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Use and misuse of opioid agonists in opioid addiction.

May 23, 2017 - 6:24am

Use and misuse of opioid agonists in opioid addiction.

Cleve Clin J Med. 2017 May;84(5):377-384

Authors: Modesto-Lowe V, Swiezbin K, Chaplin M, Hoefer G

Abstract
Although methadone (an opioid agonist) and buprenorphine (a partial opioid agonist) have evidence to support their use in treating opioid use disorder, they remain misunderstood and underutilized. In this article, we outline the risks and benefits of using these drugs as maintenance therapy in opioid-dependent patients.

PMID: 28530896 [PubMed - in process]

Association of nausea with buprenorphine analgesia for rats.

May 23, 2017 - 6:24am

Association of nausea with buprenorphine analgesia for rats.

Lab Anim (NY). 2017 May 22;46(6):242-244

Authors: Sarabia-Estrada R, Cowan A, Tyler BM, Guarnieri M

PMID: 28530682 [PubMed - in process]

The journey of opioid substitution therapy in India: Achievements and challenges.

May 23, 2017 - 6:24am
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The journey of opioid substitution therapy in India: Achievements and challenges.

Indian J Psychiatry. 2017 Jan-Mar;59(1):39-45

Authors: Rao R

Abstract
Opioids are one of the most problematic illegal substances globally. Opioid abuse is associated with complications in various spheres of the user's life, his/her family, and the society. Injecting drug use (IDU) is also linked to public health problems such as HIV infection and viral hepatitis. Medications form an important cornerstone in the treatment of opioid dependence. Treatment strategies such as "detoxification" alone or long-term treatment with opioid antagonist have limited acceptability and retention rates. Opioid substitution therapy (OST) has demonstrated better retention rates than other existing treatment strategies and helps improve the individual's functioning as well as his/her quality of life. The use of OST in India spans three decades, with initial use of low-dose buprenorphine followed by higher strength buprenorphine and buprenorphine-naloxone. Other medications such as slow-release oral morphine, and recently, methadone have also been introduced. Indian research also confirms the findings from Western literature on the effectiveness as well as acceptability of this treatment modality. OST received its biggest thrust when it became a part of the National AIDS Control Programme. In recent years, the number of OST centers in India has increased manifold. Practice guidelines, standard operating procedures, and capacity-building mechanisms have been put in place for effective OST implementation. Despite such widespread use, many challenges exist for OST implementation. The targets for ensuring adequate coverage of the population with this treatment are still far away. There is concern of OST being branded as a "harm reduction" intervention reserved only for injecting drug users. Despite three decades of advancements, certain sections of policymakers and practitioners still have reservations with this treatment modality. There is a need to overcome these barriers for OST to become easily accessible to those who need it.

PMID: 28529359 [PubMed - in process]

Innovative Program Delivery and Determinants of Frequent Visitation to a Mobile Medical Clinic in an Urban Setting.

May 23, 2017 - 6:24am
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Innovative Program Delivery and Determinants of Frequent Visitation to a Mobile Medical Clinic in an Urban Setting.

J Health Care Poor Underserved. 2017;28(2):643-662

Authors: Gibson BA, Morano JP, Walton MR, Marcus R, Zelenev A, Bruce RD, Altice FL

Abstract
The Community Health Care Van (CHCV) is a mobile medical clinic (MMC) that has served vulnerable populations in New Haven, Connecticut since 1993. This study explores utilization patterns to understand if certain populations frequently rely upon non-traditional health care within a representative MMC. Patient characteristics, services used, and visitation frequency were described and compared for 8,415 unique clients making 29,728 visits. Negative binomial regression was used to model the impact of specific indicators on visitation. Clients receiving buprenorphine had the highest visitation rates, with 2.09 visits per person-year. Increased CHCV visitation was positively associated with being foreign-born (additional 3.42 visits on average, p < .001), injection drug use (additional 1.69 visits on average, p < .001) and having hypertension (additional 1.09 visits on average, p < .001). As the Affordable Care Act has increased health insurance coverage, MMCs will continue their role in assisting entry into continuous health care and offering low-threshold acute care for urban vulnerable populations.

PMID: 28529215 [PubMed - in process]

Update on Barriers to Pharmacotherapy for Opioid Use Disorders.

May 21, 2017 - 6:09am
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Update on Barriers to Pharmacotherapy for Opioid Use Disorders.

