Citations

Background— Factors that determine survival in pulmonary arterial hypertension (PAH) drive clinical management. A quantitative survival prediction tool has not been established for research or clinical use. Methods and Results— Data from 2716 patients with PAH enrolled consecutively in the US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) were analyzed to assess predictors of 1-year survival. We identified independent prognosticators of survival and derived a multivariable, weighted risk formula for clinical use. One-year survival from the date of enrollment was 91.0% (95% confidence interval [CI], 89.9 to 92.1). In a multivariable analysis with Cox proportional hazards, variables independently associated with increased mortality included pulmonary vascular resistance >32 Wood units (hazard ratio [HR], 4.1; 95% CI, 2.0 to 8.3), PAH associated with portal hypertension (HR, 3.6; 95% CI, 2.4 to 5.4), modified New York Heart Association/World Health Organization functional class IV (HR, 3.1; 95% CI, 2.2 to 4.4), men >60 years of age (HR, 2.2; 95% CI, 1.6 to 3.0), and family history of PAH (HR, 2.2; 95% CI, 1.2 to 4.0). Renal insufficiency, PAH associated with connective tissue disease, functional class III, mean right atrial pressure, resting systolic blood pressure and heart rate, 6-minute walk distance, brain natriuretic peptide, percent predicted carbon monoxide diffusing capacity, and pericardial effusion on echocardiogram all predicted mortality. Based on these multivariable analyses, a prognostic equation was derived and validated by bootstrapping technique. Conclusions— We identified key predictors of survival based on the patient’s most recent evaluation and formulated a contemporary prognostic equation. Use of this tool may allow the individualization and optimization of therapeutic strategies. Serial follow-up and reassessment are warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214.

We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH ( P < 10 −75 ), ARMS2 ( P < 10 −59 ), C2/CFB ( P < 10 −20 ), C3 ( P < 10 −9 ), and CFI ( P < 10 −6 ). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10 −11 ), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci ( LIPC , P = 1.3 × 10 −7 ; CETP , P = 7.4 × 10 −7 ) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c—associated alleles near LPL ( P = 3.0 × 10 −3 ) and ABCA1 ( P = 5.6 × 10 −4 ). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.

Potential donors with congenital renal anomalies but normal renal function are often overlooked because of a possible increase in technical difficulty and complications associated with the surgery. However, as the waiting list for a deceased donor kidney transplant continues to grow, it is important to consider these kidneys for potential transplant. This paper describes the procurement of a crossed fused ectopic kidney, and subsequent parenchymal transection prior to transplantation as part of a combined simultaneous kidney pancreas transplant. The transplant was uncomplicated, and the graft had immediate function. The patient is now two years from transplant with excellent function.

BackgroundResearch involving incapacitated persons with dementia entails complex scientific, legal, and ethical issues, making traditional surveys of layperson views on the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD), involving balanced, detailed education and peer deliberation, on the views of those responsible for persons with dementia.MethodsOne hundred and seventy‐eight community‐recruited caregivers or primary decision‐makers for persons with dementia were randomly assigned to either an all‐day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family‐surrogate consent for dementia research (“surrogate‐based research”) from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self‐perspectives), assessed at baseline, immediately post‐DD session, and 1 month after DD date, for four research scenarios of varying risk‐benefit profiles.ResultsAt baseline, a majority in both the DD and control groups supported a policy of family consent for dementia research in all research scenarios. The support for a policy of family consent for surrogate‐based research increased in the DD group, but not in the control group. The change in the DD group was maintained 1 month later. In the DD group, there were transient changes in attitudes from surrogate or self‐perspectives. In the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective.ConclusionsIntensive, balanced, and accurate education, along with peer deliberation provided by democratic deliberation, led to a sustained increase in support for a societal policy of family consent in dementia research among those responsible for dementia patients.

Purpose This study’s main purpose was to (a) identify acoustic signatures of hypokinetic dysarthria (HKD) that are robust to phonetic variation in conversational speech and (b) determine specific characteristics of the variability associated with HKD. Method Twenty healthy control (HC) participants and 20 participants with HKD associated with idiopathic Parkinson’s disease (PD) repeated 3 isolated sentences (controlled phonetic content) and 2 min of conversational speech (phonetic content treated as a random variable). A MATLAB-based program automatically calculated measures of contrastivity: speech–pause ratio, intensity variation, median and maximum formant slope, formant range, change in the upper and lower spectral envelope, and range of the spectral envelope. t tests were used to identify which measures were sensitive to HKD and which measures differed by task. Discriminant analysis was used to identify the combination of measures that best predicted HKD, and this analysis was then used as a general measure of contrastivity (Contrastivity Index). Differential effects of HKD on maximum and typical contrastivity levels were tested with interaction of maximum, minimum, and median observations of individual speakers and with pairwise comparisons of skewness and kurtosis of the contrastivity index distributions. Results Group differences were detected with pairwise comparisons with t tests in 8 of the 9 measures. Percentage pause time and spectral range were identified as the most specific (95%) and accurate (95%) differentiators of HKD and HC conversational speech. Sentence repetition elicited significantly higher levels of contrastivity than conversational speech in both HC and HKD speakers. Maximum and minimum contrastivities were significantly lower in HKD speech, but there was no evidence that HKD affects maximum contrastivity levels more than median contrastivity levels. The HKD speakers' contrastivity distributions were significantly more skewed to lower levels of production. Conclusion HKD can be consistently distinguished from HC speech in both sentence repetition and conversational speech on the basis of intensity variation and spectral range. Although speakers with HKD were effectively able to produce higher contrastivity levels in sentence repetition tasks, they habitually performed closer to the lower end of their production ranges.