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Prospective Validation (prospective + validation)
Terms modified by Prospective Validation Selected AbstractsContractile Reserve Assessed Using Dobutamine Echocardiography Predicts Left Ventricular Reverse Remodeling after Cardiac Resynchronization Therapy: Prospective Validation in Patients with Left Ventricular DyssynchronyECHOCARDIOGRAPHY, Issue 6 2010F.R.C.P.C., Mario Sénéchal M.D. Background: The presence of viable myocardium may predict response to cardiac resynchronization therapy (CRT). The aim of this study is to evaluate in patients with left ventricular (LV) dyssynchrony whether response to CRT is related to myocardial viability in the region of the pacing lead. Methods: Forty-nine consecutive patients with advanced heart failure, LV ejection fraction < 35%, QRS duration > 120 ms and intraventricular asynchronism , 50 ms were included. Dobutamine stress echocardiography was performed within the week before CRT implantation. Resting echocardiography was performed 6 months after CRT implantation. Viability in the region of LV pacing lead was defined as the presence of viability in two contiguous segments. Response to CRT was defined by evidence of reverse LV remodeling (,15% reduction in LV end-systolic volume). Results: Thirty-one patients (63%) were identified as responders at follow-up. The average of viable segments was 5.9 ± 2 in responders and 3.2 ± 3 in nonresponders (P = 0.0003). Viability in the region of the pacing lead had a sensitivity of 94%, a specificity of 67%, a positive predictive value of 83%, and a negative predictive value of 86% for the prediction of response to CRT. Conclusions: In patients with LV dyssynchrony, reverse remodeling after CRT requires viability in the region of the pacing lead. This simple method using echocardiography dobutamine for the evaluation of local viability (i.e., viability in two contiguous segments) may be useful to the clinician in choosing the best LV lead positioning. (Echocardiography 2010;27:668-676) [source] Prospective Validation of a Modified Thrombolysis In Myocardial Infarction Risk Score in Emergency Department Patients With Chest Pain and Possible Acute Coronary SyndromeACADEMIC EMERGENCY MEDICINE, Issue 4 2010Erik P. Hess MD Abstract Objectives:, This study attempted to prospectively validate a modified Thrombolysis In Myocardial Infarction (TIMI) risk score that classifies patients with either ST-segment deviation or cardiac troponin elevation as high risk. The objectives were to determine the ability of the modified score to risk-stratify emergency department (ED) patients with chest pain and to identify patients safe for early discharge. Methods:, This was a prospective cohort study in an urban academic ED over a 9-month period. Patients over 24 years of age with a primary complaint of chest pain were enrolled. On-duty physicians completed standardized data collection forms prior to diagnostic testing. Cardiac troponin T-values of >99th percentile (,0.01 ng/mL) were considered elevated. The primary outcome was acute myocardial infarction (AMI), revascularization, or death within 30 days. The overall diagnostic accuracy of the risk scores was compared by generating receiver operating characteristic (ROC) curves and comparing the area under the curve. The performance of the risk scores at potential decision thresholds was assessed by calculating the sensitivity and specificity at each potential cut-point. Results:, The study enrolled 1,017 patients with the following characteristics: mean (±SD) age 59.3 (±13.8) years, 60.6% male, 17.9% with a history of diabetes, and 22.4% with a history of myocardial infarction. A total of 117 (11.5%) experienced a cardiac event within 30 days (6.6% AMI, 8.9% revascularization, 0.2% death of cardiac or unknown cause). The modified TIMI risk score outperformed the original with regard to overall diagnostic accuracy (area under the ROC curve = 0.83 vs. 0.79; p = 0.030; absolute difference 0.037; 95% confidence interval [CI] = 0.004 to 0.071). The specificity of the modified score was lower at all cut-points of >0. Sensitivity and specificity at potential decision thresholds were: >0 = sensitivity 96.6%, specificity 23.7%; >1 = sensitivity 91.5%, specificity 54.2%; and >2 = sensitivity 80.3%, specificity 73.4%. The lowest cut-point (TIMI/modified TIMI >0) was the only cut-point to predict cardiac events with sufficient sensitivity to consider early discharge. The sensitivity and specificity of the modified and original TIMI risk scores at this cut-point were identical. Conclusions:, The modified TIMI risk score outperformed the original with regard to overall diagnostic accuracy. However, it had lower specificity at all cut-points of >0, suggesting suboptimal risk stratification in high-risk patients. It also lacked sufficient sensitivity and specificity to safely guide patient disposition. Both scores are insufficiently sensitive and specific to recommend as the