Curr Psychiatry Rep. 2017 Jun;19(6):35

Authors: Sharma A, Kelly SM, Mitchell SG, Gryczynski J, O'Grady KE, Schwartz RP

Abstract
PURPOSE OF REVIEW: The recent heroin and prescription opioid misuse epidemic has led to a sharp increase in the number of opioid overdose deaths in the USA. Notwithstanding the availability of three FDA-approved medications (methadone, buprenorphine, and naltrexone) to treat opioid use disorder, these medications are underutilized. This paper provides an update from the recent peer-reviewed literature on barriers to the use of these medications.
FINDINGS: These barriers are interrelated and can be categorized as financial, regulatory, geographic, attitudinal, and logistic. While financial barriers are common to all three medications, other barriers are medication-specific. The adverse impact of the current opioid epidemic on public health can be reduced by increasing access to effective pharmacotherapy for opioid use disorder.

PMID: 28526967 [PubMed - in process]

Plasma concentrations of transdermal fentanyl and buprenorphine in pigs (Sus scrofa domesticus).

May 21, 2017 - 6:09am
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Plasma concentrations of transdermal fentanyl and buprenorphine in pigs (Sus scrofa domesticus).

Vet Anaesth Analg. 2017 Jan 11;:

Authors: Osorio Lujan S, Habre W, Daali Y, Pan Z, Kronen PW

Abstract
OBJECTIVE: To determine the absorption characteristics of fentanyl and buprenorphine administered transdermally in swine.
STUDY DESIGN: A randomized comparative experimental trial.
ANIMALS: Twenty-four Yorkshire gilts weighing 27.8±2.2 kg (mean±standard deviation).
METHODS: Animals were randomly assigned to different doses of transdermal patches (TPs) of fentanyl (50 μg hour(-1), 75 μg hour(-1) and 100 μg hour(-1)) or buprenorphine (35 μg hour(-1) and 70 μg hour(-1)), once or twice. Thirteen blood samples were obtained for each TP applied. Plasma concentrations were determined, and the area under the curve, peak serum concentration (Cmax) and time to Cmax were calculated.
RESULTS: Fentanyl: Cmax was observed at different time points: for the first TP application: 30 hours for 50 μg hour(-1), 6 hours for 75 μg hour(-1) and 100 μg hour(-1) patches; and for the second TP application: 30 hours for 50 μg hour(-1) and 36 hours for 75 μg hour(-1) patches. Buprenorphine: serum concentrations were not detected for the 35 μg hour(-1) patch; Cmax was observed at different times for the 70 μg hour(-1) patch: 18 hours (n = 1), 24 hours (n = 3), 30 hours (n = 1) and 42 hours (n = 1) after application of the first patch and 12 hours after the second patch.
CONCLUSIONS AND CLINICAL RELEVANCE: A relevant serum concentration obtained with fentanyl TP dosed at 75 μg hour(-1) or 100 μg hour(-1)suggests that TPs could represent an analgesia option for laboratory pigs weighing 25-30 kg. As concentrations of buprenorphine were variable, this study does not support the use of buprenorphine TPs in pigs. Consecutive fentanyl or buprenorphine TPs did not provide reliable serum concentrations. Further pharmacokinetic studies and analgesiometric tests in swine are needed to confirm the clinical adequacy of TPs.

PMID: 28526486 [PubMed - as supplied by publisher]

The State of Opioid Agonist Therapy in Canada 20 Years after Federal Oversight.

May 20, 2017 - 6:39am

The State of Opioid Agonist Therapy in Canada 20 Years after Federal Oversight.

Can J Psychiatry. 2017 Jan 01;:706743717711167

Authors: Eibl JK, Morin K, Leinonen E, Marsh DC

Abstract
Opioid agonist therapy was introduced in Canada in 1959 with the use of methadone for the treatment of opioid dependence. The regulation of methadone was the responsibility of Health Canada until 1995, when oversight was transferred to the provincial health systems. During the more than 20 years since the federal health authority transferred oversight of methadone to the provincial level, methadone programming has evolved differently in every province. The landscape of opioid dependence treatment is varied across the country, with generally increasing treatment capacity in all provinces and dramatic increases in some. Each province has an independent methadone program with differing policies, contingency management strategies, laboratory monitoring policies, and delivery methods. Treatment options have increased, with buprenorphine- and heroin-assisted treatment becoming available to limited degrees. Despite this, access remains a challenge in many parts of the country (particularly rural and remote areas) because the demand for treatment has increased even more rapidly than the capacity. Although treatment access remains a priority in many jurisdictions, there is also a need to attend to treatment quality as treatment access expands, including integration with addiction counselling, primary care, and mental health care. As well, coordinated monitoring and reporting of treatment need, quality, and delivery are required; implementing a national policy to promote planning would have tremendous value.

