dosing algorithms and can be used to predict the right coumarin dose. The effectiveness of this new dosing strategy is currently being investigated in clinical trials. PMID:23919835

Assessment of pulmonary vascular reactivity to oxygen using fractional moving blood volume in fetuses with normal lung development and pulmonary hypoplasia in congenital diaphragmatic hernia.

PubMed

DeKoninck, Philip; Jimenez, Julio; Russo, Francesca M; Hodges, Ryan; Gratacós, Eduard; Deprest, Jan

2014-10-01

The objective of this study is to evaluate whether assessment pulmonary vascular reactivity in response to maternal hyperoxygenation using fractional moving blood volume (FMBV) is associated with lesser variability between individual measurements than what is observed with direct Doppler measurements. Forty-five measurements were performed in 15 singleton fetuses with normal lung development at three time points in the latter half of pregnancy (range: 25.9-36.7 weeks). We further evaluated five fetuses with severe congenital diaphragmatic hernia. Lung perfusion was assessed using power Doppler ultrasound, and images were stored for offline FMBV calculation, both at base line and during oxygen administration (9 L/min for 10 min). The proportionate difference between both measurements is further referred to as deltaFMBV. Overall, 91% of images were of sufficient quality for further analysis. There was no correlation between pulmonary reactivity to oxygen (deltaFMBV) and gestational age in controls (12.9 ± 32.1%). Moreover, deltaFMBV showed large variability between subjects, as well as within the same fetus throughout gestation. We observed good intraobserver (0.88; 0.84) and interobserver (0.88; 0.77) reproducibility for both controls and congenital diaphragmatic hernia, respectively (intraclass correlation coefficients). Despite being a reproducible method to study the lung vasculature, the large variability of FMBV following hyperoxygenation limits its clinical translation. © 2014 John Wiley & Sons, Ltd.

Is a clinical sociolinguistics possible?

PubMed

Ball, M J

1992-01-01

This paper considers the idea of developing a clinical sociolinguistics. Various areas of the field are examined, and the importance of the 'core' area of the correlation of non-linguistic variables with linguistic variables stressed. Issues concerning language and class, region, sex, age and context of utterance are investigated, together with the implications for clinical linguistics. Finally, the difficulty of integrating such issues into clinical assessment is explored, and a tentative step forward suggested along the lines of a 'clinical sociolinguistic checklist'.

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.

Variability in large-scale wind power generation: Variability in large-scale wind power generation

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

Kiviluoma, Juha; Holttinen, Hannele; Weir, David

2015-10-25

The paper demonstrates the characteristics of wind power variability and net load variability in multiple power systems based on real data from multiple years. Demonstrated characteristics include probability distribution for different ramp durations, seasonal and diurnal variability and low net load events. The comparison shows regions with low variability (Sweden, Spain and Germany), medium variability (Portugal, Ireland, Finland and Denmark) and regions with higher variability (Quebec, Bonneville Power Administration and Electric Reliability Council of Texas in North America; Gansu, Jilin and Liaoning in China; and Norway and offshore wind power in Denmark). For regions with low variability, the maximum 1more » h wind ramps are below 10% of nominal capacity, and for regions with high variability, they may be close to 30%. Wind power variability is mainly explained by the extent of geographical spread, but also higher capacity factor causes higher variability. It was also shown how wind power ramps are autocorrelated and dependent on the operating output level. When wind power was concentrated in smaller area, there were outliers with high changes in wind output, which were not present in large areas with well-dispersed wind power.« less

Modeling continuous covariates with a "spike" at zero: Bivariate approaches.

PubMed

Jenkner, Carolin; Lorenz, Eva; Becher, Heiko; Sauerbrei, Willi

2016-07-01

In epidemiology and clinical research, predictors often take value zero for a large amount of observations while the distribution of the remaining observations is continuous. These predictors are called variables with a spike at zero. Examples include smoking or alcohol consumption. Recently, an extension of the fractional polynomial (FP) procedure, a technique for modeling nonlinear relationships, was proposed to deal with such situations. To indicate whether or not a value is zero, a binary variable is added to the model. In a two stage procedure, called FP-spike, the necessity of the binary variable and/or the continuous FP function for the positive part are assessed for a suitable fit. In univariate analyses, the FP-spike procedure usually leads to functional relationships that are easy to interpret. This paper introduces four approaches for dealing with two variables with a spike at zero (SAZ). The methods depend on the bivariate distribution of zero and nonzero values. Bi-Sep is the simplest of the four bivariate approaches. It uses the univariate FP-spike procedure separately for the two SAZ variables. In Bi-D3, Bi-D1, and Bi-Sub, proportions of zeros in both variables are considered simultaneously in the binary indicators. Therefore, these strategies can account for correlated variables. The methods can be used for arbitrary distributions of the covariates. For illustration and comparison of results, data from a case-control study on laryngeal cancer, with smoking and alcohol intake as two SAZ variables, is considered. In addition, a possible extension to three or more SAZ variables is outlined. A combination of log-linear models for the analysis of the correlation in combination with the bivariate approaches is proposed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rank-based estimation in the {ell}1-regularized partly linear model for censored outcomes with application to integrated analyses of clinical predictors and gene expression data.

PubMed

Johnson, Brent A

2009-10-01

We consider estimation and variable selection in the partial linear model for censored data. The partial linear model for censored data is a direct extension of the accelerated failure time model, the latter of which is a very important alternative model to the proportional hazards model. We extend rank-based lasso-type estimators to a model that may contain nonlinear effects. Variable selection in such partial linear model has direct application to high-dimensional survival analyses that attempt to adjust for clinical predictors. In the microarray setting, previous methods can adjust for other clinical predictors by assuming that clinical and gene expression data enter the model linearly in the same fashion. Here, we select important variables after adjusting for prognostic clinical variables but the clinical effects are assumed nonlinear. Our estimator is based on stratification and can be extended naturally to account for multiple nonlinear effects. We illustrate the utility of our method through simulation studies and application to the Wisconsin prognostic breast cancer data set.

Appropriateness of Prescriptions of Recommended Treatments in Organisation for Economic Co-operation and Development Health Systems: Findings Based on the Long-Term Registry of the European Society of Cardiology on Heart Failure.

PubMed

Maggioni, Aldo P; Van Gool, Kees; Biondi, Nelly; Urso, Renato; Klazinga, Niek; Ferrari, Roberto; Maniadakis, Nikolaos; Tavazzi, Luigi

2015-12-01

This observational study aimed to identify clinical variables and health system characteristics associated with incomplete guideline application in drug treatment of patients with chronic heart failure (HF) across 15 countries. Three data sets were used: European Society of Cardiology Heart Failure Registry, Organisation for Economic Co-operation and Development's Health System Characteristics Survey, and Organisation for Economic Co-operation and Development Health Statistics 2013. Patient and country variables were examined by multilevel, multiple logistic regression. The study population consisted of ambulatory patients with chronic HF and reduced ejection fraction. Inappropriateness of prescription of pharmacological treatments was defined as patients not prescribed at least one of the two recommended treatments (angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers and beta-blockers) or treated with both medications but at suboptimal dosage and in absence of documented contraindication/intolerance. Of 4605 patients, 1097 (23.8%) received inappropriate drug prescriptions with a large variation within and across countries, with 18.5% of the total variability accounted for by between-country health structure characteristics. Patient-level characteristics such as having mitral regurgitation (odds ratio 1.4; 95% confidence interval 1.1-1.7) was significantly associated with inappropriate prescription of recommended drugs, whereas chronic obstructive pulmonary disease (odds ratio 0.7; 95% confidence interval 0.5-0.9) was associated with more appropriate prescriptions. Among the country-level variables, incentives or obligation to comply with guidelines increased the probability of prescription appropriateness. Combining clinical variables with health system characteristics is a promising exercise to explain the appropriateness of recommended drug prescriptions. Such an understanding can help decision makers to design more effective policies to improve adherence to guidelines, improve health care outcomes, and potentially reduce costs. Copyright © 2015. Published by Elsevier Inc.

In the aftermath of SPRINT: further comparison of unattended automated office blood pressure measurement and 24-hour blood pressure monitoring.

PubMed

Seidlerová, Jitka; Gelžinský, Julius; Mateřánková, Markéta; Ceral, Jiří; König, Petr; Filipovský, Jan

2018-03-22

Several papers reported that unattended automated office blood pressure (uAutoOBP) is closely related to daytime ambulatory blood pressure monitoring (ABPM). In the present study, we aim to study uAutoOBP and its relation to 24-hour ABPM and ABPM variability. Stable treated hypertensive subjects were examined in two Czech academic hypertension centres. uAutoOBP was measured with the BP Tru device; attended BP three times with auscultatory method (AuscOBP) by the physician. ABPM was performed within one week from the clinical visit. Data on 98 subjects aged 67.7 ± 9.3 years with 24-hour ABPM 120.3 ± 10.6/72.7 ± 7.9 mm Hg are reported. uAutoOBP was lower than 24-hour (by -5.2 ± 11.3/-0.5 ± 6.9 mm Hg) and daytime (by -6.7 ± 12.82.4 ± 8.0 mm Hg) ABPM and the individual variability of the difference was very large (up to 30 mm Hg). The correlation coefficients between ABPM and uAutoOBP were similar compared to AuscOBP (p ≥ .17). Variability of uAutoOBP, but not AuscOBP, readings during one clinical visit was related to short-term blood pressure variability of ABPM. The difference between AuscOBP and uAutoOBP was larger in patients with white-coat effect compared to other blood pressure control groups (25.1 ± 7.0 vs. 2.2 ± 10.3 mm Hg; p = .0036). Our study shows that uAutoOBP is not good predictor of ambulatory blood pressure monitoring, not even of the daytime values. It might, however, indicate short-term blood pressure variability and, when compared with AuscOBP, also detect patients with white-coat effect.

Smart Energy Cryo-refrigerator Technology for the next generation Very Large Array

NASA Astrophysics Data System (ADS)

Spagna, Stefano

2018-01-01

We describe a “smart energy” cryocooler technology architecture for the next generation Very Large Array that makes use of multiple variable frequency cold heads driven from a single variable speed air cooled compressor. Preliminary experiments indicate that the compressor variable flow control, advanced diagnostics, and the cryo-refrigerator low vibration, provide a unique energy efficient capability for the very large number of antennas that will be employed in this array.

A preliminary investigation of daily variability of stuttering in adults.

PubMed

Constantino, Christopher D; Leslie, Paula; Quesal, Robert W; Yaruss, J Scott

2016-01-01

Variability in frequency of stuttering has made the results of treatment outcome studies difficult to interpret. Many factors that affect variability have been investigated; yet the typical range of variability experienced by speakers remains unknown. This study examined the day-to-day variability in the percentage of syllables containing stuttered and nonstuttered disfluencies in the speech of six adult speakers in three spontaneous speaking situations and two reading tasks. The frequency of moments stuttering during the tasks were compared within and between speakers and days to document the degree of variability in stuttering frequency and explore whether there were any consistent patterns. The Stuttering Severity Instrument-Fourth Edition (SSI-4) and Overall Assessment of the Speaker's Experience of Stuttering for Adults (OASES-A) were also tested for day-to-day variability. Correlations between frequency, severity, and life impact were made. The primary result of this study was the large range over which frequency of stuttering varied from day to day for the same individual. This variability did not correlate with any measures of stuttering severity but did correlate with life impact as measured by the OASES-A. No global pattern was detected in variability from day to day within or between participants. However, there were significantly more nonstuttered disfluencies present during the spontaneous speaking tasks than during the reading tasks. The day-to-day variability in the life impact of the disorder (OASES-A) was less than the day-to-day variability in observable stuttering behavior (percentage of syllables stuttered and SSI-4). Frequency of stuttering varies significantly from situation to situation and day to day, with observed variability exceeding the degree of change often reported in treatment outcomes studies from before to after treatment. This variability must be accounted for in future clinical and scientific work. Copyright © 2016 Elsevier Inc. All rights reserved.

X-linked retinitis pigmentosa: Report of a large kindred with loss of central vision and preserved peripheral function

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

Shastry, B.S.; Trese, M.T.

1995-11-20

X-linked retinitis pigmentosa (XLRP) is the most severe form of the inherited forms of retinitis pigmentosa and is clinically variable and genetically heterogeneous. It affects one in 20,000 live births. The affected individuals manifest degeneration of the peripheral retina during the first two decades of life on the basis of night blindness. Central vision usually is preserved until age 50, when the disease advances, affecting central vision and ultimately leading to complete loss of sight. Linkage analysis has shown two loci with a possibility of a third locus on the human X chromosome. The genetic abnormality that causes XLRP ismore » not known at present. Here we describe a large kindred which manifests central loss of field with the preservation of peripheral vision. 5 refs., 1 fig.« less

Predictive variables for the occurrence of early clinical mastitis in primiparous Holstein cows under field conditions in France.

PubMed Central

Barnouin, J; Chassagne, M

2001-01-01

Holstein heifers from 47 dairy herds in France were enrolled in a field study to determine predictors for clinical mastitis within the first month of lactation. Precalving and calving variables (biochemical, hematological, hygienic, and disease indicators) were collected. Early clinical mastitis (ECM) predictive variables were analyzed by using a multiple logistic regression model (99 cows with ECM vs. 571 without clinical mastitis throughout the first lactation). Two variables were associated with a higher risk of ECM: a) difficult calving and b) medium and high white blood cell (WBC) counts in late gestation. Two prepartum indicators were associated with a lower ECM risk: a) medium and high serum concentrations of immunoglobulin G1 (IgG1) and b) high percentage of eosinophils among white blood cells. Calving difficulty and certain biological blood parameters (IgG1, eosinophils) could represent predictors that would merit further experimental studies, with the aim of designing programs for reducing the risk of clinical mastitis in the first lactation. PMID:11195522

Recognizing and Reducing Analytical Errors and Sources of Variation in Clinical Pathology Data in Safety Assessment Studies.

PubMed

Schultze, A E; Irizarry, A R

2017-02-01

Veterinary clinical pathologists are well positioned via education and training to assist in investigations of unexpected results or increased variation in clinical pathology data. Errors in testing and unexpected variability in clinical pathology data are sometimes referred to as "laboratory errors." These alterations may occur in the preanalytical, analytical, or postanalytical phases of studies. Most of the errors or variability in clinical pathology data occur in the preanalytical or postanalytical phases. True analytical errors occur within the laboratory and are usually the result of operator or instrument error. Analytical errors are often ≤10% of all errors in diagnostic testing, and the frequency of these types of errors has decreased in the last decade. Analytical errors and increased data variability may result from instrument malfunctions, inability to follow proper procedures, undetected failures in quality control, sample misidentification, and/or test interference. This article (1) illustrates several different types of analytical errors and situations within laboratories that may result in increased variability in data, (2) provides recommendations regarding prevention of testing errors and techniques to control variation, and (3) provides a list of references that describe and advise how to deal with increased data variability.

The effects of clinical supervision on supervisees and patients in cognitive-behavioral therapy: a study protocol for a systematic review.

PubMed

Alfonsson, Sven; Spännargård, Åsa; Parling, Thomas; Andersson, Gerhard; Lundgren, Tobias

2017-05-11

Clinical supervision by a senior therapist is a very common practice in psychotherapist training and psychiatric care settings. Though clinical supervision is advocated by most educational and governing institutions, the effects of clinical supervision on the supervisees' competence, e.g., attitudes, behaviors, and skills, as well as on treatment outcomes and other patient variables are debated and largely unknown. Evidence-based practice is advocated in clinical settings but has not yet been fully implemented in educational or clinical training settings. The aim of this systematic review is to synthesize and present the empirical literature regarding effects of clinical supervision in cognitive-behavioral therapy. This study will include a systematic review of the literature to identify studies that have empirically investigated the effects of supervision on supervised psychotherapists and/or the supervisees' patients. A comprehensive search strategy will be conducted to identify published controlled studies indexed in the MEDLINE, EMBASE, PsycINFO, and Cochrane Library databases. Data on supervision outcomes in both psychotherapists and their patients will be extracted, synthesized, and reported. Risk of bias and quality of the included studies will be assessed systematically. This systematic review will rigorously follow established guidelines for systematic reviews in order to summarize and present the evidence base for clinical supervision in cognitive-behavioral therapy and may aid further research and discussion in this area. PROSPERO CRD42016046834.

Differences in clinical characteristics and disease-free survival for Latino, African American, and non-Latino white men with localized prostate cancer: data from CaPSURE.

