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Buprenorphine requires concomitant activation of NOP and MOP receptors to reduce cocaine consumption.

June 22, 2017 - 6:23am
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Buprenorphine requires concomitant activation of NOP and MOP receptors to reduce cocaine consumption.

Addict Biol. 2017 Jun 21;:

Authors: Kallupi M, Shen Q, de Guglielmo G, Yasuda D, Journigan VB, Zaveri NT, Ciccocioppo R

Abstract
Buprenorphine's clinical use is approved for the treatment of heroin addiction; however, evidence supporting its efficacy in cocaine abuse also exists. While for heroin it has been demonstrated that the effect of buprenorphine is mediated by its ability to activate μ-opioid peptide receptor (MOP) receptors, the mechanism through which it attenuates cocaine intake remains elusive. We explored this mechanism using operant models where rodents were trained to chronically self-administer cocaine for 2 hours daily. Buprenorphine (0.3, 1.0 and 3.0 mg/kg) given intraperitoneally 90 minutes before access to cocaine significantly and dose dependently reduced its intake. Pre-treatment with naltrexone or with the selective nociceptin/orphanin FQ peptide (NOP) antagonist SB-612111 did not prevent buprenorphine-induced reduction of cocaine intake. However, when naltrexone and SB-612111 were combined, the effect of buprenorphine on cocaine was completely prevented. To confirm that co-activation of MOP and NOP receptors is the underlying mechanism through which buprenorphine reduces cocaine intake, three compounds, namely, AT-034, AT-201 and AT-202, with a range of affinity and intrinsic activity profiles for MOP and NOP receptors, but weak ability for kappa-opioid peptide receptor (KOP) transmission, were tested. Consistent with our hypothesis based on buprenorphine's effects, results demonstrated that AT-034 and AT-201, which co-activate MOP and NOP receptors, reduced cocaine self-administration like buprenorphine. AT-202, which selectively stimulates NOP receptors, was not effective. Together, these data demonstrate that for buprenorphine, co-activation of MOP and NOP receptors is essential to reduce cocaine consumption. These results open new vistas on the treatment of cocaine addiction by developing compounds with mixed MOP/NOP agonist properties.

PMID: 28635181 [PubMed - as supplied by publisher]

Buprenorphine/naloxone versus methadone and lofexidine in community stabilisation and detoxification: A randomised controlled trial of low dose short-term opiate-dependent individuals.

June 21, 2017 - 4:39pm

Buprenorphine/naloxone versus methadone and lofexidine in community stabilisation and detoxification: A randomised controlled trial of low dose short-term opiate-dependent individuals.

J Psychopharmacol. 2017 Jun 01;:269881117711710

Authors: Law FD, Diaper AM, Melichar JK, Coulton S, Nutt DJ, Myles JS

Abstract
Buprenorphine/naloxone, methadone and lofexidine are medications with utility in the treatment of opiate withdrawal. We report the first randomised controlled trial to compare the effects of these two medications on withdrawal symptoms and outcome during opiate induction/stabilisation and detoxification. A double-blind randomised controlled trial was conducted in an outpatient satellite clinic of a specialist drug service. Eighty opiate dependent individuals meeting DSM-IV criteria for opiate dependence, using ⩽ ½ g heroin smoked/chased or ¼ g heroin injected or ⩽ 30mg methadone, with ⩽ 3 years of opioid dependency, underwent a short-term opiate treatment programme involving induction/stabilisation on methadone 30mg or buprenorphine/naloxone 4mg/1mg, followed by detoxification (where the methadone group was assisted by lofexidine). The main outcome measures were urine drug screens for opiates and withdrawal and craving questionnaires. There were no overall differences in positive urine drug screens and drop-outs during any phase of the study. During induction/stabilisation, withdrawal symptoms subsided more slowly for buprenorphine/naloxone than for methadone, and craving was significantly higher in the buprenorphine/naloxone group ( p<0.05, 95% confidence interval -3.5, -0.38). During detoxification, withdrawal symptoms were significantly greater and the peak of withdrawal was earlier for the methadone/lofexidine group than the buprenorphine/naloxone group ( p<0.01, 95% confidence interval 3.0, 8.3). Methadone/lofexidine and buprenorphine/naloxone had comparable outcomes during rapid outpatient stabilisation and detoxification in low dose opiate users.

PMID: 28631527 [PubMed - as supplied by publisher]

Willingness to pay for opioid agonist treatment among opioid dependent people who inject drugs in Ukraine.

June 20, 2017 - 6:09am

Willingness to pay for opioid agonist treatment among opioid dependent people who inject drugs in Ukraine.