PMID: 28525291 [PubMed - as supplied by publisher]

Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies.

May 19, 2017 - 6:24am

Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies.

Pharmacotherapy. 2017 May 18;:

Authors: Raffaeli G, Cavallaro G, Allegaert KK, Wildschut ED, Fumagalli M, Agosti M, Tibboel D, Mosca F

Abstract
Substance use among pregnant women is a major public health issue. Both prescription opioid use and illicit opioid abuse have increased dramatically in recent years. Prolonged in utero drug exposure may result in neonatal abstinence syndrome (NAS), an acute multisystemic clinical entity that occurs in the first days of life. This syndrome is caused by abrupt discontinuation of fetal exposure to licit or illicit drugs chronically consumed by the mother during pregnancy and transmitted to the fetus through the placenta. It usually requires prolonged hospitalization and may have long-term effects. The interplay of many factors contributes to its clinical heterogeneity, and its pathophysiology has not been fully unveiled. The first step in NAS management consists of nonpharmacologic interventions and includes promoting breastfeeding when not contraindicated. If withdrawal signs become severe, pharmacotherapy is needed. The Finnegan scoring system supports care providers across the pharmacotherapy process from initiation through the monitoring phase, until weaning and discontinuation. However, a standardized approach to pharmacotherapy is still lacking. Morphine is usually the first-line agent to treat NAS. Methadone is a valid option, but its safety profile is not completely known. Phenobarbital, despite its lack of effect on gastrointestinal symptoms and unfavorable pharmacologic features, has been identified as a second-line agent to be used in infants unresponsive to opiates. Although buprenorphine and clonidine seem promising, their use requires further validation. Long-term developmental effects of NAS therapy call for more comprehensive, longitudinal assessments. In this article, key points for use of recommended therapies are outlined, and directions for future research are suggested. This article is protected by copyright. All rights reserved.

PMID: 28519244 [PubMed - as supplied by publisher]

Application of a buprenorphine transdermal patch for the perioperative analgesia in patients who underwent simple lumbar discectomy.

May 18, 2017 - 6:39am

Application of a buprenorphine transdermal patch for the perioperative analgesia in patients who underwent simple lumbar discectomy.

Medicine (Baltimore). 2017 May;96(20):e6844

Authors: Tang J, Fan J, Yao Y, Cai W, Yin G, Zhou W

Abstract
This study aimed to investigate the perioperative analgesic effect of a buprenorphine transdermal patch in patients who underwent simple lumbar discectomy.In total, 96 patients were randomly divided into parecoxib intravenous injection (Group A), oral celecoxib (Group B), and buprenorphine transdermal patch groups (Group C). The pain status, degree of satisfaction, adverse effects, and condition in which the patient received tramadol hydrochloride for uncontrolled pain were recorded on the night before surgery, postoperative day 1, postoperative day 3, and postoperative day 5.The degree of patient satisfaction in Group C was higher than that in Groups A and B, with minimal adverse effects.The buprenorphine transdermal patch had a better perioperative analgesic effect in patients who underwent simple lumbar discectomy.

PMID: 28514299 [PubMed - in process]

To Stop or Not, That Is the Question: Acute Pain Management for the Patient on Chronic Buprenorphine.

May 17, 2017 - 6:26am

To Stop or Not, That Is the Question: Acute Pain Management for the Patient on Chronic Buprenorphine.

Anesthesiology. 2017 Jun;126(6):1180-1186

Authors: Anderson TA, Quaye ANA, Ward EN, Wilens TE, Hilliard PE, Brummett CM

PMID: 28511196 [PubMed - in process]

Tramadol with or without paracetamol (acetaminophen) for cancer pain.

May 17, 2017 - 6:26am

Tramadol with or without paracetamol (acetaminophen) for cancer pain.

