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Clinical trials usually involve efficient and ethical objectives. Different adaptive designs have been proposed to satisfy these needs. We combine interim analysis, the sequential estimation‐adjusted urn model (SEU), and sample size re‐estimation (SSR) in one clinical trial. We show that the asymptotic distribution, under the null hypothesis, of the proposed sequential statistic follows Brownian motion by simultaneously addressing the three sequential procedures (allocation of patients, urn composition, and sequential parameter estimators) and the sequential statistics with revised information time due to SSR. Therefore, to control the type I error rate, traditional critical values for sequential monitoring based on Brownian motion can be used for the proposed procedure. Numerical studies with three types of urn models demonstrate that our proposed approach can control the type I error rate well and also achieve efficient and ethical objectives. [ABSTRACT FROM AUTHOR]

Poor adherence to prescribed medication regimens remains an important challenge preventing successful treatment of cardiovascular diseases such as hypertension. While studies have documented differences in the time of day or weekday vs weekend on medication adherence, no study has examined whether having a medication-taking routine contributes to increased medication adherence. The purpose of this study was to: (1) identify patients' sociodemographic factors associated with consistent medication-taking routine; (2) examine associations between medication-taking consistency, medication adherence, and blood pressure ( BP) control. The study included black patients with hypertension (n = 190; 22 men and 168 women; age, mean± standard deviation 54 ± 12.08 years) who completed a practice-based randomized controlled trial. Findings showed that medication-taking consistency was significantly associated with better medication adherence ( F = 9.54, P = .002). Associations with the consistency index were not statistically significant for diastolic BP control ( odds ratio, 1.319; 95% confidence interval, 0.410-4.246; P = .642) and systolic BP control ( odds ratio, 0.621; 95% confidence interval, 0.195-1.974; P = .419). [ABSTRACT FROM AUTHOR]

The most common data structures in the biomedical studies have been matched or unmatched designs. Data structures resulting from a hybrid of the two may create challenges for statistical inferences. The question may arise whether to use parametric or nonparametric methods on the hybrid data structure. The Early Treatment for Retinopathy of Prematurity study was a multicenter clinical trial sponsored by the National Eye Institute. The design produced data requiring a statistical method of a hybrid nature. An infant in this multicenter randomized clinical trial had high-risk prethreshold retinopathy of prematurity that was eligible for treatment in one or both eyes at entry into the trial. During follow-up, recognition visual acuity was accessed for both eyes. Data from both eyes (matched) and from only one eye (unmatched) were eligible to be used in the trial. The new hybrid nonparametric method is a meta-analysis based on combining the Hodges-Lehmann estimates of treatment effects from the Wilcoxon signed rank and rank sum tests. To compare the new method, we used the classic meta-analysis with the t-test method to combine estimates of treatment effects from the paired and two sample t-tests. We used simulations to calculate the empirical size and power of the test statistics, as well as the bias, mean square and confidence interval width of the corresponding estimators. The proposed method provides an effective tool to evaluate data from clinical trials and similar comparative studies. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

After observing that several families with essential tremor (ET) clinically cosegregated with restless legs syndrome (RLS), we prospectively evaluated for the presence of RLS in 100 patients presenting to the Baylor College of Medicine with ET and prospectively examined all patients presenting with RLS for the presence of tremor during the same time frame. Of 100 consecutive ET patients (60 women and 75 with a family history of ET) seen over 19 weeks (current age, 65.2 ± 16.3 years; age at tremor onset, 37.8 ± 19.9 years) 33 met all criteria for RLS, of which 25 had never been diagnosed previously. A family history of RLS was reported in 57.6% of these 33 patients and was the only significant predictor of RLS in the ET population. Their International Restless Legs Syndrome Rating Scale score was 16.6 ± 8.1. Over 19 weeks, we also examined 68 consecutive RLS patients (63.2% women and 54.4% with a family history of RLS) for the presence of tremor. Their current age was 55.8 ± 14.4 years, and age at RLS onset was 33.7 ± 19.5 years. Overtly pathological tremor was rare, but trace tremor was very common. Overall, we found a very high rate of undiagnosed RLS in patients presenting for tremor, but unlike other 'secondary' forms of RLS, this finding was also associated with a high familial history of RLS, suggesting that they share some genetic similarities. © 2005 Movement Disorder Society [ABSTRACT FROM AUTHOR]

We completed a single site, double-blind, placebo-controlled, parallel design study of quetiapine for hallucinations in PD. Thirty-one subjects with PD and prominent visual hallucinations and Mini-Mental State Examination score >21 were randomly assigned in a 2:1 drug to placebo ratio, up to 200 mg daily of quetiapine or matching placebo given in two doses. They were seen at 3 weeks (100 mg/day) and 12 weeks (200 mg/day, with optional dose reduction). Evaluation included the Unified Parkinson's Disease Rating Scale (UPDRS), the Baylor PD Hallucination Questionnaire, and a battery of neuropsychological tests. The demographics between subjects randomized to drug (n = 21) vs. placebo (n = 10) were similar. The final dose of active drug was 200 (n = 11), 150 (n = 2), 100 (n = 3), and 75 (n = 1) mg per day. All placebo subjects were on the equivalent of 200 mg per day. The UPDRS Activities of Daily Living and Motor scores did not significantly change compared to placebo. Compared to placebo, there were no significant changes in our hallucination questionnaire, the Brief Psychiatric Rating Scale (BPRS), or question 12 (hallucination item) of the BPRS. There were no significant changes on any of the neuropsychological measures. Adverse events on drug included sedation (n = 9), but no drug-related adverse events precipitated discontinuation and none were rated as serious. Quetiapine, up to 200 mg daily, was well tolerated and did not worsen UPDRS scores; however, there was no significant improvement in psychosis rating scales compared to placebo. Larger doses of drug and greater sample sizes might be considered in future studies. © 2005 Movement Disorder Society [ABSTRACT FROM AUTHOR]

There is considerable controversy regarding the relationship between essential tremor (ET) and Parkinson's disease (PD), especially when tremor is the dominant feature of PD or there is a family history of tremor. Reduced olfaction function is one of the initial signs of PD. In contrast, ET has relatively preserved olfaction. To infer whether the tremor-dominant subgroup of PD is intrinsically different from mainstream PD, we tested olfaction using the University of Pennsylvania Smell Identification Test-40 (UPSIT) in this group and compared the findings with those of patients with non-tremor-dominant "regular" PD. We then evaluated predictors of reduced UPSIT scores within the tremor-dominant group. Overall, olfaction did not differ between tremor-dominant PD and regular PD; however, the subgroup of tremor-dominant PD with a family history of tremor had less olfaction loss than those without a family history (P = 0.0007) or those with regular PD (P = 0.0350). Other clinical features of this tremor-dominant PD with a family history of tremor group mostly resembled those without a family history. This finding suggests that patients with a family history of tremor may represent a different disease process even though, aside from differences in olfaction, they are clinically similar to other patients with tremor-dominant parkinsonism. It additionally suggests phenotypic overlap between PD and ET. [ABSTRACT FROM AUTHOR]

In this paper, we give statistical analyses and simulation studies on the Lyapunov exponents estimated from noisy chaotic time series. Through the Jacobian estimation approach, the asymptotic distribution of the estimated Lyapunov exponents are studied and characterized from the observed noisy chaotic time series. Theoretical results are visualized and verified by numerical simulations. [ABSTRACT FROM AUTHOR]