Perinatal methadone exposure produces physical dependence and altered behavioral development in the rat.

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Kunko, P M; Smith, J A; Wallace, M J; Maher, J R; Saady, J J; Robinson, S E

1996-06-01

Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that the following prenatal/postnatal exposure groups were obtained: water/water, methadone/water, water/methadone and methadone/methadone. Methadone slightly reduced litter size, particularly the number of male offspring, and reduced litter birth weight. The induction or maintenance of physical dependence in the postnatal methadone exposure groups was confirmed by an experiment in which PD19 pups were challenged with naloxone (1 mg/kg, s.c.). Methadone concentrations were assayed in pup brain on postnatal days 4, 10 and 22. Postnatal exposure to methadone via maternal milk produced measurable levels of methadone which decreased with age. Neuromuscular and physical development were assessed. Exposure to methadone accelerated acquisition of the righting reflex, but tended to delay the acquisition of the negative geotaxic response. Postnatal exposure to methadone was associated with decreased somatic growth as measured through postnatal day 21. The older pups (postnatal day 21) exposed to methadone exhibited variations in activity levels: pups exposed to methadone both prenatally and postnatally exhibited the least amount of spontaneous locomotor activity and pups exposed only postnatally exhibited the most activity. Therefore, it is possible to induce and/or maintain physical dependence via lactation in rat pups fostered to methadone-treated dams. Perinatal exposure to methadone by this route produces several subtle disruptions of pup development in the absence of gross maternal or fetal toxicity.

Craving despite extremely high methadone dosage

NARCIS (Netherlands)

de Vos, J. W.; Ufkes, J. G.; van Brussel, G. H.; van den Brink, W.

1996-01-01

A clinical case study is presented of an opiate addict, currently under methadone maintenance treatment (MMT), who claims the need of a higher daily methadone dose. He is admitted to a closed metabolic ward, where he receives 250 mg methadone per day. During 24 h both pharmacokinetic parameters and

Methadone Recycling Sustains Drug Reservoir in Tissue.

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Linares, Oscar A; Fudin, Jeffrey; Daly, Annemarie; Schiesser, William E; Boston, Raymond C

2015-09-01

We hypothesize that there is a tissue store of methadone content in humans that is not directly accessible, but is quantifiable. Further, we hypothesize the mechanism by which methadone content is sustained in tissue stores involves methadone uptake, storage, and release from tissue depots in the body (recycling). Accordingly, we hypothesize that such tissue stores, in part, determine plasma methadone levels. We studied a random sample of six opioid-naïve healthy subjects. We performed a clinical trial simulation in silico using pharmacokinetic modeling. We found a large tissue store of methadone content whose size was much larger than methadone's size in plasma in response to a single oral dose of methadone 10 mg. The tissue store measured 13-17 mg. This finding could only be explained by the contemporaneous storage of methadone in tissue with dose recycling. We found that methadone recycles 2-5 times through an inaccessible extravascular compartment (IAC), from an accessible plasma-containing compartment (AC), before exiting irreversibly. We estimate the rate of accumulation (or storage) of methadone in tissue was 0.029-7.29 mg/h. We predict 39 ± 13% to 83 ± 6% of methadone's tissue stores "spillover" into the circulation. Our results indicate that there exists a large quantifiable tissue store of methadone in humans. Our results support the notion that methadone in humans undergoes tissue uptake, storage, release into the circulation, reuptake from the circulation, and re-release into the circulation, and that spillover of methadone from tissue stores, in part, maintain plasma methadone levels in humans.

Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.

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Chiang, Yao-Chang; Ye, Li-Ci; Hsu, Kuei-Ying; Liao, Chien-Wei; Hung, Tsai-Wei; Lo, Wan-Jou; Ho, Ing-Kang; Tao, Pao-Luh

2015-03-20

Heroin use among young women of reproductive age has drawn much attention around the world. Although methadone is widely used in maintenance therapy for heroin/morphine addiction, the long-term effects of prenatal exposure to methadone and preventative therapy remain unclear. For revealing this question, female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) methadone 5 mg/kg at embryonic day 3 (E3) and then 7 mg/kg from E4 to E20, (3) dextromethorphan (DM) 3 mg/kg, and (4) methadone + DM (the rats received methadone followed by DM treatment), subcutaneously, twice a day from E3 to E20. The body weight, natural withdrawal, pain sensitivity, ED50, conditioned place preference and water maze were conducted at different postnatal stages (P1 to P79) of offspring. The quantitative real-time RT-PCR and electrophysiology were also used to measure the gene expression of opioid receptors in the spinal cord and changes of LTP/LTD in the hippocampus, separately. Prenatal exposure to methadone or DM did not affect survival rate, body weight, water maze and LTP or LTD of offspring. However, prenatal methadone significantly increased the withdrawal symptoms, pain sensitivity, addiction liability and decreased the mRNA expression of pain related opioid receptors. Co-administration of DM with methadone in the maternal rats effectively prevented these abnormalities of offspring induced by methadone. Our study clearly showed that co-administration of dextromethorphan with methadone in the maternal rats prevented the adverse effects induced by prenatal methadone exposure. It implies that dextromethorphan may have a potential to be used in combination with methadone for maintenance treatment in pregnant heroin-addicted women to prevent the adverse effects induced by methadone on offspring.

Intermittent subcutaneous methadone administration in the management of cancer pain.

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Centeno, Carlos; Vara, Francisco

2005-01-01

Methadone is a strong opioid analgesic that has been used successfully in cancer pain management. The oral route of administration is generally preferred for opioid analgesics. However that route sometimes cannot be used. Experience with continuous subcutaneous methadone infusions has produced local intolerance. The aim of this study was to analyze the use of intermittent subcutaneous methadone injections. Ten patients whose pain was well-controlled with oral methadone (average dose 30 mg, range 10 to 120 mg) participated in the study. A subcutaneous small vein needle (butterfly) was used exclusively for administration of methadone. Over a period of seven days the local discomfort of each injection was evaluated by means of a Verbal Numerical Rating Scale (NRS) and the site of infusion was observed. When any degree of erythema or inflammation was seen, the infusion site was changed. The initial subcutaneous dose was the same as the previously administered oral dose. A daily record was kept of the dose used, level of pain, and toxicity symptoms. This close vigilance was aimed at avoiding dosage errors due to variations among individuals in acceptance to previous oral medication. Changes in dosage were allowed according to standard medical criteria. Two patients were withdrawn from the study due to non-painful irritation at the infusion point. Another eight patients tolerated repeated administration of subcutaneous methadone over seven days. Any local irritation from subcutaneous methadone that occurred was managed satisfactorily by changing the infusion site and limiting doses to 30 mg. In seven of 182 repeat administration, injection site changes were necessitated by local irritation. The NRS for local discomfort was 2/10. The two patients who were intolerant of the subcutaneous injections were receiving injected doses which were significantly higher than the others (42 mg as compared to 25 mg). Dose adjustments needed when changing from the oral to the

Hepatitis C virus infection influences the S-methadone metabolite plasma concentration.

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Shiow-Ling Wu

Full Text Available Heroin-dependent patients typically contract hepatitis C virus (HCV at a disproportionately high level due to needle exchange. The liver is the primary target organ of HCV infection and also the main organ responsible for drug metabolism. Methadone maintenance treatment (MMT is a major treatment regimen for opioid dependence. HCV infection may affect methadone metabolism but this has rarely been studied. In our current study, we aimed to test the hypothesis that HCV may influence the methadone dosage and its plasma metabolite concentrations in a MMT cohort from Taiwan.A total of 366 MMT patients were recruited. The levels of plasma hepatitis B virus (HBV, HCV, human immunodeficiency virus (HIV antibodies (Ab, liver aspartate aminotransferase (AST and alanine aminotransferase (ALT, as well as methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP were measured along with the urine morphine concentration and amphetamine screening.Of the 352 subjects in our cohort with HCV test records, 95% were found to be positive for plasma anti-HCV antibody. The liver functional parameters of AST (Wilcoxon Rank-Sum test, P = 0.02 and ALT (Wilcoxon Rank-Sum test, P = 0.04, the plasma methadone concentrations (Wilcoxon Rank-Sum test, P = 0.043 and the R-enantiomer of methadone concentrations (Wilcoxon Rank-Sum test, P = 0.032 were significantly higher in the HCV antibody-positive subjects than in the HCV antibody-negative patients, but not the S-EDDP/methadone dose ratio. The HCV levels correlated with the methadone dose (β= 14.65 and 14.13; P = 0.029 and 0.03 and the S-EDDP/methadone dose ratio (β= -0.41 and -0.40; P = 0.00084 and 0.002 in both univariate and multivariate regression analyses.We conclude that HCV may influence the methadone dose and plasma S-EDDP/methadone dose ratio in MMT patients in this preliminary study.

A national study of the retention of Irish opiate users in methadone substitution treatment

LENUS (Irish Health Repository)

Mullen, Louise

2012-07-02

Background: Retention in treatment is a key indicator of methadone treatment success. The study aims to identify factors that are associated with retention. Objectives: To determine retention in treatment at 12 months for Irish opiate users in methadone substitution treatment and to indicate factors that increase the likelihood of retention. Methods: National cohort study of randomly selected opiate users commencing methadone treatment in 1999, 2001, and 2003 (n = 1269). Results: Sixty-one percent of patients attending methadone treatment remained in continuous treatment for more than 1 year. Retention in treatment at 12 months was associated with age, gender, facility type, and methadone dose. Age and gender were no longer significant when adjusted for other variables in the model. Those who attended a specialist site were twice as likely to leave methadone treatment within 12 months compared with those who attended a primary care physician. The most important predictor of retention in treatment was methadone dose. Those who received <60 mg of methadone were three times more likely to leave treatment. Conclusion: Retention in methadone treatment is high in Ireland in a variety of settings. The main factors influencing retention in methadone treatment was an adequate methadone dose and access to a range of treatment settings including from primary care physicians. Scientific Significance: Providing an adequate dose of methadone during treatment will increase the likelihood of treatment retention. Methadone treatment by the primary care physician is a successful method of retaining opioid users in treatment.

Effects of methadone hydrochloride on the growth of organotypic cerebellar cultures prepared from methadone-tolerant and control rats.

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Willson, N J; Schneider, J F; Roizin, L; Fleiss, J F; Rivers, W; Demartini, J E

1976-11-01

Male and female Sprague-Dawley rats were given dl-methadone (5 mg/kg) for at least 3 months and then mated. The drug was continued throughout pregnancy and after delivery. The newly born pups were divided into two groups. One group was tested for in vivo methadone tolerance, while the animals in the othergroup were used to prepare organotypic cerebellar cultures. Various amounts of dl-methadone were added to the media of half of these cerebellum cultures. The effect of the drug in the medium was assessed by measuring explant outgrowth. Similar experiments were carried out with control animals. Statistical analysis of the data obtained in the in vivo portion of the experiment indicates that the pups of methadone-treated mothers tolerate methadone better than those of untreated mothers. The culture experiments revealed that the addition of methadone to the medium reduced explant outgrowth size and this was a dose-related effect. Also, there was significantly less outgrowth from explants prepared using pups of methadone-treated mothers as compared to the controls. There was no significant difference in the effect of methadone on the growth of cultures prepared from the methadone-tolerant and control animals.

Prospective multicenter observational study of 260 infants born to 259 opiate-dependent mothers on methadone or high-dose buprenophine substitution.

Science.gov (United States)

Lejeune, Claude; Simmat-Durand, Laurence; Gourarier, Laurent; Aubisson, Sandrine

2006-05-20

Specialized prenatal care and substitution programs improve the perinatal prognoses of pregnant drug-abusers and their infants. Although methadone is well documented, little is known about high-dose buprenorphine (HDB). This prospective, multicenter (n = 35) observational study included 259 women on maintenance during pregnancy: 39% on methadone and 61% on HDB. Major findings were: 46% of them received good prenatal care; 62% had peridural analgesia; 12.3% delivered prematurely (hydrochloride. No baby died. Newborns were discharged with their mothers (96%) or placed in foster care (4%). Comparing methadone with HDB, respectively, mean age at the maximum Lipsitz score was 81 h versus 66 h (P = 0.066). The perinatal medical and social prognoses for these 259 drug addicts and their infants appeared to be improved by specialized prenatal care and was similar for methadone or BHD substitution during pregnancy.

Methadone and perinatal outcomes: a prospective cohort study.

LENUS (Irish Health Repository)

Cleary, Brian J

2012-08-01

  Methadone use in pregnancy has been associated with adverse perinatal outcomes and neonatal abstinence syndrome (NAS). This study aimed to examine perinatal outcomes and NAS in relation to (i) concomitant drug use and (ii) methadone dose.

Methadone conversion in infants and children: Retrospective cohort study of 199 pediatric inpatients.

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Fife, Alexandra; Postier, Andrea; Flood, Andrew; Friedrichsdorf, Stefan J

2016-01-01

Methadone administration has increased in pediatric clinical settings. This review is an attempt to ascertain an equianalgesic dose ratio for methadone in the pediatric population using standard adult dose conversion guidelines. US tertiary children's hospital. Hospitalized pediatric patients, 0-18 years of age. A retrospective chart review was conducted for patients who were converted from their initial opioid therapy regimen (morphine, hydromorphone, and/or fentanyl) to methadone. The primary endpoint was whether or not a dose correction was needed for methadone in the 6 days following conversion using standard dose conversion charts for adults. Documented clinical signs of withdrawal, unrelieved pain, or oversedation were examined. The majority (53.7 percent) of the 199 children were converted to methadone on intensive care units prior extubation or postextubation. The mean conversion ratio was 23.7 mg of oral morphine to 1 mg of oral methadone (median, 18.8 mg:1 mg, SD=25.7). Most patients experienced an adequate conversion (n=115, 57.8 percent), while 83 (41.7 percent) appeared undermedicated, and one child was oversedated. There were no associations found with conversion ratios for initial morphine dose, days to conversion, or effect of withdrawal of concomitant agents with potential for withdrawal. Opioid conversion to methadone is commonly practiced at our institution; however, dosing was significantly lower compared to adult conversion ratios, and more than 40 percent of children were undermedicated. The majority of children in this study received opioids for sedation while intubated and ventilated; therefore, safe and efficacious pediatric methadone conversion rates remain unclear. Prospective studies are needed.

Methadone Related Poisoning on the Rise in Tehran, Iran

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Kambiz Soltaninejad

2014-09-01

Full Text Available Background: In Iran, methadone has been used for methadone maintenance treatment (MMT as well as analgesic treatment in pain clinics. Recently, there are some reports regarding accidental and intentional methadone poisonings and deaths. The aim of this study was to evaluate the trend of methadone poisonings and deaths during a 10-year period in Tehran, Iran. Methods: This was a retrospective cross-sectional study over 2000 to 2010. Patients with a documented methadone poisoning who were admitted in Loghman Hakim Hospital Poison Center in Tehran, Iran were identified and included in the study. The data including patients’ age, gender, ingested dose, co-ingestants, intention of ingestion and outcome were extracted from the patients’ medical records. Results: During the study period, 1426 cases of methadone poisoning were recorded, of which, 1041 cases (73% were men. Thirty-six cases (2.5% died. Mean age of the patients was 29.9 ± 17 years. In 476 cases, the intention of poisoning could not be determined, and in the remaining, the intention was misuse (n = 273, 28.7%, suicide (n = 254, 26.7%, accidental (n = 245, 25.8% and abuse (n = 178, 18.8%. Mean of the ingested dose of methadone was 120.6 ± 306.8 mg. The incidence of acute methadone poisoning per one million population of Tehran was 0.43 in 2000 that rose to 37.62 in 2010. Conclusion: The results indicate that methadone poisoning and deaths have increased in Tehran. MMT clinics should be strictly run according to the national guideline to prevent methadone poisoning. With regard to high frequency of poly-drug use in methadone poisoning, it seems important to warn health care providers against prescription of other drugs with methadone. 

Out-of-hospital mortality among patients receiving methadone for noncancer pain.

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Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Cooper, William O; Hall, Kathi; Stein, C Michael

2015-03-01

Growing methadone use in pain management has raised concerns regarding its safety relative to other long-acting opioids. Methadone hydrochloride may increase the risk for lethal respiratory depression related to accidental overdose and life-threatening ventricular arrhythmias. To compare the risk of out-of-hospital death in patients receiving methadone for noncancer pain with that in comparable patients receiving sustained-release (SR) morphine sulfate. A retrospective cohort study was conducted using Tennessee Medicaid records from 1997 through 2009. The cohort included patients receiving morphine SR or methadone who were aged 30 to 74 years, did not have cancer or another life-threatening illness, and were not in a hospital or nursing home. At cohort entry, 32 742 and 6014 patients had filled a prescription for morphine SR or methadone, respectively. The patients' median age was 48 years, 57.9% were female, and comparable proportions had received cardiovascular, psychotropic, and other musculoskeletal medications. Nearly 90% of the patients received the opioid for back pain or other musculoskeletal pain. The median doses prescribed for morphine SR and methadone were 90 mg/d and 40 mg/d, respectively. The primary study end point was out-of-hospital mortality, given that opioid-related deaths typically occur outside the hospital. There were 477 deaths during 28 699 person-years of follow-up (ie, 166 deaths per 10 000 person-years). After control for study covariates, patients receiving methadone had a 46% increased risk of death during the follow-up period, with an adjusted hazard ratio (HR) of 1.46 (95% CI, 1.17-1.83; P Methadone doses of 20 mg/d or less, the lowest dose quartile, were associated with an increased risk of death (HR, 1.59; 95% CI, 1.01-2.51, P = .046) relative to a comparable dose of morphine SR (methadone in this retrospective cohort study, even for low doses, supports recommendations that it should not be a drug of first choice for

A randomized controlled trial of interim methadone maintenance.

Science.gov (United States)

Schwartz, Robert P; Highfield, David A; Jaffe, Jerome H; Brady, Joseph V; Butler, Carol B; Rouse, Charles O; Callaman, Jason M; O'Grady, Kevin E; Battjes, Robert J

2006-01-01

Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry. To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior. Randomized, controlled, clinical trial using 2 conditions, with treatment assignment on a 3:2 basis to interim maintenance-waiting list control. A methadone treatment program in Baltimore. A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment. Participants were randomly assigned to either interim methadone maintenance, consisting of an individually determined methadone dose and emergency counseling only for up to 120 days, or referral to community-based methadone treatment programs. Entry into comprehensive methadone maintenance therapy at 4 months from baseline; self-reported days of heroin use, cocaine use, and criminal behavior; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment (or at 4 months from baseline for participants who did not enter regular treatment). Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline (75.9%) than those assigned to the waiting list control condition (20.8%) (Pmethadone maintenance results in a substantial increase in the likelihood of entry into comprehensive treatment, and is an effective means of reducing heroin use and criminal behavior among opioid-dependent individuals awaiting entry into a comprehensive methadone treatment program.

Pharmacokinetic properties of methadone hydrochloride after single intramuscular administration in adult dairy goats.

Science.gov (United States)

Kock, M; Thompson, E; Vulliet, P R; Brooks, D L

1994-10-01

Pharmacokinetic parameters of methadone were studied in adult dairy goats. Five goats were each given methadone hydrochloride as a single 0.2 mg/kg of body weight dosage by intramuscular (IM) administration. Plasma methadone concentrations were determined for 96 h after dosing. Plasma methadone concentrations after IM administration were best described by an open one-compartment model. Overall elimination half-life (t1/2) was 1.38 h. Peak plasma concentrations were reached 0.25 h after dosing, and the actual plasma concentration averaged 37.8 ng/ml (SD = 12.76) at that time. The data obtained from this study suggest that plasma concentrations, similar to those that are analgesic in humans, can be achieved after IM administration of methadone at a dose rate of 0.2 mg/kg of body weight. In addition, these plasma concentrations can be maintained for up to 3 h after a single injection and, therefore, may provide satisfactory analgesia for such period.

Comparison of buprenorphine and methadone effects on opiate self-administration in primates.

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Mello, N K; Bree, M P; Mendelson, J H

1983-05-01

The effects of ascending and descending doses of buprenorphine (0.014-0.789 mg/kg/day) and methadone (0.179-11.86 mg/kg/day) on opiate and food intake were studied in Macaque monkeys over 195 to 245 days. Food (1-g banana pellets) and i.v. drug self-administration (heroin 0.01 or 0.02 mg/kg/injection or Dilaudid 0.02 mg/kg/injection) were maintained on a second-order schedule of reinforcement [FR 4 (VR 16:S)]. Buprenorphine (0.282-0.789 mg/kg/day) produced a significant suppression of opiate self-administration at 2.5 to 7 times the dose shown to be effective in human opiate abusers (P less than .05-.001). Methadone (1.43-11.86 mg/kg/day) did not suppress opiate self-administration in four of five monkeys across a dose range equivalent to 100 to 800 mg/day in man. The distribution of opiate self-administration across drug sessions did not account for the absence of methadone suppression as monkeys took 43% of the total daily opiate injections during the first daily drug session, 2.5 hr after methadone administration. During buprenorphine maintenance, food intake remained stable or increased significantly above base-line levels. Methadone maintenance was associated with significant decrements in food intake in four of five monkeys. Buprenorphine appeared to be significantly more effective in suppressing opiate self-administration than methadone across the dose range studied. Buprenorphine had none of the toxic side effects (seizures, respiratory depression, profound psychomotor retardation) associated with high doses of methadone over 6 to 8 months of daily drug treatment. These data are consistent with clinical studies of buprenorphine effects on heroin self-administration in human opiate addicts.

Priapism Followed by Discontinuation of Methadone: A rare Case Report

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Seyed-Ali Mostafavi

2015-10-01

Full Text Available Objective: Priapism is defined by persistent, painful penile erection which occurs without sexual stimulation. Methadone is used as an analgesic and is also used in detoxification and maintenance protocol for opioid dependence treatment. Here we will report a case of a male with priapism after rapid discontinuation doses of methadone.Case presentation: The case was a young married male who referred to a psychiatry clinic due to long-time spontaneous erections. The patient had no history of mental disorders, trauma or sickle cell anemia. He used to smoke opium for five years and used methadone for four years at a dose of 17 cc daily, which he abruptly discontinued. Then he often experienced spontaneous and painful erections without physical or mental stimulation that caused him shame and embarrassment .Conclusion: In this case, chronology indicates that rapid discontinuation of methadone was possibly responsible for the occurrence of priapism. This may have happened due to a compensatory reaction to methadone side effect of erectile dysfunction, followed by its rapid withdrawal.

Using [11C]diprenorphine to image opioid receptor occupancy by methadone in opioid addiction: clinical and preclinical studies.

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Melichar, Jan K; Hume, Susan P; Williams, Tim M; Daglish, Mark R C; Taylor, Lindsay G; Ahmad, Rabia; Malizia, Andrea L; Brooks, David J; Myles, Judith S; Lingford-Hughes, Anne; Nutt, David J

2005-01-01

Substitute methadone prescribing is one of the main modes of treatment for opioid dependence with established evidence for improved health and social outcomes. However, the pharmacology underpinning the effects of methadone is little studied despite controversies about dosing in relation to outcome. We therefore examined the relationship between methadone dose and occupation of opioid receptors in brain using the positron emission tomography (PET) radioligand [(11)C]diprenorphine in humans and rats. Eight opioid-dependent subjects stable on their substitute methadone (18-90 mg daily) had an [(11)C]diprenorphine PET scan at predicted peak plasma levels of methadone. These were compared with eight healthy controls. No difference in [(11)C]diprenorphine binding was found between the groups, with no relationship between methadone dose and occupancy. Adult male Sprague-Dawley rats that had been given an acute i.v. injection of methadone hydrochloride (0.35, 0.5, 0.7, or 1.0 mg kg(-1)) before [(11)C]diprenorphine showed a dose-dependent increase in biodistribution but no reduction in [(11)C]diprenorphine binding. We suggest that the lack of a dose-dependent relationship between methadone dose, either given chronically in human or acutely in rat, and occupancy of opioid receptor measured with [(11)C]diprenorphine PET is related to efficacy of this opioid agonist at very low levels of opioid receptor occupancy. This has implications for understanding the actions of methadone in comparison with other opioid drugs such as partial agonists and antagonists.

Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer?

Science.gov (United States)

George, Rani; Haywood, Alison; Good, Phillip; Hennig, Stefanie; Khan, Sohil; Norris, Ross; Hardy, Janet

2017-09-01

Methadone is a potent analgesic used to treat refractory cancer pain. It is administered as a racemic mixture, with the l-enantiomer being primarily a μ-receptor agonist, whereas the d-enantiomer is an N-methyl-d-aspartate antagonist and inhibits serotonin and norepinephrine reuptake. Dose requirements vary greatly among patients to achieve optimal pain control and to avoid the risk of adverse effects. The relationship between plasma and saliva methadone enantiomer concentrations was investigated to determine if saliva could be a substitute for plasma in pharmacodynamic and pharmacokinetic studies for clinical monitoring and dose optimization of methadone in patients with advanced cancer. Patients with advanced cancer who were prescribed varying doses of oral methadone for pain management were recruited to obtain paired plasma and saliva samples. Pain scores were recorded at the time of sampling. The total and unbound plasma and saliva concentrations of the l- and d-enantiomers of methadone were quantified by using an HPLC-MS/MS method. The relationship between plasma (total and unbound) and saliva concentrations were compared. The saliva-to-plasma concentration ratio was compared versus the dose administered and the time after dosing for both enantiomers. The association of methadone concentrations with reported pain scores was compared by using a Mann-Whitney U test for significance. Fifty patients receiving a mean dose of 11mg/d of methadone provided 151 paired plasma and saliva samples. The median age of the population was 61 years with an interquartile range of 53-71 years with total body weight ranging from 59-88 kg. Median (interquartile) total plasma concentrations for l- and d-methadone were 50.78 ng/mL (30.6-113.0 ng/mL) and 62.0 ng/mL (28.7-116.0 ng/mL), respectively. Median (interquartile range) saliva concentrations for l- and d-methadone were 81.5 ng/mL (28.0-203.2 ng/mL) and 44.2 (16.2-149.7 ng/mL). No relationship could be established between

Assay for methadone

International Nuclear Information System (INIS)

1980-01-01

An improved radioimmunoassay for methadone is described using a novel antigen, antibody and labelled methadone derivatives. The preparation of a hemi-ester antigen is described by reacting a methadone derivative with succinic anhydride or glutaric anhydride; this hapten is then covalently bonded through the carboxyl group to bovine serum albumin. An antibody specific to methadone is produced by inoculating a host animal with the above antigen. The unknown amount of methadone in a sample is then determined by mixing the sample with a known amount of radiolabelled methadone derivative and the above antibody and comparing the degree of binding to a standard curve obtained by mixing the antibody with known amounts of methadone and fixed amounts of labelled methadone derivative. The radioimmunoassay was used to measure methadone levels in urine from individuals attending a methadone clinic. (U.K.)

A review of common methods to convert morphine to methadone

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Eric Wong

2013-01-01

Full Text Available When dosed appropriately on carefully chosen patients, methadone can be a very safe and effective choice in managing chronic pain. Many authors have discussed important issues surrounding patient selection, drug interactions, screening for QTc prolongation and monitoring. This article will focus on the dosing dilemma that exists after the patient is deemed an appropriate candidate for methadone and a conversion is necessary from another opioid. Despite many publications dedicated to addressing this challenging topic, there is no consensus on the most appropriate method for converting an opioid regimen to methadone. Given the lack of concrete guidance, clinicians in a community setting are likely to be faced with an increased challenge if there are no available pain specialists to provide clinical support. Common methods for converting morphine to methadone will be reviewed and two clinical patient scenarios used to illustrate the outcomes of applying the methods.

Perinatal exposure to methadone affects central cholinergic activity in the weanling rat.

Science.gov (United States)

Robinson, S E; Mo, Q; Maher, J R; Wallace, M J; Kunko, P M

1996-06-01

Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. Perinatal methadone exposure disrupted cholinergic activity on postnatal day 21 as measured by the turnover rate of acetylcholine (TRACh) in both female and male rats, although there were some sexually-dimorphic responses. The most profoundly affected brain region was the striatum, where prenatal exposure to methadone increased ACh turnover, whether or not the rats continued to be exposed to methadone postnatally. It appears unlikely that neonatal withdrawal contributes to brain regional changes in ACh turnover, as continued postnatal exposure to methadone did not prevent the prenatal methadone induced changes.

The disposition and behavioral effects of methadone in Greyhounds.

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KuKanich, Butch; Borum, Stacy L

2008-05-01

To determine the behavioral effects and pharmacokinetics of methadone in healthy Greyhounds. Prospective experimental study. Three male and three female healthy Greyhounds. Methadone hydrochloride, 0.5 mg kg(-1) IV (equivalent to 0.45 mg kg(-1) methadone base), was administered as an IV bolus. Trained observers subjectively assessed the behavioral effects of methadone. Blood samples were obtained at predetermined time points and plasma methadone concentrations were measured by liquid chromatography with tandem mass spectrometry. Pharmacokinetic variables were estimated with computer software. Methadone was well tolerated by the dogs with panting and defecation observed as adverse effects. Mild sedation was present, but no vomiting, excitement, or dysphoria was observed. The elimination half-life, volume of distribution, and plasma clearance were 1.53 +/- 0.18 hours, 7.79 +/- 1.87 L kg(-1), and 56.04 +/- 9.36 mL minute(-1) kg(-1), respectively. Methadone was well tolerated by Greyhounds. The volume of distribution was larger than expected, with resultant lower plasma concentrations than expected. Higher doses may need to be administered to Greyhounds in comparison with non-Greyhound dogs in order to achieve similar plasma drug concentrations. A dosage of 1-1.5 mg kg(-1) every 3-4 hours is suggested for future studies of analgesic efficacy of methadone in Greyhounds.

Evaluation Of Methadone Poisoning in Hospitalized Children: A Short Review

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Gholamali Maamouri

2014-08-01

Full Text Available Upload poisoning is one of the most dangerous and common poisoning in Iranian children. Depression of the respiratory and central nervous systems may lead to significant toxicity. Even low doses of uploads are dangerous in pediatrics under 6 years old. Methadone is the most toxic of the uploads; small doses as low as a single tablet can lead to death. According to this information we decided to evaluate methadone poisoning in Hospitalized Children

ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.

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Coller, Janet K; Barratt, Daniel T; Dahlen, Karianne; Loennechen, Morten H; Somogyi, Andrew A

2006-12-01

The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.

The Role of Program Directors in Treatment Practices: The Case of Methadone Dose Patterns in U.S. Outpatient Opioid Agonist Treatment Programs.

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Frimpong, Jemima A; Shiu-Yee, Karen; D'Aunno, Thomas

2017-10-01

To describe changes in characteristics of directors of outpatient opioid agonist treatment (OAT) programs, and to examine the association between directors' characteristics and low methadone dosage. Repeated cross-sectional surveys of OAT programs in the United States from 1995 to 2011. We used generalized linear regression models to examine associations between directors' characteristics and methadone dose, adjusting for program and patient factors. Data were collected through telephone surveys of program directors. The proportion of OAT programs with an African American director declined over time, from 29 percent in 1995 to 16 percent in 2011. The median percentage of patients in each program receiving role in explaining variations in methadone dosage across programs and patients. Further research should investigate the causal pathways through which directors' characteristics affect treatment practices. This may lead to new, multifaceted managerial interventions to improve patient outcomes. © Health Research and Educational Trust.

Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial.

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Rich, Josiah D; McKenzie, Michelle; Larney, Sarah; Wong, John B; Tran, Liem; Clarke, Jennifer; Noska, Amanda; Reddy, Manasa; Zaller, Nickolas

2015-07-25

Methadone is an effective treatment for opioid dependence. When people who are receiving methadone maintenance treatment for opioid dependence are incarcerated in prison or jail, most US correctional facilities discontinue their methadone treatment, either gradually, or more often, abruptly. This discontinuation can cause uncomfortable symptoms of withdrawal and renders prisoners susceptible to relapse and overdose on release. We aimed to study the effect of forced withdrawal from methadone upon incarceration on individuals' risk behaviours and engagement with post-release treatment programmes. In this randomised, open-label trial, we randomly assigned (1:1) inmates of the Rhode Island Department of Corrections (RI, USA) who were enrolled in a methadone maintenance-treatment programme in the community at the time of arrest and wanted to remain on methadone treatment during incarceration and on release, to either continuation of their methadone treatment or to usual care--forced tapered withdrawal from methadone. Participants could be included in the study only if their incarceration would be more than 1 week but less than 6 months. We did the random assignments with a computer-generated random permutation, and urn randomisation procedures to stratify participants by sex and race. Participants in the continued-methadone group were maintained on their methadone dose at the time of their incarceration (with dose adjustments as clinically indicated). Patients in the forced-withdrawal group followed the institution's standard withdrawal protocol of receiving methadone for 1 week at the dose at the time of their incarceration, then a tapered withdrawal regimen (for those on a starting dose >100 mg, the dose was reduced by 5 mg per day to 100 mg, then reduced by 3 mg per day to 0 mg; for those on a starting dose >100 mg, the dose was reduced by 3 mg per day to 0 mg). The main outcomes were engagement with a methadone maintenance-treatment clinic after release from

Stress-opioid interactions: a comparison of morphine and methadone.

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Taracha, Ewa; Mierzejewski, Paweł; Lehner, Małgorzata; Chrapusta, Stanisław J; Kała, Maria; Lechowicz, Wojciech; Hamed, Adam; Skórzewska, Anna; Kostowski, Wojciech; Płaźnik, Adam

2009-01-01

The utility of methadone and morphine for analgesia and of methadone for substitution therapy for heroin addiction is a consequence of these drugs acting as opioid receptor agonists.We compared the cataleptogenic and antinociceptive effects of single subcutaneous doses of methadone hydrochloride (1-4 mg/kg) and morphine sulfate (2.5-10 mg/kg) using catalepsy and hot-plate tests, and examined the effects of the highest doses of the drugs on Fos protein expression in selected brain regions in male Sprague-Dawley rats. Methadone had greater cataleptogenic and analgesic potency than morphine. Fos immunohistochemistry revealed substantial effects on the Fos response of both the stress induced by the experimental procedures and of the drug exposure itself. There were three response patterns identified: 1) drug exposure, but not stress, significantly elevated Fos-positive cell counts in the caudate-putamen; 2) stress alone and stress combined with drug exposure similarly elevated Fos-positive cell counts in the nucleus accumbens and cingulate cortex; and 3) methadone and morphine (to a lesser extent) counteracted the stimulatory effect of nonpharmacological stressors on Fos protein expression in the somatosensory cortex barrel field, and Fos-positive cell counts in this region correlated negatively with both the duration of catalepsy and the latency time in the hot-plate test. The overlap between brain regions reacting to nonpharmacological stressors and those responding to exogenous opioids suggests that stress contributes to opioid-induced neuronal activation.

Methadone, monoamine oxidase, and depression: opioid distribution and acute effects on enzyme activity

International Nuclear Information System (INIS)

Kaufmann, C.A.; Kreek, M.J.; Raghunath, J.; Arns, P.

1983-01-01

Narcotic withdrawal is often accompanied by an atypical depression which responds to resumption of narcotics. It was hypothesized that methadone might exert its antidepressant effects through monoamine oxidase (MAO) inhibition. The current study examined 3 H-methadone distribution in rat brain and effects on regional MAO activity with acute doses (2.5 mg/kg) which approximate those found during chronic methadone maintenance in man. Limbic areas (amygdala, basomedial hypothalamus, caudate-putamen, hippocampus, preoptic nucleus), as well as pituitary and liver were assayed for MAO activity and methadone concentration. MAO activities did not differ significantly in acute methadone or saline-treated cage-mates at 1 or 24 hr. The concentrations of methadone at 1 hr ranged between 17 and 223 ng/100 mg wet wt tissue in the preoptic nucleus and pituitary, respectively. No significant correlation was found between change in MAO activity (MAO methadone/MAO saline) and methadone concentration in any region at 1 or 24 hr. This study does not support the hypothesis that methadone acts as an antidepressant through MAO inhibition, at least not following acute administration of this exogenous opioid

Comparison of tincture of opium and methadone to control opioid withdrawal in a Thai treatment centre

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Jittiwutikarn, Jaroon; Ali, Robert; White, Jason M; Bochner, Felix; Somogyi, Andrew A; Foster, David J R

2004-01-01

Aims To evaluate the effectiveness of oral tincture of opium (TOP) and methadone to control opioid withdrawal in patients in northern Thailand. Methods Open label, parallel group study in an inpatient facility compared 15 former heroin users receiving methadone 5–20 mg 12 hourly with 15 former opium smokers receiving TOP (3.33–10 mg morphine equivalents 12 hourly). At 0, 1, 3 and 8 h, blood, withdrawal scores and subjective opioid effects were collected. Results There was a reciprocal association between withdrawal scores/direct subjective opioid effects and plasma (R)-methadone, but not plasma morphine, concentrations. Withdrawal scores at the time of dosing were higher in the TOP patients (9.1 ± 3) than in the methadone patients (4.5 ± 4.6) and in the TOP patients were significantly (P = 0.001) attenuated at 3 and 8 h. Conclusions At the doses used, TOP was inferior to methadone in suppressing withdrawal. It could prove to be a cost effective and valuable drug, but only after dose size and frequency are further investigated. PMID:15521902

Clinical use of methadone.

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Layson-Wolf, Cherokee; Goode, Jean-Venable; Small, Ralph E

2002-01-01

Methadone hydrochloride is a mu-opioid agonist that has been used for the treatment of pain and for the management and maintenance of opioid withdrawal for over 50 years. Several characteristics make methadone a useful drug. However, these same characteristics and wide interpatient variability can make methadone difficult to use safely. A MEDLINE search was conducted on publications between January 1996 and May 2001 to identify literature relevant to this subject. Those publications were reviewed, and from them, other literature was identified and reviewed. Published studies demonstrate methadone's efficacy in pain management and in opioid withdrawal. However, interpatient variability in pharmacokinetic variables of methadone produces difficulties in developing guidelines for methadone use. Clinicians should not be deterred from use of this drug which has been shown to benefit patients in both pain management and methadone maintenance, but an individualized patient approach must be taken to use methadone safely.

Influence of acute and chronic administration of methadone hydrochloride on NADPH-cytochrome c reductase and cytochrome P-450 of mouse liver microsomes.

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Datta, R K; Johnson, E A; Bhattacharjee, G; Stenger, R J

1976-03-01

Administration of a single acute dose (20 mg/kg body weight) of methadone hydrochloride to both male and female mice increased the specific activity of NADPH-cytochrome c reductase and did not change much the content of cytochrome P-450 of their liver microsomes. Administration of multiple acute doses of methadone in male mice increased the specific activity of cytochrome c reductase and the content of cytochrome P-450 of their liver microsomes. Chronic administration of progressively increasing doses of methadone (up to 40 mg/kg body weight) to male mice increased the specific activity of c reductase. Similar chronic administration of methadone up to 28 mg/kg body weight also increased the microsomal content of P-450, but with higher doses of methadone, the content of P-450 declined and finally dropped slightly below control levels. The levels of c reductase activity and P-450 content returned to normal about two weeks after discontinuation of methadone administration.

In silico ordinary differential equation/partial differential equation hemodialysis model estimates methadone removal during dialysis.

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Linares, Oscar A; Schiesser, William E; Fudin, Jeffrey; Pham, Thien C; Bettinger, Jeffrey J; Mathew, Roy O; Daly, Annemarie L

2015-01-01

There is a need to have a model to study methadone's losses during hemodialysis to provide informed methadone dose recommendations for the practitioner. To build a one-dimensional (1-D), hollow-fiber geometry, ordinary differential equation (ODE) and partial differential equation (PDE) countercurrent hemodialyzer model (ODE/PDE model). We conducted a cross-sectional study in silico that evaluated eleven hemodialysis patients. Patients received a ceiling dose of methadone hydrochloride 30 mg/day. Outcome measures included: the total amount of methadone removed during dialysis; methadone's overall intradialytic mass transfer rate coefficient, km ; and, methadone's removal rate, j ME. Each metric was measured at dialysate flow rates of 250 mL/min and 800 mL/min. The ODE/PDE model revealed a significant increase in the change of methadone's mass transfer with increased dialysate flow rate, %Δkm =18.56, P=0.02, N=11. The total amount of methadone mass transferred across the dialyzer membrane with high dialysate flow rate significantly increased (0.042±0.016 versus 0.052±0.019 mg/kg, P=0.02, N=11). This was accompanied by a small significant increase in methadone's mass transfer rate (0.113±0.002 versus 0.014±0.002 mg/kg/h, P=0.02, N=11). The ODE/PDE model accurately predicted methadone's removal during dialysis. The absolute value of the prediction errors for methadone's extraction and throughput were less than 2%. ODE/PDE modeling of methadone's hemodialysis is a new approach to study methadone's removal, in particular, and opioid removal, in general, in patients with end-stage renal disease on hemodialysis. ODE/PDE modeling accurately quantified the fundamental phenomena of methadone's mass transfer during hemodialysis. This methodology may lead to development of optimally designed intradialytic opioid treatment protocols, and allow dynamic monitoring of outflow plasma opioid concentrations for model predictive control during dialysis in humans.

Disposition of nasal, intravenous, and oral methadone in healthy volunteers.

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Dale, Ola; Hoffer, Christine; Sheffels, Pamela; Kharasch, Evan D

2002-11-01

Nasal administration of many opioids demonstrates rapid uptake and fast onset of action. Nasal administration may be an alternative to intravenous and oral administration of methadone and was therefore studied in human volunteers. The study was approved by the Institutional Review Board of the University of Washington, Seattle. Eight healthy volunteers (6 men and 2 women) aged 19 to 33 years were enrolled after informed written consent was obtained. Subjects received 10 mg methadone hydrochloride nasally, orally, or intravenously on 3 separate occasions in a crossover design. Nasal methadone (50 mg/mL in aqueous solution) was given as a 100-microL spray in each nostril (Pfeiffer BiDose sprayer). Blood samples for liquid chromatography-mass spectrometry analyses of methadone and the metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were drawn for up to 96 hours. The methadone effect was measured by noninvasive infrared pupilometry coincident with blood sampling. Nasal uptake of methadone was rapid, with maximum plasma concentrations occurring within 7 minutes. The maximum effects of intravenous, nasal, and oral methadone, on the basis of dark-adapted pupil diameter, were reached in about 15 minutes, 30 minutes, and 2 hours, respectively. The respective durations were 24, 10, and 8 hours. Both nasal and oral bioavailabilities were 0.85. Subjects reported that nasal methadone caused a burning sensation. Nasal administration of methadone results in rapid absorption and onset of effect and high bioavailability, which was greater than that reported for other nasal opioids, with a similar duration of effect. Nasal administration may be an alternative route of methadone administration; however, improved formulations are desirable to reduce nasal irritation.

The Possible Effects of Methadone Maintenance Therapy on Erectile Dysfunction in Male Addicts Visiting MMT Centers of Rasht

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Morteza Rahbar Taramsari

2014-06-01

Full Text Available Background: Methadone is considered a long-acting opioid agonist which is widely used in the treatment of drug addiction. It is believed that opioids can cause erectile dysfunction (ED by inhibiting gonadotropin and testosterone release. This study is aimed at defining the possible effects of conservative treatment with methadone on erectile dysfunction in the addicts. Methods: A total of 382 male addicts visiting methadone maintenance therapy (MMT centers in Rasht, Iran, during 2010 were enrolled in this study. International Index of Erectile Function (IIEF questionnaire and patients' profiles were the main means of collecting data on demographic information, methadone dose intake, and erectile function status before and after the two months of therapy with methadone. Erectile function status was defined by the total score from questions 1, 2, 3, 4, 5, and 15 of the questionnaire. The data was analyzed by X2, McNemer’s test, and paired t-test using SPSS software 18. Results: The mean age of patients was 37.6 ± 8.9 years (range: 18-72 years. Most of the patients were married (79.3% and they were citizens of Rasht (72.3%. The most frequent substances were opium (188 patients, 49.2% and crack (129 patients, 33.8%, respectively. Most of the patients received low dose methadone (286 patients, 74.9%. No significant relationship was indicated comparing the average scores of erectile function before and after taking methadone (18.53±6.978 vs. 19.03±5.819 (P=0.138. However, the severity of erectile dysfunction was significantly related to the methadone intake dose (P<0.001. Conclusion: Although MMT increases the frequency of erectile dysfunction, appropriate doses of methadone minimize this effect.

Methadone, monoamine oxidase, and depression: opioid distribution and acute effects on enzyme activity

Energy Technology Data Exchange (ETDEWEB)

Kaufmann, C.A.; Kreek, M.J.; Raghunath, J.; Arns, P.

1983-09-01

Narcotic withdrawal is often accompanied by an atypical depression which responds to resumption of narcotics. It was hypothesized that methadone might exert its antidepressant effects through monoamine oxidase (MAO) inhibition. The current study examined /sub 3/H-methadone distribution in rat brain and effects on regional MAO activity with acute doses (2.5 mg/kg) which approximate those found during chronic methadone maintenance in man. Limbic areas (amygdala, basomedial hypothalamus, caudate-putamen, hippocampus, preoptic nucleus), as well as pituitary and liver were assayed for MAO activity and methadone concentration. MAO activities did not differ significantly in acute methadone or saline-treated cage-mates at 1 or 24 hr. The concentrations of methadone at 1 hr ranged between 17 and 223 ng/100 mg wet wt tissue in the preoptic nucleus and pituitary, respectively. No significant correlation was found between change in MAO activity (MAO methadone/MAO saline) and methadone concentration in any region at 1 or 24 hr. This study does not support the hypothesis that methadone acts as an antidepressant through MAO inhibition, at least not following acute administration of this exogenous opioid.

Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses.

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Crosignani, N; Luna, S P; Dalla Costa, T; Pimenta, E L; Detoni, C B; Guterres, S S; Puoli Filho, J N; Pantoja, J C; Pigatto, M C

2017-08-01

We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated-measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed-rank, adjusted by Bonferroni tests. Blood samples were also collected up to 6 h after dosing for plasma drug quantification by LC-MS/MS. Methadone pharmacokinetic parameters were determined by noncompartmental and compartmental approaches. There were no differences in pharmacodynamic parameters. No statistical differences were observed in the pharmacokinetic parameters from noncompartmental analysis for both groups, except a significant decrease in peak plasma concentration, increase in apparent volume of distribution per fraction absorbed (Vd ss /F) and increased mean residence time (MRT) for NANO. One-compartment open model with first order elimination best described the pharmacokinetic profiles for both groups. Neither ORAL nor NANO administered orally to horses produced antinociception. The nanoencapsulated formulation of methadone given orally to horses did not improve methadone pharmacokinetic parameters or increased systemic body exposure to methadone. © 2017 John Wiley & Sons Ltd.

Prescribing methadone for pain management in end-of-life care.

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Manfredonia, John F

2005-03-01

Methadone hydrochloride is an effective, inexpensive, and relatively safe opioid to use in the treatment of patients with chronic pain. It is especially effective in management of pain during the final stages of life, as it is the only long-acting analgesic available in liquid form. However, because methadone has a long half-life, individual wide variations, and potential for accumulation and overdosage, physicians must judiciously and conscientiously prescribe it. Also, they should closely monitor patients during the titration phase and educate them with regard to basic pharmacologic properties and potential side effects. A plan to start at low doses and proceed slowly is applicable to methadone.

Perinatal methadone exposure affects dopamine, norepinephrine, and serotonin in the weanling rat.

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Robinson, S E; Maher, J R; Wallace, M J; Kunko, P M

1997-01-01

On gestational day 7 pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. On postnatal day 21, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and their metabolites were analyzed. Perinatal methadone exposure disrupted dopaminergic, noradrenergic, and serotonergic activity in a brain region- and gender-specific fashion. The ratio of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) to DA was reduced in the frontal cortex of males exposed to methadone postnatally. No effects of perinatal methadone exposure were observed on DA and DOPAC in the striatum. The ratio of 3-methoxy-4-hydroxyphenylglycol (MOPEG) to NE in the hippocampus was increased significantly in males exposed to methadone prenatally. Striatal and parietal cortical 5-hydroxyindoleacetic acid (5-HIAA), but not its ratio to 5-HT, was increased slightly in rats exposed to methadone postnatally. Although parietal cortical 5-HT, 5-HIAA, and 5-hydroxytryptophan were all affected by perinatal methadone exposure, the ratios of metabolite and precursor to 5-HT were not affected. Effects of methadone exposure appeared to depend upon the developmental stage at which exposure occurred and did not appear to result from the phenomenon of neonatal withdrawal. Changes in activity of these three neurotransmitter systems may contribute to the effect of perinatal methadone on the activity of other neurons, such as cholinergic neurons.

Breastfeeding considerations of opioid dependent mothers and infants.

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Hilton, Tara C

2012-01-01

The American Academy of Pediatrics (AAP) has a long-standing recommendation against breastfeeding if the maternal methadone dose is above 20 mg/day. In 2001, the AAP lifted the dose restriction of maternal methadone allowing methadone-maintained mothers to breastfeed. The allowance of breastfeeding among mothers taking methadone has been met with opposition due to the uncertainty that exists related to methadone exposure of the suckling infant. Methadone-maintained mothers are at higher risk for abuse, concomitant psychiatric disorders, limited access to healthcare, and financial hardship. Breastfeeding rates among methadone-maintained women tend to be low compared to the national average. This manuscript will discuss the implications for healthcare practitioners caring for methadone-maintained mothers and infants and associated risks and benefits of breastfeeding. This population of mothers and infants stands to obtain particular benefits from the various well-known advantages of breastfeeding.

Rates of fetal polydrug exposures in methadone-maintained pregnancies from a high-risk population.

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Kaitlyn Delano

Full Text Available Methadone maintenance treatment (MMT is the standard of care during pregnancy for opioid-dependency, showing efficacy in improving prenatal care and reducing risk of relapse. By design, however, MMT is only intended to prevent withdrawal thus facilitating cognitive behavioural interventions. In order to maximize the benefits of MMT, it is essential that methadone is both properly prescribed and that additional addiction treatment is concurrently administered. This study aims to determine the effectiveness of MMT engagement in high-risk pregnant women in reducing polydrug use by objective laboratory examination of neonatal meconium.Over a 29-month period, the Motherisk Laboratory at the Hospital for Sick Children in Toronto analyzed meconium samples as per request by social services and hospitals for drugs of abuse.Of the 904 meconium samples received, 273 were tested for methadone with 164 positive and 109 negative for methadone. Almost half of the methadone positive samples (46.34% were also positive for at least one other opioid compound, which did not differ statistically from the methadone-negative control samples (46.79%; Chi square test, p=0.94. No differences were found between the methadone positive and negative groups in rates of concurrent amphetamines, cocaine, cannabis, and alcohol use indicating a similar risk of polydrug use between pregnant women taking or not taking methadone in this population.The high rates of additional opioid and other drug use in the MMT group, suggest that MMT is failing this population of patients. It is possible that methadone doses during pregnancy are not appropriately adjusted for changes in pharmacokinetic parameters (e.g. blood volume, renal function during the second and third trimesters. This may result in sub-therapeutic dosing creating withdrawal symptoms leading to additional substance use. Alternatively, these results may be demonstrating a substantial lack in delivery of addiction support

Approaches to methadone treatment

DEFF Research Database (Denmark)

Järvinen, Margaretha

2008-01-01

and does not focus on the consequences of drug use alone but also on their problematic relationship to drugs (legal as well as illegal). Furthermore, the users’ attitudes towards methadone are far more ambivalent than the staff's. For the users, methadone is not just medicine; it is also a dependence...... in the model are three dimensions (1) treatment goals at the methadone centres (abstinence vs. stabilisation) (2) treatment focus (focus on addiction vs. focus on the consequences of addiction) and (3) conceptualisation of methadone (methadone as similar to or different from heroin). The paper shows......-producing and ‘dangerous’ drug....