Cochrane Database Syst Rev. 2017 May 16;5:CD012508

Authors: Wiffen PJ, Derry S, Moore RA

Abstract
BACKGROUND: Tramadol is an opioid analgesic licensed for use in moderate to severe pain. It is considered as a low risk for abuse, so control regulations are not as stringent as for 'strong' opioids such as morphine. It has a potential role as a step 2 option of the World Health Organization (WHO) analgesic ladder.
OBJECTIVES: To assess the benefits and adverse effects of tramadol with or without paracetamol (acetaminophen) for cancer-related pain.
SEARCH METHODS: We searched the following databases using a wide range of search terms: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched three clinical trials registry databases. The date of the last search was 2 November 2016.
SELECTION CRITERIA: We selected studies that were randomised, with placebo or active controls, or both, and included a minimum of 10 participants per treatment arm. We were interested particularly in blinded studies, but also included open studies.We excluded non-randomised studies, studies of experimental pain, case reports, and clinical observations.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using a standard form and checked for agreement before entry into Review Manager 5. We included information about the number of participants treated and demographic details, type of cancer, drug and dosing regimen, study design (placebo or active control) and methods, study duration and follow-up, analgesic outcome measures and results, withdrawals, and adverse events. We collated multiple reports of the same study, so that each study, rather than each report, was the unit of interest in the review. We assessed the evidence using GRADE and created a 'Summary of findings' table.The main outcomes of interest for benefit were pain reduction of 30% or greater and 50% or greater from baseline, participants with pain no worse than mild, and participants feeling much improved or very much improved.
MAIN RESULTS: We included 10 studies (12 reports) with 958 adult participants. All the studies enrolled participants with chronic malignant tumour-related pain who were experiencing pain intensities described as moderate to severe, with most experiencing at least 4/10 with current treatment. The mean ages were 59 to 70 years, with participants aged between 24 and 87 years. Study length ranged from one day to six months. Five studies used a cross-over design. Tramadol doses ranged from 50 mg as single dose to 600 mg per day; doses of 300 mg per day to 400 mg per day were most common.Nine studies were at high risk of bias for one to four criteria (only one high risk of bias for size). We judged all the results to be very low quality evidence because of widespread lack of blinding of outcome assessment, inadequately described sequence generation, allocation concealment, and small numbers of participants and events. Important outcomes were poorly reported. There were eight different active comparators and one comparison with placebo. There was little information available for any comparison and no firm conclusions could be drawn for any outcome.Single comparisons of oral tramadol with codeine plus paracetamol, of dihydrocodeine, and of rectal versus oral tramadol provided no data for key outcomes. One study used tramadol combined with paracetamol; four participants received this intervention. One study compared tramadol with flupirtine - a drug that is no longer available. One study compared tramadol with placebo and a combination of cobrotoxin, tramadol, and ibuprofen, but the dosing schedule poorly explained.Two studies (191 participants) compared tramadol with buprenorphine. One study (131 participants) reported a similar proportion of no or mild pain at 14 days.Three studies (300 participants) compared tramadol with morphine. Only one study, combining tramadol, tramadol plus paracetamol, and paracetamol plus codeine as a single weak-opioid group reported results. Weak opioid produced reduction in pain of at least 30% from baseline in 55/117 (47%) participants, compared with 91/110 (82%) participants with morphine. Weak opioid produced reduction in pain of at least 50% in 49/117 (42%) participants, compared with 83/110 (75%) participants with morphine.There was no useful information for any other outcome of benefit or harm.
AUTHORS' CONCLUSIONS: There is limited, very low quality, evidence from randomised controlled trials that tramadol produced pain relief in some adults with pain due to cancer and no evidence at all for children. There is very low quality evidence that it is not as effective as morphine. This review does not provide a reliable indication of the likely effect. The likelihood that the effect will be substantially different is very high. The place of tramadol in managing cancer pain and its role as step 2 of the WHO analgesic ladder is unclear.

PMID: 28510996 [PubMed - as supplied by publisher]

Predictors of buprenorphine treatment success of opioid dependence in two Baltimore City grassroots recovery programs.

May 16, 2017 - 6:19am

Predictors of buprenorphine treatment success of opioid dependence in two Baltimore City grassroots recovery programs.