PubMed

Latini, David M; Elkin, Eric P; Cooperberg, Matthew R; Sadetsky, Natalia; Duchane, Janeen; Carroll, Peter R

2006-02-15

Few studies of ethnicity and prostate cancer have included Latino men in analyses of baseline clinical characteristics, treatment selection, and disease-free survival (DFS). The present study examines the impact of Latino ethnicity on these parameters in a large, multiinstitutional database of men with prostate cancer. We compared baseline disease characteristics and clinical outcomes for Latino (N = 138), non-Latino White (NLW, N = 5619), and African-American (AA, N = 608) men with localized prostate cancer by using chi-square and ANOVA for baseline variables and survival analysis to examine differences in time to recurrence. Latino men resembled AA men more than NLW on sociodemographic characteristics. AA men had higher Gleason scores and prostate-specific antigen (PSA) at diagnosis than Latino or NLW men (both P < 0.01). 10% of both Latino and AA men presented with advanced disease (T3b/T4/N+/M+) versus 4% of NLW (P < 0.01). Latino men did not receive different treatments than NLW or AA men after controlling for clinical and demographic factors; however, AA men were more likely to receive external beam radiation (OR = 1.51, 95% confidence interval [CI] = 0.99-2.31) and hormone treatment (OR = 1.56, 95% CI = 1.05-2.32) then NLW men. For prostatectomy patients, 3-year actuarial DFS rates were 83% for NLW men and 86% for Latino men versus 69% for AA men (P < 0.01). After controlling for clinical and sociodemographic variables, AA men were somewhat more likely than NLW to experience disease recurrence after radical prostatectomy (RP) (HR = 1.38, 95% CI = 0.98-1.94, P = 0.06). Latinos are more similar to African Americans on sociodemographic characteristics but more similar to NLW on clinical presentation, treatments received, and DFS. Copyright 2006 American Cancer Society.

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

PubMed

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

2017-01-01

Suicidal behavior (SB) is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct. To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance. By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS) was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs) and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA. Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT), Interpersonal-change (IC), Self-renunciation (SR) and Self-sustenance (SS). These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC) were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively. The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part of the process leading to SB. These results provide a base for further research into clinical strategies for patient management and therapy.

Clinical characterization and treatment outcome of patients with burning mouth syndrome.

PubMed

Hakeem, Abdulaziz; Fitzpatrick, Sarah G; Bhattacharyya, Indraneel; Islam, Mohammed N; Cohen, Donald M

2018-01-01

Burning mouth syndrome (BMS) is a complex condition that affects the oral cavity, and data regarding effective treatment are limited. The purpose of this study was to explore the demographic and clinical information along with treatment outcomes for patients with BMS treated in a large referral center. Clinical records of the Oral Medicine Clinic at the University of Florida College of Dentistry were retrospectively searched for patients diagnosed between 2009 and 2014. Clinical data and treatment effectiveness were recorded. The records of 64 patients were included in this study. Women represented the majority of patients (81.2%), and the average age of all patients was 65 years. The most common systemic diseases were hypertension (59.4%), psycho-logical disorders (51.6%), and gastroesophageal reflux disease (50.0%). The majority of patients were taking 5 or more medications (70.3%). Treatment frequency and efficacy were as follows: a-lipoic acid, 47.5% frequency (57 prescribed treatments of 120 total treatments) and lasting improvement reported with 45.6% of prescribed treatments; clonazepam, 17.5% frequency (21/120) and improvement reported with 33.0% of prescribed treatments; oral disintegrating clonazepam, 15.8% frequency (19/120) and improvement reported with 52.6% of prescribed treatments; and topical vitamin E, 5.0% frequency (6/120) and improvement reported with 33.0% of prescribed treatments. Chi-square analysis indicated that a significantly better response to treatment was reported by women (P = 0.010) and patients who reported involvement limited to the tongue rather than multifocal oral involvement (P = 0.040); however, the significant relationships did not persist when the variables were evaluated together using logistic regression analysis. No other clinical or demographic features showed significant differences in response to treatment. Although treatment effectiveness in this study was variable and limited for some regimens due to infrequent usage, many of the patients reported alleviation of symptoms.

Evaluation of Automated and Semi-Automated Scoring of Polysomnographic Recordings from a Clinical Trial Using Zolpidem in the Treatment of Insomnia

PubMed Central

Svetnik, Vladimir; Ma, Junshui; Soper, Keith A.; Doran, Scott; Renger, John J.; Deacon, Steve; Koblan, Ken S.

2007-01-01

Objective: To evaluate the performance of 2 automated systems, Morpheus and Somnolyzer24X7, with various levels of human review/editing, in scoring polysomnographic (PSG) recordings from a clinical trial using zolpidem in a model of transient insomnia. Methods: 164 all-night PSG recordings from 82 subjects collected during 2 nights of sleep, one under placebo and one under zolpidem (10 mg) treatment were used. For each recording, 6 different methods were used to provide sleep stage scores based on Rechtschaffen & Kales criteria: 1) full manual scoring, 2) automated scoring by Morpheus 3) automated scoring by Somnolyzer24X7, 4) automated scoring by Morpheus with full manual review, 5) automated scoring by Morpheus with partial manual review, 6) automated scoring by Somnolyzer24X7 with partial manual review. Ten traditional clinical efficacy measures of sleep initiation, maintenance, and architecture were calculated. Results: Pair-wise epoch-by-epoch agreements between fully automated and manual scores were in the range of intersite manual scoring agreements reported in the literature (70%-72%). Pair-wise epoch-by-epoch agreements between automated scores manually reviewed were higher (73%-76%). The direction and statistical significance of treatment effect sizes using traditional efficacy endpoints were essentially the same whichever method was used. As the degree of manual review increased, the magnitude of the effect size approached those estimated with fully manual scoring. Conclusion: Automated or semi-automated sleep PSG scoring offers valuable alternatives to costly, time consuming, and intrasite and intersite variable manual scoring, especially in large multicenter clinical trials. Reduction in scoring variability may also reduce the sample size of a clinical trial. Citation: Svetnik V; Ma J; Soper KA; Doran S; Renger JJ; Deacon S; Koblan KS. Evaluation of automated and semi-automated scoring of polysomnographic recordings from a clinical trial using zolpidem in the treatment of insomnia. SLEEP 2007;30(11):1562-1574. PMID:18041489

A study to derive a clinical decision rule for triage of emergency department patients with chest pain: design and methodology

PubMed Central

Hess, Erik P; Wells, George A; Jaffe, Allan; Stiell, Ian G

2008-01-01

Background Chest pain is the second most common chief complaint in North American emergency departments. Data from the U.S. suggest that 2.1% of patients with acute myocardial infarction and 2.3% of patients with unstable angina are misdiagnosed, with slightly higher rates reported in a recent Canadian study (4.6% and 6.4%, respectively). Information obtained from the history, 12-lead ECG, and a single set of cardiac enzymes is unable to identify patients who are safe for early discharge with sufficient sensitivity. The 2007 ACC/AHA guidelines for UA/NSTEMI do not identify patients at low risk for adverse cardiac events who can be safely discharged without provocative testing. As a result large numbers of low risk patients are triaged to chest pain observation units and undergo provocative testing, at significant cost to the healthcare system. Clinical decision rules use clinical findings (history, physical exam, test results) to suggest a diagnostic or therapeutic course of action. Currently no methodologically robust clinical decision rule identifies patients safe for early discharge. Methods/design The goal of this study is to derive a clinical decision rule which will allow emergency physicians to accurately identify patients with chest pain who are safe for early discharge. The study will utilize a prospective cohort design. Standardized clinical variables will be collected on all patients at least 25 years of age complaining of chest pain prior to provocative testing. Variables strongly associated with the composite outcome acute myocardial infarction, revascularization, or death will be further analyzed with multivariable analysis to derive the clinical rule. Specific aims are to: i) apply standardized clinical assessments to patients with chest pain, incorporating results of early cardiac testing; ii) determine the inter-observer reliability of the clinical information; iii) determine the statistical association between the clinical findings and the composite outcome; and iv) use multivariable analysis to derive a highly sensitive clinical decision rule to guide triage decisions. Discussion The study will derive a highly sensitive clinical decision rule to identify low risk patients safe for early discharge. This will improve patient care, lower healthcare costs, and enhance flow in our busy and overcrowded emergency departments. PMID:18254973

Comparison of temporospatial and kinetic variables of walking in small and large dogs on a pressure-sensing walkway.

PubMed

Kim, Jongmin; Kazmierczak, Kris A; Breur, Gert J

2011-09-01

To compare temporospatial variables (TSVs) and kinetic variables (KVs) for fore-limbs and hind limbs of small and large dogs of various breeds during walking and to determine associations among body weight (BW), TSVs, and KVs in these groups. 12 adult dogs with no evidence of lameness. Dogs (grouped according to BW as small [< 10 kg; n = 6] or large [> 25 kg; 6]) were walked in a straight line at their preferred velocity on a wooden platform with an embedded pressure-sensing walkway. Five valid trials were analyzed for each dog; mean TSVs and KVs were determined for each group. The TSVs and KVs for forelimbs and hind limbs were compared between groups, and correlations among BW, TSVs, and KVs were determined. Small dogs had significantly smaller TSVs and KVs than did large dogs. Temporal variables of small dogs and absolute vertical force variables of small and large dogs increased as BW increased. However, normalized peak vertical force and weight distribution values among the 4 limbs were similar between groups. Substantial similarities and differences were detected in gait characteristics between small and large dogs. Results indicated TSVs and KVs can be used for comparison of the walking gait between dogs or for comparison of variables between limbs in an individual dog. Use of the pressure-sensing walkway is a simple method for acquisition of TSVs and KVs for large and small dogs.

Expanding the functionality of speech recognition in radiology: creating a real-time methodology for measurement and analysis of occupational stress and fatigue.

PubMed

Reiner, Bruce I

2013-02-01

While occupational stress and fatigue have been well described throughout medicine, the radiology community is particularly susceptible due to declining reimbursements, heightened demands for service deliverables, and increasing exam volume and complexity. The resulting occupational stress can be variable in nature and dependent upon a number of intrinsic and extrinsic stressors. Intrinsic stressors largely account for inter-radiologist stress variability and relate to unique attributes of the radiologist such as personality, emotional state, education/training, and experience. Extrinsic stressors may account for intra-radiologist stress variability and include cumulative workload and task complexity. The creation of personalized stress profiles creates a mechanism for accounting for both inter- and intra-radiologist stress variability, which is essential in creating customizable stress intervention strategies. One viable option for real-time occupational stress measurement is voice stress analysis, which can be directly implemented through existing speech recognition technology and has been proven to be effective in stress measurement and analysis outside of medicine. This technology operates by detecting stress in the acoustic properties of speech through a number of different variables including duration, glottis source factors, pitch distribution, spectral structure, and intensity. The correlation of these speech derived stress measures with outcomes data can be used to determine the user-specific inflection point at which stress becomes detrimental to clinical performance.

Clinical development of gene- and cell-based therapies: overview of the European landscape

PubMed Central

de Wilde, Sofieke; Guchelaar, Henk-Jan; Zandvliet, Maarten Laurens; Meij, Pauline

2016-01-01

In the last decade, many clinical trials with gene- and cell-based therapies were performed and increasing interest in the development was established by (national) authorities, academic developers, and commercial companies. However, until now only eight products have received marketing authorization (MA) approval. In this study, a comprehensive overview of the clinical development of gene- and cell-based therapies in Europe is presented, with a strong focus on product-technical aspects. Public data regarding clinical trials with gene- and cell-based therapies, obtained from the European Union (EU) clinical trial database (EudraCT) between 2004 and 2014 were analyzed, including product-technical variables as potential determinants affecting development. 198 unique gene and cell therapy products were identified, which were studied in 278 clinical trials, mostly in phase 1/2 trials and with cell therapies as major group. Furthermore, most products were manufactured from autologous starting material mostly manufactured from stem cells. The majority of the trials were sponsored by academia, whereas phase 3 trials mostly by large companies. Academia dominated early-stage development by mainly using bone marrow derived products and stem cells. Conversely, commercial sponsors were more actively pursuing in vivo gene therapy medicinal product development, and cell therapies derived from differentiated tissue in later-stage development. PMID:27990447

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

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.ed; Boike, Thomas P.

Clinical implementation of spinal radiosurgery has increased rapidly in recent years, but little is known regarding human spinal cord tolerance to single-fraction irradiation. In contrast, preclinical studies in single-fraction spinal cord tolerance have been ongoing since the 1970s. The influences of field length, dose rate, inhomogeneous dose distributions, and reirradiation have all been investigated. This review summarizes literature regarding single-fraction spinal cord tolerance in preclinical models with an emphasis on practical clinical significance. The outcomes of studies that incorporate uniform irradiation are surprisingly consistent among multiple small- and large-animal models. Extensive investigation of inhomogeneous dose distributions in the rat hasmore » demonstrated a significant dose-volume effect while preliminary results from one pig study are contradictory. Preclinical spinal cord dose-volume studies indicate that dose distribution is more critical than the volume irradiated suggesting that neither dose-volume histogram analysis nor absolute volume constraints are effective in predicting complications. Reirradiation data are sparse, but results from guinea pig, rat, and pig studies are consistent with the hypothesis that the spinal cord possesses a large capacity for repair. The mechanisms behind the phenomena observed in spinal cord studies are not readily explained and the ability of dose response models to predict outcomes is variable underscoring the need for further investigation. Animal studies provide insight into the phenomena and mechanisms of radiosensitivity but the true significance of animal studies can only be discovered through clinical trials.« less

Consistency of clinical biomechanical measures between three different institutions: implications for multi-center biomechanical and epidemiological research.

PubMed

Myer, Gregory D; Wordeman, Samuel C; Sugimoto, Dai; Bates, Nathaniel A; Roewer, Benjamin D; Medina McKeon, Jennifer M; DiCesare, Christopher A; Di Stasi, Stephanie L; Barber Foss, Kim D; Thomas, Staci M; Hewett, Timothy E

2014-05-01

Multi-center collaborations provide a powerful alternative to overcome the inherent limitations to single-center investigations. Specifically, multi-center projects can support large-scale prospective, longitudinal studies that investigate relatively uncommon outcomes, such as anterior cruciate ligament injury. This project was conceived to assess within- and between-center reliability of an affordable, clinical nomogram utilizing two-dimensional video methods to screen for risk of knee injury. The authors hypothesized that the two-dimensional screening methods would provide good-to-excellent reliability within and between institutions for assessment of frontal and sagittal plane biomechanics. Nineteen female, high school athletes participated. Two-dimensional video kinematics of the lower extremity during a drop vertical jump task were collected on all 19 study participants at each of the three facilities. Within-center and between-center reliability were assessed with intra- and inter-class correlation coefficients. Within-center reliability of the clinical nomogram variables was consistently excellent, but between-center reliability was fair-to-good. Within-center intra-class correlation coefficient for all nomogram variables combined was 0.98, while combined between-center inter-class correlation coefficient was 0.63. Injury risk screening protocols were reliable within and repeatable between centers. These results demonstrate the feasibility of multi-site biomechanical studies and establish a framework for further dissemination of injury risk screening algorithms. Specifically, multi-center studies may allow for further validation and optimization of two-dimensional video screening tools. 2b.

Patient adherence to prescribed antimicrobial drug dosing regimens.

PubMed

Vrijens, Bernard; Urquhart, John

2005-05-01

The aim of this article is to review current knowledge about the clinical impact of patients' variable adherence to prescribed anti-infective drug dosing regimens, with the aim of renewing interest and exploration of this important but largely neglected area of therapeutics. Central to the estimation of a patient's adherence to a prescribed drug regimen is a reliably compiled drug dosing history. Electronic monitoring methods have emerged as the virtual 'gold standard' for compiling drug dosing histories in ambulatory patients. Reliably compiled drug dosing histories are consistently downwardly skewed, with varying degrees of under-dosing. In particular, the consideration of time intervals between protease inhibitor doses has revealed that ambulatory patients' variable execution of prescribed dosing regimens is a leading source of variance in viral response. Such analyses reveal the need for a new discipline, called pharmionics, which is the study of how ambulatory patients use prescription drugs. Properly analysed, reliable data on the time-course of patients' actual intake of prescription drugs can eliminate a major source of unallocated variance in drug responses, including the non-response that occurs and is easily misinterpreted when a patient's complete non-execution of a prescribed drug regimen is unrecognized clinically. As such, reliable compilation of ambulatory patients' drug dosing histories has the promise of being a key step in reducing unallocated variance in drug response and in improving the informational yield of clinical trials. It is also the basis for sound, measurement-guided steps taken to improve a patient's execution of a prescribed dosing regimen.

Platelet-Rich Plasma Promotes Axon Regeneration, Wound Healing, and Pain Reduction: Fact or Fiction.

PubMed

Kuffler, Damien P

2015-10-01

Platelet-rich plasma (PRP) has been tested in vitro, in animal models, and clinically for its efficacy in enhancing the rate of wound healing, reducing pain associated with injuries, and promoting axon regeneration. Although extensive data indicate that PRP-released factors induce these effects, the claims are often weakened because many studies were not rigorous or controlled, the data were limited, and other studies yielded contrary results. Critical to assessing whether PRP is effective are the large number of variables in these studies, including the method of PRP preparation, which influences the composition of PRP; type of application; type of wounds; target tissues; and diverse animal models and clinical studies. All these variables raise the question of whether one can anticipate consistent influences and raise the possibility that most of the results are correct under the circumstances where PRP was tested. This review examines evidence on the potential influences of PRP and whether PRP-released factors could induce the reported influences and concludes that the preponderance of evidence suggests that PRP has the capacity to induce all the claimed influences, although this position cannot be definitively argued. Well-defined and rigorously controlled studies of the potential influences of PRP are required in which PRP is isolated and applied using consistent techniques, protocols, and models. Finally, it is concluded that, because of the purported benefits of PRP administration and the lack of adverse events, further animal and clinical studies should be performed to explore the potential influences of PRP.

