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Buprenorphine for managing opioid withdrawal.

February 22, 2017 - 6:54am
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Buprenorphine for managing opioid withdrawal.

Cochrane Database Syst Rev. 2017 Feb 21;2:CD002025

Authors: Gowing L, Ali R, White JM, Mbewe D

Abstract
BACKGROUND: Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of substitution treatment.
OBJECTIVES: To assess the effects of buprenorphine versus tapered doses of methadone, alpha2-adrenergic agonists, symptomatic medications or placebo, or different buprenorphine regimens for managing opioid withdrawal, in terms of the intensity of the withdrawal syndrome experienced, duration and completion of treatment, and adverse effects.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2016), MEDLINE (1946 to December week 1, 2016), Embase (to 22 December 2016), PsycINFO (1806 to December week 3, 2016), and the Web of Science (to 22 December 2016) and handsearched the reference lists of articles.
SELECTION CRITERIA: Randomised controlled trials of interventions using buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha2-adrenergic agonists (clonidine or lofexidine), symptomatic medications or placebo, and different buprenorphine-based regimens.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.
MAIN RESULTS: We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction.For the comparison of buprenorphine and methadone in tapered doses, meta-analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to ameliorate opioid withdrawal, without clinically significant adverse effects. The meta-analyses that were possible support a conclusion of no difference between buprenorphine and methadone in terms of average treatment duration (mean difference (MD) 1.30 days, 95% confidence interval (CI) -8.11 to 10.72; N = 82; studies = 2; low quality) or treatment completion rates (risk ratio (RR) 1.04, 95% CI 0.91 to 1.20; N = 457; studies = 5; moderate quality).Relative to clonidine or lofexidine, buprenorphine was associated with a lower average withdrawal score (indicating less severe withdrawal) during the treatment episode, with an effect size that is considered to be small to moderate (standardised mean difference (SMD) -0.43, 95% CI -0.58 to -0.28; N = 902; studies = 7; moderate quality). Patients receiving buprenorphine stayed in treatment for longer, with an effect size that is considered to be large (SMD 0.92, 95% CI 0.57 to 1.27; N = 558; studies = 5; moderate quality) and were more likely to complete withdrawal treatment (RR 1.59, 95% CI 1.23 to 2.06; N = 1264; studies = 12; moderate quality). At the same time there was no significant difference in the incidence of adverse effects, but dropout due to adverse effects may be more likely with clonidine (RR 0.20, 95% CI 0.04 to 1.15; N = 134; studies = 3; low quality). The difference in treatment completion rates translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 6), indicating that for every four people treated with buprenorphine, we can expect that one additional person will complete treatment than with clonidine or lofexidine.For studies comparing different rates of reduction of the buprenorphine dose, meta-analysis was possible only for treatment completion, with separate analyses for inpatient and outpatient settings. The results were diverse, and we assessed the quality of evidence as being very low. It remains very uncertain what effect the rate of dose taper has on treatment outcome.
AUTHORS' CONCLUSIONS: Buprenorphine is more effective than clonidine or lofexidine for managing opioid withdrawal in terms of severity of withdrawal, duration of withdrawal treatment, and the likelihood of treatment completion.Buprenorphine and methadone appear to be equally effective, but data are limited. It remains possible that the pattern of withdrawal experienced may differ and that withdrawal symptoms may resolve more quickly with buprenorphine.It is not possible to draw any conclusions from the available evidence on the relative effectiveness of different rates of tapering the buprenorphine dose. The divergent findings of studies included in this review suggest that there may be multiple factors affecting the response to the rate of dose taper. One such factor could be whether or not the initial treatment plan includes a transition to subsequent relapse prevention treatment with naltrexone. Indeed, the use of buprenorphine to support transition to naltrexone treatment is an aspect worthy of further research.Most participants in the studies included in this review were male. None of the studies reported outcomes on the basis of sex, preventing any exploration of differences related to this variable. Consideration of sex as a factor influencing response to withdrawal treatment would be relevant research for selecting the most appropriate type of intervention for each individual.

PMID: 28220474 [PubMed - as supplied by publisher]

Pain management in total knee arthroplasty: efficacy of a multimodal opiate-free protocol.

February 22, 2017 - 6:54am
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Pain management in total knee arthroplasty: efficacy of a multimodal opiate-free protocol.