sole means of determining disposition in ED chest pain patients. ACADEMIC EMERGENCY MEDICINE,2010; 17:368,375 © 2010 by the Society for Academic Emergency Medicine [source] Prospective Validation of the Pediatric Appendicitis Score in a Canadian Pediatric Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 7 2009Maala Bhatt MD Abstract Objectives:, Clinical scoring systems attempt to improve the diagnostic accuracy of pediatric appendicitis. The Pediatric Appendicitis Score (PAS) was the first score created specifically for children and showed excellent performance in the derivation study when administered by pediatric surgeons. The objective was to validate the score in a nonreferred population by emergency physicians (EPs). Methods:, A convenience sample of children, 4,18 years old presenting to a pediatric emergency department (ED) with abdominal pain of less than 3 days' duration and in whom the treating physician suspected appendicitis, was prospectively evaluated. Children who were nonverbal, had a previous appendectomy, or had chronic abdominal pathology were excluded. Score components (right lower quadrant and hop tenderness, anorexia, pyrexia, emesis, pain migration, leukocytosis, and neutrophilia) were collected on standardized forms by EPs who were blinded to the scoring system. Interobserver assessments were completed when possible. Appendicitis was defined as appendectomy with positive histology. Outcomes were ascertained by review of the pathology reports from the surgery specimens for children undergoing surgery and by telephone follow-up for children who were discharged home. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated. The overall performance of the score was assessed by a receiver operator characteristic (ROC) curve. Results:, Of the enrolled children who met inclusion criteria (n = 246), 83 (34%) had pathology-proven appendicitis. Using the single cut-point suggested in the derivation study (PAS 5) resulted in an unacceptably high number of false positives (37.6%). The score's performance improved when two cut-points were used. When children with a PAS of ,4 were discharged home without further investigations, the sensitivity was 97.6% with a NPV of 97.7%. When a PAS of ,8 determined the need for appendectomy, the score's specificity was 95.1% with a PPV of 85.2%. Using this strategy, the negative appendectomy rate would have been 8.8%, the missed appendicitis rate would have been 2.4%, and 41% of imaging investigations would have been avoided. Conclusions:, The PAS is a useful tool in the evaluation of children with possible appendicitis. Scores of ,4 help rule out appendicitis, while scores of ,8 help predict appendicitis. Patients with a PAS of 5,7 may need further radiologic evaluation. [source] Prospective Validation of a Comprehensive In silico hERG Model and its Applications to Commercial Compound and Drug DatabasesCHEMMEDCHEM, Issue 5 2010Munikumar Abstract Ligand-based in silico hERG models were generated for 2,644 compounds using linear discriminant analysis (LDA) and support vector machines (SVM). As a result, the dataset used for the model generation is the largest publicly available (see Supporting Information). Extended connectivity fingerprints (ECFPs) and functional class fingerprints (FCFPs) were used to describe chemical space. All models showed area under curve (AUC) values ranging from 0.89 to 0.94 in a fivefold cross-validation, indicating high model consistency. Models correctly predicted 80,% of an additional, external test set; Y-scrambling was also performed to rule out chance correlation. Additionally models based on patch clamp data and radioligand binding data were generated separately to analyze their predictive ability when compared to combined models. To experimentally validate the models, 50 of the predicted hERG blockers from the Chembridge database and ten of the predicted non-hERG blockers from an in-house compound library were selected for biological evaluation. Out of those 50 predicted hERG blockers, tested at a concentration of 10,,M, 18 compounds showed more than 50,% displacement of [3H]astemizole binding to cell membranes expressing the hERG channel. Ki values of four of the selected binders were determined to be in the micromolar and high nanomolar range (Ki (VH01)=2.0,,M, Ki (VH06)=0.15,,M, Ki (VH19)=1.1,,M and Ki (VH47)=18 ,M). Of these four compounds, VH01 and VH47 showed also a second, even higher affinity binding site with Ki values of 7.4,nM and 36,nM, respectively. In the case of non-hERG blockers, all ten compounds tested were found to be inactive, showing less than 50,% displacement of [3H]astemizole binding at 10,,M. These experimentally validated models were then used to virtually screen commercial compound databases to evaluate whether they contain hERG blockers. 