Asymptotic theorems of sequential estimation-adjusted urn models

The Generalized P\'{o}lya Urn (GPU) is a popular urn model which is widely used in many disciplines. In particular, it is extensively used in treatment allocation schemes in clinical trials. In this paper, we propose a sequential estimation-adjusted urn model (a nonhomogeneous GPU) which has a wide spectrum of applications. Because the proposed urn model depends on sequential estimations of unknown parameters, the derivation of asymptotic properties is mathematically intricate and the corresponding results are unavailable in the literature. We overcome these hurdles and establish the strong consistency and asymptotic normality for both the patient allocation and the estimators of unknown parameters, under some widely satisfied conditions. These properties are important for statistical inferences and they are also useful for the understanding of the urn limiting process. A superior feature of our proposed model is its capability to yield limiting treatment proportions according to any desired allocation target. The applicability of our model is illustrated with a number of examples.Comment: Published at http://dx.doi.org/10.1214/105051605000000746 in the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

Optimal design of p-value consistent step-up procedures for multiple comparisons with a control in direction-mixed families

Ministry of Education, Singapore under its Academic Research Funding Tier

Immigrated urn models - asymptotic properties and applications

Urn models have been widely studied and applied in both scientific and social science disciplines. In clinical studies, the adoption of urn models in treatment allocation schemes has been proved to be beneficial to both researchers, by providing more efficient clinical trials, and patients, by increasing the likelihood of receiving the better treatment. In this paper, we propose a new and general class of immigrated urn (IMU) models that incorporates the immigration mechanism into the urn process. Theoretical properties are developed and the advantages of the IMU models are discussed. In general, the IMU models have smaller variabilities than the classical urn models, yielding more powerful statistical inferences in applications. Illustrative examples are presented to demonstrate the wide applicability of the IMU models. The proposed IMU framework, including many popular classical urn models, not only offers a unify perspective for us to comprehend the urn process, but also enables us to generate several novel urn models with desirable properties

Burden of upper gastrointestinal symptoms in patients prescribed dabigatran for stroke prevention

BACKGROUND: Dabigatran, a non-vitamin K antagonist oral anticoagulant, has been shown to prevent stroke in patients with non-valvular atrial fibrillation. Nonetheless, studies show that 10%-30% of those prescribed dabigatran experience dyspepsia that may eventually lead to discontinuation of therapy and loss of clinical benefit. AIM: To evaluate the gastrointestinal tolerability of dabigatran utilizing a validated questionnaire, as well as determining subsequent non-compliance and drug discontinuation. METHOD: This is an observational study. All patients were assessed by a validated questionnaire, Hong Kong dyspepsia index, prior to drug prescription and again 4 weeks later. RESULTS: In this study, 115 patients with non-valvular atrial fibrillation (mean age: 74.6 ± 11.4 years; mean CHA2DS2-VASc score was 3.39 ± 1.59) were prescribed dabigatran. At baseline, the mean Hong Kong dyspepsia index was 12.9 ± 1.6 and nine patients had significant dyspepsia (Hong Kong dyspepsia index ⩾ 16). After 4 weeks, the mean Hong Kong dyspepsia index was similar at 12.6 ± 1.9 (p = 0.23). There was no change in Hong Kong dyspepsia index after initiation of dabigatran in 59 (51.3%) patients, and improvement in 37 (32.2%). Only 19 (16.5%) patients had worsening of Hong Kong dyspepsia index, and among these 19 patients, only 1 patient (0.9%) discontinued dabigatran due to significant dyspepsia. CONCLUSION: Worsening of dyspepsia with dabigatran 110 mg twice daily was uncommon with correct drug administration and clear instructions provided. Systematic assessment of dyspeptic symptoms using a validated questionnaire (i.e. Hong Kong dyspepsia index) before and after treatment initiation allows a more objective comparison of dyspeptic symptoms

Definitive radiotherapy for early stage glottic cancer by 6 MV photons

Purpose: To evaluate the clinical outcome of early glottic cancer (GC) treated by primary radiotherapy (RT) with 6 MV photons. Methods and materials: We retrospectively reviewed the medical records of 695 consecutive patients with T1N0 and T2N0 GC treated between 1983 and 2005 by RT in our institution. Clinical outcome in terms of local control (LC), overall survival (OS) and cause- specific survival (CSS) rate were evaluated. Results: The median follow-up time was 10.5 years.The 10-year actuarial LC rates were as follows: T1A, 91%; T1B, 87%; T2, 77%. The 10-year OS were as follows: T1, 74.2%; T2, 70.7%. The 10-year CSS were as follows: T1, 97.7%; T2, 97.1%. Poorly differentiated histology and tumor biologically effective dose < 65 Gy.© 2012 Tong et al.; licensee BioMed Central Ltd.Link_to_subscribed_fulltex

The psychophysiological effects of Tai-chi and exercise in residential Schizophrenic patients: a 3-arm randomized controlled trial