A SYSTEMATIC SEARCH FOR COROTATING INTERACTION REGIONS IN APPARENTLY SINGLE GALACTIC WOLF-RAYET STARS. II. A GLOBAL VIEW OF THE WIND VARIABILITY

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

Chene, A.-N.; St-Louis, N., E-mail: achene@astro-udec.cl, E-mail: stlouis@astro.umontreal.ca

This study is the second part of a survey searching for large-scale spectroscopic variability in apparently single Wolf-Rayet (WR) stars. In a previous paper (Paper I), we described and characterized the spectroscopic variability level of 25 WR stars observable from the northern hemisphere and found 3 new candidates presenting large-scale wind variability, potentially originating from large-scale structures named corotating interaction regions (CIRs). In this second paper, we discuss an additional 39 stars observable from the southern hemisphere. For each star in our sample, we obtained 4-5 high-resolution spectra with a signal-to-noise ratio of {approx}100 and determined its variability level usingmore » the approach described in Paper I. In total, 10 new stars are found to show large-scale spectral variability of which 7 present CIR-type changes (WR 8, WR 44, WR55, WR 58, WR 61, WR 63, WR 100). Of the remaining stars, 20 were found to show small-amplitude changes and 9 were found to show no spectral variability as far as can be concluded from the data on hand. Also, we discuss the spectroscopic variability level of all single galactic WR stars that are brighter than v {approx} 12.5, and some WR stars with 12.5 < v {<=} 13.5, i.e., all the stars presented in our two papers and four more stars for which spectra have already been published in the literature. We find that 23/68 stars (33.8%) present large-scale variability, but only 12/54 stars ({approx}22.1%) are potentially of CIR type. Also, we find that 31/68 stars (45.6%) only show small-scale variability, most likely due to clumping in the wind. Finally, no spectral variability is detected based on the data on hand for 14/68 (20.6%) stars. Interestingly, the variability with the highest amplitude also has the widest mean velocity dispersion.« less

A new definition of pharmaceutical quality: assembly of a risk simulation platform to investigate the impact of manufacturing/product variability on clinical performance.

PubMed

Short, Steven M; Cogdill, Robert P; D'Amico, Frank; Drennen, James K; Anderson, Carl A

2010-12-01

The absence of a unanimous, industry-specific definition of quality is, to a certain degree, impeding the progress of ongoing efforts to "modernize" the pharmaceutical industry. This work was predicated on requests by Dr. Woodcock (FDA) to re-define pharmaceutical quality in terms of risk by linking production characteristics to clinical attributes. A risk simulation platform that integrates population statistics, drug delivery system characteristics, dosing guidelines, patient compliance estimates, production metrics, and pharmacokinetic, pharmacodynamic, and in vitro-in vivo correlation models to investigate the impact of manufacturing variability on clinical performance of a model extended-release theophylline solid oral dosage system was developed. Manufacturing was characterized by inter- and intra-batch content uniformity and dissolution variability metrics, while clinical performance was described by a probabilistic pharmacodynamic model that expressed the probability of inefficacy and toxicity as a function of plasma concentrations. Least-squares regression revealed that both patient compliance variables, percent of doses taken and dosing time variability, significantly impacted efficacy and toxicity. Additionally, intra-batch content uniformity variability elicited a significant change in risk scores for the two adverse events and, therefore, was identified as a critical quality attribute. The proposed methodology demonstrates that pharmaceutical quality can be recast to explicitly reflect clinical performance. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Measurement of Health Program Equity Made Easier: Validation of a Simplified Asset Index Using Program Data From Honduras and Senegal.

PubMed

Ergo, Alex; Ritter, Julie; Gwatkin, Davidson R; Binkin, Nancy

2016-03-01

Equitable access to programs and health services is essential to achieving national and international health goals, but it is rarely assessed because of perceived measurement challenges. One of these challenges concerns the complexities of collecting the data needed to construct asset or wealth indices, which can involve asking as many as 40 survey questions, many with multiple responses. To determine whether the number of variables and questions could be reduced to a level low enough for more routine inclusion in evaluations and research without compromising programmatic conclusions, we used data from a program evaluation in Honduras that compared a pro-poor intervention with government clinic performance as well as data from a results-based financing project in Senegal. In both, the full Demographic and Health Survey (DHS) asset questionnaires had been used as part of the evaluations. Using the full DHS results as the "gold standard," we examined the effect of retaining successively smaller numbers of variables on the classification of the program clients in wealth quintiles. Principal components analysis was used to identify those variables in each country that demonstrated minimal absolute factor loading values for 8 different thresholds, ranging from 0.05 to 0.70. Cohen's kappa statistic was used to assess correlation. We found that the 111 asset variables and 41 questions in the Honduras DHS could be reduced to 9 variables, captured by only 8 survey questions (kappa statistic, 0.634), without substantially altering the wealth quintile distributions for either the pro-poor program or the government clinics or changing the resulting policy conclusions. In Senegal, the 103 asset variables and 36 questions could be reduced to 32 variables and 20 questions (kappa statistic, 0.882) while maintaining a consistent mix of users in each of the 2 lowest quintiles. Less than 60% of the asset variables in the 2 countries' full DHS asset indices overlapped, and in none of the 8 simplified asset index iterations did this proportion exceed 50%. We conclude that substantially reducing the number of variables and questions used to assess equity is feasible, producing valid results and providing a less burdensome way for program implementers or researchers to evaluate whether their interventions are pro-poor. Developing a standardized, simplified asset questionnaire that could be used across countries may prove difficult, however, given that the variables that contribute the most to the asset index are largely country-specific. © Ergo et al.

Measurement of Health Program Equity Made Easier: Validation of a Simplified Asset Index Using Program Data From Honduras and Senegal

PubMed Central

Ergo, Alex; Ritter, Julie; Gwatkin, Davidson R; Binkin, Nancy

2016-01-01

ABSTRACT Equitable access to programs and health services is essential to achieving national and international health goals, but it is rarely assessed because of perceived measurement challenges. One of these challenges concerns the complexities of collecting the data needed to construct asset or wealth indices, which can involve asking as many as 40 survey questions, many with multiple responses. To determine whether the number of variables and questions could be reduced to a level low enough for more routine inclusion in evaluations and research without compromising programmatic conclusions, we used data from a program evaluation in Honduras that compared a pro-poor intervention with government clinic performance as well as data from a results-based financing project in Senegal. In both, the full Demographic and Health Survey (DHS) asset questionnaires had been used as part of the evaluations. Using the full DHS results as the “gold standard,” we examined the effect of retaining successively smaller numbers of variables on the classification of the program clients in wealth quintiles. Principal components analysis was used to identify those variables in each country that demonstrated minimal absolute factor loading values for 8 different thresholds, ranging from 0.05 to 0.70. Cohen’s kappa statistic was used to assess correlation. We found that the 111 asset variables and 41 questions in the Honduras DHS could be reduced to 9 variables, captured by only 8 survey questions (kappa statistic, 0.634), without substantially altering the wealth quintile distributions for either the pro-poor program or the government clinics or changing the resulting policy conclusions. In Senegal, the 103 asset variables and 36 questions could be reduced to 32 variables and 20 questions (kappa statistic, 0.882) while maintaining a consistent mix of users in each of the 2 lowest quintiles. Less than 60% of the asset variables in the 2 countries’ full DHS asset indices overlapped, and in none of the 8 simplified asset index iterations did this proportion exceed 50%. We conclude that substantially reducing the number of variables and questions used to assess equity is feasible, producing valid results and providing a less burdensome way for program implementers or researchers to evaluate whether their interventions are pro-poor. Developing a standardized, simplified asset questionnaire that could be used across countries may prove difficult, however, given that the variables that contribute the most to the asset index are largely country-specific. PMID:27016551

Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine.

PubMed

Stites, Edward C

2013-04-01

Traditional experimental biology has provided a mechanistic understanding of cancer in which the malignancy develops through the acquisition of mutations that disrupt cellular processes. Several drugs developed to target such mutations have now demonstrated clinical value. These advances are unequivocal testaments to the value of traditional cellular and molecular biology. However, several features of cancer may limit the pace of progress that can be made with established experimental approaches alone. The mutated genes (and resultant mutant proteins) function within large biochemical networks. Biochemical networks typically have a large number of component molecules and are characterized by a large number of quantitative properties. Responses to a stimulus or perturbation are typically nonlinear and can display qualitative changes that depend upon the specific values of variable system properties. Features such as these can complicate the interpretation of experimental data and the formulation of logical hypotheses that drive further research. Mathematical models based upon the molecular reactions that define these networks combined with computational studies have the potential to deal with these obstacles and to enable currently available information to be more completely utilized. Many of the pressing problems in cancer biology and cancer medicine may benefit from a mathematical treatment. As work in this area advances, one can envision a future where such models may meaningfully contribute to the clinical management of cancer patients.

Improving Translation from Preclinical Studies to Clinical Trials in Acute Kidney Injury.

PubMed

Fiorentino, Marco; Kellum, John A

2018-05-23

Several cellular and molecular targets and mechanisms have been investigated in preclinical studies of acute kidney injury (AKI), but translation in successful clinical studies has failed to date. This article reviews many issues that have limited this and the potential future perspectives in AKI prevention and treatment. Preclinical models of AKI should closely mimic the complexity of human AKI, considering the importance of several comorbidities in determining the clinical course and outcomes in the human disease. Moreover, studies should test novel interventions in models where AKI is already established, instead of focusing only at primary prevention. AKI definitions and endpoints in animal studies should be similar to those applied in clinical studies; in particular, AKI biomarkers should be implemented to guide patient selection for clinical trials and monitor intervention efficacy. In this scenario, cell-cycle arrest biomarkers have been widely investigated as AKI predictors in both preclinical and clinical studies and they serve as useful tools for future interventional studies. A better understanding of human AKI through a large collection of biological samples and kidney biopsies and omics applications, and an iterative relationship between preclinical and clinical studies are critical steps to improve future preclinical models and clinical trials. Finally, given the great variability in clinical manifestation of AKI, a strong collaboration between research centers and industry is recommended. Key messages: Several methodological issues have hampered the translation of basic research findings in clinical studies, and overcoming these obstacles is necessary to achieve success. © 2018 S. Karger AG, Basel.

Neuropsychological Test Selection for Cognitive Impairment Classification: A Machine Learning Approach

PubMed Central

Williams, Jennifer A.; Schmitter-Edgecombe, Maureen; Cook, Diane J.

2016-01-01

Introduction Reducing the amount of testing required to accurately detect cognitive impairment is clinically relevant. The aim of this research was to determine the fewest number of clinical measures required to accurately classify participants as healthy older adult, mild cognitive impairment (MCI) or dementia using a suite of classification techniques. Methods Two variable selection machine learning models (i.e., naive Bayes, decision tree), a logistic regression, and two participant datasets (i.e., clinical diagnosis, clinical dementia rating; CDR) were explored. Participants classified using clinical diagnosis criteria included 52 individuals with dementia, 97 with MCI, and 161 cognitively healthy older adults. Participants classified using CDR included 154 individuals CDR = 0, 93 individuals with CDR = 0.5, and 25 individuals with CDR = 1.0+. Twenty-seven demographic, psychological, and neuropsychological variables were available for variable selection. Results No significant difference was observed between naive Bayes, decision tree, and logistic regression models for classification of both clinical diagnosis and CDR datasets. Participant classification (70.0 – 99.1%), geometric mean (60.9 – 98.1%), sensitivity (44.2 – 100%), and specificity (52.7 – 100%) were generally satisfactory. Unsurprisingly, the MCI/CDR = 0.5 participant group was the most challenging to classify. Through variable selection only 2 – 9 variables were required for classification and varied between datasets in a clinically meaningful way. Conclusions The current study results reveal that machine learning techniques can accurately classifying cognitive impairment and reduce the number of measures required for diagnosis. PMID:26332171

Management of pericardial fluid in blunt trauma: variability in practice and predictors of operative outcome in patients with computed tomography evidence of pericardial fluid

PubMed Central

Witt, Cordelie E.; Linnau, Ken F.; Maier, Ronald V.; Rivara, Frederick P.; Vavilala, Monica S.; Bulger, Eileen M.; Arbabi, Saman

2017-01-01

Background The objectives of this study were to assess current variability in management preferences for blunt trauma patients with pericardial fluid, and to identify characteristics associated with operative intervention for patients with pericardial fluid on admission computed tomography (CT) scan. Methods This was a mixed-methods study of blunt trauma patients with pericardial fluid. The first portion was a research survey of members of the Eastern Association for the Surgery of Trauma conducted in 2016, in which surgeons were presented with four clinical scenarios of blunt trauma patients with pericardial fluid. The second portion of the study was a retrospective evaluation of all blunt trauma patients ≥14 years treated at our Level I trauma center between 1/1/2010 and 11/1/2015 with pericardial fluid on admission CT scan. Results For the survey portion of our study, 393 surgeons responded (27% response rate). There was significant variability in management preferences for scenarios depicting trace pericardial fluid on CT with concerning hemodynamics, and for scenarios depicting hemopericardium intraoperatively. For the separate retrospective portion of our study, we identified 75 blunt trauma patients with pericardial fluid on admission CT scan. Seven underwent operative management; six of these had hypotension and/or electrocardiogram changes. In multivariable analysis, pericardial fluid amount was a significant predictor of receiving pericardial window (relative risk for one category increase in pericardial fluid amount: 3.99, 95% CI 1.47-10.81) but not of mortality. Conclusions There is significant variability in management preferences for patients with pericardial fluid from blunt trauma, indicating a need for evidence-based research. Our institutional data suggest that patients with minimal to small amounts of pericardial fluid without concerning clinical findings may be observed. Patients with moderate to large amounts of pericardial fluid who are clinically stable with normal hemodynamics may also appear appropriate for observation, although confirmation in larger studies is needed. Patients with hemodynamic instability should undergo operative exploration. Level of Evidence Level IV, Therapeutic/Care Management PMID:28129264

Clinical periodontal variables in patients with and without dementia-a systematic review and meta-analysis.

PubMed

Maldonado, Alejandra; Laugisch, Oliver; Bürgin, Walter; Sculean, Anton; Eick, Sigrun

2018-06-22

Considering the increasing number of elderly people, dementia has gained an important role in today's society. Although the contributing factors for dementia have not been fully understood, chronic periodontitis (CP) seems to have a possible link to dementia. To conduct a systematic review including meta-analysis in order to assess potential differences in clinical periodontal variables between patients with dementia and non-demented individuals. The following focused question was evaluated: is periodontitis associated with dementia? Electronic searches in two databases, MEDLINE and EMBASE, were conducted. Meta-analysis was performed with the collected data in order to find a statistically significant difference in clinical periodontal variables between the group of dementia and the cognitive normal controls. Forty-two articles remained for full text reading. Finally, seven articles met the inclusion criteria and only five studies provided data suitable for meta-analysis. Periodontal probing depth (PPD), bleeding on probing (BOP), gingival bleeding index (GBI), clinical attachment level (CAL), and plaque index (PI) were included as periodontal variables in the meta-analysis. Each variable revealed a statistically significant difference between the groups. In an attempt to reveal an overall difference between the periodontal variables in dementia patients and non-demented individuals, the chosen variables were transformed into units that resulted in a statistically significant overall difference (p < 0.00001). The current findings indicate that compared to systemically healthy individuals, demented patients show significantly worse clinical periodontal variables. However, further epidemiological studies including a high numbers of participants, the use of exact definitions both for dementia and chronic periodontitis and adjusted for cofounders is warranted. These findings appear to support the putative link between CP and dementia. Consequently, the need for periodontal screening and treatment of elderly demented people should be emphasized.

