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Peripartum Anesthetic Management of the Opioid-tolerant or Buprenorphine/Suboxone-dependent Patient.

April 21, 2017 - 6:18am

Peripartum Anesthetic Management of the Opioid-tolerant or Buprenorphine/Suboxone-dependent Patient.

Clin Obstet Gynecol. 2017 Jun;60(2):447-458

Authors: Pan A, Zakowski M

Abstract
Opioid abuse and dependence continues to rise in both the general population and pregnancy, with opioid overdose deaths having quadrupled in the last 15 years. Illicit drug use in last 30 days of pregnancy was over 4% with almost 0.6% documented maternal opiate use at time of birth. The management of the opioid-tolerant, buprenorphine-dependent or methadone-dependent patient in the peripartum period is reviewed. Options for treatment of opioid dependence, acute pain management, and perioperative multimodal analgesia are discussed. The effects of maternal management on neonatal abstinence syndrome are also reviewed.

PMID: 28426507 [PubMed - in process]

Buprenorphine Treatment and Patient Use of Health Services after the Affordable Care Act in an Integrated Health Care System.

April 21, 2017 - 6:18am

Buprenorphine Treatment and Patient Use of Health Services after the Affordable Care Act in an Integrated Health Care System.

J Psychoactive Drugs. 2017 Apr 20;:1-9

Authors: Campbell CI, Parthasarathy S, Young-Wolff KC, Satre DD

Abstract
The Affordable Care Act (ACA) was expected to benefit patients with substance use disorders, including opioid use disorders (OUDs). This study examined buprenorphine use and health services utilization by patients with OUDs pre- and post-ACA in a large health care system. Using electronic health record data, we examined demographic and clinical characteristics (substance use, psychiatric and medical conditions) of two patient cohorts using buprenorphine: those newly enrolled in 2012 ("pre-ACA," N = 204) and in 2014 ("post-ACA," N = 258). Logistic and negative binomial regressions were used to model persistent buprenorphine use, and to examine whether persistent use was related to health services utilization. Buprenorphine patients were largely similar pre- and post-ACA, although more post-ACA patients had a marijuana use disorder (p < .01). Post-ACA patients were more likely to have high-deductible benefit plans (p < .01). Use of psychiatry services was lower post-ACA (IRR: 0.56, p < .01), and high-deductible plans were also related to lower use of psychiatry services (IRR: 0.30, p < .01). The relationship between marijuana use disorder and prescription opioid use is complex, and deserves further study, particularly with increasingly widespread marijuana legalization. Access to psychiatry services may be more challenging for buprenorphine patients post-ACA, especially for patients with deductible plans.

PMID: 28426332 [PubMed - as supplied by publisher]

Image Gallery: Nicolau syndrome after misuse of buprenorphine.

April 19, 2017 - 6:04am

Image Gallery: Nicolau syndrome after misuse of buprenorphine.

Br J Dermatol. 2017 Apr;176(4):e35

Authors: Espitia O, Vigneau-Victorri C, Pistorius MA

PMID: 28418123 [PubMed - in process]

Pharmacokinetics of buprenorphine following constant rate infusion for postoperative analgesia in dogs undergoing ovariectomy.

April 19, 2017 - 6:04am
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Pharmacokinetics of buprenorphine following constant rate infusion for postoperative analgesia in dogs undergoing ovariectomy.

Vet Anaesth Analg. 2017 Jan 11;:

Authors: Barbarossa A, Rambaldi J, Giunti M, Zaghini A, Cunto M, Zambelli D, Valgimigli S, Santoro F, Romagnoli N

