Association between ethnicity and treatment status in opioid dependence therapy using methadone and suboxone drugs

Opioids are drugs with opium-like qualities that are either derived from opiates (drugs created from opium, such as morphine or codeine) or chemically produced. In the U.S. opiate abuse and related deaths have been increasing and traditional maintenance treatment has been Methadone with variable success. However, since 2003 synthetic Buprenorphine has been used since it is prescribed daily by physicians in pill form and should improve outcomes. Comparative studies are limited and the effect of ethnicity on treatment outcome is unknown. ^ Data collected at one clinic from December 2005 through May 2009 were used to compare the association between ethnicity and other socioeconomic variables with treatment status, and to identify factors associated with the dropout among participants. Descriptive tables and multiple logistic regression models were used to examine the data on 1,295 total participants. Of the total, 875 participants (68%) were from the Methadone subsample and 420 participants (32%) from the Buprenorphine subsample; only about 15% stayed in treatment. ^ This study showed that with either Methadone or Buprenorphine maintenance therapy, only about 15% participants stay active over 3.5 years. Methadone treated patients that stayed active in treatment were associated with Caucasian ethnicity and were more likely to be employed. With Buprenorphine maintenance treatment only age over 40 years was associated with continuing activity in the program. Further studies that examine the reasons for the high dropout status and the implication of the socioeconomic and ethnic associations found in this data may help to improve treatment outcomes.^

Using Acceptance and Commitment Therapy during Methadone Dose Reduction: Rationale, Treatment Description, and a Case Report.

Many clients who undergo methadone maintenance (MM) treatment for heroin and other opiate dependence prefer abstinence from methadone. Attempts at methadone detoxification are often unsuccessful, however, due to distressing physical as well as psychological symptoms. Outcomes from a MM client who voluntarily participated in an Acceptance and Commitment Therapy (ACT) - based methadone detoxification program are presented. The program consisted of a 1-month stabilization and 5-month gradual methadone dose reduction period, combined with weekly individual ACT sessions. Urine samples were collected twice weekly to assess for use of illicit drugs. The participant successfully completed the program and had favorable drug use outcomes during the course of treatment, and at the one-month and one-year follow-ups. Innovative behavior therapies, such as ACT, that focus on acceptance of the inevitable distress associated with opiate withdrawal may improve methadone detoxification outcomes.

The role of substance abuse treatment in preventing human immunodeficiency virus transmission among injecting drug users

This exploratory study assesses the utility of substance abuse treatment as a strategy for preventing human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs). Data analyzed in this study were collected in San Antonio, TX, 1989 through 1995 using both qualitative and quantitative methods. Qualitative data included ethnographic interviews with 234 active IDUs; quantitative data included baseline risk assessments and HIV screening plus interviews follow-up interviews administered approximately six months later to 823 IDUs participating in a Federally-funded AIDS community outreach demonstration project.^ Findings that have particularly important implications for substance abuse treatment as an HIV prevention strategy for IDUs are listed below. (1) IDUs who wanted treatment were significantly more likely to be daily heroin users. (2) IDUs who want treatment were significantly more likely to have been to treatment previously. (3) IDUs who wanted treatment at baseline reported significantly higher levels of HIV risk than IDUs who did not want treatment. (4) IDUs who went to treatment between their baseline and follow-up interviews reported significantly higher levels of HIV risk at baseline than IDUs who did not go to treatment. (5) IDUs who went to treatment between their baseline and follow-up interviews reported significantly greater decreases in injection-related HIV risk behaviors. (6) IDUs who went to treatment reported significantly greater decreases in sexual HIV risk behaviors than IDUs who did not go to treatment.^ This study also noted a number of factors that may limit the effectiveness of substance abuse treatment in reducing HIV risk among IDUs. Findings suggest that the impact of methadone maintenance on HIV risk behaviors among opioid dependent IDUs may be limited by the negative manner in which it is perceived by IDUs as well as other elements of society. One consequence of the negative perception of methadone maintenance held by many elements of society may be an unwillingness to provide public funding for an adequate number of methadone maintenance slots. Thus many IDUs who would be willing to enter methadone maintenance are unable to enter it and many IDUs who do enter it are forced to drop out prematurely. ^