Development and validation of a prognostic nomogram for colorectal cancer after radical resection based on individual patient data from three large-scale phase III trials

PubMed Central

Akiyoshi, Takashi; Maeda, Hiromichi; Kashiwabara, Kosuke; Kanda, Mitsuro; Mayanagi, Shuhei; Aoyama, Toru; Hamada, Chikuma; Sadahiro, Sotaro; Fukunaga, Yosuke; Ueno, Masashi; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

2017-01-01

Background Few prediction models have so far been developed and assessed for the prognosis of patients who undergo curative resection for colorectal cancer (CRC). Materials and Methods We prepared a clinical dataset including 5,530 patients who participated in three major randomized controlled trials as a training dataset and 2,263 consecutive patients who were treated at a cancer-specialized hospital as a validation dataset. All subjects underwent radical resection for CRC which was histologically diagnosed to be adenocarcinoma. The main outcomes that were predicted were the overall survival (OS) and disease free survival (DFS). The identification of the variables in this nomogram was based on a Cox regression analysis and the model performance was evaluated by Harrell's c-index. The calibration plot and its slope were also studied. For the external validation assessment, risk group stratification was employed. Results The multivariate Cox model identified variables; sex, age, pathological T and N factor, tumor location, size, lymphnode dissection, postoperative complications and adjuvant chemotherapy. The c-index was 0.72 (95% confidence interval [CI] 0.66-0.77) for the OS and 0.74 (95% CI 0.69-0.78) for the DFS. The proposed stratification in the risk groups demonstrated a significant distinction between the Kaplan–Meier curves for OS and DFS in the external validation dataset. Conclusions We established a clinically reliable nomogram to predict the OS and DFS in patients with CRC using large scale and reliable independent patient data from phase III randomized controlled trials. The external validity was also confirmed on the practical dataset. PMID:29228760

Normative accuracy and response time data for the computerized Benton Facial Recognition Test (BFRT-c).

PubMed

Rossion, Bruno; Michel, Caroline

2018-03-16

We report normative data from a large (N = 307) sample of young adult participants tested with a computerized version of the long form of the classical Benton Facial Recognition Test (BFRT; Benton & Van Allen, 1968). The BFRT-c requires participants to match a target face photograph to either one or three of six face photographs presented simultaneously. We found that the percent accuracy on the BFRT-c (81%-83%) was below ceiling yet well above chance level, with little interindividual variance in this typical population sample, two important aspects of a sensitive clinical test. Although the split-half reliability on response accuracy was relatively low, due to the large variability in difficulty across items, the correct response times measured in this version-completed in 3 min, on average-provide a reliable and critical complementary measure of performance at individual unfamiliar-face matching. In line with previous observations from other measures, females outperformed male participants at the BFRT-c, especially for female faces. In general, performance was also lower following lighting changes than following head rotations, in line with previous studies that have emphasized participants' limited ability to match pictures of unfamiliar faces with important variations in illumination. Overall, this normative data set supports the validity of the BFRT-c as a key component of a battery of tests to identify clinical impairments in individual face recognition, such as observed in acquired prosopagnosia. However, this analysis strongly recommends that researchers consider the full test results: Beyond global indexes of performance based on accuracy rates only, they should consider the time taken to match individual faces as well as the variability in performance across items.

Artificial Neural Networks for differential diagnosis of breast lesions in MR-Mammography: a systematic approach addressing the influence of network architecture on diagnostic performance using a large clinical database.

PubMed

Dietzel, Matthias; Baltzer, Pascal A T; Dietzel, Andreas; Zoubi, Ramy; Gröschel, Tobias; Burmeister, Hartmut P; Bogdan, Martin; Kaiser, Werner A

2012-07-01

Differential diagnosis of lesions in MR-Mammography (MRM) remains a complex task. The aim of this MRM study was to design and to test robustness of Artificial Neural Network architectures to predict malignancy using a large clinical database. For this IRB-approved investigation standardized protocols and study design were applied (T1w-FLASH; 0.1 mmol/kgBW Gd-DTPA; T2w-TSE; histological verification after MRM). All lesions were evaluated by two experienced (>500 MRM) radiologists in consensus. In every lesion, 18 previously published descriptors were assessed and documented in the database. An Artificial Neural Network (ANN) was developed to process this database (The-MathWorks/Inc., feed-forward-architecture/resilient back-propagation-algorithm). All 18 descriptors were set as input variables, whereas histological results (malignant vs. benign) was defined as classification variable. Initially, the ANN was optimized in terms of "Training Epochs" (TE), "Hidden Layers" (HL), "Learning Rate" (LR) and "Neurons" (N). Robustness of the ANN was addressed by repeated evaluation cycles (n: 9) with receiver operating characteristics (ROC) analysis of the results applying 4-fold Cross Validation. The best network architecture was identified comparing the corresponding Area under the ROC curve (AUC). Histopathology revealed 436 benign and 648 malignant lesions. Enhancing the level of complexity could not increase diagnostic accuracy of the network (P: n.s.). The optimized ANN architecture (TE: 20, HL: 1, N: 5, LR: 1.2) was accurate (mean-AUC 0.888; P: <0.001) and robust (CI: 0.885-0.892; range: 0.880-0.898). The optimized neural network showed robust performance and high diagnostic accuracy for prediction of malignancy on unknown data. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Validation of a Screening Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose in a US Commercial Health Plan Claims Database

PubMed Central

Zedler, Barbara K; Saunders, William B; Joyce, Andrew R; Vick, Catherine C; Murrelle, E Lenn

2018-01-01

Abstract Objective To validate a risk index that estimates the likelihood of overdose or serious opioid-induced respiratory depression (OIRD) among medical users of prescription opioids. Subjects and Methods A case-control analysis of 18,365,497 patients with an opioid prescription from 2009 to 2013 in the IMS PharMetrics Plus commercially insured health plan claims database (CIP). An OIRD event occurred in 7,234 cases. Four controls were selected per case. Validity of the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), developed previously using Veterans Health Administration (VHA) patient data, was assessed. Multivariable logistic regression was used within the CIP study population to develop a slightly refined RIOSORD. The composition and performance of the CIP-based RIOSORD was evaluated and compared with VHA-based RIOSORD. Results VHA-RIOSORD performed well in discriminating OIRD events in CIP (C-statistic = 0.85). Additionally, re-estimation of logistic model coefficients in CIP yielded a 0.90 C-statistic. The resulting comorbidity and pharmacotherapy variables most highly associated with OIRD and retained in the CIP-RIOSORD were largely concordant with VHA-RIOSORD. These variables included neuropsychiatric and cardiopulmonary disorders, impaired drug excretion, opioid characteristics, and concurrent psychoactive medications. The average predicted probability of OIRD ranged from 2% to 83%, with excellent agreement between predicted and observed incidence across risk classes. Conclusions RIOSORD had excellent predictive accuracy in a large population of US medical users of prescription opioids, similar to its performance in VHA. This practical risk index is designed to support clinical decision-making for safer opioid prescribing, and its clinical utility should be evaluated prospectively. PMID:28340046

Individual patient data meta-analysis of organ failure in acute pancreatitis: protocol of the PANCREA II study.

PubMed

Das, Stephanie L M; Papachristou, George I; De Campos, Tercio; Panek, Jozefa; Poves Prim, Ignasi; Serrablo, Alejandro; Parks, Rowan W; Uomo, Generoso; Windsor, John A; Petrov, Maxim S

2013-09-10

Organ failure is a major determinant of mortality in patients with acute pancreatitis. These patients usually require admission to high dependency or intensive care units and consume considerable health care resources. Given a low incidence rate of organ failure and a lack of large non-interventional studies in the field of acute pancreatitis, the characteristics of organ failure that influence outcomes of patients with acute pancreatitis remain largely unknown. Therefore, the Pancreatitis Across Nations Clinical Research and Education Alliance (PANCREA) aims to conduct a meta-analysis of individual patient data from prospective non-interventional studies to determine the influence of timing, duration, sequence, and combination of different organ failures on mortality in patients with acute pancreatitis. Pancreatologists currently active with acute pancreatitis clinical research will be invited to contribute. To be eligible for inclusion patients will have to meet the criteria of acute pancreatitis, develop at least one organ failure during the first week of hospitalization, and not be enrolled into an intervention study. Raw data will then be collated and checked. Individual patient data analysis based on a logistic regression model with adjustment for confounding variables will be done. For all analyses, corresponding 95% confidence intervals and P values will be reported. This collaborative individual patient data meta-analysis will answer important clinical questions regarding patients with acute pancreatitis that develop organ failure. Information derived from this study will be used to optimize routine clinical management and improve care strategies. It can also help validate outcome definitions, allow comparability of results and form a more accurate basis for patient allocation in further clinical studies.

Clinical features of pure obsessive-compulsive disorder.

PubMed

Torres, Albina R; Shavitt, Roseli G; Torresan, Ricardo C; Ferrão, Ygor A; Miguel, Euripedes C; Fontenelle, Leonardo F

2013-10-01

Psychiatric comorbidity is the rule in obsessive-compulsive disorder (OCD); however, very few studies have evaluated the clinical characteristics of patients with no co-occurring disorders (non-comorbid or "pure" OCD). The aim of this study was to estimate the prevalence of pure cases in a large multicenter sample of OCD patients and compare the sociodemographic and clinical characteristics of individuals with and without any lifetime axis I comorbidity. A cross-sectional study with 955 adult patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC). Assessment instruments included the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, The USP-Sensory Phenomena Scale and the Brown Assessment of Beliefs Scale. Comorbidities were evaluated using the Structured Clinical Interview for DSM-IV Axis I Disorders. Bivariate analyses were followed by logistic regression. Only 74 patients (7.7%) presented pure OCD. Compared with those presenting at least one lifetime comorbidity (881, 92.3%), non-comorbid patients were more likely to be female and to be working, reported less traumatic experiences and presented lower scores in the Y-BOCS obsession subscale and in total DY-BOCS scores. All symptom dimensions except contamination-cleaning and hoarding were less severe in non-comorbid patients. They also presented less severe depression and anxiety, lower suicidality and less previous treatments. In the logistic regression, the following variables predicted pure OCD: sex, severity of depressive and anxious symptoms, previous suicidal thoughts and psychotherapy. Pure OCD patients were the minority in this large sample and were characterized by female sex, less severe depressive and anxious symptoms, less suicidal thoughts and less use of psychotherapy as a treatment modality. The implications of these findings for clinical practice are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical characteristics of an Afrikaner founder population recruited for a schizophrenia genetic study.

PubMed

Roos, Johannes Lodewikus; Pretorius, Herman Walter; Karayiorgou, Maria

2009-01-01

The clinical characteristics of an Afrikaner founder population sample recruited for a schizophrenia genetic study are described. Comparisons on several clinical characteristics between this sample and a U.S. sample of schizophrenia patients show that generalization of findings in a founder population to the population at large is applicable. The assessment of the frequency of the 22q11 deletion in Afrikaner schizophrenia patients is approximately 2%, similar to findings in a U.S. sample. Results of analysis of early non-psychotic deviant behavior in subjects under the age of 10 years in the Afrikaner population broadly replicated findings in a U.S. sample. Approximately half of male schizophrenia patients and a quarter of female patients in the Afrikaner schizophrenia database used or abused cannabis. Male users of cannabis with severe early deviant behavior had the lowest mean age of criteria onset, namely 18.4 years. These findings confirm previous findings, indicating that early deviance is linked to later outcome of disease. The clinical characteristics and premorbid variables in 12 childhood-onset Afrikaner schizophrenia patients thus far recruited in this study compare favorably with what is known about childhood-onset schizophrenia in a U.S. sample. The prevalence of co-morbid OCD/OCS in this Afrikaner schizophrenia founder sample was 13.2% which is in keeping with that of co-morbid OCD in schizophrenia, estimated at 12.2% by the U.S. National Institute of Mental Health. These findings confirm that the clinical characteristics of a schizophrenia sample drawn from the Afrikaner founder population can be generalized to the schizophrenia population at large when compared to findings reported in the literature.

Simultaneous Quantification of Apolipoprotein A-I and Apolipoprotein B by Liquid-Chromatography–Multiple-Reaction–Monitoring Mass Spectrometry

PubMed Central

Agger, Sean A.; Marney, Luke C.; Hoofnagle, Andrew N.

2011-01-01

BACKGROUND If liquid-chromatography–multiple-reaction–monitoring mass spectrometry (LC-MRM/MS) could be used in the large-scale preclinical verification of putative biomarkers, it would obviate the need for the development of expensive immunoassays. In addition, the translation of novel biomarkers to clinical use would be accelerated if the assays used in preclinical studies were the same as those used in the clinical laboratory. To validate this approach, we developed a multiplexed assay for the quantification of 2 clinically well-known biomarkers in human plasma, apolipoprotein A-I and apolipoprotein B (apoA-I and apoB). METHODS We used PeptideAtlas to identify candidate peptides. Human samples were denatured with urea or trifluoroethanol, reduced and alkylated, and digested with trypsin. We compared reversed-phase chromatographic separation of peptides with normal flow and microflow, and we normalized endogenous peptide peak areas to internal standard peptides. We evaluated different methods of calibration and compared the final method with a nephelometric immunoassay. RESULTS We developed a final method using trifluoroethanol denaturation, 21-h digestion, normal flow chromatography-electrospray ionization, and calibration with a single normal human plasma sample. For samples injected in duplicate, the method had intraassay CVs <6% and interassay CVs <12% for both proteins, and compared well with immunoassay (n = 47; Deming regression, LC-MRM/MS = 1.17 × immunoassay – 36.6; Sx|y = 10.3 for apoA-I and LC-MRM/MS = 1.21 × immunoassay + 7.0; Sx|y = 7.9 for apoB). CONCLUSIONS Multiplexed quantification of proteins in human plasma/serum by LC-MRM/MS is possible and compares well with clinically useful immunoassays. The potential application of single-point calibration to large clinical studies could simplify efforts to reduce day-to-day digestion variability. PMID:20923952

Comparative genome analysis of a large Dutch Legionella pneumophila strain collection identifies five markers highly correlated with clinical strains

PubMed Central

2010-01-01

Background Discrimination between clinical and environmental strains within many bacterial species is currently underexplored. Genomic analyses have clearly shown the enormous variability in genome composition between different strains of a bacterial species. In this study we have used Legionella pneumophila, the causative agent of Legionnaire's disease, to search for genomic markers related to pathogenicity. During a large surveillance study in The Netherlands well-characterized patient-derived strains and environmental strains were collected. We have used a mixed-genome microarray to perform comparative-genome analysis of 257 strains from this collection. Results Microarray analysis indicated that 480 DNA markers (out of in total 3360 markers) showed clear variation in presence between individual strains and these were therefore selected for further analysis. Unsupervised statistical analysis of these markers showed the enormous genomic variation within the species but did not show any correlation with a pathogenic phenotype. We therefore used supervised statistical analysis to identify discriminating markers. Genetic programming was used both to identify predictive markers and to define their interrelationships. A model consisting of five markers was developed that together correctly predicted 100% of the clinical strains and 69% of the environmental strains. Conclusions A novel approach for identifying predictive markers enabling discrimination between clinical and environmental isolates of L. pneumophila is presented. Out of over 3000 possible markers, five were selected that together enabled correct prediction of all the clinical strains included in this study. This novel approach for identifying predictive markers can be applied to all bacterial species, allowing for better discrimination between strains well equipped to cause human disease and relatively harmless strains. PMID:20630115

The population-based Barcelona-Asymptomatic Intracranial Atherosclerosis Study (ASIA): rationale and design.

PubMed

López-Cancio, Elena; Dorado, Laura; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Massuet, Anna; Mataró, María; Galán, Amparo; Alzamora, Maite; Pera, Guillem; Torán, Pere; Dávalos, Antoni; Arenillas, Juan F

2011-02-17

Large-artery intracranial atherosclerosis may be the most frequent cause of ischemic stroke worldwide. Traditional approaches have attempted to target the disease when it is already symptomatic. However, early detection of intracranial atherosclerosis may allow therapeutic intervention while the disease is still asymptomatic. The prevalence and natural history of asymptomatic intracranial atherosclerosis in Caucasians remain unclear. The aims of the Barcelona-ASymptomatic Intracranial Atherosclerosis (ASIA) study are (1) to determine the prevalence of ASIA in a moderate-high vascular risk population, (2) to study its prognostic impact on the risk of suffering future major ischemic events, and (3) to identify predictors of the development, progression and clinical expression of this condition. Cross-over and cohort, population-based study. A randomly selected representative sample of 1,503 subjects with a mild-moderate-high vascular risk (as defined by a REGICOR score ≥ 5%) and with neither a history of cerebrovascular nor ischemic heart disease will be studied. At baseline, all individuals will undergo extracranial and transcranial Color-Coded Duplex (TCCD) ultrasound examinations to detect presence and severity of extra and intracranial atherosclerosis. Intracranial stenoses will be assessed by magnetic resonance angiography (MRA). Clinical and demographic variables will be recorded and blood samples will be drawn to investigate clinical, biological and genetic factors associated with the presence of ASIA. A long-term clinical and sonographic follow-up will be conducted thereafter to identify predictors of disease progression and of incident vascular events. The Barcelona-ASIA is a population-based study aiming to evaluate the prevalence and clinical importance of asymptomatic intracranial large-artery atherosclerosis in Caucasians. The ASIA project may provide a unique scientific resource to better understand the dynamics of intracranial atherosclerosis from its early stages and to identify new potential therapeutic targets for this condition.

Use of complementary and alternative medicine in an urban county hospital epilepsy clinic.