Abstract
OBJECTIVE: To investigate the pharmacokinetics of buprenorphine and its main active metabolite, norbuprenorphine, after administration of an intravenous loading dose followed by constant rate infusion (CRI) in dogs.
STUDY DESIGN: Prospective, clinical study.
ANIMALS: A total of seven healthy dogs undergoing elective ovariectomy.
METHODS: Buprenorphine was administered as a loading dose (intravenous bolus of 15 μg kg(-1)) followed by CRI (2.5 μg kg(-1) hour(-1) for 6 hours). Moreover, intraoperative analgesia was supplemented by an intramuscular carprofen (4 mg kg(-1)) injection, administered prior to surgery, and by lidocaine, administrated through subcutaneous infiltration and through a splash on the ovarian vascular pedicle during surgery. Pain and sedation were scored for all animals throughout the 24-hour study period and rescue analgesia was administered when a visual analogue scale score was > 40 mm. Blood samples were collected from a jugular catheter at regular intervals, and plasma concentrations of buprenorphine and norbuprenorphine were determined by a validated liquid chromatography-tandem mass spectrometry method.
RESULTS: Buprenorphine showed a two-compartment kinetic profile. Maximum concentration was 23.92 ± 8.64 ng mL(-1) at 1 minute (maximum time); elimination half-life was 41.87 ± 17.35 minutes; area under the curve was 486.68 ± 125.66 minutes ng(-1) mL(-1); clearance was 33.61 ± 13.01 mL minute(-1) kg(-1), and volume of distribution at steady state was 1.77 ± 0.50 L kg(-1). In no case was rescue analgesia required. Norbuprenorphine resulted below the lower limit of quantification in almost all samples.
CONCLUSIONS AND CLINICAL RELEVANCE: The results suggest that a buprenorphine CRI can be a useful tool for providing analgesia in postoperative patients, considering its minor side effects and the advantages of a CRI compared to frequent boluses. The negligible contribution of norbuprenorphine to the therapeutic effect was confirmed.

PMID: 28416162 [PubMed - as supplied by publisher]

Patterns of Buprenorphine-Naloxone Treatment for Opioid Use Disorder in a Multistate Population.

April 15, 2017 - 6:16am

Patterns of Buprenorphine-Naloxone Treatment for Opioid Use Disorder in a Multistate Population.

Med Care. 2017 Apr 13;:

Authors: Saloner B, Daubresse M, Caleb Alexander G

Abstract
BACKGROUND: Buprenorphine-naloxone treatment for opioid use disorder has rapidly expanded, yet little is known about treatment outcomes among patients in the general population.
OBJECTIVE: To examine predictors of treatment duration, dosage, and continuity in a diverse community setting.
RESEARCH DESIGN: We examined QuintilesIMS Real World Data, an all-payer, pharmacy claims database, to conduct an analysis of individuals age 18 years and above initiating buprenorphine-naloxone treatment between January 2010 and July 2012 in 11 states. We used logistic regression to assess treatment duration longer than 6 months. We used accelerated failure time models to assess risk of treatment discontinuation. We used ordinary least squares regression to assess mean daily dosage. For patients with ≥3 fills, we also used logistic regression to assess whether ;an individual had a medication possession ratio of <80% and/or gaps in treatment >14 days. Models adjusted for individual demographics, prescribing physician specialty, state, and county-level variables.
RESULTS: Overall, 41% of individuals were retained in treatment for at least 6 months and the mean treatment length was 266 days. Compared with individuals who paid primarily for treatment with cash, adjusted odds of 6 month retention were significantly lower for individuals with primary payment from Medicaid fee-for-service, Medicare part D, and third-party commercial. There were substantial differences in 6-month retention across states with the lowest in Arizona and highest in New York. Low-possession ratios occurred for 30% of individuals and 26% experienced treatment episodes with gaps >14 days. Odds of low-possession and treatment gaps were largely similar across demographic groups and geographic areas.
CONCLUSIONS: Current initiatives to improve access and quality of buprenorphine-naloxone treatment should examine geographic barriers as well as the potential role of insurance benefit design in restricting treatment length.

PMID: 28410339 [PubMed - as supplied by publisher]

Treating Women Who Are Pregnant and Parenting for Opioid Use Disorder and the Concurrent Care of Their Infants and Children: Literature Review to Support National Guidance.

April 14, 2017 - 6:09am

Treating Women Who Are Pregnant and Parenting for Opioid Use Disorder and the Concurrent Care of Their Infants and Children: Literature Review to Support National Guidance.

