An analysis of relapse prevention factors and their ability to predict sustained abstinence following treatment completion.

BACKGROUND & OBJECTIVES: This study assessed the role of 14 specific relapse-prevention activities and their underlying factors in maintaining abstinence among subjects (N = 302) completing outpatient treatment for stimulant dependence. METHODS: We examined what broader dimensions might subsume the 14 items constituting the Drug Avoidance Activities checklist (Farabee et al. J Subst Abuse Treat 2002;23:343-350), and how well these derived factors predicted concurrent drug use at baseline and again 3 and 12 months later. RESULTS: Although four factors were identified consistently for the three time points, only avoidance strategies had sufficient internal consistency to be retained for further analysis. Controlling for age, gender, and ethnicity, the avoidance subscale was a significant predictor of UA results at all time periods: a one-point increase in the avoidance strategies scale was associated with an 86% increase in odds of a negative UA at baseline (OR = 1.86, 95% CI = 1.37-2.53, p < .001), a 77% increase at 3-month follow-up (OR = 1.77, CI = 1.37-2.29, p < .001), and a 37% increase at 12-month follow-up (OR = 1.37, CI = 1.04-1.81, p = .026). CONCLUSIONS: Although correlations of individual items with UA results showed statistically significant (p < .05) results for 8 of 14 items at one or more observation points, avoidance-related behaviors showed the strongest associations with sustained abstinence.

A comparison of four telephone-based counseling styles for recovering stimulant users.

The continuing development and refinement of empirically supported interventions to increase participation in posttreatment care and promote sustained abstinence from illicit drug use is a priority for the addictions field. The purpose of this study was to assess the combined and relative effectiveness of four types of counseling styles, delivered by telephone, relative to a no call control condition. Stimulant users (N = 302) were randomized to one of four low-cost, telephone support protocols (unstructured/nondirective, unstructured/directive, structured/nondirective, structured/directive) or a standard referral to aftercare without telephone counseling (control). All of the study participants were nearing the completion of (or had completed) an intensive phase of structured, outpatient stimulant abuse treatment. Drug use and aftercare participation were assessed at 3 and 12 months following randomization. Intent-to-treat analyses showed no significant time-by-group interactions for these primary outcomes. Subsequent analyses, however, revealed a significant difference between the aggregated call groups and the control group at the time of the 3-month follow-up. The mean ASI drug use severity composite score for subjects in the call conditions declining from .058 at baseline to .048 at 3 months, whereas the no call/control group average score increased from .053 to .062 (χ (1) = 4.95, p = .026). A similar-and slightly stronger-effect was found when the study sample was restricted to those reporting any use during the month prior to the baseline interview (n = 152). This study provides modest support for the telephone-based counseling approaches strategies examined in this project. Subsequent research will assess interactions between patient characteristics and counseling styles, and improved identification of which treatment graduates might be more likely to benefit from this type of continuing support. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Resistance of Staphylococcus aureus to the cationic antimicrobial agent poly(2-(dimethylamino ethyl)methacrylate) (pDMAEMA) is influenced by cell-surface charge and hydrophobicity.

Cationic antimicrobial agents may prevent device-associated infections caused by Staphylococcus epidermidis and Staphylococcus aureus. This study reports that the cationic antimicrobial polymer poly(2-(dimethylamino ethyl)methacrylate) (pDMAEMA) was more effective at antagonizing growth of clinical isolates of S. epidermidis than of S. aureus. Importantly, mature S. epidermidis biofilms were significantly inactivated by pDMAEMA. The S. aureus isolates tested were generally more hydrophobic than the S. epidermidis isolates and had a less negative charge, although a number of individual S. aureus and S. epidermidis clinical isolates had similar surface hydrophobicity and charge values. Fluorescence spectroscopy and flow cytometry revealed that fluorescently labelled pDMAEMA interacted strongly with S. epidermidis compared with S. aureus. S. aureus ΔdltA and ΔmprF mutants were less hydrophobic and therefore more susceptible to pDMAEMA than wild-type S. aureus. Although the different susceptibility of S. epidermidis and S. aureus isolates to pDMAEMA is complex, influenced in part by surface hydrophobicity and charge, these findings nevertheless reveal the potential of pDMAEMA to treat S. epidermidis infections.

High content analysis of cytotoxic effects of pDMAEMA on human intestinal epithelial and monocyte cultures.

