Detection of muscle wasting in patients with chronic heart failure using C-terminal agrin fragment: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

AIMS Skeletal muscle wasting affects 20% of patients with chronic heart failure and has serious implications for their activities of daily living. Assessment of muscle wasting is technically challenging. C-terminal agrin-fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as biomarker of muscle wasting. We sought to investigate the diagnostic properties of CAF in muscle wasting among patients with heart failure. METHODS AND RESULTS We assessed serum CAF levels in 196 patients who participated in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Muscle wasting was identified using dual-energy X-ray absorptiometry (DEXA) in 38 patients (19.4%). Patients with muscle wasting demonstrated higher CAF values than those without (125.1 ± 59.5 pmol/L vs. 103.8 ± 42.9 pmol/L, P = 0.01). Using receiver operating characteristics (ROC), we calculated the optimal CAF value to identify patients with muscle wasting as >87.5 pmol/L, which had a sensitivity of 78.9% and a specificity of 43.7%. The area under the ROC curve was 0.63 (95% confidence interval 0.56-0.70). Using simple regression, we found that serum CAF was associated with handgrip (R = - 0.17, P = 0.03) and quadriceps strength (R = - 0.31, P < 0.0001), peak oxygen consumption (R = - 0.5, P < 0.0001), 6-min walk distance (R = - 0.32, P < 0.0001), and gait speed (R = - 0.2, P = 0.001), as well as with parameters of kidney and liver function, iron metabolism and storage. CONCLUSION CAF shows good sensitivity for the detection of skeletal muscle wasting in patients with heart failure. Its assessment may be useful to identify patients who should undergo additional testing, such as detailed body composition analysis. As no other biomarker is currently available, further investigation is warranted.

Diagnosing synaesthesia with online colour pickers: Maximising sensitivity and specificity

The most commonly used method for formally assessing grapheme-colour synaesthesia (i.e., experiencing colours in response to letter and/or number stimuli) involves selecting colours from a large colour palette on several occasions and measuring consistency of the colours selected. However, the ability to diagnose synaesthesia using this method depends on several factors that have not been directly contrasted. These include the type of colour space used (e.g., RGB, HSV, CIELUV, CIELAB) and different measures of consistency (e.g., city block and Euclidean distance in colour space). This study aims to find the most reliable way of diagnosing grapheme-colour synaesthesia based on maximising sensitivity (i.e., ability of a test to identify true synaesthetes) and specificity (i.e., ability of a test to identify true non-synaesthetes). We show, applying ROC (Receiver Operating Characteristics) to binary classification of a large sample of self-declared synaesthetes and non-synaesthetes, that the consistency criterion (i.e., cut-off value) for diagnosing synaesthesia is considerably higher than the current standard in the field. We also show that methods based on perceptual CIELUV and CIELAB colour models (rather than RGB and HSV colour representations) and Euclidean distances offer an even greater sensitivity and specificity than most currently used measures. Together, these findings offer improved heuristics for the behavioural assessment of grapheme-colour synaesthesia.

Incremental value of heart-type fatty acid-binding protein in suspected acute myocardial infarction early after symptom onset.

BACKGROUND The early diagnosis of acute myocardial infarction (AMI) very soon after symptom onset remains a major clinical challenge, even when using high-sensitivity cardiac troponin (hs-cTnT). METHODS AND RESULTS We investigated the incremental value of heart-type fatty acid-binding protein (hFABP) in a pre-specified subgroup analysis of patients presenting with suspected AMI within 1 h of symptom onset to the emergency department (ED) in a multicentre study. HFABP was measured in a blinded fashion. Two independent cardiologists using all available clinical information, including hs-cTnT, adjudicated the final diagnosis. Overall, 1411 patients were enrolled, of whom 105 patients presented within 1 h of symptom onset. Of these, 34 patients (32.4%) had AMI. The diagnostic accuracy as quantified by the area under the receiver-operating characteristics curve (AUC) of hFABP was high (0.84 (95% CI 0.74-0.94)). However, the additional use of hFABP only marginally increased the diagnostic accuracy of hs-cTnT (AUC 0.88 (95% CI 0.81-0.94) for hs-cTnT alone to 0.90 (95% CI 0.83-0.98) for the combination; p=ns). After the exclusion of 18 AMI patients with ST-segment elevation, similar results were obtained. Among the 16 AMI patients without ST-segment elevation, six had normal hs-cTnT at presentation. Of these, hFABP was elevated in two (33.3%) patients. CONCLUSIONS hFABP does not seem to significantly improve the early diagnostic accuracy of hs-cTnT in the important subgroup of patients with suspected AMI presenting to the ED very early after symptom onset.

Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis.

Immunoassays are essential in the workup of patients with suspected heparin-induced thrombocytopenia. However, the diagnostic accuracy is uncertain with regard to different classes of assays, antibody specificities, thresholds, test variations, and manufacturers. We aimed to assess diagnostic accuracy measures of available immunoassays and to explore sources of heterogeneity. We performed comprehensive literature searches and applied strict inclusion criteria. Finally, 49 publications comprising 128 test evaluations in 15 199 patients were included in the analysis. Methodological quality according to the revised tool for quality assessment of diagnostic accuracy studies was moderate. Diagnostic accuracy measures were calculated with the unified model (comprising a bivariate random-effects model and a hierarchical summary receiver operating characteristics model). Important differences were observed between classes of immunoassays, type of antibody specificity, thresholds, application of confirmation step, and manufacturers. Combination of high sensitivity (>95%) and high specificity (>90%) was found in 5 tests only: polyspecific enzyme-linked immunosorbent assay (ELISA) with intermediate threshold (Genetic Testing Institute, Asserachrom), particle gel immunoassay, lateral flow immunoassay, polyspecific chemiluminescent immunoassay (CLIA) with a high threshold, and immunoglobulin G (IgG)-specific CLIA with low threshold. Borderline results (sensitivity, 99.6%; specificity, 89.9%) were observed for IgG-specific Genetic Testing Institute-ELISA with low threshold. Diagnostic accuracy appears to be inadequate in tests with high thresholds (ELISA; IgG-specific CLIA), combination of IgG specificity and intermediate thresholds (ELISA, CLIA), high-dose heparin confirmation step (ELISA), and particle immunofiltration assay. When making treatment decisions, clinicians should be a aware of diagnostic characteristics of the tests used and it is recommended they estimate posttest probabilities according to likelihood ratios as well as pretest probabilities using clinical scoring tools.

Detection of significant coronary artery disease by noninvasive anatomical and functional imaging.

BACKGROUND The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. METHODS AND RESULTS A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ≤0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88-0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69-0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65-0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001). CONCLUSIONS In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00979199.

Comparison of Bispectral Index (BIS) and Patient State Index (PSI) as objective measures of sedation and analgesia in critically ill/injured patients

Critically ill and injured patients require pain relief and sedation to reduce the body's stress response and to facilitate painful diagnostic and therapeutic procedures. Presently, the level of sedation and analgesia is guided by the use of clinical scores which can be unreliable. There is therefore, a need for an objective measure of sedation and analgesia. The Bispectral Index (BIS) and Patient State Index (PSI) were recently introduced into clinical practice as objective measures of the depth of analgesia and sedation. ^ Aim. To compare the different measures of sedation and analgesia (BIS and PSI) to the standard and commonly used modified Ramsay Score (MRS) and determine if the monitors can be used interchangeably. ^ Methods. MRS, BIS and PSI values were obtained in 50 postoperative cardiac surgery patients requiring analgesia and sedation from June to December 2004. The MRS, BIS and PSI values were assessed hourly for up to 6-h by a single observer. ^ The relationship between BIS and PSI values were explored using scatter plots and correlation between MRS, BIS and PSI was determined using Spearman's correlation coefficient. Intra-class correlation (ICC) was used to determine the inter-rater reliability of MRS, BIS and PSI. Kappa statistics was used to further evaluate the agreement between BIS and PSI at light, moderate and deep levels of sedation. ^ Results. There was a positive correlation between BIS and PSI values (Rho = 0.731, p<0.001). Intra-class correlation between BIS and PSI was 0.58, MRS and BIS 0.43 and MRS and PSI 0.27. Using Kappa statistics, agreement between MRS and BIS was 0.35 (95% CI: 0.27–0.43) and for MRS and PSI was 0.21 (95% CI: 0.15–0.28). The kappa statistic for BIS and PSI was 0.45 (95% CI: 0.37–0.52). Receiver operating characteristics (ROC) curves constructed to detect undersedation indicated an area under the curve (AUC) of 0.91 (95% CI = 0.87 to 0.94) for the BIS and 0.84 (95% CI = 0.79 to 0.88) for the PSI. For detection of oversedation, AUC for the BIS was 0.89 (95% CI = 0.84 to 0.92) and 0.80 (95% CI = 0.75 to 0.85) for the PSI. ^ Conclusions. There is a statistically significant positive correlation between the BIS and PSI but poor correlation and poor test agreement between the MRS and BIS as well as MRS and PSI. Both the BIS and PSI demonstrated a high level of prediction for undersedation and oversedation; however, the BIS and PSI can not be considered interchangeable monitors of sedation. ^