BACKGROUND: Patients with schizophrenia are characterized by high prevalence rates and chronicity that often leads to long-term institutionalization. Under the traditional medical model, treatment usually emphasizes the management of psychotic symptoms through medication, even though anti-psychotic drugs are associated with severe side effects, which can diminish patients’ physical and psychological well-being. Tai-chi, a mind-body exercise rooted in Eastern health philosophy, emphasizes the motor coordination and relaxation. With these potential benefits, a randomized controlled trial (RCT) is planned to investigate the effects of Tai-chi intervention on the cognitive and motor deficits characteristic of patients with schizophrenia. METHODS/DESIGN: A 3-arm RCT with waitlist control design will be used in this study. One hundred and fifty three participants will be randomized into (i) Tai-chi, (ii) exercise or (iii) waitlist control groups. Participants in both the Tai-chi and exercise groups will receive 12-weeks of specific intervention, in addition to the standard medication and care received by the waitlist control group. The exercise group will serve as a comparison, to delineate any unique benefits of Tai-chi that are independent of moderate aerobic exercise. All three groups will undergo three assessment phases: (i) at baseline, (ii) at 12 weeks (post-intervention), and (iii) at 24 weeks (maintenance). All participants will be assessed in terms of symptom management, motor coordination, memory, daily living function, and stress levels based on self-perceived responses and a physiological marker. DISCUSSION: Based on a promising pilot study conducted prior to this RCT, subjects in the Tai-chi intervention group are expected to be protected against deterioration of motor coordination and interpersonal functioning. They are also expected to have better symptoms management and lower stress level than the other treatment groups. TRIAL REGISTRATION: The trail has been registered in the Clinical Trials Center of the University of Hong Kong (HKCTR-1453)

International Classification of Functioning, Disability, and Health-based rehabilitation program promotes activity and participation of post-stroke patients

BackgroundThe International Classification of Functioning, Disability, and Health (ICF) model has been applied in post-stroke rehabilitation, yet limited studies explored its clinical application on enhancing patients’ Activity and Participation (ICF-A&amp;P) level.PurposeThis study gathered evidence of the effects of an ICF-based post-stroke rehabilitation program (ICF-PSRP) in enhancing community reintegration in terms of ICF-A&amp;P of post-stroke patients.MethodsFifty-two post-stroke patients completed an 8 to 12 weeks multidisciplinary ICF-PSRP after setting personal treatment goals in an outpatient community rehabilitation center. Intake and pre-discharge assessments were administered for primary outcomes of Body function (ICF-BF; e.g., muscle strength) and ICF-A&amp;P (e.g., mobility), and secondary outcomes of perceived improvements in ability (e.g., goal attainment and quality of life).ResultsThere were significantly higher levels in the ICF-BF and ICF-A&amp;P domains, except cognitive function under the ICF-BF. Improvements in the primary outcomes predicted corresponding secondary outcomes. Firstly, expressive and receptive functions (ICP-BF) were mediated by the everyday language (ICF-A&amp;P) which predicted patients’ satisfaction with the language-related quality of life. Secondly, upper extremity function (ICP-BF) was mediated by the lower extremity mobility (ICF-A&amp;P) predicting work and productivity-related quality of life. Content analyses showed that combined ICF-BF and ICF-A&amp;P contents throughout the ICF-PSRP contributed to the positive treatment effects.ConclusionThe ICF-PSRP was effective in promoting body function, and activity and participation levels of post-stroke patients. Positive treatment effects are characterized by goal-setting process, cross-domain content design, and community-setting delivery.Clinical trial registration: https://clinicaltrials.gov/study/NCT05941078?id=NCT05941078&amp;rank=1, identifier NCT05941078

Sequential algorithm to stratify liver fibrosis risk in overweight/obese metabolic dysfunction-associated fatty liver disease

BackgroundNon-diabetic overweight/obese metabolic dysfunction-associated fatty liver disease (MAFLD) represents the largest subgroup with heterogeneous liver fibrosis risk. Metabolic dysfunction promotes liver fibrosis. Here, we investigated whether incorporating additional metabolic risk factors into clinical evaluation improved liver fibrosis risk stratification among individuals with non-diabetic overweight/obese MAFLD.Materials and methodsComprehensive metabolic evaluation including 75-gram oral glucose tolerance test was performed in over 1000 participants from the New Hong Kong Cardiovascular Risk Factor Prevalence Study (HK-NCRISPS), a contemporary population-based study of HK Chinese. Hepatic steatosis and fibrosis were evaluated based on controlled attenuation parameter and liver stiffness (LS) measured using vibration-controlled transient elastography, respectively. Clinically significant liver fibrosis was defined as LS ≥8.0 kPa. Our findings were validated in an independent pooled cohort comprising individuals with obesity and/or polycystic ovarian syndrome.ResultsOf the 1020 recruited community-dwelling individuals, 312 (30.6%) had non-diabetic overweight/obese MAFLD. Among them, 6.4% had LS ≥8.0 kPa. In multivariable stepwise logistic regression analysis, abnormal serum aspartate aminotransferase (AST) (OR 7.95, p&lt;0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.5 (OR 5.01, p=0.008) were independently associated with LS ≥8.0 kPa, in a model also consisting of other metabolic risk factors including central adiposity, hypertension, dyslipidaemia and prediabetes. A sequential screening algorithm using abnormal AST, followed by elevated HOMA-IR, was developed to identify individuals with LS ≥8.0 kPa, and externally validated with satisfactory sensitivity (&gt;80%) and negative predictive value (&gt;90%).ConclusionA sequential algorithm incorporating AST and HOMA-IR levels improves fibrosis risk stratification among non-diabetic overweight/obese MAFLD individuals