Rough Sets Determined by Quasiorders

In this paper, the ordered set of rough sets determined by a quasiorder relation $R$ is investigated. We prove that this ordered set is a complete, completely distributive lattice. We show that on this lattice can be defined three different kinds of complementation operations, and we describe its completely join-irreducible elements. We also characterize the case in which this lattice is a Stone lattice. Our results generalize some results of J. Pomykala and J. A. Pomykala (1988) and M. Gehrke and E. Walker (1992) in case $R$ is an equivalence.Comment: 18 pages, major revisio

Factors associated with willingness to take extended release naltrexone among injection drug users

BACKGROUND: Although opioid-agonist therapy with methadone or buprenorphine/naloxone is currently the mainstay of medical treatment for opioid use disorder, these medications often are not well accepted or tolerated by patients. Recently, extended release naltrexone (XR-NTX), an opioid antagonist, has been advanced as an alternative treatment. The willingness of opioid-addicted patients to take XR-NTX has not been well described. METHODS: Opioid-using persons enrolled in a community-recruited cohort in Vancouver, Canada, were asked whether or not they would be willing to take XR-NTX. Logistic regression was used to independently identify factors associated with willingness to take the medication. RESULTS: Among the 657 participants surveyed between June 1, 2013, and November 30, 2013, 342 (52.1%) were willing to take XR-NTX. One factor positively associated with willingness was daily heroin injection (adjusted odds ratio [AOR] = 1.53; 95% confidence interval [CI] = 1.02–2.31), whereas Caucasian ethnicity was negatively associated (AOR = 0.59; 95% CI = 0.43–0.82). Satisfaction with agonist therapy (13.4%) and unwillingness to stop opioids being used for pain (26.9%) were the most common reasons for being unwilling to take XR-NTX. CONCLUSIONS: A high level of willingness to take XR-NTX was observed in this setting. Interestingly, daily injection heroin use was positively associated with willingness, whereas Caucasian participants were less willing to take XR-NTX. Although explanations for unwillingness were described in this study, further research is needed to investigate real-world acceptability of XR-NTX as an additional option for the treatment of opioid use disorder

Pharmacokinetics, safety, and tolerability of a depot formulation of naltrexone in alcoholics: an open-label trial

BACKGROUND: Naltrexone is an effective medication for treatment of alcohol dependence, but its efficacy is limited by lack of adherence to the oral dosage form. A long-acting depot formulation of naltrexone may increase adherence. METHODS: A single site, 6-week open label study was conducted with 16 alcohol dependent subjects each receiving 300 mg of Naltrexone Depot by intramuscular injection. The main outcomes were safety and tolerability of the Naltrexone Depot formulation, blood levels of naltrexone and its main metabolite 6-beta naltrexol, and self-reported alcohol use. All subjects received weekly individual counseling sessions. RESULTS: The medication was well tolerated with 88% of subjects completing the 6-week trial. The most common side effect experienced was injection site complications. There were no serious adverse events. Subjects had naltrexone and 6-beta-naltrexol concentrations throughout the trial with mean values ranging from 0.58 ng/mL to 2.04 ng/mL and 1.51 ng/mL to 5.52 ng/mL, respectively, at each sampling time following administration. Compared to baseline, subjects had significantly reduced number of drinks per day, heavy drinking days and proportion of drinking days. CONCLUSION: Naltrexone Depot is safe and well tolerated in alcoholics and these findings support the further investigation of its utility in larger double-blind placebo controlled trials

Psychosocial and treatment correlates of opiate free success in a clinical review of a naltrexone implant program

Background: There is on-going controversy in relation to the efficacy of naltrexone used for the treatment of heroin addiction, and the important covariates of that success. We were also interested to review our experience with two depot forms of implantable naltrexone. Methods: A retrospective review of patients' charts was undertaken, patients were recalled by telephone and by letter, and urine drug screen samples were collected. Opiate free success (OFS) was the parameter of interest. Three groups were defined. The first two were treated in the previous 12 months and comprised "implant" and "tablet" patients. A third group was "historical" comprising those treated orally in the preceding 12 months. Results: There were 102, 113 and 161 patients in each group respectively. Groups were matched for age, sex, and dose of heroin used, but not financial status or social support. The overall follow-up rate was 82%. The Kaplan Meier 12 month OFS were 82%, 58% and 52% respectively. 12 post-treatment variables were independently associated with treatment retention. In a Cox proportional hazard multivariate model social support, the number of detoxification episodes, post-treatment employment, the use of multiple implant episodes and spiritual belief were significantly related to OFS. Conclusion: Consistent with the voluminous international literature clinically useful retention rates can be achieved with naltrexone, which may be improved by implants and particularly serial implants, repeat detoxification, meticulous clinical follow-up, and social support. As depot formulations of naltrexone become increasingly available such results can guide their clinical deployment, improve treatment outcomes, and enlarge the policy options for an exciting non-addictive pharmacotherapy for opiate addiction