QTc Prolongation in Veterans With Heroin Dependence on Methadone Maintenance Treatment.

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Hassamal, Sameer; Fernandez, Antony; Moradi Rekabdarkolaee, Hossein; Pandurangi, Ananda

2015-06-01

QTc prolongation and Torsade de Ppointes have been reported in patients on methadone maintenance. In this study, QTc was compared before and after the veteran (n = 49) was on a stable dosage of methadone for 8.72 ± 4.50 years to treat heroin dependence. Risk factors were correlated with the QTc once the veteran was on a stable dose of methadone. Differences in the clinical risk factors in subgroups of veterans with below and above mean QTc change was compared. ECG data was obtained from a 12-lead electrocardiogram (pre-methadone and on methadone) on 49 veterans. Data and risk factors were retrospectively collected from the medical records. The mean QTc at baseline (pre-methadone) was 426 ± 34 msec and after being on methadone for an average of 8.72 ± 4.50 years was significantly higher at 450 ± 35 msec. No significant relationships were found between QTc prolongation and risk factors except for calcium. The methadone dosage was significantly higher in veterans with a QTc change above the mean change of ≥ 24 msec (88.48 ± 27.20 mg v.s 68.96 ± 19.84 mg). None of the veterans experienced cardiac arrhythmias. The low complexity of medical co-morbidities may explain the lack of a significant correlation between any risk factor with the QTc except calcium and methadone dosage. The absence of TdP may be explained by the low prevalence of QTc values > 500 msec as well as the retrospective design of the study. During long-term methadone treatment, there was a slight increase in the QTc interval but we did not find evidence of increased cardiac toxicity as a reason for treatment termination.

The safety of methadone hydrochloride.

Science.gov (United States)

Swegle, John M; Wensel, David D

2008-01-01

Methadone is an interesting analgesic for multiple reasons. The unique properties of the agent, low cost and widespread availability have led to increases in methadone prescribing. Despite advantages, methadone is challenging to work with, particularly in patients with high opioid requirements. Recent concerns regarding cardiac arrhythmias and respiratory depression have led to changes in the labeling of methadone. This editorial highlights some of these concerns and provides some recommendations for the appropriate use of methadone in the setting of pain.

Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy.

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Concheiro, Marta; Lendoiro, Elena; de Castro, Ana; Gónzalez-Colmenero, Eva; Concheiro-Guisan, Ana; Peñas-Silva, Patricia; Macias-Cortiña, Manuel; Cruz-Landeira, Angelines; López-Rivadulla, Manuel

2017-06-01

Drug exposure during pregnancy constitutes a major legal issue and a public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta, and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography-tandem mass spectrometry for the determination of cocaine, opioids, methadone, and amphetamines, and compared the analytical results from the four different matrices. The cases were divided in non-exposure, low, and frequent exposure, based on maternal hair concentrations and segmental analysis by trimesters. For cocaine, 62 cases tested positive in hair, 9 in meconium, 6 in placenta and 7 in umbilical cord. In the case of opioids, 14 maternal hair cases were positive, 11 meconium and umbilical cord and 9 placenta samples. For methadone, 11 cases were positive in hair, 9 in meconium and 6 in placenta and umbilical cord. For amphetamines, 18 cases were positive according to maternal hair, but all meconium, placenta, and umbilical cord tested negative. Maternal hair was the most sensitive specimen to detect drug exposure during pregnancy. Meconium, placenta, and umbilical cord tested positive if hair concentrations showed frequent drug use during the whole pregnancy, especially during the third trimester. Meconium, placenta, and umbilical cord also tested positive for morphine and metabolites, if this drug was administered during labour and delivery. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Methadone-induced Torsades de Pointes Masquerading as Seizures

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David C. Traficante

2017-01-01

Full Text Available The authors herein present the case of a 53-year-old female who was being treated as an outpatient for seizure disorder but was also receiving high-dose methadone therapy. She presented to the emergency department (ED for what appeared to be a seizure and was found to have a prolonged QT interval, as well as runs of paroxysmal polymorphic ventricular tachycardia with seizure-like activity occurring during the arrhythmia. The markedly prolonged QT interval corrected after treatment with intravenous magnesium; subsequent electroencephalogram, neurology and cardiology consultations confirmed the cause of the recurrent seizure-like episodes to be secondary to the cardiotoxic effects of methadone.

Stereoselective quantification of methadone and a d(6)-labeled isotopomer using high performance liquid chromatography-atmospheric pressure chemical ionization mass-spectrometry: application to a pharmacokinetic study in a methadone maintained subject.

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Foster, David J R; Morton, Erin B; Heinkele, Georg; Mürdter, Thomas E; Somogyi, Andrew A

2006-08-01

There is evidence that the apparent oral clearance of rac-methadone is induced during the early phase of methadone maintenance treatment. However, it is not known if this is due to changes in bioavailability or if this phenomenon is stereoselective. This knowledge can be obtained by administering a dose of stable-labeled methadone at selected times during ongoing treatment. Therefore, the authors developed a stereoselective high performance liquid chromatography-atmospheric pressure chemical ionization mass-spectrometry assay for the quantification of the enantiomers of methadone and a d(6)-labeled isotopomer. The compounds were quantified in a single assay after liquid-liquid extraction and stereoselective high performance liquid chromatograph with atmospheric pressure chemical ionization-mass spectrometry detection. The following ions were monitored: m/z 310.15 for unlabeled methadone; m/z 316.15 for methadone-d(6); and m/z 313.15 for the methadone-d(3) (internal standard). Calibration curves ranged from 0.5 to 75 ng/mL for each compound. Extraction recovery was approximately 80% for all analytes, without evidence of differences between the unlabeled and stable-labeled compounds or concentration dependency. Minor ion promotion was observed (d(3)-labeled internal standard, with peak area ratios in extracted samples identical to control injections. The isotopomers did not alter each others' ionisation, even at 10:1 concentration ratios, and 10-fold diluted samples were within 10% of the nominal concentration. Assay performance was acceptable, with interassay and intra-assay bias and precision d(6) in a patient receiving chronic oral methadone maintenance therapy.

ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics

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Barratt DT

2012-04-01

Full Text Available Daniel T Barratt1, Janet K Coller1, Richard Hallinan2, Andrew Byrne2, Jason M White1, David JR Foster3, Andrew A Somogyi1,41Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia; 2The Byrne Surgery, Specialist Drug and Alcohol Practice, Redfern, New South Wales; 3Division of Health Sciences, Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia; 4Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, South Australia, AustraliaBackground: Genetic variability in ABCB1, encoding the P-glycoprotein efflux transporter, has been linked to altered methadone maintenance treatment dose requirements. However, subsequent studies have indicated that additional environmental or genetic factors may confound ABCB1 pharmacogenetics in different methadone maintenance treatment settings. There is evidence that genetic variability in OPRM1, encoding the mu opioid receptor, and ABCB1 may interact to affect morphine response in opposite ways. This study aimed to examine whether a similar gene-gene interaction occurs for methadone in methadone maintenance treatment.Methods: Opioid-dependent subjects (n = 119 maintained on methadone (15–300 mg/day were genotyped for five single nucleotide polymorphisms of ABCB1 (61A > G; 1199G > A; 1236C > T; 2677G > T; 3435C > T, as well as for the OPRM1 18A > G single nucleotide polymorphism. Subjects’ methadone doses and trough plasma (R-methadone concentrations (Ctrough were compared between ABCB1 haplotypes (with and without controlling for OPRM1 genotype, and between OPRM1 genotypes (with and without controlling for ABCB1 haplotype.Results: Among wild-type OPRM1 subjects, an ABCB1 variant haplotype group (subjects with a wild-type and 61A:1199G:1236C:2677T:3435T haplotype combination, or homozygous for the 61A:1199G:1236C:2677T:3435T haplotype had significantly lower doses (median ± standard

QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial.

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Wedam, Erich F; Bigelow, George E; Johnson, Rolley E; Nuzzo, Paul A; Haigney, Mark C P

2007-12-10

Levomethadyl acetate, methadone hydrochloride, and buprenorphine hydrochloride are equally effective treatments for opioid dependence. Each blocks the human ether-a-go-go-related gene (hERG)-associated channel in vitro and represents a risk for QT prolongation. To compare the effects of 3 known hERG-associated channel blockers on the corrected QT (QTc), we conducted a randomized, controlled trial of opioid-addicted subjects. We analyzed 12-lead electrocardiograms collected at baseline and every 4 weeks from 165 opioid-addicted participants in a 17-week randomized double-blind clinical trial of equally effective doses of levomethadyl, methadone, and buprenorphine at a major referral center. Analyses were limited to the 154 patients with a normal baseline QTc = (QT/ radical R-R) who had at least 1 subsequent in-treatment electrocardiogram. Patients were randomized to receive treatment with levomethadyl, methadone, or buprenorphine (hereinafter, levomethadyl, methadone, and buprenorphine groups, respectively). The prespecified end points were a QTc greater than 470 milliseconds in men (or >490 milliseconds in women), or an increase from baseline in QTc greater than 60 milliseconds. Baseline QTc was similar in the 3 groups. The levomethadyl and methadone groups were significantly more likely to manifest a QTc greater than 470 or 490 milliseconds (28% for the levomethadyl group vs 23% for the methadone group vs 0% for the buprenorphine group; P methadone group [odds ratio, 8.4; 95% confidence interval, 1.9-36.4]) compared with the buprenorphine group (2% of subjects; P methadone remained fixed over at least 8 weeks, the QTc continued to increase progressively over time (P = .08 for the levomethadyl group, P = .01 for the methadone group). Buprenorphine is associated with less QTc prolongation than levomethadyl or methadone and may be a safe alternative.

Methadone hydrochloride: acute administration, disposition and effects on hepatic function in guinea pigs.

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Pak, R C; Ecobichon, D J

1981-01-01

d,1-Methadone hydrochloride was administered orally to adult female albino guinea pigs at a dose of 25 mg/kg body weight every 12 h for 10 consecutive days. Twelve hours after a dose, subgroups of animals were sacrificed at 2, 5 and 10 days for tissue (blood plasma, brain, liver and kidney) methadone residue analysis and the in vitro measurement of hepatic microsomal p-nitroanisole O-demethylase (OD), aniline hydroxylase (AH) and glucuronosyltransferase (GT) activities. No overt toxicity was observed during treatment other than a decrease in body weight. Withdrawal signs were absent during the 14-day post-treatment regression period. Tissue methadone levels were constant except for a decreased concentration in the liver at 5 and 10 days. No effect on hepatic OD and AH was observed during treatment but a significant decrease in GT activity was measured which returned to normal values 14 days after terminating treatment.

Relative bioavailability of methadone hydrochloride administered in chewing gum and tablets

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Christrup, Lona Louring; Angelo, H.R.; Bonde, J.

1990-01-01

Methadone administered in chewing gum in doses of 16.7-22.6 mg to seven patients in a study using an open balanced cross-over design, was compared with 20 mg of methadone given perorally as tablets. There was no significant difference in the AUC/D obtained after administration of chewing gum...... and tablets (p>0.05). It is concluded that the chewing gum formulation should be considered for further testing with respect to suppression of abstinence syndrome in narcotic addicts....

Relative bioavailability of methadone hydrochloride administered in chewing gum and tablets.

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Christrup, L L; Angelo, H R; Bonde, J; Kristensen, F; Rasmussen, S N

1990-01-01

Methadone administered in chewing gum in doses of 16.7-22.6 mg to seven patients in a study using an open balanced cross-over design, was compared with 20 mg of methadone given perorally as tablets. There was no significant difference in the AUC/D obtained after administration of chewing gum and tablets (p greater than 0.05). It is concluded that the chewing gum formulation should be considered for further testing with respect to suppression of abstinence syndrome in narcotic addicts.

On the mutagenicity of methadone hydrochloride. Induced dominant lethal mutation and spermatocyte chromosomal aberrations in treated males.

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Badr, F M; Rabouh, S A; Badr, R S

1979-11-01

The mutagenicity of methadone hydrochloride was tested in male mice using the dominant lethal mutation technique and the spermatocyte test of treated mice. Male mice of C3H inbred strain received one of the following doses, 1, 2, 4 or 6 mg/kg body weight once a day for 3 consecutive days. Another group of mice served as control and received saline instead. Treated males were then mated to virgin females at 3-day intervals for a period of 45 days. Pregnant females were dissected at mid-term and the corpora lutea and intrauterine contents were recorded. The spermatocytes of treated males were examined 45-50 d after treatments with methadone and abnormal pairing configurations were scored. The methadone treatment was found to increase the rate of preimplantation deaths consistently in all post-meiotic stages with all doses used. In addition, the higher doses, 4 and 6 mg, affected spermatogonia stages. Quantitatively, the dose-response relationship cannot be demonstrated though the spectrum of effect increased with higher doses as more spermatogenesis stages became more sensitive to the treatment. In many cases the frequency of live implants showed a positive correlation with preimplantation deaths in contrast with the frequency of early deaths which showed only sporadic variation. The mutation indices based on total embryonic death indicate that methadone hydrochloride affected several stages of germ-cell maturation namely, spermatozoa (M.I. 14-35), late spermatids (M.I. 15-48), early spermatids (M.I. 14-50), late spermatocytes (M.I. 15-43) and spermatogonial stages (M.I. 12-63). Chromosome analysis at diakinesis-metaphase 1 revealed significant increase in the frequency of sex chromosome and autosome univalents with different doses of methadone. The smallest dose applied was quite effective and the data represent direct dose-response relationship. Of the multivalent configuration, the most frequent type was chain quadrivalents. The frequencies of total translocations

Contrasting cardiovascular properties of the µ-opioid agonists morphine and methadone in the rat.

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Tung, Kenneth H; Angus, James A; Wright, Christine E

2015-09-05

Morphine and methadone share the property of μ-opioid receptor agonism yet have markedly different cardiovascular actions suggesting additional properties are at play. We investigated the i.v. dose-response relationships of the opioids on cardiovascular metameters in anaesthetised rats in the absence or presence of H1- and H2-receptor antagonism and the μ-opioid antagonist naloxone. In vitro tissue assays were employed to define more clearly cardiac and vascular mechanisms of action. Morphine (9, 30, 90mg/kg i.v.) decreased heart rate (HR) and mean arterial pressure (MAP) - responses that were blocked by naloxone pretreatment (10mg/kg i.v.). In contrast, methadone (3, 10, 30mg/kg i.v.) caused dramatic short-lived (1-3min) bradycardia, hypotension and lengthening of the QT interval before stabilising 5min after i.v. dosing. Only the steady-state responses of HR and MAP were blocked by naloxone. Mepyramine (10mg/kg i.v.) and cimetidine (100mg/kg i.v.) also blocked the naloxone-sensitive components. In isolated small mesenteric arteries precontracted by K(+) 62mM or endothelin-1, methadone (1-30μM) relaxed vessels while morphine (1-100μM) had no effect. Pretreatment with naloxone (10μM), indomethacin (30μM) or nitro-l-arginine (100μM) did not affect the relaxation to methadone. In rat isolated left atria, morphine and methadone inhibited inotropic responses at high concentrations (100μM). In rat papillary muscle and right atria, methadone was more than 30 times more potent at lengthening the refractory period and slowing the atrial rate than morphine. We conclude that methadone is a potent vasodilator agent, possibly through blocking L-type calcium channels. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of auditory event-related potentials in infants prenatally exposed to methadone.

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Paul, Jonathan A; Logan, Beth A; Krishnan, Ramesh; Heller, Nicole A; Morrison, Deborah G; Pritham, Ursula A; Tisher, Paul W; Troese, Marcia; Brown, Mark S; Hayes, Marie J

2014-07-01

Developmental features of the P2 auditory ERP in a change detection paradigm were examined in infants prenatally exposed to methadone. Opiate dependent pregnant women maintained on methadone replacement therapy were recruited during pregnancy (N = 60). Current and historical alcohol and substance use, SES, and psychiatric status were assessed with a maternal interview during the third trimester. Medical records were used to collect information regarding maternal medications, monthly urinalysis, and breathalyzer to confirm comorbid drug and alcohol exposures. Between birth and 4 months infant ERP change detection performance was evaluated on one occasion with the oddball paradigm (.2 probability oddball) using pure-tone stimuli (standard = 1 kHz and oddball = 2 kHz frequency) at midline electrode sites, Fz, Cz, Pz. Infant groups were examined in the following developmental windows: 4-15, 16-32, or 33-120 days PNA. Older groups showed increased P2 amplitude at Fz and effective change detection performance at P2 not seen in the newborn group. Developmental maturation of amplitude and stimulus discrimination for P2 has been reported in developing infants at all of the ages tested and data reported here in the older infants are consistent with typical development. However, it has been previously reported that the P2 amplitude difference is detectable in neonates; therefore, absence of a difference in P2 amplitude between stimuli in the 4-15 days group may represent impaired ERP performance by neonatal abstinence syndrome or prenatal methadone exposure. © 2013 Wiley Periodicals, Inc.

The methadone game

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Dahl, Helle Vibeke

2007-01-01

In this chapter it is described how methadone and methadone clinics can be seen as central means of controlling and disciplining drug addicts. It is illustrated how the clients respond to the surveillance and control of the clinic regime and finally demonstrated that, in the hands of the clients...

Methadone disrupts performance on the working memory version of the Morris water task.

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Hepner, Ilana J; Homewood, Judi; Taylor, Alan J

2002-05-01

The aim of the study was to examine if administration of the mu-opiate agonist methadone hydrochloride resulted in deficits in performance on the Morris water tank task, a widely used test of spatial cognition. To this end, after initial training on the task, Long-Evans rats were administered saline or methadone at either 1.25, 2.5 or 5 mg/kg ip 15 min prior to testing. The performance of the highest-dose methadone group was inferior to that of the controls on the working memory version of the Morris task. There were also differences between the groups on the reference memory version of the task, but this result cannot be considered reliable. These data show that methadone has its most profound effect on cognition in rats when efficient performance on the task requires attention to and retention of new information, in this case, the relationship between platform location and the extramaze cues.

Rectal methadone in cancer patients with pain. A preliminary clinical and pharmacokinetic study.

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Ripamonti, C; Zecca, E; Brunelli, C; Rizzio, E; Saita, L; Lodi, F; De Conno, F

1995-10-01

Cancer pain can be treated in most cases with oral analgesics. However, during their clinical history, 53% to 70% of patients will need alternative routes of opioid administration. The rectal administration of opioids is a simple alternative route for many patients. There are no data in the literature regarding the pharmacodynamics and pharmacokinetics of rectal methadone. We evaluated the analgesia, tolerability and absorption profile of methadone hydrochloride in six opioid-naive cancer patients with pain. A blood sample was collected before administration of a single dose of drug (10 mg) and then again after fixed times. At these fixed times the patients were asked about pain, nausea and drowsiness by means of a visual analogue scale of 0-100 mm (VAS). Pain relief was statistically significant as early as 30 minutes and up to eight hours after methadone administration. None of the patients reported significant side effects. The pharmacokinetics of rectal methadone showed rapid and extensive distribution phases followed by a slow elimination phase. Rectal methadone can be considered an effective analgesic therapy for patients with cancer pain for whom oral and/or parenteral opioids are not indicated or available.

Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses.

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Linardi, R L; Stokes, A M; Barker, S A; Short, C; Hosgood, G; Natalini, C C

2009-10-01

Methadone hydrochloride is a synthetic mu-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/mass spectrometry at predetermined time points for 24 h, and PK parameters were estimated using a noncompartmental model. Physical effects were observed and recorded by experienced clinicians. No drug toxicity, behavioural or adverse effects were observed in the horses. The disposition of methadone followed first order elimination and a biphasic serum profile with rapid absorption and elimination phases. The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (V(d)/F) and short elimination half-life (t(1/2)). The mean of the estimated t(1/2) (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was 2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated C(max) (SD) was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively.

Clinical pharmacology of methadone in dogs.

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Ingvast-Larsson, Carina; Holgersson, Anja; Bondesson, Ulf; Lagerstedt, Anne-Sofie; Olsson, Kerstin

2010-01-01

To investigate the pharmacokinetics and effects of methadone on behaviour and plasma concentrations of cortisol and vasopressin in healthy dogs. Randomized, cross-over, experimental trial. Nine adult dogs (beagle and beagle cross breeds), four males and five females. Methadone hydrochloride, 0.4 mg kg(-1), was administered intravenously (IV) and subcutaneously (SC) with a crossover design. Drug and hormone analyses in plasma were performed using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry and radioimmunoassay respectively. Behavioural data were collected using a standardized protocol. After IV administration, the plasma concentration of methadone at 10 minutes was 82.1 +/- 9.2 ng mL(-1) (mean +/- SD), the terminal half-life was 3.9 +/- 1.0 hours, the volume of distribution 9.2 +/- 3.3 L kg(-1) and plasma clearance 27.9 +/- 7.6 mL minute(-1) kg(-1). After SC administration, time to maximal plasma concentration was 1.26 +/- 1.04 hours and maximal plasma concentration of methadone was 23.9 +/- 14.4 ng mL(-1), the terminal half-life was 10.7 +/- 4.3 hours and bioavailability was 79 +/- 22%. Concentrations of both cortisol and vasopressin were increased for an hour following IV methadone. The observed behavioural effects of methadone were decreased licking and swallowing and an increase in whining after SC administration. The latter finding is notable as it can be misinterpreted as pain when methadone is used as an analgesic. When methadone was administered by the SC route, the half-life was longer, but the individual variation in plasma concentrations was greater compared with IV administration. Increased frequency of whining occurred after administration of methadone and may be a drug effect and not a sign of pain. Cortisol and vasopressin concentrations in plasma may not be suitable for evaluating analgesia after methadone treatment.

Acute Poisoning with Methadone (Dolphin (Review

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Georgy A. Livanov

2017-01-01

Full Text Available Most publications report on the use of methadone as a medication, however an increase of the illegal use of methadone has been demonstrated worldwide over the recent years, thus increasing the number of hospitalizations due to acute poisoning with this synthetic opioid. The aim of the present review was to summarize current data on the mechanisms of toxicity, selective toxicity, toxicokinetics and toxicodynamics of methadone (Dolphin. The involvement of CNS, respiratory, cardiovascular and urinary systems in acute poisoning with methadone was dis- cussed. The practice of use of methadone in many countries as a medicine for the replacement therapy for opiate addicts was analyzed. In addition, it was suggested that the results of the use of naloxone antidote therapy in acute opioid poisoning do not always clearly demonstrate its sufficient efficacy. Ways to improve of the intensive therapy of severe acute poisoning by methadone were substantiated; in addition to general critical care methods, treatment with a complex metabolic antihypoxant cytoflavin should be considered. 

Methadone for Cancer Pain

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Eric E. Prommer

2010-07-01

Full Text Available Pain is one of the most common and incapacitating symptoms experienced by patients with advanced cancer. Methadone is a potent opioid with strong affinity for the µ opioid receptor. In addition to being a potent µ opioid receptor ligand, methadone blocks the N-methyl-D-aspartic acid receptor and modulates neurotransmitters involved in descending pain modulation. These 3 properties enhance analgesic activity. Methadone’s lack of active metabolites makes it an attractive option when opioid responsiveness declines and renal insufficiency complicates opioid therapy. A lipophilic opioid, methadone can be given by multiple routes. Clinical trial data show equivalence with morphine as an analgesic in moderate to severe cancer pain. Further investigations are needed to define the role of methadone in the management of breakthrough pain and neuropathic pain and to determine whether it is truly superior to morphine, the gold standard of cancer analgesia.

Enantiomeric metabolic interactions and stereoselective human methadone metabolism.

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Totah, Rheem A; Allen, Kyle E; Sheffels, Pamela; Whittington, Dale; Kharasch, Evan D

2007-04-01

Methadone is administered as a racemate, although opioid activity resides in the R-enantiomer. Methadone disposition is stereoselective, with considerable unexplained variability in clearance and plasma R/S ratios. N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. CYP2B6 metabolism was stereoselective. CYP2C19 was less active, and stereoselectivity was opposite that for CYP2B6. CYP3A4 was not stereoselective. With all three isoforms, enantiomer N-dealkylation rates in the racemate were lower than those of (R)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (R-methadone) or (S)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (S-methadone) alone, suggesting an enantiomeric interaction and mutual metabolic inhibition. For CYP2B6, the interaction between enantiomers was stereoselective, with S-methadone as a more potent inhibitor of R-methadone N-demethylation than R-of S-methadone. In contrast, enantiomer interactions were not stereoselective with CYP2C19 or CYP3A4. For all three cytochromes P450, methadone N-demethylation was best described by two-site enzyme models with competitive inhibition. There were minor model differences between cytochromes P450 to account for stereoselectivity of metabolism and enantiomeric interactions. Changes in plasma R/S methadone ratios observed after rifampin or troleandomycin pretreatment in humans in vivo were successfully predicted by CYP2B6- but not CYP3A4-catalyzed methadone N-demethylation. CYP2B6 is a predominant catalyst of stereoselective methadone metabolism in vitro. In vivo, CYP2B6 may be a major determinant of methadone metabolism and disposition, and CYP2B6 activity and stereoselective metabolic

Evaluation of Retention in Methadone Treatment in Patients Attending Baharan Hospital Clinic in Zahedan City

Directory of Open Access Journals (Sweden)

M.D. Mohebi

2015-04-01

Full Text Available Introduction & Objectives: Substance abuse and opioid dependency refers to hazardous use of psychoactive substance .Prevention and treatment of opiate dependence has not been success-ful. Most effective drug in agonist treatment of opiates is methadone maintenance therapy (MMT.But the lack of cooperation of addicts in methadone maintenance therapy has always been a big problem to continue. The purpose of this study is to investigate the retention in the MMT. Materials & Methods: This historical cohort study analyzed the medical records of patients of Baharan hospital in Zahedan. All 912 cases of methadone maintenance clinic of Baharan hos-pital in Zahedan 2011-2012 were studied and the data were analyzed using SPSS. Tables and indexes were analyzed by the Chi-square test and survival curves were plotted using Kaplan–Meier method and analyzed by Log-Rank test. Results: This study reviewed records from 912 patients with a mean age of 34.67% and stan-dard deviation of 10.88 and the range of 15-86 years. 735 were male and 177 ware female. 1-moth retention rate was 71%, 3 months was 59%, 6 months was 47%, 1 year was 30% and 2 years was 17%. Kaplan-Meier median survival time of 8 months was estimated by relation-ship. Doses higher than 60 mg/d of methadone was associated with increased survival on MMT. Conclusion: Age increase, increase of employment time, increasing of the duration of drug abuse, increasing the daily dose of methadone, oral substance abuse increased retention rate and heroin abuse and smoking were associated with decrease retention rate of methadone maintenance therapy. So, with an emphasis on each of these factors effective steps can be taken to improve the cooperation of patients in MMT. (Sci J Hamadan Univ Med Sci 2015; 22 (1:30-36

Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects

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Gelston, Eloise A; Coller, Janet K; Lopatko, Olga V; James, Heather M; Schmidt, Helmut; White, Jason M; Somogyi, Andrew A

2012-01-01

AIMS To compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4-mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects. METHODS Ten methadone- and eight buprenorphine-maintained subjects received a single 60 mg dose of codeine phosphate. Blood was collected at 3 h and urine over 6 h and assayed for codeine, norcodeine, morphine, morphine-3- and -6-glucuronides and codeine-6-glucuronide. RESULTS The urinary metabolic ratio for O-demethylation was significantly higher (P = 0.0044) in the subjects taking methadone (mean ± SD, 2.8 ± 3.1) compared with those taking buprenorphine (0.60 ± 0.43), likewise for 6-glucuronide formation (0.31 ± 0.24 vs. 0.053 ± 0.027; P D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6. PMID:22092298

A preliminary study comparing methadone and buprenorphine in patients with chronic pain and coexistent opioid addiction.

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Neumann, Anne M; Blondell, Richard D; Jaanimägi, Urmo; Giambrone, Amanda K; Homish, Gregory G; Lozano, Jacqueline R; Kowalik, Urszula; Azadfard, Mohammadreza

2013-01-01

Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge. Fifty-four participants with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up examination, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043), and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term, low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction.

Impaired psychomotor function and plasma methadone and levo-alpha-acetylmethadol (LAAM) concentrations in opioid-substitution patients.

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Newcombe, David A L; Somogyi, Andrew A; Bochner, Felix; White, Jason M

2017-06-01

Tolerance to the psychomotor impairing effects of opioid drugs is expected to develop with repeated dosing, but may be incomplete. The relationship between plasma opioid concentration and psychomotor function in opioid-dependent patients was examined to determine whether impairment was more likely at the time of highest plasma drug concentration. Sixteen patients participating in a cross-over trial comparing methadone and LAAM completed a tracking task (OSPAT) 11 times over the dosing-interval for methadone (24-hrs) and LAAM (48-hrs). Venous blood was collected for the quantification of plasma (R)-(-)-methadone, LAAM, and nor-LAAM concentrations. The Digit Symbol Substitution Test (DSST) and Trail-Making Test were administered at the time of peak plasma concentration. Ten healthy controls (HCs) also participated. OSPAT scores (obtained for 15 patients) fluctuated significantly across the dosing-interval for both drugs and were lower in patients than HCs at the times of peak concentrations of (R)-(-)-methadone (1 hr: (mean difference; 95% CI) (2.13; 0.18-4.08); 2 hrs: (2.38; 0.48-4.28) postdosing) and LAAM (2 hrs: (1.81; 0.09-3.53), and 4 hrs (1.90: 0.9-3.71) postdosing). Within-participant analysis of the peak-change from baseline for OSPAT scores found that 10 of the 15 patients could be categorized as impaired on methadone and 9 on LAAM. No HCs were impaired. Patients performed worse on the DSST and Trails-A than HCs, but not on Trails-B. Results suggest that some patients receiving opioids long term may exhibit impairment at the time of highest plasma drug concentration. These patients should be made aware that their ability to undertake complex tasks may be affected. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Methadone

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... Updated: 09/28/2015 Medications to Treat OPIOID ADDICTION Methadone Naltrexone Buprenorphine Related SAMHSA Resources Behavioral Health ... Systems Integration Health Disparities Health Financing Health Information Technology HIV, AIDS, and Viral Hepatitis Homelessness and Housing ...

Cognitive impairment in methadone maintenance patients.

Science.gov (United States)

Mintzer, Miriam Z; Stitzer, Maxine L

2002-06-01

Few well-controlled studies have examined psychomotor and cognitive performance in methadone maintenance patients (MMP). In the present study, performance of 18 opioid-dependent MMP was evaluated relative to that of 21 control participants without substance abuse histories. The MMP and control groups were balanced with respect to gender, race, age, years of education, current employment status, current reading level, and estimated IQ score. Recent drug abstinence was verified by urine testing. Participants with a urine screen positive for benzodiazepines or a breathalyzer test positive for alcohol prior to performance testing were excluded. To avoid testing under conditions of acute heroin or cocaine intoxication, but without testing under conditions of acute withdrawal, participants with current use of heroin or cocaine were only required to abstain for 24 h prior to performance testing. MMP exhibited impairment relative to controls in psychomotor speed (digit symbol substitution and trail-making tests), working memory (two-back task), decision making (gambling task), and metamemory (confidence ratings on a recognition memory test); results also suggested possible impairment in inhibitory mechanisms (Stroop color-word paradigm). MMP did not exhibit impairment in time estimation, conceptual flexibility or long-term memory. The wide range of impaired functions is striking, and may have important implications for daily functioning in MMP. Further research is necessary to determine the clinical significance of the impairments in laboratory-based tests for daily performance in the natural environment, as well as to differentiate impairments due to acute methadone dosing, chronic methadone maintenance, chronic poly-drug abuse, and other factors. Copyright 2002 Elsevier Science Irealnd Ltd.

Transcranial route of brain targeted delivery of methadone in oil.

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Pathirana, W; Abhayawardhana, P; Kariyawasam, H; Ratnasooriya, W D

2009-05-01

The unique anatomical arrangement of blood vessels and sinuses in the human skull and the brain, the prevalence of a high density of skin appendages in the scalp, extracranial vessels of the scalp communicating with the brain via emissary veins and most importantly, the way that the scalp is used in Ayurvedic medical system in treating diseases associated with the brain show that a drug could be transcranially delivered and targeted to the brain through the scalp. The present study was to investigate by measuring the antinociceptive effect on rats whether the opioid analgesic methadone could be delivered and targeted to the brain by transcranial delivery route. A non aqueous solution of methadone base in sesame oil was used for the application on the scalp. Animal studies were carried out using six groups of male rats consisting of group 1, the oral control treated with distilled water 1 ml; group 2, the oral positive control treated with methadone hydrochloride solution 316.5 mug/ml; group 3, the negative control treated transcranially with the blank sesame oil 0.2 ml and three test groups 4, 5 and 6 treated with three different dose levels of the transcranial oil formulation of methadone base, 41.6 mug/0.2 ml, 104 mug/0.2 ml and 208 mug/0.2 ml, respectively. The antinociceptive effects were examined by subjecting the rats to the hot plate and tail flick tests. The two higher concentrations of the three transcranial methadone formulations yielded response vs time curves showing nearly equal maximum antinociceptive effects similar to that of the oral positive control. Maximum analgesic effect after transcranial administration was observed between 1st and 2nd h and declined up to 6th hour. The results indicate that the transcranial brain targeted delivery of methadone base in the form of an oil based non aqueous solution results in statistically significant antinociceptive effects under experimental conditions. Therefore, it is possible to deliver central nervous

Heroin and methadone prescriptions from a London drug clinic over the first 15 years of operation (1968-1983): old records examined.

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Strang, John; Sheridan, Janie

2006-01-01

We charted changes in the prescriptions issued to opiate addicts in treatment at a London clinic over the first 15 years of operation of one of the new National Health Service (NHS) drug clinics established in 1968. Having located the original handwritten ledger records of prescriptions issued by the drug addict treatment clinic, an SPSS data file was created of the prescriptions given to each of the clinic patients each month over the period 1968-1983 to permit examination of changes over this 15-year period in the drugs prescribed (e.g., heroin, methadone), the form (e.g., injectable or oral), the daily doses, and the extent of multiple items for single patients (e.g., both injectable ampule and oral forms). For each month, a list was available of all current patients detailing which drug(s) they had received during that month, in what form(s) and what dose(s). These items were the basic units of study. We report changes over the 15-year period for which the data were available. For the first 5 years, more than half of the prescriptions were for heroin (diamorphine hydrochloride), with the remainder of the prescriptions mostly comprising oral methadone. After 1973, methadone ampules for injection were increasingly commonly prescribed and thereafter remained at about a quarter of the prescriptions for the remaining 10 years for which data are available, whereas heroin prescriptions declined over the mid-1970s to only 20%. From 1973 onward, oral methadone was increasingly prescribed, rising from approximately one third of prescriptions in the early 1970s to more than two thirds by the early 1980s. Individual patients often received more than one drug or form of drug: From 1969 onward, oral methadone was commonly prescribed as a supplement to heroin prescriptions. This same practice was widespread with prescriptions for methadone ampules prescribed as a supplement to heroin prescriptions. Daily doses of heroin were at a mean of from 160 to 540 mg, in contrast with

Sedative and antinociceptive effects of different combinations of detomidine and methadone in standing horses.

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Gozalo-Marcilla, Miguel; Luna, Stelio Pl; Crosignani, Nadia; Filho, José Np Puoli; Possebon, Fábio S; Pelligand, Ludovic; Taylor, Polly M

2017-09-01

To evaluate intravenous (IV) detomidine with methadone in horses to identify a combination which provides sedation and antinociception without adverse effects. Randomized, placebo-controlled, blinded, crossover. A group of eight adult healthy horses aged (mean ± standard deviation) 7 ± 2 years and 372 ± 27 kg. A total of six treatments were administered IV: saline (SAL); detomidine (5 μg kg -1 ; DET); methadone (0.2 mg kg -1 ; MET) alone or combined with detomidine [2.5 (MLD), 5 (MMD) or 10 (MHD) μg kg -1 ]. Thermal, mechanical and electrical nociceptive thresholds were measured, and sedation, head height above ground (HHAG), cardiopulmonary variables and intestinal motility were evaluated at 5, 15, 30, 45, 60, 75, 90, 120 and 180 minutes. Normal data were analyzed by mixed-model analysis of variance and non-normal by Kruskal-Wallis (p detomidine (MMD, MHD) were increased above baseline to a greater degree and for longer duration (MMD: 15-30 minutes, MHD: 30-60 minutes) than in horses administered low dose with methadone or detomidine alone (MLD, DET: 5-15 minutes). No increases in nociceptive thresholds were recorded in SAL or MET. Compared with baseline, HHAG was lower for 30 minutes in MMD and DET, and for 45 minutes in MHD. No significant sedation was observed in SAL, MET or MLD. Intestinal motility was reduced for 75 minutes in MHD and for 30 minutes in all other treatments. Methadone (0.2 mg kg -1 ) potentiated the antinociception produced by detomidine (5 μg kg -1 ), with minimal sedative effects. Detomidine (5 μg kg -1 ) with methadone (0.2 mg kg -1 ) produced antinociception without the adverse effects of higher doses of detomidine. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients.

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Coller, Janet K; Michalakas, Jennifer R; James, Heather M; Farquharson, Aaron L; Colvill, Joel; White, Jason M; Somogyi, Andrew A

2012-11-01

Management of pain in opioid dependent individuals is problematic due to numerous issues including cross-tolerance to opioids. Hence there is a need to find alternative analgesics to classical opioids and tramadol is potentially one such alternative. Methadone inhibits CYP2D6 in vivo and in vitro. We aimed to investigate the effect of methadone on the pathways of tramadol metabolism: O-demethylation (CYP2D6) to the opioid-active metabolite M1 and N-demethylation (CYP3A4) to M2 in subjects maintained on methadone or buprenorphine as a control. Compared with subjects on buprenorphine, methadone reduced the clearance of tramadol to active O-desmethyl-tramadol (M1) but had no effect on N-desmethyltramadol (M2) formation. Similar to other analgesics whose active metabolites are formed by CYP2D6 such as codeine, reduced formation of O-desmethyltramadol (M1) is likely to result in reduced analgesia for subjects maintained on methadone. Hence alternative analgesics whose metabolism is independent of CYP2D6 should be utilized in this patient population. To compare the O- (CYP2D6 mediated) and N- (CYP3A4 mediated) demethylation metabolism of tramadol between methadone and buprenorphine maintained CYP2D6 extensive metabolizer subjects. METHODS Nine methadone and seven buprenorphine maintained subjects received a single 100 mg dose of tramadol hydrochloride. Blood was collected at 4 h and assayed for tramadol, methadone, buprenorphine and norbuprenorphine (where appropriate) and all urine over 4 h was assayed for tramadol and its M1 and M2 metabolites. The urinary metabolic ratio [median (range)] for O-demethylation (M1) was significantly lower (P= 0.0002, probability score 1.0) in the subjects taking methadone [0.071 (0.012-0.103)] compared with those taking buprenorphine [0.192 (0.108-0.392)], but there was no significant difference (P= 0.21, probability score 0.69) in N-demethylation (M2). The percentage of dose [median (range)] recovered as M1 was significantly lower

The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking Study

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Nik Nur Syazana Bt Nik Mohamed Kamal

2013-01-01

Full Text Available Current methadone maintenance therapy (MMT is yet to ensure 100% successful treatment as the optimum dosage has yet to be determined. Overdose leads to death while lower dose causes the opioid withdrawal effect. Single-nucleotide polymorphisms (SNP in cytochrome P450s (CYPs, the methadone metabolizers, have been showen to be the main factor for the interindividual variability of methadone clinical effects. In this study, we investigated the effect of SNPs in three major methadone metabolizers (CYP2B6, CYP2D6, and CYP3A4 on methadone binding affinity. Results showed that CYP2B6*11, CYP2B6*12, CYP2B6*18, and CYP3A4*12 have significantly higher binding affinity to R-methadone compared to wild type. S-methadone has higher binding affinity in CYP3A4*3, CYP3A4*11, and CYP3A4*12 compared to wild type. R-methadone was shown to be the active form of methadone; thus individuals with CYP alleles that binds better to R-methadone will have higher methadone metabolism rate. Therefore, a higher dosage of methadone is necessary to obtain the opiate effect compared to a normal individual and vice versa. These results provide an initial prediction on methadone metabolism rate for individuals with mutant type CYP which enables prescription of optimum methadone dosage for individuals with CYP alleles.

Comparison of the cardio-respiratory effects of methadone and morphine in conscious dogs.

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Maiante, A A; Teixeira Neto, F J; Beier, S L; Corrente, J E; Pedroso, C E B P

2009-08-01

The effects of methadone and morphine were compared in conscious dogs. Six animals received morphine sulfate (1 mg/kg) or methadone hydrochloride (0.5 mg/kg [MET0.5] or 1.0 mg/kg [MET1.0]) intravenously (i.v.) in a randomized complete block design. Cardiopulmonary variables were recorded before (baseline), and for 120 min after drug administration. One outlier was not included in the statistical analysis for hemodynamic data. Morphine decreased heart rate (HR) compared to baseline from 30 to 120 min (-15% to -26%), while cardiac index (CI) was reduced only at 120 min (-19%). Greater and more prolonged reductions in HR (-32% to -46%) and in CI (-24% to -52%) were observed after MET1.0, while intermediate reductions were recorded after MET0.5 (-19 to -28% for HR and -17% to -27% for CI). The systemic vascular resistance index (SVRI) was increased after methadone; MET1.0 produced higher SVRI values than MET0.5 (maximum increases: 57% and 165% for MET0.5 and MET1.0, respectively). Compared to morphine, oxygen partial pressure (PaO(2)) was lower (-12% to -13%) at 5 min of methadone (0.5 and 1.0 mg/kg), while carbon dioxide partial pressure (PaCO(2)) did not change significantly. It was concluded that methadone induces cardiovascular changes that are dose-related and is a more potent cardiovascular depressant agent than morphine in conscious dogs.

The nature of methadone diversion in England: a Merseyside case study

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Duffy Paul

2012-01-01

Full Text Available Abstract Background Methadone maintenance treatment (MMT is a key element in treatment for opiate addiction; however concerns about the diversion of methadone remain. More current empirical data on methadone diversion are required. This research investigated the market for diverted methadone in Merseyside, UK, in order to provide a case study which can be transferred to other areas undertaking methadone maintenance treatment on a large scale. Methods Questionnaires were completed (in interview format with 886 past year users of methadone recruited both in and out of prescribing agencies. Topic areas covered included current prescribing, obtaining and providing methadone, reasons for using illicit methadone and other drug use. Results Large proportions of participants had obtained illicit methadone for use in the past year with smaller proportions doing so in the past month. Proportions of participants buying and being given methadone were similar. Exchange of methadone primarily took place between friends and associates, with 'dealers' rarely involved. Gender, age, whether participant's methadone consumption was supervised and whether the aims of their treatment had been explained to them fully, influenced the extent to which participants were involved in diverting or using diverted methadone. Conclusion Methadone diversion is widespread although drug users generally do not make use of illicit methadone regularly (every month. The degree of altruism involved in the exchange of methadone does not negate the potential role of this action in overdose or the possibility of criminal justice action against individuals. Treatment agencies need to emphasise these risks whilst ensuring that treatment aims are effectively shared with clients to ensure adherence to treatment.

A placebo-controlled trial of dextromethorphan as an adjunct in opioid-dependent patients undergoing methadone maintenance treatment.

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Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chu, Chun-Hsien; Chen, Shih-Heng; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Wang, Tzu-Yun; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2015-02-25

Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. We provide evidence-decreased concomitant heroin use-of low-dose add-on DM's efficacy for treating opioid-dependent patients undergoing MMT. © The Author 2015. Published by Oxford University Press on behalf of CINP.

An epidemiological investigation into an outbreak of rash illness among methadone maintenance clients in Australia.

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McAnulty, Jeremy M; Jauncey, Marianne E; Monger, Claire K; Hailstone, Susan T; Alam, Noore K M; Mannes, Trish F; Capon, Adam G; Irvine, Katie; Armstrong, Paul K; Kaldor, John M

2007-05-01

In late 2004, NSW Health received several reports of a serious desquamating rash among clients of the methadone program. We sought to identify the extent and likely cause of this outbreak. We initiated active surveillance for cases throughout Australia, a survey of dosing points in NSW, and a case control study of clients receiving methadone syrup (MS) at two clinics. Between October 2004 and March 2005, 388 cases were identified, largely in NSW. The dosing point survey found almost all cases were clients prescribed MS (attack rate 4.5%). In multivariate analysis of data from dosing points that dispensed MS, use of take away doses or location of the dosing point in greater western Sydney were associated with illness. In the case control study, MS injection, use of street MS, high doses of MS, frequent takeaway doses, or use of benzodiazepines were associated with illness. Testing found no abnormality in associated batches of MS. Batches of MS temporally associated with the outbreak were quarantined from use and the outbreak subsided. While a direct causal link could not be established, available evidence suggests that a contaminant may have caused the outbreak. Epidemiological analyses are important for assessing concerns about product safety following marketing approval.

Maternal and neonatal effects of adding morphine to low‑dose ...

African Journals Online (AJOL)

2013-07-25

Jul 25, 2013 ... morphine to low‑dose bupivacaine epidural anesthesia on labor and neonatal outcomes, and maternal side effects. ... A total of 120 pregnant women were randomized into two groups with 60 .... a body mass index (BMI) >30, intrauterine growth ... BMI, satisfaction from analgesia following the first dose,.

Foucault on methadone: beyond biopower.

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Keane, Helen

2009-09-01

This essay reviews four texts which critically analyse methadone maintenance therapy using Foucault as a key theoretical framework: [Friedman, J., & Alicea, M. (2001). Surviving heroin: Interviews with women in methadone clinics. Florida: University Press of Florida], [Bourgois, P. (2000). Disciplining addictions: The bio-politics of methadone and heroin in the United States. Culture Medicine and Psychiatry, 24, 165-195], [Bull, M. (2008). Governing the heroin trade: From treaties to treatment. Ashgate: Aldershot], and [Fraser, S., & valentine, k. (2008). Substance & substitution: Methadone subjects in liberal societies. New York: Palgrave Macmillan]. Taken together these works demonstrate one trajectory in the development of critical drug studies over the past decade. While all four view MMT as a regulatory technology which aims to create productive and obedient subjects, their understandings of the power relations of the clinic are quite distinct. The first two texts emphasise the social control of drug users, the third, issues of governmentality and liberal political practice, while the fourth engages with ontological questions about substances themselves. Thus while Foucauldian analysis has become familiar in social studies of drugs and alcohol, new uses for its conceptual tools continue to emerge.

Methadone treatments in a Swiss Region, 2001–2008: a registry-based analysis

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Huissoud Thérèse

2012-12-01

Full Text Available Abstract Background To determine, in a region of Switzerland, the duration of retention in opioid substitution treatments with methadone (OSTM, duration of treatment interruptions, probability of re-entry to treatment after a treatment interruption, and associated factors. Methods A secondary analysis of registry-based data was performed with patients (n = 2880 registered in the methadone treatment register database of the Public Health Service of the canton of Vaud between January 1, 2001 and June 30, 2008. Survival analysis and multivariate analysis was conducted. Results The probability of remaining on treatment was 69% at 1 year and 45% at 3 years (n =1666. One-third of patients remained on treatment beyond 5 years. The estimated hazard of leaving treatment was increased by a ratio of 1.31 in the case of a first treatment (P = 0.001, 1.83 for those without a fixed home (P P n = 1581. Factors at the interruption of treatment associated with a higher probability of re-entering were: interruption not due to methadone withdrawal, bad physical health, and higher methadone dose. Conclusions OSTM are long-term (maintenance treatments in Switzerland. Younger age, bad living conditions at entry, and first treatment are predictors of lower retention. Approximately one-half of patients who interrupt treatment will re-enter treatment within 5 years.

Induction of hepatic aryl hydrocarbon hydroxylase and epoxide hydrase in Wistar rats pretreated with oral methadone hydrochloride.

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Bellward, G D; Gontovnick, L S; Otten, M

1977-01-01

Methadone-HCl added to the drinking water of adult female Wistar rats for 4 weeks produced an increase in the aryl hydrocarbon hydroxylase activity of the hepatic microsomal fraction to 222% of control levels. No change was seen in epoxide hydrase activity. In contrast, when male rats were treated similarly, there was an increase in epoxide hydrase activity to 212% of controls with no change in aryl hydrocarbon hydroxylase activity. No such changes were observed when the subcutaneous route of administration or chronic, low-dose, intraperitoneal injections were used. There were no differences in hepatic cytochrome P-450 or protein concentrations in treated animals as compared to their respective control groups. Control studies were carried out with quinine sulfate in the drinking water to decrease water intake to the level of the methadone-treated group. No elevation in either enzyme activity occurred in this control group. Similarly, paired-feeding studies showed the elevation of enzyme activity to be due to the methadone, not food deprivation. The effects of concurrent therapy of methadone with phenobarbital sodium or 3-methylcholanthrene were compared.

The becoming of methadone in Kenya: How an intervention's implementation constitutes recovery potential.

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Rhodes, Tim

2018-03-01

This analysis treats the recent introduction of methadone treatment in Kenya as a case of 'evidence-making intervention'. Using 30 qualitative interviews with people in receipt of methadone treatment in Nairobi, Kenya, methadone's becoming is treated as an effect of its narrative and material implementations. The interviews are shown to enact a narrative of methadone recovery potential towards normalcy beyond addiction. Such recovery potential is materialised in practice through social interactions wherein methadone's embodied effects are seen to be believed. Here, the recovering body affects others' recovery potential. In a context of competing claims about methadone's effects, including the circulation of doubt about experimenting with methadone treatment, embodied methadone effect helps moderate the multiverse of methadone knowledge. The material dynamics of methadone treatment delivery also affect its recovery potential, with the methadone queue enacting a rationing of recovery hope. Here, the experience of methadone's implementation loops back to a life with drugs. I conclude that there is a coexistence of potentiality and actuality, a 'methadone multiple', produced through its narrative and material implementations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Methadone versus buprenorphine for the treatment of opioid abuse in pregnancy: science and stigma.