External validation study of a clinical prediction rule for ambulation outcomes after traumatic spinal cord injury

The main objective of this study was to determine the external validity of a clinical prediction rule developed by the European Multicenter Study on Human Spinal Cord Injury (EM-SCI) to predict the ambulation outcomes 12 months after traumatic spinal cord injury. Data from the North American Clinical Trials Network (NACTN) data registry with approximately 500 SCI cases were used for this validity study. The predictive accuracy of the EM-SCI prognostic model was evaluated using calibration and discrimination based on 231 NACTN cases. The area under the receiver-operating-characteristics curve (ROC) curve was 0.927 (95% CI 0.894 – 0.959) for the EM-SCI model when applied to NACTN population. This is lower than the AUC of 0.956 (95% CI 0.936 – 0.976) reported for the EM-SCI population, but suggests that the EM-SCI clinical prediction rule distinguished well between those patients in the NACTN population who were able to achieve independent ambulation and those who did not achieve independent ambulation. The calibration curve suggests that higher the prediction score is, the better the probability of walking with the best prediction for AIS D patients. In conclusion, the EM-SCI clinical prediction rule was determined to be generalizable to the adult NACTN SCI population.^

Is ultrasound perfusion imaging capable of detecting mismatch? A proof-of-concept study in acute stroke patients.

In this study, we compared contrast-enhanced ultrasound perfusion imaging with magnetic resonance perfusion-weighted imaging or perfusion computed tomography for detecting normo-, hypo-, and nonperfused brain areas in acute middle cerebral artery stroke. We performed high mechanical index contrast-enhanced ultrasound perfusion imaging in 30 patients. Time-to-peak intensity of 10 ischemic regions of interests was compared to four standardized nonischemic regions of interests of the same patient. A time-to-peak >3 s (ultrasound perfusion imaging) or >4 s (perfusion computed tomography and magnetic resonance perfusion) defined hypoperfusion. In 16 patients, 98 of 160 ultrasound perfusion imaging regions of interests of the ischemic hemisphere were classified as normal, and 52 as hypoperfused or nonperfused. Ten regions of interests were excluded due to artifacts. There was a significant correlation of the ultrasound perfusion imaging and magnetic resonance perfusion or perfusion computed tomography (Pearson`s chi-squared test 79.119, p < 0.001) (OR 0.1065, 95% CI 0.06-0.18). No perfusion in ultrasound perfusion imaging (18 regions of interests) correlated highly with diffusion restriction on magnetic resonance imaging (Pearson's chi-squared test 42.307, p < 0.001). Analysis of receiver operating characteristics proved a high sensitivity of ultrasound perfusion imaging in the diagnosis of hypoperfused area under the curve, (AUC = 0.917; p < 0.001) and nonperfused (AUC = 0.830; p < 0.001) tissue in comparison with perfusion computed tomography and magnetic resonance perfusion. We present a proof of concept in determining normo-, hypo-, and nonperfused tissue in acute stroke by advanced contrast-enhanced ultrasound perfusion imaging.

Putting teeth into the developmental origins hypothesis: A longitudinal study of early childhood malnutrition, enamel hypoplasia and adolescent health in Amazonian Bolivia

Thesis (Ph.D.)--University of Washington, 2016-06

What You Get Out of Memory Depends on the Question You Ask

Following study, participants received 2 tests. The 1st was a recognition test; the 2nd was designed to tap recollection. The objective was to examine performance on Test I conditional on Test 2 performance. In Experiment 1, contrary to process dissociation assumptions, exclusion errors better predicted subsequent recollection than did inclusion errors. In Experiments 2 and 3, with alternate questions posed on Test 2, words having high estimates of recollection with one question had high estimates of familiarity with the other question. Results supported the following: (a) the 2-test procedure has considerable potential for elucidating the relationship between recollection and familiarity; (b) there is substantial evidence for dependency between such processes when estimates are obtained using the process dissociation and remember-know procedures; and (c) order of information access appears to depend on the question posed to the memory system.