J Addict Med. 2017 Apr 13;:

Authors: Klaman SL, Isaacs K, Leopold A, Perpich J, Hayashi S, Vender J, Campopiano M, Jones HE

Abstract
OBJECTIVES: The prevalence of opioid use disorder (OUD) during pregnancy is increasing. Practical recommendations will help providers treat pregnant women with OUD and reduce potentially negative health consequences for mother, fetus, and child. This article summarizes the literature review conducted using the RAND/University of California, Los Angeles Appropriateness Method project completed by the US Department of Health and Human Services Substance Abuse and Mental Health Services Administration to obtain current evidence on treatment approaches for pregnant and parenting women with OUD and their infants and children.
METHODS: Three separate search methods were employed to identify peer-reviewed journal articles providing evidence on treatment methods for women with OUD who are pregnant or parenting, and for their children. Identified articles were reviewed for inclusion per study guidelines and relevant information was abstracted and summarized.
RESULTS: Of the 1697 articles identified, 75 were included in the literature review. The perinatal use of medication for addiction treatment (MAT, also known as medication-assisted treatment), either methadone or buprenorphine, within comprehensive treatment is the most accepted clinical practice, as withdrawal or detoxification risks relapse and treatment dropout. Medication increases may be needed with advancing pregnancy, and are not associated with more severe neonatal abstinence syndrome (NAS). Switching medication prenatally is usually not recommended as it can destabilize opioid abstinence. Postnatally, breastfeeding is seen as beneficial for the infant for women who are maintained on a stable dose of opioid agonist medication. Less is known about ideal pain management and postpartum dosing regimens. NAS appears generally less severe following prenatal exposure to buprenorphine versus methadone. Frontline NAS medication treatments include protocol-driven methadone and morphine dosing in the context of nonpharmacological supports.
CONCLUSIONS: Women with OUD can be treated with methadone or buprenorphine during pregnancy. NAS is an expected and manageable condition. Although research has substantially advanced, opportunities to guide future research to improve maternal and infant outcomes are provided.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.. http://creativecommons.org/licenses/by-nc-nd/4.0.

PMID: 28406856 [PubMed - as supplied by publisher]

Safety and efficacy of transdermal buprenorphine versus oral tramadol for the treatment of post-operative pain following surgery for fracture neck of femur: A prospective, randomised clinical study.

April 14, 2017 - 6:09am
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Safety and efficacy of transdermal buprenorphine versus oral tramadol for the treatment of post-operative pain following surgery for fracture neck of femur: A prospective, randomised clinical study.

Indian J Anaesth. 2017 Mar;61(3):225-229

Authors: Desai SN, Badiger SV, Tokur SB, Naik PA

Abstract
BACKGROUND: Transdermal buprenorphine, which is used in chronic pain management, has rarely been studied for use in acute pain management. The aim of this study was to compare the safety and efficacy of transdermal buprenorphine patch to oral tramadol for post-operative analgesia, following proximal femur surgeries.
METHODOLOGY: Fifty adult patients undergoing surgery for hip fracture under spinal anaesthesia were included in this study. One group (Group TDB) received transdermal buprenorphine 10 mcg/h patch applied a day before the surgery and other group received oral tramadol 50 mg three times a day for analgesia (Group OT). They were allowed to take diclofenac and paracetamol tablets for rescue analgesia. Pain scores at rest, on movement, rescue analgesic requirement and side effects were compared between the groups over 7 days. Chi-square and independent sample t-test were used for categorical and continuous variables, respectively.
RESULTS: Resting pain scores and pain on movement were significantly lower in TDB Group on all 7 days starting from 24 h post-operatively. Rescue analgesic requirement was significantly lower in TDB Group compared to OT Group. All the patients needed rescue analgesic in OT Group whereas 68% of the patients needed the same in TDB Group. Incidence of vomiting was less and satisfaction scores were much higher in TDB Group as compared to OT Group (79% vs. 66%, P < 0.001).
CONCLUSION: Transdermal buprenorphine can be safely used for post-operative analgesia and is more efficacious in reducing post-operative pain after 24 hours, with fewer side effects when compared to oral tramadol.

PMID: 28405035 [PubMed - in process]

Injection of Pharmaceuticals Designed for Oral Use: Harms Experienced and Effective Harm Reduction Through Filtration.

April 13, 2017 - 6:55am
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Injection of Pharmaceuticals Designed for Oral Use: Harms Experienced and Effective Harm Reduction Through Filtration.