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Holbrook, Amber M

2015-01-01

The past decade has seen an increase in rates of opioid abuse during pregnancy. This clinical challenge has been met with debate regarding whether or not illicit and prescription opioid-dependent individuals require different treatment approaches; whether detoxification is preferable to maintenance; and the efficacy of methadone versus buprenorphine as treatment options during pregnancy. The clinical recommendations resulting from these discussions are frequently influenced by the comparative stigma attached to heroin abuse and methadone maintenance versus prescription opioid abuse and maintenance treatment with buprenorphine. While some studies have suggested that a subset of individuals who abuse prescription opioids may have different characteristics than heroin users, there is currently no evidence to suggest that buprenorphine is better suited to treatment of prescription opioid abuse than methadone. Similarly, despite its perennial popularity, there is no evidence to recommend detoxification as an efficacious approach to treatment of opioid dependence during pregnancy. While increased access to treatment is important, particularly in rural areas, there are multiple medical and psychosocial reasons to recommend comprehensive substance abuse treatment for pregnant women suffering from substance use disorders rather than office-based provision of maintenance medication. Both methadone and buprenorphine are important treatment options for opioid abuse during pregnancy. Methadone may still remain the preferred treatment choice for some women who require higher doses for stabilization, have a higher risk of treatment discontinuation, or who have had unsuccessful treatment attempts with buprenorphine. As treatment providers, we should advocate to expand available treatment options for pregnant women in all States.

Methadone radioimmunoassay: two simple methods

International Nuclear Information System (INIS)

Robinson, K.; Smith, R.N.

1983-01-01

Two simple and economical radioimmunoassays for methadone in blood or urine are described. Haemolysis, decomposition, common anticoagulants and sodium fluoride do not affect the results. One assay used commercially-available [1- 3 H](-)-methadone hydrobromide as the label, while the other uses a radioiodinated conjugate of 4-dimethylamino-2,2-diphenylpentanoic acid and L-tyrosine methyl ester. A commercially-available antiserum is used in both assays. Normethadone and α-methadol cross-react to a small extent with the antiserum while methadone metabolites, dextropropoxyphene, dipipanone and phenadoxone have negligible cross-reactivities. The 'cut-offs' of the two assays as described are 30 and 33 ng ml -1 for blood, and 24 and 21 ng ml -1 for urine. The assay using the radioiodinated conjugate can be made more sensitive if required by increasing the specific activity of the label. (author)

Prenatal methadone exposure is associated with altered neonatal brain development

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Victoria J. Monnelly

Full Text Available Methadone is used for medication-assisted treatment of heroin addiction during pregnancy. The neurodevelopmental outcome of children with prenatal methadone exposure can be sub-optimal. We tested the hypothesis that brain development is altered among newborn infants whose mothers were prescribed methadone.20 methadone-exposed neonates born after 37weeks' postmenstrual age (PMA and 20 non-exposed controls underwent diffusion MRI at mean PMA of 39+2 and 41+1weeks, respectively. An age-optimized Tract-based Spatial Statistics (TBSS pipeline was used to perform voxel-wise statistical comparison of fractional anisotropy (FA data between exposed and non-exposed neonates.Methadone-exposed neonates had decreased FA within the centrum semiovale, inferior longitudinal fasciculi (ILF and the internal and external capsules after adjustment for GA at MRI (p<0.05, TFCE corrected. Median FA across the white matter skeleton was 12% lower among methadone-exposed infants. Mean head circumference (HC z-scores were lower in the methadone-exposed group (−0.52 (0.99 vs 1.15 (0.84, p<0.001; after adjustment for HC z-scores, differences in FA remained in the anterior and posterior limbs of the internal capsule and the ILF. Polydrug use among cases was common.Prenatal methadone exposure is associated with microstructural alteration in major white matter tracts, which is present at birth and is independent of head growth. Although the findings cannot be attributed to methadone per se, the data indicate that further research to determine optimal management of opioid use disorder during pregnancy is required. Future studies should evaluate childhood outcomes including infant brain development and long-term neurocognitive function. Keywords: Prenatal, Methadone, Brain, Neonate, MRI, Opioid

Synthesis and physico-chemical properties of (R,S)-6-ditrideuteriomethylamino-4,4-diphenylheptan-3-one hydrochloride (methadone-d6)

International Nuclear Information System (INIS)

Gerardy, B.M.; Poupaert, J.H.; Vandervorst, D.; Dumont, P.; Declerq, J.-P.; Meerssche, M. van; Portoghese, P.S.

1985-01-01

A reaction sequence is described to synthesize (R,S)-6-ditrideuteriomethylamino-4,4-diphenylheptan-3-one hydrochloride (methado-ne-d 6 .HC1) in 10.5% overall yield starting from dimethylamine-d 6 hydrochloride. While methadone-d 6 .HC1 had rather similar physicochemical properties compared to methadone.HC1 in the solid phase, a divergent behaviour was observed in solution (pKa, chromatographic and 13 C-NMR data). A higher basicity along with a more important hydrophilicity were observed for the d 6 -derivative. A 13 C-NMR study showed significant differences in the 13 C chemical shifts, which were attributed in part to the intrinsic nature of D itself and in part to a conformational perturbation. The longer duration of antinociceptive action, along with higher tsub(1/2) and clearance, and the depression of the metabolic N-demethylation process were the only biological properties modified by the deuteration. (author)

Opium tincture versus methadone syrup in management of acute raw opium withdrawal: A randomized, double-blind, controlled trial.

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Tabassomi, Farzaneh; Zarghami, Mehran; Shiran, Mohammad-Reza; Farnia, Samaneh; Davoodi, Mohsen

2016-01-01

The aim of this study was to evaluate the effectiveness of opium tincture versus methadone syrup in the management of acute withdrawal syndrome in opium dependent patients during the detoxification period. In this double-blind randomized controlled study, a total of 74 adult male raw opium dependent patients were treated with opium tincture or methadone syrup 2 times daily for 5 consecutive days. Detoxification was initiated by tapered dose reductions to reach abstinence. At the end of the 10th day, the medications were discontinued. The Objective Opioid Withdrawal Scale was used to assess withdrawal symptoms every day. Significant decreases on the Objective Opioid Withdrawal Scale were found for both treatment methods during the study period (p Opium tincture can be considered as a potential substitute for methadone syrup for suppression of raw opium withdrawal symptoms, with minimal adverse effects.

Evaluation of poly-drug use in methadone-related fatalities using segmental hair analysis

DEFF Research Database (Denmark)

Nielsen, Marie Katrine Klose; Johansen, Sys Stybe; Linnet, Kristian

2015-01-01

segmental hair analysis. The study included 99 methadone-related fatalities collected in Denmark from 2008 to 2011, where both blood and hair were available. The cases were divided into three subgroups based on the cause of death; methadone poisoning (N=64), poly-drug poisoning (N=28) or methadone poisoning...... combined with fatal diseases (N=7). No significant differences between methadone concentrations in the subgroups were obtained in both blood and hair. The methadone blood concentrations were highly variable (0.015-5.3, median: 0.52mg/kg) and mainly within the concentration range detected in living...... methadone users. In hair, methadone was detected in 97 fatalities with concentrations ranging from 0.061 to 211ng/mg (median: 11ng/mg). In the remaining two cases, methadone was detected in blood but absent in hair specimens, suggesting that these two subjects were methadone-naive users. Extensive poly...

Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.

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Crist, Richard C; Li, James; Doyle, Glenn A; Gilbert, Alex; Dechairo, Bryan M; Berrettini, Wade H

2018-01-01

Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration. Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341). Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68.7% male). Genotypes were then used to determine the metabolism phenotype for each pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for association with dropout rate and mean dose. Genotype for 5-HTTLPR in the SLC6A4 gene was nominally associated with dropout rate when the methadone and buprenorphine/naloxone groups were combined. When the most significant variants associated with dropout rate were analyzed using pairwise analyses, SLC6A4 (5-HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with dropout rate in methadone patients. None of the genes analyzed in the study was associated with mean dose of methadone or buprenorphine/naloxone. This study suggests that functional polymorphisms related to synaptic dopamine or serotonin levels may predict dropout rates during methadone treatment. Patients with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met in COMT may require additional treatment to improve their chances of completing addiction treatment. Replication in other methadone patient populations will be necessary to ensure the validity of these findings.

Comparison of postoperative analgesia with methadone versus morphine in cardiac surgery

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Ana Carolina Carvalho

2018-03-01

Full Text Available Background and objectives: Pain is an aggravating factor of postoperative morbidity and mortality. The aim of this study was to compare the effects of methadone versus morphine using the numerical rating scale of pain and postoperative on-demand analgesia in patients undergoing myocardial revascularization. Method: A randomized, double-blind, parallel clinical trial was performed with patients undergoing coronary artery bypass grafting. The subjects were randomly divided into two groups: morphine group and methadone group. At the end of cardiac surgery, 0.1 mg.kg−1 adjusted body weight of methadone or morphine was administered intravenously. Patients were referred to the ICU, where the following was assessed: extubation time, time to first analgesic request, number of analgesic and antiemetic drug doses within 36 h, numerical pain scale at 12, 24, and 36 h postoperatively, and occurrence of adverse effects. Results: Each group comprised 50 patients. Methadone showed 22% higher efficacy than morphine as it yielded a number-needed-to-treat score of 6 and number-needed-to-harm score of 16. The methadone group showed a mean score of 1.9 ± 2.2 according to the numerical pain scale at 24 h after surgery, whereas as the morphine group showed a mean score of 2.9 ± 2.6 (p = 0.029. The methadone group required less morphine (29% than the morphine group (43% (p = 0.002. However, the time to first analgesic request in the postoperative period was 145.9 ± 178.5 min in the methadone group, and 269.4 ± 252.9 in the morphine group (p = 0.005. Conclusions: Methadone was effective for analgesia in patients undergoing coronary artery bypass grafting without extracorporeal circulation. Resumo: Justificativa e objetivos: A dor é fator agravante da morbidade e mortalidade pós-operatória. O objetivo foi comparar o efeito da metadona versus morfina quanto à dor e demanda de analgesia pós-operatória em pacientes submetidos à revasculariza

Moving toward Personalized Medicine in the Methadone Maintenance Treatment Program: A Pilot Study on the Evaluation of Treatment Responses in Taiwan

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Hsin-Ya Lee

2013-01-01

Full Text Available This pilot study simultaneously evaluated the effects of various factors, including genetic variations of CYP2B6, CYP2C19, and ABCB1, demographic characteristics, disease states, methadone-drug interactions (MDIs, and poly-substance use, on the treatment responses among non-HIV patients in the methadone maintenance treatment program (MMTP in Taiwan. A total of 178 patients were recruited from two major hospitals that provided MMTP services in southern Taiwan, and information regarding concomitant medications and diseases was acquired from the National Health Insurance (NHI program. The results demonstrated that the methadone maintenance dose, CYP2B6 785G allele, and ABCB1 2677T allele have positive effects on the methadone plasma concentration. In contrast, patients with HCV coinfection, alcohol problems, and psychiatric diseases may have a negative response to treatment. Thus, a comprehensive evaluation of treatment responses in the MMTP should include not only genetic polymorphisms in methadone metabolism and transporter proteins, but also concomitant diseases, MDIs, and poly-substance use. The results also suggest that personalized medicine may be indispensable for a better outcome of the MMTP.

Plasma levels and symptom complaints in patients maintained on daily dosage of methadone hydrochloride.

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Horns, W H; Rado, M; Goldstein, A

1975-06-01

Plasma methadone levels, symptom complaints, and urine tests for illicit opiate use were followed weekly in 17 patients on a methadone maintenance program. There were very large differences between patients in the plasma level established at a given dosage, implying large differences in the rate of methadone metabolism. Despite virtually constant daily dosage, the plasma methadone levels fluctuated greatly from week to week and from day to day in individual patients. With rate exceptions there was no relationship between plasma methadone level and symptom complaints or between weekly chamges in plasma methadone level and changes in symptom complaints. Except possible to identify the ocassional patient with unusually low plasam methadone levels, the determination of methadone levels is not likely to be or practical value in methadone programs.

Attitudes and beliefs towards methadone maintenance treatment among Australian prison health staff.

Science.gov (United States)

Gjersing, Linn R; Butler, Tony; Caplehorn, John R M; Belcher, Josephine M; Matthews, Richard

2007-09-01

Justice Health NSW has one of the most extensive prison-based methadone programmes in the world. We examine prison health staff attitudes towards methadone treatment and compare these with community methadone staff. A cross-sectional survey of 202 staff employed by Justice Health New South Wales was undertaken in 2003. Results. The mean scores on the various sub-scales were: abstinence-orientation (AO) 2.9 (95% CI 2.8 - 3.0); disapproval of drug use (DDU) 3.3 (95% CI 3.2 - 3.4); knowledge (Know) 2.7 (95% CI 2.4 - 2.9); and toxicity 4.6 (95% CI 4.2 - 5.0). Both the AO and DDU score were correlated negatively with the Know score (r = -0.37 and r = -0.13, respectively). Prison health staff had higher AO (2.9 vs. 2.6, p US community methadone staff about the toxicity of methadone (4.6 vs. 0.0, p prison health staff attitudes to methadone treatment. Correctional health staff tend to be more abstinence-orientated, more likely to disapprove of drug use, and less knowledgeable about the risks and benefits of methadone than Australian community methadone staff. The findings have important implications for training health staff working in the prison environment with regard to client retention on methadone treatment.

Bioavailability of morphine, methadone, hydromorphone, and oxymorphone following buccal administration in cats.

Science.gov (United States)

Pypendop, B H; Ilkiw, J E; Shilo-Benjamini, Y

2014-06-01

Buccal administration of buprenorphine is commonly used to treat pain in cats. It has been argued that absorption of buprenorphine through the buccal mucosa is high, in part due to its pKa of 8.24. Morphine, methadone, hydromorphone, and oxymorphone have a pKa between 8 and 9. This study characterized the bioavailability of these drugs following buccal administration to cats. Six healthy adult female spayed cats were used. Buccal pH was measured prior to drug administration. Morphine sulfate, 0.2 mg/kg IV or 0.5 mg/kg buccal; methadone hydrochloride, 0.3 mg/kg IV or 0.75 mg/kg buccal; hydromorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal; or oxymorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal were administered. All cats received all treatments. Arterial blood was sampled immediately prior to drug administration and at various times up to 8 h thereafter. Bioavailability was calculated as the ratio of the area under the time-concentration curve following buccal administration to that following IV administration, each indexed to the administered dose. Mean ± SE (range) bioavailability was 36.6 ± 5.2 (12.7-49.5), 44.2 ± 7.9 (18.7-70.5), 22.4 ± 6.9 (6.4-43.4), and 18.8 ± 2.0 (12.9-23.5)% for buccal administration of morphine, methadone, hydromorphone, and oxymorphone, respectively. Bioavailability of methadone was significantly higher than that of oxymorphone. © 2013 John Wiley & Sons Ltd.

Evaluation of poly-drug use in methadone-related fatalities using segmental hair analysis.

Science.gov (United States)

Nielsen, Marie Katrine Klose; Johansen, Sys Stybe; Linnet, Kristian

2015-03-01

In Denmark, fatal poisoning among drug addicts is often related to methadone. The primary mechanism contributing to fatal methadone overdose is respiratory depression. Concurrent use of other central nervous system (CNS) depressants is suggested to heighten the potential for fatal methadone toxicity. Reduced tolerance due to a short-time abstinence period is also proposed to determine a risk for fatal overdose. The primary aims of this study were to investigate if concurrent use of CNS depressants or reduced tolerance were significant risk factors in methadone-related fatalities using segmental hair analysis. The study included 99 methadone-related fatalities collected in Denmark from 2008 to 2011, where both blood and hair were available. The cases were divided into three subgroups based on the cause of death; methadone poisoning (N=64), poly-drug poisoning (N=28) or methadone poisoning combined with fatal diseases (N=7). No significant differences between methadone concentrations in the subgroups were obtained in both blood and hair. The methadone blood concentrations were highly variable (0.015-5.3, median: 0.52mg/kg) and mainly within the concentration range detected in living methadone users. In hair, methadone was detected in 97 fatalities with concentrations ranging from 0.061 to 211ng/mg (median: 11ng/mg). In the remaining two cases, methadone was detected in blood but absent in hair specimens, suggesting that these two subjects were methadone-naive users. Extensive poly-drug use was observed in all three subgroups, both recently and within the last months prior to death. Especially, concurrent use of multiple benzodiazepines was prevalent among the deceased followed by the abuse of morphine, codeine, amphetamine, cannabis, cocaine and ethanol. By including quantitative segmental hair analysis, additional information on poly-drug use was obtained. Especially, 6-acetylmorphine was detected more frequently in hair specimens, indicating that regular abuse of

Methadone-Related Overdose Deaths in a Liberal Opioid Maintenance Treatment Programme

DEFF Research Database (Denmark)

Tjagvad, C.; Skurtveit, Svetlana; Linnet, K.

2016-01-01

methadone-related overdose deaths in a liberal OMT programme. Methods: Drug-overdose deaths (n = 130) with detection of methadone in Copenhagen, Aarhus, and Odense Municipality, Denmark, during the period 2008-2011 were identified from a registry. Cases with and without prescribed methadone as OMT were...

Methadone induced torsades de pointes and ventricular fibrillation: A case review

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Somayeh Khalesi

2014-11-01

Full Text Available BACKGROUND: Methadone is a synthetic opioid, which has been successfully used in treating heroin addiction and chronic pain syndrome in palliative care for more than 30 years. This drug is a potent blocker of the delayed rectifier potassium ion channel, which may result in corrected QT (QTc interval prolongation and increased risk of torsades de pointes (TdP in susceptible individuals. CASE REPORT: We describe here a case of methadone-induced TdP that deteriorated into ventricular fibrillation, which was resolved after treatment with IV magnesium, potassium, and Lidocaine. Our purpose in this case review was to highlight the risk of cardiac arrhythmias, in particular QTc interval prolongation leading to TdP in a heroin-dependent patient receiving methadone substitution therapy, and then to present a perspective on treatment and prevention strategies of methadone induced prolonged QTc. CONCLUSION: Methadone-induced TdP is a potentially fatal complication of methadone therapy. As the popularity of methadone use grows, clinicians will encounter more cases of methadone induced TdP, especially in our region, Iran. Hence, a thorough patient history and electrocardiogram monitoring are essential for patients treated with this agent, and alterations in treatment options may be necessary.    Normal 0 false false false EN-US X-NONE AR-SA

In silico ordinary differential equation/partial differential equation hemodialysis model estimates methadone removal during dialysis

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Linares OA

2015-07-01

Full Text Available Oscar A Linares,1 William E Schiesser,2 Jeffrey Fudin,3–6 Thien C Pham,6 Jeffrey J Bettinger,6 Roy O Mathew,6 Annemarie L Daly7 1Translational Genomic Medicine Lab, Plymouth Pharmacokinetic Modeling Study Group, Plymouth, MI, 2Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA, 3University of Connecticut School of Pharmacy, Storrs, CT, 4Western New England College of Pharmacy, Springfield, MA, 5Albany College of Pharmacy and Health Sciences, Albany, NY, 6Stratton VA Medical Center, Albany, NY, 7Grace Hospice of Ann Arbor, Ann Arbor, MI, USA Background: There is a need to have a model to study methadone’s losses during hemodialysis to provide informed methadone dose recommendations for the practitioner. Aim: To build a one-dimensional (1-D, hollow-fiber geometry, ordinary differential equation (ODE and partial differential equation (PDE countercurrent hemodialyzer model (ODE/PDE model. Methodology: We conducted a cross-sectional study in silico that evaluated eleven hemodialysis patients. Patients received a ceiling dose of methadone hydrochloride 30 mg/day. Outcome measures included: the total amount of methadone removed during dialysis; methadone’s overall intradialytic mass transfer rate coefficient, km; and, methadone’s removal rate, jME. Each metric was measured at dialysate flow rates of 250 mL/min and 800 mL/min. Results: The ODE/PDE model revealed a significant increase in the change of methadone’s mass transfer with increased dialysate flow rate, %Δ km=18.56, P=0.02, N=11. The total amount of methadone mass transferred across the dialyzer membrane with high dialysate flow rate significantly increased (0.042±0.016 versus 0.052±0.019 mg/kg, P=0.02, N=11. This was accompanied by a small significant increase in methadone’s mass transfer rate (0.113±0.002 versus 0.014±0.002 mg/kg/h, P=0.02, N=11. The ODE/PDE model accurately predicted methadone’s removal during dialysis. The absolute value

Prenatal exposure to a low fipronil dose disturbs maternal behavior and reflex development in rats.

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Udo, Mariana S B; Sandini, Thaísa M; Reis, Thiago M; Bernardi, Maria Martha; Spinosa, Helenice S

2014-01-01

Fipronil (FPN) is a phenylpyrazole insecticide used in veterinary services and agriculture, and it is of considerable concern to public health. It inhibits the chloride channels associated with gamma-amino butyric acid (GABA) receptors in mammals and also inhibits the chloride channels associated with GABA and glutamate (Glu) receptors in insects. In this study, a commercial product containing fipronil was orally administered to pregnant Wistar rats at dose levels of 0.1, 1.0, or 10.0mg/kg/day from the sixth to twentieth day of gestation (n=10 pregnant rats/group). Its toxicity was evaluated based on maternal toxicity, reproductive quality, maternal behavior, and offspring physical as well as reflex development. All parameters observed in the observed offspring were assigned to one ink-marked couple in each litter (n=20 animals/group - 10 males and 10 females). The offspring couple represented the litter. Slight maternal toxicity presented during the second week of gestation for each fipronil dose and during the third gestational week at the highest dose due to lower chow intake. However, no effects were observed for gestational weight gain or gestation time, and the reproductive quality was not impaired, which suggests no adverse maternal effects from the doses during pregnancy. Moreover, the lowest fipronil dose compromised the active and reflexive maternal responses, but the highest dose induced a stereotyped active response without interfering in the reflexive reaction. For offspring development, no differences in physical growth parameters were observed between the groups. However, considering reflex development, our results showed that negative geotaxis reflex development was delayed in the offspring at the lowest fipronil dose, and palmar grasp was lost earlier at the lowest and intermediate fipronil doses. These results suggest that the alterations observed herein may be due to either the GABAergic system or endocrine disruption, considering that fipronil

Dealing with aggressive methadone patients in community pharmacy: a critical incident study.

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Irwin, Amy; Laing, Christianne; Mearns, Kathryn

2012-01-01

Community pharmacists are an important link between methadone patients and the health service in the United Kingdom. However, many pharmacists feel ill prepared to deal with methadone patients, with aggressive behavior a particular concern. To assess the perceived impact of methadone patient aggression on pharmacy practice. Sixteen registered pharmacists with a minimum of 3 years' work experience were recruited from within 3 Scottish health boards. Critical incident interviews were conducted to assess pharmacist behavior during an interaction with an aggressive methadone patient. Factors considered by pharmacists to have a negative impact on an interaction with an aggressive methadone patient included intoxication of the patient, the presence of a new or an inexperienced pharmacist, and a restricted time frame for dispensing methadone. Positive factors when dealing with aggressive patients were authoritative behavior by the pharmacist, a separate dispensing area for methadone patients, or a solid counter and a positive relationship between pharmacist and patient. Aggression from methadone patients is a risk when dispensing methadone. However, action can be taken by the pharmacist to minimize the impact of that aggression on pharmacy practice. The provision of further training and support, particularly to inexperienced pharmacists, could further reduce the negative impact of patient aggression. The present study indicates that such training could be based on nontechnical skills to strengthen current leadership and teamwork behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.

Neonatal Abstinence Syndrome (NAS): Transitioning Methadone Treated Infants From An Inpatient to an Outpatient Setting

Science.gov (United States)

Backes, Carl H.; Backes, Carl R.; Gardner, Debra; Nankervis, Craig A.; Giannone, Peter J.; Cordero, Leandro

2013-01-01

Background Each year in the US approximately 50,000 neonates receive inpatient pharmacotherapy for the treatment of neonatal abstinence syndrome (NAS). Objective To compare the safety and efficacy of a traditional inpatient only approach with a combined inpatient and outpatient methadone treatment program. Design/Methods Retrospective review (2007-9). Infants were born to mothers maintained on methadone or buprenorphine in an antenatal substance abuse program. All infants received methadone for NAS treatment as inpatient. Methadone weaning for the traditional group (75 pts) was inpatient while the combined group (46 pts) was outpatient. Results Infants in the traditional and combined groups were similar in demographics, obstetrical risk factors, birth weight, GA and the incidence of prematurity (34 & 31%). Hospital stay was shorter in the combined than in the traditional group (13 vs 25d; p < 0.01). Although the duration of treatment was longer for infants in the combined group (37 vs 21d, p<0.01), the cumulative methadone dose was similar (3.6 vs 3.1mg/kg, p 0.42). Follow-up: Information was available for 80% of infants in the traditional and 100% of infants in the combined group. All infants in the combined group were seen ≤ 72 hours from hospital discharge. Breast feeding was more common among infants in the combined group (24 vs. 8% p<0.05). Following discharge there were no differences between the two groups in hospital readmissions for NAS. Prematurity (<37w GA) was the only predictor for hospital readmission for NAS in both groups (p 0.02, OR 5). Average hospital cost for each infant in the combined group was $13,817 less than in the traditional group. Conclusions A combined inpatient and outpatient methadone treatment in the management of NAS decreases hospital stay and substantially reduces cost. Additional studies are needed to evaluate the potential long term benefits of the combined approach on infants and their families. PMID:21852772

Contribution of maternal radionuclide burdens to prenatal radiation doses: Relationships between annual limits on intake and prenatal doses

International Nuclear Information System (INIS)

Sikov, M.R.; Hui, T.E.

1993-10-01

This addendum describes approaches for calculating and expressing radiation doses to the embryo/fetus from maternal intakes of radionuclides at levels corresponding to fractions or multiples of the Annual Limits on Intake (ALI). Information, concerning metabolic or dosimetric characteristics and the placental transfer of selected, occupationally significant radionuclides was presented in NUREG/CR-5631, Revision 1. That information was used to estimate levels of radioactivity in the embryo/fetus as a function of stage of pregnancy and time after entry. Extension of MIRD methodology to accommodate gestational-stage-dependent characteristics allowed dose calculations for the simplified situation based on introduction of 1 μCi into the woman's transfer compartment (blood). The expanded scenarios in this addendum include repeated or chronic ingestion or inhalation intakes by a woman during pregnancy and body burdens at the beginning of pregnancy. Tables present dose equivalent to the embryo/fetus relative to intakes of these radionuclides in various chemical or physical forms and from preexisting maternal burdens corresponding to ALI; complementary intake values (fraction of an ALI and μCi) that yield a dose equivalent of 0.05 rem are included. Similar tables give these measures of dose equivalency to the uterus from intakes of radionuclides for use as surrogates for embryo/fetus dose when biokinetic information is not available

Fatal methadone and heroin overdoses : Time trends in England and Wales

NARCIS (Netherlands)

Neeleman, J; Farrell, M

Study objective-Although the total number of self poisonings in England and Wales has dropped by 32%, the number involving methadone and/or heroin rose by 900% in 1974-92. Because of concern about the role of methadone in this increase, the part played by methadone and heroin in poisoning deaths in

Methadone Overdose and Its Complications in Patients Admitted to the Toxicology Emergency Ward of Baharloo Hospital of Tehran in 2011-2012

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Behnam Behnoush

2014-11-01

Full Text Available Background: To date, studies on methadone overdose in adults have not been reported in Iran. Hence, this study was performed to determine the frequency of methadone overdose and its associated complications in Baharloo Hospital of Tehran between August 2011 and August 2012. Methods: This cross-sectional study was done on 390 cases. All patients with methadone overdoses and positive urine screen test for methadone were included in this case study through census method. Demographic data and overdose complications, such as loss of consciousness, respiratory complications, arrhythmia, hemodynamic disturbances, and QTC interval, were recorded in the questionnaire. Data were analyzed by SPSS software and Kolmogorov Smirnov, t-test, and Chi-square tests were used for data analysis. Results: Overall, 84.1% of the samples were male and the mean age of the samples was 35.53±11.25 years (range: 15-84 years. Mean of the methadone dose used in current admissions was 96.13±52.34 mg. Concomitant drug abuse and concomitant uses of medications were seen in 25.9% and 36.9% of the patients, respectively. Respiratory depression, pulmonary edema, pneumonia, aspiration, and arrhythmia were seen in 87.9%, 26.2%, 3.3%, 7.4%, and 15.4% of the patients, respectively. There were significant differences between concomitant medications, duration of methadone use, and QTc interval prolongation and arrhythmia (P<0.05. Conclusion: Based on the findings of the present study, initial screening of ECG changes and QT interval prolongation as well as arrhythmias should be considered in patients on methadone therapy and concurrent drug abuse and co-administration of medications that lead to QT prolongation should be avoided in them.

In silico ordinary differential equation/partial differential equation hemodialysis model estimates methadone removal during dialysis

Science.gov (United States)

Linares, Oscar A; Schiesser, William E; Fudin, Jeffrey; Pham, Thien C; Bettinger, Jeffrey J; Mathew, Roy O; Daly, Annemarie L

2015-01-01

Background There is a need to have a model to study methadone’s losses during hemodialysis to provide informed methadone dose recommendations for the practitioner. Aim To build a one-dimensional (1-D), hollow-fiber geometry, ordinary differential equation (ODE) and partial differential equation (PDE) countercurrent hemodialyzer model (ODE/PDE model). Methodology We conducted a cross-sectional study in silico that evaluated eleven hemodialysis patients. Patients received a ceiling dose of methadone hydrochloride 30 mg/day. Outcome measures included: the total amount of methadone removed during dialysis; methadone’s overall intradialytic mass transfer rate coefficient, km; and, methadone’s removal rate, jME. Each metric was measured at dialysate flow rates of 250 mL/min and 800 mL/min. Results The ODE/PDE model revealed a significant increase in the change of methadone’s mass transfer with increased dialysate flow rate, %Δkm=18.56, P=0.02, N=11. The total amount of methadone mass transferred across the dialyzer membrane with high dialysate flow rate significantly increased (0.042±0.016 versus 0.052±0.019 mg/kg, P=0.02, N=11). This was accompanied by a small significant increase in methadone’s mass transfer rate (0.113±0.002 versus 0.014±0.002 mg/kg/h, P=0.02, N=11). The ODE/PDE model accurately predicted methadone’s removal during dialysis. The absolute value of the prediction errors for methadone’s extraction and throughput were less than 2%. Conclusion ODE/PDE modeling of methadone’s hemodialysis is a new approach to study methadone’s removal, in particular, and opioid removal, in general, in patients with end-stage renal disease on hemodialysis. ODE/PDE modeling accurately quantified the fundamental phenomena of methadone’s mass transfer during hemodialysis. This methodology may lead to development of optimally designed intradialytic opioid treatment protocols, and allow dynamic monitoring of outflow plasma opioid concentrations for model

Fetal shielding combined with state of the art CT dose reduction strategies during maternal chest CT

Energy Technology Data Exchange (ETDEWEB)

Chatterson, Leslie C., E-mail: lch088@mail.usask.ca [Department of Diagnostic Imaging, University of Saskatchewan (Canada); Leswick, David A.; Fladeland, Derek A. [Department of Diagnostic Imaging, University of Saskatchewan (Canada); Hunt, Megan M.; Webster, Stephen [Saskatchewan Ministry of Labour Relations and Workplace Safety (Canada); Lim, Hyun [Department of Community Health and Epidemiology, College of Medicine, University of Saskatchewan (Canada)

2014-07-15

Purpose: Custom bismuth-antimony shields were previously shown to reduce fetal dose by 53% on an 8DR (detector row) CT scanner without dynamic adaptive section collimation (DASC), automatic tube current modulation (ATCM) or adaptive statistical iterative reconstruction (ASiR). The purpose of this study is to compare the effective maternal and average fetal organ dose reduction both with and without bismuth-antimony shields on a 64DR CT scanner using DASC, ATCM and ASiR during maternal CTPA. Materials and methods: A phantom with gravid prosthesis and a bismuth-antimony shield were used. Thermoluminescent dosimeters (TLDs) measured fetal radiation dose. The average fetal organ dose and effective maternal dose were determined using 100 kVp, scanning from the lung apices to the diaphragm utilizing DASC, ATCM and ASiR on a 64DR CT scanner with and without shielding in the first and third trimester. Isolated assessment of DASC was done via comparing a new 8DR scan without DASC to a similar scan on the 64DR with DASC. Results: Average third trimester unshielded fetal dose was reduced from 0.22 mGy ± 0.02 on the 8DR to 0.13 mGy ± 0.03 with the conservative 64DR protocol that included 30% ASiR, DASC and ATCM (42% reduction, P < 0.01). Use of a shield further reduced average third trimester fetal dose to 0.04 mGy ± 0.01 (69% reduction, P < 0.01). The average fetal organ dose reduction attributable to DASC alone was modest (6% reduction from 0.17 mGy ± 0.02 to 0.16 mGy ± 0.02, P = 0.014). First trimester fetal organ dose on the 8DR protocol was 0.07 mGy ± 0.03. This was reduced to 0.05 mGy ± 0.03 on the 64DR protocol without shielding (30% reduction, P = 0.009). Shields further reduced this dose to below accurately detectable levels. Effective maternal dose was reduced from 4.0 mSv on the 8DR to 2.5 mSv on the 64DR scanner using the conservative protocol (38% dose reduction). Conclusion: ASiR, ATCM and DASC combined significantly reduce effective maternal and fetal

Fetal shielding combined with state of the art CT dose reduction strategies during maternal chest CT

International Nuclear Information System (INIS)

Chatterson, Leslie C.; Leswick, David A.; Fladeland, Derek A.; Hunt, Megan M.; Webster, Stephen; Lim, Hyun

2014-01-01

Purpose: Custom bismuth-antimony shields were previously shown to reduce fetal dose by 53% on an 8DR (detector row) CT scanner without dynamic adaptive section collimation (DASC), automatic tube current modulation (ATCM) or adaptive statistical iterative reconstruction (ASiR). The purpose of this study is to compare the effective maternal and average fetal organ dose reduction both with and without bismuth-antimony shields on a 64DR CT scanner using DASC, ATCM and ASiR during maternal CTPA. Materials and methods: A phantom with gravid prosthesis and a bismuth-antimony shield were used. Thermoluminescent dosimeters (TLDs) measured fetal radiation dose. The average fetal organ dose and effective maternal dose were determined using 100 kVp, scanning from the lung apices to the diaphragm utilizing DASC, ATCM and ASiR on a 64DR CT scanner with and without shielding in the first and third trimester. Isolated assessment of DASC was done via comparing a new 8DR scan without DASC to a similar scan on the 64DR with DASC. Results: Average third trimester unshielded fetal dose was reduced from 0.22 mGy ± 0.02 on the 8DR to 0.13 mGy ± 0.03 with the conservative 64DR protocol that included 30% ASiR, DASC and ATCM (42% reduction, P < 0.01). Use of a shield further reduced average third trimester fetal dose to 0.04 mGy ± 0.01 (69% reduction, P < 0.01). The average fetal organ dose reduction attributable to DASC alone was modest (6% reduction from 0.17 mGy ± 0.02 to 0.16 mGy ± 0.02, P = 0.014). First trimester fetal organ dose on the 8DR protocol was 0.07 mGy ± 0.03. This was reduced to 0.05 mGy ± 0.03 on the 64DR protocol without shielding (30% reduction, P = 0.009). Shields further reduced this dose to below accurately detectable levels. Effective maternal dose was reduced from 4.0 mSv on the 8DR to 2.5 mSv on the 64DR scanner using the conservative protocol (38% dose reduction). Conclusion: ASiR, ATCM and DASC combined significantly reduce effective maternal and fetal

Effect of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold, following intravenous or buccal administration to cats.

Science.gov (United States)

Pypendop, Bruno H; Shilo-Benjamini, Yael; Ilkiw, Jan E

2016-11-01

To determine the effects of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold in cats, following buccal and intravenous (IV) administration. Randomized crossover study. Six healthy adult female ovariohysterectomized cats weighing 4.5 ± 0.4 kg. Morphine sulfate (0.2 mg kg -1 IV or 0.5 mg kg -1 buccal), methadone hydrochloride (0.3 mg kg -1 IV or 0.75 mg kg -1 buccal), hydromorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) or oxymorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) were administered. All cats were administered all treatments. Skin temperature and thermal threshold were measured in duplicate prior to drug administration, and at various times up to 8 hours after drug administration. The difference between thermal threshold and skin temperature (ΔT) was analyzed. Administration of methadone and hydromorphone IV resulted in significant increases in ΔT at 40 minutes after drug administration. Buccal administration of methadone resulted in significant increases in thermal threshold, although no significant difference from baseline measurement was detected at any time point. IV administration of morphine and oxymorphone, and buccal administration of morphine, hydromorphone and oxymorphone did not cause significant thermal antinociception. At the doses used in this study, IV administration of methadone and hydromorphone, and buccal administration of methadone resulted in transient thermal antinociception. The results of this study do not allow us to predict the usefulness of these drugs for providing analgesia in clinical patients. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses.

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Linardi, Renata L; Stokes, Ashley M; Keowen, Michael L; Barker, Steven A; Hosgood, Giselle L; Short, Charles R

2012-02-01

To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses. 6 healthy adult horses. Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects. In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration. Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.

Review of cancer pain management in patients receiving maintenance methadone therapy.

LENUS (Irish Health Repository)

Rowley, Dominic

2011-05-01

Methadone is commonly used in the treatment of heroin addiction. Patients with a history of opioid misuse or on methadone maintenance therapy (MMT) with cancer often have difficult to manage pain. We studied 12 patients referred to the palliative care service with cancer pain who were on MMT. All had difficult to control pain, and a third required 5 or more analgesic agents. Two patients had documented \\'\\'drug-seeking\\'\\' behavior. Methadone was used subcutaneously as an analgesic agent in 1 patient. We explore why patients on MMT have difficult to manage pain, the optimal management of their pain, and the increasing role of methadone as an analgesic agent in cancer pain.

Retention in methadone maintenance treatment in mainland China, 2004-2012: a literature review.

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Zhou, Kaina; Zhuang, Guihua

2014-01-01

Methadone maintenance treatment (MMT) was implemented in mainland China since 2004. Numerous individual studies have investigated MMT retention but the overview still remains unclear. The aim of the study was to review MMT retention rates and predicting factors in mainland China during 2004-2012. Chinese and English databases of literature were searched for studies reporting on retention rates and predicting factors in non-transfer MMT patients of fixed-site clinics in mainland China (2004-2012). Qualitative methods were used to synthesize the results. Nineteen studies were eligible for review, with sample size ranging from 29 to 3758. Retention rates varied between 30.0% at 6 months in Shanghai and 70.3% at 12 months in Xi'an. Predicting factors were non-treatment including sociodemographics (n=14), support system and social function (n=9), economic status (n=2) and psychological status (n=1), and treatment-related including drug use (n=15), methadone use (n=12), MMT clinics (n=9), MMT participation (n=7), awareness on MMT (n=5) and HIV serostatus (n=3). Methadone dose (n=12) and age (n=7) were the first two important specific factors. In mainland China, MMT retention rates are heterogeneous and relatively lower, and predicting factors mainly focus on objective aspects. Future work should further explore subjective predicting factors regarding MMT retention. © 2013.

Incarcerated intravenous heroin users: predictors of post-release utilization of methadone maintenance treatment.

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Lin, Huang-Chi; Wang, Peng-Wei; Yang, Yi-Hsin; Tsai, Jih-Jin; Yen, Cheng-Fang

2016-01-01

Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may facilitate entry of methadone maintenance treatment for incarcerated intravenous heroin

A randomized clinical trial of methadone maintenance for prisoners: results at 12 months postrelease.

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Kinlock, Timothy W; Gordon, Michael S; Schwartz, Robert P; Fitzgerald, Terrence T; O'Grady, Kevin E

2009-10-01

This study examined the impact of prison-initiated methadone maintenance at 12 months postrelease. Males with pre-incarceration heroin dependence (N = 204) were randomly assigned to (a) Counseling Only: counseling in prison, with passive referral to treatment upon release; (b) Counseling + Transfer: counseling in prison with transfer to methadone maintenance treatment upon release; and (c) Counseling + Methadone: counseling and methadone maintenance in prison, continued in the community upon release. The mean number of days in community-based drug abuse treatment were, respectively, Counseling Only, 23.1; Counseling + Transfer, 91.3; and Counseling + Methadone, 166.0 (p Counseling + Methadone participants were also significantly less likely than participants in each of the other two groups to be opioid-positive or cocaine-positive according to urine drug testing. These results support the effectiveness of prison-initiated methadone for males in the United States. Further study is required to confirm the findings for women.

Sexual dysfunction improved in heroin-dependent men after methadone maintenance treatment in Tianjin, China.

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Minying Zhang

Full Text Available OBJECTIVE: To investigate whether methadone maintenance treatment (MMT is correlated with sexual dysfunction in heroin-dependent men and to determine the prevalence and risk factors of sexual dysfunction among men on MMT. METHODS: The study included a retrospective survey and a cross-sectional survey which contained interviews of 293 men who are currently engaged in MMT. The results of the two surveys were compared. For a subset of 43 participants, radioimmunoassay was additionally conducted using retrospective and prospective blood samples to test the levels of plasma testosterone and luteinizing hormone. Other study evaluations were the International Index of Erectile Function (IIEF-15, and Self-rating Depression Scale. RESULTS: Sexual dysfunction in all five IIEF-15 domains (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction was strongly associated with long-term use of heroin. A decrease in the severity of sexual dysfunction was associated with MMT initiation. Erectile dysfunction, lack of sexual desire, inability to orgasm, and lack of intercourse satisfaction were significantly correlated with increasing age of the participants. Methadone dose and duration of methadone treatment were not found to be associated with sexual dysfunction. The level of plasma testosterone significantly declined during methadone treatment, but results from multivariate analysis indicated low levels of testosterone were not the main cause of sexual dysfunction. No correlation between reported depression status and sexual function was found. CONCLUSIONS: While high levels of sexual dysfunction were reported by heroin-dependent men in our study before and after MMT initiation, MMT appears to be correlated with improved sexual function in the population of the study.

The impact of benzodiazepine use on methadone maintenance treatment outcomes.

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Brands, Bruna; Blake, Joan; Marsh, David C; Sproule, Beth; Jeyapalan, Renuka; Li, Selina

2008-01-01

The purposes of this study were to examine predictors of benzodiazepine use among methadone maintenance treatment patients, to determine whether baseline benzodiazepine use influenced ongoing use during methadone maintenance treatment, and to assess the effect of ongoing benzodiazepine use on treatment outcomes (i.e., opioid and cocaine use and treatment retention). A retrospective chart review of 172 methadone maintenance treatment patients (mean age = 34.6 years; standard deviation = 8.5 years; 64% male) from January 1997 to December 1999 was conducted. At baseline, 29% were "non-users" (past year) of benzodiazepine, 36% were "occasional users," and 35% were "regular/problem users." Regular/problem users were more likely to have started opioid use with prescription opioids, experienced more overdoses, and reported psychiatric comorbidity. Being female, more years of opioid use, and a history of psychiatric treatment were significant predictors of baseline benzodiazepine use. Ongoing benzodiazepine users were more likely to have opioid-positive and cocaine-positive urine screens during methadone maintenance treatment. Only ongoing cocaine use was negatively related to retention. Benzodiazepine use by methadone maintenance treatment patients is associated with a more complex clinical picture and may negatively influence treatment outcomes.

Heroin-assisted treatment showed better efficacy than methadone

OpenAIRE

ANSSEAU, Marc; Demaret, Isabelle

2014-01-01

Background: A fraction of patients receiving methadone treatment pursues their use of street heroin. In Switzerland, a new treatment with prescribed diacetylmorphine (pharmaceutical heroin) was developed to help these heroin addicts resistant to methadone treatment to decrease their street heroin use. In this heroin-assisted treatment (HAT), diacetylmorphine is prescribed to severe heroin user and diacetylmorphine is administered by patients under the supervision of nurses in a...

Chronic methadone use, poor bowel visualization and failed colonoscopy: A preliminary study

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Verma, Siddharth; Fogel, Joshua; Beyda, David J; Bernstein, Brett; Notar-Francesco, Vincent; Mohanty, Smruti R

2012-01-01

AIM: To examine effects of chronic methadone usage on bowel visualization, preparation, and repeat colonoscopy. METHODS: In-patient colonoscopy reports from October, 2004 to May, 2009 for methadone dependent (MD) patients were retrospectively evaluated and compared to matched opioid naive controls (C). Strict criteria were applied to exclude patients with risk factors known to cause constipation or gastric dysmotility. Colonoscopy reports of all eligible patients were analyzed for degree of bowel visualization, assessment of bowel preparation (good, fair, or poor), and whether a repeat colonoscopy was required. Bowel visualization was scored on a 4 point scale based on multiple prior studies: excellent = 1, good = 2, fair = 3, or poor = 4. Analysis of variance (ANOVA) and Pearson χ2 test were used for data analyses. Subgroup analysis included correlation between methadone dose and colonoscopy outcomes. All variables significantly differing between MD and C groups were included in both univariate and multivariate logistic regression analyses. P values were two sided, and < 0.05 were considered statistically significant. RESULTS: After applying exclusionary criteria, a total of 178 MD patients and 115 C patients underwent a colonoscopy during the designated study period. A total of 67 colonoscopy reports for MD patients and 72 for C were included for data analysis. Age and gender matched controls were randomly selected from this population to serve as controls in a numerically comparable group. The average age for MD patients was 52.2 ± 9.2 years (range: 32-72 years) years compared to 54.6 ± 15.5 years (range: 20-81 years) for C (P = 0.27). Sixty nine percent of patients in MD and 65% in C group were males (P = 0.67). When evaluating colonoscopy reports for bowel visualization, MD patients had significantly greater percentage of solid stool (i.e., poor visualization) compared to C (40.3% vs 6.9%, P < 0.001). Poor bowel preparation (35.8% vs 9.7%, P < 0.001) and

Methadone induces CAD degradation and AIF-mediated necrotic-like cell death in neuroblastoma cells.

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Perez-Alvarez, Sergio; Iglesias-Guimarais, Victoria; Solesio, María E; Melero-Fernandez de Mera, Raquel María; Yuste, Víctor J; Galindo, María F; Jordán, Joaquín

2011-04-01

Methadone (d,l-methadone hydrochloride) is a full-opioid agonist, originally developed as a substitution for heroin or other opiates abusers. Nowadays methadone is also being applied as long-lasting analgesics in cancer, and it is proposed as a promising agent for leukemia therapy. Previously, we have demonstrated that high concentrations of methadone (0.5mM) induced necrotic-like cell death in SH-SY5Y cells. The pathway involved is caspase-independent but involves impairment of mitochondrial ATP synthesis and mitochondrial cytochrome c release. However, the downstream mitochondrial pathways remained unclear. Here, we studied the participation of apoptosis inducing factor (AIF) in methadone-induced cell death. Methadone resulted in a translocation of AIF from mitochondria to the nucleus. Translocation was inhibited by cyclosporine A, but not by lack of Bax protein. Therefore the effect seems mediated by the formation of the mitochondrial transition pore, but is apparently independent of Bax. Furthermore, methadone-treated SH-SY5Y nuclei show characteristics that are typical for stage I nuclear condensation. Methadone did not induce degradation of DNA into oligonucleosomal fragments or into high molecular weight DNA fragments. Absence of DNA fragmentation coincided with a considerable decrease in the levels of the caspase-actived endonuclase DNase and its chaperone-inhibitor ICAD. In conclusion, our results provide mechanistic insights into the molecular mechanisms that underlie methadone-induced cell death. This knowledge may prove useful to develop novel strategies to prevent toxic side-effects of methadone thereby sustaining its use as therapeutical agent against tumors. Copyright © 2010 Elsevier Ltd. All rights reserved.

Harm reduction program use, psychopathology and medical severity in patients with methadone maintenance treatment.

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Martínez-Luna, Nieves Gudelia; Rodríguez-Cintas, Laia; Esojo, Abderraman; Palma-Álvarez, Raúl Felipe; Robles-Martínez, María; Grau-López, Lara; Perea, Marta; Roncero, Carlos

2018-01-15

Methadone maintenance programs (MMP) for opioid dependence treatment have been widely used due to their effective therapeutic outcomes. Harm reduction programs (HRP) are complementary programs for severe patients with high risk behaviors and when abstinence is not possible. This study aims to compare patients in MMP that use HRP (MMP-HRP) and patients in MMP who do not use HRP (MMP-NO HRP). The sample was composed of 143 patients (MMP-HRP = 42 vs. MMP-NO HRP = 101). An additional subanalysis was performed with patients under 45 years of age (n = 116; MMP-HRP = 38 vs. MMP-NO HRP = 78). All patients were assessed with an ad hoc socio-demographic questionnaire, EuropASI, SCID-I, and SCID-II. Results show that MMP-HRP patients were younger with more frequent use of intravenous drugs and with a high prevalence of Cluster B personality disorders. MMP-NO HRP patients had lower methadone doses compared to MMP-HRP patients and preferred to use drugs by smoked route more frequently. In the subanalysis of patients under 45, MMP-HRP patients were younger, had a higher prevalence of liver diseases, more intravenous drug use, greater severity on the drug use scale, less social and family support in the suescales of EUROP-ASI than compared to patients under 45 years in the group MMP-NO HRP. In conclusion, MMP-HRP patients are younger compared to MMP-NO HRP patients, they also receive higher doses of methadone and had more intravenous use. The above findings imply that the early onset of high risk drug use and long-term exposure to heroin have more severe outcomes such as higher comorbidities (e.g. infectious diseases, medical and psychiatric disorders), and consequently, these patients are a more vulnerable group with a worse prognosis.

Maternal hair analysis for the detection of illicit drugs, medicines, and alcohol exposure during pregnancy.

Science.gov (United States)

Lendoiro, Elena; González-Colmenero, Eva; Concheiro-Guisán, Ana; de Castro, Ana; Cruz, Angelines; López-Rivadulla, Manuel; Concheiro, Marta

2013-06-01

Drug of abuse consumption throughout pregnancy is a serious public health problem and an important economic cost to the health system. The aim of this work was to compare maternal interview and hair analysis to determine drug consumption throughout pregnancy and to study relations among maternal interview, hair results, and neonatal outcomes. Two hundred nine mothers agreed to participate. After delivery, they were interviewed and a hair sample collected. Hair samples were segmented in trimesters and analyzed for 35 drugs [opioids, cocaine, amphetamines, Δ-tetrahydrocannabinol (THC), ketamine, methadone, antidepressants, benzodiazepines, and hypnotics; limits of quantification 5-100 pg/mg] and for ethyl glucuronide (limit of quantification 10 pg/mg) by liquid chromatography-tandem mass spectrometry. Statistical analysis was performed with χ test and t test. In the interview, 4.3% mothers declared using illicit drugs during pregnancy (cocaine 1.4%, THC 2.9%, and opiates 1%), 3.3% medicines (methadone 1.9%, benzodiazepines 1.9%, and antidepressants 0.5%), 21.5% tobacco, and 13.7% alcohol. Hair analysis showed 15.4% prevalence in illicit drugs (cocaine 12.4%, THC 3.8%, opiates 1%, and ketamine 1%), 22.5% in medicines (methadone 3.3%, benzodiazepines 11%, antidepressants 9.1%, zopiclone 1%, and fentanyl 1.4%), and 3.9% in alcohol. Neonatal abstinence syndrome was developed in 8.1% newborns, all of them from mothers with high methadone-positive hair results (>926.2 pg/mg). Statistically significant lower newborn weight and length were found in neonates from declared smokers compared with nonsmokers (P drug use during pregnancy, except for alcohol. In this preliminary study, no statistically significant differences were found between exposed and nonexposed newborns to drugs, except for tobacco consumption.