Addict Behav. 2017 May 10;73:129-132

Authors: Damian AJ, Mendelson T, Agus D

Abstract
INTRODUCTION: Despite evidence for the efficacy of buprenorphine treatment in primary care, few studies have identified factors associated with treatment success, nor have such factors been evaluated in community settings. Identifying correlates of treatment success can facilitate the development of treatment models tailored for distinct populations, including low-income communities of color. The current study examined client-level socio-demographic factors associated with treatment success in community-based buprenorphine programs serving vulnerable populations.
METHODS: Data were abstracted from client records for participants (N=445) who met DSM-IV criteria for opioid dependence and sought treatment at one of Behavioral Health Leadership Institute's two community-based recovery programs in Baltimore City from 2010 to 2015. Logistic regression estimated the odds ratios of treatment success (defined as retention in treatment for ≥90days) by sociodemographic predictors including age, race, gender, housing, legal issues and incarceration.
RESULTS: The odds of being retained in treatment ≥90days increased with age (5% increase with each year of age; p<0.001), adjusting for other sociodemographic factors. Clients who reported unstable housing had a 41% decreased odds of remaining in treatment for 90 or more days compared to clients who lived independently at intake. Treatment success did not significantly differ by several other client-level characteristics including gender, race, employment, legal issues and incarceration.
CONCLUSIONS: In vulnerable populations, the age factor appears sufficiently significant to justify creating models formulated for younger populations. The data also support attention to housing needs for people in treatment. Findings from this paper can inform future research and program development.

PMID: 28505488 [PubMed - as supplied by publisher]

Drug binding poses relate structure with efficacy in the μ opioid receptor.

May 16, 2017 - 6:19am
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Drug binding poses relate structure with efficacy in the μ opioid receptor.

J Mol Biol. 2017 May 11;:

Authors: Sutcliffe KJ, Henderson G, Kelly E, Sessions RB

Abstract
The μ-opioid receptor (MOPr) is a clinically important G protein-coupled receptor (GPCR) which couples to Gi/o proteins and arrestins. At present the receptor conformational changes that occur following agonist binding and activation are poorly understood. This study has employed molecular dynamics simulations to investigate the binding mode and receptor conformational changes induced by structurally similar opioid ligands of widely differing intrinsic agonist efficacy, norbuprenorphine, buprenorphine and diprenorphine. Bioluminescence resonance energy transfer (BRET) assays for Gi activation and arrestin-3 recruitment in HEK 293 cells confirmed that norbuprenorphine is a high efficacy agonist, buprenorphine a low efficacy agonist, and diprenorphine an antagonist at the MOPr. Molecular dynamics simulations revealed that these ligands adopt distinct binding poses and engage different subsets of residues, despite sharing a common morphinan scaffold. Notably, norbuprenorphine interacted with sodium ion - coordinating residues W293(6.48) and N150(3.35), whilst buprenorphine and diprenorphine did not. Principal component analysis of the movements of the receptor transmembrane domains showed that the buprenorphine-bound receptor occupied a distinct set of conformations to the norbuprenorphine-bound receptor. Addition of an allosteric sodium ion caused the receptor and ligand to adopt an inactive conformation. The differences in ligand-residue interactions and receptor conformations observed here may underlie the differing efficacies for cellular signalling outputs for these ligands.

PMID: 28502792 [PubMed - as supplied by publisher]

Development and evaluation of a community-based buprenorphine treatment intervention.

May 14, 2017 - 6:02am
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Development and evaluation of a community-based buprenorphine treatment intervention.

Harm Reduct J. 2017 May 12;14(1):23

Authors: Fox AD, Sohler NL, Frost T, Lopez C, Cunningham CO

Abstract
BACKGROUND: The majority of Americans with opioid use disorder remain out of treatment. Operating in 33 states, Washington DC, and Puerto Rico, harm reduction agencies, which provide sterile syringes and other health services to people who inject drugs, are a key venue to reach out-of-treatment opioid users. Aiming to link out-of-treatment individuals with opioid use disorder to buprenorphine treatment, we developed a community-based buprenorphine treatment (CBBT) intervention in collaboration with New York City harm reduction agencies.
METHODS: Intervention development included formative data collection, feasibility testing at one harm reduction agency, and pilot testing for preliminary effectiveness at a second harm reduction agency. We used a pre-post design for both feasibility and pilot testing. In the CBBT intervention, we trained harm reduction agency staff to provide (1) buprenorphine education, (2) motivational interviewing, (3) referrals to buprenorphine-prescribing doctors, and (4) treatment retention support. We assessed feasibility by measuring staff satisfaction with the intervention and changes in knowledge about buprenorphine. We assessed preliminary effectiveness by comparing rates of buprenorphine initiation among groups of harm reduction agency clients before and after intervention implementation.
RESULTS: Among staff members at the first harm reduction agency, knowledge increased from 52% correct answers pre-intervention to 79% correct post-intervention. Among clients at the second harm reduction agency, initiation of buprenorphine treatment was low and did not differ between pre- and post-intervention groups.
CONCLUSIONS: The CBBT intervention was feasible and well-received, but initiation of buprenorphine treatment among harm reduction agency clients was low. More robust interventions may be necessary to increase initiation of buprenorphine treatment.