Relevant drug to drug interactions between itraconazole and non-nucleoside reverse transcriptase inhibitors in HIV-infected patients on maintenance therapy for disseminated histoplasmosis

Objective. Itraconazole is recommended life-long for preventing relapse of disseminated histoplasmosis in HIV-infected patients. I sought to determine if serum itraconazole levels are affected by the type of Highly Active Anti-Retroviral Therapy (NNRTI or PI) being taken concomitantly to treat HIV. ^ Design. Retrospective cohort. ^ Methods. De-identified data were used from an IRB-approved parent study which identified patients on HAART and maintenance itraconazole for confirmed disseminated histoplasmosis between January 2003 and December 2006. Available itraconazole blood levels were abstracted as well as medications taken by each patient at the time of the blood tests. Mean itraconazole levels were compared using the student's t-test. ^ Results. 11 patients met study criteria. Patient characteristics were: median age 36, 91% men, 18% white, 18% black, 55% Hispanic and 9% Asians, median CD4 cell count 120 cells/mm3. 14 blood levels were available for analysis—8 on PI, 4 on NNRTI and 2 on both. 8/8 itraconazole levels obtained while taking concomitant PI were therapeutic (>0.4 μg/mL) in contrast to 0/4 obtained while taking NNRTI. Two patients switched from NNRTI to PI and reached therapeutic levels. Mean levels on NNRTI (0.05 μg/mL, s.d. 0.0) and on PI (2.45 μg/mL, s.d. 0.21) for these two patients were compared via a paired t-test (t = 16.00, d.f. = 1, P = 0.04). Remaining patient levels were compared using an unpaired t-test. Mean itraconazole on concomitant PI (n = 6) was 1.37 μg/mL (s.d. 0.74), while the mean on concomitant NNRTI was 0.05 μg/mL (s.d. 0.0), t = 2.39, d.f. = 6, P = 0.05. ^ Conclusions. Co-administration of NNRTI and itraconazole results in significant decreases in itraconazole blood levels, likely by inducing the CYP3A4 enzyme system. Itraconazole drug levels should be monitored in patients on concomitant NNRTI. PI-based HAART may be preferred over NNRTI-based HAART when using itraconazole to treat HIV-infected patients with disseminated histoplasmosis. ^

Opioid dependence treatment: options in pharmacotherapy.

The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long-term efficacy, and patient discomfort remains a significant therapy challenge. Buprenorphine's effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the USA is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence; however, randomized clinical trials are needed.

The impact of functional impairment on the survival of patients with Alzheimer's disease

Alzheimer's disease (AD), the most common form of dementia, is the fifth leading cause of death among U.S. adults aged 65 or older. Most AD patients have shorter life expectancy compared with older people without dementia. This disease has become an enormous challenge in the aging society and is also a global problem. Not only do families of patients with Alzheimer's disease need to pay attention to this problem, but also the healthcare system and society as a whole have to confront. In dementia, functional impairment is associated with basic activities of daily living (ADL) and instrumental activities of daily living (IADL). For patients with Alzheimer's disease, problems typically appear in performing IADL and progress to the inability of managing less complex ADL functions of personal care. Thus, assessment of ADLs can be used for early accurate diagnosis of Alzheimer's disease. It should be useful for patients, caregivers, clinicians, and policy planners to estimate the survival of patients with Alzheimer's disease. However, it is unclear that when making predictions of patient outcome according to their histories, time-dependent covariates will provide us with important information on how changes in a patient's status can effect the survival. In this study, we examined the effect of impaired basic ADL as measured by the Physical Self-Maintenance Scale (PSMS) and utilized a multistate survival analysis approach to estimate the probability of death in the first few years of initial visit for AD patients taking into consideration the possibility of impaired basic ADL. The dataset used in this study was obtained from the Baylor Alzheimer's Disease and Memory Disorders Center (ADMDC). No impaired basic ADL and older age at onset of impaired basic ADL were associated with longer survival. These findings suggest that the occurrence of impaired basic ADL and age at impaired basic ADL could be predictors of survival among patients with Alzheimer's disease. ^