Determination of methadone hydrochloride in a maintenance dosage formulation.

Science.gov (United States)

Hoffmann, T J; Thompson, R D

1975-07-01

A colorimetric method for direct quantitative assay of methadone hydrochloride in liquid oral dosage forms is presented. The procedure involves the formation of a dye complex with bromothymol blue buffer solution. The resultant complex is extracted with benzene and measured spectrophotometrically. Duplicate tests on the formulation showed 99.2% of the labeled amount of methadone.

Attitudes and practices regarding the use of methadone in US state and federal prisons.

Science.gov (United States)

Rich, Josiah D; Boutwell, Amy E; Shield, David C; Key, R Garrett; McKenzie, Michelle; Clarke, Jennifer G; Friedmann, Peter D

2005-09-01

In the United States, vigorous enforcement of drug laws and stricter sentencing guidelines over the past 20 years have contributed to an expanded incarcerated population with a high rate of drug use. One in five state prisoners reports a history of injection drug use, and many are opiate dependent. For over 35 years, methadone maintenance therapy has been an effective treatment for opiate dependence; however, its use among opiate-dependent inmates in the United States is limited. In June 2003, we conducted a survey of the medical directors of all 50 US states and the federal prison system to describe their attitudes and practices regarding methadone. Of the 40 respondents, having jurisdiction over 88% (n =1,266,759) of US prisoners, 48% use methadone, predominately for pregnant inmates or for short-term detoxification. Only 8% of respondents refer opiate-dependent inmates to methadone programs upon release. The results highlight the need to destigmatize the use of methadone in the incarcerated setting, expand access to methadone during incarceration, and to improve linkage to methadone treatment for opiate-dependent offenders who return to the community.

The effect of P-glycoprotein on methadone hydrochloride flux in equine intestinal mucosa.

Science.gov (United States)

Linardi, R L; Stokes, A M; Andrews, F M

2013-02-01

Methadone is an effective analgesic opioid that may have a place for the treatment of pain in horses. However, its absorption seems to be impaired by the presence of a transmembrane protein, P-glycoprotein, present in different tissues including the small intestine in other species. This study aims to determine the effect of the P-glycoprotein on methadone flux in the equine intestinal mucosa, as an indicator of in vivo drug absorption. Jejunum tissues from five horses were placed into the Ussing chambers and exposed to methadone solution in the presence or absence of Rhodamine 123 or verapamil. Electrical measurements demonstrated tissue viability for 120 min, and the flux of methadone across the jejunal membrane (mucosal to submucosal direction) was calculated based on the relative drug concentration measured by ELISA. The flux of methadone was significantly higher only in the presence of verapamil. P-glycoprotein was immunolocalized in the apical membrane of the jejunal epithelial cells (enterocytes), mainly located in the tip of the villi compared to cells of the crypts. P-glycoprotein is present in the equine jejunum and may possibly mediate the intestinal transport of methadone. This study suggests that P-glycoprotein may play a role in the poor intestinal absorption of methadone in vivo. © 2012 Blackwell Publishing Ltd.

[Use of methadone in the elderly with cancer pain: a systematic review].

Science.gov (United States)

Taberna, Miren; Villavicencio-Chávez, Christian; González-Barboteo, Jesús

2014-01-01

To identify the clinical use of methadone as an analgesic in the management of cancer pain in elderly patients. We performed a systemic review of the literature on the specific use of methadone in elderly with cancer pain in MEDLINE, COCHRANE DATABASE and SCOPUS. A second search was conducted in MEDLINE to look for clinical trials and systematic review of the use of methadone in cancer pain, selecting only those in which the mean age of patients was ≥ 65 years old. Four articles were obtained in the first search, and from the second 7 clinical trials, none of them specific to methadone use in elderly patients with cancer. There are insufficient data on the use of methadone as an analgesic in the elderly with cancer. Given its pharmacological characteristics it must be used by trained personnel. Several recommendations are proposed for its use as an analgesic in the treatment of cancer pain in the elderly. Copyright © 2013 SEGG. Published by Elsevier Espana. All rights reserved.

Using poison center exposure calls to predict methadone poisoning deaths.

Directory of Open Access Journals (Sweden)

Nabarun Dasgupta

Full Text Available PURPOSE: There are more drug overdose deaths in the Untied States than motor vehicle fatalities. Yet the US vital statistics reporting system is of limited value because the data are delayed by four years. Poison centers report data within an hour of the event, but previous studies suggested a small proportion of poisoning deaths are reported to poison centers (PC. In an era of improved electronic surveillance capabilities, exposure calls to PCs may be an alternate indicator of trends in overdose mortality. METHODS: We used PC call counts for methadone that were reported to the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS® System in 2006 and 2007. US death certificate data were used to identify deaths due to methadone. Linear regression was used to quantify the relationship of deaths and poison center calls. RESULTS: Compared to decedents, poison center callers tended to be younger, more often female, at home and less likely to require medical attention. A strong association was found with PC calls and methadone mortality (b=0.88, se=0.42, t=9.5, df=1, p<0.0001, R(2 =0.77. These findings were robust to large changes in a sensitivity analysis assessing the impact of underreporting of methadone overdose deaths. CONCLUSIONS: Our results suggest that calls to poison centers for methadone are correlated with poisoning mortality as identified on death certificates. Calls received by poison centers may be used for timely surveillance of mortality due to methadone. In the midst of the prescription opioid overdose epidemic, electronic surveillance tools that report in real-time are powerful public health tools.

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

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Stine, S M; Grillon, C G; Morgan, C A; Kosten, T R; Charney, D S; Krystal, J H

2001-03-01

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the

Challenges of using methadone in the Indian pain and palliative care practice

Directory of Open Access Journals (Sweden)

Vidya Viswanath

2018-01-01

Full Text Available Palliative care providers across India lobbied to gain access to methadone for pain relief and this has finally been achieved. Palliative care activists will count on the numerous strengths for introducing methadone in India, including the various national and state government initiatives that have been introduced recognizing the importance of palliative care as a specialty in addition to improving opioid accessibility and training. Adding to the support are the Non-Governmental Organizations (NGOs, the medical fraternity and the international interactive and innovative programs such as the Project Extension for Community Health Outcome. As compelling as the need for methadone is, many challenges await. This article outlines the challenges of procuring methadone and also discusses the challenges specific to methadone. Balancing the availability and diversion in a setting of opioid phobia, implementing the amended laws to improve availability and accessibility in a country with diverse health-care practices are the major challenges in implementing methadone for relief of pain. The unique pharmacology of the drug requires meticulous patient selection, vigilant monitoring, and excellent communication and collaboration with a multidisciplinary team and caregivers. The psychological acceptance of the patient, the professional training of the team and the place where care is provided are also challenges which need to be overcome. These challenges could well be the catalyst for a more diligent and vigilant approach to opioid prescribing practices. Start low, go slow could well be the way forward with caregiver education to prescribe methadone safely in the Indian palliative care setting.

Challenges of Using Methadone in the Indian Pain and Palliative Care Practice.

Science.gov (United States)

Viswanath, Vidya; Palat, Gayatri; Chary, Srini; Broderick, Ann

2018-01-01

Palliative care providers across India lobbied to gain access to methadone for pain relief and this has finally been achieved. Palliative care activists will count on the numerous strengths for introducing methadone in India, including the various national and state government initiatives that have been introduced recognizing the importance of palliative care as a specialty in addition to improving opioid accessibility and training. Adding to the support are the Non-Governmental Organizations (NGOs), the medical fraternity and the international interactive and innovative programs such as the Project Extension for Community Health Outcome. As compelling as the need for methadone is, many challenges await. This article outlines the challenges of procuring methadone and also discusses the challenges specific to methadone. Balancing the availability and diversion in a setting of opioid phobia, implementing the amended laws to improve availability and accessibility in a country with diverse health-care practices are the major challenges in implementing methadone for relief of pain. The unique pharmacology of the drug requires meticulous patient selection, vigilant monitoring, and excellent communication and collaboration with a multidisciplinary team and caregivers. The psychological acceptance of the patient, the professional training of the team and the place where care is provided are also challenges which need to be overcome. These challenges could well be the catalyst for a more diligent and vigilant approach to opioid prescribing practices. Start low, go slow could well be the way forward with caregiver education to prescribe methadone safely in the Indian palliative care setting.

Removal of methadone by extended dialysis using a high cut-off dialyzer: implications for the treatment of overdose and for pain management in patients undergoing light chain removal.

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Arelin, Viktor; Schmidt, Julius J; Kayser, Nathalie; Kühn-Velten, W Nikolaus; Suhling, Hendrik; Eden, Gabriele; Kielstein, Jan T

2016-06-01

The synthetic opioid methadone hydrochloride has a low molecular weight of 346 D, a high volume of distribution (4 - 7 L/kg), and is lipophilic. It is used as an analgesic and for the maintenance treatment of opiate dependence. In drug addicts, methadone is frequently involved in mixed intoxications that can lead to death. Here we present the case of a drug addict in whom a high cut-off dialysis membrane together with extended dialysis was used in the setting of suspected overdose and acute kidney injury. Although the observed dialyzer plasma clearance (31.5 mL/min) and reduction ratio (38%) were higher than previously reported for standard hemodialysis, the total amount of methadone in the spent dialysate after 1 extended dialysis session was quite low. Hence, even extended dialysis with a high cut-off membrane does not seem to offer a clinically relevant benefit in the setting of overdose for enhanced methadone removal. On the other hand, in patients undergoing high cut-off dialysis for the removal of light chains, methadone could still be used as an analgesic without an additional dose after high cut-off hemodialysis.

Twelve-Month Prevalence of DSM-5 Gambling Disorder and Associated Gambling Behaviors Among Those Receiving Methadone Maintenance.

Science.gov (United States)

Himelhoch, Seth S; Miles-McLean, Haley; Medoff, Deborah; Kreyenbuhl, Julie; Rugle, Loreen; Brownley, Julie; Bailey-Kloch, Marie; Potts, Wendy; Welsh, Christopher

2016-03-01

This study sought to: (1) determine the prevalence of gambling disorder using the Diagnostic and Statistical Manual of Mental Disorders Version 5 (DSM-5; American Psychiatric Association in Diagnostic and statistical manual of mental disorders, American Psychiatric Publishing, Arlington, 2013) criteria; (2) identify the frequency and amount of money spent on gambling behaviors; and (3) determine demographic and treatment related predictors associated with gambling disorder in a substance using population. People receiving methadone maintenance treatment (N = 185) in an urban medical center consented to participate in the study. We used DSM-5 criteria to assess the 12-month prevalence of gambling disorder. Questions adapted from a previously developed measure were used to identify, describe and quantify the frequency of use and amount of money spent on gambling behaviors. Most participants were African-American (71.4 %), male (54.1 %), unmarried (76.8 %), unemployed (88.1 %) and had an income of DSM-5 criteria for gambling disorder. Compared to those without gambling disorder, those with gambling disorder did not differ significantly with respect to demographic characteristics nor methadone dose. However, those with gambling disorder had been in methadone maintenance treatment for significantly less time. Those with gambling disorder were significantly more likely to report engaging in a variety of gambling behaviors. Given that the 12-month prevalence of DSM-5 defined gambling disorder was nearly 50 % future efforts to screen and treat gambling disorder in the context of methadone maintenance treatment are clearly warranted.

Retention Rate in Methadone Maintenance Therapy

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G Dastjerdi

2010-08-01

Full Text Available Introduction: Methadone maintenance therapy is a well-known approach to the treatment of drug use disorders and harm reduction. But the main challenge is retention rate in MMT Methods: Through simple random sampling, 155 addicts aged between 18-60 years who referred to drug addiction center of university and underwent MMT were followed for at least one year and up to two and half years. Results: Of the total, 3.9% female, 62% married, 37.4% workers and 27.1% were jobless. 80% had education level of less than diploma, 43.2% abused marijuana, 54.2% abused alcohol and 49.7% were living in rented houses. 60% referred to this center because of economical problems, 15.5% because of legal issues and 67.7% because of family pressure. 31.6% were opium and opium resin addicts, 60% were heroin addicts, 8.4% were crack addicts and 21.9% were IV abusers. 76.8% had at least one high risk behavior. Average dose of methadone was 86.5+35 mg/day. Mean survival time was 80 weeks. Relapse rate was 3.3% in the first month, 13.9% in three months, 23.2% in six months, 31.7% in first year and 41. 7% was a total relapse rate. Survival rate had a direct significant statistical relationship with the age, type of drug and method of use. Conclusion: According to the results of the present study that indicate a survival rate of 68.2% in a year and 58.3% after a year and also considering the results of other studies, we can conclude that MMP could be an effective method in the treatment of opiate drug disorders.

Correlates of illicit methadone use in New York City: A cross-sectional study

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Frye Victoria

2008-10-01

Full Text Available Abstract Background Despite growing concern about illicit methadone use in the US and other countries, there is little data about the prevalence and correlates of methadone use in large urban areas. We assessed the prevalence and examined correlates of lifetime and recent illicit methadone use in New York City (NYC. Methods 1,415 heroin, crack, and cocaine users aged 15–40 years were recruited in NYC between 2000 and 2004 to complete interviewer-administered questionnaires. Results In multivariable logistic regression, non-injection drug users who used illicit methadone were more likely to be heroin dependent, less than daily methamphetamine users and to have a heroin using sex partner in the last two months. Injection drug users who used illicit methadone were more likely to use heroin daily, share injection paraphernalia and less likely to have been in a detoxification program and to have not used marijuana in the last six months. Conclusion The results overall suggest that illicit (or street methadone use is likely not a primary drug of choice, but is instead more common in concert with other illicit drug use.

Economic Cost of the Therapeutic Workplace Intervention Added to Methadone Maintenance

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Knealing, Todd W.; Roebuck, M. Christopher; Wong, Conrad J.; Silverman, Kenneth

2008-01-01

The therapeutic workplace is a novel intervention that uses access to paid training and employment to reinforce drug abstinence within the context of standard methadone maintenance. We used the Drug Abuse Treatment Cost Analysis Program as a standard method of estimating the economic costs of this intervention. Over a one-year period, the therapeutic workplace served 122 methadone maintenance clients who had a median length of stay of 22 weeks. The workplace maintained a mean daily census of 48 clients. The combined cost of methadone maintenance and the therapeutic workplace was estimated at $362 per week. This cost is less than other treatments that might be used to promote abstinence in individuals who continue to use drugs during methadone treatment. Given prior evidence of effectiveness, these cost data may be useful to policymakers, social service agencies, and researchers interested in using or further developing the therapeutic workplace intervention. PMID:17614239

Forensic Toxicology Perspectives of Methadone-associated Deaths in Tehran, Iran, a 7-year Overview.

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Akhgari, Maryam; Amini-Shirazi, Noushin; Iravani, Fariba Sardari

2018-04-01

Methadone has a long history of pain relief and successful substitute for maintenance treatment in heroin and narcotic addiction. The aim of the study was to assess the trends of methadone-associated deaths in Tehran, Iran, in 2009-2015, from a forensic toxicology point of view. All methadone-associated deaths during this 7-year study period were evaluated according to demographic parameters and forensic toxicology analysis results. Results showed that 1274 cases of methadone-associated deaths were investigated during the study period. The incidence rate of methadone-associated deaths had risen 7.7 times in 2015 in comparison with 2009 (p < 0.05). The majority of cases were men (90.35%), aged from 20 to 40 years. About 80% of cases had shown positive results for other drugs and poisons in combination with methadone. Methamphetamine and tramadol were the most drugs detected in post-mortem samples. Death rates among methadone users in Tehran, Iran, increased year by year during 2009-2015. These findings raise the attention to the concomitant use of drugs with the need for changes in regulation and regulatory policy to restrict access and use of controlled drugs. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Nebulized naloxone gently and effectively reverses methadone intoxication.

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Mycyk, Mark B; Szyszko, Amy L; Aks, Steven E

2003-02-01

A 46-year-old woman presented to the Emergency Department with lethargy and respiratory depression after ingesting methadone. Initial oxygen saturation of 61% on room air did not improve with supplemental oxygenation. As venous access was initially unobtainable, naloxone was administered by nebulizer. Within 5 min oxygen saturation was 100% and mental status was normal. The patient did not develop severe withdrawal symptoms. Naloxone hydrochloride has been administered by various routes to treat opioid toxicity. Our report describes the successful use of nebulized naloxone for methadone toxicity.

Methadone as an inducer of apoptotic process in cheek mucosae cells in rats

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Małgorzata Stępień

2017-11-01

Full Text Available Methadone is an opioid medication which can reduce withdrawal symptoms in people addicted to heroin and other drugs. Methadone is used also as a pain reliever and as part of drug addiction detoxification program. Apoptosis is the physiological process that plays a critical role in development and tissue homeostasis. The progress of apoptosis is regulated by signal cascades. The aim of this study was to asses how methadone induces apoptotic process in cheek mucosae cells in rats. Forty albino rats wares divided into two parts and five subgroups each. The biggest histological changes of cheek mucosae was observed in the groups with methadone. There is no indication of ability to regeneration in short time after treatment.

Problem based review: The patient taking methadone.

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Arora, Alok; Williams, Karen

2013-01-01

Methadone maintenance treatment (MMT) is an effective therapy for opioid-dependence; its use is based on a harm reduction philosophy and represents one of a range of treatment approaches for opioid-dependent individuals. The medical literature supports MMT as a well established and cost-effective treatment for opioid-dependence that allows a return-to-normal physiological, psychological and societal functioning. The effectiveness of MMT is enhanced by psycho-social interventions such as contingency management and addressing other co-existing health and social needs. MMT saves lives and reduces violent and non-violent crime, drug use and the transmission of HIV, hepatitis C and other communicable diseases. For some people, MMT may continue for life, while others may eventually be able to discontinue and remain abstinent. Methadone interacts with numerous drugs and prolongs the corrected QT interval (QTc) with risk of sudden cardiac death. It has a prolonged half-life and premature discharge of patients after methadone overdose may be fatal. Each patient must be assessed, treated and monitored on an individual basis. Successful outcomes through MMT require knowledge, experience, vigilance, and diligence on the part of the physician, the patient and all of those involved in treatment.

Impulsivity in men with prescription of benzodiazepines and methadone in prison.

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Moreno-Ramos, Luis; Fernández-Serrano, María José; Pérez-García, Miguel; Verdejo-García, Antonio

2016-06-14

Benzodiazepines and methadone use has been associated with various neuropsychological impairments. However, to the best of our knowledge, no studies have been carried out on the effect of these substances (either separately or combined) on impulsive personality, including studies in prisoners. The aim of this study is to examine the impulsive personality of a sample of 134 male prisoners using the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (Torrubia, Avila, Molto, & Caseras, 2001) and the UPPS-P Scale (Cyders et al., 2007). Some of these were methadone users, methadone and benzodiazepines users, polydrug users in abstinence and non-dependent drug users. The results showed that drug users have greater sensitivity to reward, positive urgency, negative urgency and sensation seeking than non-dependent users. Methadone users showed more sensitivity to punishment and lack of perseverance with respect to other users. No differences were found between methadone+benzodiazepines users and other groups. The secondary aim is to examine which impulsive personality dimensions are related to the two motivational systems proposed by Gray (BIS-BAS) using exploratory factor analysis. Results showed two different components. One component was defined by the subscales sensitivity to reinforcement, positive urgency, negative urgency and sensation seeking. The second component was defined by the subscales sensitivity to punishment, lack of perseverance and lack of premeditation.

Methadone, commonly used as maintenance medication for outpatient treatment of opioid dependence, kills leukemia cells and overcomes chemoresistance.

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Friesen, Claudia; Roscher, Mareike; Alt, Andreas; Miltner, Erich

2008-08-01

The therapeutic opioid drug methadone (d,l-methadone hydrochloride) is the most commonly used maintenance medication for outpatient treatment of opioid dependence. In our study, we found that methadone is also a potent inducer of cell death in leukemia cells and we clarified the unknown mechanism of methadone-induced cell killing in leukemia cells. Methadone inhibited proliferation in leukemia cells and induced cell death through apoptosis induction and activated apoptosis pathways through the activation of caspase-9 and caspase-3, down-regulation of Bcl-x(L) and X chromosome-linked inhibitor of apoptosis, and cleavage of poly(ADP-ribose) polymerase. In addition, methadone induced cell death not only in anticancer drug-sensitive and apoptosis-sensitive leukemia cells but also in doxorubicin-resistant, multidrug-resistant, and apoptosis-resistant leukemia cells, which anticancer drugs commonly used in conventional therapies of leukemias failed to kill. Depending on caspase activation, methadone overcomes doxorubicin resistance, multidrug resistance, and apoptosis resistance in leukemia cells through activation of mitochondria. In contrast to leukemia cells, nonleukemic peripheral blood lymphocytes survived after methadone treatment. These findings show that methadone kills leukemia cells and breaks chemoresistance and apoptosis resistance. Our results suggest that methadone is a promising therapeutic approach not only for patients with opioid dependence but also for patients with leukemias and provide the foundation for new strategies using methadone as an additional anticancer drug in leukemia therapy, especially when conventional therapies are less effective.

Methadone Maintenance as Last Resort

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Järvinen, Margaretha; Miller, Gale

2010-01-01

Drawing on qualitative interviews with drug addicts in Copenhagen, Denmark, this article offers a phenomenological reading of a methadone maintenance program. The program is set within the principles of harm reduction, meaning that its aim is not to cure the participants’ addiction but to keep them...

Tramadol versus methadone for the management of acute opioid withdrawal: an add-on study

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M Salehi

2006-07-01

Full Text Available BACKGROUND: Opioid agonists such as methadone have been used widely in controlling opioid withdrawal symptoms. Tramadol, a partial opioid agonist, also has been prescribed to manage acute and chronic pain. We sought to compare the efficacy of tramadol and methadone in reducing the severity of opioid withdrawal symptoms. METHODS: In a double blind clinical trial 70 opioid dependent patients who used daily opium equal to 15 mg methadone randomly were assigned in two groups. In one group, methadone was started at 15 mg/day while in the other group 450 mg/day tramadol was prescribed. Both drugs were tapered in a week and placebo was prescribed in the 2nd week. The severity of withdrawal symptoms were assessed five times by short opioid withdrawal scale (SOWS. Data were analyzed by Repeated Measures Analysis of Variance, Mann-Whitney U, and Wilcoxon tests. RESULTS: There were statistically significant differences between two groups in the severity of anxiety (P = 0.015, irritability (P = 0.044, palpitation (P = 0.018, agitation (P = 0.037, and dysphoria (P = 0.044 that all were more common in methadone group. Comparison of side effects revealed statistically significant differences in sweating (P = 0.003 and drowsiness (P = 0.019 between two groups that were more frequent in methadone group. DISCUSSION: Tramadol was more efficacious in controlling opioid withdrawal symptoms with lower side effects. KEYWORDS: Methadone, tramadol, opioid withdrawal.

Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial.

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Rigo, Flavia Karine; Trevisan, Gabriela; Godoy, Maria C; Rossato, Mateus Fortes; Dalmolin, Gerusa D; Silva, Mariane A; Menezes, Mirian S; Caumo, Wolnei; Ferreira, Juliano

2017-03-01

Methadone and ketamine are used in neuropathic pain management. However, the benefits of both drugs association are uncertain in the treatment of neuropathic pain. Our primary objective was test the hypothesis that oral methadone combined with oral ketamine is more effective than oral methadone or ketamine alone in reducing neuropathic pain. We conducted a randomized, double blind, active-controlled parallel-group clinical trial. Forty-two patients with neuropathic pain refractory to conventional therapy were randomly assigned to receive oral methadone (n = 14), ketamine (n = 14), or methadone plus ketamine (n = 14) over a 3-month period. During these 90 days, we observed pain scores using a visual analogical scale (VAS), allodynia, burning/shooting pain, and some side effects. All treatments were effective in reducing pain scores by at least 40%. However, a significant improvement in pain was observed only in the ketamine alone group compared with both the methadone or methadone/ketamine groups. No significant differences were observed among the treatment groups for the reduction of burning or shooting pain, while ketamine alone was more effective than methadone or methadone/ketamine for the reduction of allodynia. Formal assessment for awareness of the allocation was not performed, some co-intervention bias may have occurred, our results could be only relevant to the patient population investigated and the use of VAS as the primary outcome detect changes in pain intensity but not to assess neuropathic pain symptoms. This study indicates that ketamine was better than methadone or methadone/ketamine for treating neuropathic pain.Key words: Multimodal analgesia, refractory pain, NMDA receptor, opioid.

Maternal and Neonatal Complications of Substance Abuse in Iranian Pregnant Women

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Maryam Hosseinnezhad-Yazdi

2012-06-01

Full Text Available There is an increased prevalence of maternal substance abuse during pregnancy in younger women in all socioeconomic classes and races. Our aim was to determine the prevalence and correlates of self-reported substance abuse among pregnant women and obstetric complications or neonatal outcomes in Iran. This retrospective cohort study is covering a five year period on medical records of pregnant women attending the maternity unit of four major hospitals (Mahdieh, Taleghani, Imam Hossein and Akbarabadi Hospitals. Women who reported using opium, heroin, crack, cannabis or methamphetamine were compared with women with no reported history of drug abuse for obstetric complications and prenatal morbidity and neonatal mortality. From 100,620 deliveries substance abuse was recorded for 519 women giving a prevalence of 0.5%. Opium was the most prevalent substance abused followed by crack (a mix of heroin and amphetamines. The exposed group had significantly more obstetric complications including preterm low birth weight and postpartum hemorrhage than the non-exposed group. The exposed group had significantly worse prenatal outcomes including more admissions to intensive care unit and higher infant mortality than the non-exposed group. None of the women in the exposed group was on methadone treatment at time of delivery. Risks of maternal and neonatal complications were increased in substance using pregnant women, especially preterm birth and low birth weight. We recommend a multidisciplinary team to provide methadone maintenance therapy for substance using pregnant women and urinary screen of all pregnant women presenting to hospital.

Methadone maintenance and the problem with alcohol.

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Siassi, I; Alston, D C

1976-01-01

There is a growing concern with the rapid pace of physical and psychosocial deterioration of methadone patients who abuse alcohol. The need for a sample method for determining the extent of the problem, as well as the presence of an alcohol problem in individual patients, led the authors to test the validity of the Michigan Alcoholism Sreen Test (MAST) in a small urban methadone maintenance clinic (N = 125). The MAST was administered to every patient by their counselors, and the nursing staff was asked to independently rate each patient according to Keller's definition of alcoholism. The authors compared the patients' MAST scores with the global ratings of the nursing staff. Forty-six percent (n = 58) of the patients scored in the alcoholism range of the MAST questionnaire, while 34% (n = 43) of the patients were diagnosed as alcoholics by the nursing staff. There was 75% (n = 94) agreement between the MAST findings and the nurses' global ratings (p less than .001). The authors suggest that the MAST could be an effective screening tool in the area of alcohol abuse in methadone clinics. Going beyond the data, the authors recommend reexamination by psychiatrists of their peripheral role in the treatment of these difficult and multihandicapped patients.

A randomized clinical trial of methadone maintenance for prisoners: findings at 6 months post-release.

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Gordon, Michael S; Kinlock, Timothy W; Schwartz, Robert P; O'Grady, Kevin E

2008-08-01

This study examined the effectiveness of methadone maintenance initiated prior to or just after release from prison at 6 months post-release. A three-group randomized controlled trial was conducted between September 2003 and June 2005. A Baltimore pre-release prison. Two hundred and eleven adult pre-release inmates who were heroin-dependent during the year prior to incarceration. Participants were assigned randomly to the following: counseling only: counseling in prison, with passive referral to treatment upon release (n = 70); counseling + transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n = 70); and counseling + methadone: methadone maintenance and counseling in prison, continued in a community-based methadone maintenance program upon release (n = 71). Addiction Severity Index at study entry and follow-up. Additional assessments at 6 months post-release were treatment record review; urine drug testing for opioids, cocaine and other illicit drugs. Counseling + methadone participants were significantly more likely than both counseling only and counseling + transfer participants to be retained in drug abuse treatment (P = 0.0001) and significantly less likely to have an opioid-positive urine specimen compared to counseling only (P = 0.002). Furthermore, counseling + methadone participants reported significantly fewer days of involvement in self-reported heroin use and criminal activity than counseling only participants. Methadone maintenance, initiated prior to or immediately after release from prison, increases treatment entry and reduces heroin use at 6 months post-release compared to counseling only. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.

Response to methadone maintenance treatment is associated with the MYOCD and GRM6 genes.

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Fonseca, Francina; Gratacòs, Mònica; Escaramís, Geòrgia; De Cid, Rafael; Martín-Santos, Rocío; Fernández-Espejo, Emilio; Estivill, Xavier; Torrens, Marta

2010-06-01

There is increasing interest in the pharmacogenetic basis for explaining differences between patients in treatment outcome among methadone-treated subjects. Most studies have focused on genetic polymorphisms related to methadone pharmacokinetics and, to a lesser extent, those genes implicated in the pharmacodynamics of methadone. This study aimed to investigate the associations between response to methadone maintenance treatment (MMT) and polymorphisms in genes coding for the OPRM1 opioid receptor, the metabotropic glutamate receptors GRM6 and GRM8, the nuclear receptor NR4A2, the photolyase enzyme cryptochrome 1 (CRY1), and the transcription factor myocardin (MYOCD), which have previously been associated with the risk of opioid dependence disorder. The study used an association, case-control design, conducted in the setting of an MMT program in a drug abuse outpatient center in Barcelona, Spain. We recruited 169 opioid-dependent patients (diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders [4th Edition] criteria) receiving MMT. The inclusion criteria included Caucasian ethnicity, being enrolled in MMT for at least 6 months, and receiving a stable methadone dose for the previous 2 months. The exclusion criteria included language-related barriers, severe cognitive impairment, or any medical disorder that would interfere with the research assessments. Single nucleotide polymorphism (SNP) variants in several candidate genes and regions were genotyped: MYOCD (rs1714984), GRM8 (rs1034576), CRY1 (rs1861591), GRM6 (rs953741), OPRM1 (rs1074287), NR4A2 (rs1405735), and the intergenic variants rs965972 (1q31.2) and rs1867898 (2q21.2). MMT response status was assessed by the number of opioid-positive controls detected by random urinalysis in the previous 2 months. We used the chi-squared test and p-value for the allele frequencies of the eight SNPs in responders versus nonresponders, and multivariate logistic regression analyses to examine

Efficacy and Safety of Two Methadone Titration Methods for the Treatment of Cancer-Related Pain: The EQUIMETH2 Trial (Methadone for Cancer-Related Pain).

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Poulain, Philippe; Berleur, Marie-Pierre; Lefki, Shimsi; Lefebvre, Danièle; Chvetzoff, Gisèle; Serra, Eric; Tremellat, Fibra; Derniaux, Alain; Filbet, Marilène

2016-11-01

In the European Association for Palliative Care recommendations for cancer pain management, there was no consensus regarding the indications, titration, or monitoring of methadone. This national, randomized, multicenter trial aimed to compare two methadone titration methods (stop-and-go vs. progressive) in patients with cancer-related pain who were inadequately relieved by or intolerant to Level 3 opioids. The primary end point was the rate of success/failure at Day 4, defined as pain relief (reduction of at least two points on the visual scale and a pain score methods were considered equally easy to perform by nearly 60% of the clinicians. Methadone is an effective and sustainable second-line alternative opioid for the treatment of cancer-related pain. The methods of titration are comparable in terms of efficacy, safety, and ease of use. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Determining Smoking Cessation Related Information, Motivation, and Behavioral Skills among Opiate Dependent Smokers in Methadone Treatment.

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Cooperman, Nina A; Richter, Kimber P; Bernstein, Steven L; Steinberg, Marc L; Williams, Jill M

2015-04-01

Over 80% of people in methadone treatment smoke cigarettes, and existing smoking cessation interventions have been minimally effective. To develop an Information-Motivation-Behavioral Skills (IMB) Model of behavior change based smoking cessation intervention for methadone maintained smokers, we examined smoking cessation related IMB factors in this population. Current or former smokers in methadone treatment (n = 35) participated in focus groups. Ten methadone clinic counselors participated in an individual interview. A content analysis was conducted using deductive and inductive approaches. Commonly known IMB factors related to smoking cessation were described. These factors included: the health effects of smoking and treatment options for quitting (information); pregnancy and cost of cigarettes (motivators); and coping with emotions, finding social support, and pharmacotherapy adherence (behavioral skills). IMB factors specific to methadone maintained smokers were also described. These factors included: the relationship between quitting smoking and drug relapse (information), the belief that smoking is the same as using drugs (motivator); and coping with methadone clinic culture and applying skills used to quit drugs to quitting smoking (behavioral skills). IMB strengths and deficits varied by individual. Methadone maintained smokers could benefit from research on an IMB Model based smoking cessation intervention that is individualized, addresses IMB factors common among all smokers, and also addresses IMB factors unique to this population.

Blockade of rat alpha3beta4 nicotinic receptor function by methadone, its metabolites, and structural analogs.

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Xiao, Y; Smith, R D; Caruso, F S; Kellar, K J

2001-10-01

The opioid agonist properties of (+/-)-methadone are ascribed almost entirely to the (-)-methadone enantiomer. To extend our knowledge of the pharmacological actions of methadone at ligand-gated ion channels, we investigated the effects of the two enantiomers of methadone and its metabolites R-(+)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium perchlorate (EDDP) and R-(+)-2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline hydrochloride (EMDP), as well as structural analogs of methadone, including (-)-alpha-acetylmethadol hydrochloride (LAAM) and (+)-alpha-propoxyphene, on rat alpha3beta4 neuronal nicotinic acetylcholine receptors (nAChRs) stably expressed in a human embryonic kidney 293 cell line, designated KXalpha3beta4R2. (+/-)-methadone inhibited nicotine-stimulated 86Rb+ efflux from the cells in a concentration-dependent manner with an IC50 value of 1.9 +/- 0.2 microM, indicating that it is a potent nAChR antagonist. The (-)- and (+)-enantiomers of methadone have similar inhibitory potencies on nicotine-stimulated 86Rb+ efflux, with IC50 values of approximately 2 microM. EDDP, the major metabolite of methadone, is even more potent, with an IC50 value of approximately 0.5 microM, making it one of the most potent nicotinic receptor blockers reported. In the presence of (+/-)-methadone, EDDP, or LAAM, the maximum nicotine-stimulated 86Rb+ efflux was markedly decreased, but the EC50 value for nicotine stimulation was altered only slightly, if at all, indicating that these compounds block alpha3beta4 nicotinic receptor function by a noncompetitive mechanism. Consistent with a noncompetitive mechanism, (+/-)-methadone, its metabolites, and structural analogs have very low affinity for nicotinic receptor agonist binding sites in membrane homogenates from KXalpha3beta4R2 cells. We conclude that both enantiomers of methadone and its metabolites as well as LAAM and (+)-alpha-propoxyphene are potent noncompetitive antagonists of alpha3beta4 nAChRs.

Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale?

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Mujtaba, Sobia; Romero, Jorge; Taub, Cynthia C

2013-12-01

Methadone is a drug that has found widespread utility in the management of opioid addiction and pain. Along with its popularity, methadone has also earned an infamous reputation for causing prolongation of the QT interval and an increased risk of torsades de pointes. In this article we will give a brief overview of the long QT syndromes, followed by an in-depth look at the current pathophysiologic mechanisms of methadone induced QT prolongation, a review of the existing literature and the current concepts regarding the prevention and management of methadone induced torsades de pointes. In addition, we explore the idea and implications of a genetic link between methadone induced prolongation of the QT interval and torsades de pointes.

An evaluation of the histological effects of intra-articular methadone in the canine model.

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Jones, Timothy A; Hand, Walter R; Ports, Michael D; Unger, Daniel V; Herbert, Daniel; Pellegrini, Joseph E

2003-02-01

Methadone hydrochloride is an opiate that has pharmacodynamic and pharmacokinetic properties that suggest it may provide longer analgesia than morphine when administered via the intra-articular route. However, no studies to date have been conducted examining the effects of intra-articular methadone hydrochloride on local tissues. Therefore, the purpose of this study was to determine the histopathologic effects of intra-articular methadone hydrochloride on local tissues in the canine knee. Nine canines, 1 to 4 years old, weighing between 20 kg and 23 kg were used. All canines had their knees randomized to receive either bupivacaine, 0.5% with epinephrine 1:200,000 (4.5 mL), and 5 mg methadone hydrochloride (0.5 mL) for the study knee, or bupivacaine, 0.5% with epinephrine 1:200,000 (4.5 mL), and 0.5 mL normal saline for the control knee. Serum methadone hydrochloride levels were obtained on all canines at 6 and 24 hours. Canines were randomly assigned to 1 of 3 groups to be euthanized at either 24 hours, 14 days, or 28 days. Following euthanization and necropsy, synovial fluid levels and tissue samples were obtained and examined for histopathologic changes. Synovial fluid samples noted a few white blood cells at 24 hours and none at 14 and 28 days. Tissue samples showed no histopathologic changes, and serum concentration levels of methadone hydrochloride were negligible.

When to Use Methadone for pain: A Case-Based Approach.

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Palat, Gayatri; Vallath, Nandini; Chary, Srini; Broderick, Ann

2018-01-01

The case studies are written in this article to illustrate how methadone might be used for pain in the Indian context. These cases might be used for discussion in a multidisciplinary team, or for individual study. It is important to understand that pain requires a multidisciplinary approach as opioids will assist only with physical, i.e. neuropathic and nociceptive pain, but not emotional, spiritual, or relational pain or the pain of immobility. The social determinants of pain were included to demonstrate how emotional, relational, and psychological dimensions of pain amplify the physical aspects of pain. The case studies follow a practical step-wise approach to pain while undergoing cancer treatment, pain toward the end-of-life and needing longer acting opioid. Methadone in children, and methadone in conditions of opioid toxicity or where there is a need for absorption in the proximal intestine cases are included.

[Family typology and deterioration related to opioids use, in a methadone treatment patients group].

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Garrido Fernández, M; Torrado Val, E; Marcos Sierra, J A

2010-01-01

In this article the familiar functioning of subjects addict to opioids included in a maintenance programme with methadone will be analyzed, trying to identify whether belonging to one type of family (family typology) or another, according to Olson's Familiar Functioning Model, is related to the level of deterioration or severity of addiction of the different areas associated to consumption . The sample is composed by 69 subjects (N=69) users of the Servicio de Atención a las Drogodependencias (SAD) in Centro de Servicios Sociales Comunitarios del Ayuntamiento de Alcalá de Guadaíra (Seville). In order to evaluate the functioning and the family typology of these subjects the Escala de Cohesión y Adaptación Familiar--CAF-1--Spanish version of FACES III was used. In order to evaluate the level of deterioration, the Spanish version of the 5th edition of the personal, clinical semistructured interview Addiction Severity Index--ASI4--was applied. The results indicate that the subjects included in balanced families present more addiction severity in two dimensions of the ASI: Alcohol and Employment/Support and are, moreover, the ones that take greater doses of methadone.

Methadone Detoxification Versus Traditional Gradual Decrease in the Consumed Amount of Refined Opium Dross (Shireh: The Preferred Method for Controlling Withdrawal Syndrome

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Mohammadreza Farsinejad

2012-08-01

Full Text Available Background: The aim of this study was to compare the effectiveness of methadone detoxification with traditional method of gradual decrement in the abused amount of the refined opium dross (Shireh to control withdrawal syndrome in Shireh-addicted patients. Methods: In this study, two groups of Shireh addicts were compared. The first group was treated by methadone and the second group by gradual decrement in the amount of consumed Shireh. Those experiencing the adverse effects of the treatment were excluded from the study. Methadone dose was calculated based on the amount of the Shireh consumed and detoxification was performed during a 21-day period. In the second group, the amount of the consumed Shireh was gradually decreased within 21 days and some of the withdrawal symptoms were selected as indicators for patient evaluation. Results: A total of 35 patients (16 versus 19 patients in the first and second groups were evaluated. Their mean age was 43 ± 4 years and all were male. A statistically significant difference was found between these two groups in terms of severity and duration of withdrawal symptoms within the first five days and their duration after the 21st day of the onset of detoxification (P< 0.05. Conclusion: In comparison with methadone detoxification, traditional method of gradually decreasing the consumed amount of Shireh controls the severity and duration of withdrawal symptoms better in the course of detoxification.

Administration of venlafaxine after chronic methadone detoxification blocks post-depression relapse in rats

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Meysam Fadaei-Kenarsary

2017-08-01

Full Text Available ABSTRACT Relapse is highly prevalent after detoxification and depression. Due to the advantages of venlafaxine compared with other antidepressants, it is expected that venlafaxine administration may reduce relapse after detoxification and depression. This study aimed to evaluate the effects of venlafaxine on depression-induced relapse to morphine dependence after methadone detoxification. Eighty Sprague-Dawley rats were habituated and conditioned with morphine (10 mg/kg, S.C., for 4 days. After that, primary forced swimming and conditioned place preference (CPP were tested. They were followed by methadone (70 mg/kg/day, P.O., for 7 days administration, extinguishing, forced swimming stress (FSS and administration of venlafaxine (80 mg/kg/day, I.P., for 7 days. Finally same tests were performed. Administration of venlafaxine resulted in a decrement in final preference scores associated with a prime morphine injection (PMI compared to the primary scores in methadone treated (MTD+ animals. In a swimming test, venlafaxine increased the amount of final floating and decreased final activity scores compared with the primary scores after administration of methadone. Venlafaxine reduced locomotor activity in MTD+ animals in the final test with PMI. There was a positive correlation between the final activity and preference scores after PMI. In conclusion, venlafaxine improved anxiety and depression-induced relapse on methadone detoxified rats.

Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women.

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Tran, Tran H; Griffin, Brooke L; Stone, Rebecca H; Vest, Kathleen M; Todd, Timothy J

2017-07-01

Pregnant women with opioid use disorder can be treated with methadone, buprenorphine, or naltrexone to reduce opioid use and improve retention to treatment. In this review, we compare the pregnancy outcomes of methadone, buprenorphine, and naltrexone in clinical trials and discuss the potential behavioral and developmental effects of these agents seen in offspring in animal studies. Important clinical considerations in the management of opioid use disorder in pregnant women and their infants are also discussed. Outside of pregnancy, buprenorphine is used in combination with naloxone to reduce opioid abuse and diversion. During pregnancy, however, the use of buprenorphine as a single agent is preferred to prevent prenatal naloxone exposure. Both methadone and buprenorphine are widely used to treat opioid use disorder; however, compared with methadone, buprenorphine is associated with shorter treatment duration, less medication needed to treat neonatal abstinence syndrome (NAS) symptoms, and shorter hospitalizations for neonates. Despite being the standard of care, medication-assisted treatment with methadone or buprenorphine is still underused, making it apparent that more options are necessary. Naltrexone is not a first-line treatment primarily because both detoxification and an opioid-free period are required. More research is needed to determine naltrexone safety and benefits in pregnant women. Animal studies suggest that changes in pain sensitivity, developmental processes, and behavioral responses may occur in children born to mothers receiving methadone, buprenorphine, or naltrexone and is an area that warrants future studies. © 2017 Pharmacotherapy Publications, Inc.

Correlations of Maternal Buprenorphine Dose, Buprenorphine, and Metabolite Concentrations in Meconium with Neonatal Outcomes

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Kacinko, SL; Jones, HE; Johnson, RE; Choo, RE; Huestis, MA

2009-01-01

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS ) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS. PMID:18701886

Pharmacological Characterization of the Mechanisms Involved in Delayed Calcium Deregulation in SH-SY5Y Cells Challenged with Methadone

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Sergio Perez-Alvarez

2012-01-01

Full Text Available Previously, we have shown that SH-SY5Y cells exposed to high concentrations of methadone died due to a necrotic-like cell death mechanism related to delayed calcium deregulation (DCD. In this study, we show that, in terms of their Ca2+ responses to 0.5 mM methadone, SH-SY5Y cells can be pooled into four different groups. In a broad pharmacological survey, the relevance of different Ca2+-related mechanisms on methadone-induced DCD was investigated including extracellular calcium, L-type Ca2+ channels, μ-opioid receptor, mitochondrial inner membrane potential, mitochondrial ATP synthesis, mitochondrial Ca2+/2Na+-exchanger, reactive oxygen species, and mitochondrial permeability transition. Only those compounds targeting mitochondria such as oligomycin, FCCP, CGP 37157, and cyclosporine A were able to amend methadone-induced Ca2+ dyshomeostasis suggesting that methadone induces DCD by modulating the ability of mitochondria to handle Ca2+. Consistently, mitochondria became dramatically shorter and rounder in the presence of methadone. Furthermore, analysis of oxygen uptake by isolated rat liver mitochondria suggested that methadone affected mitochondrial Ca2+ uptake in a respiratory substrate-dependent way. We conclude that methadone causes failure of intracellular Ca2+ homeostasis, and this effect is associated with morphological and functional changes of mitochondria. Likely, this mechanism contributes to degenerative side effects associated with methadone treatment.

Determining Smoking Cessation Related Information, Motivation, and Behavioral Skills among Opiate Dependent Smokers in Methadone Treatment

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Cooperman, Nina A.; Richter, Kimber P.; Bernstein, Steven L.; Steinberg, Marc L.; Williams, Jill M.

2015-01-01

Background Over 80% of people in methadone treatment smoke cigarettes, and existing smoking cessation interventions have been minimally effective. Objective To develop an Information-Motivation-Behavioral Skills (IMB) Model of behavior change based smoking cessation intervention for methadone maintained smokers, we examined smoking cessation related information, motivation, and behavioral skills in this population. Methods Current or former smokers in methadone treatment (n=35) participated in focus groups. Ten methadone clinic counselors participated in an individual interview. A content analysis was conducted using deductive and inductive approaches. Results Commonly known information, motivation, and behavioral skills factors related to smoking cessation were described. These factors included: the health effects of smoking and treatment options for quitting (information); pregnancy and cost of cigarettes (motivators); and coping with emotions, finding social support, and pharmacotherapy adherence (behavioral skills). Information, motivation, and behavioral skills factors specific to methadone maintained smokers were also described. These factors included: the relationship between quitting smoking and drug relapse (information), the belief that smoking is the same as using drugs (motivator); and coping with methadone clinic culture and applying skills used to quit drugs to quitting smoking (behavioral skills). Information, motivation, and behavioral skills strengths and deficits varied by individual. Conclusions Methadone maintained smokers could benefit from research on an IMB Model based smoking cessation intervention that is individualized, addresses IMB factors common among all smokers, and also addresses IMB factors unique to this population. PMID:25559697

Implementation of methadone therapy for opioid use disorder in Russia - a modeled cost-effectiveness analysis.

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Idrisov, Bulat; Murphy, Sean M; Morrill, Tyler; Saadoun, Mayada; Lunze, Karsten; Shepard, Donald

2017-01-20

Opioid agonist therapy using methadone, an effective treatment of opioid use disorders (OUD) for people who inject drugs (PWID), is recommended by the World Health Organization as essential to curtail the growing HIV epidemic. Yet, despite increasing prevalence of OUD and HIV, methadone therapy has not yet been implemented in Russia. The aim of this modeling study was to estimate the cost-effectiveness of methadone therapy for Russian adults with a diagnosed OUD. We modeled the projected program implementation costs and estimated disability-adjusted life years (DALYs) averted over a 10-year period, associated with the provision of methadone therapy for a hypothetical, unreplenished cohort of Russian adults with an OUD (n = 249,000), in comparison to the current therapies at existing addiction treatment facilities. Our model compared four distinct scenarios of treatment coverage in the cohort ranging from 3.1 to 55%. Providing methadone therapy to as few as 3.1% of adults with an OUD amounted to an estimated almost 50,000 DALYs averted over 10 years at a cost of just over USD 17 million. Further expanding service coverage to 55% resulted in an estimated almost 900,000 DALYs averted, at a cost of about USD 308 million. Our study indicated that implementing opioid agonist therapy with methadone to treat OUD at existing facilities in Russia is highly cost-effective.

Fetal organ dosimetry for the Techa River and Ozyorsk Offspring Cohorts. Pt. 2. Radionuclide S values for fetal self-dose and maternal cross-dose

International Nuclear Information System (INIS)

Maynard, Matthew R.; Bolch, Wesley E.; Shagina, Natalia B.; Tolstykh, Evgenia I.; Degteva, Marina O.; Fell, Tim P.

2015-01-01

One of the many objectives of the European Union's SOLO (Epidemiological Studies of Exposed Southern Urals Populations) project is to quantify the radiation dose-response following chronic in utero exposures to ionizing radiation. The project is presently conducting a pooled analysis of two cohorts of individuals born to exposed mothers - the Techa River Offspring Cohort (TROC) and the Ozyorsk Offspring Cohort (OOC). The TROC includes the offspring of mothers with external exposures to contaminated riverbanks and internal ingestions of 89 Sr, 90 Sr/ 90 Y, and 137 Cs/ 137m Ba, while the OOC includes the offspring of mothers with external exposures seen within the Mayak plutonium production facilities and internal inhalation of 239 Pu and possibly 131 I. In the present study, a newly created Urals-based series of fetal and maternal models is employed to assess S values for all seven radionuclides. Among all fetal ages, S values ranged in magnitude from 10 -14 to 10 -10 Gy per Bq-s for fetal source organs and from 10 -18 to 10 -14 Gy per Bq-s from maternal source organs, depending upon particle type, particle energy, and fetal age. For a given radionuclide and fetal age, S values for fetal source organs were approximately two orders of magnitude higher than for maternal source organs. Little variation in S values was observed among fetal source organs, while variations of over 100 % with respect to the mean were observed for maternal source organs near the fetus. S value variations from maternal cross-fire were highly dependent on fetal position and separation distance from the maternal source organ. These radionuclide S values have been coupled with biokinetic models for use in cohort dose assessment within the SOLO project. (orig.)

Lack of influence of CYP2D6 genotype on the clearance of (R)-, (S)- and racemic-methadone

DEFF Research Database (Denmark)

Coller, J K; Joergensen, C; Foster, D J R

2007-01-01

OBJECTIVE: To investigate the influence of CYP2D6 genotype on the oral clearance of (R)-, (S)- and rac-methadone. METHODS: In this retrospective study, CYP2D6 genotypes were identified in 56 methadone maintained subjects. Plasma concentrations of (R)-, (S)- and rac-methadone were determined by st...