Int J Drug Policy. 2017 Jun 16;45:56-63

Authors: Makarenko I, Mazhnaya A, Marcus R, Bojko MJ, Madden L, Filippovich S, Dvoriak S, Altice FL

Abstract
BACKGROUND: In the context of decreasing external and limited Ukrainian governmental funding for opioid agonist treatments (OAT) for opioid dependent people who inject drugs in Ukraine, information on sustainable financial models is needed.
METHODS: Data on 855 opioid dependent people who inject drugs (PWID) were drawn from a cross-sectional nationwide survey of 1613 PWID. They comprised 434 participants who were receiving OAT and 421 who were on OAT in the past or have never been on OAT and were interested in receiving the treatment. Multivariate logistic regression was used to examine factors associated with willingness-to-pay (WTP) for OAT, stratified by OAT experience. Variation in the price which respondents were willing to pay for OAT and its effect on their monthly income among PWID with different OAT experience were assessed as a continuous variable using one-way ANOVA and Kruskal-Wallis test.
RESULTS: Overall, 378 (44%) expressed WTP for OAT. Factors independently associated with WTP differed by OAT experience. Among those using OAT, independent predictors of WTP included: city (Dnipro - aOR=1.9; 95%CI=1.1-4.8 and Lviv - (aOR=2.2; 95%CI=1.1-4.8) compared to those elsewhere in Ukraine), higher income (aOR=1.8; 95%CI=1.2-2.7) and receiving psychosocial counseling (aOR=1.8; 95%CI=1.2-2.7). Among those who had previously been on OAT, positive attitude towards OAT (aOR=1.3; 95%CI=1.1-1.6) and family support of OAT (aOR=2.5; 95%CI=1.1-5.7) were independently associated with WTP. Among PWID who had never been on OAT, being male (aOR=2.2; 95%CI=1.1-4.2), younger age (aOR=1.9; 95%CI=1.2-3.2), higher income (aOR=2.0; 95%CI=1.2-3.4) and previous unsuccessful attempts to enter OAT (aOR=2.3; 95%CI=1.1-4.7) were independently associated with WTP. PWID were willing to commit a large percentage of their monthly income for OAT, which, however, varied significantly based on OAT experience: current OAT: 37% of monthly income, previous OAT: 53%, and never OAT: 60% (p-value=0.0009).
CONCLUSIONS: WTP for OAT was substantial among PWID in Ukraine, supporting the implementation of self-pay or co-payment programs. Such strategies, however, must remain affordable, provide better access to OAT, and consider specific needs of PWID.

PMID: 28628853 [PubMed - as supplied by publisher]

Trends in Receipt of Buprenorphine and Naltrexone for Opioid Use Disorder Among Adolescents and Young Adults, 2001-2014.

June 20, 2017 - 6:09am

Trends in Receipt of Buprenorphine and Naltrexone for Opioid Use Disorder Among Adolescents and Young Adults, 2001-2014.

JAMA Pediatr. 2017 Jun 19;:

Authors: Hadland SE, Wharam JF, Schuster MA, Zhang F, Samet JH, Larochelle MR

Abstract
Importance: Opioid use disorder (OUD) frequently begins in adolescence and young adulthood. Intervening early with pharmacotherapy is recommended by major professional organizations. No prior national studies have examined the extent to which adolescents and young adults (collectively termed youth) with OUD receive pharmacotherapy.
Objective: To identify time trends and disparities in receipt of buprenorphine and naltrexone among youth with OUD in the United States.
Design, Setting, and Participants: A retrospective cohort study was conducted using deidentified data from a national commercial insurance database. Enrollment and complete health insurance claims of 9.7 million youth, aged 13 to 25 years were analyzed, identifying individuals who received a diagnosis of OUD between January 1, 2001, and June 30, 2014, with final follow-up date December 31, 2014. Analysis was conducted from April 25 to December 31, 2016. Time trends were identified and multivariable logistic regression was used to determine sociodemographic factors associated with medication receipt.
Exposures: Sex, age, race/ethnicity, neighborhood education and poverty levels, geographic region, census region, and year of diagnosis.
Main Outcomes and Measures: Dispensing of a medication (buprenorphine or naltrexone) within 6 months of first receiving an OUD diagnosis.
Results: Among 20 822 youth diagnosed with OUD (0.2% of the 9.7 million sample), 13 698 (65.8%) were male and 17 119 (82.2%) were non-Hispanic white. Mean (SD) age was 21.0 (2.5) years at the first observed diagnosis. The diagnosis rate of OUD increased nearly 6-fold from 2001 to 2014 (from 0.26 per 100 000 person-years to 1.51 per 100 000 person-years). Overall, 5580 (26.8%) youth were dispensed a medication within 6 months of diagnosis, with 4976 (89.2%) of medication-treated youth receiving buprenorphine and 604 (10.8%) receiving naltrexone. Medication receipt increased more than 10-fold, from 3.0% in 2002 (when buprenorphine was introduced) to 31.8% in 2009, but declined in subsequent years (27.5% in 2014). In multivariable analyses, younger individuals were less likely to receive medications, with adjusted probability for age 13 to 15 years, 1.4% (95% CI, 0.4%-2.3%); 16 to 17 years, 9.7% (95% CI, 8.4%-11.1%); 18 to 20 years, 22.0% (95% CI, 21.0%-23.0%); and 21 to 25 years, 30.5% (95% CI, 30.0%-31.5%) (P < .001 for difference). Females (7124 [20.3%]) were less likely than males (13 698 [24.4%]) to receive medications (P < .001), as were non-Hispanic black (105 [14.8%]) and Hispanic (1165 [20.0%]) youth compared with non-Hispanic white (17 119 [23.1%]) youth (P < .001).
Conclusions and Relevance: In this first national study of buprenorphine and naltrexone receipt among youth, dispensing increased over time. Nonetheless, only 1 in 4 commercially insured youth with OUD received pharmacotherapy, and disparities based on sex, age, and race/ethnicity were observed.

PMID: 28628701 [PubMed - as supplied by publisher]

Regional cerebral blood flow in opiate dependence relates to substance use and neuropsychological performance.

June 20, 2017 - 6:09am

Regional cerebral blood flow in opiate dependence relates to substance use and neuropsychological performance.

Addict Biol. 2017 Jun 19;:

Authors: Murray DE, Durazzo TC, Schmidt TP, Murray TA, Abé C, Guydish J, Meyerhoff DJ

Abstract
Neuroimaging of opiate-dependent individuals indicates both altered brain structure and function. Magnetic resonance-based arterial spin labeling has been used to measure noninvasively cerebral blood flow (i.e. perfusion) in alcohol, tobacco and stimulant dependence; only one arterial spin labeling paper in opiate-dependent individuals demonstrated frontal and parietal perfusion deficits. Additional research on regional brain perfusion in opiate dependence and its relationship to cognition and self-regulation (impulsivity, risk taking and decision making) may inform treatment approaches for opiate-dependent individuals. Continuous arterial spin labeling magnetic resonance imaging at 4 T and neuropsychological measures assessed absolute brain perfusion levels, cognition and self-regulation in 18 cigarette smoking opiate-dependent individuals (sODI) stable on buprenorphine maintenance therapy. The sODI were compared with 20 abstinent smoking alcohol-dependent individuals (a substance-dependent control group), 35 smoking controls and 29 nonsmoking controls. sODI had lower perfusion in several cortical and subcortical regions including regions within the brain reward/executive oversight system compared with smoking alcohol-dependent individuals and nonsmoking controls. Perfusion was increased in anterior cingulate cortex and globus pallidus of sODI. Compared with all other groups, sODI had greater age-related declines in perfusion in most brain reward/executive oversight system and some other regions. In sODI, lower regional perfusion related to greater substance use, higher impulsivity and weaker visuospatial skills. Overall, sODI showed cortical and subcortical hypoperfusion and hyperperfusion. Relating to neuropsychological performance and substance use quantities, the frontal perfusion alterations are clinically relevant and constitute potential targets for pharmacological and cognitive-based therapeutic interventions to improve treatment outcome in opiate dependence.

PMID: 28627790 [PubMed - as supplied by publisher]

Effects of local and spinal administrations of mu-opioids on postoperative pain in aged versus adult mice.

June 20, 2017 - 6:09am
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Effects of local and spinal administrations of mu-opioids on postoperative pain in aged versus adult mice.

Pain Rep. 2017 Jan;2(1):

Authors: Mecklenburg J, Patil MJ, Koek W, Akopian AN

PMID: 28626834 [PubMed - in process]

Staring down the opioid epidemic.

June 20, 2017 - 6:09am
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Staring down the opioid epidemic.

J Fam Pract. 2017 Jan;66(1):8

Authors: Unger JR

Abstract
Nearly 80 people die every day in America from an opioid overdose. At the same time, sales of prescription painkillers have increased 4-fold since 1999.