Curr Top Behav Neurosci. 2017 Apr 02;:

Authors: McLean S, Patel R, Bruno R

Abstract
Several pharmaceutical products are liable to 'abuse' or use outside their prescription, which frequently involves their injection. Examples are slow-release forms of morphine and oxycodone, and sublingual buprenorphine. During injection preparation, the drug is extracted into water, after crushing and heating the tablet if considered necessary. Since these products are designed for oral administration, they can contain excipients (ingredients other than the drug) which are poorly soluble, resulting in suspension of particles in the injection solution. Injected particles are able to produce medical complications such as the blockage of small blood vessels leading to ischaemia (inadequate blood flow) and tissue damage. Filtration can be used to remove particles from the suspension; including bacteria if the porosity is small enough (0.2 μm). However, filters are liable to blockage when overloaded, especially if the pore size is small. This problem can be minimised by using a larger pore size (e.g. 5-10 μm), but the resulting filtrate will contain many residual small particles. The use of two filters, coarse and fine, either sequentially or in a double membrane device, enables removal of the majority of particles as well as bacteria, although not quite meeting pharmaceutical standards for safe injection. Although not yet evaluated by a clinical trial, this highly effective filtration process would be expected to greatly reduce the risk of vascular and related complications, as well as non-viral infections. Careful technique ensures that drug is not lost by filtration, a priority for most drug consumers. Practical issues that affect acceptability of filtration by injecting drug users, including ease of use and cost, will need to be considered. However, given the laboratory evidence demonstrating the effectiveness of filters it is time to consider these tools as essential for safe injection as sterile needles/syringes for the world's approximately 16 million people who inject drugs.

PMID: 28401523 [PubMed - as supplied by publisher]

Rural Opioid Use Disorder Treatment Depends on Family Physicians.

April 13, 2017 - 6:55am
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Rural Opioid Use Disorder Treatment Depends on Family Physicians.

Am Fam Physician. 2016 Oct 01;94(7):546

Authors: Wingrove P, Park B, Bazemore A

PMID: 27929214 [PubMed - indexed for MEDLINE]

[The peculiarities of the comprehensive study of buprenorphine].

April 12, 2017 - 6:45am

[The peculiarities of the comprehensive study of buprenorphine].

Sud Med Ekspert. 2017;60(2):30-35

Authors: Lobacheva GK, Simonov EA, Kuzovlev VY, Kairgaliev DV, Gavrilin YV, Atroshchenko YM

Abstract
The authors describe the methods of pharmaceutical and criminalistics analysis that are finding the increasingly wider application for the drug expertise (identification) and elucidation of the circumstances conducive to the commission of an offence. The special emphasis is laid on the buprenorphine studies with the use of the colour chemical reactions, thin-layer chromatography, gas chromatographic analysis, high-performance liquid chromatography, IR spectrometry, and other modern techniques. The methods based on the recent achievements in pharmaceutical and criminalistics sciences can be employed in the activities intended to control the illegal drug circulation. Moreover, they may be of importance for obtaining valuable information about the actions of the persons involved in the trafficking or synthesis (production) of the prohibited substances after they are brought to criminal responsibility and/or appear before the court.

PMID: 28399084 [PubMed - in process]

An interventionist adherence scale for a specialized brief negotiation interview focused on treatment engagement for opioid use disorders.

April 12, 2017 - 6:45am

An interventionist adherence scale for a specialized brief negotiation interview focused on treatment engagement for opioid use disorders.

Subst Abus. 2017 Feb 23;:1-9

Authors: Pantalon MV, Dziura J, Li FY, Owens PH, O'Connor PG, D'Onofrio G

Abstract
BACKGROUND: No psychometrically validated instrument for evaluating the extent to which interventionists correctly implement brief interventions designed to motivate treatment engagement for opioid use disorders has been reported in the literature. The objective of this study was to develop and examine the psychometric properties of the Brief Negotiation Interview (BNI) Adherence Scale for Opioid Use Disorders (BAS-O).
METHODS: In the context of a randomized controlled trial evaluating the efficacy of 3 models of emergency department care for opioid use disorders, the authors developed and subsequently examined the psychometric properties of the BAS-O, a 38-item scale that required raters to answer whether or not ("Yes" or "No") each of the critical actions of the BNI was correctly implemented by the research interventionist. BAS-O items pertained to the BNI's 4 steps: (1) Raise the Subject, (2) Provide Feedback, (3) Enhance Motivation, and (4) Negotiate and Advise. A total of 215 audio-recorded BNI and 88 control encounters were rated by 3 trained raters who were independent of the study team and blind to study hypotheses, treatment, and assignment.
RESULTS: The results indicated the BAS-O has fair to excellent psychometric properties, in terms of good internal consistency, excellent interrater reliability, discriminant validity, and construct validity, and fair predictive validity. A 13-item, 2-factor solution accounted for nearly 80% of the variance, where factor 1 addressed "Autonomy and Planning" (7 items) and factor 2 addressed "Motivation and Problems" (6 items). However, predictive validity was found for only one of the BAS-O factor items (i.e., Telling patients that treatment will address a range of issues related to their opioid use disorder).
CONCLUSIONS: This study suggests that the BAS-O is a psychometrically valid measure of adherence to the specialized BNI for motivating treatment engagement in patients with opioid use disorders, thus providing a brief (13-item), objective method of evaluating BNI skill performance.