109,784 (23,%) of Chembridge, 133,175 (38,%) of Chemdiv, 111,737 (31,%) of Asinex and 11,116 (18,%) of the Maybridge database were predicted to be hERG blockers by at least two of the models, a prediction which could, for example, be used as a pre-filtering tool for compounds with potential hERG liabilities. [source] Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma,HEPATOLOGY, Issue 1 2008Alejandro Forner This study prospectively evaluates the accuracy of contrast-enhanced ultrasound (CEUS) and dynamic magnetic resonance imaging (MRI) for the diagnosis of nodules 20 mm or smaller detected during ultrasound (US) surveillance. We included 89 patients with cirrhosis [median age, 65 years; male 53, hepatitis C virus 68, Child-Pugh A 80] without prior hepatocellular carcinoma (HCC) in whom US detected a small solitary nodule (mean diameter, 14 mm). Hepatic MRI, CEUS, and fine-needle biopsy (gold standard) (FNB) were performed at baseline. Non-HCC cases were followed (median 23 months) by CEUS/3 months and MRI/6 months. FNB was repeated up to 3 times and on detection of change in aspect/size. Intense arterial contrast uptake followed by washout in the delayed/venous phase was registered as conclusive for HCC. Final diagnoses were: HCC (n = 60), cholangiocarcinoma (n = 1), and benign lesions (regenerative/dysplastic nodule, hemangioma, focal nodular hyperplasia) (n = 28). Sex, cirrhosis cause, liver function, and alpha-fetoprotein (AFP) levels were similar between HCC and non-HCC groups. HCC patients were older and their nodules significantly larger (P < 0.0001). First biopsy was positive in 42 of 60 HCC patients. Sensitivity, specificity, and positive and negative predictive values of conclusive profile were 61.7%, 96.6%, 97.4%, and 54.9%, for MRI, 51.7%, 93.1%, 93.9%, and 50.9%, for CEUS. Values for coincidental conclusive findings in both techniques were 33.3%, 100%, 100%, and 42%. Thus, diagnosis of HCC 20 mm or smaller can be established without a positive biopsy if both CEUS and MRI are conclusive. However, sensitivity of these noninvasive criteria is 33% and, as occurs with biopsy, absence of a conclusive pattern does not rule out malignancy. These results validate the American Association for the Study of Liver Disease (AASLD) guidelines. (HEPATOLOGY 2007.) [source] Prospective validation of P2/MS noninvasive index using complete blood counts for detecting oesophageal varices in B-viral cirrhosisLIVER INTERNATIONAL, Issue 6 2010Beom Kyung Kim Abstract Backgrounds: Periodic endoscopic screening for oesophageal varices (OVs) and prophylactic treatment for high-risk OVs (HOVs; medium/large OVs or small OVs plus red sign/decompensation) are currently recommended for all cirrhotic patients. However, if a simple, noninvasive test is available, many low-risk patients may reliably avoid endoscopy. Aims: We conducted a large-scale validation study of a simple, noninvasive test called P2/MS based on complete blood counts, (platelet count)2/[monocyte fraction (%) × segmented neutrophil fraction (%)], and compared it with other predictive tests for HOVs in B-viral cirrhotic patients. Methods: From 2008 to 2009, we prospectively enrolled 318 consecutive B-viral cirrhotic patients. All underwent endoscopy and laboratory evaluation. Results: An area under the receiver operating characteristic curve of P2/MS was 0.941 for HOVs, comparable with those of the age,spleen platelet ratio index (0.922, P=0.317) and spleen,platelet ratio index (0.922, P=0.324), and better than those of age,platelet index (0.653, P<0.001), aspartate aminotransferase (AST),platelet ratio index (0.871, P<0.006) and AST-alanine aminotransferase ratio (0.644, P<0.001). P2/MS<11 reliably identified 83 patients as having HOVs (94.0% positive predictive value), while at a cutoff of 25 and 179 as not having HOVs (94.4% negative predictive value). Overall, P2/MS reliably determined the likelihood of HOVs in 262 patients (82.4%). These cutoffs were validated internally using bootstrap resampling methods, which showed good agreement. Conclusions: P2/MS is a simple, accurate and economical method, reducing the need for endoscopy in B-viral cirrhosis. Patients with P2/MS<11 should be considered for appropriate prophylactic treatments, while those with P2/MS>25 may avoid endoscopy reliably. [source] Peripheral blood MDS score: A new flow cytometric tool for the diagnosis of myelodysplastic syndromes,CYTOMETRY, Issue 1 2005Sindhu Cherian Abstract Background Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders diagnosed using morphologic and clinical findings supported by cytogenetics. Because abnormalities may be subtle, diagnosis using these approaches can be challenging. Flow cytometric (FCM) approaches have been described; however the value of bone marrow immunophenotyping in MDS remains unclear due to the variability in detected abnormalities. We sought to refine the FCM approach by using peripheral blood (PB) to create a clinically useful tool for the diagnosis of MDS. Methods PB from 15 patients with MDS was analyzed by multiparametric flow cytometry using an extensive panel of monoclonal antibodies. Patterns of neutrophil