PMID: 28188310 [PubMed - indexed for MEDLINE]

Evaluation of Pain Assessment Techniques and Analgesia Efficacy in a Female Guinea Pig (Cavia porcellus) Model of Surgical Pain.

June 18, 2017 - 6:24am
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Evaluation of Pain Assessment Techniques and Analgesia Efficacy in a Female Guinea Pig (Cavia porcellus) Model of Surgical Pain.

J Am Assoc Lab Anim Sci. 2017 Jun 15;:

Authors: L Oliver V, Athavale S, E Simon K, V Kendall L, A Nemzek J, L Lofgren J

Abstract
Guinea pigs (Cavia porcellus) are a frequently used species in research, often involving potentially painful procedures.Therefore, evidence-based recommendations regarding analgesia are critically needed to optimize their wellbeing. Ourlaboratory examined the efficacy of carprofen and extended-release (ER) buprenorphine, alone and as a multimodal combination,for relieving postsurgical pain in guinea pigs. Animals were assessed by using evoked (mechanical hypersensitivity),nonevoked (video ethogram, cageside ethogram, time-to-consumption test), and clinical (weight loss) measurements for 96 h during baseline, anesthesia-analgesia, and hysterectomy conditions. In addition, ER buprenorphine was evaluated pharmacologically. Guinea pigs treated with a single analgesic showed increased mechanical sensitivity for at least 96 h and indices of pain according to the video ethogram for as long as 8 h, compared with levels recorded during anesthesia-analgesia. In contrast, animals given both analgesics demonstrated increased mechanical sensitivity and behavioral evidence of pain for only 2 h after surgery compared with anesthesia-analgesia. The cageside ethogram and time-to-consumption tests failed to identify differences between conditions or treatment groups, highlighting the difficulty of identifying pain in guinea pigs without remote observation. Guinea pigs treated with multimodal analgesia or ER buprenorphine lost at least 10% of their baseline weights, whereas weight loss in carprofen animals was significantly lower (3%). Plasma levels for ER buprenorphine exceeded 0.9 ng/mL from 8 to 96 h after injection. Of the 3 analgesia regimens evaluated, multimodal analgesia provided the most effective pain control in guinea pigs. However the weight loss in the ER buprenorphine-treated animals may need to be considered during analgesia selection.

PMID: 28621258 [PubMed - as supplied by publisher]

The economic burden of neonatal abstinence syndrome in the United States.

June 15, 2017 - 10:54am
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The economic burden of neonatal abstinence syndrome in the United States.

Addiction. 2017 Jun 13;:

Authors: Corr TE, Hollenbeak CS

Abstract
BACKGROUND AND AIMS: While hospital charges related to neonatal abstinence syndrome (NAS) have increased recently, there are no data available regarding costs. Therefore, we sought to describe the NAS population and compare with the non-NAS population, determine the incidence of NAS in the United States and estimate the total annual costs and hospital days of NAS admissions, and estimate the incremental costs and length of stay of an NAS admission compared with a non-NAS admission.
DESIGN: Retrospective, observational study. Data were obtained from the Kids' Inpatient Database (2003-12). Survey-weighting was used to obtain national counts of NAS births. The incremental burden of costs and length of stay were estimated for NAS admissions and compared to non-NAS admissions.
SETTING: United States hospitals from states participating in the Kids' Inpatient Database (KID), a nationally representative sample of all-payer in-patient pediatric discharges.
PARTICIPANTS: Infants with a diagnosis of NAS (27 943) were identified from the KID using ICD-9-CM codes and compared with non-NAS infants (3 783 629).
MEASUREMENTS: Primary outcome measures were provider costs and length of stay for NAS and non-NAS admissions. Costs were calculated using cost-to-charge ratios and were adjusted for inflation to 2014 US dollars.
FINDINGS: Between 2003 and 2012, NAS admissions increased more than fourfold, resulting in a surge in annual costs from US$61 million and 67 869 hospital days in 2003 to nearly US$316 million and 291 168 hospital days in 2012. For an infant affected by NAS, the hospital stay was nearly 3.5 times as long (16.57 hospital days compared with 4.98 for a non-NAS patient, P < 0.001) and the costs more than three times greater (US$16 893 compared to US$5610 for a non-affected infant, P < 0.001).
CONCLUSION: The incidence of neonatal abstinence syndrome is increasing in the United States, and carries an enormous burden in terms of hospital days and costs. The number of US hospital admissions involving neonatal abstinence syndrome increased more than fourfold between the years 2003 and 2012. In 2012, neonatal abstinence syndrome cost nearly $316 million in the United States.

PMID: 28612362 [PubMed - as supplied by publisher]

Hepatitis C in injection drug users: It is time to treat.