Poly(2-(dimethylamino ethyl)methacrylate) (pDMAEMA) is a cationic polymer with potential as an antimicrobial agent and as a non-viral gene delivery vector. The aim was to further elucidate the cytotoxicity of a selected pDMAEMA low molecular weight (MW) polymer against human U937 monocytes and Caco-2 intestinal epithelial cells using a novel multi-parameter high content analysis (HCA) assay and to investigate histological effects on isolated rat intestinal mucosae. Seven parameters of cytotoxicity were measured: nuclear intensity (NI), nuclear area (NA), intracellular calcium ([Ca(2+)]i), mitochondrial membrane potential (MMP), plasma membrane permeability (PMP), cell number (CN) and phospholipidosis. Histological effects of pDMAEMA on excised rat ileal and colonic mucosae were investigated in Ussing chambers. Following 24-72 h exposure, 25-50 microg/ml pDMAEMA induced necrosis in U937 cells, while 100-250 microg/ml induced apoptosis in Caco-2. pDMAEMA increased NA and NI and decreased [Ca(2+)]i, PMP, MMP and CN in U937 cells. In Caco-2, it increased NI and [Ca(2+)]i, but decreased NA, PMP, MMP and CN. Phospholipidosis was not observed in either cell line. pDMAEMA (10 mg/ml) did not induce any histological damage on rat colonic tissue and only mild damage to ileal tissue following exposure for 60 min. In conclusion, HCA reveals that pDMAEMA induces cytotoxicity in different ways on different cell types at different concentrations. HCA has potential for high throughput toxicity screening in drug formulation programmes.

Antibacterial effects of poly(2-(dimethylamino ethyl)methacrylate) against selected gram-positive and gram-negative bacteria.

Antimicrobial coatings can reduce the occurrence of medical device-related bacterial infections. Poly(2-(dimethylamino ethyl)methacrylate) (pDMAEMA) is one such polymer that is being researched in this regard. The aims of this study were to (1) elucidate pDMAEMA's antimicrobial activity against a range of Gram-positive and Gram-negative bacteria and (2) to investigate its antimicrobial mode of action. The methods used include determination of minimum inhibitory concentration (MIC) values against various bacteria and the effect of pH and temperature on antimicrobial activity. The ability of pDMAEMA to permeabilise bacterial membranes was determined using the dyes 1-N-phenyl-naphthylamine and calcein-AM. Flow cytometry was used to investigate pDMAEMA's capacity to be internalized by bacteria and to determine effects on bacterial cell cycling. pDMAEMA was bacteriostatic against Gram-negative bacteria with MIC values between 0.1-1 mg/mL. MIC values against Gram-positive bacteria were variable. pDMAEMA was active against Gram-positive bacteria around its pK(a) and at lower pH values, while it was active against Gram-negative bacteria around its pK(a) and at higher pH values. pDMAEMA inhibited bacterial growth by binding to the outside of the bacteria, permeabilizing the outer membrane and disrupting the cytoplasmic membrane. By incorporating pDMAEMA with erythromycin, it was found that the efficacy of the latter was increased against Gram-negative bacteria. Together, the results illustrate that pDMAEMA acts in a similar fashion to other cationic biocides.

A tertiary amino-containing polymethacrylate polymer protects mucus-covered intestinal epithelial monolayers against pathogenic challenge.

PURPOSE: We examined the cytoprotective influences of the mucoadhesive polymer, poly(DMAEMA), on human mucus-producing intestinal epithelial monolayers against two bacterial exotoxins and S. typhimurium. Direct anti-bacterial effects were also assessed against S. typhimurium. METHODS: In the presence and absence of mucus, untreated or poly(DMAEMA)-exposed monolayers were challenged with S. typhimurium or supernatants containing either cholera (CTx) or C. difficile toxins. Assays included LDH, cytokine secretion, cyclic AMP (cAMP) and microscopy to visualise bacterial adherence by monolayers. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of poly(DMAEMA) against S. typhimurium were established, along with a time-kill study. RESULTS: CTx and C. difficile toxin induced LDH release from E12 monolayers. CTx also elevated intracellular epithelial cAMP, while S. typhimurium induced basolateral IL-8 secretion. Pre-treatment of E12 monolayers with poly(DMAEMA) reduced these effects, but only in the presence of mucus. The polymer co-localised with S. typhimurium in mucus and reduced bacteria-epithelia association. Poly(DMAEMA) was directly bactericidal against S. typhimurium at 1 mg/ml within 30 min. CONCLUSIONS: Poly(DMAEMA) may have potential as a non-absorbed polymer therapeutic against infection. These effects were mediated by a combination of physical interaction with mucus and by direct bacterial killing.