ROC Curves within the Framework of Neural Network Assembly Memory Model: Some Analytic Results

On the basis of convolutional (Hamming) version of recent Neural Network Assembly Memory Model (NNAMM) for intact two-layer autoassociative Hopfield network optimal receiver operating characteristics (ROCs) have been derived analytically. A method of taking into account explicitly a priori probabilities of alternative hypotheses on the structure of information initiating memory trace retrieval and modified ROCs (mROCs, a posteriori probabilities of correct recall vs. false alarm probability) are introduced. The comparison of empirical and calculated ROCs (or mROCs) demonstrates that they coincide quantitatively and in this way intensities of cues used in appropriate experiments may be estimated. It has been found that basic ROC properties which are one of experimental findings underpinning dual-process models of recognition memory can be explained within our one-factor NNAMM.

A Bayesian Spatial Mixture Model for FMRI Analysis

We develop, implement and study a new Bayesian spatial mixture model (BSMM). The proposed BSMM allows for spatial structure in the binary activation indicators through a latent thresholded Gaussian Markov random field. We develop a Gibbs (MCMC) sampler to perform posterior inference on the model parameters, which then allows us to assess the posterior probabilities of activation for each voxel. One purpose of this article is to compare the HJ model and the BSMM in terms of receiver operating characteristics (ROC) curves. Also we consider the accuracy of the spatial mixture model and the BSMM for estimation of the size of the activation region in terms of bias, variance and mean squared error. We perform a simulation study to examine the aforementioned characteristics under a variety of configurations of spatial mixture model and BSMM both as the size of the region changes and as the magnitude of activation changes.

Use of Hemoglobin A1C to Detect Haitian-Americans with Undiagnosed Type 2 Diabetes

OBJECTIVE: To evaluate the validity of hemoglobin A1C (A1C) as a diagnostic tool for type 2 diabetes and to determine the most appropriate A1C cutoff point for diagnosis in a sample of Haitian-Americans. SUBJECTS AND METHODS: Subjects (n = 128) were recruited from Miami-Dade and Broward counties, FL. Receiver operating characteristics (ROC) analysis was run in order to measure sensitivity and specificity of A1C for detecting diabetes at different cutoff points. RESULTS: The area under the ROC curve was 0.86 using fasting plasma glucose ≥ 7.0 mmol/L as the gold standard. An A1C cutoff point of 6.26% had sensitivity of 80% and specificity of 74%, whereas an A1C cutoff point of 6.50% (recommended by the American Diabetes Association – ADA) had sensitivity of 73% and specificity of 89%. CONCLUSIONS: A1C is a reliable alternative to fasting plasma glucose in detecting diabetes in this sample of Haitian-Americans. A cutoff point of 6.26% was the optimum value to detect type 2 diabetes.

Obésité abdominale et autres déterminants du risque cardiométabolique dans deux populations urbaines noires apparentées : Port-au-Prince (Haïti) et Cotonou (Bénin)