June 15, 2017 - 10:54am
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Hepatitis C in injection drug users: It is time to treat.

World J Gastroenterol. 2017 May 28;23(20):3569-3571

Authors: Grassi A, Ballardini G

Abstract
Injection drug users (IDUs) are at risk of hepatitis C virus (HCV) infection, due to needle and syringe sharing. Chronic HCV infection is a major cause of liver-related morbidity and mortality but can be cured with antiviral treatment leading to sustained viral response (SVR). It is well demonstrated that, when close cooperation between specialists in drug addiction and psychiatrists is assured, patients on maintenance treatment with methadone/buprenorphine can be treated for HCV with response rate, tolerability and side effects similar to those reported in non-IDUs. Current guidelines recommend that active injection drug use should not exclude patients from HCV treatment, but many services remain reluctant to treat IDUs. No significant pharmacodynamic interactions were reported between approved direct anti-viral agents (DAAs) and buprenorphine or methadone. Dose adjustments are not recommended; therefore DAAs appear to be the "perfect" therapy for patients taking opiate substitutive therapy. These suggestions have been recently recognized by the European Association for the Study of the Liver (EASL) and included in EASL Recommendations on Treatment of Hepatitis C 2016. Guidelines confirm that HCV treatment for IDUs should be considered on an individualized basis and delivered within a multidisciplinary team setting; a history of intravenous drug use and recent drug use at treatment initiation are not associated with reduced SVR and decisions to treat must be made on a case-by-case basis.

PMID: 28611509 [PubMed - in process]

Fatal and non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone.

June 14, 2017 - 6:24am

Fatal and non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone.

Int J Drug Policy. 2017 Jun 10;46:54-60

Authors: Kelty E, Hulse G

Abstract
BACKGROUND: Illicit opioid use is associated with high rates of fatal and non-fatal opioid overdose. This study aims to compare rates of fatal and serious but non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone, and to identify risk factors for fatal opioid overdose.
METHODS: Opioid dependent patients treated with methadone (n=3515), buprenorphine (n=3250) or implant naltrexone (n=1461) in Western Australia for the first time between 2001 and 2010, were matched against state mortality and hospital data. Rates of fatal and non-fatal serious opioid overdoses were calculated and compared for the three treatments. Risk factors associated with fatal opioid overdose were examined using multivariate cox proportional hazard models.
RESULTS: No significant difference was observed between the three groups in terms of crude rates of fatal or non-fatal opioid overdoses. During the first 28days of treatment, rates of non-fatal opioid overdose were high in all three groups, as were fatal opioid overdoses in patients treated with methadone. However, no fatal opioid overdoses were observed in buprenorphine or naltrexone patients during this period. Following the first 28 days, buprenorphine was shown to be protective, particularly in terms of non-fatal opioid overdoses. After the cessation of treatment, rates of fatal and non-fatal opioid overdoses were similar between the groups, with the exception of lower rates of non-fatal opioid overdose in the naltrexone treated patients compared with the methadone treated patients. After the commencement of treatment, gender, and hospitalisations with a diagnosis of opioid poisoning, cardiovascular or mental health problems were significant predictors of subsequent fatal opioid overdose.
CONCLUSIONS: Rates of fatal and non-fatal opioid overdose were not significantly different in patients treated with methadone, buprenorphine or implant naltrexone. Gender and prior cause-specific hospitalisations can be used to identify patients at a high risk of fatal opioid overdose.

PMID: 28609749 [PubMed - as supplied by publisher]

Prescription Opioid Misuse and Public Health Approach in Australia.

June 13, 2017 - 6:39am

Prescription Opioid Misuse and Public Health Approach in Australia.

Subst Use Misuse. 2017 Jun 12;:1-6

Authors: Kovitwanichkanont T, Day C

Abstract
The number of opioid prescriptions has increased significantly over the last few years due to multiple factors, such as physicians' heightened attention to pain management, greater prevalence of chronic pain due to the aging population, and the availability of sustained-release opioid preparations. Correspondingly, this has been associated with a rise in considerable harm due to opioid misuse, which is recognized as a national health priority in Australia. This article outlines the major public health approaches that have been introduced in Australia to address this issue. Opioid misuse can be addressed through establishing a real-time prescription drug monitoring program, ensuring adequate access to affordable and high quality medication-assisted treatment, and promoting physicians' use of the evidence-based guideline on appropriate opioid prescribing.

PMID: 28605278 [PubMed - as supplied by publisher]

Cost-effectiveness of subdermal implantable buprenorphine versus sublingual buprenorphine to treat opioid use disorder.