Effect of Eight Weeks Forced Swimming Training with Methadone Supplementation on Aspartate Aminotransferase, Alanine Aminotransferase, and Alkaline Phosphatase of Rats

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Seyed Ali Hoseini

2016-12-01

Full Text Available Background & Objective: Narcotics abuse can induce liver disorders; nevertheless, exercises improve liver disorders. The present research aimed to review the effect of eight weeks forced swimming training with methadone supplementation on liver enzymes of rats. Material & Method: In this experimental research, 48 rats were selected, and after one week adaptation to lab environment, they were randomly divided into four groups of 12 rats including (1 forced swimming training, (2 methadone supplementation, (3 forced swimming training with methadone supplementation, and (4 control. Groups 2 and 3 used 2 mg/kg methadone daily for 8 weeks. Also, groups 1 and 3 swam for 8 weeks, three sessions per week and each session for 30 minutes. For statistical analysis of data, one way ANOVA and Tukey post hoc tests were used (α≤0.05. Results: Findings showed that forced swimming training, methadone supplementation, and forced swimming training with methadone supplementation had no significant effect on AST (P=0.90 and ALT (P=0.99 enzymes; forced swimming training had significant effect on increase of ALP (P=0.001; also, forced swimming training, compared with methadone supplementation and combination of forced swimming training with methadone supplementation, had significant effect on increase of ALP (P=0.001. Conclusion: Accordingly, 8 weeks of forced swimming training with methadone has possibly no significant effect on liver enzymes.

False sense of safety by daily QTc interval monitoring during methadone IVPCA titration in a patient with chronic pain

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Miranda-Grajales H

2013-05-01

Full Text Available Hector Miranda-Grajales, Joy Hao, Ricardo A CrucianiDepartment of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, NY, USAAbstract: It has been proposed that some deaths attributed to methadone are related to prolongation of the QTc interval; however, there are no clear recommendations on electrocardiogram (ECG monitoring in patients undergoing intravenous methadone infusion. This is a report on a patient receiving methadone intravenous patient-controlled analgesia titration for the treatment of chronic pain. Initially, her daily ECGs showed QTc intervals within normal limits; however, she experienced a rapid increase in QTc interval from 317 ms to 784 ms within a 24-hour period after methadone had been discontinued for excessive sedation. QTc interval greater than 500 ms is considered to be high risk for the fatal arrhythmia Torsades de Pointes. Daily ECGs did not detect a gradual increase in the QTc interval that would have alerted the medical staff of the need to decrease or stop the methadone before reaching a prolonged QTc interval associated with cardiotoxicity. In selected cases where aggressive methadone titration is required, more intensive monitoring, such as telemetry or ECG determinations every 12 hours, might help detect changes in QTc interval duration that might otherwise be missed by daily ECG determinations.Keywords: methadone, QTc prolongation, opioids, opioid side effects, IVPCA methadone

Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon).

Science.gov (United States)

Scala, Christopher; Marsot, Amélie; Limoges, Marie-Josée; Locatelli, Yann; Simon, Nicolas; Alvarez, Jean-Claude

2015-03-01

To assess the population pharmacokinetics of methadone in deer. Prospective non-randomized experimental trial. Twelve healthy adult sika deer (nine males and three females). Deer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg(-1) or 1 mg kg(-1) . Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM). A two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour(-1) ), metabolic clearance (34.6 L hour(-1) ), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour(-1) ), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour(-1) , 121.0 L hour (-1) , 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration. Following intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Reducing the Risk of Methadone Overdose

Centers for Disease Control (CDC) Podcasts

2012-07-03

This podcast is based on the July 2012 CDC Vital Signs report. Approximately 14 people die every day of overdoses related to methadone. Listen to learn how to reduce your risk of an overdose.  Created: 7/3/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/3/2012.

Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

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Chen HH

2015-03-01

Full Text Available Hwei-Hsien Chen,1,2,* Yao-Chang Chiang,3,4,* Zung Fan Yuan,5,6 Chung-Chih Kuo,5,6 Mei-Dan Lai,2 Tsai-Wei Hung,1 Ing-kang Ho,1,3,4 Shao-Tsu Chen2,7 1Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan; 2Master and PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan; 3Center for Drug Abuse and Addiction, China Medical University Hospital, 4Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 5Master Program in Physiological and Anatomical Medicine, 6Department of Physiology, School of Medicine, Tzu Chi University, 7Department of Psychiatry, Buddhist Tzu Chi General Hospital, Hualien, Taiwan *These authors contributed equally to this work Abstract: Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female

A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison.

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Gordon, Michael S; Kinlock, Timothy W; Couvillion, Kathryn A; Schwartz, Robert P; O'Grady, Kevin

2012-05-01

The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly assigned to one of three treatment conditions: counseling only (counseling in prison; n= 70); counseling plus transfer (counseling in prison with transfer to methadone maintenance treatment upon release; n= 70); and counseling plus methadone (methadone maintenance in prison, continued in a community-based methadone maintenance program upon release; n= 71). Entered prison treatment (p prison treatment (pprison sentences may have better outcomes than younger individuals with shorter sentences, meaning they are more likely to enter and complete prison-based treatment. Furthermore, implications for the treatment of prisoners with prior heroin dependence and for conducting clinical trials may indicate the importance of examining individual characteristics and the possibility of the examination of patient preference.

Differences in methylphenidate abuse rates among methadone maintenance treatment patients in two clinics.

Science.gov (United States)

Peles, Einat; Schreiber, Shaul; Linzy, Shirley; Domani, Yoav; Adelson, Miriam

2015-07-01

Methylphenidate, an amphetamine-like prescription medication for attention deficit hyperactivity disorder (ADHD) was suspected as being abused among methadone maintenance treatment (MMT) patients. We tested its presence in the routine urine monitoring of all patients in both Tel Aviv and Las Vegas MMT clinics. Data on demographic and addiction history, ADHD (Wender Utah Rating Scale), cognitive impairment (Mini Mental State Exam), and lifetime DSM-IV-TR psychiatric diagnosis from admission were retrieved, and retention following 6 months. None of the 190 patients in Las Vegas tested positive for methylphenidate, while 14.7% (45/306) did in Tel Aviv. Abusers were less educated (p = 0.01), had higher ADHD scores (p = 0.02), lower cognitive scores (p = 0.05), and a higher benzodiazepine (BDZ) abuse rate (p cannabis, opiates, and cocaine abuse and infectious disease. Of the methylphenidate abuse 42.2% have take-home methadone dose privileges. Not like opiate use, being methylphenidate positive did not relate to 6-months retention. Compared to Tel Aviv, Las Vegas patients were more educated, with lower BDZ, and cocaine abuse. The greater abuse of methylphenidate among ADHD subjects might indicate their using it as self-medication, raising a possible indication for its prescription for that subgroup of MMT patients. The high rate of methylphenidate abuse in Israel needs future study. Copyright © 2015 Elsevier Inc. All rights reserved.

Structure of complications, causes of mortality, clinical and morphological parallels in acute poisoning with methadone hydrochloride

OpenAIRE

Andryuishchenko, V.V.; Kalish, N.M.; Kurdil, N.V.

2018-01-01

Background. The relevance of the study of methadone poisoning in Kyiv is determined by a significant increase in the number of poisonings among the population in recent years and high rates of mortality. The purpose of this study is to determine the factors that caused the fatal methadone poisonings in order to develop measures for reducing mortality among this category of patients. Materials and methods. The subject of the study is 35 cases of deaths due to the “street” methadone poisoning i...

Metabolic syndrome among individuals with heroin use disorders on methadone therapy: Prevalence, characteristics, and related factors.

Science.gov (United States)

Vallecillo, Gabriel; Robles, María José; Torrens, Marta; Samos, Pilar; Roquer, Albert; Martires, Paula K; Sanvisens, Arantza; Muga, Roberto; Pedro-Botet, Juan

2018-01-02

Observational studies have reported a high prevalence of obesity and diabetes in subjects on methadone therapy; there are, however, limited data about metabolic syndrome. The aim of the study was to evaluate the prevalence of metabolic syndrome and related factors in individuals with heroin use disorder on methadone therapy. A cross-sectional study in individuals with heroin use disorder on methadone therapy at a drug abuse outpatient center. Medical examinations and laboratory analyses after a 12-hour overnight fast were recorded. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. One hundred and twenty-two subjects were included, with a mean age of 46.1 ± 9 years, a median body mass index (BMI) of 25.3 kg/m 2 (interquartile range [IQR]: 21.2-28), and 77.9% were men. Median exposure to methadone therapy was 13 years (IQR: 5-20). Overweight and obesity were present in 29.5% and 17.2% of the participants, respectively. Metabolic syndrome components were low high-density lipoprotein (HDL) cholesterol (51.6%), hypertriglyceridemia (36.8%), high blood pressure (36.8%), abdominal obesity (27.0%), and raised blood glucose levels (18.0%). Abdominal obesity was more prevalent in women (52% vs. 20%, P = >0.01) and high blood pressure more prevalent in men (41.1% vs. 22.2%, P = .07). Prevalence of metabolic syndrome was 29.5% (95% confidence interval [CI]: 16.6-31.8). In the multivariate logistic regression analysis, BMI (per 1 kg/m 2 increase odds ratio [OR]: 1.49, 95% CI: 1.27-1.76) and exposure time to methadone therapy (per 5 years of treatment increase OR: 1.38, 95% CI: 1.28-1.48) were associated with metabolic syndrome. Overweight and metabolic syndrome are prevalent findings in individuals with heroin use disorder on methadone therapy. Of specific concern is the association of methadone exposure with metabolic syndrome. Preventive measures and clinical routine screening should be

Determination of the unbound fraction of R- and S-methadone in human brain

DEFF Research Database (Denmark)

Holm, Karen M D; Linnet, Kristian

2016-01-01

According to the free drug hypothesis, only the unbound fraction (f u ) of a given drug is biologically available in terms of its pharmacologic activity. Methadone shows large interpersonal variation in toxicity. The goal of the work presented here was to examine whether isolating the unbound...... fraction of the active R-methadone enantiomer from brain matter could be of value as a forensic tool. A method applying equilibrium dialysis to postmortem brain samples was validated and showed good reproducibility for the previously published f u values for eight common drugs (alprazolam, citalopram...... with multiple drugs, methadone poisoning, and deaths unrelated to methadone), but these are thought to be too low to be of any forensic value....

Pharmacokinetic Effects of Isavuconazole Coadministration With the Cytochrome P450 Enzyme Substrates Bupropion, Repaglinide, Caffeine, Dextromethorphan, and Methadone in Healthy Subjects.

Science.gov (United States)

Yamazaki, Takao; Desai, Amit; Goldwater, Ronald; Han, David; Howieson, Corrie; Akhtar, Shahzad; Kowalski, Donna; Lademacher, Christopher; Pearlman, Helene; Rammelsberg, Diane; Townsend, Robert

2017-01-01

This report describes phase 1 clinical trials performed to assess interactions of oral isavuconazole at the clinically targeted dose (200 mg, administered as isavuconazonium sulfate 372 mg, 3 times a day for 2 days; 200 mg once daily [QD] thereafter) with single oral doses of the cytochrome P450 (CYP) substrates: bupropion hydrochloride (CYP2B6; 100 mg; n = 24), repaglinide (CYP2C8/CYP3A4; 0.5 mg; n = 24), caffeine (CYP1A2; 200 mg; n = 24), dextromethorphan hydrobromide (CYP2D6/CYP3A4; 30 mg; n = 24), and methadone (CYP2B6/CYP2C19/CYP3A4; 10 mg; n = 23). Compared with each drug alone, coadministration with isavuconazole changed the area under the concentration-time curves (AUC ∞ ) and maximum concentrations (C max ) as follows: bupropion, AUC ∞ reduced 42%, C max reduced 31%; repaglinide, AUC ∞ reduced 8%, C max reduced 14%; caffeine, AUC ∞ increased 4%, C max reduced 1%; dextromethorphan, AUC ∞ increased 18%, C max increased 17%; R-methadone, AUC ∞ reduced 10%, C max increased 3%; S-methadone, AUC ∞ reduced 35%, C max increased 1%. In all studies, there were no deaths, 1 serious adverse event (dextromethorphan study; perioral numbness, numbness of right arm and leg), and adverse events leading to study discontinuation were rare. Thus, isavuconazole is a mild inducer of CYP2B6 but does not appear to affect CYP1A2-, CYP2C8-, or CYP2D6-mediated metabolism. © 2016 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Awareness of the need for safe storage of Methadone at home is not improved by the use of protocols on recording information giving

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Crome Ilana B

2008-04-01

Full Text Available Abstract Background Methadone is a synthetic, narcotic analgesic used in the treatment of drug misuse. Tragedies involving children being poisoned by the accidental ingestion of methadone are no longer a rare occurrence. Following an audit of the effectiveness of the provision and recall of information to patients attending an NHS Methadone Clinic a protocol was introduced to ensure that staff documented the provision of such information and patients gave a written confirmation that they had received the information. Methods The study was undertaken in the setting of an NHS methadone clinic with the aim of re- auditing the storage of methadone at home following the introduction of the new protocols. 174 patients completed an anonymous questionnaire regarding where they store methadone at home and whether they recall being given advice about safe storage. Community pharmacists were contacted by telephone to assess the level of advice given to methadone patients regarding safety. Results Only 49 (28.2% patients recalled being given advice about safe storage, 24 (13.8% recalled that information was provided by clinic staff. 170 (97.7% patients regard methadone as being dangerous. (28.2%. Methadone is most commonly stored in a cupboard (37.9%. All methadone is dispensed in a bottle with a child resistant cap on it. All patients reported they stored their methadone in the original bottle provided by the pharmacist. Conclusion Recall of information on safety issues is very poor. Provision of written as well as verbal information is needed. The use of printed safety information cards which patients can take away for future reference may be of use. It is the responsibility of health professionals to ensure they provide information and advice to methadone users on the safe storage of their methadone at home.

Psychopathology and urine toxicology in methadone patients

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Gamal Sadek

2015-06-01

Full Text Available Several studies reported high rates of psychiatric commorbidity among methadone patients. We examined the relationships of measures of psychopathology to outcomes of screening urine tests for cocaine, opiates, and benzodiazepines in a sample of 56 methadone patients. They also completed the Symptom Check List-90-Revised (SCL-90-R. The highest scales in the SCL-90-R profile of our patients were those indicating somatic discomfort, anger, phobic anxiety, paranoid ideation, and also obsessive-compulsive disorder symptoms (scores above the 39th percentile. The only significant correlations between urine tests and SCL-90-R psychopathology were those involving benzodiazepines: patients with urine tests positive for benzodiazepines had lower social self-confidence (r=0.48, were more obsessive-compulsive (r=0.44, reported a higher level of anger (r=0.41, of phobic tendencies (r=40, of anxiety (r=0.39, and of paranoid tendencies (r=0.38, and also reported more frequent psychotic symptoms (r=0.43.

Methadone Poisoning in Children: A Systematic Review and Meta-Analysis in Iran

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Yasaman Allameh

2017-05-01

Full Text Available Context Symptoms of methadone poisoning, as one of the most dangerous types of poisoning, are very serious in children. Objectives The aim of this study was to describe causes and clinical symptoms of methadone poisoning in children admitted to hospitals in Iran. Data Sources Relevant studies published in national and international journals before January 29, 2016 were identified by studying the available databases, including PubMed, Web of Sciences, Google Scholar, Scopus, SID, Iranmedex, MagIran, and Irandoc. Study Selection After excluding duplicate, irrelevant, and low-quality articles, relevant papers were entered into the meta-analysis. The prevalence, mean, and standard deviation of methadone poisoning symptoms in children were statistically analyzed, using Stata version 11, and causes of methadone poisoning were presented in tables. Data Extraction Studies with unknown sample sizes, abstracts without access to full text, articles with quality assessment scores below 15.5, and studies carried out on non-Iranian populations were excluded from the meta-analysis. Results During the initial advanced search, 1594 articles were identified. After quality assessment, 12 papers were found eligible for the final systematic review and meta-analysis, based on the inclusion and exclusion criteria. The reported symptoms included drowsiness, vomiting, apnea, cyanosis, seizure, ataxia, and delirium. In the meta-analysis, prevalence of symptoms in referred patients was estimated at 44% (0.95% confidence interval, 0.288 to 0.609. The causes of poisoning in children included accidental feeding by parents, storage of drugs in inappropriate containers, parental addiction, and low educational level of parents. Conclusions It is important to keep methadone in a suitable container away from children. Also, it is essential to focus on educating parents on health issues of their children.

Medicaid Coverage for Methadone Maintenance and Use of Opioid Agonist Therapy in Specialty Addiction Treatment.

Science.gov (United States)

Saloner, Brendan; Stoller, Kenneth B; Barry, Colleen L

2016-06-01

This study examined differences in opioid agonist therapy (OAT) utilization among Medicaid-enrolled adults receiving public-sector opioid use disorder treatment in states with Medicaid coverage of methadone maintenance, states with block grant funding only, and states without public coverage of methadone. Person-level treatment admission data, which included information on reason for treatment and use of OAT from 36 states were linked to state-level Medicaid policies collected in a 50-state survey. Probabilities of OAT use among Medicaid enrollees in opioid addiction treatment were calculated, with adjustment for demographic characteristics and patterns of substance use. In adjusted analysis, 45.0% of Medicaid-enrolled individuals in opioid addiction treatment in states with Medicaid coverage for methadone maintenance used OAT, compared with 30.1% in states with block grant coverage only and 17.0% in states with no coverage. Differences were widest in nonintensive outpatient settings. Medicaid methadone maintenance coverage is critical for encouraging OAT among individuals with opioid use disorders.

Methadone-induced delayed posthypoxic encephalopathy: clinical, radiological, and pathological findings.

Science.gov (United States)

Mittal, Manoj; Wang, Yunxia; Reeves, Alan; Newell, Kathy

2010-01-01

Objective. To describe the clinical, radiological and pathological findings in a patient with methadone-induced delayed posthypoxic encephalopathy (DPHE). Case Report. A Thirty-eight-year-old man was found unconscious for an unknown duration after methadone and diazepam ingestion. His initial vitals were temperature 104 degree Fahrenheit, heart rate 148/minute, respiratory rate 50/minute, and blood pressure 107/72 mmhg. He developed renal failure, rhabdomyolysis, and elevated liver enzymes which resolved completely in 6 days. After 2 weeks from discharge he had progressive deterioration of his cognitive, behavioral and neurological function. Brain MRI showed diffuse abnormal T2 signal in the corona radiata, centrum semiovale, and subcortical white matter throughout all lobes. Extensive work up was negative for any metabolic, infectious or autoimmune disorder. Brain biopsy showed significant axonal injury in the white matter. He was treated successfully with combination of steroids and antioxidants. Follow up at 2 year showed no residual deficits. Conclusion. Our observation suggests that patients on methadone therapy should be monitored for any neurological or psychiatric symptoms, and in suspected cases MRI brain may help to make the diagnosis of DPHE. A trial of steroids and antioxidants may be considered in these patients.

High-performance liquid chromatographic analysis of methadone hydrochloride oral solution.

Science.gov (United States)

Beasley, T H; Ziegler, H W

1977-12-01

A direct and rapid high-performance liquid chromatographic assay for methadone hydrochloride in a flavored oral solution dosage form is described. A syrup sample, one part diluted with three parts of water, is introduced onto a column packed with octadecylsilane bonded on 10 micrometer porous silica gel (reversed phase). A formic acid-ammonium formate-buffered mobile phase is linear programmed with acetonitrile. The absorbance is monitored continuously at 280 or 254 nm, using a flow-through, UV, double-beam photometer. An aqueous methadone hydrochloride solution is used for external standardization. The relative standard deviation was not more than 1.0%. Drug recovery from a syrup base was better than 99.8%.

Exploring the health concerns of people taking methadone

LENUS (Irish Health Repository)

James, P

2012-01-01

This article reports on a study to uncover the health concerns of clients attending a methadone maintenance programme in an addiction service in Ireland. This is an extended version of the article published in Nursing Times; 104: 35, 26–27.

Methadone maintenance therapy as evidence based drug abuse ...

African Journals Online (AJOL)

Methadone maintenance therapy as evidence based drug abuse planning in ... drugs are being used as artificial problem-solvers such as frustrations, stress or ... Drug use is a problem to users when it begins to cause some damage to their ...

Use of general practice by intravenous heroin users on a methadone programme.

OpenAIRE

Leaver, E J; Elford, J; Morris, J K; Cohen, J

1992-01-01

Users of intravenous heroin represent a major challenge for general practice. A study was undertaken in a general practice in central London in 1990 to investigate the use of general practice made by intravenous heroin users who were on a methadone programme. Using information recorded in the patients' notes, 29 intravenous heroin users on a methadone programme were identified; 58 non-drug users (two controls per case) were matched for age, sex and general practitioner. A study of the number ...

Opioid Addiction and Abuse in Primary Care Practice: A Comparison of Methadone and Buprenorphine as Treatment Options

Science.gov (United States)

Bonhomme, Jean; Shim, Ruth S.; Gooden, Richard; Tyus, Dawn; Rust, George

2014-01-01

Opioid abuse and addiction have increased in frequency in the United States over the past 20 years. In 2009, an estimated 5.3 million persons used opioid medications nonmedically within the past month, 200 000 used heroin, and approximately 9.6% of African Americans used an illicit drug. Racial and ethnic minorities experience disparities in availability and access to mental health care, including substance use disorders. Primary care practitioners are often called upon to differentiate between appropriate, medically indicated opioid use in pain management vs inappropriate abuse or addiction. Racial and ethnic minority populations tend to favor primary care treatment settings over specialty mental health settings. Recent therapeutic advances allow patients requiring specialized treatment for opioid abuse and addiction to be managed in primary care settings. The Drug Addiction Treatment Act of 2000 enables qualified physicians with readily available short-term training to treat opioid-dependent patients with buprenorphine in an office-based setting, potentially making primary care physicians active partners in the diagnosis and treatment of opioid use disorders. Methadone and buprenorphine are effective opioid replacement agents for maintenance and/or detoxification of opioid-addicted individuals. However, restrictive federal regulations and stigmatization of opioid addiction and treatment have limited the availability of methadone. The opioid partial agonist-antagonist buprenorphine/naloxone combination has proven an effective alternative. This article reviews the literature on differences between buprenorphine and methadone regarding availability, efficacy, safety, side-effects, and dosing, identifying resources for enhancing the effectiveness of medication-assisted recovery through coordination with behavioral/psychological counseling, embedded in the context of recovery-oriented systems of care. PMID:23092049

Methadone for the treatment of Prescription Opioids Dependence. A retrospective chart review.

Science.gov (United States)

Barrio, Pablo; Ezzeldin, Mohamed; Bruguera, Pol; Pérez, Ana; Mansilla, Sara; Fàbrega, Marina; Lligoña, Anna; Mondón, Sílvia; Balcells, Mercè

2016-06-14

Prescription opioids (PO) addiction is increasing to an epidemic level. Few studies exist regarding its treatment. Although buprenorphine has been the mainstay so far, other treatment options might be considered, such as methadone. We conducted a retrospective assessment of all patients admitted to a psychiatry ward for PO detoxification using methadone between 2010 and 2013. The assessment and description was carried out during a 3-month follow-up period after their discharge. Although this is a retrospective chart review, our exploration included sociodemographic and treatment variables in addition to the abstinence rates for the whole sample. Eleven patients were included, mostly women (81.8%), with a median age of 50 years. The median duration of dependence was 8 years. Dependence on other substances and psychiatric comorbidities were high. Eight patients were monitored during three months. Of these, 7 (87.5%) were abstinent after that period. The results suggest that methadone deserves further exploration as a potentially efficacious treatment option for PO dependence.

Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.

Science.gov (United States)

Oliveto, A H; Feingold, A; Schottenfeld, R; Jatlow, P; Kosten, T R

1999-09-01

Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10. In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence. Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Trends in drug overdose deaths in England and Wales 1993-98: methadone does not kill more people than heroin.

Science.gov (United States)

Hickman, Matthew; Madden, Peter; Henry, John; Baker, Allan; Wallace, Chris; Wakefield, Jon; Stimson, Gerry; Elliott, Paul

2003-04-01

To test the hypothesis that methadone is responsible for a greater increase in overdose deaths than heroin, and causes proportionally more overdose deaths than heroin at weekends. Multivariate analysis of 3961 death certificates mentioning heroin, morphine and/or methadone held on the Office for National Statistics drug-related poisoning mortality database from 1993 to 1998 in England and Wales. Percentage increase in deaths by year by drug, odds ratio (OR) of dying at the weekend from methadone-related overdose compared to dying from heroin/morphine overdose. From 1993 to 1998, annual opiate overdose deaths increased from 378 to 909. There was a 24.7% (95% confidence interval (CI) 22-28%) yearly increase in heroin deaths compared to 9.4% (95% CI 6-13%) for methadone only. This difference was significant (P < 0.001 by test of interaction) after adjustment for sex, age group, polydrug use, area of residence and underlying cause of death. The largest number of deaths occurred on Saturday (673). The OR of death from methadone overdose on Saturday and Sunday was 1.48 (95% CI 1.29-1.71) for methadone-only deaths compared to dying from heroin/morphine at the weekend after adjustment for other covariates, but the OR was not significant (1.09, 95% CI 0.95-1.25) if the weekend was defined as Friday and Saturday. There was no evidence that the threefold increase in deaths over time was due to methadone. There was equivocal support only for the hypothesis that there was an excess of deaths from methadone at weekends. Increased interventions to prevent overdose among injectors in England and Wales are long overdue.

Association between the DRD2 A1 allele and response to methadone and buprenorphine maintenance treatments.

Science.gov (United States)

Barratt, Daniel T; Coller, Janet K; Somogyi, Andrew A

2006-06-05

The TaqI A polymorphism (A(1)) of the dopamine D(2) receptor gene (DRD2), although not a specific predictor of opioid dependence, has been strongly associated with high levels of prior heroin use and poor treatment outcomes among methadone maintenance patients. The aims of this study were to confirm these findings via a retrospective analysis of A(1) allele frequency in methadone (n = 46) and buprenorphine (n = 25) patients, and non-opioid-dependent controls (n = 95). Subjects were genotyped at the DRD2 TaqI A locus using PCR amplification followed by TaqI restriction enzyme digestion and gel electrophoresis. For methadone and buprenorphine subjects, heroin use (prior to treatment), treatment outcomes, and withdrawal occurrence were determined from comprehensive case notes. No significant differences in A(1) allele frequency (%) were observed between: methadone (19.6%), buprenorphine (18.0%), and control (17.9%) groups (P > 0.7); successful and poor treatment outcome groups, methadone: 20.0% and 19.2%, respectively (P = 1.0); buprenorphine: 18.4% and 20.0%, respectively (P = 1.0). Also, there were no significant relationships between TaqI A genotype and prior heroin use (P = 0.47). However, among the successful methadone subjects, significantly fewer A(1) allele carriers experienced withdrawal than non-A(1) carriers (P = 0.04). In conclusion, the DRD2 genotype effects did not affect opioid maintenance treatment outcomes. This suggests the need for a further prospective investigation into the role of the DRD2 A(1) allele in heroin use and response to maintenance pharmacotherapies for opioid dependence.

COMMUNICATING RISK IN THE CONTEXT OF METHADONE FORMULATION CHANGES: A QUALITATIVE STUDY OF OVERDOSE WARNING POSTERS IN VANCOUVER, CANADA

Science.gov (United States)

Markwick, Nicole; McNeil, Ryan; Anderson, Solanna; Small, Will; Kerr, Thomas

2015-01-01

BACKGROUND British Columbia, Canada’s provincial methadone program recently replaced their existing methadone formulation with a formulation ten times more concentrated. The transition raised concerns about heightened risk of accidental overdose, leading two organizations to disseminate methadone overdose warning posters during the transitional period. This study explores people who use drugs’ (PWUD) perceptions of these warning posters. METHODS Qualitative interviews were conducted with thirty-four PWUD enrolled in methadone maintenance treatment in Vancouver. Participants were recruited from ongoing cohort studies of drug-using individuals. Interview transcripts were analyzed thematically, focusing on participants’ perceptions of the warning posters and potential impacts on drug-related risks. RESULTS Overdose warning posters constituted a key source of information about the methadone formulation change, but did not provide adequate information for all participants. Participants articulated a preference for descriptive language, focusing on changes in concentration rather than “strength”, and universal hazard symbols to effectively communicate overdose risks. CONCLUSION Participants indicated that warnings employing descriptive language more effectively communicated risk of methadone overdose. Future overdose warnings for drug-using populations must provide adequate information for the intended audience, and be communicated to PWUD through multiple channels. PMID:26644025

A comparison of intraoperative morphine sulfate and methadone hydrochloride on postoperative visual analogue scale pain scores and narcotic requirements.

Science.gov (United States)

Laur, D F; Sinkovich, J; Betley, K

1995-02-01

Morphine sulfate and methadone hydrochloride exhibit very different half-lives but are described as having an analgesic potency of one. The use of a drug like methadone may provide prolonged and constant analgesia in the perioperative setting. This double-blinded investigation used methadone and morphine intraoperatively and measured pain scores and narcotic requirements in the first 24 hours postoperatively. Thirty American Society of Anesthesiology (ASA) patients, physical status I through III, between the ages of 18 to 65 years were scheduled for orthopedic surgery and randomly assigned to receive morphine or methadone at 0.30 mg/kg. Fifteen patients received morphine and fifteen patients received methadone. There was no significant difference between the two groups in terms of age, height, weight, and ASA status. No statistically significant difference was observed among the two groups between the amount of analgesic requirements postoperatively or in the visual analogue scale pain score.

Enhancing the quality of nursing care in methadone substitute clinics using action research: a process evaluation

NARCIS (Netherlands)

Loth, Christien; Schippers, Gerard M.; Hart, Harm't; van de Wijngaart, Goof

2007-01-01

AIM: This paper is a report of a study to answer the research question: can participative action research help to halt the deterioration in methadone substitution treatment and develop new care strategies which are better geared toward the patients' needs? BACKGROUND: In the Netherlands, methadone

High-dose buprenorphine: perioperative precautions and management strategies.

Science.gov (United States)

Roberts, D M; Meyer-Witting, M

2005-02-01

Buprenorphine has been in clinical use in anaesthesia for several decades. Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser, Slough, U.K.) has been increasingly used as maintenance therapy in opioid dependence, as an alternative to methadone and other pharmacological therapies. Buprenorphine has unique pharmacological properties making it well suited for use as a maintenance therapy in opioid dependence. However, these same properties may cause difficulty in the perioperative management of pain. Buprenorphine is a partial opioid agonist, attenuating the effects of supplemental illicit or therapeutic opioid agonists. As a result of its high receptor affinity, supplemental opioids do not readily displace buprenorphine from the opioid receptor in standard doses. High-dose buprenorphine has an extended duration of action that prolongs both of these effects. The perioperative management of patients stabilized on high-dose buprenorphine and undergoing surgery requires consideration of the likely analgesic requirements. Where possible the buprenorphine should be continued. Pain management should focus on maximizing non-opioid analgesia, local anaesthesia and non-pharmacological techniques. Where pain may not be adequately relieved by these methods, the addition of a full opioid agonist such as fentanyl or morphine at appropriate doses should be considered, accompanied by close monitoring in a high dependency unit. In situations where this regimen is unlikely to be effective, preoperative conversion to morphine or methadone may be an option. Where available, liaison with a hospital-based alcohol and drug service should always be considered.

Porous silicon mass spectrometry as an alternative confirmatory assay for compliance testing of methadone.

Science.gov (United States)

Guinan, Taryn M; Neldner, Declan; Stockham, Peter; Kobus, Hilton; Della Vedova, Christopher B; Voelcker, Nicolas H

2017-05-01

Porous silicon based surface-assisted laser desorption ionization mass spectrometry (pSi SALDI-MS) is an analytical technique well suited for high throughput analysis of low molecular weight compounds from biological samples. A potential application of this technology is the compliance monitoring of opioid addiction programmes, where methadone is used as a pharmacological treatment for drugs such as heroin. Here, we present the detection and quantification of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) from water and clinical samples (saliva, urine, and plasma) from opioid dependent participants using pSi SALDI-MS. A one-step solvent phase extraction using chloroform was developed for the detection of methadone from clinical samples for analysis by pSi SALDI-MS. Liquid chromatography-mass spectrometry (LC-MS) was used as a comparative technique for the quantification of methadone from clinical saliva and plasma samples. In all cases, we obtained a good correlation of pSi SALDI-MS and LC-MS results, suggesting that pSi SALDI-MS may be an alternative procedure for high-throughput screening and quantification for application in opioid compliance testing. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Severe cerebellitis following methadone poisoning

International Nuclear Information System (INIS)

Mills, Fionnghuala; MacLennan, Suzanna C.; Devile, Catherine J.; Saunders, Dawn E.

2008-01-01

We report a 3-year-old girl with an unusual presentation of cerebellitis following ingestion of methadone. CT showed diffuse symmetrical swelling and oedema of the cerebellum resulting in compression of the fourth ventricle and hydrocephalus. The changes were confirmed on MRI with the addition of watershed injuries. These findings represent a toxic encephalopathy and have been reported in previous cases of heroin intoxication by inhalation, but rarely following opioid ingestion. The aetiology of the watershed infarcts is discussed. (orig.)

Severe cerebellitis following methadone poisoning

Energy Technology Data Exchange (ETDEWEB)

Mills, Fionnghuala; MacLennan, Suzanna C.; Devile, Catherine J.; Saunders, Dawn E. [Great Ormond Street Hospital, Department of Paediatric Neurology, London (United Kingdom)

2008-02-15

We report a 3-year-old girl with an unusual presentation of cerebellitis following ingestion of methadone. CT showed diffuse symmetrical swelling and oedema of the cerebellum resulting in compression of the fourth ventricle and hydrocephalus. The changes were confirmed on MRI with the addition of watershed injuries. These findings represent a toxic encephalopathy and have been reported in previous cases of heroin intoxication by inhalation, but rarely following opioid ingestion. The aetiology of the watershed infarcts is discussed. (orig.)

Opioid Use Disorder Induces Oxidative Stress and Inflammation: The Attenuating Effect of Methadone Maintenance Treatment

Directory of Open Access Journals (Sweden)

Ali Salarian

2018-02-01

Full Text Available Objective: Frequent use of opioids produces reactive oxygen species, upregulates inflammatory factors, and contributes to opiate dependence. In this study, we examined perturbations of plasma oxidative and inflammatory markers in patients with opioid use disorder in two phases. In the first phase, we compared the oxidative status in patients with opioid use disorders and in healthy controls; and in the second phase, we examined oxidative changes before and after methadone maintenance treatment.Method: To explore whether oxidative changes were associated with opioid use disorder, we compared plasma oxidative and inflammatory markers in patients with opioid use disorder and in smoking and non-smoking healthy participants. All participants completed measures of catalase (CAT, glutathione (GSH, malondialdehyde (MDA, superoxide dismutase (SOD, matrix metalloproteinase (MMP-9, and TNF-α at baseline. Baseline measures were compared using Kruskal-Wallis test. In the second phase, to explore oxidative changes during transition from opium use to methadone, blood and urine samples of patients with opioid use disorder were re-evaluated on Days 3, 7, and 14 after methadone therapy. Repeated measures analysis was used to determine the relative contribution of intervention to changes in CAT, GSH, MDA, SOD, MMP-9, and TNF-α level over time.Results: We observed lower SOD and catalase activities, and higher TNF-α and MMP-9 level in patients compared to the two comparison groups. Opioids exacerbated the oxidative imbalance and superimposed the underlying oxidative injury in smoker comparison group. Methadone therapy was associated with lower MMP-9 and TNF-α level, and higher SOD and catalase activities two weeks after therapy; showing an improvement in oxidative profile.Conclusion: This was an investigation indicating an oxidative imbalance before methadone therapy and during early days of transition from opium use to methadone. Being aware of redox status is

Use of solid-phase microextraction (SPME) for the determination of methadone and EDDP in human hair by GC-MS.

Science.gov (United States)

Lucas, A C; Bermejo, A M; Tabernero, M J; Fernández, P; Strano-Rossi, S

2000-01-10

Solid-phase microextraction (SPME) is a new extraction technique with many advantages: small sample volume, simplicity, quickness and solvent-free. It is mainly applied to environmental analysis, but is also useful for the extraction of drugs from biological samples. In this paper the use of SPME is proposed for the determination of methadone and its main metabolite EDDP in hair by GC-MS. The hair samples were washed, cut into 1-mm segments, and incubated with Pronase E for 12 h. A 100-micron polydimethylsiloxane (PDMS) film fibre was submerged for 30 min in a diluted solution of the hydrolysis liquid (1:4 with borax buffer) containing methadone-d3 and EDDP-d3 as internal standards. Once the microextraction was concluded the fibre was directly inserted into the CG injection port. Linearity was found for methadone and EDDP in the range studied, 1.0-50 ng/mg hair, with correlation coefficients higher than 0.99. Interassay relative standard deviation (R.S.D) was determined to be less than 13.30% for methadone and less than 8.94% for EDDP, at 3.0 and 30.0 ng/mg. Analytical recoveries were close to 100% for both compounds on spiked samples. The method was applied to the analysis of real hair samples from eight patients of a methadone maintenance programme. The concentration of methadone in hair ranged from 2.45 to 78.10 ng/mg, and for EDDP from 0.98 to 7.76 ng/mg of hair.

Methadone-Induced Delayed Posthypoxic Encephalopathy: Clinical, Radiological, and Pathological Findings

Directory of Open Access Journals (Sweden)

Manoj Mittal

2010-01-01

Full Text Available Objective. To describe the clinical, radiological and pathological findings in a patient with methadone-induced delayed posthypoxic encephalopathy (DPHE. Case Report. A Thirty-eight-year-old man was found unconscious for an unknown duration after methadone and diazepam ingestion. His initial vitals were temperature 104 degree Fahrenheit, heart rate 148/minute, respiratory rate 50/minute, and blood pressure 107/72 mmhg. He developed renal failure, rhabdomyolysis, and elevated liver enzymes which resolved completely in 6 days. After 2 weeks from discharge he had progressive deterioration of his cognitive, behavioral and neurological function. Brain MRI showed diffuse abnormal T2 signal in the corona radiata, centrum semiovale, and subcortical white matter throughout all lobes. Extensive work up was negative for any metabolic, infectious or autoimmune disorder. Brain biopsy showed significant axonal injury in the white matter. He was treated successfully with combination of steroids and antioxidants. Follow up at 2 year showed no residual deficits. Conclusion. Our observation suggests that patients on methadone therapy should be monitored for any neurological or psychiatric symptoms, and in suspected cases MRI brain may help to make the diagnosis of DPHE. A trial of steroids and antioxidants may be considered in these patients.

Treatment of early AIDS dementia in intravenous drug users : High versus low dose peptide T

NARCIS (Netherlands)

Kosten, TR; Rosen, MI; McMahon, TL; Bridge, TP; OMalley, SS; Pearsall, R; OConnor, PG

1997-01-01

This placebo-controlled, double blind, cross-over study tested the efficacy of two different doses of Peptide T in the treatment of nine intravenous drug users with early AIDS dementia who were also receiving methadone and AZT. Subjects received Peptide T doses of either 15 or 1.5 mg daily for four

Maternal Buprenorphine Dose, Placenta Buprenorphine and Metabolite Concentrations and Neonatal Outcomes

Science.gov (United States)

Concheiro, Marta; Jones, Hendreé E.; Johnson, Rolley E.; Choo, Robin; Shakleya, Diaa M.; Huestis, Marilyn A.

2010-01-01

Buprenorphine is approved as pharmacotherapy for opioid dependence in non-pregnant patients in multiple countries, and is currently under investigation for pregnant women in the US and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in 5 term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships between maternal buprenorphine dose, placenta concentrations, and neonatal outcomes following controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (CV<27.5%, 4 locations), except for buprenorphine in 3 placentas. In 2 of these, buprenorphine was not detected in some locations and, in the 3rd placenta, was totally absent. Median (range) concentrations were buprenorphine 1.6ng/g (not detected to 3.2), norbuprenorphine 14.9ng/g (6.2 to 24.2), buprenorphine-glucuronide 3ng/g (1.3 to 5.0) and norbuprenorphine-glucuronide 14.7ng/g (11.4 to 25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15–70 fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration, and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome (NAS) onset and duration, and for norbuprenorphine/norbuprenorphine-glucuronide ratio and maximum NAS score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women. PMID:20216119

Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale?

OpenAIRE

Mujtaba, Sobia; Romero, Jorge; Taub, Cynthia C.

2013-01-01

Methadone is a drug that has found widespread utility in the management of opioid addiction and pain. Along with its popularity, methadone has also earned an infamous reputation for causing prolongation of the QT interval and an increased risk of torsades de pointes.

Methadone treatment, bruxism, and temporomandibular disorders among male prisoners.

Science.gov (United States)

Enguelberg-Gabbay, Judith V; Schapir, Lior; Israeli, Yair; Hermesh, Haggai; Weizman, Abraham; Winocur, Ephraim

2016-06-01

There is little information on bruxism related to illicit drug use. Prolonged drug use may damage the stomatognathic system via oral motor overactivity. The aim of the present study was to compare the rates of bruxism and temporomandibular disorders (TMDs) between prisoners with and without drug-use disorders, to evaluate the association between methadone treatment and bruxism and to assess the possible relationship between bruxism and pain. The sample included 152 male prisoners, 69 of whom were drug users maintained on methadone. All prisoners were examined by an experienced dentist and completed a questionnaire on their oral habits, with the aim of detecting signs or symptoms of TMD and/or bruxism. Additional data were collected from medical files. The prevalence of sleep bruxism and awake bruxism, but not of TMDs, was significantly higher among drug-user than non-drug user prisoners (52.2% vs. 34.9% for sleep bruxism, 59.7% vs. 30.1% for awake bruxism, and 46.3% vs. 25.6% for TMDs, respectively). Participants with awake bruxism were statistically more sensitive to muscle palpation compared with participants with sleep bruxism [rating scores (mean ± SD): 0.32 ± 0.21 vs. 0.19 ± 0.28, respectively]. An association was found between sleep bruxism and awake bruxism. It seems that there is a direct or an indirect association between methadone maintenance treatment and sleep bruxism or awake bruxism in male prisoners. © 2016 Eur J Oral Sci.

Barriers and facilitators to primary care or human immunodeficiency virus clinics providing methadone or buprenorphine for the management of opioid dependence.

Science.gov (United States)

Turner, Barbara J; Laine, Christine; Lin, Yi-Ting; Lynch, Kevin

Federal initiatives aim to increase office-based treatment of opioid dependence, but, to our knowledge, factors associated with willingness to deliver this care have not been defined. The objective of this study was to describe clinics' willingness to provide methadone hydrochloride or buprenorphine hydrochloride for opioid dependence. The design of the study was a survey conducted in New York State. Two hundred sixty-one directors of primary care and/or human immunodeficiency virus specialty clinics (response rate, 61.1%) that serve Medicaid enrollees were questioned. Outcomes were willingness to provide methadone and buprenorphine. Predictors included clinic characteristics, attitudes about drug users and their treatment, and reported barriers and facilitators to treatment. Clinics were more willing to provide buprenorphine than methadone treatment (59.8% vs 32.6%; P methadone. Willingness was positively associated with continuing medical education credits for training, but negatively associated with greater concern about medication abuse. Immediate telephone access to an addiction expert was associated with willingness to provide buprenorphine (AOR, 2.08; 95% CI, 1.15-3.76). Greater willingness to provide methadone was associated with a belief that methadone-treated patients should be seen along with other patients (AOR, 6.20; 95% CI, 1.78-21.64), methadone program affiliation (AOR, 4.76; 95% CI, 1.64-13.82), and having more patients with chronic pain in the clinic (AOR, 2.80; 95% CI, 1.44-5.44). These clinics serving Medicaid enrollees were more receptive to buprenorphine than methadone treatment. Willingness to provide this care was greater in clinics offering human immunodeficiency virus services, treating more chronic pain, or affiliated with methadone programs. Accessible addiction experts and continuing medical education for training may facilitate adoption of this care.

The Comparison of Alexithymia and Spiritual Intelligence in Addicts, Addicts under Methadone Treatment, and Non-Addicts

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Mohammad Narimani

2012-08-01

Full Text Available Introduction: The purpose of the present study was to compare of the rate of alexithymia and spiritual intelligence in addicts, addicts under Methadone Treatment, and non-Addicts. Method: A causal-comparative research design was used. The study sample included 30 individuals under Methadone Treatment, 30 drug-dependent Addicted, and 30 non-addicted individuals selected by convenience sampling procedure. Toronto alexithymia scale and King's spiritual intelligence self-report inventory were administered among selected sample. Results: Findings revealed significant differences among addicted individuals and non-addicted adults also among individuals under methadone treatment and non-addicted adults in total alexithymia scores as well as on all three subscale scores. Furthermore, addicted individuals differed from those under methadone treatment in their scores on the subscale pertaining to difficulty in identifying feelings. Results also indicated differences among addicted individuals and those under methadone treatment in total spiritual intelligence and its four component scale scores, while addicted individuals differed from non-addicted individuals in total spiritual intelligence scores and only three of its component scale scores (personal meaning production, transcendental awareness, and conscious state expansion. Conclusion: Findings of this study indicate the advantages of the ability to control, emotional regulation and spiritual intelligence as a defense against addiction. By development of these characteristics addicts can be helped to gain relief from their addiction.

Effect of prenatal methadone and ethanol on opioid receptor development in rats

Energy Technology Data Exchange (ETDEWEB)

Peters, M.A.; Braun, R.L. (Loma Linda Univ., CA (United States))

1991-03-11

The current literature shows that the offspring of female rats exposed to methadone or ethanol display similar neurochemical and neurobehavioral alterations, and suggests that these drugs may be operating through a common mechanism. If this hypothesis is true, their effect on the endogenous opioid systems should be qualitatively similar. In this study virgin females were treated with methadone or 10% ethanol oral solution starting prior to conception and continued throughout gestation. When the offspring had reached 15 or 30 days of age they were sacrificed, the brain was removed and prepared for opioid receptor binding studies. ({sup 3}H)DAGO and ({sup 3}H)DADLE were used as ligands for the mu and delta receptors, respectively. These studies show significant treatment-related differences in both the number of mu and delta binding sites as well as in apparent receptor affinity. Significant sex- and age-related differences between treatments were also observed. These data show that methadone and ethanol, while manifesting some similar neurochemical and behavioral effects, have unique effects on opioid receptor binding, suggesting that they may be acting by different mechanisms.

Dextromethorphan attenuated inflammation and combined opioid use in humans undergoing methadone maintenance treatment.

Science.gov (United States)

Chen, Shiou-Lan; Lee, Sheng-Yu; Tao, Pao-Luh; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2012-12-01

Recent studies show that proinflammatory cytokines might be related to the development of opioid dependence (physiological, psychological, or both). In a double-blind, randomly stratified clinical trial investigating whether add-on dextromethorphan (60-120 mg/day) attenuated inflammation and the combined use of opioids in heroin-dependent patients undergoing methadone maintenance treatment, we evaluated whether inflammation is related to the progression of opioid dependence. All participants (107 heroin-dependent patients and 84 nondependent healthy controls) were recruited from National Cheng Kung University Hospital. Their plasma cytokine levels were measured to evaluate the effect of add-on dextromethorphan. Plasma TNF-α and IL-8 levels were significantly higher in long-term heroin-dependent patients than in healthy controls (p dextromethorphan. Moreover, both tolerance to methadone and the combined use of opioids were significantly (p dextromethorphan. We conclude that dextromethorphan might be a feasible adjuvant therapeutic for attenuating inflammation and inhibiting methadone tolerance and combined opioid use in heroin-dependent patients.

Antinociceptive effects of methadone combined with detomidine or acepromazine in horses.

Science.gov (United States)

Lopes, C; Luna, S P L; Rosa, A C; Quarterone, C; Crosignani, N; Taylor, P M; Pantoja, J C; Puoli, J N P

2016-09-01

To investigate two protocols to provide antinociception in horses. To evaluate the antinociceptive effects of intravenous methadone combined with detomidine or acepromazine in adult horses. Randomised, blinded, crossover study. Mechanical, thermal and electrical stimuli were applied to the dorsal left and right metacarpus and coronary band of the left thoracic limb, respectively. A thermal stimulus was applied caudal to the withers. The horses were treated with saline (C), a combination of methadone (0.2 mg/kg bwt) and detomidine (10 μg/kg bwt) (MD) or methadone (0.2 mg/kg bwt) and acepromazine (0.05 mg/kg bwt) (MA) at 1 week intervals. Nociceptive thresholds were measured before and at 15 min intervals until 150 min after treatment. Wilcoxon rank-sum and Wilcoxon signed rank tests were used to compare data between groups at each time point and over time within each group, followed by the Bonferroni method to adjust the P value. The mechanical stimulus was the most sensitive test to differentiate the antinociceptive effects of the treatments. Mechanical thresholds were greater after MD than MA between 15 and 30 min and with both MD and MA these thresholds were greater than C from 15 to 60 min. Electrical and thermal limb thresholds were greater after MD than C at 15 and 45 min and at 15, 30, 45, 75 and 105 min, respectively. Thermal limb thresholds were greater with MA than C at 30 min. Thoracic thermal threshold in MD and MA were higher than C at 45, 75, 90 and 120 min and from 30 to 75 min, respectively. Methadone and acepromazine produced less pronounced mechanical antinociception than MD. © 2015 EVJ Ltd.

Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen

DEFF Research Database (Denmark)

Fanoe, Søren; Hvidt, Christian; Ege, Peter Preben

2007-01-01

Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too many episodes...

Postmortem Blood Concentrations of R- and S-Enantiomers of Methadone and EDDP in Drug Users: Influence of Co-Medication and P-glycoprotein Genotype

DEFF Research Database (Denmark)

Buchard, Anders; Linnet, Kristian; Johansen, Sys Stybe

2010-01-01

We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S-enantiome......We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S...

Buprenorphine vs methadone treatment: A review of evidence in both developed and developing worlds

Directory of Open Access Journals (Sweden)

Paul J Whelan

2012-01-01

Full Text Available Heroin dependence is a major health and social problem associated with increased morbidity and mortality that adversely affects social circumstances, productivity, and healthcare and law enforcement costs. In the UK and many other Western countries, both methadone and buprenorphine are recommended by the relevant agencies for detoxification from heroin and for opioid maintenance therapy. However, despite obvious benefits due to its unique pharmacotherapy (eg, greatly reduced risk of overdose, buprenorphine has largely failed to overtake methadone in managing opioid addiction. The experience from the developing world (based on data from India is similar. In this article we compare the advantages and disadvantages of the use methadone and buprenorphine for the treatment of opioid addiction from both a developed and developing world perspective; and explore some of the reasons why buprenorphine has not fulfilled the expectations predicted by many in the addictions field.

Medicaid Coverage of Methadone Maintenance and the Use of Opioid Agonist Therapy Among Pregnant Women in Specialty Treatment.

