Association of coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older persons.
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Biomedical subjects
Publications and source records attributed to C Ahn.
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OBJECTIVE: To investigate whether ingested human recombinant interferon-alpha2a (IFN-alpha2a) was safe and whether treatment reduces the number of gadolinium-enhanced lesions on serial MRI in patients with active relapsing-remitting MS (RRMS). METHODS: Entry criteria included clinically definite RRMS and one or more gadolinium-enhanced lesions on a screening MRI. RESULTS: Of 80 patients screened, 33 were eligible and 30 patients were enrolled for treatment. Patients were randomized (10 per group) to placebo, 10,000 or 30,000 IU IFN-alpha2a ingested on alternate days for 9 months. They were examined clinically and with monthly cerebral MRI. Sample size projections were based on the assumption of a parenteral IFN-like effect, a 90% reduction of enhancing lesions evident within 1 month of the initiation of treatment in the active treatment groups sustained during the 9-month study as the primary outcome variable. RESULTS: There was no significant effect on enhancing lesions. However, post hoc analysis suggested a possible treatment effect in the 10,000 IU group. By direct monthly comparison of placebo and 10,000 IU group in treatment month 5, there were 73% (p < 0.05) fewer enhancements in the 10,000 IU group than in the placebo group. There was a decrease of tumor necrosis factor-alpha protein secretion at months 4 and 5. Relapses and adverse events were not different among the treatment groups. Ingested IFN-alpha2a did not induce systemic anti-IFN-alpha antibodies. CONCLUSIONS: This trial showed no benefit based on the primary outcome measure. Because changes were detected in immune response and post hoc analysis suggested that a smaller dose could have an effect, IFN-alpha may deserve further study.
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A simple adjustment to the Pearson chi-square test has been proposed for comparing proportions estimated from clustered binary observations. However, the assumptions needed to assure the validity of this test have not yet been thoroughly addressed. These assumptions will hold for experimental comparisons, but could be violated for some observational comparisons. In this paper we investigate the conditions under which the adjusted chi-square statistic is valid and examine its performance when these assumptions are violated. We also introduce some alternative test statistics that do not require these assumptions. The test statistics considered are then compared through simulation and an example presented based on real data. The simulation study shows that the adjusted chi-square statistic generally produces empirical type I errors close to nominal under the assumption of a common intracluster correlation coefficient. Even if the intracluster correlations are different, the adjusted chi-square statistic performs well when the groups have equal numbers of clusters.
In this paper we propose a sample size calculation method for testing on a binomial proportion when binary observations are dependent within clusters. In estimating the binomial proportion in clustered binary data, two weighting systems have been popular: equal weights to clusters and equal weights to units within clusters. When the number of units varies cluster by cluster, performance of these two weighting systems depends on the extent of correlation among units within each cluster. In addition to them, we will also use an optimal weighting method that minimizes the variance of the estimator. A sample size formula is derived for each of the estimators with different weighting schemes. We apply these methods to the sample size calculation for the sensitivity of a periodontal diagnostic test. Simulation studies are conducted to evaluate a finite sample performance of the three estimators. We also assess the influence of misspecified input parameter values on the calculated sample size. The optimal estimator requires equal or smaller sample sizes and is more robust to the misspecification of an input parameter than those assigning equal weights to units or clusters.
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Of 613 persons, mean age 79 +/- 9 years, with prior myocardial infarction and diabetes mellitus, 68 (11%) had contraindications to beta blockers; 289 of 545 persons (53%) without contraindications to beta blockers were treated with beta blockers. The Cox regression model showed that significant independent predictors of new coronary events were age (risk ratio 1.02 for an increment of 1 year of age), systemic hypertension (risk ratio 2.0), serum low-density lipoprotein cholesterol > or =125 mg/dl (risk ratio 1.4), serum high-density lipoprotein cholesterol < or =35 mg/dl (risk ratio 1.6), and use of beta blockers (risk ratio 0.73).
A retrospective analysis of 171 women and 119 men, mean age 76 +/- 9 years, with aortic stenosis diagnosed by Doppler echocardiography, who had follow-up Doppler echocardiograms, showed that the reduction in aortic valve area per year was not significantly different in older persons with mild, moderate, and severe aortic stenosis. The decrease in aortic valve area per year was significantly greater in men 60 to 74 years old than in women 60 to 74 years old (p = 0.025), in women > or =75 years old than in women 60 to 74 years old (p = 0.006), and in persons with mitral annular calcium than in persons without mitral annular calcium (p = 0.046).