Joints. 2016 Oct-Dec;4(4):222-227

Authors: Canata GL, Casale V, Chiey A

Abstract
PURPOSE: this study was conducted to identify the most effective method of postoperative pain management, comparing the intravenous opiate infusion protocol with the use of a single periarticular local anesthetic infiltration (LAI) in patients undergoing total knee arthroplasty (TKA) surgery.
METHODS: 50 patients submitted to TKA surgery between 2013 and 2015 were divided into two groups. Buprenorphine was administered intravenously to the patients in Group A, while the Group B patients received a single periarticular LAI (ropivacaine and ketorolac) during surgery. Pain was assessed using a visual analog scale (VAS) and the knee injury and osteoarthritis outcome score. Hemoglobin and hematocrit were measured in the early postoperative period and at 40 days post-surgery. Range of motion and inflammatory markers were also assessed. Statistical analysis was performed using Student's t-test.
RESULTS: student's t-test showed no significant difference between the groups in functional outcomes or blood values, but a difference in VAS score on the day of surgery was found (p < 0.0001), in favor of Group B.
CONCLUSIONS: LAI considerably reduces postoperative pain, allowing rapid mobilization and accelerating functional recovery.
LEVEL OF EVIDENCE: Level I, prospective single-blind randomized trial.

PMID: 28217658 [PubMed - in process]

[Misuse and dependence on prescription opioids: Prevention, identification and treatment].

February 19, 2017 - 9:32am
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[Misuse and dependence on prescription opioids: Prevention, identification and treatment].

Rev Med Interne. 2017 Feb 14;:

Authors: Rolland B, Bouhassira D, Authier N, Auriacombe M, Martinez V, Polomeni P, Brousse G, Schwan R, Lack P, Bachellier J, Rostaing S, Bendimerad P, Vergne-Salle P, Dematteis M, Perrot S

Abstract
Since the 1990s, the use of prescription opioids has largely spread, which has brought a real progress in the treatment of pain. The long-term use of prescription opioid is sometimes required, and may lead to pharmacological tolerance and withdrawal symptoms, i.e. pharmacological dependence on prescription opioids. Occasionally, this may also lead to misuse of prescription opioids (MPO). MPO preferentially occurs in vulnerable individuals, i.e., those with a young age, history of other addictive or psychiatric disorders, especially anxious and depressive disorders. MPO is associated with numerous complications, including an increased risk of fatal overdose. Prevention of MPO begins before the opioid prescription, with the identification of potential vulnerability factors. A planned and personalized monitoring should be systematically implemented. In vulnerable patients, contractualizing the prescription is warranted. During follow-up, the relevance of the prescription should be regularly reconsidered, according to the benefit observed on pain and the potential underlying signs of MPO. Patients with suspected MPO should be referred early to pain or addiction centers. The treatment of MPO should be based on multidisciplinary strategies, involving both the addiction and pain aspects: progressive opioid withdrawal, non-pharmacological measures against pain, or switching to medication-assisted treatment of addiction (i.e., buprenorphine or methadone).

PMID: 28214183 [PubMed - as supplied by publisher]

Adjuvant Agents in Regional Anesthesia in the Ambulatory Setting.

February 18, 2017 - 9:24am
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Adjuvant Agents in Regional Anesthesia in the Ambulatory Setting.

Curr Pain Headache Rep. 2017 Jan;21(1):6

Authors: Koyyalamudi V, Sen S, Patil S, Creel JB, Cornett EM, Fox CJ, Kaye AD

Abstract
PURPOSE OF REVIEW: A majority of surgical practice has involved ambulatory centers with the number of outpatient operations in the USA doubling to 26.8 million per year. Local anesthesia delivery provides numerous benefits, including increased satisfaction, earlier discharge, and reduction in unplanned hospital admission. Further, with the epidemic of opioid mediated overdoses, local anesthesia can be a key tool in providing an opportunity to reduce the need for other analgesics postoperatively.
RECENT FINDINGS: Adjuvants such as epinephrine and clonidine enhance local anesthetic clinical utility. Further, dexmedetomidine prolongs regional blockade duration effects. There has also been a significant interest recently in the use of dexamethasone. Studies have demonstrated a significant prolongation in motor and sensory block with perineural dexamethasone. Findings are conflicting as to whether intravenous dexamethasone has similar beneficial effects. However, considering the possible neurotoxicity effects, which perineural dexamethasone may present, it would be prudent not to consider intravenously administered dexamethasone to prolong regional block duration. Many studies have also demonstrated neurotoxicity from intrathecally administered midazolam. Therefore, midazolam as an adjuvant is not recommended. Magnesium prolongs regional block duration but related to paucity of studies as of yet, cannot be recommended. Tramadol yields inconsistent results and ketamine is associated with psychotomimetic adverse effects. Buprenorphine consistently increases regional block duration and reduce opioid requirements by a significant amount. Future studies are warranted to define best practice strategies for these adjuvant agents. The present review focuses on the many roles of local anesthetics in current ambulatory practice.