PMID: 28499432 [PubMed - in process]

Validated Spectrophtometric Method for Simultaneous Determination of Buprenorphine and Naloxone in Pharmaceutical Dosage Forms.

May 13, 2017 - 6:47am
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Validated Spectrophtometric Method for Simultaneous Determination of Buprenorphine and Naloxone in Pharmaceutical Dosage Forms.

Iran J Pharm Res. 2017;16(1):112-119

Authors: Souri E, Ahmadi FS, Barazandeh Tehrani M, Hosseini MM, Fadaye Vatan S

Abstract
Buprenorphine is a partial mu agonist and kappa antagonist which is used for the treatment of pain and opioid addiction. A mixture of buprenorphine hydrochloride and naloxone hydrochloride has been approved for the treatment of opioid dependence. In this study a third order derivative spectrophotometric method based on zero-crossing technique has been used for the simultaneous determination of buprenorphine hydrochloride and naloxone hydrochloride in tablets. The measurements were carried out at wavelengths of 257.8 (zero-crossing point of naloxone hydrochloride) and 252.2 nm (zero-crossing point of buprenorphice hydrochloride) for buprenorphine hydrochloride and naloxone hydrochloride, respectively in the third order derivative spectra obtained in methanol and 0.1 M NaOH (50:50) as solvent. The method was found to be linear in the range of 20-80 µg/mL for buprenorphine hydrochloride and 5-20 µg/mL for naloxone hydrochloride. The within-day and between-day coefficient of variation and error values were less than 2.5% and 1.8%, respectively. The proposed method was successfully used for simultaneous determination of these drugs in pharmaceutical dosage form without any interference from excipients or need to prior separation before analysis.

PMID: 28496466 [PubMed - in process]

Elbasvir-Grazoprevir to Treat Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy: A Randomized Trial.

May 13, 2017 - 6:47am
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Elbasvir-Grazoprevir to Treat Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy: A Randomized Trial.

Ann Intern Med. 2016 Nov 01;165(9):625-634

Authors: Dore GJ, Altice F, Litwin AH, Dalgard O, Gane EJ, Shibolet O, Luetkemeyer A, Nahass R, Peng CY, Conway B, Grebely J, Howe AY, Gendrano IN, Chen E, Huang HC, Dutko FJ, Nickle DC, Nguyen BY, Wahl J, Barr E, Robertson MN, Platt HL, C-EDGE CO-STAR Study Group

Abstract
Background: Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID).
Objective: To evaluate elbasvir-grazoprevir in treating HCV infection in PWID.
Design: Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688).
Setting: Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States.
Patients: 301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT).
Intervention: The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks.
Measurements: The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events.
Results: The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebo-phase DTG (1 of 100) discontinued treatment because of an adverse event.
Limitation: These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID.
Conclusion: Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT.
Primary Funding Source: Merck & Co.

PMID: 27537841 [PubMed - indexed for MEDLINE]

Drop-out from a drug treatment clinic and associated reasons.

May 12, 2017 - 6:30am

Drop-out from a drug treatment clinic and associated reasons.

East Mediterr Health J. 2017 May 01;23(3):173-181

Authors: Hoseinie L, Gholami Z, Shadloo B, Mokri A, Amin-Esmaeili M, Rahimi-Movaghar A

Abstract
The aim of this study was to assess drop-out rates and associated reasons among patients at the Iranian National Center for Addiction Studies (INCAS) clinic. In a one-year period (April 2014 to March 2015), all patients with drug dependence who had been referred for treatment and attended for a first assessment were included in this study (N=242). Those who received treatment were followed until March 2016. Survival analysis showed that 70.2% had dropped out from treatment. Log rank test showed that treatment drop-out rates differed between the different approaches used (P < 0.001), with the lowest slope inbuprenorphine maintenance treatment and the highest in the detoxification programme. Drop-out rates within the first three months was 62% (SE= 0.05) and 82.4% (SE=0.03) for opioids and stimulants dependence, respectively. Analyses were performed using SPSS (Version 21.0) and STATA software, (version 13.0). From the patients' perspective, motivational inconsistencies were considered as the main reason for not starting or leaving treatment. The findings of this study could give service providers a better grasp of drop-out rates and the associated reasons.