Science.gov (United States)

Bachhuber, Marcus A; Mehta, Pooja K; Faherty, Laura J; Saloner, Brendan

2017-12-01

Opioid agonist therapy (OAT) is the standard of care for pregnant women with opioid use disorder (OUD). Medicaid coverage policies may strongly influence OAT use in this group. To examine the association between Medicaid coverage of methadone maintenance and planned use of OAT in the publicly funded treatment system. Retrospective cross-sectional analysis of treatment admissions in 30 states extracted from the Treatment Episode Data Set (2013 and 2014). Medicaid-insured pregnant women with OUD (n=3354 treatment admissions). The main outcome measure was planned use of OAT on admission. The main exposure was state Medicaid coverage of methadone maintenance. Using multivariable logistic regression models adjusting for sociodemographic, substance use, and treatment characteristics, we compared the probability of planned OAT use in states with Medicaid coverage of methadone maintenance versus states without coverage. A total of 71% of pregnant women admitted to OUD treatment were 18-29 years old, 85% were white non-Hispanic, and 56% used heroin. Overall, 74% of admissions occurred in the 18 states with Medicaid coverage of methadone maintenance and 53% of admissions involved planned use of OAT. Compared with states without Medicaid coverage of methadone maintenance, admissions in states with coverage were significantly more likely to involve planned OAT use (adjusted difference: 32.9 percentage points, 95% confidence interval, 19.2-46.7). Including methadone maintenance in the Medicaid benefit is essential to increasing OAT among pregnant women with OUD and should be considered a key policy strategy to enhance outcomes for mothers and newborns.

Short-course diphenoxylate hydrochloride for treatment of methadone withdrawal symptoms.

Science.gov (United States)

Ives, T J; Stults, C C

1983-11-01

The authors conducted a preliminary trial of a 5-day course of diphenoxylate in the treatment of out-patients with methadone withdrawal symptoms. Diphenoxylate provided substantial relief from detoxification symptoms with no drug-associated adverse effects.

[Use of methadone in the treatment of psychotic patients with heroin dependence].

Science.gov (United States)

Walby, F A; Borg, P; Eikeseth, P H; Neegaard, E; Kjerpeseth, K; Bruvik, S; Waal, H

2000-01-20

Comorbidity of psychosis and substance abuse has gained increased attention for some time. However, pharmacological treatment for opioid dependence among psychotic patients is seldom described. We present the treatment of four opioid dependent psychotic patients with methadone and antipsychotic medication. Three of the four patients had initially a period of increased psychotic symptoms, but all four patients have shown marked improvement following the introduction of methadone. Compliance with treatment has increased, they have had enduring non-psychotic periods and a markedly reduced use of illegal substances. The results should obviously be interpreted with caution, given the small number of subjects. Further research is therefore important.

Reducing the Risk of Methadone Overdose PSA (:60)

Centers for Disease Control (CDC) Podcasts

2012-07-03

This 60 second PSA is based on the July 2012 CDC Vital Signs report. Approximately 14 people die every day of overdoses related to methadone. Listen to learn how to reduce your risk of an overdose.  Created: 7/3/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/3/2012.

Methadone detoxification of tramadol dependence.

Science.gov (United States)

Leo, R J; Narendran, R; DeGuiseppe, B

2000-10-01

Tramadol hydrochloride is a centrally acting analgesic with a partial affinity for the opiate receptor (mu), having an analgesic potency estimated to be one tenth that of morphine. While preclinical investigations suggested that abuse liability associated with tramadol use is low, there are increasing numbers of cases reported to the U.S. Food and Drug Administration of abuse, dependence, and withdrawal associated with tramadol use. A case of a patient with tramadol dependence requiring detoxification with methadone is presented. Acute management of significant tramadol dependence has not yet been reported in the literature. Long-term treatment issues are also discussed.

Cost utility analysis of co-prescribed heroin compared with methadone maintenance treatment in heroin addicts in two randomised trials

NARCIS (Netherlands)

Dijkgraaf, Marcel G. W.; van der Zanden, Bart P.; de Borgie, Corianne A. J. M.; Blanken, Peter; van Ree, Jan M.; van den Brink, Wim

2005-01-01

Objective To determine the cost utility of medical co-prescription of heroin compared with methadone maintenance treatment for chronic, treatment resistant heroin addicts. Design Cost utility analysis of two pooled open label randomised controlled trials. Setting Methadone maintenance programmes in

Maternal and neonatal effects of adding morphine to low-dose bupivacaine for epidural labor analgesia.

Science.gov (United States)

Dostbil, A; Celik, M; Alici, H A; Erdem, A F; Aksoy, M; Ahiskalioglu, A

2014-01-01

Labor is one of the most painful experiences a woman may face during her lifetime. One of the most effective methods used for eliminating this pain is epidural analgesia. The aim of this study to determine the impact of adding morphine to low-dose bupivacaine epidural anesthesia on labor and neonatal outcomes, and maternal side effects. This is a prospective randomized double-blind study comparing two regimens of anesthetic agents used for epidural anesthesia in labor. A total of 120 pregnant women were randomized into two groups with 60 subjects in each study arm. A catheter was inserted, and 0.1% bupivacaine + 2 μg/mL fentanyl in 15 mL saline were given to Group bupivacaine-fentanyl (Group BF), while 0.0625% bupivacaine + 2 μg/ml fentanyl + 2 mg morphine in 15 mL saline were given to Group bupivacaine-fentanyl-morphine (Group BFM) with no test dosing from the needle. No morphine was added to the subsequent epidural injections in Group BFM. The total dose of bupivacaine was significantly lower in Group BFM relative to Group BF (P = 0.0001). The visual analogu scalescores at 15, 30, and 45 min were significantly lower in Group BF compared to thosein Group BFM (P = 0.0001, P = 0.001, and P = 0.006, respectively). The second stage of labor was significantly shorter in Group BFM relative to Group BF (P = 0.027 and P = 0.003, respectively). The satisfaction with analgesia following the first dose was higher in the nonmorphine group (P = 0.0001). However, maternal postpartum satisfaction was similar in both groups. Either nausea or vomiting was recorded in eight patients in Group BFM. We believe that epidural analgesia comprised of a low-dose local anaesthetic and 2 mg morphine provides a painless labor that significantly reducesthe use of local anesthetic without changing the efficiency of the analgesic, ensuring the mother's satisfaction without leading to an adverse effect on the mother or foetus, while mildly (but significantly) shortening the second stage of

Sublingual Buprenorphine and Methadone Maintenance Treatment: A Three-Year Follow-Up of Quality of Life Assessment

Directory of Open Access Journals (Sweden)

Salvatore M. Giacomuzzi

2005-01-01

Full Text Available This study was conducted to compare long-term outcome effects on the quality of life (QOL of oral methadone with sublingual buprenorphine maintenance treatment. The QOL status of opioid-dependent patients was assessed using the German version (“Berlin Quality of Life Profile” of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opiate Withdrawal Scale (OWS. Urine tests were carried out randomly to detect additional consumption. In the first study period, 53 opioid-dependent subjects were enrolled and 25 could be reached after 3 years. The retention rate was 50% for methadone and 45% for buprenorphine (p = 0.786. Baseline values of the total sample (completers and noncompleters QOL and somatic complaints did not show significant differences between the two treatment groups. QOL characteristics at 6 months of treatment of the buprenorphine completer and noncompleter groups differed significantly regarding job (p = 0.013, family, and total score of physical symptoms (p = 0.002, in which the completer group showed the more favorable values. Concerning physical symptoms at 36 months, logistic regression revealed significantly less stomach cramps (p = 0.037 and fatigue and tiredness (p = 0.034 in buprenorphine compared to the methadone. Moreover, the buprenorphine-maintained group showed significantly less additional consumption of benzodiazepines (p = 0.015 compared with methadone participants. It is concluded that opioid addicts improved their QOL and health status when treated with methadone or buprenorphine. In summary, regarding QOL and health status, the present data indicate that buprenorphine is also a useful long-term alternative for maintenance treatment of opioid-dependent patients.

Integrating Fieldwork into Employment Counseling for Methadone-Treatment Patients

Science.gov (United States)

Blankertz, Laura; Spinelli, Michael; Magura, Stephen; Bali, Priti; Madison, Elizabeth M.; Staines, Graham L.; Horowitz, Emily; Guarino, Honoria; Grandy, Audrey; Fong, Chunki; Gomez, Augustin; Dimun, Amy; Friedman, Ellen

2005-01-01

An innovative employment counseling model, Customized Employment Supports, was developed for methadone-treatment patients, a population with historically low employment rates. The effectiveness of a key component of the model, "vocational fieldwork," the delivery of services in the community rather than only within the clinic, was assessed through…

Self-association of analgesics in aqueous solution: micellar properties of dextropropoxyphene hydrochloride and methadone hydrochloride.

Science.gov (United States)

Attwood, D; Tolley, J A

1980-08-01

The solution properties of several analgesics including dextropropoxyphene hydrochloride, methadone hydrochloride, dextromoramide acid tartrate and dipipanone hydrochloride have been examined using light scattering, conductivity, vapour pressure osmometry and surface tension techniques. A micellar pattern of association was established for dextropropoxyphene hydrochloride and methadone hydrochloride and critical micelle concentrations and aggregation numbers are reported. The hydrophobic contribution to the free energy of micellization of dextropropoxyphene was determined from measurement of the critical micelle concentration in the presence of added electrolyte.

Factors associated with health-related quality of life among injection drug users at methadone clinics in Taipei, Taiwan

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Yung-Feng Yen

2015-05-01

Conclusion: Poor HRQOL was associated with a number of factors among IDUs at methadone clinics in Taipei, Taiwan. To improve HRQOL in this population, future programs should focus on IDUs with a history of drug overdose. In addition, methadone programs and social support should be integrated to improve HRQOL among this socially marginalized population.

Medically assisted recovery from opiate dependence within the context of the UK drug strategy: methadone and Suboxone (buprenorphine-naloxone) patients compared.

Science.gov (United States)

McKeganey, Neil; Russell, Christopher; Cockayne, Lucinda

2013-01-01

The focus of drug policy in the UK has shifted markedly in the past 5 years to move beyond merely emphasising drug abstinence towards maximising individuals' opportunities for recovery. The UK government continues to recognise the prescribing of narcotic medications indicated for opiate dependence as a key element of these individuals' recovery journey. This article describes a small, naturalistic comparison of the efficacy of the two most commonly prescribed opiate substitute medications in the UK--methadone hydrochloride (methadone oral solution) and Suboxone (buprenorphine-naloxone sublingual tablets)--for reducing current heroin users' (n = 34) days of heroin use, and preventing short-term abstainers (n = 37) from relapsing to regular heroin use. All patients had been prescribed either methadone or Suboxone for maintenance for 6 months prior to intake. Results showed that when controlling for a number of patient-level covariates, both methadone and Suboxone significantly reduced current users' days of heroin use between the 90 days prior to intake and at the 8-month follow-up, with Suboxone yielding a significantly larger magnitude reduction in heroin use days than methadone. Methadone and Suboxone were highly and equally effective for preventing relapse to regular heroin use, with all but 3 of 37 (91.9%) patients who were abstinent at intake reporting past 90-day point prevalence heroin abstinence at the 8-month follow-up. Overall, prescribing methadone or Suboxone for eight continuous months was highly effective for initiating abstinence from heroin use, and for converting short-term abstinence to long-term abstinence. However, the study design, which was based on a relatively small sample size and was not able randomise patients to medication and so could not control for the effects of potential prognostic factors inherent within each patient group, means that these conclusions can only be made tentatively. These positive but preliminary indications of the

Somatic comorbidity and other factors related to suicide attempt among Polish methadone maintenance patients

Science.gov (United States)

Fudalej, Sylwia; Ilgen, Mark; Kołodziejczyk, Iwona; Podgórska, Anna; Serafin, Piotr; Barry, Kristen; Wojnar, Marcin; Blow, Frederic C.; Bohnert, Amy

2015-01-01

Objectives Fatal and non-fatal suicide attempts are far more common in opioid dependent individuals than in the general population. More research is needed to understand the specific risk factors for suicidal behaviors in this patient population, particularly outside of the U.S. and Western Europe. This study investigated the correlates of suicide attempts among Polish patients in methadone maintenance treatment and interpreted results in the context of findings from other countries. Methods The study was based on a sample of 240 individuals recruited from a methadone maintenance clinic in Poland. Participants were interviewed using standardized measures. Results Consistent with studies in other countries, sexual abuse, depression, alcohol dependence and impulsivity were associated with suicide attempt. Additionally, those patients with somatic comorbidity had an increase in odds (OR=2.6) of suicide attempt. Conclusion The results of our study suggest a potential benefit to treatment approaches that address somatic concerns of methadone maintenance patients. More research is needed to identify, assess and understand possible cultural and regional differences between opioid dependent populations to better tailor prevention strategies. PMID:26335004

Clinical characteristics and risk behavior as a function of HIV status among heroin users enrolled in methadone treatment in northern Taiwan

Directory of Open Access Journals (Sweden)

Shih Chien-Yu

2011-04-01

Full Text Available Abstract Background Methadone treatment was introduced in Taiwan in 2006 as a harm-reduction program in response to the human immunodeficiency virus (HIV, which is endemic among Taiwanese heroin users. The present study was aimed at examining the clinical and behavioral characteristics of methadone patients in northern Taiwan according to their HIV status. Methods The study was conducted at four methadone clinics. Participants were patients who had undergone methadone treatment at the clinics and who voluntarily signed a consent form. Between August and November 2008, each participant completed a face-to-face interview that included questions on demographics, risk behavior, quality of life, and psychiatric symptoms. Data on HIV and hepatitis C virus (HCV infections, methadone dosage, and morphine in the urine were retrieved from patient files on the clinical premises, with permission of the participants. Results Of 576 participants, 71 were HIV positive, and 514 had hepatitis C. There were significant differences between the HIV-positive and HIV-negative groups on source of treatment payment, HCV infection, urine test results, methadone dosage, and treatment duration. The results indicate that HIV-negative heroin users were more likely to have sexual intercourse and not use condoms during the 6 months prior to the study. A substantial percent of the sample reported anxiety (21.0%, depression (27.2%, memory loss (32.7%, attempted suicide (32.7%, and administration of psychiatric medications (16.1%. There were no significant differences between the HIV-positive and HIV-negative patients on psychiatric symptoms or quality of life. Conclusions HIV-positive IDUs were comorbid with HCV, indicating the need to refer both HIV- and HCV-infected individuals for treatment in methadone clinics. Currently, there is a gap between psychiatric/psychosocial services and patient symptoms, and more integrated medical services should be provided to heroin

Opioid dependence and substitution therapy: thymoquinone as potential novel supplement therapy for better outcome for methadone maintenance therapy substitution therapy

Science.gov (United States)

Adnan, Liyana Hazwani Mohd; Bakar, Nor Hidayah Abu; Mohamad, Nasir

2014-01-01

Methadone is widely being used for opioid substitution therapy. However, the administration of methadone to opioid dependent individual is frequently accompanied by withdrawal syndrome and chemical dependency develops. Other than that, it is also difficult to retain patients in the treatment programme making their retention rates are decreasing over time. This article is written to higlights the potential use of prophetic medicines, Nigella sativa, as a supplement for opioid dependent receiving methadone. It focuses on the potential role of N. sativa and its major active compound, Thymoquinone (TQ) as a calcium channel blocking agent to reduce withdrawal syndrome and opioid dependency. PMID:25859295

Low doses of 17α-ethinyl estradiol alter the maternal brain and induce stereotypies in CD-1 mice exposed during pregnancy and lactation.

Science.gov (United States)

Catanese, Mary C; Vandenberg, Laura N

2017-10-01

Maternal care is critical for the survival, development and long-term success of offspring. Despite our current understanding of the role of endogenous estrogen in both maternal behavior and the maternal brain, the potential effects of exogenous estrogens on these endpoints remain poorly understood. Here, pregnant CD-1 mice were exposed to low doses of 17α-ethinyl estradiol (EE2), commonly used as a positive control in studies of other xenoestrogens, from day 9 of pregnancy until weaning. Using traditional maternal behavior assays, we document no significant changes in maternal behavior throughout the lactational period. However, EE2 induced increases in repetitive tail retrieval, which may indicate a stereotypy or obsessive compulsive (OCD)-like behavior. We also observed a significant reduction in tyrosine hydroxylase (TH) immunoreactivity in the ventral tegmental area (VTA), a region important for maternal motivation. These results suggest that pregnant adult females are not immune to the effects of this compound. Copyright © 2017 Elsevier Inc. All rights reserved.

Dominance of pre-analytical over analytical variation for measurement of methadone and its main metabolite in postmortem femoral blood

DEFF Research Database (Denmark)

Linnet, Kristian; Johansen, Sys Stybe; Buchard, Anders

2008-01-01

cases comprising mainly drug addicts. A chiral LC-MS/MS method was used for measurement of the R- and S-enantiomers of methadone and its main metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium (EDDP). The analytical CV% was determined to be in the range 3-4% for methadone enantiomers and 4...

Prevalence of problem alcohol use among patients attending primary care for methadone treatment

LENUS (Irish Health Repository)

Ryder, Niamh

2009-06-11

Abstract Background Problem alcohol use is associated with adverse health outcomes among current or former heroin users and primary care is providing methadone treatment for increasing numbers of this population. This study aimed todetermine the prevalence of problem alcohol use among current or former heroin users attending primary care for methadone treatment and to describe the socio-demographic characteristics and health service utilisation characteristics associated with problem alcohol uses. Methods We conducted a cross sectional survey of patients sampled from a national database of patients attending general practice for methadone treatment. Participants were recruited by their general practitioner and data was collected using an interviewer-administered questionnaire, which included the Alcohol Use Disorders Identification Test (\\'AUDIT\\'), with a score of >7 considered abnormal (ie \\'AUDIT positive cases\\') and socio-demographic, medical and substance use characteristics. Results We interviewed 196 patients (71% of those invited, 31% of those sampled, 11% of the national database). The median age was 32 years, 55% were hepatitis C positive, 79% had used illicit drugs in the previous month and 68% were male. Sixty-eight \\'AUDIT positive\\' cases were identified (prevalence of 35%, 95% CI = 28–41%) and these were more likely to have attended a local Emergency Department in the previous year (p < 0.05) and less likely to have attended a hospital clinic in the previous year (p < 0.05). Twenty-seven (14%) scored 20 or higher indicating possible alcohol dependence. Conclusion Problem alcohol use has a high prevalence among current or former heroin users attending primary care for methadone treatment and interventions that address this issue should be explored as a priority. Interventions that address problem alcohol use in this population should be considered as a priority, although the complex medical and psychological needs of this population may make

Sexual Dysfunction in Heroin Dependents: A Comparison between Methadone and Buprenorphine Maintenance Treatment.

Directory of Open Access Journals (Sweden)

Anne Yee

Full Text Available Methadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT and methadone maintenance treatment (MMT. The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients.Two hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15, and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal-IIEF 15 scores while controlling for all the possible confounders.The study population consisted of 171 patients (71.8% on MMT and 67 (28.2% on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012 and overall satisfaction (p = 0.043 domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008 compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026 and overall satisfaction (p = 0.039 were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables.Sexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus, clinicians may consider the former when

Prevalence of problem alcohol use among patients attending primary care for methadone treatment.

LENUS (Irish Health Repository)

Ryder, Niamh

2012-02-01

BACKGROUND: Problem alcohol use is associated with adverse health outcomes among current or former heroin users and primary care is providing methadone treatment for increasing numbers of this population. This study aimed to determine the prevalence of problem alcohol use among current or former heroin users attending primary care for methadone treatment and to describe the socio-demographic characteristics and health service utilisation characteristics associated with problem alcohol uses. METHODS: We conducted a cross sectional survey of patients sampled from a national database of patients attending general practice for methadone treatment. Participants were recruited by their general practitioner and data was collected using an interviewer-administered questionnaire, which included the Alcohol Use Disorders Identification Test (\\'AUDIT\\'), with a score of >7 considered abnormal (ie \\'AUDIT positive cases\\') and socio-demographic, medical and substance use characteristics. RESULTS: We interviewed 196 patients (71% of those invited, 31% of those sampled, 11% of the national database). The median age was 32 years, 55% were hepatitis C positive, 79% had used illicit drugs in the previous month and 68% were male. Sixty-eight \\'AUDIT positive\\' cases were identified (prevalence of 35%, 95% CI = 28-41%) and these were more likely to have attended a local Emergency Department in the previous year (p < 0.05) and less likely to have attended a hospital clinic in the previous year (p < 0.05). Twenty-seven (14%) scored 20 or higher indicating possible alcohol dependence. CONCLUSION: Problem alcohol use has a high prevalence among current or former heroin users attending primary care for methadone treatment and interventions that address this issue should be explored as a priority. Interventions that address problem alcohol use in this population should be considered as a priority, although the complex medical and psychological needs of this population may make this

On the Comparison of Cognitive Function in Substance Abusers and Addicts under Methadone Treatment with Normal Individuals

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reza mohammadzadeghan

2015-09-01

Full Text Available Objective: This study was an attempt to compare cognitive functioning in substance abusers and addicts under methadone treatment with normal individuals. Method: The current study was a causal-comparative one. The statistical population of this research consisted of all male substance abusers who had referred to addiction treatment centers of Khoy city in 2013. The total of 40 addicts under methadone treatment, 40 active drug users, and 40 non-addicts were selected as the participants of this study via convenience sampling method. Wisconsin Card Sorting Test and Wechsler Memory Scale were administered to the three groups for data collection purposes. Results: The results showed that the substance abusers’ scores in Wisconsin card sorting test and Wechsler memory scale were significantly different from those of addicts under methadone treatment and normal individuals. In the same way, there was a significant difference between addicts under methadone treatment and normal individuals in terms of cognitive function however, there was no significant difference between these two groups in terms of perseveration error. Conclusion: It can be concluded that chronic use of psychoactive substances causes damage to multiple brain regions such as prefrontal cortex and hippocampus and, thereby, it leads to cognitive malfunctioning in these areas.

Opioid dependence and substitution therapy: thymoquinone as potential novel supplement therapy for better outcome for methadone maintenance therapy substitution therapy

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Liyana Hazwani Mohd Adnan

2015-12-01

Full Text Available Methadone is widely being used for opioid substitution therapy. However, the administration of methadone to opioid dependent individual is frequently accompanied by withdrawal syndrome and chemical dependency develops. Other than that, it is also difficult to retain patients in the treatment programme making their retention rates are decreasing over time. This article is written to higlights the potential use of prophetic medicines, Nigella sativa, as a supplement for opioid dependent receiving methadone. It focuses on the potential role of N. sativa and its major active compound, Thymoquinone (TQ as a calcium channel blocking agent to reduce withdrawal syndrome and opioid dependency.

Comparison of craving for opioid in opioid-dependent individuals and people under methadone maintenance treatment

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Azita Chehri

2014-02-01

Full Text Available Background: Methadone Maintenance Therapy (MMT is the most important treatment for opioid -dependency recurrence. The aim of this study was to compare the craving level in opioid-dependent individuals and people under methadone maintenance therapy. Methods: In this case – control study, 120 men with opioid dependency were selected through cluster sampling method. They were divided into two groups, 60 people in opioid-dependent group and 60 people in MMT group. Both groups were matched for age, sex, marital status, education, duration of opioid dependency and method of consumption. Then, they completed INCAS Substance Abuse Profile (ISAP, opiate withdrawal symptoms checklist, self–report of craving, Desire for Drug Questionnaire (DDQ, Obsessive Compulsive Drug Use Scale (OCDUS and visual cue-induced craving questionnaire. Data were analyzed by SPSS 15 using t-test and ANOVA. Results: Mean craving for drug significantly was lower in MMT group comparing opioid-dependent group (P<0.01. Conclusion: Methadone Maintenance Therapy decreased the craving for drugs and substances This can have an important role in relapse prevention.

[Stabilizing the social and health status of drug dependent patients with methadone. Long-term maintainance therapy--Vienna results].

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Loimer, N; Werner, E; Hollerer, E; Pfersmann, V; Schmid-Siegel, B; Presslich, O

1991-01-01

On September 25th, 1987 methadone was legalized in Austria for therapeutic use in drug addiction treatment in case of: 1. Long-term drug addiction with intravenous application of the drug, and several unsuccessful withdrawal therapies and/or 2. opiate addiction through intravenous application of the drug along with an existing HIV-1 infection. Since than, 291 patients were treated with methadone at the drug-dependency outpatient clinic of the Psychiatric Clinic of the University of Vienna. In 1990, 96 patients treated for more than one year were investigated using a standardized questionnaire. The image in which crime, prostitution, poverty, ill health all merge was broken by this decriminalization. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society.

The Effect of Cognitive Behavior Therapy in Insomnia due to Methadone Maintenance Therapy: A Randomized Clinical Trial

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Robabeh Soleimani

2015-09-01

Full Text Available Background: Sleep disturbance is a common complaint of patients undergoing methadone maintenance therapy (MMT. There are limited studies about the effect of different treatments on insomnia due to MMT. In this study, we evaluated the effect of cognitive-behavioral treatment for insomnia (CBTI on sleep disorders in patients undergoing MMT. Methods: Twenty-two patients with insomnia due to MMT (aged 18-60 years participated in this randomized double-blind clinical trial. The intervention group received CBTI from a clinical psychologist for 8 weeks, whereas the control group received behavioral placebo therapy (BPT. The duration of individual sessions was 45 minutes, which was conducted once a week. The primary outcome was sleep disturbance assessed with Pittsburgh Sleep Quality Index (PSQI. Data were analyzed using SPSS software version 19. Results: Eleven patients were assigned to each group. Two groups were matched according to demographic characteristics (age, marital status, education, and daily methadone doses. Although PSQI score was significantly reduced during weeks 5 and 8 after both interventions, there was a significant difference in intervention versus time interaction (P<0.02. The effects of CBTI versus placebo were significantly different (P<0.001. The time course was also significant (P<0.001. Conclusion: This study showed that CBTI is more effective than BPT in overall sleep quality. We recommend further studies, with a larger sample, on CBTI in patients undergoing MMT.

Neonatal withdrawal syndrome after chronic maternal consumption of 4-methylethcathinone.

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Pichini, Simona; Rotolo, Maria Concetta; García, Jordi; Girona, Noelia; Leal, Lorna; García-Algar, Oscar; Pacifici, Roberta

2014-12-01

Synthetic cathinones have been markedly present in the Spanish drug market in recent years. These substances can be easily obtained in "smart shops", smoke shops, gas stations and web sites where they can be bought and received anonymously avoiding normal law controls. For the first time we present a case of a neonatal withdrawal syndrome in a baby born to a woman who was a chronic consumer of 4-methylethcathinone. The newborn presented with increased jitteriness and irritability, highpitched cry, hypertonia in the limbs and brisk tendon reflexes. 4-Methylethcathinone was identified and quantified by liquid chromatography tandem mass spectrometry in the four subsequent 3cm segments of maternal hair (4.3, 4.0, 4.0 and 3.9ng/mg hair starting from most proximal segment) accounting for maternal consumption during the whole pregnancy and before and in neonatal meconium (0.7ng/g) confirming fetal exposure during intrauterine life. Methadone and its metabolite were also measured in maternal and neonatal matrices. Counseling pregnant women and women who may become pregnant on the consequences of fetal drug exposure to new designer drugs like 4-methylethcathinone is critical to preventing poor neonatal outcomes. This case report is informative to those studying designer drugs and those clinically involved with pregnant women abusing psychoactive substances. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Paediatric dose measurements for chest X-ray examinations at Maternity and Children Hospital in Najran - Saudi Arabia

International Nuclear Information System (INIS)

Saeed, M.K.; Al-Qahtani, J.M.

2012-01-01

The entrance skin dose (ESD) of chest X-ray examinations for AP and PA projections of paediatric patients at Maternity and Children Hospital in Najran, Saudi Arabia have been obtained using DoseCal software. The majority of the results obtained show low measured ESD for chest X-ray examinations. The mean of ESD for the AP projection was found to be 37.5, 40.5, 41.3, and 52.3μGy for age groups 0−1, >1−5, >5−10, and >10−15 years respectively. However, the ESD for PA projection was found to be 50.7 and 56.7μGy for age groups >5−10, and >10−15 years respectively.

NPS and the methadone queue: Spillages of space and time.

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Alexandrescu, Liviu

2017-02-01

Between 2008 and 2013, powder-stimulants sold by 'head shops' as novel psychoactive substances (NPS) or 'legal highs' have displaced heroin among groups of injecting substance users in Bucharest, Romania. Rising HIV-infection rates and other medical or social harms have been reported to follow this trend. The study builds on two sets of original (N=30) and existing (N=20) interview data and on observations collected mainly at the site of a methadone substitution treatment facility. By disentangling the space-time continuum of the methadone queue, this paper argues that injecting drug users' (IDUs) passage from opiates to amphetamine-type stimulants (ATS) can be understood as 'spillages' of space and time. IDUs thus 'spill' out of the disciplinary flows of methadone treatment in two ways. The first is that of space and materiality. Drawing on actor-network theory (ANT), ATS/NPS appear embedded in reconfigured practices and rituals of injecting use. Such spillages see the pleasure-seeking self being fluidised in forming connections with, or spilling into, nonhuman actants such as substances, settings or objects. The second dimension of spilling is that of time. In this sense, heroin use is a 'cryogenic strategy' of inhabiting history and facing the transition to the market society that Romanian opiate injectors spill out of, not able to appropriate choice and legitimate consumption. The phenomenological qualities of stimulants that seem to accelerate lived time and generalise desire thus present them with an opportunity to alleviate a form of what a post-communist moral imaginary of transition frames as debilitating nostalgia. ATS/NPS are revealed as fluid entities that do not only shape risk conditions but also alter shared meanings and contextual configurations of bodies, substances and disciplinary regimes in unpredictable ways. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment of family functioning in families of patients on methadone maintenance treatment

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Marković Jasminka

2015-01-01

Full Text Available Addiction has multi-factorial etiopathogenesis. Morbidity risk factors include both individual and social factors. Social factors are considered to be very important, especially at the initial stage of taking the substance. Family and the social environment, with their behavior and social norms, are the primary psychosocial determinants. Family functioning has an impact on both the development and the maintenance of addictions, so it is an important research topic. The aim of this study was to determine if families of drug addicts who are on methadone maintenance treatment differ in the level of functionality from families without addiction problems. The study sample included 100 persons divided into two groups - clinical and control. The clinical group consisted of 50 persons - drug addicts who are on methadone maintenance treatment, whereas the control group consisted of 50 persons without addiction problems. FACES IV and General questionnaire were used as instruments for the control group, and POMPIDU questionnaire for the clinical group. The results show that the families of addicts who are in methadone substitution treatment program vary in the level of functionality compared to families in which there is no problem of addiction and in a way that the families of the control group are more functional. These results in our region confirmed earlier results on the connection between family dysfunction and substance abuse, which may have significant implications in the treatment and prevention programs of addictions.

Psychiatric comorbidity reduces quality of life in chronic methadone maintained patients

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Carpentier, Pieter J; Krabbe, Paul F M; van Gogh, Mijke T; Knapen, Lieke J M; Buitelaar, Jan K; de Jong, Cor A J

2009-01-01

Despite the efficacy of methadone maintenance treatment (MMT), opioid dependence still involves severe impairment of functioning and low quality of life. This study examines the influence of the psychiatric comorbidity of MMT patients on their quality of life. A total of 193 middle-aged patients in

ABSTINENCE OF ILLICIT DRUGS, ALCOHOL AND TOBACCO IN THETREATMENT WITH METHADONE

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Jasna Čuk Rupnik

2008-06-01

In this research by the abstinence of heroin the program of CPTAID fits to successful ones.By smoking of tobacco the patients treated with methadone are very endangered population. The percentage of chronicaly infected by hepatitis C viruses is lower compared to themajority of other European countries

Genetic influence on methadone treatment outcomes in patients undergoing methadone maintenance treatment for opioid addiction: a pilot study

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Samaan Z

2014-08-01

Full Text Available Zainab Samaan,1–4 Monica Bawor,3,4 Brittany B Dennis,2,3 Carolyn Plater,5 Michael Varenbut,5 Jeffrey Daiter,5 Andrew Worster,5,6 David C Marsh,5,7 Charlie Tan,8 Dipika Desai,3 Lehana Thabane,2,9,10 Guillaume Pare11 1Department of Psychiatry and Behavioural Neurosciences, 2Department of Clinical Epidemiology and Biostatistics, 3Population Genomics Program, Chanchlani Research Centre, 4MiNDS Neuroscience Program, McMaster University, Hamilton, Ontario, Canada; 5Ontario Addiction Treatment Centres, Richmond Hill, Ontario, Canada; 6Department of Medicine, McMaster University, Hamilton, Ontario, Canada; 7Northern Ontario School of Medicine, Laurentian University, Sudbury, Ontario, Canada; 8Michael G. DeGroote School of Medicine, McMaster University, 9Biostatistics Unit, Centre for Evaluation of Medicine, 10System Linked Research Unit, 11Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada Introduction: Treatment of opioid addiction with methadone is effective; however, it is known to produce interindividual variability. This may be influenced in part by genetic variants, which can increase the initial risk of developing opioid addiction as well as explain differences in response to treatment. This pilot study aimed to assess the feasibility of conducting a full-scale genetic analysis to identify genes that predict methadone treatment outcomes in this population. Methods: This was a cross-sectional observational study of patients admitted to a methadone maintenance treatment program for opioid addiction. We obtained demographic and clinical characteristics in addition to blood and urine samples, for the assessment of treatment outcomes. Results: The recruitment process yielded 252 patients, representing a 20% recruitment rate. We conducted genetic testing based on a 99.6% rate of provision of DNA samples. The average retention in treatment was 3.4 years, and >50% of the participants reported psychiatric and

Gender Differences Among Patients With Hepatitis C Virus Undergoing Rehabilitation Through Methadone Maintenance Treatment

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Omid Massah

2018-03-01

Discussion: The study results demonstrated some gender differences in baseline characteristics and psychological problems. Such differences may have important impacts on methadone treatment outcomes. Further studies are suggested.

Day treatment versus enhanced standard methadone services for opioid-dependent patients: a comparison of clinical efficacy and cost.

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Avants, S K; Margolin, A; Sindelar, J L; Rounsaville, B J; Schottenfeld, R; Stine, S; Cooney, N L; Rosenheck, R A; Li, S H; Kosten, T R

1999-01-01

This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services--a day treatment program and enhanced standard care--for the treatment of opioid-dependent patients maintained on methadone hydrochloride. A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master's-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups' use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost.

Methadone and its role in drug-related fatalities in Cologne 1989-2000.

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Grass, H; Behnsen, S; Kimont, H-G; Staak, M; Käferstein, H

2003-04-08

All drug-associated deaths from 1989 to 2000 were analysed at the Institute of Forensic Medicine in Cologne. Information concerning sex, gender, drug consumption, time, place and circumstances of death were analysed. A number of 605 cases were recorded; in 518 cases a toxicological analysis was possible and in 171 an autopsy was performed. When it was possible to determine the cause of death form the information available, acute drug intoxication was recorded in 65%. Heroin head the list of identified substances. Sixty-three percent of the specimens showed a combination of several substances, especially a combination of morphine, benzodiazepines, other medications and alcohol. In comparison with other studies the percentage of methadone-positive specimens is low, even though the proportion of specimens positive for methadone increased from 1989 to 2000. This analysis is discussed using background information concerning the management of substitution therapy and the available literature.

Use of radiotelemetry to evaluate respiratory depression produced by chronic methadone administration.

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Lewanowitsch, Tanya; White, Jason M; Irvine, Rodney J

2004-01-26

Illicit and therapeutic opioid administration can result in overdose due to opioid-induced respiratory depression. Research investigating the respiratory depressant effects of opioids has been limited due to difficulties associated with acquiring long-term respiratory data. This study examined the novel use of radiotelemetry to measure respiratory rate, heart rate, locomotor activity and blood pressure in rats treated chronically with methadone. Over 4 days of treatment, respiratory rate decreased, but partial tolerance appeared to develop during active (night) periods. Decreased heart rate was observed during the night periods and tolerance appeared to develop to this effect. Activity and blood pressure did not change with treatment. The effects of naloxone hydrochloride and naloxone methiodide administration on the methadone-treated rats were also examined and both antagonists increased respiratory rate and heart rate, with only naloxone hydrochloride producing significant increases in activity. Radiotelemetry offers a means of evaluating drug effects on respiratory rate continually in ambulatory, unstressed animals.

The Comparison of Effectiveness of Cognitive-Behavioral Group Therapy Based on Coping Skills and Methadone Maintenance Treatment in Improvement of Emotional Regulation Strategies and Relapse Prevention

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Tahereh Ghorbany

2011-05-01

Full Text Available Purpose: This study compared the effectiveness of group cognitive-behavioral therapy based on coping skills (CBT and methadone maintenance therapy (MMT in improvement of emotional regulation strategies and prevention of relapse. Method: The method of the present study was semi-experimental research design (pre-test-post-test with witness group. For sampling 45 substance abuse people who had referred to addiction treatment centers were selected and assigned to three groups of cognitive behavior therapy, methadone maintenance treatment and witness group randomly. The participants in all three groups completed the emotional intelligence questionnaire before and after the intervention. Data were analyzed by covariance method. Results: The results showed that cognitive-behavior therapy in comparison to methadone maintenance therapy and witness group led to significant improvement of emotional regulation in substance abusers, but there was no significant difference between the methadone maintenance treatment group and control group. Also, the rate of relapse in individuals who assigned to cognitive-behavior therapy group in comparison to methadone maintenance therapy and the witness group was significantly lower, but there was no significant difference between methadone therapy and witness. Conclusion: Cognitive-behavior therapy was an effective treatment that can change the cognitive and behavioral variables related to substance abuse, such as emotional regulation strategies. Thus, results suggested that drug abuse treatment programs must target these mediator variables.

Model-based comparison of maternal and foetal organ doses from 99mTc pertechnetate, DMSA, DTPA, HDP, MAA and MAG3 diagnostic intakes during pregnancy

International Nuclear Information System (INIS)

Saunders, Margaret; Palmer, Maria; Preece, Alan; Millard, Roger

2002-01-01

Organ residence times were calculated for diagnostic intakes of 99m Tc pertechnetate, 2,3-dimercaptosuccinic acid (DMSA), diethylene triamine penta-acetic acid (DTPA), hydroxymethylene diphosphonate (HDP), macroaggregated albumin (MAA) and mercapto-acetyltriglycine (MAG 3 ) during the 1st and 3rd stages of pregnancy and used with the MIRDOSE3 pregnant female phantoms for generation of dose estimates. At stage 3 individual foetal organ doses were estimated via a surrogate phantom based on that for the new-born but with mean dose/cumulated activity (S) values scaled for compatibility with foetal whole body S. Stage 1 or 3 whole foetus doses ranged from 5.2 to 0.77 μGy MBq -1 respectively, analogous to current ICRP estimates for these agents using similar in vivo biodistribution model databases. Most stage 3 maternal and foetal organ doses were similar within a factor of 3, being higher in the foetus than the mother with pertechnetate, DTPA and MAG 3 , and lower with DMSA, HDP and MAA. Doses were more uniformly distributed among foetal organs than in the mother. Placental transfer was greatest with pertechnetate, where dose to the stage 3 foetal thyroid was 60-140 μGy MBq -1 . With each agent there was more placental transfer in stage 3 than in stage 1, but doses to stage 1 whole foetus were always higher, with the contribution from the mother dominant. For DMSA, HDP and MAG 3 the maternal contribution to total foetal body dose exceeded 93% for both stages. (orig.)

Pharmacokinetics of dexmedetomidine combined with methadone following oral-transmucosal and intramuscular administration in dogs

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Federica Di Cesare

2017-05-01

Full Text Available Oral-transmucosal (OTM drug delivery refers to noninvasive and painless administration of medical preparations through any oral cavity membrane to achieve systemic effects (Sattar et al., 2014. Regarding sedative drugs, OTM administration is very attractive in veterinary medicine, especially for patients difficult to inject and restrain (Messenger et al., 2016. This study aims to compare the pharmacokinetics of dexmedetomidine after OTM and intramuscular (IM administration combined with methadone. After obtaining Ethical Committee approval and owner’s written consent, eight dogs, were administered with dexmedetomidine (10 mg/kg and methadone (0.4 mg/kg by OTM and other 4 dogs by IM route. Blood samples were collected at prefixed times up to four hours. Dexmedetomidine was quantified by a validated HPLC-MS method. On dexmedetomidine concentrations, a pharmacokinetic analysis was carried out with a noncompartmental approach (Phoenix WinNonlin® 7.0, Pharsight, Cary, NC. Mean ± SD terminal half-lives of dexmedetomidine were 187.42 ± 109.66 and 94.78 ± 34.08 min after OTM and IM administration, respectively. Maximum serum (Cmax concentrations were 0.83 ± 0.32 and 9.09 ± 2.46 ng/mL for OTM and IM administration, respectively. Time to maximum concentration (Tmax were 44.38 ± 32.16 and 21.25±11.39 min by OTM and IM administration, respectively. Area under the curve from 0 to the last measured concentration (AUClast were 103.75 ± 30.23 and 614.87 ± 77.15 min*ng/mL for OTM and IM administration, respectively. Cmax, Tmax and AUClast values by OTM route demonstrate a lower and delayed absorption of the drug compared to IM. To complete the study, the pharmacokinetic analysis of methadone is foreseen, so as a clinical trial to compare the clinical effects of the combination of dexmedetomidine and methadone by OTM and IM administration and to establish an effective dosage of oral-transumucosal route in dogs for this association.

Ethnic Differences in HIV Risk Behaviors Among Methadone-Maintained Women Receiving Contingency Management for Cocaine Use Disorders

Science.gov (United States)

Barry, Danielle; Weinstock, Jeremiah; Petry, Nancy M.

2008-01-01

Objective To identify ethnic differences in HIV risk behaviors among cocaine using women receiving methadone maintenance for opioid dependence, and to evaluate the efficacy of contingency management (CM) for cocaine use disorders in reducing HIV risk behaviors. Methods African American (N=47), Hispanic (N=47), and White women (N = 29) were randomized to standard methadone treatment or standard methadone treatment plus a CM intervention. They completed the HIV Risk Behavior Scale (HRBS) indicating frequency of drug use and sexual behaviors across the lifetime, in the month before baseline, and in the 3 months following clinical trial participation. Ethnic group differences and the effect of CM on change in HIV risk behaviors between baseline and follow-up were evaluated. Results White women reported significantly higher lifetime rates of risky drug use and sexual behaviors on the HRBS than African American women; neither group differed significantly from Hispanic women. No ethnic group differences in HIV risk behaviors were identified in the month prior to baseline. At follow-up, African American women reported fewer high-risk drug use behaviors than White or Hispanic women, and Hispanic women reported more high-risk sexual behaviors than White or African American women. CM was associated with reduction in high-risk drug use behaviors regardless of ethnicity, but did not affect high-risk sexual behaviors. Conclusions White women receiving methadone maintenance engage in more lifetime HIV risk behaviors than African American women. CM for cocaine use reduces risky drug use behaviors, but certain ethnic groups may benefit from additional targeted HIV prevention efforts. PMID:18684571

The Effectiveness of Group Spiritual Intervention on Self-esteem and Happiness among Men Undergoing Methadone Maintenance Treatment.

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Jalali, Amir; Behrouzi, Mahvash Kashkouli; Salari, Nader; Bazrafshan, Mohammad-Rafi; Rahmati, Mahmoud

2018-05-10

Drug dependence or substance use disorder not only affects a person's life but also brings a lot of challenges for families and communities and imposes heavy burdens on them. There are various therapies in the domain of addiction whose main purposes are to reduce or to cut down substance abuse. This study aimed to determine the effectiveness of group spiritual intervention on self-esteem and happiness among male clients undergoing methadone maintenance treatment. This study was an intervention study in which 60 clients affected with substance abuse and undergoing methadone maintenance treatment were recruited. The study samples were selected through convenience sampling method and then divided randomly into two groups of 30 individuals: intervention and control. The intervention group attended group spiritual interventions for 10 sessions. Self-esteem and happiness among the study participants were also measured through Coopersmith Self-Esteem Inventory and Oxford Happiness Questionnaire before and after the intervention. The results showed a significant difference between both intervention and control groups in terms of self-esteem and happiness (P˂0.05); so that the participants in the intervention group demonstrated a significant improvement in their self-esteem and happiness. It was concluded that group spiritual intervention as a useful method could be effective in enhancing self-esteem and happiness among addicted individuals undergoing methadone maintenance treatment. The given treatment could be also used as a complementary therapy beside methadone maintenance treatment to reduce the likelihood of people returning to substance abuse. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dose-Dependent Effects of Multiple Acute Cocaine Injections on Maternal Behavior and Aggression in Sprague-Dawley Rats

OpenAIRE

Johns, Josephine M.; Nelson, Christina J.; Meter, Kathleen E.; Lubin, Deborah A.; Couch, C. Destine; Ayers, Andy; Walker, Cheryl H.

1998-01-01

Rat dams, which had no prior drug treatment, were either nontreated controls or were injected subcutaneously 4 times during a 10-day period with a single dose of 30, 15 or 7.5 mg/kg of cocaine hydrochloride HCl, or normal saline. Injections were given immediately postpartum following delivery of their final pup (PPD 1), and again on postpartum day 3 (PPD 3), postpartum day 6 (PPD 6) and postpartum day 10 (PPD 10). Dams were observed 30 min following injections for maternal behavior (MB) towar...

Messages about methadone and buprenorphine in reality television: a content analysis of celebrity rehab with Dr. Drew.

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Roose, Robert; Fuentes, Liza; Cheema, Mandeep

2012-08-01

Medication-assisted treatment for opioid dependence is safe and effective, yet negative perceptions about methadone and buprenorphine may discourage patients from entering treatment. One source of information that may influence viewers' perceptions is television. We performed a content analysis of a popular reality television program on addiction treatment. Although many patients had histories of opioid use, there were no positive messages about methadone or buprenorphine. The two main messages were that they (1) are primarily drugs of abuse, and (2) not acceptable treatment options. These messages reinforce negative stereotypes and may perpetuate stigma. There were multiple missed opportunities to provide evidence-based information.

Treadmill exercise attenuates the severity of physical dependence, anxiety, depressive-like behavior and voluntary morphine consumption in morphine withdrawn rats receiving methadone maintenance treatment.

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Alizadeh, Maryam; Zahedi-Khorasani, Mahdi; Miladi-Gorji, Hossein

2018-05-30

This study was designed to examine whether treadmill exercise would attenuate the severity of physical dependence, methadone-induced anxiety, depression and voluntary morphine consumption in morphine withdrawn rats receiving methadone maintenance treatment (MMT). The rats were chronically treated with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 14 days. The exercising rats receiving MMT were forced to run on a motorized treadmill for 30 days during morphine withdrawal. Then, rats were tested for the severity of morphine dependence, the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that naloxone- precipitated opioid withdrawal signs were decreased in exercising morphine-dependent rats receiving MMT than sedentary rats. Also, the exercising morphine-dependent rats receiving MMT exhibited an increased time on open arms, preference for sucrose and a lower morphine preference ratio than sedentary rats. We conclude that treadmill exercise decreased the severity of physical dependence, anxiety/depressive-like behaviors and also the voluntary morphine consumption in morphine withdrawn rats receiving MMT. Thus, exercise may benefit in the treatment of addicts during MMT. Copyright © 2018. Published by Elsevier B.V.

Clinical Efficacy of Traditional Chinese Medicine, Suan Zao Ren Tang, for Sleep Disturbance during Methadone Maintenance: A Randomized, Double-Blind, Placebo-Controlled Trial

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Chan, Yuan-Yu; Chen, Yi-Hung; Yang, Szu-Nian; Lo, Wan-Yu; Lin, Jaung-Geng

2015-01-01

Methadone maintenance therapy is an effective treatment for opiate dependence, but more than three-quarters of persons receiving the treatment report sleep quality disturbances. In this double-blind, randomized, controlled trial, we recruited 90 individuals receiving methadone for at least one month who reported sleep disturbances and had Pittsburgh Sleep Quality Index (PSQI) scores > 5. The purpose of this study was to determine whether Suan Zao Ren Tang, one of the most commonly prescribed traditional Chinese medications for treatment of insomnia, improves subjective sleep among methadone-maintained persons with disturbed sleep quality. Ninety patients were randomly assigned to intervention group (n = 45) and placebo group (n = 45), and all participants were analyzed. Compared with placebo treatment, Suan Zao Ren Tang treatment for four weeks produced a statistically significant improvement in the mean total PSQI scores (P = 0.007) and average sleep efficiency (P = 0.017). All adverse events (e.g., lethargy, diarrhea, and dizziness) were mild in severity. Suan Zao Ren Tang is effective for improving sleep quality and sleep efficiency among methadone-maintained patients with sleep complaints. PMID:26346534

Clinical Efficacy of Traditional Chinese Medicine, Suan Zao Ren Tang, for Sleep Disturbance during Methadone Maintenance: A Randomized, Double-Blind, Placebo-Controlled Trial

Directory of Open Access Journals (Sweden)

Yuan-Yu Chan

2015-01-01

Full Text Available Methadone maintenance therapy is an effective treatment for opiate dependence, but more than three-quarters of persons receiving the treatment report sleep quality disturbances. In this double-blind, randomized, controlled trial, we recruited 90 individuals receiving methadone for at least one month who reported sleep disturbances and had Pittsburgh Sleep Quality Index (PSQI scores > 5. The purpose of this study was to determine whether Suan Zao Ren Tang, one of the most commonly prescribed traditional Chinese medications for treatment of insomnia, improves subjective sleep among methadone-maintained persons with disturbed sleep quality. Ninety patients were randomly assigned to intervention group (n=45 and placebo group (n=45, and all participants were analyzed. Compared with placebo treatment, Suan Zao Ren Tang treatment for four weeks produced a statistically significant improvement in the mean total PSQI scores (P=0.007 and average sleep efficiency (P=0.017. All adverse events (e.g., lethargy, diarrhea, and dizziness were mild in severity. Suan Zao Ren Tang is effective for improving sleep quality and sleep efficiency among methadone-maintained patients with sleep complaints.

Methadone dosage and its relationship to quality of life, satisfaction, psychopathology, cognitive performance and additional consumption of non-prescribed drugs.

Science.gov (United States)

Pedrero-Pérez, Eduardo J; MethaQoL, Grupo

2016-06-14

The effectiveness of methadone maintenance treatment is beyond any doubt, but there remains some incertitude about the appropriate and effective dosage and the objectives that should be achieved by this therapy. Some authors maintain that only doses higher than 50-60 mg/day ought to be considered effective, since only these block all the opioid receptors. But others propose the use of doses adjusted to the needs of the patient, based on their recovery process. Quality of life, satisfaction with treatment, psychopathological symptoms, cognitive performance and additional intake of illegal and unprescribed drugs were evaluated in a representative sample of all patients treated with opioid agonists in the Addiction Institute of Madrid (N = 1898, n = 450) and the Junta de Extremadura (N = 100, n = 65). The results revealed a negative relationship between dose and quality of life, psychopathological symptoms and cognitive performance. Satisfaction with treatment, based on doses negotiated together by doctor and patient, was very high, regardless of the dose. To establish hypothetical causal dependencies among the studied variables structural equation modelling was performed. The results reject the need for high dosage if not required by the patient, and highlight the benefits of other psychosocial interventions that lead to recovery, despite the chronification that could imply the use of high doses. Whereas high dosage programmes provide better indicators of social control, the patient's quality of life must be one of the main indicators of a successful treatment, as in any other health problem.