PMID: 28210917 [PubMed - in process]

KB220Z™ a Pro-Dopamine Regulator Associated with the Protracted, Alleviation of Terrifying Lucid Dreams. Can We Infer Neuroplasticity-induced Changes in the Reward Circuit?

February 18, 2017 - 9:24am
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KB220Z™ a Pro-Dopamine Regulator Associated with the Protracted, Alleviation of Terrifying Lucid Dreams. Can We Infer Neuroplasticity-induced Changes in the Reward Circuit?

J Reward Defic Syndr Addict Sci. 2016;2(1):3-13

Authors: McLaughlin T, Febo M, Badgaiyan RD, Barh D, Dushaj K, Braverman ER, Li M, Madigan MA, Blum K

Abstract
BACKGROUND: Recent reports by our laboratory have indicated that lucid dreams may be linked to psychiatric conditions, including Attention Deficit Hyperactivity Disorder (ADHD) and other Reward Deficiency Syndrome-related diagnoses. In the latter case, it has been our observation that such lucid dreams can be unpleasant and frequently terrifying.
CASE PRESENTATIONS: We present four cases of a dramatic and persistent alleviation of terrifying, lucid dreams in patients diagnosed with ADHD/PTSD and/or opiate/opioid addiction. The amelioration of such dreams could well be permanent, since the patients had stopped taking the nutraceutical for between 10 to 12 months, without their recollection or recurrence. In the first case, the patient is a 47-year-old, married male who required continued Buprenorphine/ Naloxone (Suboxone) treatment. The second case involved a 32-year-old female with the sole diagnosis of ADHD. The third case involves a 38-year-old male who carried the diagnoses of Substance Use Dependence and ADHD. The fourth case involved a 50-year-old female with the diagnoses of Alcohol Abuse, ADHD and Posttraumatic Stress Disorder.
RESULTS: In order to attempt to understand the possibility of neuroplasticity, we evaluated the effect of KB220Z in non-opioid-addicted rats utilizing functional Magnetic Resonance Imaging methodology. While we cannot make a definitive claim because rat brain functional connectivity may not be exactly the same as humans, it does provide some interesting clues. We did find following seeding of the dorsal hippocampus, enhanced connectivity volume across several Regions of Interest (ROI), with the exception of the pre- frontal cortex. Interestingly, the latter region is only infrequently activated in lucid human dreaming, when the dreamer reports that he/she had the thought that they were dreaming during the lucid dream.
CONCLUSIONS: The four patients initially reported a gradual but, then, complete amelioration of their long-term, terrifying, lucid dreams, while taking KB220Z. The persistent amelioration of these dreams continued for up to 12 months, after a self-initiated, cessation of use of KB220Z. These particular cases raise the scientific possibility that KB200Z increases both dopamine stability as well as functional connectivity between networks of brain reward circuitry in both rodents and humans. The increase in connectivity volume in rodents suggest the induction of neuroplasticity changes, which may be analogous to those involved in human lucid dreaming as well as Rapid Eye Movement sleep. The possibility that the complex induces long-term, neuroplasticity changes must await more intensive investigations, involving large-population, double-blinded studies.

PMID: 28210713 [PubMed - in process]

Evaluation of 6 remote First Nations community-based buprenorphine programs in northwestern Ontario: Retrospective study.

February 18, 2017 - 9:24am
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Evaluation of 6 remote First Nations community-based buprenorphine programs in northwestern Ontario: Retrospective study.

Can Fam Physician. 2017 Feb;63(2):137-145

Authors: Mamakwa S, Kahan M, Kanate D, Kirlew M, Folk D, Cirone S, Rea S, Parsons P, Edwards C, Gordon J, Main F, Kelly L

Abstract
OBJECTIVE: To evaluate established opioid addiction treatment programs that use traditional healing in combination with buprenorphine-naloxone maintenance treatment in 6 First Nations communities in the Sioux Lookout region of northwestern Ontario.
DESIGN: Retrospective cohort study.
SETTING: Six First Nations communities in northwestern Ontario.
PARTICIPANTS: A total of 526 First Nations participants in opioid-dependence treatment programs.
INTERVENTION: Buprenorphine-naloxone substitution therapy and First Nations healing programming.
MAIN OUTCOME MEASURES: Retention rates and urine drug screening (UDS) results.
RESULTS: Treatment retention rates at 6, 12, and 18 months were 84%, 78%, and 72%, respectively. We estimate that the rate at 24 months will also be more than 70%. The UDS programming varied and was implemented in only 1 community. Initially urine testing was voluntary and it then became mandatory. Screening with either method found the proportion of urine samples with negative results for illicit opioids ranged between 84% and 95%.
CONCLUSION: The program's treatment retention rates and negative UDS results were higher than those reported for most methadone and buprenorphine-naloxone programs, despite a patient population where severe posttraumatic stress disorder is endemic, and despite the programs' lack of resources and addiction expertise. Community-based programs like these overcome the initial challenge of cultural competence. First Nations communities in other provinces should establish their own buprenorphinenaloxone programs, using local primary care physicians as prescribers. Sustainable core funding is needed for programming, long-term aftercare, and trauma recovery for such initiatives.

