Statistical Inferences For Two-stage Treatment Regimes for Time-to-Event and Longitudinal Data

Adaptive treatment regime is a set of rules that governs the assignment of time-varying treatment based on observed covariates and intermediate response. Treatment choices are made sequentially as patients make transition from one health state to another. Specifically, in two stage randomization designs, patients are randomized to one of the initial treatments, and at the end of the first stage, they are randomized to one of the second stage treatments depending on the outcome of the initial treatment. The goal is to find the best treatment regime which produces the best terminal outcome. For time-to-event data, the best outcome is the longest survival time, and for longitudinal data, the best outcome is greatest reduction (or increase) in some scores such as reduction 24-item Hamilton Rating Scale of Depression (HRSD24) score. For time-to-event data, we propose a weighted Kaplan-Meier estimator based on the method of inverse-probability weighting and compare its properties to that of the standard Kaplan-Meier estimator, and two other existing methods such as marginal mean model based estimator and weighted risk set estimator. For longitudinal data, outcome such as HRSD24 scores are collected repeatedly to monitor the progress of the subject. We propose three methods incorporating inverse probability weighting, mixed models, multiple imputations, and pattern mixture models to assess the effect of treatment regimes on the longitudinal HRSD24 scores. Methods are compared through simulation studies with an application to a depression study. Assessing the effect of treatment regimes on longitudinally observed outcome data is important in Public Health since clinicians will be able to identify effective treatment regimes for treating chronic diseases. Proposed statistical methods provide useful tools for unbiased estimation of the effects of treatment regimes from sequentially randomized designs. Availability of these methods will help advance the research in AIDS, cancer, depression, hepatitis and other disease areas

Randomized trial of minocycline in the treatment of HIV-associated cognitive impairment

OBJECTIVE: To evaluate the efficacy and safety of minocycline in the management of HIV-associated cognitive impairment. METHODS: We enrolled HIV-positive participants with a CD4 count of 250 to 500 cells/μL in a randomized, double-blind, placebo-controlled study. They received 100 mg of minocycline or matching placebo orally every 12 hours for 24 weeks. Cognitive function was measured using the Uganda neuropsychological test battery summary measure (U NP Sum) and the Memorial Sloan-Kettering (MSK) scale. The primary efficacy measure was the 24-week change in an average of 9 standardized U NP Sum z scores. RESULTS: Seventy-three participants were enrolled. Of these, 90% were female, 49% were between the ages 30 and 39 years, and 74% had 6 or more years of education. One participant had MSK score of stage 1 (i.e., mild HIV dementia), and 72 participants had MSK stage 0.5 (i.e., equivocal or subclinical dementia) at the baseline evaluation. The minocycline effect on the 24-week change of the U NP Sum compared with placebo was 0.03 (95% confidence interval -0.51, 0.46; p = 0.37). CONCLUSION: Minocycline was safe and well tolerated in HIV-positive individuals. However, it did not improve HIV-associated cognitive impairment. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that 100 mg of minocycline given orally every 12 hours for 24 weeks had no significant effect compared with placebo in the improvement of cognitive function in antiretroviral therapy-naive, HIV-positive patients

Neurocognition with maraviroc compared with tenofovir in HIV

To determine whether maraviroc (MVC) has unique neurocognitive benefits in the context of initial antiretroviral therapy (ART)

Examination of density and mixing ratio of barium preparations, using an originally created phantom

胃Ⅹ線検査に造影剤として用いられる硫酸バリウム懸濁液の濃度を,簡便に,客観的に決定する目的で,歯科用アルギン酸塩印象材を用いて,コインの図柄を写しとったファントムを制作した｡これを使って二種類の硫酸バリウム製剤の適正濃度(PD)を調べた結果,BARITOP PとBARICON MEALを単体,若くは混合した場合には,おおよそ,PD(W/V%)=0.75C+165(ただし,CはBARICON MEALの混合比(%))となった｡また,BARICON MEALはコントラストが高く,精密検査に有利だと考えられ,BARITOP PとBARICON MEALを混合すると濃度の許容範囲が広がるため,通常の検査に都合がよいと考えられた｡更に,このファントムは簡便に作成することができ,しかも,硫酸バリウム懸濁 液との親和性も良いことから,硫酸バリウム製剤やⅩ線TV装置の評価,増感紙･フィルム系の評価等にも応用できると考えられた｡A phantom copied designs of coins was created with alginate dental impression material to establish a objective, simple and easy method for deciding density of barium sulfate suspensions which are used for stomach X-ray examination as contrast media. As a result of examining proper density (PD) of two kind of barium preparations with this phantom, in case of BARITOP P and BARICON MEAL, PD were almost shown by the next equation : PD(W/V%)=0.75C+165(C meant content of BARICON MEAL (%)). As BARICON MEAL resulted in hight contrast, it was thought to be suitable for a close examination. Mixture of BARITOP P and BARICON MEAL was thought to be suited to a routine examination becouse of wide permissible level of density. This phantom would be able to apply to the test of balium preparations, X-ray TV systems, screen/film systems and so on

Risk factors for early mortality on antiretroviral therapy in advanced HIV-infected adults.

CAPRISA, 2017.Abstract available in pdf

The functional impact of subsyndromal depressive symptoms in bipolar disorder: Data from STEP-BD

Background This report describes baseline characteristics and functional outcomes of subjects who have prospectively observed subsyndromal symptoms after a major depressive episode (MDE). Methods All subjects were participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). We identified subjects with at least 2 years of observation whose prior or current episode was a MDE, and who were in a stable clinical state of either recovered (no more than 2 moderate symptoms for at least 8 weeks), a MDE by DSM IV criteria, or with continued subsyndromal symptoms. The subsyndromal group was defined a priori as 3 or more moderate affective symptoms but without meeting diagnostic criteria for major depression. Results The final cohort included 1094 recovered, 112 subsyndromal, and 310 individuals in a MDE. The average time spent in each clinical status ranged from 120 to 132 days. The subsyndromal group was most similar to those in a MDE, differing only on the intensity of depressive symptoms and the number of work days missed due to ongoing symptoms. Reported sadness, inability to feel and lassitude were each associated with multiple measures of impairment. Limitations This study is limited by the cross sectional approach to defining outcomes. Conclusions These findings are consistent with studies in unipolar major depression that indicate that functional impairment observed in the context of subsyndromal depressive symptoms is comparable to that of a full episode. This work underscores the need to include subsyndromal symptoms in study outcomes and to target full remission in clinical practice.Psycholog