PubMed

McConnell, B V; Applegate, M; Keniston, A; Kluger, B; Maa, E H

2014-05-01

We examined self-reported complementary and alternative medicine (CAM) use among a largely indigent population with epilepsy. Overall CAM use was 70%, with the most frequently reported complementary and alternative medicines (CAMs) being medical marijuana (33%), prayer/spirituality (31%), meditation (19%), vitamins (19%), and stress management (16%). Forty-four percent of patients reported improved seizure control with CAMs. Stress management accounted for perceived seizure reduction in 74%, followed by marijuana (54%), prayer (49%), and yoga (42%). Among the most commonly used and helpful CAMs, stress management was not associated with specific demographic or clinical variables; marijuana use was significantly associated with lower age (users=35.2±10 years vs. nonusers=41.6±12; p<0.01) and lower income (under $15,000 40% use vs. 14% over $15,000; p<0.05); and prayer was significantly associated with female gender (male=21% vs. female=45%; p<0.01) and Black ethnicity (Black=55% vs. Hispanic=30% vs. White=23%; p<0.05). Taken together, our study was notable for the high rate of CAM utilization in a largely indigent population, with high rates of perceived efficacy among several CAM modalities. Copyright © 2014 Elsevier Inc. All rights reserved.

A recurrent 16p12.1 microdeletion suggests a two-hit model for severe developmental delay

PubMed Central

Girirajan, Santhosh; Rosenfeld, Jill A.; Cooper, Gregory M.; Antonacci, Francesca; Siswara, Priscillia; Itsara, Andy; Vives, Laura; Walsh, Tom; McCarthy, Shane E.; Baker, Carl; Mefford, Heather C.; Kidd, Jeffrey M.; Browning, Sharon R.; Browning, Brian L.; Dickel, Diane E.; Levy, Deborah L.; Ballif, Blake C.; Platky, Kathryn; Farber, Darren M.; Gowans, Gordon C.; Wetherbee, Jessica J.; Asamoah, Alexander; Weaver, David D.; Mark, Paul R.; Dickerson, Jennifer; Garg, Bhuwan P.; Ellingwood, Sara A.; Smith, Rosemarie; Banks, Valerie C.; Smith, Wendy; McDonald, Marie T.; Hoo, Joe J.; French, Beatrice N.; Hudson, Cindy; Johnson, John P.; Ozmore, Jillian R.; Moeschler, John B.; Surti, Urvashi; Escobar, Luis F.; El-Kechen, Dima; Gorski, Jerome L.; Kussman, Jennifer; Salbert, Bonnie; Lacassie, Yves; Biser, Alisha; McDonald-McGinn, Donna M.; Zackai, Elaine H.; Deardorff, Matthew A.; Shaikh, Tamim H.; Haan, Eric; Friend, Kathryn L.; Fichera, Marco; Romano, Corrado; Gécz, Jozef; deLisi, Lynn E.; Sebat, Jonathan; King, Mary-Claire; Shaffer, Lisa G.; Eichler, Evan E.

2010-01-01

We report the identification of a recurrent 520-kbp 16p12.1 microdeletion significantly associated with childhood developmental delay. The microdeletion was detected in 20/11,873 cases vs. 2/8,540 controls (p=0.0009, OR=7.2) and replicated in a second series of 22/9,254 cases vs. 6/6,299 controls (p=0.028, OR=2.5). Most deletions were inherited with carrier parents likely to manifest neuropsychiatric phenotypes (p=0.037, OR=6). Probands were more likely to carry an additional large CNV when compared to matched controls (10/42 cases, p=5.7×10-5, OR=6.65). Clinical features of cases with two mutations were distinct from and/or more severe than clinical features of patients carrying only the co-occurring mutation. Our data suggest a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity suggests that this two-hit model may be more generally applicable to neuropsychiatric disease. PMID:20154674

ERPs and Psychopathology. I. Behavioral process issues.

PubMed

Roth, W T; Tecce, J J; Pfefferbaum, A; Rosenbloom, M; Callaway, E

1984-01-01

The clinical study of ERPs has an inherent defect--a self-selection of clinical populations that hampers equating of clinically defined groups on factors extraneous to the independent variables. Such ex post facto studies increase the likelihood of confounding variables in the interpretation of findings. Hence, the development of lawful relationships between clinical variables and ERPs is impeded and the fulfillment of description, explanation, prediction, and control in brain science is thwarted. Proper methodologies and theory development can increase the likelihood of establishing these lawful relationships. One methodology of potential value in the clinical application of ERPs, particularly in studies of aging, is that of divided attention. Two promising theoretical developments in the understanding of brain functioning and aging are the distraction-arousal hypothesis and the controlled-automatic attention model. The evaluation of ERPs in the study of brain-behavior relations in clinical populations might be facilitated by the differentiation of concurrent, predictive, content, and construct validities.

Job satisfaction and work related variables in Chinese cardiac critical care nurses.

PubMed

Liu, Yun-E; While, Alison; Li, Shu-Jun; Ye, Wen-Qin

2015-05-01

To explore critical care nurses' views of their job satisfaction and the relationship with job burnout, practice environment, coping style, social support, intention to stay in current employment and other work-related variables. Nurse shortage is a global issue, especially in critical care. Job satisfaction is the most frequently cited factor linked to nurses' turnover. A convenience sample of cardiac critical care nurses (n = 215; 97.7% response rate) from 12 large general hospitals in Shanghai was surveyed from December 2010 to March 2011. Over half of the sample reported satisfaction with their jobs. Nurses with 10-20 years of professional experience and those who had taken all their holiday entitlement reported higher levels of job satisfaction. The independent variables of practice environment, intention to stay, emotional exhaustion, personal accomplishment and positive coping style explained about 55% of the variance in job satisfaction. Chinese cardiac critical care nurses' job satisfaction was related to work related variables, which are amenable to managerial action. Our findings highlight the imperative of improving intrinsic and extrinsic rewards, together with the flexibility of work schedules to promote job satisfaction and staff retention. A clinical ladder system is needed to provide promotion opportunities for Chinese nurses. © 2013 John Wiley & Sons Ltd.

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

PubMed Central

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

2017-01-01

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

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.

Opportunities and challenges in developing risk prediction models with electronic health records data: a systematic review.

PubMed

Goldstein, Benjamin A; Navar, Ann Marie; Pencina, Michael J; Ioannidis, John P A

2017-01-01

Electronic health records (EHRs) are an increasingly common data source for clinical risk prediction, presenting both unique analytic opportunities and challenges. We sought to evaluate the current state of EHR based risk prediction modeling through a systematic review of clinical prediction studies using EHR data. We searched PubMed for articles that reported on the use of an EHR to develop a risk prediction model from 2009 to 2014. Articles were extracted by two reviewers, and we abstracted information on study design, use of EHR data, model building, and performance from each publication and supplementary documentation. We identified 107 articles from 15 different countries. Studies were generally very large (median sample size = 26 100) and utilized a diverse array of predictors. Most used validation techniques (n = 94 of 107) and reported model coefficients for reproducibility (n = 83). However, studies did not fully leverage the breadth of EHR data, as they uncommonly used longitudinal information (n = 37) and employed relatively few predictor variables (median = 27 variables). Less than half of the studies were multicenter (n = 50) and only 26 performed validation across sites. Many studies did not fully address biases of EHR data such as missing data or loss to follow-up. Average c-statistics for different outcomes were: mortality (0.84), clinical prediction (0.83), hospitalization (0.71), and service utilization (0.71). EHR data present both opportunities and challenges for clinical risk prediction. There is room for improvement in designing such studies. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of Intensive Oral Hygiene Regimen During Pregnancy on Periodontal Health, Cytokine Levels, and Pregnancy Outcomes: A Pilot Study

PubMed Central

Kaur, Maninder; Geisinger, Maria L.; Geurs, Nicolaas C.; Griffin, Russell; Vassilopoulos, Philip J.; Vermeulen, Lisa; Haigh, Sandra; Reddy, Michael S.

2015-01-01

Background Data are limited on the potential effect of intensive oral hygiene regimens and periodontal therapy during pregnancy on periodontal health, gingival crevicular fluid (GCF) and serum cytokines, and pregnancy outcomes. Methods A clinical trial was conducted on 120 community-dwelling, 16- to 35-year-old pregnant women at 16 to 24 weeks of gestation. Each participant presented with clinical evidence of generalized, moderate-to-severe gingivitis. Oral hygiene products were provided, together with instructions for an intensive daily regimen of hygiene practices. Non-surgical therapy was provided at baseline. Oral examinations were completed at baseline and again at 4 and 8 weeks. In addition, samples of blood and GCF were collected at baseline and week 8. Mean changes in clinical variables and GCF and serum cytokine levels (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α) between baseline and week 8 were calculated using paired t test. Pregnancy outcomes were recorded at parturition. Results Results indicated a statistically significant reduction in all clinical variables (P <0.0001) and decreased levels of TNF-α (P = 0.0076) and IL-1β (P = 0.0098) in GCF during the study period. The rate of preterm births (<37 weeks of gestation) was 6.7% (P = 0.113) and low birth weight (<2,500 g) was 10.2% (P = 1.00). Conclusions Among the population studied, intensive instructions and non-surgical periodontal therapy provided during 8 weeks at early pregnancy resulted in decreased gingival inflammation and a generalized improvement in periodontal health. Large-scale, randomized, controlled studies are needed to substantiate these findings. PMID:25079400

Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans.

PubMed

Tuijnenburg, Paul; Lango Allen, Hana; Burns, Siobhan O; Greene, Daniel; Jansen, Machiel H; Staples, Emily; Stephens, Jonathan; Carss, Keren J; Biasci, Daniele; Baxendale, Helen; Thomas, Moira; Chandra, Anita; Kiani-Alikhan, Sorena; Longhurst, Hilary J; Seneviratne, Suranjith L; Oksenhendler, Eric; Simeoni, Ilenia; de Bree, Godelieve J; Tool, Anton T J; van Leeuwen, Ester M M; Ebberink, Eduard H T M; Meijer, Alexander B; Tuna, Salih; Whitehorn, Deborah; Brown, Matthew; Turro, Ernest; Thrasher, Adrian J; Smith, Kenneth G C; Thaventhiran, James E; Kuijpers, Taco W

2018-03-02

The genetic cause of primary immunodeficiency disease (PID) carries prognostic information. We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource-Rare Diseases cohort. In the predominantly European study population of principally sporadic unrelated PID cases (n = 846), a novel Bayesian method identified nuclear factor κB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n = 390) in the cohort. Amino acid substitutions predicted to be pathogenic were assessed by means of analysis of structural protein data. Immunophenotyping, immunoblotting, and ex vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype cosegregation analyses. Both sporadic and familial cases demonstrated evidence of the noninfective complications of CVID, including massive lymphadenopathy (24%), unexplained splenomegaly (48%), and autoimmune disease (48%), features prior studies correlated with worse clinical prognosis. Although partial penetrance of clinical symptoms was noted in certain pedigrees, all carriers have a deficiency in B-lymphocyte differentiation. Detailed assessment of B-lymphocyte numbers, phenotype, and function identifies the presence of an increased CD21 low B-cell population. Combined with identification of the disease-causing variant, this distinguishes between healthy subjects, asymptomatic carriers, and clinically affected cases. We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Minimal clinically important difference and the effect of clinical variables on the ankle osteoarthritis scale in surgically treated end-stage ankle arthritis.

PubMed

Coe, Marcus P; Sutherland, Jason M; Penner, Murray J; Younger, Alastair; Wing, Kevin J

2015-05-20

There is much debate regarding the best outcome tool for use in foot and ankle surgery, specifically in patients with ankle arthritis. The Ankle Osteoarthritis Scale (AOS) is a validated, disease-specific score. The goals of this study were to investigate the clinical performance of the AOS and to determine a minimal clinically important difference (MCID) for it, using a large cohort of 238 patients undergoing surgery for end-stage ankle arthritis. Patients treated with total ankle arthroplasty or ankle arthrodesis were prospectively followed for a minimum of two years at a single site. Data on demographics, comorbidities, AOS score, Short Form-36 results, and the relationship between expectations and satisfaction were collected at baseline (preoperatively), at six and twelve months, and then yearly thereafter. A linear regression analysis examined the variables affecting the change in AOS scores between baseline and the two-year follow-up. An MCID in the AOS change score was then determined by employing an anchor question, which asked patients to rate their relief from symptoms after surgery. Surgical treatment of end-stage ankle arthritis resulted in a mean improvement (and standard deviation) of 31.2 ± 22.7 points in the AOS score two years after surgery. The MCID of the AOS change score was a mean of 28.0 ± 17.9 points. The change in AOS score was significantly affected by the preoperative AOS score, smoking, back pain, and age. Patients undergoing arthroplasty or arthrodesis for end-stage ankle arthritis experienced a mean improvement in AOS score that was greater than the estimated MCID (31.2 versus 28.0 points). Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Official Positions for FRAX® clinical regarding rheumatoid arthritis from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

PubMed

Broy, Susan B; Tanner, S Bobo

2011-01-01

Rheumatoid arthritis is the only secondary cause of osteoporosis that is considered independent of bone density in the FRAX(®) algorithm. Although input for rheumatoid arthritis in FRAX(®) is a dichotomous variable, intuitively, one would expect that more severe or active disease would be associated with a greater risk for fracture. We reviewed the literature to determine if specific disease parameters or medication use could be used to better characterize fracture risk in individuals with rheumatoid arthritis. Although many studies document a correlation between various parameters of disease activity or severity and decreased bone density, fewer have associated these variables with fracture risk. We reviewed these studies in detail and concluded that disability measures such as HAQ (Health Assessment Questionnaire) and functional class do correlate with clinical fractures but not morphometric vertebral fractures. One large study found a strong correlation with duration of disease and fracture risk but additional studies are needed to confirm this. There was little evidence to correlate other measures of disease such as DAS (disease activity score), VAS (visual analogue scale), acute phase reactants, use of non-glucocorticoid medications and increased fracture risk. We concluded that FRAX(®) calculations may underestimate fracture probability in patients with impaired functional status from rheumatoid arthritis but that this could not be quantified at this time. At this time, other disease measures cannot be used for fracture prediction. However only a few, mostly small studies addressed other disease parameters and further research is needed. Additional questions for future research are suggested. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Hematologic and biochemical variables of hedgehogs (Erinaceus europaeus) after overwintering in rehabilitation centers.

PubMed

Rossi, Gabriele; Mangiagalli, Gerard; Paracchini, Giulia; Paltrinieri, Saverio

2014-03-01

Information about laboratory reference intervals (RIs) of European Hedgehog (Erinaceus europaeus) hospitalized at rehabilitation centers is scarce. The purpose of this study was to establish hematologic and biochemical RIs for rehabilitated hedgehogs before the release into the wild, and to assess whether sex and management of the center influence laboratory results. Blood was collected from 50 hedgehogs at 3 centers. Thirty-eight animals were included in the study based on normal body weight, absence of clinical signs of disease, Bunnell index > 0.80, and absence of hibernation during overwintering. CBCs were performed using an automated laser cell counter followed by morphologic analysis of blood smears. Clinical biochemistry was performed using an automated spectrophotometer. RIs were determined as recommended by the ASVCP guidelines. Hematology profiles revealed a prevalence of lymphocytes, a constant presence of nucleated RBCs, Howell-Jolly bodies and basophils, and bilobed nuclei in neutrophils and eosinophils. Biochemistry profiles were characterized by higher creatinine and urea concentrations, and higher ALP and GGT activities compared with other domestic species. The sex did not influence the results. Conversely, numbers of eosinophils, activated and large granular lymphocytes, and concentrations of total protein, glucose and cholesterol were different among the centers, likely due to different management practices (eg, antiparasitic treatments, environmental exposure to microorganisms, diet). The RIs established in this study can be used to monitor the health status of hedgehogs in rehabilitation centers. As management practices appeared to influence some variables, it is recommended to standardize the management protocols to minimize their influence on laboratory data. © 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.

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.

Within-subject template estimation for unbiased longitudinal image analysis.

PubMed

Reuter, Martin; Schmansky, Nicholas J; Rosas, H Diana; Fischl, Bruce

2012-07-16

Longitudinal image analysis has become increasingly important in clinical studies of normal aging and neurodegenerative disorders. Furthermore, there is a growing appreciation of the potential utility of longitudinally acquired structural images and reliable image processing to evaluate disease modifying therapies. Challenges have been related to the variability that is inherent in the available cross-sectional processing tools, to the introduction of bias in longitudinal processing and to potential over-regularization. In this paper we introduce a novel longitudinal image processing framework, based on unbiased, robust, within-subject template creation, for automatic surface reconstruction and segmentation of brain MRI of arbitrarily many time points. We demonstrate that it is essential to treat all input images exactly the same as removing only interpolation asymmetries is not sufficient to remove processing bias. We successfully reduce variability and avoid over-regularization by initializing the processing in each time point with common information from the subject template. The presented results show a significant increase in precision and discrimination power while preserving the ability to detect large anatomical deviations; as such they hold great potential in clinical applications, e.g. allowing for smaller sample sizes or shorter trials to establish disease specific biomarkers or to quantify drug effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of Subjective Refraction under Binocular and Monocular Conditions in Myopic Subjects.

