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Score Alone (score + alone)
Selected AbstractsInterpreting missense variants: comparing computational methods in human disease genes CDKN2A, MLH1, MSH2, MECP2, and tyrosinase (TYR),,HUMAN MUTATION, Issue 7 2007Philip A. Chan Abstract The human genome contains frequent single-basepair variants that may or may not cause genetic disease. To characterize benign vs. pathogenic missense variants, numerous computational algorithms have been developed based on comparative sequence and/or protein structure analysis. We compared computational methods that use evolutionary conservation alone, amino acid (AA) change alone, and a combination of conservation and AA change in predicting the consequences of 254 missense variants in the CDKN2A (n = 92), MLH1 (n = 28), MSH2 (n = 14), MECP2 (n = 30), and tyrosinase (TYR) (n = 90) genes. Variants were validated as either neutral or deleterious by curated locus-specific mutation databases and published functional data. All methods that use evolutionary sequence analysis have comparable overall prediction accuracy (72.9,82.0%). Mutations at codons where the AA is absolutely conserved over a sufficient evolutionary distance (about one-third of variants) had a 91.6 to 96.8% likelihood of being deleterious. Three algorithms (SIFT, PolyPhen, and A-GVGD) that differentiate one variant from another at a given codon did not significantly improve predictive value over conservation score alone using the BLOSUM62 matrix. However, when all four methods were in agreement (62.7% of variants), predictive value improved to 88.1%. These results confirm a high predictive value for methods that use evolutionary sequence conservation, with or without considering protein structural change, to predict the clinical consequences of missense variants. The methods can be generalized across genes that cause different types of genetic disease. The results support the clinical use of computational methods as one tool to help interpret missense variants in genes associated with human genetic disease. Hum Mutat 28(7), 683,693, 2007. Published 2007 Wiley-Liss, Inc. [source] Assessment of the 10-Year Probability of Osteoporotic Hip Fracture Combining Clinical Risk Factors and Heel Bone Ultrasound: The EPISEM Prospective Cohort of 12,958 Elderly Women,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2008Didier Hans Abstract This study aimed to develop a hip screening tool that combines relevant clinical risk factors (CRFs) and quantitative ultrasound (QUS) at the heel to determine the 10-yr probability of hip fractures in elderly women. The EPISEM database, comprised of ,13,000 women ,70 yr of age, was derived from two population-based white European cohorts in France and Switzerland. All women had baseline data on CRFs and a baseline measurement of the stiffness index (SI) derived from QUS at the heel. Women were followed prospectively to identify incident fractures. Multivariate analysis was performed to determine the CRFs that contributed significantly to hip fracture risk, and these were used to generate a CRF score. Gradients of risk (GR; RR/SD change) and areas under receiver operating characteristic curves (AUC) were calculated for the CRF score, SI, and a score combining both. The 10-yr probability of hip fracture was computed for the combined model. Three hundred seven hip fractures were observed over a mean follow-up of 3.2 yr. In addition to SI, significant CRFs for hip fracture were body mass index (BMI), history of fracture, an impaired chair test, history of a recent fall, current cigarette smoking, and diabetes mellitus. The average GR for hip fracture was 2.10 per SD with the combined SI + CRF score compared with a GR of 1.77 with SI alone and of 1.52 with the CRF score alone. Thus, the use of CRFs enhanced the predictive value of SI alone. For example, in a woman 80 yr of age, the presence of two to four CRFs increased the probability of hip fracture from 16.9% to 26.6% and from 52.6% to 70.5% for SI Z-scores of +2 and ,3, respectively. The combined use of CRFs and QUS SI is a promising tool to assess hip fracture probability in elderly women, especially when access to DXA is limited. [source] Can inclusion of serum creatinine values improve the Child,Turcotte,Pugh score and challenge the prognostic yield of the model for end-stage liver disease score in the short-term prognostic assessment of cirrhotic patients?,LIVER INTERNATIONAL, Issue 5 2004Edoardo Giannini Abstract: Background: The model for end-stage liver disease (MELD) score is a useful tool to assess prognosis in critically ill cirrhotic patients. However, its short-term prognostic superiority over the traditional Child,Turcotte,Pugh (CTP) score has not been definitely confirmed. The creatinine serum level is an important predictor of survival in patients with liver cirrhosis. Aims: To evaluate and compare the short-term prognostic accuracy of the CTP, the creatinine-modified CTP, and the MELD scores in patients with liver cirrhosis. Methods: CTP, creatinine-modified CTP, and MELD scores were calculated in a cohort of 145 cirrhotic patients. The creatinine-modified CTP was calculated as follows: we assessed the mean creatinine serum level and standard deviation (SD) of the 145 study patients, then assigned a score of 1 to patients with creatinine serum levels , to the mean, a score of 2 to patients with creatinine levels between the mean and the mean+1 SD, and a score of 3 to patients with creatinine levels above the mean+1 SD. The creatinine-modified CTP was then calculated by simply adding each patients' creatinine score to their traditional CTP scores. We calculated and compared the accuracy (c -index) of the three parameters in predicting 3-month survival. Results: The creatinine-modified CTP score showed better prognostic accuracy as compared with the traditional CTP (P=0.049). However, the MELD score proved to be better at defining patients' prognosis in the short-term as compared with both the traditional CTP score (P=0.012) and the creatinine-modified CTP (P=0.047). The excellent short-term prognostic accuracy of the MELD score was confirmed even when patients with abnormal creatinine serum levels were excluded from the analysis (c -index=0.935). Conclusions: Adding creatinine values to the CTP slightly improves the prognostic usefulness of the traditional CTP score alone. The MELD score has a short-term prognostic yield that is better than what is provided by both the CTP and CTP creatinine-modified scores, even in cirrhotic patients who are not critically ill. The positive results obtained by using the MELD score were confirmed even after excluding patients with impaired renal function. [source] The use of Butea superba (Roxb.) compared to sildenafil for treating erectile dysfunctionBJU INTERNATIONAL, Issue 2 2010Jeff R. Cortés-González Study Type , Therapy (case control) Level of Evidence 3b OBJECTIVE To evaluate the effect of an extract of Butea superba (Roxb.) (BS) compared to sildenafil for treating erectile dysfunction (ED). PATIENTS AND METHODS An open label study was carried out among 32 men with organic ED to evaluate the response on the International Index of Erectile Function 5 (IIEF-5) to BS, a ,natural health' product (100 mg), compared to 50 mg of sildenafil (a phosphodiesterase-5 inhibitor). After a 1-week wash-out, responders to BS received either 100 mg starch or 100 mg of another batch of BS (double-blind). RESULTS Of the patients in the BS group, 27 (84%) responded positively, compared with 26 (81%) in the sildenafil group. When assessing the score alone, 12 (38%) had a better score after taking BS, compared to seven (22%) after sildenafil, and eight (25%) had the same score. The results were surprising and could not be repeated in the double-blind part of the study, where no effect of BS was recorded. CONCLUSIONS A ,natural' health product containing BS was more effective than sildenafil in the first part of the study, but in the second, using another batch of BS, the positive result could not be repeated and no effect was recorded. The conclusion is that the first preparation of BS was most likely blended with a phosphodiesterase-5 inhibitor, later confirmed by the supplier of BS (a natural health products company) after their own analysis. [source] | ||||||||||