L’obésité est un problème de santé publique reconnu. Dans la dernière décennie l’obésité abdominale (OA) a été considérée comme une maladie métabolique qui contribue davantage au risque de diabète et de maladies cardiovasculaires que l’obésité générale définie par l’indice de masse corporelle. Toutefois, dans les populations d’origine africaine, la relation entre l’OA et les autres biomarqueurs de risque cardiométabolique (RCM) demeure obscure à cause du manque d’études chez ces populations et de l’absence de valeurs-seuils spécifiques pour juger d’une OA. Cette étude visait à comparer la prévalence des biomarqueurs de RCM (OA, hypertension artérielle, hyperglycémie, dyslipidémie, résistance à l'insuline et inflammation pré-clinique) chez les Béninois de Cotonou et les Haïtiens de Port-au-Prince (PAP), à étudier l’association de l’OA avec les autres biomarqueurs de RCM, à documenter le rôle du niveau socio-économique (NSE) et du mode de vie dans cette association et à ’identifier les indicateurs anthropométriques de l’OA -tour de taille (TT) et le ratio TT/hauteur (TT/H)- et les seuils qui prédisent le mieux le RCM à Cotonou et à PAP. Il s’est agi d’une analyse de données transversales chez 452 adultes (52 % hommes) apparemment en bonne santé, âgés de 25 à 60 ans, avec 200 sujets vivant à Cotonou (Bénin) et 252 sujets à PAP (Haïti). Les biomarqueurs de RCM considérés étaient : le syndrome métabolique (SMet) d’après les critères harmonisés de 2009 et ses composantes individuelles - une OA à partir d’un TT ≥ 94cm chez les hommes et ≥ 80cm chez les femmes, une hypertension, une dyslipidémie et une hyperglycémie; la résistance à l’insuline définie chez l’ensemble des sujets de l’étude à partir du 75e centile de l’Homeostasis Model Assessment (HOMA-IR); un ratio d’athérogénicité élevé (Cholestérol sérique total/HDL-Cholestérol); et l’inflammation pré-clinique mesurée à partir d’un niveau de protéine C-réactive ultrasensible (PCRus) entre 3 et 10 mg/l. Le ratio TT/H était aussi considéré pour définir l’OA à partir d’un seuil de 0,5. Les données sur les habitudes alimentaires, la consommation d’alcool, le tabagisme, les caractéristiques sociodémographiques et les conditions socio-économiques incluant le niveau d’éducation et un proxy du revenu (basé sur l’analyse par composante principale des biens et des possessions) ont été recueillies au moyen d’un questionnaire. Sur la base de données de fréquence de consommation d’aliments occidentaux, urbains et traditionnels, des schémas alimentaires des sujets de chaque ville ont été identifiés par analyse typologique. La validité et les valeurs-seuils de TT et du ratio TT/H prédictives du RCM ont été définies à partir des courbes ROC (Receiver Operating Characteristics). Le SMet était présent chez 21,5 % et 16,1 % des participants, respectivement à Cotonou et à PAP. La prévalence d’OA était élevée à Cotonou (52,5 %) qu’à PAP (36%), avec une prévalence plus élevée chez les femmes que chez les hommes. Le profil lipidique sérique était plus athérogène à PAP avec 89,3 % d’HDL-c bas à PAP contre 79,7 % à Cotonou et un ratio CT/HDL-c élevé de 73,4 % à PAP contre 42 % à Cotonou. Les valeurs-seuils spécifiques de TT et du TT/H étaient respectivement 94 cm et 0,59 chez les femmes et 80 cm et 0,50 chez les hommes. Les analyses multivariées de l’OA avec les biomarqueurs de RCM les plus fortement prévalents dans ces deux populations montraient que l’OA était associée à un risque accru de résistance à l’insuline, d’athérogénicité et de tension artérielle élevée et ceci, indépendamment des facteurs socio-économiques et du mode de vie. Deux schémas alimentaires ont émergé, transitionnel et traditionnel, dans chaque ville, mais ceux-ci ne se révélaient pas associés aux biomarqueurs de RCM bien qu’ils soient en lien avec les variables socio-économiques. La présente étude confirme la présence de plusieurs biomarqueurs de RCM chez des sujets apparemment sains. En outre, l’OA est un élément clé du RCM dans ces deux populations. Les seuils actuels de TT devraient être reconsidérés éventuellement à la lumière d’études de plus grande envergure, afin de mieux définir l’OA chez les Noirs africains ou d’origine africaine, ce qui permettra une surveillance épidémiologique plus adéquate des biomarqueurs de RCM.

Probabilistic Evaluation of Three-Dimensional Reconstructions from X-Ray Images Spanning a Limited Angle

An important part of computed tomography is the calculation of a three-dimensional reconstruction of an object from series of X-ray images. Unfortunately, some applications do not provide sufficient X-ray images. Then, the reconstructed objects no longer truly represent the original. Inside of the volumes, the accuracy seems to vary unpredictably. In this paper, we introduce a novel method to evaluate any reconstruction, voxel by voxel. The evaluation is based on a sophisticated probabilistic handling of the measured X-rays, as well as the inclusion of a priori knowledge about the materials that the object receiving the X-ray examination consists of. For each voxel, the proposed method outputs a numerical value that represents the probability of existence of a predefined material at the position of the voxel while doing X-ray. Such a probabilistic quality measure was lacking so far. In our experiment, false reconstructed areas get detected by their low probability. In exact reconstructed areas, a high probability predominates. Receiver Operating Characteristics not only confirm the reliability of our quality measure but also demonstrate that existing methods are less suitable for evaluating a reconstruction.