PubMed

Kobashi, Hidenaga; Kamiya, Kazutaka; Handa, Tomoya; Ando, Wakako; Kawamorita, Takushi; Igarashi, Akihito; Shimizu, Kimiya

2015-07-28

To compare subjective refraction under binocular and monocular conditions, and to investigate the clinical factors affecting the difference in spherical refraction between the two conditions. We examined thirty eyes of 30 healthy subjects. Binocular and monocular refraction without cycloplegia was measured through circular polarizing lenses in both eyes, using the Landolt-C chart of the 3D visual function trainer-ORTe. Stepwise multiple regression analysis was used to assess the relations among several pairs of variables and the difference in spherical refraction in binocular and monocular conditions. Subjective spherical refraction in the monocular condition was significantly more myopic than that in the binocular condition (p < 0.001), whereas no significant differences were seen in subjective cylindrical refraction (p = 0.99). The explanatory variable relevant to the difference in spherical refraction between binocular and monocular conditions was the binocular spherical refraction (p = 0.032, partial regression coefficient B = 0.029) (adjusted R(2) = 0.230). No significant correlation was seen with other clinical factors. Subjective spherical refraction in the monocular condition was significantly more myopic than that in the binocular condition. Eyes with higher degrees of myopia are more predisposed to show the large difference in spherical refraction between these two conditions.

Comparison of Subjective Refraction under Binocular and Monocular Conditions in Myopic Subjects

PubMed Central

Kobashi, Hidenaga; Kamiya, Kazutaka; Handa, Tomoya; Ando, Wakako; Kawamorita, Takushi; Igarashi, Akihito; Shimizu, Kimiya

2015-01-01

To compare subjective refraction under binocular and monocular conditions, and to investigate the clinical factors affecting the difference in spherical refraction between the two conditions. We examined thirty eyes of 30 healthy subjects. Binocular and monocular refraction without cycloplegia was measured through circular polarizing lenses in both eyes, using the Landolt-C chart of the 3D visual function trainer-ORTe. Stepwise multiple regression analysis was used to assess the relations among several pairs of variables and the difference in spherical refraction in binocular and monocular conditions. Subjective spherical refraction in the monocular condition was significantly more myopic than that in the binocular condition (p < 0.001), whereas no significant differences were seen in subjective cylindrical refraction (p = 0.99). The explanatory variable relevant to the difference in spherical refraction between binocular and monocular conditions was the binocular spherical refraction (p = 0.032, partial regression coefficient B = 0.029) (adjusted R2 = 0.230). No significant correlation was seen with other clinical factors. Subjective spherical refraction in the monocular condition was significantly more myopic than that in the binocular condition. Eyes with higher degrees of myopia are more predisposed to show the large difference in spherical refraction between these two conditions. PMID:26218972

Belonging and doing: important factors for satisfaction with sexual relations as perceived by people with persistent mental illness.

PubMed

Eklund, Mona; Ostman, Margareta

2010-07-01

It is increasingly acknowledged that satisfaction with sexual relations forms an important aspect of people's lives, but little is known of factors associated with this phenomenon among people with mental illness. This study aimed to investigate how demographic, social, clinical, and health-related factors were related to satisfaction with sexual relations. Patients with persistent mental illness (N = 103), recruited from an outpatient unit, were assessed regarding the target variables. No clinical variable, and only one demographic factor, namely being a cohabitant, was found to be important to satisfaction with sexual relations. Several social factors, pertaining to how everyday occupations were valued and how the social network was perceived, were shown to be of importance. General quality of life, but not self-rated health or interviewer-assessed psychopathology, was also important for satisfaction with sexual relations. A multivariate analysis showed that the most significant factor for satisfaction with sexual relations was how everyday activities were valued, and being a cohabitant explained some additional variation. Previous research indicates that the mental health care services largely neglect sexual problems among people with mental illness, and the findings may provide additional knowledge that may be used in the support of this target group.

hs-CRP is strongly associated with coronary heart disease (CHD): A data mining approach using decision tree algorithm.

PubMed

Tayefi, Maryam; Tajfard, Mohammad; Saffar, Sara; Hanachi, Parichehr; Amirabadizadeh, Ali Reza; Esmaeily, Habibollah; Taghipour, Ali; Ferns, Gordon A; Moohebati, Mohsen; Ghayour-Mobarhan, Majid

2017-04-01

Coronary heart disease (CHD) is an important public health problem globally. Algorithms incorporating the assessment of clinical biomarkers together with several established traditional risk factors can help clinicians to predict CHD and support clinical decision making with respect to interventions. Decision tree (DT) is a data mining model for extracting hidden knowledge from large databases. We aimed to establish a predictive model for coronary heart disease using a decision tree algorithm. Here we used a dataset of 2346 individuals including 1159 healthy participants and 1187 participant who had undergone coronary angiography (405 participants with negative angiography and 782 participants with positive angiography). We entered 10 variables of a total 12 variables into the DT algorithm (including age, sex, FBG, TG, hs-CRP, TC, HDL, LDL, SBP and DBP). Our model could identify the associated risk factors of CHD with sensitivity, specificity, accuracy of 96%, 87%, 94% and respectively. Serum hs-CRP levels was at top of the tree in our model, following by FBG, gender and age. Our model appears to be an accurate, specific and sensitive model for identifying the presence of CHD, but will require validation in prospective studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Pelvic-floor strength in women with incontinence as assessed by the brink scale.

PubMed

FitzGerald, Mary P; Burgio, Kathryn L; Borello-France, Diane F; Menefee, Shawn A; Schaffer, Joseph; Kraus, Stephen; Mallett, Veronica T; Xu, Yan

2007-10-01

The purpose of this study was to describe how clinical pelvic-floor muscle (PFM) strength (force-generating capacity) is related to patient characteristics, lower urinary tract symptoms, and fecal incontinence symptoms. Data were obtained from 643 women who were participating in a randomized surgical trial for treatment of stress urinary incontinence. Patient demographic variables, baseline urinary and fecal incontinence symptom questionnaires, urodynamic data and urinary diary data, pad test results, and standardized assessment of pelvic organ support were compared with PFM strength as described by the Brink scoring system. Bivariate analysis of factors associated with the Brink scale score was done using analysis of variance and linear regression. Multivariate analysis included patient variables that were significant on bivariate analysis. The mean Brink scale score was 9 (SD=2) and did not vary widely in this large, but highly select, patient sample. We found a weak, but statistically strong, relationship between age and Brink score. Brink scores were not related to diary and pad test measures of incontinence severity. Overall, PFM strength was good in this sample of women with stress incontinence. Scores tended to be similar, and it is possible that the Brink scale does not reflect real clinical differences in PFM strength.

Generic OCs bioequivalent, but much maligned.

PubMed

1989-06-01

Although generic oral contraceptives (OCs) are bioequivalent to brand-name formulations, many family planning professionals do not prescribe the significantly lower-priced generics. The Planned Parenthood Federation of America, for example, has refused to approve generic OCs for use in the organization's clinics, presumably because of concerns about their equivalent efficacy and safety. However, much of this skepticism may be fueled by misleading marketing by brand-name OC manufacturers. Sales representatives have reportedly told clinicians that generic OCs can be as much as 20% different from brand-name formulations, despite evidence collected by the US Food and Drug Administration confirming that there is virtually no difference except in terms of inert ingredients. In the case of many formulations, the variability between the generic and brand-name products is no different than the variability found between different lots of the same brand-name drug. Another obstacle to wider use of generic OCs is that discounts for large volume purchases make brand-name OCs the best buy for family planning clinics. Clinicians also note that clients complain of minor side effects whenever OC brands are changed, even if the compounds are the same. As the price of medication continues to rise, the more widespread availability of generic OCs will be especially important for teenagers and other low-income clients.

Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader-Willi syndrome.

PubMed

Muscatelli, F; Abrous, D N; Massacrier, A; Boccaccio, I; Le Moal, M; Cau, P; Cremer, H

2000-12-12

Prader-Willi syndrome (PWS) is a complex neurogenetic disorder with considerable clinical variability that is thought in large part to be the result of a hypothalamic defect. PWS results from the absence of paternal expression of imprinted genes localized in the 15q11-q13 region; however, none of the characterized genes has so far been shown to be involved in the etiology of PWS. Here, we provide a detailed investigation of a mouse model deficient for NECDIN: Linked to the mutation, a neonatal lethality of variable penetrance is observed. Viable NECDIN: mutants show a reduction in both oxytocin-producing and luteinizing hormone-releasing hormone (LHRH)-producing neurons in hypothalamus. This represents the first evidence of a hypothalamic deficiency in a mouse model of PWS. NECDIN:-deficient mice also display increased skin scraping activity in the open field test and improved spatial learning and memory in the Morris water maze. The latter features are reminiscent of the skin picking and improved spatial memory that are characteristics of the PWS phenotype. These striking parallels in hypothalamic structure, emotional and cognitive-related behaviors strongly suggest that NECDIN is responsible for at least a subset of the multiple clinical manifestations of PWS.

Relaxation training for anxiety: a ten-years systematic review with meta-analysis.

PubMed

Manzoni, Gian Mauro; Pagnini, Francesco; Castelnuovo, Gianluca; Molinari, Enrico

2008-06-02

Relaxation training is a common treatment for anxiety problems. Lacking is a recent quantitative meta-analysis that enhances understanding of the variability and clinical significance of anxiety reduction outcomes after relaxation treatment. All studies (1997-2007), both RCT, observational and without control group, evaluating the efficacy of relaxation training (Jacobson's progressive relaxation, autogenic training, applied relaxation and meditation) for anxiety problems and disorders were identified by comprehensive electronic searches with Pubmed, Psychinfo and Cochrane Registers, by checking references of relevant studies and of other reviews. Our primary outcome was anxiety measured with psychometric questionnaires. Meta-analysis was undertaken synthesizing the data from all trials, distinguishing within and between effect sizes. 27 studies qualified for the inclusion in the meta-analysis. As hypothesized, relaxation training showed a medium-large effect size in the treatment of anxiety. Cohen's d was .57 (95% CI: .52 to .68) in the within analysis and .51 (95% CI: .46 to .634) in the between group analysis. Efficacy was higher for meditation, among volunteers and for longer treatments. Implications and limitations are discussed. The results show consistent and significant efficacy of relaxation training in reducing anxiety. This meta-analysis extends the existing literature through facilitation of a better understanding of the variability and clinical significance of anxiety improvement subsequent to relaxation training.

Multiple and variable speed electrical generator systems for large wind turbines

NASA Technical Reports Server (NTRS)

Andersen, T. S.; Hughes, P. S.; Kirschbaum, H. S.; Mutone, G. A.

1982-01-01

A cost effective method to achieve increased wind turbine generator energy conversion and other operational benefits through variable speed operation is presented. Earlier studies of multiple and variable speed generators in wind turbines were extended for evaluation in the context of a specific large sized conceptual design. System design and simulation have defined the costs and performance benefits which can be expected from both two speed and variable speed configurations.

Impact of advanced monitoring variables on intraoperative clinical decision-making: an international survey.

PubMed

Joosten, Alexandre; Desebbe, Olivier; Suehiro, Koichi; Essiet, Mfonobong; Alexander, Brenton; Ricks, Cameron; Rinehart, Joseph; Faraoni, David; Cecconi, Maurizio; Van der Linden, Philippe; Cannesson, Maxime

2017-02-01

To assess the relationship between the addition of advanced monitoring variables and changes in clinical decision-making. A 15-questions survey was anonymously emailed to international experts and physician members of five anesthesia societies which focused on assessing treatment decisions of clinicians during three realistic clinical scenarios measured at two distinct time points. The first is when typical case information and basic monitoring (T1) were provided, and then once again after the addition of advanced monitoring variables (T2). We hypothesized that the addition of advanced variables would increase the incidence of an optimal therapeutic decision (a priori defined as the answer with the highest percentage of expert agreement) and decrease the variability among the physician's suggested treatments. The survey was completed by 18 experts and 839 physicians. Overall, adding advanced monitoring did not significantly increase physician response accuracy, with the least substantial changes noted on questions related to volume expansion or vasopressor administration. Moreover, advanced monitoring data did not significantly decrease the high level of initial practice variability in physician suggested treatments (P = 0.13), in contrast to the low variability observed within the expert group (P = 0.039). Additionally, 5-10 years of practice (P < 0.0001) and a cardiovascular subspecialty (P = 0.048) were both physician characteristics associated with a higher rate of optimal therapeutic decisions. The addition of advanced variables was of limited benefit for most physicians, further indicating the need for more in depth education on the clinical value and technical understanding of such variables.

[Prescribing monitoring in clinical practice: from enlightened empiricism to rational strategies].

PubMed

Buclin, Thierry; Herzig, Lilli

2013-05-15

Monitoring of a medical condition is the periodic measurement of one or several physiological or biological variables to detect a signal regarding its clinical progression or its response to treatment. We distinguish different medical situations between diagnostic, clinical and therapeutic process to apply monitoring. Many clinical, variables can be used for monitoring, once their intrinsic properties (normal range, critical difference, kinetics, reactivity) and external validity (pathophysiological importance, predictive power for clinical outcomes) are established. A formal conceptualization of monitoring is being developed and should support the rational development of monitoring strategies and their validation through appropriate clinical trials.

The search for an elusive cutoff remains: Problems of binary classification of heavy drinking as an endpoint for alcohol clinical trials.

PubMed

Pearson, Matthew R; Bravo, Adrian J; Kirouac, Megan; Witkiewitz, Katie

2017-02-01

To examine whether a clinically meaningful alcohol consumption cutoff can be created for clinical samples, we used receiver operator characteristic (ROC) curves to derive gender-specific consumption cutoffs that maximized sensitivity and specificity in the prediction of a wide range of negative consequences from drinking. We conducted secondary data analyses using data from two large clinical trials targeting alcohol use disorders: Project MATCH (n=1726) and COMBINE (n=1383). In both studies, we found that the ideal cutoff for men and women that maximized sensitivity/specificity varied substantially both across different alcohol consumption variables and alcohol consequence outcomes. Further, the levels of sensitivity/specificity were poor across all consequences. These results fail to provide support for a clinically meaningful alcohol consumption cutoff and suggest that binary classification of levels of alcohol consumption is a poor proxy for maximizing sensitivity/specificity in the prediction of negative consequences from drinking. Future research examining consumption-consequence associations should take advantage of continuous measures of alcohol consumption and alternative approaches for assessing the link between levels of consumption and consequences (e.g., ecological momentary assessment). Clinical researchers should consider focusing more directly on the consequences they aim to reduce instead of relying on consumption as a proxy for more clinically meaningful outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

How large must a treatment effect be before it matters to practitioners? An estimation method and demonstration.

PubMed

Miller, William R; Manuel, Jennifer Knapp

2008-09-01

Treatment research is sometimes criticised as lacking in clinical relevance, and one potential source of this friction is a disconnection between statistical significance and what clinicians regard to be a meaningful difference in outcomes. This report demonstrates a novel methodology for estimating what substance abuse practitioners regard to be clinically important differences. To illustrate the estimation method, we surveyed 50 substance abuse treatment providers participating in the National Institute on Drug Abuse (NIDA) Clinical Trials Network. Practitioners identified thresholds for clinically meaningful differences on nine common outcome variables, indicated the size of effect that would justify their learning a new treatment method and estimated current outcomes from their services. Clinicians judged a difference between two treatments to be meaningful if outcomes were improved by about 10 - 12 points on the percentage of patients totally abstaining, arrested for driving while intoxicated, employed or having abnormal liver enzymes. A 5 percentage-point reduction in patient mortality was regarded as clinically significant. On continuous outcome measures (such as percentage of days abstinent or drinks per drinking day), practitioners judged an outcome to be significant when it doubled or halved the base rate. When a new treatment meets such criteria, practitioners were interested in learning it. Effects that are statistically significant in clinical trials may be unimpressive to practitioners. Clinicians' judgements of meaningful differences can inform the powering of clinical trials.

The Search for an Elusive Cutoff Remains: Problems of Binary Classification of Heavy Drinking as an Endpoint for Alcohol Clinical Trials

PubMed Central

Pearson, Matthew R.; Bravo, Adrian J.; Kirouac, Megan; Witkiewitz, Katie

2017-01-01

Background To examine whether a clinically meaningful alcohol consumption cutoff can be created for clinical samples, we used receiver operator characteristic (ROC) curves to derive gender-specific consumption cutoffs that maximized sensitivity and specificity in the prediction of a wide range of negative consequences from drinking. Methods We conducted secondary data analyses using data from two large clinical trials targeting alcohol use disorders: Project MATCH (n = 1,726) and COMBINE (n = 1,383). Results In both studies, we found that the ideal cutoff for men and women that maximized sensitivity/specificity varied substantially both across different alcohol consumption variables and alcohol consequence outcomes. Further, the levels of sensitivity/specificity were poor across all consequences. Conclusions These results fail to provide support for a clinically meaningful alcohol consumption cutoff and suggest that binary classification of levels of alcohol consumption is a poor proxy for maximizing sensitivity/specificity in the prediction of negative consequences from drinking. Future research examining consumption-consequence associations should take advantage of continuous measures of alcohol consumption and alternative approaches for assessing the link between levels of consumption and consequences (e.g., ecological momentary assessment). Clinical researchers should consider focusing more directly on the consequences they aim to reduce instead of relying on consumption as a proxy for more clinically meaningful outcomes. PMID:28038361

Dense Annotation of Free-Text Critical Care Discharge Summaries from an Indian Hospital and Associated Performance of a Clinical NLP Annotator.