Physical activity among breast and prostate cancer survivors: Barriers, facilitators and maintenance following the FRESH START trial

Research provides evidence of the positive health effects associated with regular physical activity participation in all populations. Activity may prove to be especially beneficial in those with chronic conditions such as cancer. However, the majority of cancer patients and survivors do not participate in the recommended amount of physical activity. The purpose of this dissertation was to identify factors associated with physical activity participation, describe how these factors change as result of a diet and exercise intervention, and to evaluate correlates of long term physical activity maintenance. ^ For this dissertation, I analyzed data from the FRESH START trial, a randomized, single-blind, phase II clinical trial focused on improving diet and physical activity among recently diagnosed breast and prostate cancer survivors. Analyses included both parametric and non-parametric statistical tests. Three separate studies were conducted, with sample sizes ranging from 400 to 486. ^ Common barriers to exercise, such as “no willpower,” “too busy,” and “I have pain,” were reported among breast and prostate cancer survivors; however, these barriers were not significantly associated with minutes of physical activity. Breast cancer survivors reported a greater number of total barriers to exercise as well as higher proportions reporting individual barriers, compared to prostate cancer survivors. Just less than half of participants reduced their total number of barriers to exercise from baseline to 1-year follow-up, and those who did reduce barriers reported greater increases in minutes of physical activity compared to those who reported no change in barriers to exercise. Participants in both the tailored and standardized intervention groups reported greater minutes of physical activity at 2-year follow-up compared to baseline. Overall, twelve percent of participants reached recommended levels of physical activity at both 1- and 2-year follow-up. Self-efficacy was positively associated with physical activity maintenance, and the number of total barriers to exercise was inversely associated with physical activity maintenance. ^ Results from this dissertation are novel and informative, and will help to guide future physical activity interventions among cancer survivors. Thoughtfully designed interventions may encourage greater participation in physical activity and ultimately improve overall quality of life in this population. ^

TRANSCRIPTIONAL AND POST-TRANSLATIONAL MECHANISMS CONTRIBUTE TO MAINTENANCE OF REST IN NEURAL TUMORS

The RE-1 silencing transcription factor (REST) is an important regulator of normal nervous system development. It negatively regulates neuronal lineage specification in neural progenitors by binding to its consensus RE-1 element(s) located in the regulatory region of its target neuronal differentiation genes. The developmentally coordinated down-regulation of REST mRNA and protein in neural progenitors triggers terminal neurogenesis. REST is overexpressed in pediatric neural tumors such as medulloblastoma and neuroblastoma and is associated with poor neuronal differentiation. High REST protein correlate with poor prognosis for patients with medulloblastoma, however similar studies have not been done with neuroblastoma patients. Mechanism(s) underlying elevated REST levels medulloblastoma and neuroblastoma are unclear, and is the focus of this thesis project. We discovered that transcriptional and post-translational mechanisms govern REST mis-regulation in medulloblastoma and neuroblastoma. In medulloblastoma, REST transcript is aberrantly elevated in a subset of patient samples. Using loss of function and gain of function experiments, we provide evidence that the Hairy Enhancer of Split (HES1) protein represses REST transcription in medulloblastoma cell lines, modulates the expression of neuronal differentiation genes, and alters the survival potential of these cells in vitro. We also show that REST directly represses its own expression in an auto-regulatory feedback loop. Interestingly, our studies identified a novel interaction between REST and HES1. We also observed their co-occupancy at the RE-1 sites, thereby suggesting potential for co-regulation of REST expression. Our pharmacological studies in neuroblastoma using retinoic acid revealed that REST levels are controlled by transcriptional and post-transcriptional mechanisms. Post-transcriptional mechanisms are mediated by modulation of E3 ligase or REST, SCFβ-TRCP, and contribute to resistance of some cells to retinoic acid treatment.