June 13, 2017 - 6:39am

Cost-effectiveness of subdermal implantable buprenorphine versus sublingual buprenorphine to treat opioid use disorder.

J Med Econ. 2017 Jun 10;:1-20

Authors: Carter JA, Dammerman R, Frost M

Abstract
AIMS: Subdermal implantable buprenorphine (BSI) was recently approved to treat opioid use disorder (OUD) in clinically-stable adults. In the pivotal clinical trial, BSI was associated with a higher proportion of completely-abstinent patients (85.7% vs 71.9%; P = 0.03) versus sublingual buprenorphine (SL-BPN). Elsewhere, relapse to illicit drug use is associated with diminished treatment outcomes and increased costs. Herein, we evaluated the cost-effectiveness of BSI versus SL-BPN from a US societal perspective.
METHODS: A Markov model simulated BSI and SL-BPN cohorts (clinically-stable adults) transiting through four mutually-exclusive health states for 12 months. Cohorts accumulated direct medical costs from drug acquisition/administration; treatment-diversion/abuse; newly-acquired hepatitis-C; emergency room, hospital, and rehabilitation services; and pediatric poisonings. Non-medical costs of criminality, lost wages/work-productivity, and out-of-pocket expenses were also included. Transition probabilities to a relapsed state were derived from the aforementioned trial. Other transition probabilities, costs, and health-state utilities were derived from observational studies and adjusted for trial characteristics. Outcomes included incremental cost per quality-adjusted-life-year (QALY) gained and incremental net-monetary-benefit (INMB). Uncertainty was assessed by univariate and probabilistic sensitivity analysis (PSA).
RESULTS: BSI was associated with lower total costs (-$4,386), more QALYs (+0.031), and favorable INMB at all willingness-to-pay (WTP) thresholds considered. Higher drug acquisition costs for BSI (+$6492) were outpaced primarily by reductions in emergency room/hospital utilization (-$8040) and criminality (-$1212). BSI was cost-effective in 89% of PSA model replicates and had a significantly higher INMB at $50,000/QALY ($20,783 vs $15,007; P < 0.05).
CONCLUSIONS: BSI was preferred over SL-BPN from a health-economic perspective for treatment of OUD in clinically-stable adults. These findings should be interpreted carefully due to some relationships having been modeled from inputs derived from multiple sources, and would benefit from comparison with outcomes from studies that employ administrative claims data or a naturalistic comparative design.

PMID: 28604141 [PubMed - as supplied by publisher]

The profile of drug users in Tunisia: Implications for prevention.

June 13, 2017 - 6:39am
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The profile of drug users in Tunisia: Implications for prevention.

Tunis Med. 2016 Aug - Sep;94(8-9):531-534

Authors: Sellami R, Feki I, Zahaf A, Masmoudi J

Abstract
BACKGROUND: Despite cultural, religious, and legal constraints on Muslims against the consumption of drugs, usage and misuse do exist. Drug addiction in Tunisia is a wide-spread problem and is destroying the lives of many individuals and families.
AIMS: To examine the socio-demographic characteristics of substance users and to identify the drugs commonly used.
METHODS: In this cross-sectional study, all the patients admitted at the addiction treatment center ''Aide et Ecoute'' in the period from January 2014 to September 2014 formed the sample of the present study.
RESULTS: Only two hundred males were found to get treatment in the addiction center for various addictions. Among them, 65.9% were not married and 59.5 % had involvement with criminal justice. The mean age was 33.32 years and the mean age for starting substance use was 17.30 years. Substance use was higher (90.6%) in less educated people (secondary or below) and in urban population (73.2%). The most common substance misused was Buprenorphine (34.8%). There was a significant relation between buprenorphine consumption and immigration p= 0.013.
CONCLUSION: Our observations point towards the vulnerability of younger age and immigrated population towards substance use and hence, it is proposed preventive health policies in this regard.

PMID: 28603825 [PubMed - in process]

Influence of opioids on immune function in patients with cancer pain: from bench to bedside.

June 9, 2017 - 7:01am
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Influence of opioids on immune function in patients with cancer pain: from bench to bedside.