PubMed

Ramanan, S V; Radhakrishna, Kedar; Waghmare, Abijeet; Raj, Tony; Nathan, Senthil P; Sreerama, Sai Madhukar; Sampath, Sriram

2016-08-01

Electronic Health Record (EHR) use in India is generally poor, and structured clinical information is mostly lacking. This work is the first attempt aimed at evaluating unstructured text mining for extracting relevant clinical information from Indian clinical records. We annotated a corpus of 250 discharge summaries from an Intensive Care Unit (ICU) in India, with markups for diseases, procedures, and lab parameters, their attributes, as well as key demographic information and administrative variables such as patient outcomes. In this process, we have constructed guidelines for an annotation scheme useful to clinicians in the Indian context. We evaluated the performance of an NLP engine, Cocoa, on a cohort of these Indian clinical records. We have produced an annotated corpus of roughly 90 thousand words, which to our knowledge is the first tagged clinical corpus from India. Cocoa was evaluated on a test corpus of 50 documents. The overlap F-scores across the major categories, namely disease/symptoms, procedures, laboratory parameters and outcomes, are 0.856, 0.834, 0.961 and 0.872 respectively. These results are competitive with results from recent shared tasks based on US records. The annotated corpus and associated results from the Cocoa engine indicate that unstructured text mining is a viable method for cohort analysis in the Indian clinical context, where structured EHR records are largely absent.

Intra- and Interobserver Variability of Cochlear Length Measurements in Clinical CT.

PubMed

Iyaniwura, John E; Elfarnawany, Mai; Riyahi-Alam, Sadegh; Sharma, Manas; Kassam, Zahra; Bureau, Yves; Parnes, Lorne S; Ladak, Hanif M; Agrawal, Sumit K

2017-07-01

The cochlear A-value measurement exhibits significant inter- and intraobserver variability, and its accuracy is dependent on the visualization method in clinical computed tomography (CT) images of the cochlea. An accurate estimate of the cochlear duct length (CDL) can be used to determine electrode choice, and frequency map the cochlea based on the Greenwood equation. Studies have described estimating the CDL using a single A-value measurement, however the observer variability has not been assessed. Clinical and micro-CT images of 20 cadaveric cochleae were acquired. Four specialists measured A-values on clinical CT images using both standard views and multiplanar reconstructed (MPR) views. Measurements were repeated to assess for intraobserver variability. Observer variabilities were evaluated using intra-class correlation and absolute differences. Accuracy was evaluated by comparison to the gold standard micro-CT images of the same specimens. Interobserver variability was good (average absolute difference: 0.77 ± 0.42 mm) using standard views and fair (average absolute difference: 0.90 ± 0.31 mm) using MPR views. Intraobserver variability had an average absolute difference of 0.31 ± 0.09 mm for the standard views and 0.38 ± 0.17 mm for the MPR views. MPR view measurements were more accurate than standard views, with average relative errors of 9.5 and 14.5%, respectively. There was significant observer variability in A-value measurements using both the standard and MPR views. Creating the MPR views increased variability between experts, however MPR views yielded more accurate results. Automated A-value measurement algorithms may help to reduce variability and increase accuracy in the future.

Clinico-pathological and biological prognostic variables in squamous cell carcinoma of the vulva.

PubMed

Gadducci, Angiolo; Tana, Roberta; Barsotti, Cecilia; Guerrieri, Maria Elena; Genazzani, Andrea Riccardo

2012-07-01

Several clinical-pathological parameters have been related to survival of patients with invasive squamous cell carcinoma of the vulva, whereas few studies have investigated the ability of biological variables to predict the clinical outcome of these patients. The present paper reviews the literature data on the prognostic relevance of lymph node-related parameters, primary tumor-related parameters, FIGO stage, blood variables, and tissue biological variables. Regarding these latter, the paper takes into account the analysis of DNA content, cell cycle-regulatory proteins, apoptosis-related proteins, epidermal growth factor receptor [EGFR], and proteins that are involved in tumor invasiveness, metastasis and angiogenesis. At present, the lymph node status and FIGO stage according to the new 2009 classification system are the main predictors for vulvar squamous cell carcinoma, whereas biological variables do not have yet a clinical relevance and their role is still investigational. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Identification of chronic rhinosinusitis phenotypes using cluster analysis.

PubMed

Soler, Zachary M; Hyer, J Madison; Ramakrishnan, Viswanathan; Smith, Timothy L; Mace, Jess; Rudmik, Luke; Schlosser, Rodney J

2015-05-01

Current clinical classifications of chronic rhinosinusitis (CRS) have been largely defined based upon preconceived notions of factors thought to be important, such as polyp or eosinophil status. Unfortunately, these classification systems have little correlation with symptom severity or treatment outcomes. Unsupervised clustering can be used to identify phenotypic subgroups of CRS patients, describe clinical differences in these clusters and define simple algorithms for classification. A multi-institutional, prospective study of 382 patients with CRS who had failed initial medical therapy completed the Sino-Nasal Outcome Test (SNOT-22), Rhinosinusitis Disability Index (RSDI), Medical Outcomes Study Short Form-12 (SF-12), Pittsburgh Sleep Quality Index (PSQI), and Patient Health Questionnaire (PHQ-2). Objective measures of CRS severity included Brief Smell Identification Test (B-SIT), CT, and endoscopy scoring. All variables were reduced and unsupervised hierarchical clustering was performed. After clusters were defined, variations in medication usage were analyzed. Discriminant analysis was performed to develop a simplified, clinically useful algorithm for clustering. Clustering was largely determined by age, severity of patient reported outcome measures, depression, and fibromyalgia. CT and endoscopy varied somewhat among clusters. Traditional clinical measures, including polyp/atopic status, prior surgery, B-SIT and asthma, did not vary among clusters. A simplified algorithm based upon productivity loss, SNOT-22 score, and age predicted clustering with 89% accuracy. Medication usage among clusters did vary significantly. A simplified algorithm based upon hierarchical clustering is able to classify CRS patients and predict medication usage. Further studies are warranted to determine if such clustering predicts treatment outcomes. © 2015 ARS-AAOA, LLC.

Molecular and Clinical Characterization of Albinism in a Large Cohort of Italian Patients

PubMed Central

Gargiulo, Annagiusi; Testa, Francesco; Rossi, Settimio; Di Iorio, Valentina; Fecarotta, Simona; de Berardinis, Teresa; Iovine, Antonello; Magli, Adriano; Signorini, Sabrina; Fazzi, Elisa; Galantuomo, Maria Silvana; Fossarello, Maurizio; Montefusco, Sandro; Ciccodicola, Alfredo; Neri, Alberto; Macaluso, Claudio; Simonelli, Francesca; Surace, Enrico Maria

2011-01-01

Purpose. The purpose of this study was to identify the molecular basis of albinism in a large cohort of Italian patients showing typical ocular landmarks of the disease and to provide a full characterization of the clinical ophthalmic manifestations. Methods. DNA samples from 45 patients with ocular manifestations of albinism were analyzed by direct sequencing analysis of five genes responsible for albinism: TYR, P, TYRP1, SLC45A2 (MATP), and OA1. All patients studied showed a variable degree of skin and hair hypopigmentation. Eighteen patients with distinct mutations in each gene associated with OCA were evaluated by detailed ophthalmic analysis, optical coherence tomography (OCT), and fundus autofluorescence. Results. Disease-causing mutations were identified in more than 95% of analyzed patients with OCA (28/45 [62.2%] cases with two or more mutations; 15/45 [33.3%] cases with one mutation). Thirty-five different mutant alleles were identified of which 15 were novel. Mutations in TYR were the most frequent (73.3%), whereas mutations in P occurred more rarely (13.3%) than previously reported. Novel mutations were also identified in rare loci such as TYRP1 and MATP. Mutations in the OA1 gene were not detected. Clinical assessment revealed that patients with iris and macular pigmentation had significantly higher visual acuity than did severe hypopigmented phenotypes. Conclusions. TYR gene mutations represent a relevant cause of oculocutaneous albinism in Italy, whereas mutations in P present a lower frequency than that found in other populations. Clinical analysis revealed that the severity of the ocular manifestations depends on the degree of retinal pigmentation. PMID:20861488

A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations.

PubMed

Iype, Thomas; Alakbarzade, Vafa; Iype, Mary; Singh, Royana; Sreekantan-Nair, Ajith; Chioza, Barry A; Mohapatra, Tribhuvan M; Baple, Emma L; Patton, Michael A; Warner, Thomas T; Proukakis, Christos; Kulkarni, Abhi; Crosby, Andrew H

2015-11-10

The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance. We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features. We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.

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.

Is There Evidence of Failing to Fail in Our Schools of Nursing?

PubMed

Docherty, Angie; Dieckmann, Nathan

2015-01-01

To assess evidence for "failing to fail" in undergraduate nursing programs. Literature on grading practices largely focuses on clinical or academic grading. Reviewing both as distinct entities may miss a more systemic grading problem. A cross-sectional survey targeted 235 faculty within university and community colleges in a western state. Chi-square tests of independence explored the relation between institutional and faculty variables. The response rate was 34 percent. Results suggest failing to fail may be evident across the sector in both clinical and academic settings: 43 percent of respondents had awarded higher grades than merited; 17.7 percent had passed written examinations they felt should fail; 66 percent believed they had worked with students who should not have passed their previous placement. Failing to fail cuts across instructional settings. Further exploration is imperative if schools are to better engender a climate for rigorously measuring student attainment.

Lipoprotein(a): Biology and Clinical Importance

PubMed Central

McCormick, Sally P A

2004-01-01

Lipoprotein(a) [Lp(a)] is a unique lipoprotein that has emerged as an independent risk factor for developing vascular disease. Plasma Lp(a) levels above the common cut-off level of 300 mg/L place individuals at risk of developing heart disease particularly if combined with other lipid and thrombogenic risk factors. Studies in humans have shown Lp(a) levels to be hugely variable and under strict genetic control, largely by the apolipoprotein(a) [apo(a)] gene. In general, Lp(a) levels have proven difficult to manipulate, although some factors have been identified that can influence levels. Research has shown that Lp(a) has a high affinity for the arterial wall and displays many athero-thrombogenic properties. While a definite function for Lp(a) has not been identified, the last two decades of research have provided much information on the biology and clinical importance of Lp(a). PMID:18516206

Challenges of stroke prevention in patients with atrial fibrillation in clinical practice.

PubMed

Hobbs, F D Richard; Leach, I

2011-09-01

Strokes and transient ischaemic attacks in patients with atrial fibrillation (AF) can be largely prevented. Risk stratification and appropriate prophylactic regimens help to alleviate the burden of AF-related thromboembolism. Guidelines recommend routine anticoagulation with oral vitamin K antagonists (VKAs) for patients at moderate-to-high risk of stroke, and acetylsalicylic acid (ASA) for those at low risk of stroke. ASA is less effective at reducing the risk of stroke than VKAs; however, ASA does not require monitoring or dose adjustment. Trials of anticoagulants show consistent benefits of oral VKAs for primary and secondary stroke prevention in patients with AF. Nevertheless, VKAs do require frequent coagulation monitoring and dose adjustment because of their variable dose-response profile, narrow therapeutic window, increased risk for bleeding complications and numerous food and drug interactions. This review aims to provide an overview of the clinical challenges of anticoagulant therapy for the prevention of stroke in patients with AF.

Novel ETFDH mutation and imaging findings in an adult with glutaric aciduria type II.

PubMed

Rosenbohm, Angela; Süssmuth, Sigurd D; Kassubek, Jan; Müller, Hans-Peter; Pontes, Christina; Abicht, Angela; Bulst, Stefanie; Ludolph, Albert C; Pinkhardt, Elmar

2014-03-01

Glutaric aciduria type II (GAII) is a rare autosomal recessive disorder with variable clinical course. The disorder is caused by a defect in the mitochondrial electron transfer flavoprotein or the electron transfer flavoprotein dehydrogenase (ETFDH). We performed clinical characterization, brain and whole body MRI, muscle histopathology, and genetic analysis of the ETFDH gene in a young woman. She presented with rhabdomyolysis and severe quadriparesis. We identified a novel homozygous missense mutation in ETFDH (c.1544G>T, p.Ser515Ile). Body fat MRI revealed a large amount of subcutaneous fat but no increase in visceral fat despite steatosis of liver and muscle. Diffusion tensor imaging (DTI) of cerebral MRI revealed reduced directionality of the white matter tracts. Histopathological findings showed lipid storage myopathy. In this study, we highlight diagnostic clues and body fat MRI in this rare metabolic disorder. Copyright © 2013 Wiley Periodicals, Inc.

Tilmicosin as a single injection treatment for respiratory disease of feedlot cattle

PubMed Central

Gorham, Paul E.; Carroll, Lamar H.; McAskill, Jack W.; Watkins, Lee E.; Ose, Earl E.; Tonkinson, Lealon V.; Merrill, John K.

1990-01-01

Tilmicosin, a new semi-synthetic macrolide antibiotic, was evaluated in eight field trials as a single subcutaneous injection at dosages of 0 (placebo), 5, 10 and 20 mg/kg for the treatment of naturally occurring respiratory disease in feedlot cattle. Animals for these trials were selected from large groups of recently-shipped feeder cattle at the time clinical signs of respiratory disease and body temperature of 40.6°C or higher were observed. Treated animals were evaluated daily for 10 days and finally at day 28. Each animal was weighed on the first day and again on day 28. Animals that died were necropsied. All treatment dosages were effective in significantly lowering mortality, improving weight gains, lowering body temperature, and reducing the severity of clinical signs when compared to the placebo-treated controls. Body temperature was the only variable with statistically significant differences among the dose levels. PMID:17423706

Anaplasia and grading in medulloblastomas.

PubMed

Eberhart, Charles G; Burger, Peter C

2003-07-01

The variable clinical outcomes of medulloblastoma patients have prompted a search for markers with which to tailor therapies to individuals. In this review, we discuss clinical, histological and molecular features that can be used in such treatment customization, focusing on how histopathological grading can impact both patient care and research on the molecular basis of CNS embryonal tumors. Medulloblastomas span a histological spectrum ending in overtly malignant large cell/anaplastic lesions characterized by increased nuclear size, marked cytological anaplasia, and increased mitotic and apoptotic rates. These "high-grade" lesions make up approximately one quarter of medulloblastomas, and recur and metastasize more frequently than tumors lacking anaplasia. We believe anaplastic change represents a type of malignant progression common to many medulloblastoma subtypes and to other CNS embryonal lesions as well. Correlation of these histological changes with the accumulation of genetic events suggests a model for the histological and molecular progression of medulloblastoma.

The Asthma Mobile Health Study, a large-scale clinical observational study using ResearchKit.

PubMed

Chan, Yu-Feng Yvonne; Wang, Pei; Rogers, Linda; Tignor, Nicole; Zweig, Micol; Hershman, Steven G; Genes, Nicholas; Scott, Erick R; Krock, Eric; Badgeley, Marcus; Edgar, Ron; Violante, Samantha; Wright, Rosalind; Powell, Charles A; Dudley, Joel T; Schadt, Eric E

2017-04-01

The feasibility of using mobile health applications to conduct observational clinical studies requires rigorous validation. Here, we report initial findings from the Asthma Mobile Health Study, a research study, including recruitment, consent, and enrollment, conducted entirely remotely by smartphone. We achieved secure bidirectional data flow between investigators and 7,593 participants from across the United States, including many with severe asthma. Our platform enabled prospective collection of longitudinal, multidimensional data (e.g., surveys, devices, geolocation, and air quality) in a subset of users over the 6-month study period. Consistent trending and correlation of interrelated variables support the quality of data obtained via this method. We detected increased reporting of asthma symptoms in regions affected by heat, pollen, and wildfires. Potential challenges with this technology include selection bias, low retention rates, reporting bias, and data security. These issues require attention to realize the full potential of mobile platforms in research and patient care.

Implications of genome-wide association studies in cancer therapeutics.

