Predictors of Retention and Drug Use Among Patients With Opioid Use Disorder Transferred to a Specialty "Second Chance" Methadone Program.

Background: Many patients in methadone treatment have difficulty achieving or maintaining drug abstinence, and many clinics have policies that lead to discharging these patients. We designed a pilot "Second Chance" (SC) program for patients scheduled to be discharged from other local methadone clinics to be transferred to our clinic. Aim: Determine whether SC patients' retention and opioid use is related to physical or mental health conditions, non-opioid substance use, or treatment features. Methods: From December 2012 to December 2014, this program enrolled 70 patients who were discharged from other clinics in the area; we were their last remaining option for methadone treatment. Unlike the clinic's standard policies, the treatment focus for SC patients was retention rather than abstinence. This program focused on connection to care (eg, psychiatric services) and enabled patients to continue receiving services despite ongoing substance use. Each patient was assessed at treatment entry and followed until June 2016 to evaluate outcomes. Results: SC patients receiving disability benefits (n = 37) vs. non-disabled (n = 33) had significantly (P < .05) higher rates of current DSM-IV Axis I psychiatric diagnosis (97% vs 70%), prescriptions for opioids (84% vs 55%) and benzodiazepines (65% vs 27%), and higher methadone doses at admission (58 vs 46 mg) but did not differ significantly in rates of 6-month or 1-year retention (77% and 56%, respectively) or all-drug use (39% positive urine drug screens). Methadone doses >65 mg predicted significantly longer retention and less opioid use, but these effects were not moderated by baseline characteristics. Conclusions: Patients in methadone treatment struggling to achieve abstinence may benefit from retention-oriented harm-reduction programs. Higher methadone doses can improve retention and opioid abstinence despite psychiatric comorbidities. Further work is needed to improve program implementation and outcomes in this complex population.

A peroxisome proliferator-activated receptor alpha/gamma dual agonist with a unique in vitro profile and potent glucose and lipid effects in rodent models of type 2 diabetes and dyslipidemia.

LSN862 is a novel peroxisome proliferator-activated receptor (PPAR)alpha/gamma dual agonist with a unique in vitro profile that shows improvements on glucose and lipid levels in rodent models of type 2 diabetes and dyslipidemia. Data from in vitro binding, cotransfection, and cofactor recruitment assays characterize LSN862 as a high-affinity PPARgamma partial agonist with relatively less but significant PPARalpha agonist activity. Using these same assays, rosiglitazone was characterized as a high-affinity PPARgamma full agonist with no PPARalpha activity. When administered to Zucker diabetic fatty rats, LSN862 displayed significant glucose and triglyceride lowering and a significantly greater increase in adiponectin levels compared with rosiglitazone. Expression of genes involved in metabolic pathways in the liver and in two fat depots from compound-treated Zucker diabetic fatty rats was evaluated. Only LSN862 significantly elevated mRNA levels of pyruvate dehydrogenase kinase isozyme 4 and bifunctional enzyme in the liver and lipoprotein lipase in both fat depots. In contrast, both LSN862 and rosiglitazone decreased phosphoenol pyruvate carboxykinase in the liver and increased malic enzyme mRNA levels in the fat. In addition, LSN862 was examined in a second rodent model of type 2 diabetes, db/db mice. In this study, LSN862 demonstrated statistically better antidiabetic efficacy compared with rosiglitazone with an equivalent side effect profile. LSN862, rosiglitazone, and fenofibrate were each evaluated in the humanized apoA1 transgenic mouse. At the highest dose administered, LSN862 and fenofibrate reduced very low-density lipoprotein cholesterol, whereas, rosiglitazone increased very low-density lipoprotein cholesterol. LSN862, fenofibrate, and rosiglitazone produced maximal increases in high-density lipoprotein cholesterol of 65, 54, and 30%, respectively. These findings show that PPARgamma full agonist activity is not necessary to achieve potent and efficacious insulin-sensitizing benefits and demonstrate the therapeutic advantages of a PPARalpha/gamma dual agonist.

Gender-specific predictors of retention and opioid abstinence during methadone maintenance treatment.