Br J Pharmacol. 2017 Jun 08;:

Authors: Boland JW, Graham Pockley A

Abstract
In patients with cancer, opioids are principally used for the management of acute surgical and chronic cancer-related pain. However, opioids have many non-analgesic effects, including direct and indirect effects on cancer cells and on anti-tumour immunity (natural killer (NK) cells, macrophages and T-cells). Direct effects on immune cells are manifested via opioid and non-opioid Toll-like receptors, whereas indirect effects are manifested via the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. Opioids can also decrease/alter immune cell infiltration into the tumour microenvironment. Animal models have shown that this is not a class effect, in that morphine and fentanyl suppress NK cell cytotoxicity; buprenorphine does not affect NK cell cytotoxicity, whereas tramadol increases NK cell cytotoxicity, reducing metastasis. In healthy individuals, morphine suppresses and fentanyl enhances NK cell cytotoxicity. In patients undergoing surgery, fentanyl decreased and tramadol increased NK cell cytotoxicity; clinical outcomes were not determined. Meta-analyses of opioid-sparing surgical studies report an association between improved recurrence-free and/or overall survival with regional/neuraxial anaesthesia compared with systemic opioids. In patients receiving opioids for non-surgical cancer-related pain, morphine has variable effects on immunity; clinical outcomes were not assessed. Although there is a potential association between systemic opioid administration and shorter survival in cancer patients with a prognosis of months to years, studies have not been designed to primarily assess survival, as a consequence of which causality cannot be apportioned. Pain is immunosuppressive, so analgesia is important. Opioids for cancer-related pain will continue to be recommended until definitive data on the effects of opioids on clinical outcomes in specific patient groups becomes available.

PMID: 28593737 [PubMed - as supplied by publisher]

Morbidity and mortality in opioid dependent patients after entering an opioid pharmacotherapy compared with a cohort of non-dependent controls.

June 8, 2017 - 9:51am
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Morbidity and mortality in opioid dependent patients after entering an opioid pharmacotherapy compared with a cohort of non-dependent controls.

J Public Health (Oxf). 2017 Jun 07;:1-6

Authors: Kelty E, Hulse G

Abstract
Aims: To compare morbidity and mortality in opioid dependence patients following the commencement of treatment with the general population.
Methods: Morbidity and mortality in all patients treated with methadone, buprenorphine or implant naltrexone for opioid dependence for the first time between 2001 and 2010 in Western Australia was compared to a cohort of age and gender matched controls using state health records.
Results: Compared to community controls rates of all-cause mortality, hospital admissions and Emergency Department attendances are significantly elevated in opioid dependent persons following the commencement of their first treatment. Not surprisingly, rates of opioid and non-opioid drug poisoning, and intentional self-harm/suicide mortality and hospital admissions were significantly elevated in opioid dependent patients compared with non-dependent controls. However, significant increases in mortality and hospital admissions for conditions which are not generally associated with opioid use were also identified including cardiovascular, respiratory and traffic accidents. Life-time prevalence of both HBV and HCV were significantly elevated in opioid dependent patients compared with non-dependent patients.
Conclusions: Even after the commencement of treatment, opioid dependent patients are at a high risk of morbidity and mortality compared with non-dependent age and gender matched controls.

PMID: 28591852 [PubMed - as supplied by publisher]

Computer-aided design and synthesis of a highly selective molecularly imprinted polymer for the extraction and determination of buprenorphine in biological fluids.

June 8, 2017 - 9:51am
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Computer-aided design and synthesis of a highly selective molecularly imprinted polymer for the extraction and determination of buprenorphine in biological fluids.

J Sep Sci. 2017 Jun 07;:

Authors: Ganjavi F, Ansari M, Kazemipour M, Zeidabadinejad L

Abstract
Buprenorphine is widely used to aid the cessation of opioids in addicted patients. To the best of our knowledge, there is no selective extraction method for buprenorphine from biological fluids. Here we describe the synthesis of a molecularly imprinted polymer with the aid of computational design and its application for selective extraction of buprenorphine from plasma and urine. Computational design was used to study inter-molecular interactions in the pre-polymerization mixture by the comparison of the binding energy between buprenorphine (template) and functional monomers. The largest interaction energy of template-monomers was obtained at ratio of 1:5 buprenorphine/acrylic acid monomers. Afterwards, the molecularly imprinted polymer was synthesized through precipitation polymerization technique and was employed for selective extraction of buprenorphine. Optimization of various parameters of the molecularly imprinted polymer solid-phase extraction of buprenorphine was carried out by a design of experiment approach using a central composite design and the analyte was determined by employing high-performance liquid chromatography with UV detection. Equilibrium isotherms were studied, and results revealed that the sorption process was in adoption with Langmuir model. Maximum enrichment capacity and Langmuir constant were calculated as 18.2 mg g(-1) and 0.797 L mg(-1) , respectively. Kinetic studies indicated the sorption process followed a pseudo-second-order model. This article is protected by copyright. All rights reserved.