PMID: 28209683 [PubMed - in process]

Translational Interpretations of Combined Bupivacaine-Clonidine-Buprenorphine-Dexamethasone.

February 17, 2017 - 2:17pm
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Translational Interpretations of Combined Bupivacaine-Clonidine-Buprenorphine-Dexamethasone.

Reg Anesth Pain Med. 2017 Mar/Apr;42(2):271-272

Authors: Williams BA, Ibinson JW, Ezaru CS, Rakesh H, Mangione MP

PMID: 28207646 [PubMed - in process]

An overview of available drugs for management of opioid abuse during pregnancy.

February 17, 2017 - 2:17pm
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An overview of available drugs for management of opioid abuse during pregnancy.

Matern Health Neonatol Perinatol. 2017;3:4

Authors: Laslo J, Brunner JM, Burns D, Butler E, Cunningham A, Killpack R, Pyeritz C, Rinard K, Childers J, Horzempa J

Abstract
The prevalence of opioid abuse in the United States has been steadily increasing over the last several years among many major demographics, including pregnant women. Rise in prenatal opioid abuse has resulted in subsequent escalation of neonatal abstinence syndrome incidence, prompting the US Congress to pass the Protecting Our Infants Act of 2015. This act specifically calls for a critical review of current treatment options for prenatal opioid abuse which may ultimately lead to the development of better therapies and a decreased incidence of neonatal abstinence syndrome. Currently, the American College of Obstetricians and Gynecologists recommends methadone, buprenorphine, or buprenorphine/naloxone in the treatment of prenatal opioid abuse. In this review, each maintenance therapy treatment option is discussed and compared revealing inconsistencies in postpartum retention rates, effects on fetal development, and availability to patients due to restrictions in health care coverage. Although each of these treatment options reduces opioid abuse and potential negative outcomes for the fetus, the shortcomings of these drugs highlight the overarching need for an improved standard of care. Drug developers and lawmakers should consider that affordability, coverage by health insurance, and success in retention rates substantially impacts the decision of the patient and healthcare provider regarding utilization of a particular opioid maintenance therapy.

PMID: 28203387 [PubMed - in process]

Emergency Department-Initiated Buprenorphine for Opioid Dependence with Continuation in Primary Care: Outcomes During and After Intervention.

February 15, 2017 - 6:54am

Emergency Department-Initiated Buprenorphine for Opioid Dependence with Continuation in Primary Care: Outcomes During and After Intervention.

J Gen Intern Med. 2017 Feb 13;:

Authors: D'Onofrio G, Chawarski MC, O'Connor PG, Pantalon MV, Busch SH, Owens PH, Hawk K, Bernstein SL, Fiellin DA

Abstract
BACKGROUND: Emergency department (ED)-initiated buprenorphine/naloxone with continuation in primary care was found to increase engagement in addiction treatment and reduce illicit opioid use at 30 days compared to referral only or a brief intervention with referral.
OBJECTIVE: To evaluate the long-term outcomes at 2, 6 and 12 months following ED interventions.
DESIGN: Evaluation of treatment engagement, drug use, and HIV risk among a cohort of patients from a randomized trial who completed at least one long-term follow-up assessment.
PARTICIPANTS: A total of 290/329 patients (88% of the randomized sample) were included. The followed cohort did not differ significantly from the randomized sample.
INTERVENTIONS: ED-initiated buprenorphine with 10-week continuation in primary care, referral, or brief intervention were provided in the ED at study entry.
MAIN MEASURES: Self-reported engagement in formal addiction treatment, days of illicit opioid use, and HIV risk (2, 6, 12 months); urine toxicology (2, 6 months).
KEY RESULTS: A greater number of patients in the buprenorphine group were engaged in addiction treatment at 2 months [68/92 (74%), 95% CI 65-83] compared with referral [42/79 (53%), 95% CI 42-64] and brief intervention [39/83 (47%), 95% CI 37-58; p < 0.001]. The differences were not significant at 6 months [51/92 (55%), 95% CI 45-65; 46/70 (66%) 95% CI 54-76; 43/76 (57%) 95% CI 45-67; p = 0.37] or 12 months [42/86 (49%) 95% CI 39-59; 37/73 (51%) 95% CI 39-62; 49/78 (63%) 95% CI 52-73; p = 0.16]. At 2 months, the buprenorphine group reported fewer days of illicit opioid use [1.1 (95% CI 0.6-1.6)] versus referral [1.8 (95% CI 1.2-2.3)] and brief intervention [2.0 (95% CI 1.5-2.6), p = 0.04]. No significant differences in illicit opioid use were observed at 6 or 12 months. There were no significant differences in HIV risk or rates of opioid-negative urine results at any time.
CONCLUSIONS: ED-initiated buprenorphine was associated with increased engagement in addiction treatment and reduced illicit opioid use during the 2-month interval when buprenorphine was continued in primary care. Outcomes at 6 and 12 months were comparable across all groups.