Clocinnamox antagonism of opioid suppression of schedule-controlled responding in rhesus monkeys

The antagonist effects of clocinnamox were evaluated against opioid agonists, acting at μ, κ and ∂-receptors, in rhesus monkeys ( n =3–4) responding under a fixed-ratio 30 (FR 30) schedule for food delivery. Clocinnamox (0.032–0.1 mg/kg) dose-dependently antagonized fentanyl (0.001–0.32 mg/kg) after either a 3-h or 1-day pretreatment; there was substantial recovery of agonist potency by 1 week after clocinnamox. Etonitazene (0.0001–0.01 mg/kg) was also antagonized by clocinnamox (0.1 mg/kg), but to a lesser extent than fentanyl. The smaller extent of antagonism was not due to the appearance of non μ-opioid response-decreasing effects of etonitazene, since the competitive antagonist quadazocine (0.1 mg/kg) shifted the etonitazene dose-effect curve in the presence of clocinnamox (0.1 mg/kg). Clocinnamox (0.1–0.32 mg/kg) did not antagonize the rate-suppressing effects of the ∂-agonist BW373U86 (0.0.01-1.0 mg/kg) or the κ-agonist U69,593 (0.001–0.032 mg/kg). These results are consistent with previous in vivo and in vitro evidence that characterized clocinnamox as an insurmountable antagonist, with selectivity for μ-over κ- and δ-receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46352/1/213_2005_Article_BF02246641.pd

Deficit of circulating stem – progenitor cells in opiate addiction: a pilot study

A substantial literature describes the capacity of all addictive drugs to slow cell growth and potentiate apoptosis. Flow cytometry was used as a means to compare two lineages of circulating progenitor cells in addicted patients. Buprenorphine treated opiate addicts were compared with medical patients. Peripheral venous blood CD34+ CD45+ double positive cells were counted as haemopoietic stem cells (HSC's), and CD34+ KDR+ (VEGFR2+) cells were taken as endothelial progenitor cells (EPC's). 10 opiate dependent patients with substance use disorder (SUD) and 11 non-addicted (N-SUD) were studied. The ages were (mean + S.D.) 36.2 + 8.6 and 56.4 + 18.6 respectively (P <0.01). HSC's were not different in the SUD (2.38 + 1.09 Vs. 3.40 + 4.56 cells/mcl). EPC's were however significantly lower in the SUD (0.09 + 0.14 Vs. 0.26 + 0.20 cells/mcl; No. > 0.15, OR = 0.09, 95% C.I. 0.01–0.97), a finding of some interest given the substantially older age of the N-SUD group. These laboratory data are thus consistent with clinical data suggesting accelerated ageing in addicted humans and implicate the important stem cell pool in both addiction toxicology and ageing. They carry important policy implications for understanding the fundamental toxicology of addiction, and suggest that the toxicity both of addiction itself and of indefinite agonist maintenance therapies may have been seriously underestimated

Memantine increases NMDA receptor level in the prefrontal cortex but fails to reverse apomorphine-induced conditioned place preference in rats

Studies have shown that inflammation and neurodegeneration may accompany the development of addiction to apomorphine and that the glutamate NMDA receptor antagonist, memantine, may be neuroprotective. The similarity between apomorphine and dopamine with regard to their chemical, pharmacological and toxicological properties provided a basis for investigating the mechanism of action of the former agent. In this study, we investigated whether memantine would suppress apomorphine-seeking behavior in rats subjected to apomorphine-induced place preference conditioning, through modulation of NMDA receptors in the prefrontal cortex. Repeated apomorphine (1 mg/kg) treatment induced conditioned place preference (CPP) and had no significant effect on NMDA receptor levels in the prefrontal cortex. Prior treatment with memantine (5 mg/kg or 10 mg/kg) increased the levels of NMDA receptors in the prefrontal cortex but did not suppress CPP induced by apomorphine. These data give further support to the addictive effect of apomorphine and demonstrate that blockade of NMDA receptors by memantine is unable to suppress apomorphine-seeking behavior