PMID: 28493264 [PubMed - in process]

Overcoming Barriers to Initiating Medication-assisted Treatment for Heroin Use Disorder in a General Medical Hospital: A Case Report and Narrative Literature Review.

May 12, 2017 - 6:30am

Overcoming Barriers to Initiating Medication-assisted Treatment for Heroin Use Disorder in a General Medical Hospital: A Case Report and Narrative Literature Review.

J Psychiatr Pract. 2017 May;23(3):221-229

Authors: Hassamal S, Goldenberg M, Ishak W, Haglund M, Miotto K, Danovitch I

Abstract
Deaths due to heroin overdoses are increasing and are the leading cause of death among intravenous heroin users. Although medication-assisted treatment (MAT) improves morbidity and mortality in patients with opioid use disorders, it is underutilized. Most efforts to expand access to MAT have focused on outpatient settings. Although the inpatient medical setting presents a critical opportunity to initiate treatment, general hospitals are often unfamiliar with MAT, creating a number of barriers to its use. In this report, we describe the case of a woman with heroin use disorder who was initiated on buprenorphine maintenance treatment while hospitalized for cardiac disease related to her intravenous heroin use. Barriers to initiating buprenorphine in this case included patient, practitioner, and organizational factors, and, ultimately, shared misperceptions about the feasibility of administering buprenorphine in a general medical hospital. These barriers were addressed, buprenorphine was initiated, and the patient demonstrated reduced craving, improved postoperative pain control, improved overall well-being, increased engagement in discharge planning, and acceptance of referral for addiction specialty aftercare. Our experience with this patient suggests that it is feasible to initiate buprenorphine in acute medical settings and that such treatment can improve patient outcomes. Our review of the literature reveals emerging evidence supporting the value of this practice.

PMID: 28492461 [PubMed - in process]

Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats.

May 12, 2017 - 6:30am
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Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats.

J Vet Med. 2017;2017:3102567

Authors: Guarnieri M, Brayton C, Sarabia-Estrada R, Tyler B, McKnight P, DeTolla L

Abstract
A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy.

PMID: 28492060 [PubMed - in process]

Use of opioid substitution therapies in the treatment of opioid use disorder: results of a UK cost-effectiveness modelling study.

May 11, 2017 - 1:28pm
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Use of opioid substitution therapies in the treatment of opioid use disorder: results of a UK cost-effectiveness modelling study.

J Med Econ. 2017 May 10;:1-23

Authors: Kenworthy J, Yi Y, Wright A, Brown J, Madrigal AM, Dunlop WCN

Abstract
AIMS: We investigated the cost-effectiveness of buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT) versus no opioid substitution therapy (OST) for the treatment of opioid use disorder, from the UK National Health Service (NHS)/personal social services (PSS) and societal perspectives over one year.
METHODS: Cost-effectiveness of OST versus no OST was evaluated by first replicating and then expanding an existing UK health technology assessment model. The expanded model included the impact of OST on infection rates of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection.
RESULTS: Versus no OST, incremental cost-effectiveness ratios (ICERs) for BMT and MMT were £13,923 and £14,206 per quality-adjusted life year (QALY), respectively, from a NHS/PSS perspective. When total costs (NHS/PSS and societal) are considered, there are substantial savings associated with adopting OST; these savings are in excess of £14,032 for BMT versus no OST and £17,174 for MMT versus no OST over one year, respectively. This is primarily driven by a reduction in victim costs. OST treatment also impacted other aspects of criminality and healthcare resource use.
LIMITATIONS: The model's one-year timeframe means long-term costs and benefits and the influence of changes over time are not captured.
CONCLUSIONS: OST can be considered cost-effective versus no OST from the UK NHS/PSS perspective, with a cost per QALY well below the UK's willingness-to-pay threshold. There were only small differences between BMT and MMT. The availability of two or more cost-effective options is beneficial to retaining patients in OST programs. From a societal perspective, OST is estimated to save over £14,032 and £17,174 per year for BMT and MMT versus no OST respectively, due to savings in victim costs. Further work is required to fully quantify the clinical and health economic impacts of different OST formulations and their societal impact over the long term.

PMID: 28489467 [PubMed - as supplied by publisher]

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