PMID: 28398192 [PubMed - as supplied by publisher]

Inhibition of Voltage-Gated Na+ Channels by Bupivacaine Is Enhanced by the Adjuvants Buprenorphine, Ketamine, and Clonidine.

April 11, 2017 - 6:42am

Inhibition of Voltage-Gated Na+ Channels by Bupivacaine Is Enhanced by the Adjuvants Buprenorphine, Ketamine, and Clonidine.

Reg Anesth Pain Med. 2017 Apr 07;:

Authors: Stoetzer C, Martell C, de la Roche J, Leffler A

Abstract
BACKGROUND AND OBJECTIVES: Regional anesthesia includes application of local anesthetics (LAs) into the vicinity of peripheral nerves. Prolongation or improvement of nerve blocks with LAs can be accomplished by coapplication with adjuvants, including buprenorphine, ketamine, and clonidine. While the mechanisms mediating prolonged or improved LA-induced effects by adjuvants are poorly understood, we hypothesized that they are likely to increase LA-induced block of voltage-gated Na channels. In this study, we investigated the inhibitory effects of the LA bupivacaine alone and in combination with the adjuvants on neuronal Na channels.
METHODS: Effects of bupivacaine, buprenorphine, ketamine, and clonidine on endogenous Na channels in ND7/23 neuroblastoma cells were investigated with whole-cell patch clamp.
RESULTS: Bupivacaine, buprenorphine, ketamine, and clonidine are concentration- and state-dependent inhibitors of Na currents in ND7/23 cells. Tonic block of resting channels revealed an order of potency of bupivacaine (half-maximal inhibitory concentration [IC50] 178 ± 8 μM) > buprenorphine (IC50 172 ± 25) > clonidine (IC50 824 ± 55 μM) > ketamine (IC50 1377 ± 92 μM). Bupivacaine and buprenorphine, but not clonidine and ketamine, induced a strong use-dependent block at 10 Hz. Except for clonidine, all substances enhanced fast and slow inactivation. The combination of bupivacaine with one of the adjuvants resulted in a concentration-dependent potentiation bupivacaine-induced block.
CONCLUSIONS: We demonstrate that buprenorphine, ketamine, and clonidine directly inhibit Na channels and that they potentiate the blocking efficacy of bupivacaine on Na channels. These data indicate that block of Na channels may account for the additive effects of adjuvants used for regional anesthesia.

PMID: 28394849 [PubMed - as supplied by publisher]

Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

April 11, 2017 - 6:42am

Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

Neuropsychopharmacology. 2017 Apr 10;:

Authors: Santoro GC, Carrion J, Patel K, Vilchez C, Veith J, Brodie JD, Dewey SL

Abstract
Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex-specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared to males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using (18)FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal grey were noted. However, compared to males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared to sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, while buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic efficacy, while these post-treatment sex differences contribute to clinical treatment failure more commonly experienced by the former.Neuropsychopharmacology accepted article preview online, 10 April 2017. doi:10.1038/npp.2017.69.

PMID: 28393895 [PubMed - as supplied by publisher]

HIV And HCV infection among opiate-dependent patients and methadone doses: the PROTEUS study.

April 11, 2017 - 6:42am

HIV And HCV infection among opiate-dependent patients and methadone doses: the PROTEUS study.

