Citations

Abstract Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987–. ©2013 AACR.

Background: Cardiovascular (CV) disease is the leading cause of death in U.S. women. Although women are becoming more aware of CV disease, there remains a dichotomy between awareness and perceived risk. We sought to characterize this dichotomy in women attracted to a CV health–screening event, in order to improve strategies to reduce CV risk. Methods: During CV health events held in Rochester, Minnesota, from 2007 through 2011, 294 women underwent screening for blood chemistry, body mass index, and blood pressure. Participants also completed surveys about knowledge of CV disease, risk factors, and perceived risk. Risk level was determined from the 2011 American Heart Association Effectiveness-Based Guidelines for Women. Results: Among participants (age, mean [standard deviation], 53 [15.3] years; white, 98%), 99% were aware that CV disease is the leading cause of death in women. Almost half (47%) perceived themselves to be at personal risk, although 65% were determined to be “at risk” and 12% to be at “high risk” according to guidelines, while 22% were uncategorized. Of the 228 participants “at risk” or “high risk,” 48% and 21%, respectively, did not perceive themselves to be at any risk. Conclusions : Women attracted to CV health events were aware that CV disease is the leading cause of death for women. However, the magnitude of awareness did not directly translate into perception or understanding of actual personal risk. To decrease the rate of CV disease in women, continued efforts are needed to personalize the importance of, and the methods for reducing, CV risk factors.

Background: Single infusions of ketamine have been used successfully to achieve improvement in depressed patients. Side effects during the infusions have been common. It is not known whether serial infusions or lower infusion rates result in greater efficacy. Methods: Ten depressed patients were treated with twice weekly ketamine infusions of ketamine 0.5 mg/kg administered over 100 min until either remission was achieved or four infusions were given. Side effects were assessed with the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). Patients were followed naturalistically at weekly intervals for four weeks after completion of the infusions. Results: Five of 10 patients achieved remission status. There were no significant increases on the BPRS or YMRS. Two of the remitting patients sustained their improvement throughout the four week follow-up period. Conclusions: Ketamine infusions at a lower rate than previously reported have demonstrated similar efficacy and excellent tolerability and may be more practically available for routine clinical care. Serial ketamine infusions appear to be more effective than a single infusion. Further research to test relapse prevention strategies with continuation ketamine infusions is indicated.

BackgroundIn recent years, percutaneous device closure has become commonplace for treatment of atrial septal defect (ASD) and patent foramen ovale (PFO). However, the effect of device closure on aortic valve regurgitation (AR) has been questioned.ObjectiveThe purpose of this study was to define changes in AR using echocardiography, before and after device closure of ASD or PFO.MethodsWe retrospectively reviewed all patients who had percutaneous device closure of ASD or PFO at our institution between 2005 and 2009. We compared the preprocedure echocardiogram to the most recent follow‐up study. All investigators were blinded to referral diagnosis, patient demographics, and size and type of the device placed. Aortic regurgitation was graded as none/trivial, mild, moderate, or severe.ResultsOverall, 322 patients qualified for inclusion; 204 with PFO and 118 with ASD. Mean age at time of closure was 48 ± 20 years (range 3–85 years). Mean duration of follow‐up was 1.2 years (range 2 months to 5 years). Only two patients (0.6%) demonstrated any appreciable increase in AR severity. However, both of these patients manifested a clinically insignificant change from a trivial to mild grade of aortic regurgitation.ConclusionsPercutaneous device closure of PFO or ASD does not increase the incidence or severity of AR over medium‐term follow‐up. © 2012 Wiley Periodicals, Inc.