PubMed

Patel, Jai N; McLeod, Howard L; Innocenti, Federico

2013-09-01

Genome wide association studies (GWAS) provide an agnostic approach to identifying potential genetic variants associated with disease susceptibility, prognosis of survival and/or predictive of drug response. Although these techniques are costly and interpretation of study results is challenging, they do allow for a more unbiased interrogation of the entire genome, resulting in the discovery of novel genes and understanding of novel biological associations. This review will focus on the implications of GWAS in cancer therapy, in particular germ-line mutations, including findings from major GWAS which have identified predictive genetic loci for clinical outcome and/or toxicity. Lessons and challenges in cancer GWAS are also discussed, including the need for functional analysis and replication, as well as future perspectives for biological and clinical utility. Given the large heterogeneity in response to cancer therapeutics, novel methods of identifying mechanisms and biology of variable drug response and ultimately treatment individualization will be indispensable. © 2013 The British Pharmacological Society.

Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family.

PubMed

Kullar, Peter J; Gomez-Duran, Aurora; Gammage, Payam A; Garone, Caterina; Minczuk, Michal; Golder, Zoe; Wilson, Janet; Montoya, Julio; Häkli, Sanna; Kärppä, Mikko; Horvath, Rita; Majamaa, Kari; Chinnery, Patrick F

2018-01-01

The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons for the highly variable clinical penetrance are not known. Exome sequencing identified a heterozygous start loss mutation in SSBP1, encoding the single stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi-generational family transmitting m.1555A>G, associated with mtDNA depletion and multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific manner. This family demonstrates the importance of rare trans-acting genetic nuclear modifiers in the clinical expression of mtDNA disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Deletion 21pterq22.11: Report of a Patient with Dysmorphic Features, Hypertonia, and Café-au-Lait Macules and Review of the Literature.

PubMed

Malinverni, Andréa C M; Yamashiro Coelho, Érika M; Chen, Kelin; Colovati, Mileny E; Soares Pinho Cernach, Mirlene C; Bragagnolo, Silvia; Melaragno, Maria Isabel

2017-01-01

Partial monosomy 21 results in a great variability of clinical features that may be associated with the size and location of the deletion. In this study, we report a 22-month-old girl who showed a 45,XX,add(12)(p13)dn,-21 karyotype. The final cytogenomic result was 45,XX,der(12)t(12;21)(p13;q22.11) dn,-21.arr[hg19] 21q11.2q22.11(14824453_33868129)×1 revealing a deletion from 21pter to 21q22.11. Clinical manifestation of the patient included hypertonia, a long philtrum, epicanthic folds, low-set ears, and café-au-lait macules - a phenotype considered as mild despite the relatively large size of the deletion compared to patients from the literature. © 2017 S. Karger AG, Basel.

NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017.

PubMed

Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Baehring, Joachim; Brem, Henry; Butowski, Nicholas; Fenstermaker, Robert A; Forsyth, Peter; Hattangadi-Gluth, Jona; Holdhoff, Matthias; Howard, Steven; Junck, Larry; Kaley, Thomas; Kumthekar, Priya; Loeffler, Jay S; Moots, Paul L; Mrugala, Maciej M; Nagpal, Seema; Pandey, Manjari; Parney, Ian; Peters, Katherine; Puduvalli, Vinay K; Ragsdale, John; Rockhill, Jason; Rogers, Lisa; Rusthoven, Chad; Shonka, Nicole; Shrieve, Dennis C; Sills, Allen K; Swinnen, Lode J; Tsien, Christina; Weiss, Stephanie; Wen, Patrick Yung; Willmarth, Nicole; Bergman, Mary Anne; Engh, Anita

2017-11-01

For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas. Copyright © 2017 by the National Comprehensive Cancer Network.

Origins of timed cancer treatment: early marker rhythm-guided individualized chronochemotherapy*

PubMed Central

Halberg, Franz; Prem, Konald; Halberg, Francine; Norman, Catherine; Cornélissen, Germaine

2008-01-01

A 21-year old patient who presented in 1973 with a rare and highly malignant ovarian endodermal sinus tumor with spillage into the peritoneal cavity is alive and well today after receiving chronochemotherapy. During the first four courses of treatment, medications were given at different circadian stages. Complete blood counts and marker variables such as mood, vigor, nausea, and temperature were monitored around the clock and analyzed by cosinor to seek times of highest tolerance. Remaining treatment courses were administered at a time corresponding to the patient's best drug tolerance, rather than extrapolating the timing of optimal cyclophosphamide administration from also-implemented parallel laboratory studies on mice. Notwithstanding remaining hurdles in bringing chronochemotherapy to the clinic for routine care, merits of marker rhythm-guided chronotherapy documented in this and other case reports have led to the doubling of the two-year disease-free survival of patients with large perioral tumors in a clinical trial. PMID:17228525

Hypothyroidism after x irradiation to the neck: three case reports and a brief review of the literature

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

Adler, R.A.; Corrigan, D.F.; Wartofsky, L.

1976-05-01

Three patients who developed hypothyroidism after x irradiation to the neck are presented. The first two cases demonstrate that patients can develop clinical and chemical hypothyroidism after a very short interval following radiotherapy. Hypothyroidism developed in the first patient in the absence of surgical manipulation of the neck, or a large iodine load 4 months after receiving 6800 rad of x-ray therapy to his neck for carcinoma of the larynx. The second patient developed hypothyroidism approximately 6 months after his radiotherapy for carcinoma of the esophagus. Both of these patients demonstrated high titers of serum antithyroid antibodies. A third patientmore » with Hodgkin's disease did not manifest clinical symptoms and signs of hypothyroidism until 6 years after radiation therapy. These cases demonstrate the variability of onset of hypothyroidism after radiotherapy and emphasize the need for careful evaluation of thyroid function before and after neck irradiation.« less

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.

Clinicians' perceptions of organizational readiness for change in the context of clinical information system projects: insights from two cross-sectional surveys.

PubMed

Paré, Guy; Sicotte, Claude; Poba-Nzaou, Placide; Balouzakis, George

2011-02-28

The adoption and diffusion of clinical information systems has become one of the critical benchmarks for achieving several healthcare organizational reform priorities, including home care, primary care, and integrated care networks. However, these systems are often strongly resisted by the same community that is expected to benefit from their use. Prior research has found that early perceptions and beliefs play a central role in shaping future attitudes and behaviors such as negative rumors, lack of involvement, and resistance to change. In this line of research, this paper builds on the change management and information systems literature and identifies variables associated with clinicians' early perceptions of organizational readiness for change in the specific context of clinical information system projects. Two cross-sectional surveys were conducted to test our research model. First, a questionnaire was pretested and then distributed to the future users of a mobile computing technology in 11 home care organizations. The second study took place in a large teaching hospital that had approved a budget for the acquisition of an electronic medical records system. Data analysis was performed using partial least squares. Scale items used in this study showed adequate psychometric properties. In Study 1, four of the hypothesized links in the research model were supported, with change appropriateness, organizational flexibility, vision clarity, and change efficacy explaining 75% of the variance in organizational readiness. In Study 2, four hypotheses were also supported, two of which differed from those supported in Study 1: the presence of an effective project champion and collective self-efficacy. In addition to these variables, vision clarity and change appropriateness also helped explain 75% of the variance in the dependent variable. Explanations for the similarities and differences observed in the two surveys are provided. Organizational readiness is arguably a key factor involved in clinicians' initial support for clinical information system initiatives. As healthcare organizations continue to invest in information technologies to improve quality and continuity of care and reduce costs, understanding the factors that influence organizational readiness for change represents an important avenue for future research.

Clinicians' perceptions of organizational readiness for change in the context of clinical information system projects: insights from two cross-sectional surveys

PubMed Central

2011-01-01

Background The adoption and diffusion of clinical information systems has become one of the critical benchmarks for achieving several healthcare organizational reform priorities, including home care, primary care, and integrated care networks. However, these systems are often strongly resisted by the same community that is expected to benefit from their use. Prior research has found that early perceptions and beliefs play a central role in shaping future attitudes and behaviors such as negative rumors, lack of involvement, and resistance to change. In this line of research, this paper builds on the change management and information systems literature and identifies variables associated with clinicians' early perceptions of organizational readiness for change in the specific context of clinical information system projects. Methods Two cross-sectional surveys were conducted to test our research model. First, a questionnaire was pretested and then distributed to the future users of a mobile computing technology in 11 home care organizations. The second study took place in a large teaching hospital that had approved a budget for the acquisition of an electronic medical records system. Data analysis was performed using partial least squares. Results Scale items used in this study showed adequate psychometric properties. In Study 1, four of the hypothesized links in the research model were supported, with change appropriateness, organizational flexibility, vision clarity, and change efficacy explaining 75% of the variance in organizational readiness. In Study 2, four hypotheses were also supported, two of which differed from those supported in Study 1: the presence of an effective project champion and collective self-efficacy. In addition to these variables, vision clarity and change appropriateness also helped explain 75% of the variance in the dependent variable. Explanations for the similarities and differences observed in the two surveys are provided. Conclusions Organizational readiness is arguably a key factor involved in clinicians' initial support for clinical information system initiatives. As healthcare organizations continue to invest in information technologies to improve quality and continuity of care and reduce costs, understanding the factors that influence organizational readiness for change represents an important avenue for future research. PMID:21356080

Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis.

PubMed

Zampeli, Evanthia; Gizis, Michalis; Siakavellas, Spyros I; Bamias, Giorgos

2014-08-15

Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve (primary non-response) or lose response after a period of improvement (secondary non-response/loss of response). In addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters that may predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. Included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular (immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy.

Diagnostic accuracy of clinical examination features for identifying large rotator cuff tears in primary health care

PubMed Central

Cadogan, Angela; McNair, Peter; Laslett, Mark; Hing, Wayne; Taylor, Stephen

2013-01-01

Objectives: Rotator cuff tears are a common and disabling complaint. The early diagnosis of medium and large size rotator cuff tears can enhance the prognosis of the patient. The aim of this study was to identify clinical features with the strongest ability to accurately predict the presence of a medium, large or multitendon (MLM) rotator cuff tear in a primary care cohort. Methods: Participants were consecutively recruited from primary health care practices (n = 203). All participants underwent a standardized history and physical examination, followed by a standardized X-ray series and diagnostic ultrasound scan. Clinical features associated with the presence of a MLM rotator cuff tear were identified (P<0.200), a logistic multiple regression model was derived for identifying a MLM rotator cuff tear and thereafter diagnostic accuracy was calculated. Results: A MLM rotator cuff tear was identified in 24 participants (11.8%). Constant pain and a painful arc in abduction were the strongest predictors of a MLM tear (adjusted odds ratio 3.04 and 13.97 respectively). Combinations of ten history and physical examination variables demonstrated highest levels of sensitivity when five or fewer were positive [100%, 95% confidence interval (CI): 0.86–1.00; negative likelihood ratio: 0.00, 95% CI: 0.00–0.28], and highest specificity when eight or more were positive (0.91, 95% CI: 0.86–0.95; positive likelihood ratio 4.66, 95% CI: 2.34–8.74). Discussion: Combinations of patient history and physical examination findings were able to accurately detect the presence of a MLM rotator cuff tear. These findings may aid the primary care clinician in more efficient and accurate identification of rotator cuff tears that may require further investigation or orthopedic consultation. PMID:24421626

Atrial Fibrillation in Hypertrophic Cardiomyopathy: Prevalence, Clinical Correlations, and Mortality in a Large High‐Risk Population

PubMed Central

Siontis, Konstantinos C.; Geske, Jeffrey B.; Ong, Kevin; Nishimura, Rick A.; Ommen, Steve R.; Gersh, Bernard J.

2014-01-01

Background Atrial fibrillation (AF) is a common sequela of hypertrophic cardiomyopathy (HCM), but evidence on its prevalence, risk factors, and effect on mortality is sparse. We sought to evaluate the prevalence of AF, identify clinical and echocardiographic correlates, and assess its effect on mortality in a large high‐risk HCM population. Methods and Results We identified HCM patients who underwent evaluation at our institution from 1975 to 2012. AF was defined by known history (either chronic or paroxysmal), electrocardiogram, or Holter monitoring at index visit. We examined clinical and echocardiographic variables in association with AF. The effect of AF on overall and cause‐specific mortality was evaluated with multivariate Cox proportional hazards models. Of 3673 patients with HCM, 650 (18%) had AF. Patients with AF were older and more symptomatic (P<0.001). AF was less common among patients with obstructive HCM phenotype and was associated with larger left atria, higher E/e’ ratios, and worse cardiopulmonary exercise tolerance (all P values<0.001). During median (interquartile range) follow‐up of 4.1 (0.2 to 10) years, 1069 (29%) patients died. Patients with AF had worse survival compared to those without AF (P<0.001). In multivariate analysis adjusted for established risk factors of mortality in HCM, the hazard ratio (95% confidence interval) for the effect of AF on overall mortality was 1.48 (1.27 to 1.71). AF did not have an effect on sudden or nonsudden cardiac death. Conclusions In this large referral HCM population, approximately 1 in 5 patients had AF. AF was a strong predictor of mortality, even after adjustment for established risk factors. PMID:24965028

A novel COL4A3 mutation causes autosomal-recessive Alport syndrome in a large Turkish family.

PubMed

Uzak, Asli Subasioglu; Tokgoz, Bulent; Dundar, Munis; Tekin, Mustafa

2013-03-01

Alport syndrome (AS) is a genetically heterogeneous disorder that is characterized by hematuria, progressive renal failure typically resulting in end-stage renal disease, sensorineural hearing loss, and variable ocular abnormalities. Only 15% of cases with AS are autosomal recessive and are caused by mutations in the COL4A3 or COL4A4 genes, encoding type IV collagen. Clinical data in a large consanguineous family with four affected members were reviewed, and genomic DNA was extracted. For mapping, 15 microsatellite markers flanking COL4A3, COL4A4, and COL4A5 in 16 family members were typed. For mutation screening, all coding exons of COL4A3 were polymerase chain reaction- amplified and Sanger-sequenced from genomic DNA. The disease locus was mapped to chromosome 2q36.3, where COL4A3 and COL4A4 reside. Sanger sequencing revealed a novel mis-sense mutation (c.2T>C; p.M1T) in exon 1 of COL4A3. The identified nucleotide change was not found in 100 healthy ethnicity-matched controls via Sanger sequencing. We present a large consanguineous Turkish family with AS that was found to have a COL4A3 mutation as the cause of the disease. Although the relationship between the various genotypes and phenotypes in AS has not been fully elucidated, detailed clinical and molecular analyses are helpful for providing data to be used in genetic counseling. It is important to identify new mutations to clarify their clinical importance, to assess the prognosis of the disease, and to avoid renal biopsy for final diagnosis.

Disclosure control using partially synthetic data for large-scale health surveys, with applications to CanCORS.

PubMed

Loong, Bronwyn; Zaslavsky, Alan M; He, Yulei; Harrington, David P

2013-10-30

Statistical agencies have begun to partially synthesize public-use data for major surveys to protect the confidentiality of respondents' identities and sensitive attributes by replacing high disclosure risk and sensitive variables with multiple imputations. To date, there are few applications of synthetic data techniques to large-scale healthcare survey data. Here, we describe partial synthesis of survey data collected by the Cancer Care Outcomes Research and Surveillance (CanCORS) project, a comprehensive observational study of the experiences, treatments, and outcomes of patients with lung or colorectal cancer in the USA. We review inferential methods for partially synthetic data and discuss selection of high disclosure risk variables for synthesis, specification of imputation models, and identification disclosure risk assessment. We evaluate data utility by replicating published analyses and comparing results using original and synthetic data and discuss practical issues in preserving inferential conclusions. We found that important subgroup relationships must be included in the synthetic data imputation model, to preserve the data utility of the observed data for a given analysis procedure. We conclude that synthetic CanCORS data are suited best for preliminary data analyses purposes. These methods address the requirement to share data in clinical research without compromising confidentiality. Copyright © 2013 John Wiley & Sons, Ltd.

Early studies reported extreme findings with large variability: a meta-epidemiologic study in the field of endocrinology.

PubMed

Wang, Zhen; Alahdab, Fares; Almasri, Jehad; Haydour, Qusay; Mohammed, Khaled; Abu Dabrh, Abd Moain; Prokop, Larry J; Alfarkh, Wedad; Lakis, Sumaya; Montori, Victor M; Murad, Mohammad Hassan

2016-04-01

To evaluate the presence of extreme findings and fluctuation in effect size in endocrinology. We systematically identified all meta-analyses published in 2014 in the field of endocrinology. Within each meta-analysis, the effect size of the primary binary outcome was compared across studies according to their order of publication. We pooled studies using the DerSimonian and Laird random-effects method. Heterogeneity was evaluated using the I(2) and tau(2). Twelve percent of the included 100 meta-analyses reported the largest effect size in the very first published study. The largest effect size occurred in the first 2 earliest studies in 31% of meta-analyses. When the effect size was the largest in the first published study, it was three times larger than the final pooled effect (ratio of rates, 3.26; 95% confidence interval: 1.80, 5.90). The largest heterogeneity measured by I(2) was observed in 18% of the included meta-analyses when combining the first 2 studies or 17% when combing the first 3 studies. In endocrinology, early studies reported extreme findings with large variability. This behavior of the evidence needs to be taken into account when used to formulate clinical policies. Copyright © 2016 Elsevier Inc. All rights reserved.