The Relationship between Sugar-Containing Methadone and Dental Caries: A Systematic Review

Science.gov (United States)

Tripathee, Sheela; Akbar, Tahira; Richards, Derek; Themessl-Huber, Markus; Freeman, Ruth

2013-01-01

Objectives: To review the evidence of a relationship between sugar-containing methadone and dental caries. Data sources: A systematic search of Cochrane Library, PubMed, PsychINFO, EMBASE, MEDLINE, Current Controlled Trials, WHO, OHRN, SIGLE and ERIC databases was conducted from January 1978 up to June 2010. Study selection: Articles were assessed…

Maternal and developmental toxicity of ayahuasca in Wistar rats.

Science.gov (United States)

Oliveira, Carolina Dizioli Rodrigues; Moreira, Camila Queiroz; de Sá, Lilian Rose Marques; Spinosa, Helenice de Souza; Yonamine, Mauricio

2010-06-01

Ayahuasca is a psychotropic plant beverage initially used by shamans throughout the Amazon region during traditional religious cult. In recent years, ayahuasca has also been used in ceremonies of a number of modern syncretic religious groups, including pregnant women. However, no documented study has been performed to evaluate the risk of developmental toxicity of ayahuasca. In the present work, maternal and developmental toxicity was evaluated in Wistar rats. Ayahuasca was administered to pregnant rats in three different doses [the equivalent typical dose (TD) administered to humans, five-fold TD and 10-fold TD] during the gestational period (6-20 days). Dams treated with the highest ayahuasca dose showed maternal toxicity with decrease of weight gain and food intake. Visceral fetal findings were observed in all treatment groups. Skeletal findings were observed in the intermediate- and high-dose groups. The fetuses deriving from the highest dose group also presented a decrease in body weight. From these results, it is possible to conclude that there is a risk of maternal and developmental toxicity following ayahuasca exposure and that the level of toxicity appears to be dose-dependent.

The Evaluation of Relationship between Sexual Self-concept and Sexual Dysfunction in Individuals Undergoing Methadone Maintenance Treatment

Science.gov (United States)

Rajabizadeh, Ghodratolah; Yazdanpanah, Fatemeh; Ramezani, Mohammad Arash

2017-01-01

Background The present study was conducted with the aim of designing a causal model for the evaluation of sexual dysfunctions based on the variables of methadone dosage and sexual self-concept among individuals undergoing methadone maintenance treatment (MMT). Methods The study population of the present study consisted of married men of 20 to 45 years of age with sexual ýrelations and undergoing MMT for a minimum of 8 weeks referring to all MMT clinics of Kerman, Iran, in ýý2015-2016. ýThe subjects were selected through multi-stage cluster sampling (n = 250). Data were collected using the General Health Questionnaire (GHQ-28), Multi-Dimensional Sexual Self-concept Questionnaire (MSSQ), and Internal Index for Erectile Function (IIEF). Data were analyzed using path analysis method and Pearson correlation coefficient. The suggested model was evaluated using structural equation model (SEM), and indirect relationships were assessed using Bootstrap method. Findings The suggested model showed acceptable fitness with the data, and all routes, except methadone use route, to sexual function were significant. The result of the multiple ýindirect route showed that sexual function had a significant relationship with methadone use through ýsexual self-concept. In total, 60% of variance in sexual dysfunction was explained using the variables of the suggested model. Conclusion Further studies are suggested to be conducted regarding psychological factors effective on the sexual dysfunctions among individuals undergoing MMT, such as sexual self-concept. Moreover, more detailed evaluation of each subscale of positive and negative sexual self-concept is recommended to assess the psychological causes of sexual dysfunctions in these individuals and design psychological, behavioral, and cognitive-behavioral treatment interventions for them. PMID:29299211

The Evaluation of Relationship between Sexual Self-concept and Sexual Dysfunction in Individuals Undergoing Methadone Maintenance Treatment.

Science.gov (United States)

Rajabizadeh, Ghodratolah; Yazdanpanah, Fatemeh; Ramezani, Mohammad Arash

2017-04-01

The present study was conducted with the aim of designing a causal model for the evaluation of sexual dysfunctions based on the variables of methadone dosage and sexual self-concept among individuals undergoing methadone maintenance treatment (MMT). The study population of the present study consisted of married men of 20 to 45 years of age with sexual ýrelations and undergoing MMT for a minimum of 8 weeks referring to all MMT clinics of Kerman, Iran, in ýý2015-2016. ýThe subjects were selected through multi-stage cluster sampling (n = 250). Data were collected using the General Health Questionnaire (GHQ-28), Multi-Dimensional Sexual Self-concept Questionnaire (MSSQ), and Internal Index for Erectile Function (IIEF). Data were analyzed using path analysis method and Pearson correlation coefficient. The suggested model was evaluated using structural equation model (SEM), and indirect relationships were assessed using Bootstrap method. The suggested model showed acceptable fitness with the data, and all routes, except methadone use route, to sexual function were significant. The result of the multiple ýindirect route showed that sexual function had a significant relationship with methadone use through ýsexual self-concept. In total, 60% of variance in sexual dysfunction was explained using the variables of the suggested model. Further studies are suggested to be conducted regarding psychological factors effective on the sexual dysfunctions among individuals undergoing MMT, such as sexual self-concept. Moreover, more detailed evaluation of each subscale of positive and negative sexual self-concept is recommended to assess the psychological causes of sexual dysfunctions in these individuals and design psychological, behavioral, and cognitive-behavioral treatment interventions for them.

Tapering and discontinuation of methadone for chronic pain.

Science.gov (United States)

Breivik, Harald

2015-06-01

How to taper and discontinue methadone therapy for chronic pain management is illustrated through a case report. This report is adapted from paineurope 2014; Issue 4, ©Haymarket Medical Publications Ltd, and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be viewed via the website: www.paineurope.com at which health professionals can find links to the original articles and request copies of the quarterly publication and access additional pain education and pain management resources.

Harm reduction measures in prison (Methadone treatment and its effects on quality of life promotion

Directory of Open Access Journals (Sweden)

Iraj Esmaili

2009-02-01

Conclusion: In a look, it is obvious that the harm reduction measures which have been taken for prisoners under the coverage of Methadone treatment will be effective in improving their quality of life conditions.

Measles vaccination in the presence or absence of maternal measles antibody

DEFF Research Database (Denmark)

Aaby, Peter; Martins, Cesário L; Garly, May-Lill

2014-01-01

vaccinated with MV in the presence of maternal antibody and 32.3 per 1000 person-years without maternal antibody (mortality rate ratio [MRR], 0.0; 95% confidence interval [CI], 0-.52). In trial II (2003-2007), the mortality rate was 4.2 per 1000 person-years among children vaccinated in presence of maternal...... mortality than children with no maternal antibody, the MRR being 0.22 (95% CI, .07-.64) between 4-6 months and 5 years. CONCLUSIONS: Child mortality in low-income countries may be reduced by vaccinating against measles in the presence of maternal antibody, using a 2-dose schedule with the first dose at 4......BACKGROUND: Measles vaccine (MV) has a greater effect on child survival when administered in early infancy, when maternal antibody may still be present. METHODS: To test whether MV has a greater effect on overall survival if given in the presence of maternal measles antibody, we reanalyzed data...

Clinical effects of dexmedetomidine combined with methadone after intranasal and intramuscular administration in dogs

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Daniela Gioeni

2018-06-01

Full Text Available The intranasal (IN route shows promise for chemical restraint given the large area offered for drugs absorption. The nasal turbinates increase nasal mucosa surface, which have a greater blood flow than muscle, brain and liver tissue . Aim of the study is to compare the clinical effects and sedation scores following either IN or intramuscular (IM administration of dexmedetomidine-methadone in dogs. Twenty mixed-breed, client-owned, healthy dogs, undergoing soft tissue surgery or diagnostic procedures, were randomly allocated in two groups (n = 10 to receive dexmedetomidine (0.01 mg kg-1 together with methadone (0.4 mg kg-1 IN (IN-group or IM (IM-group. Temperament was evaluated before premedication (1 = calm and friendly, 4 = very excitable or nervous (Maddern et al. 2010. Heart rate (HR, respiratory frequency (fR, body temperature, and side effects were recorded before (T0 and 10 (T10, 20 (T20 and 30 (T30 minutes after premedication. Sedation was scored 3 times (every 10 minutes after drugs administration using a descriptive sedation scale (0 = no sedation, 13 = extremely sedated. Induction was performed at T30 with titrate-to-effect propofol and the dosage was recorded. Student T-test was performed. Weight, age, temperament, body temperature and propofol dose were not different between groups. At each time point, excluding T0, IM-group showed a statistically lower HR and fRcompared to IN-group. No undesirable effects were observed in both groups. Sedation score in IM-group was significantlyhigher compared to IN-group at each time point. In conclusion, despite statistical differences, IN administration produces a satisfactory clinical sedation with more gradual hemodynamic effects compared to IM injection; this is probably due to a direct transport of drugs from cranial nerves (I-V to brain with limited systemic absorption. However, the high variability recorded in sedation score between subjects in IN-group (min 1/13; max 13/13 at T30

Treatment readiness, attitudes toward, and experiences with methadone and buprenorphine maintenance therapy among people who inject drugs in Malaysia

Science.gov (United States)

Vijay, Aishwarya; Bazazi, Alexander R.; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L.

2016-01-01

Background Little is known about attitudes toward and experiences with opioid maintenance therapy (OMT) among people who inject drugs in Malaysia, a country where people who inject drugs comprise 1.3% of the adult population. Methods In 2010, 460 people who inject drugs in Greater Kuala Lumpur, Malaysia were surveyed to evaluate attitudes toward and experience with OMT and treatment readiness. Attitudes towards OMT with both methadone and buprenorphine were assessed using an opinions scale. Multivariable linear regression was used to assess correlates of treatment readiness, measured with the 19-item Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Results All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Few had had previous experience with methadone (9.3%) or buprenorphine (12.6%) maintenance therapy, yet many had used methadone (55.2%) or buprenorphine (51.7%) outside of treatment settings. Fifteen percent had injected buprenorphine in the past month, and of the few that were currently receiving buprenorphine maintenance therapy, almost all were injecting it. The majority of subjects exhibited a moderate level of treatment readiness and a preference for methadone over buprenorphine. Those with low treatment readiness scores were more likely to have previous experience with compulsory drug detention centers (p<0.01), needle/syringe exchange programs (p<0.005), or be of Indian ethnicity (p<0.001). Past use of methadone (p<0.01), older age (p<0.001), stress symptom severity (p<0.001), and sharing of needles or syringes (p<0.05) were associated with higher treatment readiness scores. Conclusion There are suboptimal levels of OMT experience among people who inject drugs that may be improved by addressing factors that influence patient attitudes. Those individuals with moderate treatment readiness may be targeted by brief motivational and cognitive interventions in primary care, prisons or OMT clinics

Model-based comparison of maternal and foetal organ doses from {sup 99m}Tc pertechnetate, DMSA, DTPA, HDP, MAA and MAG{sub 3} diagnostic intakes during pregnancy

Energy Technology Data Exchange (ETDEWEB)

Saunders, Margaret; Palmer, Maria; Preece, Alan; Millard, Roger [Centre for Physics and Engineering Research in Medicine, University of Bristol, Bristol Oncology Centre, Horfield Road, Bristol BS2 8ED (United Kingdom)

2002-10-01

Organ residence times were calculated for diagnostic intakes of {sup 99m}Tc pertechnetate, 2,3-dimercaptosuccinic acid (DMSA), diethylene triamine penta-acetic acid (DTPA), hydroxymethylene diphosphonate (HDP), macroaggregated albumin (MAA) and mercapto-acetyltriglycine (MAG{sub 3}) during the 1st and 3rd stages of pregnancy and used with the MIRDOSE3 pregnant female phantoms for generation of dose estimates. At stage 3 individual foetal organ doses were estimated via a surrogate phantom based on that for the new-born but with mean dose/cumulated activity (S) values scaled for compatibility with foetal whole body S. Stage 1 or 3 whole foetus doses ranged from 5.2 to 0.77 {mu}Gy MBq{sup -1} respectively, analogous to current ICRP estimates for these agents using similar in vivo biodistribution model databases. Most stage 3 maternal and foetal organ doses were similar within a factor of 3, being higher in the foetus than the mother with pertechnetate, DTPA and MAG{sub 3}, and lower with DMSA, HDP and MAA. Doses were more uniformly distributed among foetal organs than in the mother. Placental transfer was greatest with pertechnetate, where dose to the stage 3 foetal thyroid was 60-140 {mu}Gy MBq{sup -1}. With each agent there was more placental transfer in stage 3 than in stage 1, but doses to stage 1 whole foetus were always higher, with the contribution from the mother dominant. For DMSA, HDP and MAG{sub 3} the maternal contribution to total foetal body dose exceeded 93% for both stages. (orig.)

Treatment readiness, attitudes toward, and experiences with methadone and buprenorphine maintenance therapy among people who inject drugs in Malaysia.

Science.gov (United States)

Vijay, Aishwarya; Bazazi, Alexander R; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L

2015-07-01

Little is known about attitudes toward and experiences with opioid maintenance therapy (OMT) among people who inject drugs in Malaysia, a country where people who inject drugs comprise 1.3% of the adult population. In 2010, 460 people who inject drugs in Greater Kuala Lumpur, Malaysia were surveyed to evaluate attitudes toward and experiences with OMT and treatment readiness. Attitudes towards OMT with both methadone and buprenorphine were assessed using an opinions scale. Multivariable linear regression was used to assess correlates of treatment readiness, measured with the 19-item Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Few had had previous experience with methadone (9.3%) or buprenorphine (12.6%) maintenance therapy, yet many had used methadone (55.2%) or buprenorphine (51.7%) outside of treatment settings. Fifteen percent had injected buprenorphine in the past month, and of the few that were currently receiving buprenorphine maintenance therapy, almost all were injecting it. The majority of subjects exhibited a moderate level of treatment readiness and a preference for methadone over buprenorphine. Those with low treatment readiness scores were more likely to have previous experience with compulsory drug detention centers (polder age (ppeople who inject drugs that may be improved by addressing factors that influence patient attitudes. Those individuals with moderate treatment readiness may be targeted by brief motivational and cognitive interventions in primary care, prisons or OMT clinics aimed at improving entry into and retention in treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

The Effectiveness of Stress Management Program on Quality of Life among Methadone Maintenance Treatment Members

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s Zarei

2014-11-01

Full Text Available Objective: The aim of present study was to investigate the effectiveness of stress management program on quality of life among methadone maintenance treatment members. Method: In this pre-test, post-test experimental study, 30 individual who referred to Saba MMT center in Pakdasht were randomly divided into experimental group (n=15 participants and control group (n=15 participants. The experimental group was undergone ten 90 minutes sessions of stress management program and the control group didn’t receive any treatment program. Quality of life questionnaire (SF-36 was administered. Result: The results showed that the mean sf-36 score in the experimental group had significant higher increased in comparison of control group. Conclusion: It can be concluded stress management program is effective on increasing of quality of life among methadone maintenance treatment members.

Developing an electronic health record (EHR) for methadone treatment recording and decision support.

LENUS (Irish Health Repository)

Xiao, Liang

2011-02-01

In this paper, we give an overview of methadone treatment in Ireland and outline the rationale for designing an electronic health record (EHR) with extensibility, interoperability and decision support functionality. Incorporating several international standards, a conceptual model applying a problem orientated approach in a hierarchical structure has been proposed for building the EHR.

Methadone Maintenance Therapy in Vietnam: An Overview and Scaling-Up Plan

Directory of Open Access Journals (Sweden)

Tam T. M. Nguyen

2012-01-01

Full Text Available Vietnam is among the countries with the highest rate of HIV transmission through injecting drug users. HIV prevalence among injecting drug users is 20% and up to 50% in many provinces. An estimated number of drug users in the country by the end of 2011 were 171,000 in which the most common is heroin (85%. Detoxification at home, community, and in rehabilitation centers have been the main modalities for managing heroin addiction until Methadone Maintenance Treatment (MMT was piloted in 2008. Recent reports have demonstrated positive treatment outcomes. Incidence of HIV was found remarkably low among patients on MMT. Treatment has significantly improved the quality of life as well as stability for society. The government has granted the Ministry of Health (MoH to expand Methadone treatment to at least 30 provinces to provide treatment for more than 80,000 drug users by 2015. The Vietnam Administration for HIV/AIDS Control (VAAC and MOH have outlined the role and responsibility of key departments at the central and local levels in implementing and maintaining MMT treatment. This paper will describe the achievements of the MMT pilot program and the scaling-up plan as well as strategies to ensure quality and sustainability and to overcome the challenges in the coming years.

An investigation of an open-access model for scaling up methadone maintenance treatment.

Science.gov (United States)

Madden, Lynn M; Farnum, Scott O; Eggert, Kathryn F; Quanbeck, Andrew R; Freeman, Robert M; Ball, Samuel A; Schottenfeld, Richard S; Shi, Julia M; Savage, Mary Ellen; Barry, Declan T

2018-02-17

To examine retrospectively patient and programmatic outcomes following the development and implementation of an 'open-access' model in which prospective patients were enrolled rapidly in methadone maintenance treatment, irrespective of ability to pay, and provided real-time access to multiple voluntary treatment options. Medical and administrative records were abstracted to compare data for 1 year before and 9 years after initiating the implementation of an open-access treatment model in May 2007. Methadone maintenance treatment center in Connecticut, USA. Individuals with opioid use disorder entering treatment between July 2006 and June 2015. In June 2015, 64% (n = 2594) of the sample were men and 80% (n = 3133) reported that they were white. The Network for the Improvement of Addiction Treatment-informed open-access treatment model uses process improvement strategies to improve treatment access and capacity. Census, waiting time, retention, non-medical opioid use, patient mortality and financial sustainability (net income and state-block grants as proportions of revenue). In the 9 years following the initial implementation of the open-access model, patient census increased by 183% from 1431 to 4051, and average waiting-time days decreased from 21 to 0.3 (same day) without apparent deleterious effects on rates of retention, non-medical opioid use or mortality. Between fiscal years (FY) 06 and FY 15, net operating margin rose from 2 to 10%, while state-block grant revenues declined 14% and the proportion of total revenue from state-block grant revenue decreased from 49 to 24%. An open-access model for rapid enrolment of people with opioid use disorder in methadone treatment appears to improve treatment access, capacity, and financial sustainability without evidence of deleterious effects on treatment outcomes. © 2018 Society for the Study of Addiction.

Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

Science.gov (United States)

Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

2014-11-01

Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

Clonidine hydrochloride detoxification from methadone treatment--the value of naltrexone aftercare.

Science.gov (United States)

Rawson, R A; Washton, A M; Resnick, R B; Tennant, F S

1984-01-01

Treatment outcomes were compared for 2 groups of subjects detoxified from methadone using clonidine. One group of 12 subjects was encouraged to continue in treatment with naltrexone, while the other 12 subjects did not have naltrexone treatment available. Results suggested that those subjects who had naltrexone available were more successful at completing the 10 day detoxification treatment and that the relapse rate at 30 days post-treatment was significantly reduced by naltrexone treatment.

Risks and realities: dyadic interaction between 6-month-old infants and their mothers in opioid maintenance treatment.

Science.gov (United States)

Sarfi, Monica; Smith, Lars; Waal, Helge; Sundet, Jon Martin

2011-12-01

A number of studies point to methadone exposure in utero as a possible risk factor in the developing mother-infant relationship in the first year of life. This study is part of a larger, national follow-up of 38 infants prenatally exposed to methadone or buprenorphine and 36 comparison, low-risk infants. The aim of the present paper is to assess the quality of mother-infant relationship when the infants are 6 months old. Videotaped mother-infant interactions were rated in a global scale (NICHD). Maternal and infant contributions collapsed into the variables "infant style" and "maternal style" showed that the only factor making significant contribution to the outcome measure "dyadic mutuality" was maternal style. The importance of group membership (exposed versus non-exposed), was reduced when controlling for maternal drug use prior to opioid maintenance treatment (OMT), maternal depression and parenting stress as well as infants' developmental status and sensory-integrative functions. This suggests that prediction of dyadic mutuality should be based on individual characteristics rather than group characteristics. These results support previous research findings that methadone and buprenorphine use per se does not have direct influence on the quality of early mother-infant relationship, but tailored follow-up procedures targeting drug-free pregnancies and parenting support are beneficial for women in OMT and their children. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinical Efficacy of Traditional Chinese Medicine, Suan Zao Ren Tang, for Sleep Disturbance during Methadone Maintenance: A Randomized, Double-Blind, Placebo-Controlled Trial

OpenAIRE

Chan, Yuan-Yu; Chen, Yi-Hung; Yang, Szu-Nian; Lo, Wan-Yu; Lin, Jaung-Geng

2015-01-01

Methadone maintenance therapy is an effective treatment for opiate dependence, but more than three-quarters of persons receiving the treatment report sleep quality disturbances. In this double-blind, randomized, controlled trial, we recruited 90 individuals receiving methadone for at least one month who reported sleep disturbances and had Pittsburgh Sleep Quality Index (PSQI) scores > 5. The purpose of this study was to determine whether Suan Zao Ren Tang, one of the most commonly prescribed ...

Minimum recommended physical activity, and perceived barriers and benefits of exercise in methadone maintained persons.

Science.gov (United States)

Caviness, Celeste M; Bird, Jessica L; Anderson, Bradley J; Abrantes, Ana M; Stein, Michael D

2013-04-01

Methadone-maintained persons are at increased risk for many physical and mental health disorders compared to the general population. Increased physical activity could offset these risks. We assessed physical activity level, and perceived benefits and barriers to exercise in a group of 305 methadone-maintained smokers. Mean participant age was 39.9 years, 50.2% were male, 79.7% were non-Hispanic White, and mean body mass index was 29.8. Nearly 45% endorsed fair or poor physical health. Although participants perceived many benefits of exercise and few barriers, only 38% of participants met weekly recommendations for physical activity, and nearly 25% reported no physical activity. Those who met recommended guidelines were significantly more likely to endorse relapse prevention as a benefit of exercise. Motivating MMT patients to increase physical activity could have important physical, mental health, and drug treatment benefits. Copyright © 2013 Elsevier Inc. All rights reserved.

Mapping the Barriers and Facilitators of HCV Treatment Initiation in Methadone Maintenance Therapy Patients: Implications for Intervention Development.

Science.gov (United States)

Bass, Sarah Bauerle; Jessop, Amy; Maurer, Laurie; Gashat, Muhamed; Al Hajji, Mohammed; Gutierrez, Mercedes

2018-01-01

An estimated 70-90% of current methadone users have Hepatitis C (HCV). Current treatments have few side effects and can cure infection in 8-12 weeks, but less than 10% of methadone patients initiate treatment. Engaging this group in treatment is an important strategy to lower both morbidity and mortality from liver disease and eliminate a significant reservoir of HCV in communities. To understand how to address this treatment gap we used commercial marketing techniques called perceptual mapping and vector message modeling to analyze survey data from 100 HCV+ methadone patients from four centers in Philadelphia. Results were used to understand barriers and facilitators to treatment initiation and to devise targeted message strategies to adapt to a mobile health communication intervention. Results indicate that focusing on how treatment can make one feel "in charge", positive interactions with healthcare providers, the positive attributes of the new vs. old HCV treatments, and providing strategies to address tangible barriers to getting treatment, would be important to address in a communication intervention. These marketing methods allow for focusing on specific variables to "move" the group toward a treatment decision, making them an innovative technique to use in developing highly targeted health communication messages.

NEGOTIATING STRUCTURAL VULNERABILITY FOLLOWING REGULATORY CHANGES TO A PROVINCIAL METHADONE PROGRAM IN VANCOUVER, CANADA: A QUALITATIVE STUDY

Science.gov (United States)

McNeil, Ryan; Kerr, Thomas; Anderson, Solanna; Maher, Lisa; Keewatin, Chereece; Milloy, MJ; Wood, Evan; Small, Will

2015-01-01

While regulatory frameworks governing methadone maintenance therapy (MMT) require highly regimented treatment programs that shape treatment outcomes, little research has examined the effects of regulatory changes to these programs on those receiving treatment, and located their experiences within the wider context of socialstructural inequities. In British Columbia (BC), Canada, provincial regulations governing MMT have recently been modified, including: replacing the existing methadone formulation with Methadose® (pre-mixed and 10 times more concentrated); prohibiting pharmacy delivery of methadone; and, prohibiting pharmacies incentives for methadone dispensation. We undertook this study to examine the impacts of these changes on a structurally vulnerable population enrolled in MMT in Vancouver, BC. Qualitative interviews were conducted with 34 people enrolled in MMT and recruited from two ongoing observational prospective cohort studies comprised of drug-using individuals in the six-month period in 2014 following these regulatory changes. Interview transcripts were analyzed thematically, and by drawing on the concept of ‘structural vulnerability’. Findings underscore how these regulatory changes disrupted treatment engagement, producing considerable health and social harms. The introduction of Methadose® precipitated increased withdrawal symptoms. The discontinuation of pharmacy delivery services led to interruptions in MMT and codispensed HIV medications due to constraints stemming from their structural vulnerability (e.g., poverty, homelessness). Meanwhile, the loss of pharmacy incentives limited access to material supports utilized by participants to overcome barriers to MMT, while diminishing their capacity to assert some degree of agency in negotiating dispensation arrangements with pharmacies. Collectively, these changes functioned to compromise MMT engagement and increased structural vulnerability to harm, including re-initiation of injection drug

Eye Movement Evidence of Attentional Bias for Substance-Related Cues in Heroin Dependents on Methadone Maintenance Therapy.

Science.gov (United States)

Zhao, Hui; Yang, Bo; Zhu, Qian; Zhang, Guangqun; Xiao, Yuqin; Guo, Xiao; Huang, Xiu; Zhang, Zhuo

2017-03-21

Attentional biases toward substance-related stimuli might play a contributing role in addictive behaviors. This study investigated the selective attention to substance-related stimuli in heroin dependents receiving methadone maintenance therapy. Thirty outpatients receiving methadone maintenance treatment for heroin dependence and 38 healthy controls completed a visual probe task with concurrent eye movement monitoring. The results showed that the heroin group reacted faster to probes associated with substance-related pictures than neutral pictures, and they directed more initial fixations and maintained longer initial fixation durations toward substance-related pictures than neutral pictures. However, attentional bias was not correlated with addiction severity in the heroin group. These findings suggest that attentional bias towards substance-related cues occurs in heroin dependents, although this bias might not be associated with the severity of drug-using behavior.

Comorbid Psychopathology and Alcohol Use Patterns among Methadone Maintenance Treatment Patients

Directory of Open Access Journals (Sweden)

Georgios Moussas

2015-01-01

Full Text Available 130 patients from a methadone maintenance treatment program agreed to complete Symptoms Checklist 90-Revised (SCL-90R and Alcohol Use Disorders Identification Test (AUDIT self-report scales. Scores higher than the proposed cut-score on SCL-90R scale were observed on depression, obsessions-compulsions, paranoid ideation, anxiety, anger-hostility, somatization, interpersonal sensitivity, and psychoticism subscales. In sum, 42.9% of our sample exhibited depressive symptomatology, 34.9% obsessive-compulsive symptoms, 29.1% somatization, 27.2% anxiety symptoms, 22.2% paranoid ideation, 19% phobic anxiety, 15.1% psychoticism, and 15.1% hostility and 11.9% presented with symptoms of interpersonal sensitivity. Mean score on AUDIT scale was 6.9±7.9. 63.0% of our participants scored below cut-off and were classified as having a low level of alcohol-related problems; 24.4% scored in the range of 8–15 which is an indication of alcohol abuse whereas 12.6% scored 16 and above indicative of serious abuse/addiction. Scores on AUDIT scale were positively correlated with length of time on methadone treatment, but not with length of time on drug use or age of our participants. Positive correlations were observed among AUDIT and SCL-90R scores, namely, with global severity index score, positive symptom distress index, positive symptom total, and all primary symptom dimensions subscales except phobic anxiety.

Evaluation of an oral transmucosal administration of dexmedetomidine-butorphanol and dexmedetomidine-methadone in dogs.

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Daniela Gioeni

2017-05-01

Full Text Available Oral transmucosal (OTM delivery is a simple and painless method for sedative administration in veterinary medicine and allows a rapid absorption without a first-pass metabolism by the liver (Porters et al. 2014.. OTM is particularly useful in aggressive animals (Santos et al. 2010. The aim of this study is to evaluate the efficacy of the OTM route in dogs for sedative administration in comparison with intramuscular (IM injection. 24 mix-bread dogs undergoing soft tissue surgery or diagnostic procedures were randomly divided in 4 groups (n = 6: two groups received OTM administration of dexmedetomidine (10 µg/kg-1 together with butorphanol (0.2 mg/kg-1, BTF-OTM group or methadone (0.2mg/kg-1, MTD-OTM group; two groups received intramuscular (IM administration of dexmedetomidine (5 µg/kg-1 together with butorphanol (0.2 m/kg-1, BTF-IM group or methadone (0.2 mg/kg-1, MTD-IM. Heart rate (HR, respiratory rate (RR, sedation score (Gruney et al. 2009 and side effects were recorded 10 (T10, 20 (T20 and 30 (T30 minutes after premedication. Induction was performed at T30 with titrate-to-effect propofol administration and the dosage required was recorded. At each time point BTF-IM group showed a statistically lower HR compared to BTF-OTM; RR was statistically lower at T10 in MTD-OTM group (21.33 ± 8.64 pm compared to BTF-OTM (46.16 ± 17.98; Dogs in group MTD-IM reached a higher sedation scores at each time point compared to MTD-OTM. The induction dose of propofol appears comparable among groups. Marked vasoconstriction was observed after OTM administration, as probably related to α2-agonists use. Emesis and sialorrhea occurred in two subjects of MTD-OTM group while only one dog presented sialorrhea in BTF-OTM group. In conclusion, OTM administration appears effective and easy to perform; it takes a longer time to achieve a good sedation score, probably related to a gradual absorption of drugs that also leads to a more gradual hemodynamic effects.

Impact of a Casino Opening on Gambling Behaviors of People Engaged in Methadone Maintenance.

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Palmer-Bacon, Jessica; Miles-McLean, Haley; Welsh, Christopher; Rugle, Loreen; Medoff, Deborah; Potts, Wendy; Himelhoch, Seth

2017-06-01

This study examined gambling behavior in the context of a newly opening casino, comparing disordered gamblers to non-disordered gamblers, in a population of individuals involved in methadone maintenance treatment. Disordered gamblers (N = 50) and non-disordered gamblers (N = 50) were surveyed before and after the opening of a new casino on gambling behaviors, substance use, and psychological symptoms. No statistically significant changes in gambling behaviors were observed for disordered gamblers or non-disordered gamblers across time points; however, non-disordered gamblers demonstrated non-significant increases in horse and dog race betting, electronic games, and casino table games. As expected, disordered gamblers were found to spend significantly more money on electronic games and casino table games (p casino did not appear to have a major impact on gambling behaviors of individuals attending methadone maintenance treatment, though the non-significant increases in gambling among non-disordered gamblers may indicate that this population is preferentially impacted by the opening of a new casino. Future investigation into the longer term effects of opening a new casino on this population may be warranted.

Progesterone promotes maternal-fetal tolerance by reducing human maternal T-cell polyfunctionality and inducing a specific cytokine profile.

Science.gov (United States)

Lissauer, David; Eldershaw, Suzy A; Inman, Charlotte F; Coomarasamy, Aravinthan; Moss, Paul A H; Kilby, Mark D

2015-10-01

Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4(+) and CD8(+) T cells, with reductions not only in potentially deleterious IFN-γ and TNF-α production but also in IL-10 and IL-5. Conversely, production of IL-4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL-4. This was accompanied by reduced T-cell proliferation. Using fetal and viral antigen-specific CD8(+) T-cell clones, we confirmed that this as a direct, nonantigen-specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4(+) and CD8(+) T cells responded to progesterone in a dose-dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal-fetal interface. This characterization of how progesterone modulates T-cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Erectile dysfunction in methadone maintenance patients: a cross sectional study in northern iran.

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Seyed Hamzeh Hosseini

2013-12-01

Full Text Available Erectile dysfunction affects quality of life and is a common dysfunction in drug abusers. The aim of this study was to evaluate the frequency of erectile dysfunction in drug abusers on methadone maintenance therapy to reduce this drug side effect in the future studies.This cross-sectional study was conducted with two hundred addicted individuals on methadone maintenance therapy. Erectile dysfunction was surveyed using the International Index of Erectile Function (IIEF. Finally, all data were collected and analyzed by descriptive statistics such as measures of variability and central tendency and Chi-squared (χ(2 test using SPSS Version18.0 software.The amount of the total frequency of erectile dysfunction was pointed 30 or less among the two hundred patients and included the moderate and severe cases. In this study, the number of patients with erectile dysfunction was fifty three (26.5%.The frequency of erectile dysfunction in our study was approximately 1.5 times of prevalence of the public (16.1%. In this study, all the factors related to sexual function such as erectile function, libido, orgasm, and sexual pleasure showed a decline among drug abusers.

Pain and Opioid Addiction: A Systematic Review and Evaluation of Pain Measurement in Patients with Opioid Dependence on Methadone Maintenance Treatment.

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Dennis, B B; Bawor, M; Paul, J; Plater, C; Pare, G; Worster, A; Varenbut, M; Daiter, J; Marsh, D C; Desai, D; Thabane, L; Samaan, Z

2016-01-01

While chronic pain has been said to impact patient's response to methadone maintenance treatment for opioid dependence, the reported findings are inconsistent. These discrepancies may be a direct result of variations in the measurement of chronic pain or definitions of response to methadone treatment. The goal of this study is to evaluate the association between pain and substance use behaviour to determine the real impact of comorbid pain in the methadone population. We also aim to examine sources of variation across the literature with a specific focus on the measurement of pain. We performed a systematic review using an electronic search strategy across CINAHL, MEDLINE, Web of Science, PsychINFO, EMBASE, and the Cochrane Library including Cochrane Reviews and the Cochrane Central Register of Controlled Trials databases. Title, abstract, as well as full text screening and extraction were performed in duplicate. Studies evaluating the association between chronic pain and methadone maintenance treatment response were eligible for inclusion in this review. Using a sample of 297 methadone patients from the Genetics of Opioid Addiction (GENOA) research collaborative, we assessed the reliability of patient self-reported pain and the validated Brief Pain Inventory (BPI) assessment tool. After screening 826 articles we identified five studies eligible for full text extraction, of which three showed a significant relationship between the presence of pain and the increase in substance abuse among patients on methadone for the treatment of opioid dependence. Studies varied largely in the definitions and measurement of both pain and response to treatment. Results from our validation of pain measurement in the GENOA sample (n=297) showed the use of a simple self-reported pain question is highly correlated to the use of the BPI. Simply asking patients whether they have pain showed a 44.2% sensitivity, 88.8% specificity, 84.4% PPV and 53.6% NPV to the BPI. The area under the

Psychotropic drugs in opioid addicts on methadone treatment.

Science.gov (United States)

Ferris, G N

1976-07-01

Psychotropic drug treatment of persons on methadone maintenance is discussed. Patients with clear target symptoms, such as anxiety, depression, or psychosis responded just as non-opioid addicts would to the major psychotropic agents. The minor tranquilizers are felt to be of doubtful value, and subject to abuse. Sleep disturbances cannot be treated by the usual means, as the drugs needed again are abused. However, chlorpromazine shows some promise here. Methods of drug delivery and goals of treatment must be adapted to the realities of this patient-group's characteristics, particularly anti-social traits, poor motivation and unreliability. Psychotropic drugs are unlikely to be of aid in multiple drug abusers, personality and character disorders, and opioid withdrawal. Four case histories are presented.

Very long Detection Times after High and repeated intake of Heroin and Methadone, measured in Oral Fluid

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Vindenes V.

2014-12-01

Full Text Available When detection times for psychoactive drugs in oral fluid are reported, they are most often based on therapeutic doses administered in clinical studies. Repeated ingestions of high doses, as seen after drug abuse, are however likely to cause positive samples for extended time periods. Findings of drugs of abuse in oral fluid might lead to negative sanctions, and the knowledge of detection times of these drugs are important to ensure correct interpretation. The aim of this study was to investigate the detection times of opioids in oral fluid. 25 patients with a history of heavy drug abuse admitted to a detoxification ward were included. Oral fluid and urine were collected daily and, if the patient gave consent, a blood sample was drawn during the first five days after admission. Morphine, codeine and/or 6-monoacetyl morphine (6-MAM were found in oral fluid and/or urine from 20 patients. The maximum detection times in oral fluid for codeine, morphine and 6-MAM were 1, 3 and 8 days, respectively. Positive oral fluid samples were interspersed with negative samples, mainly for concentrations around cut off. Elimination curves for methadone in oral fluid were found for two subjects, and the detection times were 5 and 8 days. Oral fluid is likely to become a good method for detection of drug abuse in the future

Effect of low-dose irradiation on pregnant mouse haemopoiesis

International Nuclear Information System (INIS)

Weinberg, S.R.; McCarthy, E.G.; MacVittie, T.J.; Baum, S.J.

1981-01-01

The effects of low-dose gamma radiation to haemopoietic progenitor cell compartments of the marrow and spleen of virgin female mice and pregnant mice were studied. Microplasma clot cultures were used to assess burst-forming uniterythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) activity, and double-layer agar cultures were established to evaluate granulocyte-macrophage colony-forming cell (GM-CFC) and macrophage colony-forming cell (M-CFC). The apparent shift in maternal erythropoiesis from the bone marrow to the enlarged spleen was reflected by an increase in CFU-E and BFU-E per spleen and a concomitant decrease in CFU-E and BFU-E per femur. Whereas maternal GM-CFC values per femur increased 36%, maternal GM-CFC per spleen increased by 172% compared to virgin values. Total-body irradiation to the day-10.5 pregnant mouse caused a further suppression of day-14.5 medullary erythropoiesis (i.e. decreased CFU-E values) compared to the virgin female mouse. An ability of the maternal spleen to support further compensatory erythropoiesis following increasing doses of radiation was demonstrated. Four days after 1.0 Gy exposure, maternal values for GM-CFC per femur or spleen decreased to nonirradiated virgin mice values. M-CFC per maternal femur decreased to nonirradiated virgin mice values. M-CFC per maternal femur decreased following 1.5 Gy, but M-CFC per spleen appeared to be unaffected with doses from 0.5 to 2.0 Gy. (author)

Dopamine antagonists during parturition disrupt maternal care and the retention of maternal behavior in rats.

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Byrnes, Elizabeth M; Rigero, Beth A; Bridges, Robert S

2002-11-01

Brief contact with pups at parturition enables the female rat to establish and retain the full repertoire of maternal behaviors, allowing her to respond rapidly to pups in the future. To determine whether the dopamine system is involved in the retention of maternal behavior, females were continuously infused with dopamine antagonists during the periparturitional period and then allowed either a brief interaction period with pups (3 h) or no interaction with pups (pups removed as they were born). Females were exposed to either the D1-like antagonist SCH 23390 (0.1 or 1.0 mg/kg/day) or the D2-like antagonist clebopride (0.5 or 1.0 mg/kg/day). The high dose of either DA antagonist resulted in significant attenuation of maternal care immediately postpartum. When tested for the retention of maternal behavior 7 days later, however, only the females exposed to the D2 antagonist displayed a delayed response to shown full maternal behavior (FMB) towards donor pups. Thus, while both dopamine receptor subtypes appear necessary for the full and rapid expression of maternal behavior during the early postpartum period, only the D2 receptor subtype appears to be involved in the retention of this behavior.

Average fetal depth in utero: data for estimation of fetal absorbed radiation dose

International Nuclear Information System (INIS)

Ragozzino, M.W.; Breckle, R.; Hill, L.M.; Gray, J.E.

1986-01-01

To estimate fetal absorbed dose from radiographic examinations, the depth from the anterior maternal surface to the midline of the fetal skull and abdomen was measured by ultrasound in 97 pregnant women. The relationships between fetal depth, fetal presentation, and maternal parameters of height, weight, anteroposterior (AP) thickness, gestational age, placental location, and bladder volume were analyzed. Maternal AP thickness (MAP) can be estimated from gestational age, maternal height, and maternal weight. Fetal midskull and abdominal depths were nearly equal. Fetal depth normalized to MAP was independent or nearly independent of maternal parameters and fetal presentation. These data enable a reasonable estimation of absorbed dose to fetal brain, abdomen, and whole body

A preliminary, controlled investigation of magnesium L-aspartate hydrochloride for illicit cocaine and opiate use in methadone-maintained patients.

Science.gov (United States)

Margolin, Arthur; Kantak, Kathleen; Copenhaver, Michael; Avants, S Kelly

2003-01-01

Based on pre-clinical studies suggesting that magnesium (Mg) reduces cocaine self-administration and potentiates the antinociceptive effects of morphine, we conducted a preliminary randomized clinical trial investigating Mg for the treatment of illicit cocaine and opiate use. Eighteen methadone-maintained patients who used illicit opiates and cocaine received either Mg (732 mg/day) or placebo for 12 weeks. Overall, findings showed that the percentage of urine screens testing positive for opiates in the Mg group (22.6%) was half that of the placebo group (46.4%), p = .04; the difference was even greater in the "medication compliant" sample (Mg: 16.3%, placebo: 47.9%), p = .02. Cocaine craving was lower in the Mg compared to the placebo group, but there was no difference between groups in cocaine use. These preliminary findings suggest that Mg may have a beneficial effect for reducing illicit opiate use. It is possible that a higher dose of Mg than was used in this study may be needed to decrease cocaine use.

Effects of lower-cost incentives on stimulant abstinence in methadone maintenance treatment: a National Drug Abuse Treatment Clinical Trials Network study.

Science.gov (United States)

Peirce, Jessica M; Petry, Nancy M; Stitzer, Maxine L; Blaine, Jack; Kellogg, Scott; Satterfield, Frank; Schwartz, Marion; Krasnansky, Joe; Pencer, Eileen; Silva-Vazquez, Lolita; Kirby, Kimberly C; Royer-Malvestuto, Charlotte; Roll, John M; Cohen, Allan; Copersino, Marc L; Kolodner, Ken; Li, Rui

2006-02-01

Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence have improved treatment outcomes of substance abusers, but have not been widely implemented in community drug abuse treatment settings. To compare outcomes achieved when a lower-cost prize-based contingency management treatment is added to usual care in community methadone hydrochloride maintenance treatment settings. Random assignment to usual care with (n = 198) or without (n = 190) abstinence incentives during a 12-week trial. Six community-based methadone maintenance drug abuse treatment clinics in locations across the United States. Three hundred eighty-eight stimulant-abusing patients enrolled in methadone maintenance programs for at least 1 month and no more than 3 years. Participants submitting stimulant- and alcohol-negative samples earned draws for a chance to win prizes; the number of draws earned increased with continuous abstinence time. Total number of stimulant- and alcohol-negative samples provided, percentage of stimulant- and alcohol-negative samples provided, longest duration of abstinence, retention, and counseling attendance. Submission of stimulant- and alcohol-negative samples was twice as likely for incentive as for usual care group participants (odds ratio, 1.98; 95% confidence interval, 1.42-2.77). Achieving 4 or more, 8 or more, and 12 weeks of continuous abstinence was approximately 3, 9, and 11 times more likely, respectively, for incentive vs usual care participants. Groups did not differ on study retention or counseling attendance. The average cost of prizes was 120 dollars per participant. An abstinence incentive approach that paid 120 dollars in prizes per participant effectively increased stimulant abstinence in community-based methadone maintenance treatment clinics.

Social and structural barriers for adherence to methadone maintenance treatment among Vietnamese opioid dependence patients.

Science.gov (United States)

Tran, Bach Xuan; Nguyen, Long Hoang; Tran, Tung Thanh; Latkin, Carl A

2018-01-01

Methadone maintenance treatment (MMT) services may reduce the risk of HIV transmission if patients completely adhere to the treatment. Identifying adherence patterns and potential related factors is vital for the sustainability of MMT program in Vietnam. This study examined social and structural factors associated with adherence to MMT among patients in different service delivery models. A total of 510 patients at three MMT clinics in Hanoi were interviewed. Measures of self-reported adherence included the number of missed doses in the past 7 days and the level of adherence in the past 30 days using a visual analog scale (VAS) scoring from 0 (non-adherence) to 100 (perfect adherence). Multivariate regressions were employed to identify factors associated with non-adherence to MMT. A total of 17.7% of participants reported incomplete MMT adherence in the last 30 days and 8.3% reported missing a dose in the last seven days, respectively. Living with HIV/AIDS, poor self-care and usual activities, and disclosure of health issues to spouses or intimate partners were associated with non-adherence. Those patients with pain or depression were more likely to report better adherence. Disclosing health status to spouse/partner increased the risk of incomplete adherence, while disclosing to friends reduced the number of missed dose in the last seven days. Patients attending clinics with comprehensive services had a lower VAS score of adherence compared to those enrolling in clinics with only MMT and general health care. Sustaining the compliance of patients to MMT is principal in the rapid expansion of this service in Vietnam. It is necessary to address the complexity of health care demands of drug users, their difficulties to be rehabilitated into workforce and society, and the stigmatization to maximize the outcomes of MMT program.

Development and validation of a magnetic solid-phase extraction with high-performance liquid chromatography method for the simultaneous determination of amphetamine and methadone in urine.

Science.gov (United States)

Taghvimi, Arezou; Hamishehkar, Hamed; Ebrahimi, Mahmoud

2016-06-01

The simultaneous determination of amphetamine and methadone was carried out by magnetic graphene oxide nanoparticles, a magnetic solid-phase extraction adsorbent, as a new sample treatment technique. The main factors (the amounts of sample volume, amount of adsorbent, type and amount of extraction organic solvent, time of extraction and desorption, pH, the ionic strength of extraction medium, and agitation rate) influencing the extraction efficiency were investigated and optimized. Under the optimized conditions, good linearity was observed in the range of 100-1500 ng/mL for amphetamine and 100-1000 ng/mL for methadone. The method was evaluated for determination of AM and methadone in positive urine samples, satisfactory results were obtained, therefore magnetic solid-phase extraction can be applied as a novel method for the determination of drugs of abuse in forensic laboratories. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Measles Vaccination in the Presence or Absence of Maternal Measles Antibody: Impact on Child Survival

Science.gov (United States)

Aaby, Peter; Martins, Cesário L.; Garly, May-Lill; Andersen, Andreas; Fisker, Ane B.; Claesson, Mogens H.; Ravn, Henrik; Rodrigues, Amabelia; Whittle, Hilton C.; Benn, Christine S.

2014-01-01

Background. Measles vaccine (MV) has a greater effect on child survival when administered in early infancy, when maternal antibody may still be present. Methods. To test whether MV has a greater effect on overall survival if given in the presence of maternal measles antibody, we reanalyzed data from 2 previously published randomized trials of a 2-dose schedule with MV given at 4–6 months and at 9 months of age. In both trials antibody levels had been measured before early measles vaccination. Results. In trial I (1993–1995), the mortality rate was 0.0 per 1000 person-years among children vaccinated with MV in the presence of maternal antibody and 32.3 per 1000 person-years without maternal antibody (mortality rate ratio [MRR], 0.0; 95% confidence interval [CI], 0–.52). In trial II (2003–2007), the mortality rate was 4.2 per 1000 person-years among children vaccinated in presence of maternal measles antibody and 14.5 per 1000 person-years without measles antibody (MRR, 0.29; 95% CI, .09–.91). Possible confounding factors did not explain the difference. In a combined analysis, children who had measles antibody detected when they received their first dose of MV at 4–6 months of age had lower mortality than children with no maternal antibody, the MRR being 0.22 (95% CI, .07–.64) between 4–6 months and 5 years. Conclusions. Child mortality in low-income countries may be reduced by vaccinating against measles in the presence of maternal antibody, using a 2-dose schedule with the first dose at 4–6 months (earlier than currently recommended) and a booster dose at 9–12 months of age. Clinical Trials Registration. NCT00168558. PMID:24829213

Magnesium supplement in pregnancy-induced hypertension: effects on maternal and neonatal magnesium and calcium homeostasis

DEFF Research Database (Denmark)

Rudnicki, M; Frølich, A; Fischer-Rasmussen, W

1991-01-01

The objective of this study was to evaluate the effect of low dose magnesium supplement upon maternal and fetal serum levels of mineral status in pregnancies complicated with hypertension (PIH). Twenty-five patients with PIH agreed to participate and were randomly allocated, in a double-blind man......The objective of this study was to evaluate the effect of low dose magnesium supplement upon maternal and fetal serum levels of mineral status in pregnancies complicated with hypertension (PIH). Twenty-five patients with PIH agreed to participate and were randomly allocated, in a double...... period despite a significant increased loss of calcium during the first 24 h of inclusion. Low dose maternal magnesium treatment did not cause neonatal hypocalcemia....

Developing an electronic health record (EHR) for methadone treatment recording and decision support

Science.gov (United States)

2011-01-01

Background In this paper, we give an overview of methadone treatment in Ireland and outline the rationale for designing an electronic health record (EHR) with extensibility, interoperability and decision support functionality. Incorporating several international standards, a conceptual model applying a problem orientated approach in a hierarchical structure has been proposed for building the EHR. Methods A set of archetypes has been designed in line with the current best practice and clinical guidelines which guide the information-gathering process. A web-based data entry system has been implemented, incorporating elements of the paper-based prescription form, while at the same time facilitating the decision support function. Results The use of archetypes was found to capture the ever changing requirements in the healthcare domain and externalises them in constrained data structures. The solution is extensible enabling the EHR to cover medicine management in general as per the programme of the HRB Centre for Primary Care Research. Conclusions The data collected via this Irish system can be aggregated into a larger dataset, if necessary, for analysis and evidence-gathering, since we adopted the openEHR standard. It will be later extended to include the functionalities of prescribing drugs other than methadone along with the research agenda at the HRB Centre for Primary Care Research in Ireland. PMID:21284849

Relationships of dissociative disorders and personality traits in opium addicts on methadone treatment.

Science.gov (United States)

Ghafarinezhad, Alireza; Rajabizadeh, Ghodratollah; Shahriari, Vahid

2013-01-01

Drug abuse is a major public health problem. Some believe that when dissociation fails to defend against emotional, physical, or sexual trauma, the person will find relief from unpleasant thoughts and emotions in opium use. On the other hand, personality disorders are considered as important predictors of treatment outcomes in drug abusers. Due to lack of adequate research in this regard, we evaluated dissociative disorders and personality traits of opium addicts on methadone treatment. This cross-sectional analytic study included 111 non-psychotic subjects on methadone treatment (case group) and 69 non-addicts (control group). After recording demographic characteristics, Dissociative Experiences Scale (DES) and Millon Multiaxial Inventory III were applied to assess dissociative symptoms and clinical personality patterns of all participants. Dissociative symptoms were significantly more common in the case group than in the control group (P = 0.044). While hysterionic personality disorder was more frequent in the control group (P = 0.008), sadistic, antisocial, and schizotypal personality disorders were significantly more common in the case group (P = 0.008, 0.002, and 0.023, respectively). We found relations between history of drug dependence, dissociative symptoms, and personality disorders. Therefore, the mentioned disorders need to be kept in mind while planning addiction treatment modalities and identifying high risk groups.