AIDS Care. 2017 Apr 09;:1-6

Authors: Roncero C, Fuster D, Palma-Álvarez RF, Rodriguez-Cintas L, Martinez-Luna N, Álvarez FJ

Abstract
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are prevalent infections in opiate-dependent patients. Opiate replacement treatment (ORT) with methadone or buprenorphine is associated with several important outcomes among patients with opiate dependence. However, little is known about outcomes in patients with HIV and/or HCV infections that are in ORT. Also, it is not well established whether the presence of HCV or HIV infection could be associated with higher methadone doses. This paper reanalyzes the database of PROTEUS study, using two principal variables: methadone dose and presence of HIV and/or HCV infection. PROTEUS recruited 621 patients (84.1% were male, mean age: 38.9 years, SD: 7.9), information about the presence of HIV in status was available for 390 patients. Of those, 134 (34.4%) were HIV-infected. Whilst, information about HCV infection was available for 377 patients. Of those, 315 (83.6%) were HCV-infected. Information on HIV/HCV coinfection was available for 376 patients, of those, 112 (29.8%) had this coinfection. HIV-infected and HIV/HCV-coinfected patients received higher methadone doses than those without these infections. Antiretroviral therapy (ART) was used in 80% of patients with HIV infection. The proportion of patients taking antiretroviral drugs was significantly higher for patients treated with higher methadone doses (p < 0.01). Findings suggest that HIV-infected and HIV/HVC-coinfected patients in ORT require higher methadone dose.

PMID: 28393548 [PubMed - as supplied by publisher]

A case report on the treatment of complex chronic pain and opioid dependence by a multidisciplinary transitional pain service using the ACT Matrix and buprenorphine/naloxone.

April 11, 2017 - 6:42am
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A case report on the treatment of complex chronic pain and opioid dependence by a multidisciplinary transitional pain service using the ACT Matrix and buprenorphine/naloxone.

J Pain Res. 2017;10:747-755

Authors: Weinrib AZ, Burns LC, Mu A, Azam MA, Ladak SS, McRae K, Katznelson R, Azargive S, Tran C, Katz J, Clarke H

Abstract
In an era of growing concern about opioid prescribing, the postsurgical period remains a critical window with the risk of significant opioid dose escalation, particularly in patients with a history of chronic pain and presurgical opioid use. The purpose of this case report is to describe the multidisciplinary care of a complex, postsurgical pain patient by an innovative transitional pain service (TPS). A 59-year-old male with complex chronic pain, as well as escalating long-term opioid use, presented with a bleeding duodenal ulcer requiring emergency surgery. After surgery, the TPS provided integrated pharmacological and behavioral treatment, including buprenorphine combined with naloxone and acceptance and commitment therapy (ACT) using the ACT Matrix. The result was dramatic pain reduction and improved functioning and quality of life after 40+ years of chronic pain, thus changing the pain trajectory of a chronic, complex, opioid-dependent patient.

PMID: 28392713 [PubMed - in process]

Vermont Hub-and-Spoke Model of Care For Opioid Use Disorder: Development, Implementation, and Impact.

April 6, 2017 - 6:06am

Vermont Hub-and-Spoke Model of Care For Opioid Use Disorder: Development, Implementation, and Impact.

J Addict Med. 2017 Apr 04;:

Authors: Brooklyn JR, Sigmon SC

Abstract
BACKGROUND: Opioid use disorders (OUDs) are reaching epidemic proportions in the United States, and many geographic areas struggle with a persistent shortage in availability of opioid agonist treatment. Over the past 5 years, Vermont addiction medicine physicians and public health leaders have responded to these challenges by developing an integrated hub-and-spoke opioid treatment network.
METHODS: In the present report, we review the development, implementation, and impact of this novel hub-and-spoke model for expanding OUD treatment in Vermont.
RESULTS: Vermont's hub-and-spoke system has been implemented state-wide and well-received by providers and patients alike. Adoption of this model has been associated with substantial increases in the state's OUD treatment capacity, with Vermont now having the highest capacity for treating OUD in the United States with 10.56 people in treatment per 1000. There has been a 64% increase in physicians waivered to prescribe buprenorphine, a 50% increase in patients served per waivered physician, and a robust bidirectional transfer of patients between hubs and spokes based upon clinical need. Challenges to system implementation and important future directions are discussed.
CONCLUSIONS: Development and implementation of a hub-and-spoke system of care has contributed substantially to improvements in opioid agonist treatment capacity in Vermont. This system may serve as a model for other states grappling with the current opioid use epidemic.

PMID: 28379862 [PubMed - as supplied by publisher]

Targeting multiple opioid receptors - improved analgesics with reduced side effects?