AIMS: Retention in methadone maintenance treatment (MMT) for 1 year is associated with positive outcomes including opioid abstinence, however, most studies have not investigated gender differences. We hypothesized that predictors of retention and opioid abstinence would differ between men and women, and aimed to determine which factors best predict retention and abstinence for each gender. METHODS: Data were available for 290 patients (173 M, 117 F) admitted to outpatient MMT. Regression analyses, stratified by gender, were conducted to identify unique predictors of MMT retention (<1 vs. >1 year) and opioid abstinence rate (proportion of opioid-free urine samples up to 1 year retention). RESULTS: Gender did not significantly predict treatment retention (mean = 231 days, 39% retained > 1 year) or opioid abstinence (49% overall). For males, significant predictors of > 1-year retention were urine samples negative for opioids (odds ratio [OR] = 6.67) and cannabinoids (OR = 5.00) during the first month, and not cocaine dependent (OR = 2.70). Significant predictors of higher long-term opioid abstinence were first-month urine samples negative for opioids and cocaine metabolites. For females, significant predictors of >1-year retention were first-month urine samples negative for cocaine metabolites (OR = 4.00) and cannabinoids (OR = 9.26), and no history of sexual victimization (OR = 3.03). The only significant predictor of higher opioid abstinence rate was first-month opioid-free urine samples. CONCLUSIONS: These findings indicate gender-specific predictors of MMT retention and opioid abstinence. Future studies on MMT outcomes should examine each gender separately, and consider unique pathways by which females and males adhere to, and benefit from MMT.

Predicting cocaine group treatment outcome in cocaine-abusing methadone patients.

The authors examined predictors of cocaine group treatment outcome in methadone maintenance treatment (MMT) patients, including cocaine urinalysis at intake and demographic variables. Clinic policy is that patients identified as using cocaine must attend a weekly cocaine-focused, cognitive-behavioral therapy (CBT) group. Cocaine treatment is based on a behavioral (escape) contingency model whereby completers must attend group-counseling sessions and produce cocaine-negative urinalysis results. Among the 113 patients enrolled in the cocaine group, 43 (38%) were treatment completers (who attended 6 consecutive weeks of group and produced 6 consecutive weeks of cocaine-free urine tests) and 70 (62%) were treatment noncompleters. Treatment completion (i.e., cocaine abstinence) was significantly associated with baseline cocaine-free urinalysis and higher methadone dose.

Synthesis and evaluation of aminomethyl dihydrocinnamates as a new class of PPAR ligands.

PPAR ligands with varied subtype selectivity have been synthesized using an achiral aminomethyl dihydrocinnamate template. Several compounds in this series have demonstrated potent plasma glucose and triglyceride lowering capability in rodent models of type 2 diabetes.

DNA immunization against respiratory syncytial virus (RSV) in infant rhesus monkeys.

A DNA vaccine was tested in infant Rhesus macaques to evaluate its safety, immunogenicity and protective efficacy. Monkeys were vaccinated and challenged with a clinical isolate of human RSV. Vaccinated animals developed humoral and cellular responses following inoculation with plasmid DNA encoding the fusion (F) and nucleoprotein (N), from closely related bovine RSV. Vaccinated monkeys had decreased RSV in their lungs post-infection, and there was a qualitative difference in histopathology observed between vaccinated and unvaccinated animals. The combined result of safety and immunogenicity in a neonatal primate model is encouraging, suggesting the feasibility of DNA vaccines against RSV in infants.

A multilevel ecological approach to promoting walking in rural communities.

BACKGROUND: Walking is a key focus of public health interventions yet is particularly uncommon in rural residents. This study's purpose was to determine whether a multilevel community intervention affected rates of moderate physical activity, in particular walking. METHODS: A quasi-experimental design examined changes in walking in six rural intervention communities in Missouri and six comparison communities in Arkansas and Tennessee in 2003-2004. Interventions were developed with community input and included individually tailored newsletters; interpersonal activities that stressed social support and health provider counseling; and community-wide events such as fun walks. A dose variable estimated exposure to intervention activities. Primary outcomes were rates of walking and moderate physical activity in the past week. RESULTS: At follow-up (n = 1531), the percentage of respondents who met the recommendation for walking was the same across the intervention and comparison areas. Among the dependent variables, walking showed some evidence of a positive linear trend across dose categories (P = 0.090). After adjusting for covariates and baseline rates, intervention participants in the moderate and high dose categories were about three times more likely to meet recommended guidelines for walking. CONCLUSIONS: Some evidence of effectiveness was shown for a multilevel intervention approach to promote walking.