PMID: 28194688 [PubMed - as supplied by publisher]

Open Port Probe Sampling Interface for the Direct Coupling of Biocompatible Solid-Phase Microextraction to Atmospheric Pressure Ionization Mass Spectrometry.

February 15, 2017 - 6:54am

Open Port Probe Sampling Interface for the Direct Coupling of Biocompatible Solid-Phase Microextraction to Atmospheric Pressure Ionization Mass Spectrometry.

Anal Chem. 2017 Feb 13;:

Authors: Gómez-Ríos GA, Liu C, Tascon M, Reyes-Garcés N, Arnold DW, Covey TR, Pawliszyn J

Abstract
In recent years, the direct coupling of solid phase microextraction (SPME) and mass spectrometry (MS) has shown its great potential to improve limits of quantitation, accelerate analysis throughput, and diminish potential matrix effects when compared to direct injection to MS. In this study, we introduce the open port probe (OPP) as a robust interface to couple biocompatible SPME (Bio-SPME) fibers to MS systems for direct electrospray ionization. The presented design consisted of minimal alterations to the front-end of the instrument and provided better sensitivity, simplicity, speed, wider compound coverage, and high-throughput in comparison to the LC-MS based approach. Quantitative determination of clenbuterol, fentanyl, and buprenorphine was successfully achieved in human urine. Despite the use of short extraction/desorption times (5 min/5 s), limits of quantitation below the minimum required performance levels (MRPL) set by the world antidoping agency (WADA) were obtained with good accuracy (≥90%) and linearity (R(2) > 0.99) over the range evaluated for all analytes using sample volumes of 300 μL. In-line technologies such as multiple reaction monitoring with multistage fragmentation (MRM(3)) and differential mobility spectrometry (DMS) were used to enhance the selectivity of the method without compromising analysis speed. On the basis of calculations, once coupled to high throughput, this method can potentially yield preparation times as low as 15 s per sample based on the 96-well plate format. Our results demonstrated that Bio-SPME-OPP-MS efficiently integrates sampling/sample cleanup and atmospheric pressure ionization, making it an advantageous configuration for several bioanalytical applications, including doping in sports, in vivo tissue sampling, and therapeutic drug monitoring.

PMID: 28192911 [PubMed - as supplied by publisher]

Newborn birth-weight of pregnant women on methadone or buprenorphine maintenance treatment: A national contingency management approach trial.

February 14, 2017 - 6:50am

Newborn birth-weight of pregnant women on methadone or buprenorphine maintenance treatment: A national contingency management approach trial.

Am J Addict. 2017 Feb 13;:

Authors: Peles E, Sason A, Schreiber S, Adelson M

Abstract
BACKGROUND AND OBJECTIVES: Methadone maintenance treatment (MMT) is the gold standard for pregnant women with opioid use disorders. Still, low birth-weights were reported, in particular of mothers who became pregnant before admission to MMT. We studied whether an escalating incentive contingency-management approach may contribute to better newborn birth-weights.
METHODS: A nationwide controlled randomized trial among all Israeli methadone/buprenorphine maintenance treatment (MBMT), newly or already in treatment pregnant women was performed. A modified contingency-management protocol with coupons of escalating value depending upon reduction of drug use, cigarette smoking, and alcohol consumption was compared to standard care arm. Drugs in urine, smoking (Fagerstrom score), alcohol use, and depression were monitored.
RESULTS: Thirty-five women had 46 pregnancies. In their first pregnancy, 19 from the contingency-management and 16 from the standard care arms were studied. Contingency-management group as compared to the standard care arm included more newly admitted women (36.8% vs. 6.3%, p = .05), with benzodiazepine and cannabis onset at a younger age, and higher proportion of any drug abuse while pregnant (100% vs. 68.8%, p = .01). Fifteen of the contingency-management and 14 of the control arm gave birth (78.9% vs. 87.5%, p = .3) with similar proportions of normal (>2,500 g) birth-weight (71.4% vs. 61.5%, p = .8).
CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Newborns' birth-weight was comparable among the two study arms indicating no contribution of the contingency-management approach. Small sample and baseline differences between arms might have influenced results. Intensive intervention should be evaluated on a larger scale of participants. (Am J Addict 2017;XX:1-9).