ABSTRACTObjectives:Children with nonalcoholic fatty liver disease (NAFLD) experience compromised quality of life (QOL) akin to those with other chronic disease. Our objectives were to examine the association between NAFLD and QOL as well as other psychosocial outcomes, to compare psychosocial outcomes to obese children without known NAFLD, and to determine whether present standard care for NAFLD results in weight loss and improvement in psychosocial outcomes longitudinally.Methods:Children with NAFLD between 8 and 18 years and obese control children without known NAFLD were consented to complete a brief psychosocial battery examining depression (Children's Depression Inventory), QOL (Pediatric Quality of Life Inventory; PedsQL), and effect of weight on self‐esteem (Body‐Esteem Scale for Adolescents and Adults) at baseline; and additionally for the NAFLD group after at least 6 months.Results:A total of 48 children with NAFLD and 40 obese control children were enrolled. The PedsQL scores were not significantly different but the CDI total score and subscales of negative mood, ineffectiveness, and negative self‐esteem as well as all of the 3 subscales of BESAA, appearance, attribution, and weight were worse in the NAFLD group compared with obese controls. The PedsQL scores also did not change after standard care in the 33 patients with NAFLD who completed the follow‐up evaluations, but the CDI score differed between those whose body mass index improved or not.Conclusions:Children with NAFLD have higher levels of depression than obese controls. Outcomes did not improve with standard care. Larger longitudinal studies and appropriate interventions are required in this area.

Background— Cardiopulmonary exercise testing (CPX) with measurement of peak oxygen uptake (V o 2 ) is a powerful test for assessment and quantification of functional impairment resulting from cardiovascular disease. The safety of CPX has been established in patients with coronary artery disease and congestive heart failure, but clinical use of CPX in other cardiac diseases has been limited, in part because of a paucity of safety data. This study investigates the safety of CPX in a heterogeneous cohort of patients with a wide variety of underlying high-risk cardiac diagnoses. Methods and Results— This single-center retrospective review examined 5060 CPX studies performed in 4250 unique patients, including 1748 (35%) female subjects and 686 (14%) subjects aged ≥75 years. The primary end point was major adverse event during stress testing. The study population included patients with a variety of high-risk cardiac diseases, including congestive heart failure (n=1289, 25.5%), hypertrophic cardiomyopathy (n=598, 11.8%), pulmonary hypertension (n=194, 3.8%), and aortic stenosis (n=212, 4.2%). This patient population generally had severe functional impairment, including 1192 (24%) patients with peak V o 2 <14 mL/kg/min. Eight adverse events occurred during CPX, for an adverse event rate of 0.16%. The most common adverse event (n=6) was sustained ventricular tachycardia. There were no fatal events. Conclusions— CPX is generally a safe procedure, even in a population with underlying high-risk cardiovascular diagnoses.

Background Classification of risk of ischemic stroke is important for medical care and public health reasons. Whether addition of biomarkers adds to predictive power of the Framingham Stroke Risk or other traditional risk factors has not been studied in older women. Methods The Hormones and Biomarkers Predicting Stroke Study is a case-control study of blood biomarkers assayed in 972 ischemic stroke cases and 972 controls, nested in the Women's Health Initiative Observational Study of 93 676 postmenopausal women followed for an average of eight-years. We evaluated additive predictive value of two commercially available biomarkers: C-reactive protein and lipoprotein-associated phospholipase A 2 to determine if they added to risk prediction by the Framingham Stroke Risk Score or by traditional risk factors, which included lipids and other variables not included in the Framingham Stroke Risk Score. As measures of additive predictive value, we used the C-statistic, net reclassification improvement, category-less net reclassification improvement, and integrated discrimination improvement index. Results Addition of C-reactive protein to Framingham risk models or additional traditional risk factors overall modestly improved prediction of ischemic stroke and resulted in overall net reclassification improvement of 6·3%, (case net reclassification improvement = 3·9%, control net reclassification improvement = 2·4%). In particular, high-sensitivity C-reactive protein was useful in prediction of cardioembolic strokes (net reclassification improvement = 12·0%; 95% confidence interval 4·3–19·6%) and in strokes occurring in less than three-years (net reclassification improvement = 7·9%, 95% confidence interval 0·8–14·9%). Lipoprotein-associated phospholipase A 2 was useful in risk prediction of large artery strokes (net reclassification improvement = 19·8%, 95% confidence interval 7·4–32·1%) and in early strokes (net reclassification improvement = 5·8%, 95% confidence interval 0·4–11·2%). Conclusions C-reactive protein and lipoprotein-associated phospholipase A 2 can improve prediction of certain subtypes of ischemic stroke in older women, over the Framingham stroke risk model and traditional risk factors, and may help to guide surveillance and treatment of women at risk.