2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents.

Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.

Prior DNA vaccination does not interfere with the live-attenuated measles vaccine.

The currently used live-attenuated measles vaccine is very effective although maternal antibody prevents its administration prior to 6 months of age. We are investigating the ability of a DNA vaccine encoding the measles viral hemagglutinin, fusion and nucleoprotein to protect newborn infants from measles. Here, we show that a measles DNA vaccine protects juvenile macaques from pathogenic measles virus challenge and that macaques primed and boosted with this DNA vaccine have anemnestic antibody and cell-mediated responses after vaccination with a live-attenuated canine distemper-measles vaccine. Therefore, this DNA vaccine administered to newborn infants may not hinder the subsequent use of live-attenuated measles vaccine.

Protection against challenge with measles virus (MV) in infant macaques by an MV DNA vaccine administered in the presence of neutralizing antibody.

Measles virus (MV) infection is the major cause of vaccine-preventable death in infants and children worldwide. It is difficult to achieve immunity to MV infection by use of vaccines in infants during the first 6-9 months of life because of the presence of maternal antibody. Morbidity and mortality due to MV infection would decrease substantially if a vaccine administered at birth could prime immunity in the presence of maternal antibody. We demonstrate here that an MV DNA vaccine administered to infant macaques in the presence of maternal antibody primes MV-specific T cell responses but not de novo neutralizing antibody. This vaccine protected 80% of the infant macaques from skin rash and MV-induced immunosuppression. A molecular interleukin-2 adjuvant was required for protection with this vaccine. This macaque model shows that infants can be vaccinated against MV in the presence of maternal antibody. These results suggest that it is possible to develop an MV DNA vaccine that could protect infants in developing countries during the first months of life.

DNA vaccination of infants in the presence of maternal antibody: a measles model in the primate.

To eradicate measles in developing nations a vaccine capable of being administered at birth may be necessary. We immunized newborn rhesus macaques with naked DNA encoding the measles virus hemagglutinin, fusion and nucleoprotein genes. Prior to vaccination we passively transferred measles immunoglobulin to mimic maternal antibody. In the presence or absence of measles immunoglobulin, 23 of 25 infant macaques had detectable cell mediated immunity and 16 had protective levels of neutralizing antibody. The co-administration of an IL-2/IgG plasmid augmented the vaccine, increasing cell mediated immunity in all infants and increasing the antibody response in infants vaccinated without immunoglobulin. We show for the first time that DNA vaccination can protect a newborn primate from the high-level viremia that correlates with severe measles, even in the presence of maternal antibody. Further, the addition of a molecular IL-2 adjuvant augments this DNA vaccine.

Improving on-time counseling attendance in a methadone treatment program: a contingency management approach.

Two studies were conducted to investigate the effectiveness of contingency management techniques in promoting punctual counseling attendance among methadone maintenance patients. In Study 1, 50 participants were recruited from an inner-city methadone maintenance program. Study 1 used an A-B-A design with baseline, intervention, and return-to-baseline phases. On-time attendance was reinforced during the intervention phase with a voucher that was redeemable for a draw out of a box containing 100 tokens with values varying from 0.00 dollars to 100.00 dollars. Methadone maintenance patients who exhibited poor attendance during baseline showed a significant positive response during the contingency management intervention phase. Study 2 used the same design as Study 1 except that the 52 participants were randomized into reinforcement groups that received either the variable rate of reinforcement as in Study 1 or a fixed value reinforcer of 3.25 dollars. As in Study 1, Poor Attenders significantly improved counseling attendance during the intervention. There were no differences between the variable and fixed reinforcement groups. Overall, results suggest that targeting Poor Attenders with contingency management techniques may be a cost-effective method of improving counseling attendance. Targeting Poor Attenders early in treatment may be especially important for improving treatment outcomes.