Browsing by Author "Zhang, Hongbin"

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A longitudinal analysis of albendazole treatment effect on neurocysticercosis cyst evolution using multistate models
(2019) Hauser, Allen
© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. BACKGROUND: In neurocysticercosis, the larval form of the pork tapeworm Taenia solium appears to evolve through three phases-active, degenerative and sometimes calcification-before disappearance. The antihelmintic drug, albendazole, has been shown to hasten the resolution of active cysts in neurocysticercosis. Little is known about the time cysts take to progress through each phase, with or without treatment. METHODS: We reconfigured brain imaging data from patient level to cyst level for 117 patients in a randomized clinical trial of albendazole in which images were taken at baseline, 1, 6, 12 and 24 mo. Applying a multistate model, we modelled the hazard of a cyst evolving to subsequent cyst phases before the next imaging (vs no change). We examined the impact of albendazole treatment overall and by patient and cyst characteristics on the hazard. RESULTS: Albendazole accelerated the evolution from the active to degenerative phase (HR=2.7, 95% CI 1.3 to 6.5) and from the degenerative phase to disappearance (HR=1.9, 95% CI 1.1 to 3.9). Albendazole's impact was stronger for patients who were male, did not have calcified cysts at baseline and who had multiple cysts in different locations. CONCLUSIONS: This research provides a better understanding of where in the cyst trajectory albendazole has the greatest impact.
A multistate joint model for interval-censored event-history data subject to within-unit clustering and informative missingness, with application to neurocysticercosis research
(2020) Zhang, Hongbin; Kelvin, Elizabeth; Carpio Rodas, Luis Arturo; Hauser, Willard Allen
We propose a multistate joint model to analyze interval-censored event-history data subject to within-unit clustering and nonignorable missing data. The model is motivated by a study of the neurocysticercosis (NC) cyst evolution at the cyst-level, taking into account the multiple cysts phases with intermittent missing data and loss to follow-up, as well as the intra-brain clustering of observations made on a predefined data collection schedule. Of particular interest in this study is the description of the process leading to cyst resolution, and whether this process varies by antiparasitic treatment. The model uses shared random effects to account for within-brain correlation and to explain the hidden heterogeneity governing the missing data mechanism. We developed a likelihood-based method using a Monte Carlo EM algorithm for the inference. The practical utility of the methods is illustrated using data from a randomized controlled trial on the effect of antiparasitic treatment with albendazole on NC cysts among patients from six hospitals in Ecuador. Simulation results demonstrate that the proposed methods perform well in the finite sample and misspecified models that ignore the data complexities could lead to substantial biases.
Exploring the complex associations over time among albendazole treatment, cyst evolution, and seizure outcomes in neurocysticercosis
(2019) Zhang, Hongbin
Wiley Periodicals, Inc. © 2019 International League Against Epilepsy Objective: To develop a causal model for the occurrence of neurocysticercosis (NC)-related seizures and test hypotheses generated from the model. Methods: We used data from a randomized controlled trial comparing albendazole with placebo among patients newly diagnosed with NC. Based on our causal model, we explored the associations among albendazole treatment, NC cyst evolution, and seizure outcomes over 24 months of follow-up using generalized linear mixed effect models. Results: We included 153 participants, of whom 51% received albendazole. The association between seizure outcomes and treatment over time demonstrated lack of linearity and heterogeneity, requiring the inclusion of time-treatment interaction terms for valid modeling. Participants in the albendazole group had fewer seizures overall and of partial onset at all time points compared with the placebo group, but the difference increased over the first few months following treatment, then decreased over time. Generalized seizures exhibited a more complex association; those in the albendazole group had fewer seizures compared with those in the placebo group for the first few months after treatment, and then the association reversed and those in the placebo arm had fewer seizures. Adjusting for the number of NC cysts in each phase resulted in an attenuation of the strength of association between albendazole and seizure outcomes, consistent with mediation. Among participants in whom all cysts had disappeared (n = 21), none continued to have seizures. Significance: Albendazole treatment is associated with a possible reduction in focal seizures in the short term (3-6 months), perhaps by hastening the resolution of the cysts. However, the effect is not discernible over the long term, because most cysts either calcify or resolve completely, regardless of whether treated with albendazole. The stage of evolution of the cysticercus is an important consideration in the evaluation of albendazole effect on seizure outcome.