PMID: 28191917 [PubMed - as supplied by publisher]

Maternal buprenorphine treatment and fetal neurobehavioral development.

February 12, 2017 - 6:40am

Maternal buprenorphine treatment and fetal neurobehavioral development.

Am J Obstet Gynecol. 2017 Feb 07;:

Authors: Jansson LM, Velez M, McConnell K, Spencer N, Tuten M, Jones HE, King VL, Gandotra N, Milio LA, Voegtline K, DiPietro JA

Abstract
BACKGROUND: Gestational opioid use/misuse is escalating in the United States, however, little is understood about the fetal effects of medications used to treat maternal opioid use disorders.
OBJECTIVE: The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development.
STUDY DESIGN: Forty-nine buprenorphine-maintained women attending a substance use disorder treatment facility with generally uncomplicated pregnancies underwent fetal monitoring for 60 minutes at times of trough and peak maternal buprenorphine levels. Data were collected at 24, 28, 32, and 36 weeks gestation. Fetal neurobehavioral indicators (i.e., heart rate, motor activity and their integration (fetal movement-fetal heart rate coupling)) were collected via an actocardiograph, digitized and quantified. Longitudinal data analysis relied on hierarchical linear modeling.
RESULTS: Fetal heart rate, heart rate variability and heart rate accelerations were significantly reduced at peak versus trough maternal buprenorphine levels. Effects were significant either by or after 28 weeks of gestation, and tended to intensify with advancing gestation. Fetal motor activity and fetal movement-fetal heart rate coupling were depressed from peak to trough at 36 weeks of gestation. Polysubstance-exposure did not significantly affect fetal neurobehavioral parameters, with the exception that fetuses of heavier smokers moved significantly less than those of lighter smokers at 36 weeks. By the end of gestation, higher maternal buprenorphine dose was related to depression of baseline fetal cardiac measures at trough.
CONCLUSIONS: Maternal buprenorphine administration has acute suppressive effects on fetal heart rate and movement, and the magnitude of these effects increases as gestation progresses. Higher dose (> 13 mg) appears to exert greater depressive effects on measures of fetal heart rate and variability. These findings should be balanced against comparisons to gestational methadone effects, relatively good outcomes of buprenorphine-exposed infants, and recognition of the benefits of medication assisted treatment for pregnant women with opioid use disorders in optimizing pregnancy outcomes.

PMID: 28188773 [PubMed - as supplied by publisher]

Genetic variation in the behavioral effects of buprenorphine in female mice derived from a murine model of the OPRM1 A118G polymorphism.

February 12, 2017 - 6:40am

Genetic variation in the behavioral effects of buprenorphine in female mice derived from a murine model of the OPRM1 A118G polymorphism.

Neuropharmacology. 2017 Feb 07;:

Authors: Browne CA, Erickson RL, Blendy JA, Lucki I

Abstract
Pharmacogenetic studies have identified the non-synonymous single nucleotide polymorphism (A118G) in the human mu opioid receptor (MOR) gene (OPRM1) as a critical genetic variant capable of altering the efficacy of opioid therapeutics. To date few studies have explored the potential impact of the OPRM1 A118G polymorphism on the pharmacological effects of buprenorphine (BPN), a potent MOR partial agonist and kappa opioid receptor antagonist, which is approved by the FDA for the treatment of opioid addiction and chronic pain. The goal of these studies was to determine whether the MOR-mediated behavioral effects of BPN were altered in the Oprm1 A112G mouse model of the human OPRM1 A118G SNP. All studies were conducted in female, AA, AG and GG mice. BPN's maximal analgesic effect in the hot plate test was significantly blunted in AG and GG mice compared to wild type AA mice. Similarly, the BPN-induced reduction of latency to consume food in the novelty induced hypophagia test was blocked entirely in AG and GG mice compared to their AA littermates. In addition, GG mice exhibited marked reductions in psychostimulant hyperlocomotor activity compared to the AA group. In contrast, reduced immobility in the forced swim test, an effect of BPN mediated by kappa opioid receptors, was not affected by genotype. These studies demonstrate the ability of the Oprm1 A112G SNP to attenuate the analgesic, anxiolytic and hyperlocomotor effects of BPN. Overall, these data suggest that the OPRM1 A118G SNP will significantly impact the clinical efficacy of BPN in its therapeutic applications.

PMID: 28188737 [PubMed - as supplied by publisher]

Pharmacologic Treatment of Opioid Addiction During Pregnancy.