April 6, 2017 - 6:06am
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Targeting multiple opioid receptors - improved analgesics with reduced side effects?

Br J Pharmacol. 2017 Apr 05;:

Authors: Günther T, Dasgupta P, Mann A, Miess E, Kliewer A, Fritzwanker S, Steinborn R, Schulz S

Abstract
Classical opioid analgesics, including morphine, mediate all of their desired and undesired effects by specific activation of the μ-opioid receptor (μ receptor). The use of morphine for treating chronic pain, however, is limited by the development of constipation, respiratory depression, tolerance and dependence. Analgesic effects can also be mediated through other members of the opioid receptor family such as the κ-opioid receptor (κ receptor), δ-opioid receptor (δ receptor) and the nociceptin/orphanin FQ peptide receptor (NOP receptor). Currently, a new generation of opioid analgesics is being developed that can simultaneously bind with high affinity to multiple opioid receptors. With this new action profile, it is hoped that additional analgesic effects and fewer side effects can be achieved. Recent research is mainly focused on the development of bifunctional μ/NOP receptor agonists, which has already led to novel lead structures such as the spiroindole-based cebranopadol and a compound class with a piperidin-4-yl-1,3-dihydroindol-2-one backbone (SR16835/AT-202 and SR14150/AT-200). In addition, the ornivol BU08028 is an analogue of the clinically well-established buprenorphine. Moreover, the morphinan-based nalfurafine exerts its effect with a dominant κ receptor-component and is therefore utilized in the treatment of pruritus. The very potent dihydroetorphine is a true multi-receptor opioid ligand in that it binds to μ, κ and δ receptor. The main focus of this review is to assess the paradigm of opioid ligands targeting multiple receptors with a single chemical entity. We reflect on this rationale by discussing the biological actions of selected multi-opioid receptor ligands, but not on their medicinal chemistry and design.

PMID: 28378462 [PubMed - as supplied by publisher]

Six-Year Outcome of Opioid Maintenance Treatment in Heroin-Dependent Patients: Results from a Naturalistic Study in a Nationally Representative Sample.

April 5, 2017 - 6:57am

Six-Year Outcome of Opioid Maintenance Treatment in Heroin-Dependent Patients: Results from a Naturalistic Study in a Nationally Representative Sample.

Eur Addict Res. 2017 Apr 05;23(2):97-105

Authors: Soyka M, Strehle J, Rehm J, Bühringer G, Wittchen HU

Abstract
BACKGROUND: In many countries, the opioid agonists, buprenorphine and methadone, are licensed for maintenance treatment of opioid dependence. Many short-term studies have been performed, but little is known about long-term effects. Therefore, this study described over 6 years (1) mortality, retention and abstinence rates and (2) changes in concomitant drug use and somatic and mental health.
METHODS: A prevalence sample of n = 2,694 maintenance patients, recruited from a nationally representative sample of n = 223 substitution doctors, was evaluated in a 6-year prospective-longitudinal naturalistic study. At 72 months, n = 1,624 patients were assessed for outcome; 1,147 had full outcome data, 346 primary outcome data and 131 had died; 660 individuals were lost to follow-up.
RESULTS: The 6-year retention rate was 76.6%; the average mortality rate was 1.1%. During follow-up, 9.4% of patients became "abstinent" and 1.9% were referred for drug-free addiction treatment. Concomitant drug use decreased and somatic health status and social parameters improved.
CONCLUSIONS: The study provides further evidence for the efficacy and safety of maintenance treatment with opioid agonists. In the long term, the number of opioid-free patients is low and most patients are more or less continuously under opioid maintenance therapy. Further implications are discussed.

PMID: 28376505 [PubMed - as supplied by publisher]

Effectiveness and cost-effectiveness of unsupervised buprenorphine-naloxone for the treatment of heroin dependence in a randomized waitlist controlled trial.

April 4, 2017 - 6:49am

Effectiveness and cost-effectiveness of unsupervised buprenorphine-naloxone for the treatment of heroin dependence in a randomized waitlist controlled trial.