antigen expression were compared with those of normal controls (n = 16) to establish light scatter and/or immunophenotypic abnormalities that correlated with MDS. A scoring algorithm was developed and validated prospectively on a blinded patient set. Results PB neutrophils from patients with MDS had lower side scatter and higher expression of CD66 and CD11a than did controls. Some MDS PB neutrophils demonstrated abnormal CD116 and CD10 expression. Because none of these abnormalities proved consistently diagnostic, we sought to increase the power of the assay by devising a scoring system to allow the association of multiple abnormalities and account for phenotypic variations. The PB MDS score differentiated patients with MDS from controls (P < 0.0001) in the test set. In a prospective validation, the PB MDS score successfully identified patients with MDS (sensitivity 73%, specificity 90%). Conclusions FCM analysis of side scatter and only four additional immunophenotypic parameters of PB neutrophils using the PB MDS score proved more sensitive than standard laboratory approaches and may provide an additional, more reliable diagnostic tool in the identification of MDS. © 2005 Wiley-Liss, Inc. [source] Anaphylaxis: Clinical concepts and research prioritiesEMERGENCY MEDICINE AUSTRALASIA, Issue 2 2006Simon GA Brown Abstract Anaphylaxis is a severe immediate-type hypersensitivity reaction characterized by life-threatening upper airway obstruction bronchospasm and hypotension. Although many episodes are easy to diagnose by the combination of characteristic skin features with other organ effects, this is not always the case and a workable clinical definition of anaphylaxis and useful biomarkers of the condition have been elusive. A recently proposed consensus definition is ready for prospective validation. The cornerstones of management are the supine position, adrenaline and volume resuscitation. An intramuscular dose of adrenaline is generally recommended to initiate treatment. If additional adrenaline is required, then a controlled intravenous infusion might be more efficacious and safer than intravenous bolus administration. Additional bronchodilator treatment with continuous salbutamol and corticosteroids are used for severe and/or refractory bronchospasm. Aggressive volume resuscitation, selective vasopressors, atropine (for bradycardia), inotropes that bypass the ,-adrenoreceptor and bedside echocardiographic assessment should be considered for hypotension that is refractory to treatment. Management guidelines continue to be opinion- and consensus-based, with retrospective studies accounting for the vast majority of clinical research papers on the topic. The clinical spectrum of anaphylaxis including major disease subgroups requires clarification, and validated scoring systems and outcome measures are needed to enable good-quality prospective observational studies and randomized controlled trials. A systematic approach with multicentre collaboration is required to improve our understanding and management of this disease. [source] Disseminated intravascular coagulation in acute leukemia: clinical and laboratory features at presentationEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2006Masamitsu Yanada Abstract:,Background:,Although there are two major scoring systems for the clinical diagnosis of disseminated intravascular coagulation (DIC), the validity of these systems for leukemia-associated DIC remains to be confirmed. Methods:,By analyzing 125 newly diagnosed acute leukemia patients, we investigated clinical and laboratory features of leukemia-associated DIC, and determined the validity of the two established criteria. Results:,A total of 36 patients (29%) were diagnosed with DIC according to expert opinion, a method regarded as the de facto gold standard. Leukemia-associated DIC is characterized by rare manifestation of organ failure because of thrombosis and no relevance of the platelet count for the diagnosis. The results of receiver operating characteristics analysis favored fibrin degradation product (FDP) rather than D-dimer as the fibrin-related marker test. Although prothrombin time, plasma fibrinogen, and serum FDP levels were significantly different for patients with and without DIC, multivariate analysis identified FDP levels to be the only factor associated with DIC diagnosis. The cut-off level of 15 ,g/mL for FDP was found to be the most effective to differentiate DIC from non-DIC, resulting in diagnostic sensitivity and specificity of 92% and 96%, respectively. The diagnostic results for our patients produced with this FDP-based system were at least comparable with or superior to those obtained with the two currently available scoring systems. Conclusions:,Our findings suggest that an FDP-based criterion may be applicable for the diagnosis of leukemia-associated DIC. Although it appears to be simple and practicable enough for clinical use, prospective validation of this criterion is