Browsing by Subject "treatment response"

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    Clinical predictors of non-response to lithium treatment in the Pharmacogenomics of Bipolar Disorder (PGBD) study
    (Wiley, 2021) Lin, Yian; Maihofer, Adam X.; Stapp, Emma; Ritchey, Megan; Alliey‐Rodriguez, Ney; Anand, Amit; Balaraman, Yokesh; Berrettini, Wade H.; Bertram, Holli; Bhattacharjee, Abesh; Calkin, Cynthia V.; Conroy, Carla; Coryell, William; D'Arcangelo, Nicole; DeModena, Anna; Biernacka, Joanna M.; Fisher, Carrie; Frazier, Nicole; Frye, Mark; Gao, Keming; Garnham, Julie; Gershon, Elliot; Glazer, Kara; Goes, Fernando S.; Goto, Toyomi; Karberg, Elizabeth; Harrington, Gloria; Jakobsen, Petter; Kamali, Masoud; Kelly, Marisa; Leckband, Susan G.; Lohoff, Falk W.; Stautland, Andrea; McCarthy, Michael J.; McInnis, Melvin G.; Mondimore, Francis; Morken, Gunnar; Nurnberger, John I.; Oedegaard, Ketil J.; Syrstad, Vigdis Elin Giever; Ryan, Kelly; Schinagle, Martha; Schoeyen, Helle; Andreassen, Ole A.; Shaw, Marth; Shilling, Paul D.; Slaney, Claire; Tarwater, Bruce; Calabrese, Joseph R.; Alda, Martin; Nievergelt, Caroline M.; Zandi, Peter P.; Kelsoe, John R.; Psychiatry, School of Medicine
    Background Lithium is regarded as a first-line treatment for bipolar disorder (BD), but partial response and non-response commonly occurs. There exists a need to identify lithium non-responders prior to initiating treatment. The Pharmacogenomics of Bipolar Disorder (PGBD) Study was designed to identify predictors of lithium response. Methods The PGBD Study was an eleven site prospective trial of lithium treatment in bipolar I disorder. Subjects were stabilized on lithium monotherapy over 4 months and gradually discontinued from all other psychotropic medications. After ensuring a sustained clinical remission (defined by a score of ≤3 on the CGI for 4 weeks) had been achieved, subjects were followed for up to 2 years to monitor clinical response. Cox proportional hazard models were used to examine the relationship between clinical measures and time until failure to remit or relapse. Results A total of 345 individuals were enrolled into the study and included in the analysis. Of these, 101 subjects failed to remit or relapsed, 88 achieved remission and continued to study completion, and 156 were terminated from the study for other reasons. Significant clinical predictors of treatment failure (p < 0.05) included baseline anxiety symptoms, functional impairments, negative life events and lifetime clinical features such as a history of migraine, suicidal ideation/attempts, and mixed episodes, as well as a chronic course of illness. Conclusions In this PGBD Study of lithium response, several clinical features were found to be associated with failure to respond to lithium. Future validation is needed to confirm these clinical predictors of treatment failure and their use clinically to distinguish who will do well on lithium before starting pharmacotherapy.
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    Efficacy of Post-Induction Therapy for High-risk Neuroblastoma Patients with End-Induction Residual Disease
    (Wiley, 2022) Desai, Ami V.; Applebaum, Mark A.; Karrison, Theodore G.; Oppong, Akosua; Yuan, Cindy; Berg, Katherine R.; MacQuarrie, Kyle; Sokol, Elizabeth; Hall, Anurekha G.; Pinto, Navin; Wolfe, Ian; Mody, Rajen; Shusterman, Suzanne; Smith, Valeria; Foster, Jennifer H.; Nassin, Michele; LaBelle, James L.; Bagatell, Rochelle; Cohn, Susan L.; Radiology and Imaging Sciences, School of Medicine
    Background: High-risk neuroblastoma patients with end-induction residual disease commonly receive post-induction therapy in an effort to increase survival by improving response prior to autologous stem cell transplant (ASCT). We conducted a multi-center, retrospective study to investigate the efficacy of this approach. Methods: Patients diagnosed between 2008 and 2018 without progressive disease (PD) with ≤ partial response (PR) at end-induction were stratified according to post-induction treatment: i) no additional therapy prior to ASCT (Cohort 1); ii) post-induction “bridge” therapy prior to ASCT (Cohort 2); and iii) post-induction therapy without ASCT (Cohort 3). Chi-square tests were used to compare patient characteristics. Three-year event-free survival (EFS) and overall survival (OS) were estimated by the Kaplan-Meier method and survival curves were compared by log-rank test. Results: The study cohort consisted of 201 patients; Cohort 1 (n=123); Cohort 2 (n=51); and Cohort 3 (n=27). Although end-induction response was better for Cohort 1 than Cohorts 2 and 3, outcome for Cohort 1 and 2 was not significantly different (EFS; p=0.77 and OS; p=0.85). Inferior outcome was observed for Cohort 3 (EFS; p<0.001 and OS; p=0.06). Among patients with end-induction stable metastatic disease, 3-year EFS was significantly improved for Cohort 2 compared to Cohort 1 (p=0.04). Cohort 3 patients with complete response (CR) in metastatic sites following post-induction therapy had significantly better 3-year EFS compared to those with residual metastatic disease (p=0.01). Conclusions: Prospective studies to confirm the benefits of bridge treatment and the prognostic significance of metastatic response observed in this study are warranted.