Drug Alcohol Depend. 2017 Mar 01;174:181-191

Authors: Dunlop AJ, Brown AL, Oldmeadow C, Harris A, Gill A, Sadler C, Ribbons K, Attia J, Barker D, Ghijben P, Hinman J, Jackson M, Bell J, Lintzeris N

Abstract
BACKGROUND: Access to opioid agonist treatment can be associated with extensive waiting periods with significant health and financial burdens. This study aimed to determine whether patients with heroin dependence dispensed buprenorphine-naloxone weekly have greater reductions in heroin use and related adverse health effects 12-weeks after commencing treatment, compared to waitlist controls and to examine the cost-effectiveness of this strategy.
METHODS: An open-label waitlist RCT was conducted in an opioid treatment clinic in Newcastle, Australia. Fifty patients with DSM-IV-TR heroin dependence (and no other substance dependence) were recruited. The intervention group (n=25) received take-home self-administered sublingual buprenorphine-naloxone weekly (mean dose, 22.7±5.7mg) and weekly clinical review. Waitlist controls (n=25) received no clinical intervention. The primary outcome was heroin use (self-report, urine toxicology verified) at weeks four, eight and 12. The primary cost-effectiveness outcome was incremental cost per additional heroin-free-day.
RESULTS: Outcome data were available for 80% of all randomized participants. Across the 12-weeks, treatment group heroin use was on average 19.02days less/month (95% CI -22.98, -15.06, p<0.0001). A total 12-week reduction in adjusted costs including crime of $A5,722 (95% CI 3299, 8154) in favor of treatment was observed. Excluding crime, incremental cost per heroin-free-day gained from treatment was $A18.24 (95% CI 4.50, 28.49).
CONCLUSION: When compared to remaining on a waitlist, take-home self-administered buprenorphine-naloxone treatment is associated with significant reductions in heroin use for people with DSM-IV-TR heroin dependence. This cost-effective approach may be an efficient strategy to enhance treatment capacity.

PMID: 28371689 [PubMed - as supplied by publisher]

Efficacy and safety of buprenorphine in peripheral nerve blocks: A meta-analysis of randomised controlled trials.

April 4, 2017 - 6:49am

Efficacy and safety of buprenorphine in peripheral nerve blocks: A meta-analysis of randomised controlled trials.

Eur J Anaesthesiol. 2017 Mar 31;:

Authors: Schnabel A, Reichl SU, Zahn PK, Pogatzki-Zahn EM, Meyer-Frieem CH

Abstract
BACKGROUND: The duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, a variety of additives to local anaesthetics have been investigated to prolong postoperative analgesia following single-shot nerve blocks.
OBJECTIVE(S): The aims of the current meta-analysis were to assess the efficacy and safety of the addition of perineural buprenorphine to local anaesthetic compared with local anaesthetic alone, or combined with systemic administration of buprenorphine, or other perineural opioids for peripheral nerve blocks.
DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs).
DATA SOURCES: The following data sources were systematically searched: MEDLINE, CENTRAL and EMBASE (till 03/2016).
ELIGIBILITY CRITERIA: All RCTs focusing on the efficacy and safety of perineural buprenorphine combined with local anaesthetic compared with local anaesthetic alone, or in combination with systemic buprenorphine, or other perineural opioids for peripheral nerve blocks were included.
RESULTS: We included 13 RCTs (685 patients). Participants treated with perineural buprenorphine combined with local anaesthetic showed a longer duration of analgesia compared with those receiving local anaesthetic alone [mean difference 8.64 h, 95% confidence interval (CI) (6.44 to 10.85); P < 0.01]. However, the buprenorphine group had a significantly higher relative risk (RR) for postoperative nausea and vomiting (PONV) [RR 5.0, 95% CI (1.12 to 22.27); P = 0.03]. The perineural administration of buprenorphine provided a longer duration of analgesia than an intramuscular application [mean difference 6.87 h, 95% CI (4.02 to 9.71); P < 0.01] without evidence of a difference in the incidence of PONV between the modes of administration [RR 0.76, 95% CI (0.28 to 2.03); P = 0.58].
CONCLUSION: This meta-analysis revealed that the addition of buprenorphine to a local anaesthetic peripheral nerve block prolongs postoperative analgesia for about 8 h but significantly increases the risk for PONV. Perineural administration is more effective than systemic application but is associated with a similar risk of PONV. However, these results were influenced by heterogeneity so that further trials (especially head-to-head comparisons) are needed in the future.
TRIAL REGISTRATION: PROSPERO(www.crd.york.ac.uk) identifier: CRD42016036054.

PMID: 28368971 [PubMed - as supplied by publisher]

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