needed. [source] The galectin family and digestive disease,THE JOURNAL OF PATHOLOGY, Issue 1 2008P Demetter Abstract The soluble-type lectins or galectins constitute a family of proteins defined by shared consensus amino acid sequence and affinity for beta-galactose-containing oligosaccharides. These molecules are widely distributed in the animal kingdom; to date, 15 mammalian galectins have been described but more are likely to be discovered. These proteins are involved in many biological processes including cell,cell and cell,matrix adhesion, growth regulation, signaling, and cytokine secretion. Over the last decade, a vast amount of reports has shown the importance of several galectins in the development and progression of malignancies in the digestive tract, mainly colorectal cancers. More recent data indicate that some of these molecules are also involved in inflammatory bowel diseases. This review focuses on the current knowledge of galectin expression and putative functions in the oesophagus, stomach, small intestine, and colon. It also highlights that the rapid accumulation of research data promises future scenarios in which individual members of the galectin family and/or their ligands will be used as diagnostic and therapeutic modalities for neoplastic as well as inflammatory disorders. However, the concretization of these potential modalities requires substantial improvements in terms of standardization of galectin expression evaluation together with prospective validation of the present data. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Association between serum lipoprotein (a) level and progression of non-proliferative diabetic retinopathy in Type 2 diabetesACTA OPHTHALMOLOGICA, Issue 5 2009Hideharu Funatsu Abstract. Purpose:, To investigate independent risk factors related to the progression of non-proliferative diabetic retinopathy (NPDR) for Japanese Type 2 diabetic patients. Methods:, One hundred and six patients with NPDR were followed up for 2 years. Diabetic retinopathy (DR) was determined by colour fundus photography. Multivariate logistic regression analysis was performed to assess variables independently associated with the progression of NPDR. Serum concentrations of novel risk factors for atherosclerotic vascular disease, including lipoprotein (a) [Lp(a)] and fibrinogen, were measured. Results:, Thirty-three patients (31%) had progressed by two scale steps or more in 2 years. The progression of NPDR was significantly associated with HbA1c [odds ratio (OR) 2.12; 95% confidence interval (CI) 1.14,4.87], systolic blood pressure (OR 1.72; 95% CI 1.14,2.91), Lp(a) (OR 2.70; 95% CI 1.09,5.12) and fibrinogen (OR 1.68; 95% CI 1.03,3.08). Multivariate logistic regression analysis showed that HbA1c (OR 1.74; 95% CI 1.12,3.21) and Lp(a) level (OR 1.90; 95% CI 1.06,4.33) were significant and independent predictors of the progression of NPDR. Conclusion:, These data suggest that serum Lp(a) level is an independent risk factor for the progression of NPDR in Type 2 diabetes patients. We recommend that further prospective validation of our findings be undertaken to confirm these observations. [source] A systematic review of the features that indicate intentional scalds in childrenCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 1 2009Richard Reading A systematic review of the features that indicate intentional scalds in children . MaguireS., MoynihanS., MannM., PotokarT. & KempA. M. ( 2008 ) Burns , 34 , 1072 , 1081 . DOI: 10.1016/j.burns.2008.02.011 . Background Most intentional burns are scalds, and distinguishing these from unintentional causes is challenging. Aim To conduct a systematic review to identify distinguishing features of intentional and unintentional scalds. Methods We performed an all language literature search of 12 databases 1950,2006. Studies were reviewed by two paediatric/burns specialists, using standardized methodology. Included: Primary studies of validated intentional or accidental scalds in children 0,18 years old and ranked by confirmation of intentional or unintentional origin. Excluded: Neglectful scalds; management or complications; studies of mixed burn type or mixed adult and child data. Results A total of 258 studies were reviewed, and 26 included. Five comparative studies ranked highly for confirmation of intentional/unintentional cause of injury. The distinguishing characteristics were defined based on best evidence. Intentional scalds were commonly immersion injuries, caused by hot tap water, affecting the extremities, buttocks or perineum or both. The scalds were symmetrical with clear upper margins, and associated with old fractures and unrelated injuries. Unintentional scalds were more commonly due to spill injuries of other hot liquids, affecting the upper body with irregular margins and depth. Conclusions We propose an evidence-based triage tool to aid in distinguishing intentional from unintentional scalds, requiring prospective validation. [source] | ||||||||||