PMID: 28590045 [PubMed - as supplied by publisher]

Effects of Time and Storage Conditions on the Chemical and Microbiologic Stability of Diluted Buprenorphine for Injection.

June 8, 2017 - 9:51am
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Effects of Time and Storage Conditions on the Chemical and Microbiologic Stability of Diluted Buprenorphine for Injection.

J Am Assoc Lab Anim Sci. 2017 Jun 06;:

Authors: M DenHerder J, L Reed R, L Sargent J, Bobe G, F Stevens J, E Diggs H

Abstract
Buprenorphine is a partial μ-opioid agonist used for analgesia. Due to the small size of laboratory rodents, buprenorphineHCl is typically diluted 10- or 20-fold with a sterile diluent, such as saline, for accurate dosing. Protocols for preparing andstoring diluted buprenorphine vary by institution, and little published information is available regarding stability andbeyond-use dating of specific buprenorphine preparations. The purpose of this study was to determine the chemical andmicrobiologic stability of diluted buprenorphine stored for a maximum of 180 d. Buprenorphine HCl was diluted 1:10 intosterile bacteriostatic saline by using aseptic technique. Diluted samples were stored in glass vials or plastic syringes, protectedfrom light, and maintained at refrigerated or room temperature for as long as 180 d. Aerobic and anaerobic cultures on allstored samples were negative for bacterial and fungal growth. According to HPLC analysis, diluted buprenorphine storedin glass vials experienced less than 10% loss when stored for 180 d at either refrigerated or room temperature. However, theconcentration of buprenorphine stored in syringes declined rapidly to more than 80% loss at room temperature and 28% lossin the refrigerator after 180 d. According to the results of this study, diluted buprenorphine stored in glass vials retains morethan 90% of the initial concentration and is microbiologically stable for 180 d. However, our data suggest that, regardless ofthe duration, storing diluted buprenorphine in plastic syringes is inadvisable.

PMID: 28589874 [PubMed - as supplied by publisher]

Comparing the effect of buprenorphine and methadone in the reduction of methamphetamine craving: a randomized clinical trial.

June 8, 2017 - 9:51am
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Comparing the effect of buprenorphine and methadone in the reduction of methamphetamine craving: a randomized clinical trial.

Trials. 2017 Jun 06;18(1):259

Authors: Ahmadi J, Razeghian Jahromi L

Abstract
BACKGROUND: We sought to test the effectiveness of methadone and buprenorphine in the treatment of methamphetamine withdrawal craving over a 17-day treatment period.
METHODS: Patients were randomized into one of two groups. The study sample comprised 40 male subjects dependent on methamphetamine who met criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, for methamphetamine dependence and withdrawal and were seeking treatment. Furthermore, they should have a history of daily methamphetamine use for at least 6 months and should have discontinued their use just before starting the protocol. Patients received 40 mg of methadone or 8 mg of buprenorphine per day and were treated in an inpatient psychiatric hospital. We used methamphetamine craving score, negative urine drug screening test (thin-layer chromatography) during the study, and retention in treatment.
RESULTS: All 40 patients completed the study. Both drugs were effective in decreasing methamphetamine craving during methamphetamine withdrawal. Reduction of craving in the buprenorphine group was significantly more than in the methadone group (P < 0.05).
CONCLUSIONS: The results favor the efficacy and safety of buprenorphine as a short-term treatment for methamphetamine withdrawal craving. We should mention that it is to be expected that craving declines over time without any medication. Therefore, the conclusion may not be that methadone and buprenorphine both reduce the craving. Because buprenorphine is superior to methadone, only buprenorphine surely reduces craving.
TRIAL REGISTRATION: Iranian Registry of Clinical Trials identifier: IRCT2015112125160N1 . Registered on 4 June 2016.

PMID: 28587620 [PubMed - in process]

Technical Communication: Admixture of Bupivacaine-Clonidine-Buprenorphine-Dexamethasone at the Bedside in a Tertiary Care Hospital Block Room Is Not Associated with Any Apparent Burdens of Endotoxin or Microbial Growth.

June 7, 2017 - 6:09am

Technical Communication: Admixture of Bupivacaine-Clonidine-Buprenorphine-Dexamethasone at the Bedside in a Tertiary Care Hospital Block Room Is Not Associated with Any Apparent Burdens of Endotoxin or Microbial Growth.

Pain Med. 2017 Apr 01;18(4):781-785

Authors: Williams BA, Podnar SM, Bonant SA, Schanck AM

PMID: 28586444 [PubMed - in process]

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