February 12, 2017 - 6:40am

Pharmacologic Treatment of Opioid Addiction During Pregnancy.

Nurs Womens Health. 2017 Feb - Mar;21(1):34-44

Authors: Keough L, Fantasia HC

Abstract
Opioid addiction during pregnancy presents a treatment challenge to clinicians and women alike. Untreated addiction can lead to poor maternal and fetal health outcomes. Medication-assisted treatment is the standard of care, and methadone is the current drug of choice for treatment. Emerging evidence also supports the use of buprenorphine during pregnancy. Both methadone and buprenorphine have risks and benefits that should be explored before initiating treatment. Clinicians who work in obstetrics and in addiction treatment can collaborate and coordinate treatment to ensure optimal maternal and fetal outcomes. Women undergoing treatment will require frequent monitoring, particularly in the third trimester. Neonates born to women receiving treatment may have withdrawal symptoms and require additional treatment.

PMID: 28187838 [PubMed - in process]

Advances in the treatment of opioid use disorders.

February 12, 2017 - 6:40am
Related Articles

Advances in the treatment of opioid use disorders.

F1000Res. 2017;6:87

Authors: Woody GE

Abstract
The development of medications for treating persons with opioid use disorders has expanded the number of evidence-based treatment options, particularly for persons with the most severe disorders. It has also improved outcomes compared to psychosocial treatment alone and expanded treatment availability by increasing the number of physicians involved in treatment and the settings where patients can be treated. The medications include methadone, buprenorphine, buprenorphine/naloxone, and extended-release injectable naltrexone. Studies have shown that they are most effective when used over an extended, but as-yet-unspecified, period of time and with counseling and other services, particularly for the many with psychosocial problems. Though controversial in some cultures, well-designed studies in Switzerland, the Netherlands, Germany, and Canada have demonstrated the efficacy of supervised heroin injecting for persons who responded poorly to other treatments, and this treatment option has been approved by Switzerland and a few other E.U. countries. The degree to which medication-assisted therapies are available is dependent on many variables, including national and local regulations, preferences of individual providers and their geographical location, treatment costs, and insurance policies. Greater availability of medication-assisted therapies has become a major focus in the U.S. and Canada, where there has been a marked increase in deaths associated with heroin and prescription opioid use. This paper provides a brief summary of these developments.

PMID: 28184294 [PubMed - in process]

Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids.

February 10, 2017 - 6:30am

Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids.

J Pain Res. 2017;10:233-240

Authors: Hale M, Urdaneta V, Kirby MT, Xiang Q, Rauck R

Abstract
BACKGROUND: This open-label, single-arm study was conducted to evaluate the long-term safety and efficacy of a novel buprenorphine formulation, buprenorphine buccal film, in the treatment of moderate-to-severe chronic pain requiring around-the-clock opioids.
METHODS: The primary purpose of this study was to evaluate the long-term safety and tolerability of buprenorphine buccal film. Five hundred and six patients who completed previous studies with buprenorphine buccal film (n=445; rollover patients) or were recruited de novo for this study (n=61) were enrolled in this study. All patients underwent a dose titration period of ≤6 weeks, during which doses of buprenorphine buccal film were adjusted to a maximum 900 µg every 12 hours, depending on tolerability and the need for rescue medication. An optimal dose was defined as the dose that the patient found satisfactory for both pain relief and tolerability, without the need for rescue medication or with ≤2 tablets of rescue medication per day. Once the optimal dose was reached, treatment was continued for ≤48 weeks. Pain intensity was measured throughout the study using a 0-10 numerical rating scale.
RESULTS: Of 435 patients achieving an optimal dose of buprenorphine buccal film who commenced long-term treatment, 158 (36.3%) completed 48 weeks of treatment. Treatment-related adverse events occurred in 116 patients (22.9%) during the titration phase and 61 patients (14.0%) during the long-term treatment phase, and adverse events leading to discontinuation of treatment occurred in 14 (2.8%) and 14 (3.2%) patients, respectively. The most common adverse events were those typically associated with opioids, such as nausea, constipation, and headache. In both rollover and de novo patients, pain intensity scores remained constant at approximately 3-4 during long-term treatment, and the dose of buprenorphine buccal film remained unchanged in 86.2% of patients.
CONCLUSION: In appropriate patients, buprenorphine buccal film demonstrated tolerability and efficacy in the long-term management of chronic pain.

PMID: 28182123 [PubMed - in process]

Lixisenatide.

February 10, 2017 - 6:30am
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Lixisenatide.

Hosp Pharm. 2017 Jan;52(1):65-80

Authors: Baker DE, Levien TL

Abstract
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. The January 2017 monograph topics are bezlotoxumab, buprenorphine buccal, deflazacort, dupilumab, and olaratumab. The DUE is on buprenorphine buccal.

