Correlates of depression outcomes in collaborative care for HIV.

BACKGROUND: Collaborative care can treat depression in HIV but existing studies have been limited by excluding patients with acute or severe depression. The purpose of this analysis is to determine if real-world implementation of collaborative care in HIV is associated with improvement in depression, and to identify correlates of depression outcomes. METHODS: Collaborative care was implemented as part of a large practice transformation initiative. Change in depression, measured by PHQ-9 score, at baseline compared to 12 months post-enrollment was the outcome, which was operationalized as remission, response, and neither response nor remission. Bivariate and multivariate associations were assessed between several variables at baseline and the outcome. RESULTS: Out of 416, 99 (23.79%) patients remitted and 89 (21.39%) responded (without remission). In the bivariate analysis having a documented psychiatric comorbidity was associated with low remission [31 (16.58%)]; p = 0.008. Having generalized anxiety disorder was associated with low remission [18 (15.00%)] and response rates [26 (21.67%)]; p = 0.022. Having a substance use disorder (alcohol, cocaine, or amphetamine) - was associated with poor remission [29 (16.67%)] and response [33 (18.97%)]; p = 0.004. Social isolation was correlated with lower response and remission rates (p = 0.0022). In the multivariate analysis older age was associated with higher remission rates (OR: 1.10; 95% CI: 1.005-1.194) whereas being a Medicaid beneficiary (OR: 0.652; 95% CI: 1.123-2.797), having comorbid generalized anxiety disorder (OR: 0.267; 95% CI: 0.122-0.584) or a stimulant use disorder (cocaine [OR: 0.413; 95% CI: 0.222-0.926] or amphetamines [OR: 0.185; 95% CI: 0.037-0.766]), was associated with lower remission rates. CONCLUSION: We found that depression improved in our study subjects. We identified several modifiable correlates of depression outcomes.

Novel approach to therapeutic targeting of castration-resistant prostate cancer.

Development of resistance to anti-androgen therapy limits the usefulness of second-generation androgen receptor (AR) antagonists including enzalutamide and abiraterone in castration resistant prostate cancer (CRPC) patients. Recent genomic studies reveal that AR-regulated genes contribute to CRPC emergence. Several reasons for the development of resistance towards anti-androgens have been hypothesized, including intracellular testosterone production, androgen overexpression, somatic mutations of AR resulting in a gain of function, constitutive activation of AR splice variants, imbalance in AR regulators, and bypass of AR in CRPC progression. Recent findings suggest that epigenetic alterations are involved in the deregulation of AR signaling. Overexpression of enhancer of zeste homolog 2 (EZH2), the enzymatic member of the polycomb repressor complex PRC2, has emerged as a key activator of AR in CRPC. Studies indicate that overabundance of EZH2 in localized prostate tumors increases the risk of biochemical recurrence after surgery, as it activates AR by enhancing methylation, resulting in the suppression of tumor suppressor genes and activation of oncogenes. This apparent association between EZH2 and AR in activating target genes by cooperative recruitment might play a critical role in the emergence of CRPC. Our hypothesis is that combination treatment targeting EZH2 and AR may be a novel efficacious therapeutic regime for the treatment of castrate resistant prostate cancer, and we propose to investigate this possibility.

Depressive Symptom Trajectories Among People Living with HIV in a Collaborative Care Program.

Depressive symptoms may differ in severity and change over time in people living with HIV (PLWH). Describing depression trajectories and associated clinical characteristics of PLWH in an interventional study may help in developing a more personalized medicine approach. Using latent class growth analysis four, 15-month self-reported depression trajectories were identified in 416 PLWH participating in a collaborative care program. The four subgroups were characterized by improving (58.4% [of participants]), worsening (9.4%), highly responsive (19.5%) and persistently severe (12.7%) depressive symptoms. A high proportion of individuals were in trajectories marked by improvement. Further, the highly responsive group had on average, over 50% reduction of self-reported depressive symptoms. Self-reported trauma, posttraumatic stress disorder, lower neighborhood-level education and fewer HIV and psychiatry clinic visits were associated with worsening or persistently severe depressive symptom trajectories. Members of the persistently severe group were less likely to be virally suppressed after 12-months. Identifying subgroups of PLWH based on changes in self-reported depressive symptoms may further inform intervention approaches that can advance care.