BACKGROUND: Thrombomodulin (TM) is expressed on the endothelial surface and plays an important role in vasoprotection. A common polymorphism of TM at amino acid position 455 with an alanine (A) to valine (V) transition was previously reported to be associated cross-sectionally with acute myocardial infarction. Whether this single nucleotide polymorphism predicts risk of developing coronary heart disease (CHD) is unclear. METHODS AND RESULTS: Within a large cohort study, we identified 467 incident CHD cases during an average of 5 years of follow-up. We determined TM-455 genotypes on 376 CHD cases (23% black, 77% white) and a reference sample of 461. The AA genotype was significantly more prevalent in noncases than in cases (P:=0.016). The prevalences of the AA genotype in noncase blacks and whites were 93% and 67%, respectively. The AA genotype frequency was significantly reduced in black cases versus noncases (P:=0.018). It was also lower in white cases than in noncases, but the difference was not statistically significant (P:=0.066). Weighted proportional hazards regression analysis after adjustment for age, sex, and other CHD risk factors showed that having the V allele increased risk of CHD by 6.1-fold (risk ratio 6.1, 95% CI 1.7 to 22.9) in blacks but did not significantly increase the risk in whites. CONCLUSIONS: The TM A455V polymorphism predicts risk of developing CHD in blacks.
In a prospective study of 651 older persons with congestive heart failure after prior myocardial infarction, persons with atrial fibrillation had a significantly higher mortality than those with sinus rhythm if they had an abnormal (p = 0.005) or normal (p = 0.0001) left ventricular ejection fraction. The Cox regression model showed that significant independent risk factors for total mortality were age (risk ratio 1.03 for an increment of 1 year of age), hypertension (risk ratio 1.2), diabetes mellitus (risk ratio 1.4), abnormal left ventricular ejection fraction (risk ratio 2.1), and atrial fibrillation (risk ratio 1.5).
The 1400 kb genomic sequence between the markers D16S406 and D16S423 on chromosome 16p13.3 has been recently sequenced and the interval contains a transcription factor, AP-4, that was identified as a ligand for immunoglobulin-kappa promoter E-box elements,(1)suggesting that AP-4 may be related to immunodeficiency diseases. In addition, chromosome 16p13.3 includes a number of genes including the PKD1 gene,(2,3)the autosomal dominant polycystic kidney disease (ADPKD) gene. ADPKD is characterized by progressive development and enlargement of renal cysts.(4)The size and genomic complexity of the PKD1 gene makes it impractical to detect mutations for prenatal diagnosis. Therefore, pedigree-based linkage analysis remains useful for diagnosis of ADPKD. To increase the number of polymorphic markers in the region around AP-4 gene, we performed database searches of 1400 kb of genomic sequence (from contig NT000677 to NT001573: http://www.ncbi.gov/genome/seq.cgi) across the 16p13.3. A number of dinucleotide or tetranucleotide repeats were found, and 20 microsatellites that contain more than 15 contiguous repeats were chosen for further investigation.
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We investigated the use of flue-gas-desulfurization (FGD) by-products from electric power plant wet scrubbers as liners in wetlands constructed to improve water quality. Mesocosm experiments were conducted over two consecutive growing seasons with different phosphorus loadings. Wetland mesocosms using FGD liners retained more total and soluble reactive phosphorus, with lower concentrations in the leachate (first year) and higher concentrations in the surface water (second year). Leachate was higher in conductivity (second year) and pH (both years) in lined mesocosms. Surface outflow did not reveal any significant difference in physicochemical characteristics between lined and unlined mesocosms. There was no significant difference in total biomass production of wetland plants between lined and unlined mesocosms although lower average stem lengths and fewer stems bearing flowers were observed in mesocosms with FGD liners. Potentially phytotoxic boron was significantly higher in the belowground biomass of plants grown in lined mesocosms with low phosphorus loading. A larger-scale, long-term wetland experiment close to full scale is recommended from this two-year mesocosm study to better predict the potentially positive and negative effects of using FGD by-products in constructed wetlands.
Controlled clinical trials in neuropsychopharmacology, as in numerous other clinical research domains, tend to employ a conventional parallel-groups design with repeated measurements. The hypothesis of primary interest in the relatively short-term, double-blind trials, concerns the difference between patterns or magnitudes of change from baseline. A simple two-stage approach to the analysis of such data involves calculation of an index or coefficient of change in stage 1 and testing the significance of difference between group means on the derived measure of change in stage 2. This article has the aim of introducing formulas and a computer program for sample size and/or power calculations for such two-stage analyses involving each of three definitions of change, with or without baseline scores entered as a covariate, in the presence of homogeneous or heterogeneous (autoregressive) patterns of correlation among the repeated measurements. Empirical adjustments of sample size for the projected dropout rates are also provided in the computer program.
PURPOSE: The -455G/A (HaeIII) polymorphism of the beta-fibrinogen gene influences levels of plasma fibrinogen. We determined whether it influences risk of coronary heart disease. METHODS: We conducted a case-cohort study nested within a prospective investigation, the Atherosclerosis Risk in Communities Study. We accumulated 398 incident coronary heart disease cases over a median of 5.3 years of follow-up and compared their -455G/A status with a random sample of the cohort (n = 498). RESULTS: Plasma fibrinogen was higher (p = 0.04) in AA homozygous participants (341 mg/dL) than in persons carrying the G allele: GA (290 mg/dL), GG (298 mg/dL). However, there was no significant association between -455G/A and incident CHD. CONCLUSIONS: Although a small effect cannot be excluded, -455G/A does not appear to be an important genetic determinant of CHD.