PMID: 28179743 [PubMed - in process]

Distribution of bupivacaine hydrochloride after sciatic and femoral nerve blocks in cats: A magnetic resonance imaging study.

February 9, 2017 - 6:27am
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Distribution of bupivacaine hydrochloride after sciatic and femoral nerve blocks in cats: A magnetic resonance imaging study.

Res Vet Sci. 2017 Jan 27;115:61-65

Authors: Evangelista MC, de Lassalle J, Chevrier C, Carmel EN, Fantoni DT, Steagall PV

Abstract
The objective of this study was to evaluate the distribution of bupivacaine hydrochloride using magnetic resonance imaging (MRI) after electrical nerve stimulator (ENS)-guided sciatic (ScN) and femoral (FN) nerve blocks in cats. Six adult cats (body weight 4.8±0.6kg) were anesthetized with acepromazine-buprenorphine-propofol-isoflurane. Transverse and sagittal plan sequences of pelvic limbs were obtained using a high-field magnet (1.5T). Afterwards, the ScN and FN blocks (one block per limb) were performed using 0.1mL/kg of bupivacaine 0.5% per site and the MRI sequence was repeated after each block. The injection was considered successful when bupivacaine was in contact with the nerve. Injectate location and complications were recorded. The length (mm) of contact (spread) between bupivacaine and nerves was measured and classified as fair (<15mm) or adequate (≥15mm). Five out of six ScN injections were successful; of these, four had adequate spread over the nerve [26 (13-39) mm]. All FN injections were successful, but in one case bupivacaine was administered over the motor branch of FN, distally to the bifurcation between the femoral and saphenous nerve. It was not possible to measure neither the length of contact between bupivacaine and FN nor to identify iatrogenic trauma caused by the injections. MRI can be used for the evaluation of bupivacaine distribution, but not complications, following ENS-guided ScN and FN blocks in cats. Despite most of the injections were considered successful, individual variability regarding the injectate location may explain differences in efficacy in the clinical setting.

PMID: 28171798 [PubMed - as supplied by publisher]

Commentary on Nikoo et al. (2017): The role of research.

February 9, 2017 - 6:27am
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Commentary on Nikoo et al. (2017): The role of research.

Addiction. 2017 Mar;112(3):430-431

Authors: Bell J

PMID: 28168791 [PubMed - in process]

Volatility and Change in Chronic Pain Severity Predict Outcomes of Treatment for Prescription Opioid Addiction.

February 7, 2017 - 6:46am
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Volatility and Change in Chronic Pain Severity Predict Outcomes of Treatment for Prescription Opioid Addiction.

Addiction. 2017 Feb 05;:

Authors: Worley MJ, Heinzerling KG, Shoptaw S, Ling W

Abstract
BACKGROUND AND AIMS: Buprenorphine-naloxone (BUP-NLX) can be used to manage prescription opioid addiction among persons with chronic pain, but post-treatment relapse is common and difficult to predict. This study estimated whether changes in pain over time and pain volatility during BUP-NLX maintenance would predict opioid use during the taper BUP-NLX taper.
DESIGN: Secondary analysis of a multisite clinical trial for prescription opioid addiction, using data obtained during a 12-week BUP-NLX stabilization and 4-week BUP-NLX taper.
SETTING: Community clinics affiliated with a national clinical trials network in 10 U.S. cities.
PARTICIPANTS: Subjects with chronic pain who entered the BUP-NLX taper phase (N = 125) with enrollment occurring from June, 2006 to July 2009 (52% male, 88% Caucasian, 31% married).
MEASUREMENTS: Outcomes were weekly biologically-verified and self-reported opioid use from the 4-week taper phase. Predictors were estimates of baseline severity, rate of change, and volatility in pain from weekly self-reports during the 12-week maintenance phase.
FINDINGS: Controlling for baseline pain and treatment condition, increased pain (OR = 2.38, p = .02) and greater pain volatility (OR = 2.43, p = .04) predicted greater odds of positive opioid urine screen during BUP-NLX taper. Increased pain (IRR = 1.40, p = .04) and greater pain volatility (IRR = 1.66, p = .009) also predicted greater frequency of self-reported opioid use.
CONCLUSIONS: Adults with chronic pain receiving outpatient treatment with buprenorphine-naloxone (BUP-NLX) for prescription opioid addiction have elevated risk for opioid use when tapering off of maintenance treatment. Those with relative persistence in pain over time and greater volatility in pain during treatment are less likely to sustain abstinence during BUP-NLX taper.

PMID: 28164407 [PubMed - as supplied by publisher]

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