Citations

Background— There is a paucity of randomized trials regarding diagnostic testing in women with suspected coronary artery disease (CAD). It remains unclear whether the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise treadmill test (ETT) provides incremental information to improve clinical decision making in women with suspected CAD. Methods and Results— We randomized symptomatic women with suspected CAD, an interpretable ECG, and ≥5 metabolic equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies: ETT or exercise MPI. The primary end point was 2-year incidence of major adverse cardiac events, defined as CAD death or hospitalization for an acute coronary syndrome or heart failure. A total of 824 women were randomized to ETT or exercise MPI. For women randomized to ETT, ECG results were normal in 64%, indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI results were normal in 91%, mildly abnormal in 3%, and moderate to severely abnormal in 6%. At 2 years, there was no difference in major adverse cardiac events (98.0% for ETT and 97.7% for MPI; P =0.59). Compared with ETT, index testing costs were higher for exercise MPI ( P <0.001), whereas downstream procedural costs were slightly lower ( P =0.0008). Overall, the cumulative diagnostic cost savings was 48% for ETT compared with exercise MPI ( P <0.001). Conclusions— In low-risk, exercising women, a diagnostic strategy that uses ETT versus exercise MPI yields similar 2-year posttest outcomes while providing significant diagnostic cost savings. The ETT with selective follow-up testing should be considered as the initial diagnostic strategy in symptomatic women with suspected CAD. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00282711.

Background—Current clinical diagnosis of long-QT syndrome (LQTS) includes genetic testing of family members of mutation-positive patients. The present study was designed to assess the clinical course of individuals who are found negative for the LQTS-causing mutation in their families.Methods and Results—Multivariate Cox proportional hazards model was used to assess the risk for cardiac events (comprising syncope, aborted cardiac arrest [ACA], or sudden cardiac death [SCD]) from birth through age 40 years among 1828 subjects from the LQTS Registry who were found negative for their family LQTS-causing mutation. The median QTc of study subjects was 423 ms (interquartile range, 402–442 ms). The cumulative probability of a first syncope through age 40 years was 15%. However, only 2 patients (0.1%) had ACA, and none died suddenly during follow-up. Independent risk factors for syncope in genotype-negative subjects included female sex (hazard ratio [HR], 1.60;P=0.002), prolonged QTc (HR=1.63 per 100 ms increment,P=0.02), family history of ACA or SCD (HR=1.89,P=0.002), and LQT2 versus LQT1 family mutation (HR=1.41,P=0.03). Subgroup analysis showed that the presence of theK897Tpolymorphism in the LQT2 gene in an affected family was associated with an 11-fold (P=0.001) increase in the risk of recurrent syncope in genotype-negative subjects.Conclusions—Our findings suggest that cardiac events among genotype-negative family members of LQTS patients are dominated by nonfatal syncopal episodes without occurrence of sudden cardiac death. The risk for nonfatal events in this population may be mediated by the presence of common polymorphisms in LQTS genes.

Abstract Background: Single nucleotide polymorphisms (SNP) in microRNA-related genes have been associated with epithelial ovarian cancer (EOC) risk in two reports, yet associated alleles may be inconsistent across studies. Methods: We conducted a pooled analysis of previously identified SNPs by combining genotype data from 3,973 invasive EOC cases and 3,276 controls from the Ovarian Cancer Association Consortium. We also conducted imputation to obtain dense coverage of genes and comparable genotype data for all studies. In total, 226 SNPs within 15 kb of 4 miRNA biogenesis genes (DDX20, DROSHA, GEMIN4, and XPO5) and 23 SNPs located within putative miRNA binding sites of 6 genes (CAV1, COL18A1, E2F2, IL1R1, KRAS, and UGT2A3) were genotyped or imputed and analyzed in the entire dataset. Results: After adjustment for European ancestry, no overall association was observed between any of the analyzed SNPs and EOC risk. Conclusions: Common variants in these evaluated genes do not seem to be strongly associated with EOC risk. Impact: This analysis suggests earlier associations between EOC risk and SNPs in these genes may have been chance findings, possibly confounded by population admixture. To more adequately evaluate the relationship between genetic variants and cancer risk, large sample sizes are needed, adjustment for population stratification should be carried out, and use of imputed SNP data should be considered. Cancer Epidemiol Biomarkers Prev; 20(8); 1793–7. ©2011 AACR.

Better tools for assessing cognitive impairment in the early stages of Alzheimer's disease (AD) are required to enable diagnosis of the disease before substantial neurodegeneration has taken place and to allow for detection of subtle changes in the early stages of progression of the disease. The National Institute on Aging and the Alzheimer's Association convened a meeting to discuss state‐of‐the art methods for cognitive assessment, including computerized batteries, as well as new approaches in the pipeline. Speakers described research using novel tests of object recognition, spatial navigation, attentional control, semantic memory, semantic interference, prospective memory, false memory, and executive function as among the tools that could provide earlier identification of individuals with AD. In addition to early detection, there is a need for assessments that reflect real‐world situations so as to better assess functional disability. It is especially important to develop assessment tools that are useful in ethnically, culturally, and linguistically diverse populations as well as in individuals with neurodegenerative disease other than AD.

The Florida Initiative for Quality Cancer Care has identified how multiple aspects of breast cancer care can be improved.