Developing an electronic health record (EHR) for methadone treatment recording and decision support

LENUS (Irish Health Repository)

Xiao, Liang

2011-02-01

Abstract Background In this paper, we give an overview of methadone treatment in Ireland and outline the rationale for designing an electronic health record (EHR) with extensibility, interoperability and decision support functionality. Incorporating several international standards, a conceptual model applying a problem orientated approach in a hierarchical structure has been proposed for building the EHR. Methods A set of archetypes has been designed in line with the current best practice and clinical guidelines which guide the information-gathering process. A web-based data entry system has been implemented, incorporating elements of the paper-based prescription form, while at the same time facilitating the decision support function. Results The use of archetypes was found to capture the ever changing requirements in the healthcare domain and externalises them in constrained data structures. The solution is extensible enabling the EHR to cover medicine management in general as per the programme of the HRB Centre for Primary Care Research. Conclusions The data collected via this Irish system can be aggregated into a larger dataset, if necessary, for analysis and evidence-gathering, since we adopted the openEHR standard. It will be later extended to include the functionalities of prescribing drugs other than methadone along with the research agenda at the HRB Centre for Primary Care Research in Ireland.

Comparison of the effect of Olanzapine and Sertraline on patients suffering from personality disorder, receiving methadone maintenance therapy

Directory of Open Access Journals (Sweden)

mozhgan Jariani

2009-03-01

Full Text Available Background: Borderline Personality disorder is a disabling disease affecting 2% of general population. Various drugs have been suggested for treatment of borderline Personality disorder. If a drug could alleviate a wide range of symptoms, it would be more suitable. In these disorders drug addiction is very common. This fact makes the symptoms complicated and the treatment more difficult. This study is designed to evaluate the effect of Olanzapine and Sertraline in patients suffering from personality disorders who are on methadone maintenance therapy. Materials and Methods: This clinical trial study was carried out on 120 male and female cases chosen for methadone maintenance therapy through interview by a psychiatrist based on DSM-IV-TR diagnostic criteria for BPD. Afterwards they were randomly divided into two groups. These groups separately received Olanzapine (5-10 mg daily and Sertraline (50-100 mg daily therapy. The SCL-90 questionnaire was filled out by the participants before treatment and at the 4th, 8th and 12th weeks of the treatment. Results: According to this clinical trial, Olanzapine and Sertraline were effective in ameliorating symptoms of depression, anxiety and aggression, reducing sensitivity in interpersonal relationship and alleviating obsessive symptoms, pessimistic behaviors and somatization disorders in patients with personality disorders on methadone maintenance therapy. Conclusion: As results of this study stated that Olanzapine and Sertraline are definitely effective in alleviating symptoms of patients with personality disorder, prescribing theses drugs are highly recommended for these patients. .

The comparison of Updating function of Working Memory in Three Groups of Substance Abusers (Heroin, Opium, Those Treated with Methadone and normal controls

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Gholamrezayee S

2016-11-01

Full Text Available Introduction: Chronic use of opiates is associated with a wide range of neuropsychological deficits. Therefore, this study aimed to evaluate one of the neuropsychological functions, updating function of working memory, in three groups, including substance abusers (heroin and opium, those under treatment with methadone, and normal controls. Methods:The method of this study was causal-comparative. Ninty individuals in three groups, including substance abusers (n = 30, those under treatment with methadone (n = 30, and normal controls (n = 30 were selected from people referred to the addiction treatment Clinics in Shiraz (2015 with the purposeful sampling method. All subjects were evaluated regarding working memory updating and self-reported mental effort scale and the results were analyzed by Multiple Analysis of Variance (MANOVA test and Tukey post hoc test with SPSS software (version 23. Results:The results showed a significant difference between the three groups in the updating function of working memory; so that effectiveness and efficiency of processing in the normal group was better than the other two groups and the performance effectiveness and efficiency of processing in the group under methadone treatment was better than substance abusers group. conclusions:substance abuse has a negative effect on neurological function. Given that the group of methadone treatment had better performance in the updating function of working memory than the group of substance abusers, these results provide hope that the effects of examined drugs on working memory is not permanent and we can look for psychological interventions to treat these patients and prevent problems recurrence.

Effectiveness of Methadone in Reduction of High Risk Behaviors in Clients of MMT Center

Directory of Open Access Journals (Sweden)

F Ehsani

2010-09-01

Full Text Available Introduction: Addiction as a social, health problem with its specific complications threatens societies. High risk behaviors such as violence, self mutilation, tattooing, shared injections and unprotected sex behaviors are some of the problems in addicts that need to be treated. One of these treatments is methadone therapy. The purpose of this study was to evaluate effectiveness of methadone in prevention or reduction of high risk behaviors in clients of a MMT center of Shaheed Sadoughi University of medical sciences of Yazd. Methods: This study was done on 93 clients of a MMT center.Questionnaire for this study included items from MAP and questions about some other risky behaviors. This questionnaire was completed at onset of treatment and 6 months after. Data was analyzed with SPSS software program Results: 89.2% of participants were married and 10.8% were single. 63.5% of them were in the20-40 years age group. Most commonly abused substances were heroin and opium. Before onset of treatment, 37.6% of participants had history of imprisonment, 35.5% had shared injections, 32.3%had had unprotected sex, 22.6%had tattooing and 5.4%had mutilated their own selves. Only 36.6% didn’t have any high risk behavior. These behaviors were more common in heroin users and in the20-40 years age group. After onset of treatment and during 6 month of MMT, 86% of clients didn’t have any risky behavior. Only 14%of them continued to have unsafe sex behaviors Conclusion: Addiction can cause high risk behaviors. Data in this paper suggests that young age, heroin use, low education level and no or inadequate information about addictive substances and their consequences are effective and important factors that cause high risk behaviors. Treatment of addicts with methadone maintenance therapy plays an important role in reduction of risky behaviors. Development of appropriate and more MMT centers are recommended.

Comparison of the isoflurane concentration of using dexketoprofen or methadone at premedication during orthopedic surgery in dogs.

Science.gov (United States)

Navarrete-Calvo, Rocío; Gutiérrez-Bautista, Álvaro J; Granados, María M; Domínguez, Juan M; Fernández-Sarmiento, J Andrés; Quirós-Carmona, Setefilla; Morgaz, J

2016-04-01

Thirty-two dogs were used in this prospective, randomized, clinical and double-blinded study. Dexmedetomidine was administered at 1 μg/kg IV, and randomly each dog received dexketoprofen 1 mg/kg IV (group DK) or methadone 0.2 mg/kg IV (group M). Dogs were induced with propofol and maintained with isoflurane in 100% oxygen. During surgery, the isoflurane concentration was changed depending on clinical signs of depth of anesthesia. Fentanyl and propofol could be used as required. Qualities of sedation and recovery were evaluated. A generalized linear mixed model or Mann-Whiney U test was used, and Pdexketoprofen at 1 mg/kg IV at premedication required a similar isoflurane concentration to maintain anesthesia as methadone at 0.2 mg/kg IV during orthopedic surgery in dogs. Further analgesia is recommended intraoperatively, because of the need of fentanyl and propofol in same animals in both groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

Psychological and physiological stress negatively impacts early engagement and retention of opioid-dependent individuals on methadone maintenance.

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Jaremko, Kellie M; Sterling, Robert C; Van Bockstaele, Elisabeth J

2015-01-01

The present study investigated whether psychological and/or physiological measures of stress would impede induction onto methadone maintenance and predict early (scale (PSS) and post-traumatic stress disorder checklist (PCLC); 60% exhibited abnormal cortisol. Addiction severity index (ASI), drug-use, and stress indices explained between 17 and 37% of the variance in engagement including attendance, opioid abstinence, and methadone stabilization. Participants who discontinued treatment displayed poor engagement, abnormal cortisol, elevated withdrawal symptoms, higher distress, and increased ongoing opioid use versus compliant individuals. Discontinuation was initially related to drug-use severity; however, by 6 months, retention depended primarily upon cortisol abnormalities, which increased an individual's discontinuation risk by 7.7-fold. These findings support admission screening with the ASI/cortisol for drop out, and stress/drug-use indices for engagement that together may enable clinically-relevant early recognition and interventions for prevention of stress-induced relapse in opioid-dependent populations. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of rate of administration of propofol or alfaxalone on induction dose requirements and occurrence of apnea in dogs.

Science.gov (United States)

Bigby, Sarah E; Beths, Thierry; Bauquier, Sébastien; Carter, Jennifer E

2017-11-01

To evaluate the effect of rate of administration of propofol or alfaxalone on induction dose requirements and incidence of postinduction apnea (PIA) in dogs following premedication with methadone and dexmedetomidine. Prospective, randomized clinical trial. Thirty-two healthy American Society of Anesthesiologists class I client-owned dogs (seven females, 25 males), aged between 5 and 54 months, weighing between 2.0 and 48.2 kg. Dogs were premedicated intramuscularly with 0.5 mg kg -1 methadone and 5 μg kg -1 dexmedetomidine. Thirty minutes after premedication, dogs were preoxygenated for 5 minutes before the induction agent was administered intravenously via a syringe driver until orotracheal intubation was achieved. Dogs were randomized to receive alfaxalone 0.5 mg kg -1  minute -1 (A-Slow), alfaxalone 2 mg kg -1  minute -1 (A-Fast), propofol 1 mg kg -1  minute -1 (P-Slow), or propofol 4 mg kg -1 minute -1 (P-Fast). Oxygen saturation of hemoglobin (SpO 2 ), end-tidal carbon dioxide and respiratory rate were monitored. If PIA (≥30 seconds without a breath) occurred, the time to the first spontaneous breath was measured. If SpO 2 decreased below 90%, the experiment was stopped and manual ventilation initiated. The mean±standard deviation induction doses of alfaxalone and propofol were lower in the A-Slow [A-Slow 0.9±0.3 mg kg -1 , A-Fast 2.2±0.5 mg kg -1 (p≤0.001)] and P-Slow [P-Slow 1.8±0.6 mg kg -1 , P-Fast 4.1±0.7 mg kg -1 (p≤0.001)] groups, respectively. The incidence of PIA was 25% for the A-Slow and P-Slow groups and 100% for the A-Fast and P-Fast groups (p = 0.007). Both propofol and alfaxalone following methadone and dexmedetomidine premedication caused PIA. Induction dose requirement and incidence of PIA were affected by the rate of administration of both drugs. When possible, propofol and alfaxalone doses should be reduced and administered slowly to reduce PIA. Copyright © 2017 Association of Veterinary

Disposition of cefixime in the material-fetal unit after an i.v. dose to pregnant rats

International Nuclear Information System (INIS)

Halperin-Walega, E.; Barr, A.; Tonelli, A.P.; Shin, K.; Batra, V.K.

1986-01-01

Cefixime, a potent, broad spectrum oral cephalosporin, is currently undergoing clinical trials. To determine the extent of transfer of cefixime across the placenta to the fetus, a single dose of 17.8 mg/kg 14 C-cefixime was administered to rats on day 18 of gestation via the caudal vein. Maternal serum and urine, fetal plasma and tissues, and placentae were sampled at appropriate times after dosing. Separate rats were subjected to whole body autoradiography. The half-life for elimination of radioactivity from both maternal serum and placentae was 6.9 hours. Elimination from fetal plasma and tissues was somewhat longer, 12.5 and 13.7 hours, respectively. However, based on a comparison of area under the curve, relative to maternal dose, exposure of the fetuses to cefixime was far less than that of placentae. Peak radioactivity in fetal plasma occurred at 2 hours and was less than 2% of the maternal peak at 0.5 hours after dosing. Whole body autoradiography showed the greatest radioactivity in maternal liver, kidney and intestines. Somewhat less radioactivity appeared in placentae and virtually none could be visualized within the amniotic sac. Overall, the data indicate that exposure of the rat fetus to cefixime after a single maternal dose is limited by the placenta

Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen

DEFF Research Database (Denmark)

Fanoe, Søren; Hvidt, C; Ege, P

2007-01-01

were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 ( 52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed...

A comparison of detomidine in combination with saline, morphine or methadone in horses submitted to experimental oral stimuli

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Rafael Costa Guilhen

2015-12-01

Full Text Available This study aimed to compare the sedative and cardiopulmonary effects of detomidine in combination with saline, morphine or methadone and to determine whether the addition of these opioids increases the degree of sedation in horses submitted to experimental oral stimuli. In a blinded, randomized, experimental study, six adult mares were evaluated using a crossover design with at least 15 days between trials: 10?g/kg detomidine in combination with saline (D/SAL, 0.1mg/kg morphine (D/ MORPH or 0.1mg/kg methadone (D/METH. The degree of sedation, response to oral stimuli and cardiopulmonary parameters were monitored for 120 minutes. Parametric data were analyzed using the ANOVA and Tukey’s tests, and non- parametric data were analyzed with the Kruskal-Wallis and Friedman’s tests with the post-Dunn test (P<0.05. The degree of sedation was significantly greater for the D/SAL than for the D/MORPH and D/METH treatments at 30 min. The horses´ responses to the oral stimuli decreased significantly following all treatments at 5 and 30 min from baseline values. The heart rate, respiratory rate, arterial pH and blood gas variables were all similar among the treatment groups. Mean arterial blood pressure was significantly higher in the D/MORPH group when compared with the D/SAL group between 75 and 120 min. It was concluded that all treatments provided sedative effects with mild cardiopulmonary changes. However the addition of morphine or methadone to detomidine did not improve the degree of sedation in horses submitted to experimental oral stimuli.

Long-term effects of the Focus on Families project on substance use disorders among children of parents in methadone treatment.

Science.gov (United States)

Haggerty, Kevin P; Skinner, Martie; Fleming, Charles B; Gainey, Randy R; Catalano, Richard F

2008-12-01

This study examines the efficacy of the Focus on Families project (currently called Families Facing the Future), a preventive intervention to reduce substance use disorders among children in families with a parent in methadone treatment. One hundred and thirty families were assigned randomly to a methadone clinic treatment-as-usual control condition or treatment-as-usual plus the Focus on Families intervention between 1991 and 1993. Setting Participants were recruited from two methadone clinics in the Pacific Northwest. This study examines the development of substance use disorders among the 177 children (56.84% male) involved in the program using data from a long-term follow-up in 2005, when these participants ranged in age from 15 to 29 years. The intervention was delivered through group parent-training workshops at the methadone clinics and through individualized home-based services. The intervention taught parenting skills and skills for avoiding relapse to drug abuse. At long-term follow-up, substance use disorders were measured by the Composite International Diagnostic Interview (CIDI). Survival analyses were used to assess intervention versus control differences in the hazard of developing substance use disorders. Overall, intervention and control participants did not differ significantly in risk of developing substance use disorders. However, there was evidence of a significant difference in intervention effect by gender. There was a significant reduction in the risk of developing a substance use disorder for intervention group males compared to control group males (hazard ratio = 0.53, P = 0.03), while intervention versus control differences among females were non-significant and favored the control condition. Results from this study suggest that helping parents in recovery focus on both reducing their drug use and improving their parenting skills may have long-term effects on reducing substance use disorders among their male children. However, the overall

Irradiation of the foetus from maternal intakes of plutonium

International Nuclear Information System (INIS)

Adams, N.; Stather, J.W.

1984-01-01

A brief review is given of published animal data on the initial uptake of activity by the foetal and maternal tissues following entry of plutonium into body fluids at various stages during gestation, on the extent to which activity deposited in maternal tissues is subsequently translocated to the foetus and on its distribution in the tissues of the developing foetus. The limited data available from these animal studies do not readily allow the development of a comprehensive human foetal metabolic model but they do suggest a method for estimating radiation doses to the foetus from maternal intakes of plutonium. (U.K.)

Excusing exclusion: Accounting for rule-breaking and sanctions in a Swedish methadone clinic.

Science.gov (United States)

Petersson, Frida J M

2013-11-01

Methadone maintenance treatment has been subjected to much debate and controversy in Sweden during the last decades. Thresholds for getting access are high and control policies strict within the programmes. This article analyses how professionals working in a Swedish methadone clinic discuss and decide on appropriate responses to clients' rule-breaking behaviour. The research data consist of field notes from observations of three interprofessional team meetings where different clients' illicit drug use is discussed. A micro-sociological approach and accounts analysis was applied to the data. During their decision-oriented talk at the meetings, the professionals account for: (1) sanctions, (2) nonsanction, (3) mildness. In accounting for (2) and (3), they also account for clients' rule-breaking behaviour. Analysis shows how these ways of accounting are concerned with locating blame and responsibility for the act in question, as well as with constructing excuses and justifications for the clients and for the professionals themselves. In general, these results demonstrate that maintenance treatment in everyday professional decision-making, far from being a neutral evidence-based practice, involves a substantial amount of professional discretion and moral judgements. Sanctions are chosen according to the way in which a deviance from the rules is explained and, in doing so, a certain behaviour is deemed to be serious, dangerous and unacceptable - or excusable. Copyright © 2013 Elsevier B.V. All rights reserved.

Personality Patterns in Narcotics Anonymous Members versus Individuals with Addiction Receiving Methadone Maintenance Therapy.

Science.gov (United States)

Akhondzadeh, Shahin; Shabrang, Moslem; Rezaei, Omid; Rezaei, Farzin

2014-07-01

Therapeutic interventions can be classified into two distinct approaches: abstinent and maintenance method. Currently, there are no clear criteria for referring addicted patients to one of these modalities. We aimed to compare the personality characteristics of individuals with addiction who attended narcotics anonymous sessions with those who received methadone maintenance therapy. This was a cross- sectional study. The participants were NA members and patients who were undergoing methadone maintenance treatment in outpatient clinics. Using the randomized cluster sampling method, 200 individuals with opioid dependence were selected (each group 100 persons). Data were collected through a demographic questionnaire and the five-factor personality inventory (NEO-FFI). Comparison of the mean scores of NEO-PPI in the two groups was performed by independent t test, and qualitative variables were compared using the Chi-square test. We found a significant difference between the MMT and NA groups with respect to neuroticism, extroversion, and agreeableness. No significant difference was found in the subscales of conscientious and openness. People who regularly attended the NA sessions had lower neuroticism and higher agreeableness than patients who were under the maintenance modality. Whether this is the cause or effect of attending NA sessions requires future large-scale cohort studies.

Personality Patterns in Narcotics Anonymous Members versus Individuals with Addiction Receiving Methadone Maintenance Therapy.

Directory of Open Access Journals (Sweden)

Shahin Akhondzadeh

2014-09-01

Full Text Available Therapeutic interventions can be classified into two distinct approaches: abstinent and maintenance method. Currently, there are no clear criteria for referring addicted patients to one of these modalities. We aimed to compare the personality characteristics of individuals with addiction who attended narcotics anonymous sessions with those who received methadone maintenance therapy.This was a cross- sectional study. The participants were NA members and patients who were undergoing methadone maintenance treatment in outpatient clinics. Using the randomized cluster sampling method, 200 individuals with opioid dependence were selected (each group 100 persons. Data were collected through a demographic questionnaire and the five-factor personality inventory (NEO-FFI. Comparison of the mean scores of NEO-PPI in the two groups was performed by independent t test, and qualitative variables were compared using the Chi-square test.We found a significant difference between the MMT and NA groups with respect to neuroticism, extroversion, and agreeableness. No significant difference was found in the subscales of conscientious and openness.People who regularly attended the NA sessions had lower neuroticism and higher agreeableness than patients who were under the maintenance modality. Whether this is the cause or effect of attending NA sessions requires future large-scale cohort studies.

Elevated Hair Cortisol Levels among Heroin Addicts on Current Methadone Maintenance Compared to Controls.

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Jin Yang

Full Text Available Whether methadone maintenance treatment (MMT can improve the basal function of the hypothalamic-pituitary-adrenal (HPA axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p0.05 when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity.

Behavioral factors predicting response to employment-based reinforcement of cocaine abstinence in methadone patients

OpenAIRE

Holtyn, August F.; Washington, Wendy Donlin; Knealing, Todd W.; Wong, Conrad J.; Kolodner, Ken; Silverman, Kenneth

2016-01-01

We sought to identify behavioral factors associated with response to an employment-based intervention, in which participants had to provide drug-free urine samples to gain access to paid employment. The present secondary analysis included data from a randomized clinical trial. The trial evaluated whether employment-based reinforcement could decrease cocaine use in community methadone patients. Participants (N=56) in the trial worked in a model workplace for 4 hr every weekday and earned about...

Maternal vitamin D status during pregnancy and risk of childhood asthma: A meta-analysis of prospective studies.

Science.gov (United States)

Song, Huihui; Yang, Lei; Jia, Chongqi

2017-05-01

Mounting evidence suggests that maternal vitamin D status during pregnancy may be associated with development of childhood asthma, but the results are still inconsistent. A dose-response meta-analysis was performed to quantitatively summarize evidence on the association of maternal vitamin D status during pregnancy with the risk of childhood asthma. A systematic search was conducted to identify all studies assessing the association of maternal 25-hydroxyvitamin D (25(OH)D) during pregnancy with risk of childhood asthma. The fixed or random-effect model was selected based on the heterogeneity test among studies. Nonlinear dose-response relationship was assessed by restricted cubic spline model. Fifteen prospective studies with 12 758 participants and 1795 cases were included in the meta-analysis. The pooled relative risk of childhood asthma comparing the highest versus lowest category of maternal 25(OH)D levels was 0.87 (95% confidence interval, CI, 0.75-1.02). For dose-response analysis, evidence of a U-shaped relationship was found between maternal 25(OH)D levels and risk of childhood asthma (P nonlinearity = 0.02), with the lowest risk at approximately 70 nmol/L of 25(OH)D. This dose-response meta-analysis suggested a U-shaped relationship between maternal blood 25(OH)D levels and risk of childhood asthma. Further studies are needed to confirm the association. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

Science.gov (United States)

Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin

2012-01-01

The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly…

“Don’t Judge a Book by Its Cover”: A Qualitative Study of Methadone Patients’ Experiences of Stigma

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Julia Woo

2017-02-01

Full Text Available Introduction: Despite its efficacy and widespread use, methadone maintenance treatment (MMT continues to be widely stigmatized. Reducing the stigma surrounding MMT will help improve the accessibility, retention, and treatment outcomes in MMT. Methods: Semi-structured interviews were conducted with 18 adults undergoing MMT. Thematic content analysis was used to identify overarching themes. Results: In total, 78% of participants reported having experienced stigma surrounding MMT. Common stereotypes associated with MMT patients included the following: methadone as a way to get high, incompetence, untrustworthiness, lack of willpower, and heroin junkies. Participants reported that stigma resulted in lower self-esteem; relationship conflicts; reluctance to initiate, access, or continue MMT; and distrust toward the health care system. Public awareness campaigns, education of health care workers, family therapy, and community meetings were cited as potential stigma-reduction strategies. Discussion and Conclusion: Stigma is a widespread and serious issue that adversely affects MMT patients’ quality of life and treatment. More efforts are needed to combat MMT-related stigma.

Cardiorespiratory and electrocardiographic effects of methadone or morphine in the perioperative period in anesthetized dogs with continuous rate infusion of propofol and submitted to ovariohysterectomy

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Priscila Pavini Cintra

2017-03-01

Full Text Available The aims of this study were compare the electrocardiogram (ECG and cardiopulmonary effects of methadone or morphine, both injected intravenously (IV in dogs anesthetized with continuous infusion of propofol. Sixteen healthy female mongrel dogs were used in this study for elective ovariohysterectomy. The animals were allocated in random order into two groups assigned GME (methadone 0.3 mg kg-1, IV or GMO (morphine 0.3 mg kg-1, IV. Parameters were evaluated: heart rate (HR, P-wave amplitude (Ps and PmV, interval between Ps and R waves (PR, QRS duration (QRS, R-wave amplitude (R, duration the interval between the Q and T waves (QT, systolic blood pressure (SBP, rectal temperature (RT, respiratory rate (RR, end tidal of carbon dioxide (ETCO2 and periferic oxyhemoglobin saturation (SpO2. Postoperative analgesia was assessed by mechanical nociceptive stimulus based on the scale proposed by Firth and Haldane (1999 and rescue analgesia based on the visual analogue scale. HR was lower in GME in relation to GMO. The P, PmV, PR, QRS, R and QT values remained within their normality tracks, showing no clinical importance. Apnea and ETCO2 increased in both groups. There was no difference between groups of the analgesic effects. It can be concluded that methadone and morphine promote similar cardiovascular effects after IV injection during surgery in dogs anesthetized with propofol by continuous rate infusion, however, when methadone used, assisted ventilation is required. In addition, both drugs promote postoperative analgesia until six hours.

The Effect of Acepromazine Alone or in Combination with Methadone, Morphine, or Tramadol on Sedation and Selected Cardiopulmonary Variables in Sheep

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Lilian Toshiko Nishimura

2017-01-01

Full Text Available The sedative and selected cardiopulmonary effects of acepromazine alone or in combination with methadone, morphine, or tramadol were compared in sheep. Six ewes were randomly assigned to treatments: A (0.05 mg/kg acepromazine, AM (A plus 0.5 mg/kg methadone, AMO (A plus 0.5 mg/kg morphine, and AT (A plus 5 mg/kg tramadol. Parameters were assessed before sedative drug administration (baseline and every 15 minutes thereafter, for two hours. Treatments A and AM were associated with increases in sedation score for 60 minutes and treatments AMO and AT for 30 minutes; however, there were no significant differences between treatments. There was a decrease in mean arterial pressure compared to baseline values in treatment A at 15, 45, 60, and 90 minutes, in treatment AM at 15 minutes, and in treatment AT from 45 to 120 minutes. Arterial blood carbon dioxide pressure increased at all time points in all treatments. Arterial oxygen pressure decreased in treatment AMO at 15, 30, and 120 minutes and in treatment AT at 15–45, 105, and 120 minutes, compared to baseline. Acepromazine alone causes a level of sedation similar to that observed when it is coadministered with opioids methadone, morphine, and tramadol. These combinations did not cause clinical cardiopulmonary changes.

Combined Norepinephrine / Serotonergic Reuptake Inhibition: Effects on Maternal Behavior, Aggression and Oxytocin in the Rat

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Elizabeth Thomas Cox

2011-06-01

Full Text Available BACKGROUND: Few systematic studies exist on the effects of chronic reuptake of monoamine neurotransmitter systems during pregnancy on the regulation of maternal behavior, although many drugs act primarily through one or more of these systems. Previous studies examining fluoxetine and amfonelic acid treatment during gestation on subsequent maternal behavior in rodents indicated significant alterations in postpartum maternal care, aggression and oxytocin levels. In this study, we extended our studies to include chronic gestational treatment with desipramine or amitriptyline to examine differential effects of reuptake inhibition of norepinephrine and combined noradrenergic and serotonergic systems on maternal behavior, aggression, and oxytocin system changes. METHODS: Pregnant Sprague-Dawley rats were treated throughout gestation with saline or one of three doses of either desipramine, which has a high affinity for the norepinephrine monoamine transporter, or amitriptyline, an agent with high affinity for both the norepinephrine and serotonin monoamine transporters. Maternal behavior and postpartum aggression were assessed on postpartum days one and six respectively. Oxytocin levels were measured in relevant brain regions on postpartum day seven. Predictions were that amitriptyline would decrease maternal behavior and increase aggression relative to desipramine, particularly at higher doses. Amygdaloidal oxytocin was expected to decrease with increased aggression. RESULTS: Amitriptyline and desiprimine differentially reduced maternal behavior, and at higher doses reduced aggressive behavior. Hippocampal oxytocin levels were lower after treatment with either drug but were not correlated with specific behavioral effects. These results, in combination with previous findings following gestational treatment with other selective neurotransmitter reuptake inhibitors, highlight the diverse effects of multiple monoamine systems thought to be involved in

Social and psychological functioning of opiate dependent patients in methadone maintenance treatment – longitudinal research report

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Magdalena Nalaskowska

2014-09-01

Results: After six months of methadone treatment, patients displayed a statistically significant change in sense of coherence. The respondents believed life to be more understandable, predictable and meaningful. A significant increase in the realisation of all developmental tasks was also observed, but not of specific tasks. There were no significant changes in cognitive emotional regulation strategies and intensity of psychopathological symptoms.

Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering : abstinence rates and withdrawal distress experiences

NARCIS (Netherlands)

Krabbe, Paul F M; Koning, Jeroen P F; Heinen, Nadia; Laheij, Robert J F; van Cauter, R M Victory; De Jong, Cor A J

The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the

Rapid detoxification from opioid dependence under general anaesthesia versus standard methadone tapering: abstinence rates and withdrawal distress experiences.

NARCIS (Netherlands)

Krabbe, P.F.M.; Koning, J.P.; Heinen, N.; Laheij, R.J.F.; Cauter, R.M.V. van; Jong, C.A.J. de

2003-01-01

The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anaesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the

Severity of psychiatric and physical problems is associated with lower quality of life in methadone patients in Indonesia

NARCIS (Netherlands)

Iskandar, S.; Crevel, R. van; Hidayat, T.; Siregar, I.M.P.; Achmad, T.H.; Ven, A.J.A.M. van der; Jong, C.A.J. de

2013-01-01

Background and Objectives: The goal of methadone maintenance treatment (MMT) is to reduce the harm and to improve patients' quality of life (Qol). However, the Qol is also influenced by other co-occurring disorders. Data regarding the Qol and the co-occurrence of these disorders is lacking in

Severity of psychiatric and physical problems is associated with lower quality of life in methadone patients in Indonesia

NARCIS (Netherlands)

Iskandar, S.; Crevel, R. van; Hidayat, T.; Siregar, I.M.; Achmad, T.H.; Ven, A.J.A.M. van der; Jong, C.A.J. de

2013-01-01

BACKGROUND AND OBJECTIVES: The goal of methadone maintenance treatment (MMT) is to reduce the harm and to improve patients' quality of life (Qol). However, the Qol is also influenced by other co-occurring disorders. Data regarding the Qol and the co-occurrence of these disorders is lacking in

Fetal doses from plutonium-239 and polonium-210

International Nuclear Information System (INIS)

Harrison, J.D.; Morgan, A.; Stather, J.W.

1992-01-01

The transfer of 239 Pu and 210 Po from the maternal circulation to the developing embryo and fetus was studied in rodents. The highest concentrations of both isotopes were measured in the yolk sac. In utero doses to haemopoietic tissue have been calculated taking account of transfer to the blastocyst/egg cylinder, yolk sac, liver and bone marrow. From animal data, the concentration ratios relative to maternal liver for these tissues were taken to be 0.1, 2, 0.01 and o.02, respectively for 239 Pu; and 1, 2, 0.1 and 0.1, respectively, for 210 Po. These concentration ratios were applied to periods of human gestation of 0-2.5 weeks, 2.5-6 weeks, 6-12 weeks and 12-38 weeks, and used to calculate fetal tissue doses for chronic maternal intake by ingestion of 1 kBq 239 Pu or 2 kBq 210 Po in the year of pregnancy (1 ALI for a member of the public). On this basis, the total in utero dose to haemopoietic tissue was about 1 μSv from 239 Pu and 60 μSv from 210 Po compared with red bone marrow doses to the mother in the year of 19 μSv from 239 Pu and 160 μSv from 210 Po. The yolk sac and bone marrow dominated in utero doses from both nuclides. For 239 Pu, because of its long half life, an important consideration was activity present in the offspring at birth and committed dose equivalents to red bone marrow in the child and mother. The total dose to haemopoietic tissue in the offspring to age 70 years, including in utero doses, was calculated as 13 μSv compared with a maternal dose to red bone marrow of 1400 μSv. For both isotopes the risk of leukaemia in the year of pregnancy was estimated to be of the same order for mother and fetus. For 239 Pu, the overall risk to 70 years of age was two orders of magnitude higher for the mother than her offspring. For 239 Pu, an acute intake of 1 kBq by ingestion during the period of yolk sac haemopoiesis would result in the highest in utero dose, estimated at about 20 μSv. However, activity at birth would be lower and the overall

Methadone Management of Withdrawal Associated With Loperamide-related Opioid Use Disorder.

Science.gov (United States)

Leo, Raphael J; Ghazi, Muhammad A; Jaziri, Kelly S

: Loperamide hydrochloride is an over-the-counter anti-diarrheal agent, acting via mu-opioid receptor agonist effects in the intestinal myenteric plexus. Although preclinical investigations suggested that abuse liability associated with loperamide use is low, there are increasing numbers of cases reported to the US Food and Drug Administration, of abuse, dependence, and withdrawal associated with loperamide use. A case of a patient with opioid use disorder, that is, in the form of protracted loperamide excess use, requiring management of withdrawal with methadone is presented. Management of withdrawal from abrupt loperamide discontinuation has not been discussed in the literature. Long-term treatment issues are also described.

Effectiveness of Relapse Prevention Cognitive-Behavioral Model in Opioid-Dependent Patients Participating in the Methadone Maintenance Treatment in Iran.

Science.gov (United States)

Pashaei, Tahereh; Shojaeizadeh, Davoud; Rahimi Foroushani, Abbas; Ghazitabatabae, Mahmoud; Moeeni, Maryam; Rajati, Fatemeh; M Razzaghi, Emran

2013-08-01

To evaluate the effectiveness of a relapse prevention cognitive-behavioral model, based on Marlatt treatment approach, in Opioid-dependent patients participating in the Methadone Maintenance Treatment (MMT) in Iran. The study consisted of 92 individuals treated with methadone in Iranian National Center of Addiction Studies (INCAS). Participants were randomized into two groups: educational intervention group (N=46) and control group (N=46). The intervention was comprised of 10 weekly 90 minute sessions, done during a period of 2.5 months based on the most high risk situations determined using Inventory Drug Taking Situation instrument. Relapse was defined as not showing up for MMT, drug use for at least 5 continuous days, and a positive urinary morphine test. While, only 36.4% of the intervention group relapsed into drug use, 63.6% of the control group relapsed. The result of the logistic regressions showed that the odd ratio of the variable of intervention program for the entire follow up period was 0.43 (P<0.01). Further, the odd ratio of this variable in one month, three months, and 195 days after the therapy were 0.48 (P<.03), 0.31 (P<.02), and 0.13 (P<.02) respectively that revealed that on average, the probability of relapse among individuals in the intervention group was lower than patients in control group. Relapse prevention model based on Marlatt treatment approach has an effective role in decreasing relapse rate. This model can be introduced as a complementary therapy in patients treated with methadone maintenance.

Alexithymia level and response to computer-based training in cognitive behavioral therapy among cocaine-dependent methadone maintained individuals.

Science.gov (United States)

Morie, Kristen P; Nich, Charla; Hunkele, Karen; Potenza, Marc N; Carroll, Kathleen M

2015-07-01

Alexithymia, a characteristic marked by poor ability to identify, define and communicate emotions, has been associated with poorer treatment outcome, including traditional clinician delivered CBT. Computerized cognitive behavioral therapy (CBT4CBT), an effective adjunct to treatment, may provide a means of conveying skills without requiring interaction with a clinician. Seventy-three methadone maintained, cocaine dependent individuals participating in an 8-week randomized clinical trial comparing standard methadone maintenance to methadone maintenance plus CBT4CBT completed the Toronto Alexithymia Scale (TAS-20) at pretreatment, post-treatment, and follow-ups conducted one, two, and 6 months after treatment. There were no statistically significant differences on baseline TAS-20 scores by multiple demographic and substance use variables including gender and substance use severity. Higher TAS-20 scores were associated with somewhat higher levels of distress as measured by the Beck Depression Inventory and multiple Brief Severity Index scales. TAS-20 scores remained relatively stable throughout the duration of treatment and follow-up. Indicators of treatment process, including treatment retention, adherence and therapeutic alliance, were not significantly correlated with TAS-20 scores. There was a significant interaction of alexithymia and treatment condition, such that individuals with higher baseline scores on the TAS-20 submitted significantly higher percentages of cocaine-negative urine toxicology specimens and reported a higher percentage of abstinence days, and longer periods of consecutive abstinence within treatment when assigned to CBT4CBT compared with treatment as usual. These findings suggest that individuals with increased alexithymia may benefit from computerized CBT; possibly via reduced demands on interpersonal skills and interactions associated with computerized therapies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely hospitalized elderly medical patients

DEFF Research Database (Denmark)

Glintborg, B.; Olsen, L.; Poulsen, H.

2008-01-01

Undisclosed use of illicit drugs and prescription controlled substances is frequent in some settings. The aim of the present study was to estimate the reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely...

The relationship between substance use and posttraumatic stress disorder in a methadone maintenance treatment program.

Science.gov (United States)

Villagonzalo, Kristi-Ann; Dodd, Seetal; Ng, Felicity; Mihaly, Stephen; Langbein, Amy; Berk, Michael

2011-01-01

Posttraumatic stress disorder (PTSD) is frequently linked with substance abuse. The self-medication hypothesis suggests that some people may use illicit substances in an attempt to self-treat psychiatric symptoms. This study explores the relationship between substance abuse and PTSD symptom clusters in a methadone maintenance population. Clients of a methadone maintenance program at a public Drug and Alcohol Service were invited to complete the PTSD Checklist-Civilian Version, a screening tool for PTSD. Information about their history of substance use was also collected. Eighty clients (43 female, 37 male), aged 35 ± 8.0 years (mean ± SD), participated in the study, of which 52.7% screened positive for PTSD. Severity of marijuana use was significantly associated with a number of reexperiencing and hyperarousal symptoms and with overall severity of PTSD symptoms. Opiate, amphetamine, and benzodiazepine use did not appear to be related to PTSD symptoms. In this sample, marijuana may be used to self-treat certain PTSD symptoms, supporting the self-medication hypothesis. Further research is required to confirm the association between a diagnosis of PTSD and substance use. Given the high prevalence of PTSD in the substance-using population, routine PTSD screening in the substance abuse treatment setting may be justified. Copyright © 2011 Elsevier Inc. All rights reserved.

Different patterns of sexual dysfunctions associated with psychiatric disorders and psychopharmacological treatment. Results of an investigation by semistructured interview of schizophrenic and neurotic patients and methadone-substituted opiate addicts.

Science.gov (United States)

Teusch, L; Scherbaum, N; Böhme, H; Bender, S; Eschmann-Mehl, G; Gastpar, M

1995-05-01

Little is known about sexual dysfunctions associated with psychiatric disorders and psychopharmacological treatment. In the present study schizophrenic patients (n = 45, mostly under neuroleptic treatment), neurotic patients (n = 50, mostly treated without medication), methadone-substituted opiate addicts (n = 37), and normal controls (n = 41) were included. They were interviewed with the aid of a sex-differentiated semistructured questionnaire on sexual function. All the methadone-substituted opiate addicts and nearly all the schizophrenic patients suffered from dysfunctions in at least one criterion. The three clinical groups differed significantly from the controls in sexual interest, emotional arousal, physiological arousal (erectile function/vaginal lubrication), performance (ejaculatory function/vaginism, dyspareunia), and orgasm satisfaction. Characteristic patterns of dysfunction were found in the male patients. The schizophrenic patients had significantly more dysfunctions of interest, physiological arousal, performance, and orgasm than the controls. Emotional arousal, erectile and ejaculatory functions, and orgasm satisfaction were impaired more frequently in the male schizophrenics than in the neurotic patients. Reduced sexual interest, emotional arousal, and orgasm satisfaction were reported more frequently by the methadone-substituted opiate addicts than by the neurotic men. Emotional arousal was even more frequently reduced than in the schizophrenic men. There was no correlation between sexual dysfunction and particular neuroleptics or neuroleptic or methadone dosage. The results are compared with the literature and suggestions made for further investigations.

Naloxone-induced electrographic seizures in the primate.

Science.gov (United States)

Snyder, E W; Shearer, D E; Beck, E C; Dustmann, R E

1980-01-01

Electrographic seizure activity was recorded shortly following naxolone injections in artificially ventilated, methadone-treated stump-tailed macaques. Plasma-methadone concentrations prior to seizure activity were many times higher than those that have produced respiratory depression and death in nonventilated monkeys. The duration of seizure activity was clearly related to the dose of naloxone. Naloxone was without epileptogenic properties in animals that had not been pretreated with methadone. The results suggest that methadone and naloxone have additive epileptogenic properties when high blood levels of methadone are achieved in the artificially ventilated primate. Naloxone was devoid of antagonistic properties with respect to opiate-induced electroencephalographic spiking activity.

Cost-effectiveness of methadone maintenance therapy as HIV prevention in an Indonesian high-prevalence setting: a mathematical modeling study

NARCIS (Netherlands)

Wammes, J.J.G.; Siregar, A.Y.M.; Hidayat, T.; Raya, R.P.; van Crevel, R.; Ven, A.J.A.M. van der; Baltussen, R.M.

2012-01-01

BACKGROUND: Indonesia faces an HIV epidemic that is in rapid transition. Injecting drug users (IDUs) are among the most heavily affected risk populations, with estimated prevalence of HIV reaching 50% or more in most parts of the country. Although Indonesia started opening methadone clinics in 2003,

Psychiatric comorbidity and additional abuse of drugs in maintenance treatment with L- and D,L-methadone.

Science.gov (United States)

Wedekind, Dirk; Jacobs, Stefan; Karg, Iris; Luedecke, Christel; Schneider, Udo; Cimander, Konrad; Baumann, Pierre; Ruether, Eckart; Poser, Wolfgang; Havemann-Reinecke, Ursula

2010-03-01

Sixty D,L- or L-methadone treated patients in maintenance therapy were interviewed for additional drug abuse and psychiatric comorbidity; 51.7% of the entire population had a comorbid Axis-I disorder, with a higher prevalence in females (P=0.05). Comorbid patients tended to have higher abuse of benzodiazepines, alcohol, cannabis, and cocaine, but not of heroin. They had received a significantly lower D,L- (Pabuse.

Contribution of maternal radionuclide burdens to prenatal radiation doses

International Nuclear Information System (INIS)

Sikov, M.R.; Hui, T.E.

1996-05-01

This report describes approaches to calculating and expressing radiation doses to the embryo/fetus from internal radionuclides. Information was obtained for selected, occupationally significant radioelements that provide a spectrum of metabolic and dosimetric characteristics. Evaluations are also presented for inhaled inert gases and for selected radiopharmaceuticals. Fractional placental transfer and/or ratios of concentration in the embryo/fetus to that in the woman were calculated for these materials. The ratios were integrated with data from biokinetic transfer models to estimate radioactivity levels in the embryo/fetus as a function of stage of pregnancy and time after entry into the transfer compartment or blood of the pregnant woman. These results are given as tables of deposition and retention in the embryo/fetus as a function of gestational age at exposure and elapsed time following exposure. Methodologies described by MIRD were extended to formalize and describe details for calculating radiation absorbed doses to the embryo/fetus. Calculations were performed using a model situation that assumed a single injection of 1 μCi into a woman's blood; independent calculations were performed for administration at successive months of pregnancy. Gestational -stage-dependent dosimetric tabulations are given together with tables of correlations and relationships. Generalized surrogate dose factors and categorizations are provided in the report to provide for use in operational radiological protection situations. These approaches to calculation yield radiation absorbed doses that can be converted to dose equivalent by multiplication by quality factor. Dose equivalent is the most common quantity for stating prenatal dose limits in the United States and is appropriate for the types of effect that are usually associated with prenatal exposure. If it is desired to obtain alternatives for other purposes, this value can be multiplied by appropriate weighting factors

Contribution of maternal radionuclide burdens to prenatal radiation doses

Energy Technology Data Exchange (ETDEWEB)

Sikov, M.R.; Hui, T.E.

1996-05-01

This report describes approaches to calculating and expressing radiation doses to the embryo/fetus from internal radionuclides. Information was obtained for selected, occupationally significant radioelements that provide a spectrum of metabolic and dosimetric characteristics. Evaluations are also presented for inhaled inert gases and for selected radiopharmaceuticals. Fractional placental transfer and/or ratios of concentration in the embryo/fetus to that in the woman were calculated for these materials. The ratios were integrated with data from biokinetic transfer models to estimate radioactivity levels in the embryo/fetus as a function of stage of pregnancy and time after entry into the transfer compartment or blood of the pregnant woman. These results are given as tables of deposition and retention in the embryo/fetus as a function of gestational age at exposure and elapsed time following exposure. Methodologies described by MIRD were extended to formalize and describe details for calculating radiation absorbed doses to the embryo/fetus. Calculations were performed using a model situation that assumed a single injection of 1 {mu}Ci into a woman`s blood; independent calculations were performed for administration at successive months of pregnancy. Gestational -stage-dependent dosimetric tabulations are given together with tables of correlations and relationships. Generalized surrogate dose factors and categorizations are provided in the report to provide for use in operational radiological protection situations. These approaches to calculation yield radiation absorbed doses that can be converted to dose equivalent by multiplication by quality factor. Dose equivalent is the most common quantity for stating prenatal dose limits in the United States and is appropriate for the types of effect that are usually associated with prenatal exposure. If it is desired to obtain alternatives for other purposes, this value can be multiplied by appropriate weighting factors.

Usefulness of the Brief Pain Inventory in Patients with Opioid Addiction Receiving Methadone Maintenance Treatment.

Science.gov (United States)

Dennis, Brittany B; Roshanov, Pavel S; Bawor, Monica; Paul, James; Varenbut, Michael; Daiter, Jeff; Plater, Carolyn; Pare, Guillame; Marsh, David C; Worster, Andrew; Desai, Dipika; Thabane, Lehana; Samaan, Zainab

2016-01-01

Chronic pain is implicated as a risk factor for illicit opioid use among patients with opioid addiction treated with methadone. However, there exists conflicting evidence that supports and refutes this claim. These discrepancies may stem from the large variability in pain measurement reported across studies. We aim to determine the clinical and demographic characteristics of patients reporting pain and evaluate the prognostic value of different pain classification measures in a sample of opioid addiction patients. Multi-center prospective cohort study. Methadone maintenance treatment facilities for managing patients with opioid addiction. This study includes participants from the Genetics of Opioid Addiction (GENOA) prospective cohort study. We assessed the prognostic value of different pain measures for predicting opioid relapse. Pain measures include the Brief Pain Inventory (BPI) and patients' response to a direct pain question all study participants were asked from the GENOA case report form (CRF) "are you currently experiencing or have been diagnosed with chronic pain?" Performance characteristics of the GENOA CRF pain measure was estimated with sensitivity and specificity using the BPI as the gold standard reference. Prognostic value was assessed using pain classification as the primary independent variable in an adjusted analysis using 1) the percentage of positive opioid urine screens and 2) high-risk opioid use (= 50% positive opioid urine screens) as the dependent variables in a linear and logistic regression analyses, respectively. Among participants eligible for inclusion (n = 444) the BPI was found to be highly sensitive, classifying a large number of GENOA participants with pain (n = 281 of the 297 classified with pain, 94.6%) in comparison to the GENOA CRF (n = 154 of 297 classified with pain, 51.8%). Participants concordantly classified as having pain according to the GENOA CRF and BPI were found to have an estimated 7.79% increase in positive

Attendance Rates in a Workplace Predict Subsequent Outcome of Employment-Based Reinforcement of Cocaine Abstinence in Methadone Patients

Science.gov (United States)

Donlin, Wendy D.; Knealing, Todd W.; Needham, Mick; Wong, Conrad J.; Silverman, Kenneth

2008-01-01

This study assessed whether attendance rates in a workplace predicted subsequent outcome of employment-based reinforcement of cocaine abstinence. Unemployed adults in Baltimore methadone programs who used cocaine (N = 111) could work in a workplace for 4 hr every weekday and earn $10.00 per hour in vouchers for 26 weeks. During an induction…

Matching of treatment-resistant heroin-dependent patients to medical prescription of heroin or oral methadone treatment: results from two randomized controlled trials

NARCIS (Netherlands)

Blanken, Peter; Hendriks, Vincent M.; Koeter, Maarten W. J.; van Ree, Jan M.; van den Brink, Wim

2005-01-01

AIMS: To investigate which baseline patient characteristics of treatment-resistant heroin addicts differentially predicted treatment response to medical heroin prescription compared to standard methadone maintenance treatment. DESIGN: Two open-label randomized controlled trials; pooled data.

Maternal peanut exposure during pregnancy and lactation reduces peanut allergy risk in offspring.

Science.gov (United States)

López-Expósito, Iván; Song, Ying; Järvinen, Kirsi M; Srivastava, Kamal; Li, Xiu-Min

2009-11-01

Maternal allergy is believed to be a risk factor for peanut allergy (PNA) in children. However, there is no direct evidence of maternal transmission of PNA susceptibility, and it is unknown whether maternal peanut exposure affects the development of PNA in offspring. To investigate the influence of maternal PNA on offspring reactions to the first peanut exposure, and whether maternal low-dose peanut exposure during pregnancy and lactation influences these reactions and peanut sensitization in a murine model. Five-week-old offspring of PNA C3H/HeJ mothers (PNA-Ms) were challenged intragastrically with peanut (first exposure), and reactions were determined. In a subset of the experiment, PNA-Ms were fed a low dose of peanut (PNA-M/PN) or not fed peanut (PNA-M/none) during pregnancy and lactation. Their 5-week-old offspring were challenged intragastrically with peanut, and reactions were determined. In another subset of the experiment, offspring of PNA-M/PN or PNA-M/none were sensitized with peanut intragastrically for 6 weeks, and serum peanut-specific antibodies were determined. PNA-M offspring exhibited anaphylactic reactions at first exposure to peanut that were associated with peanut-specific IgG(1) levels and prevented by a platelet activation factor antagonist. In a subset experiment, PNA-M/PN offspring showed significantly reduced first-exposure peanut reactions, increased IgG(2a), and reduced mitogen-stimulated splenocyte cytokine production compared with PNA-M/none offspring. In an additional experiment, PNA-M/PN offspring showed reduction of peanut-specific IgE to active peanut sensitization. We show for the first time maternal transmission of susceptibility to first-exposure peanut reactions and active peanut sensitization. Low-dose peanut exposure during pregnancy and lactation reduced this risk.

Successful Treatment of Opioid-Refractory Cancer Pain with Short-Course, Low-Dose Ketamine.

Science.gov (United States)

Waldfogel, Julie M; Nesbit, Suzanne; Cohen, Steven P; Dy, Sydney M

2016-12-01

Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA). After treatment with short-course, low-dose ketamine, his opioid requirements decreased by 99% and pain ratings by 50%, with the majority of this decrease occurring in the first 48 hours. As this patient's pain and opioid regimen escalated, he likely experienced some component of central sensitization and hyperalgesia. Administration of ketamine reduced opioid consumption by 99% and potentially "reset" neuronal hyperexcitability and reduced pain signaling, allowing for improved pain control.

Survey of relationship between spiritual health and mental health in patients undergoing methadone maintenance treatment (MMT

Directory of Open Access Journals (Sweden)

abolhassan naghibi

2015-12-01

Full Text Available Introduction and goal: Religiosity and spirituality decreasesof the impact of life stress on the tendency to substance use. Everyday addedto the number of people who believe that spirituality is the way to treat neuroses and mental problems. This study aimed to determine the relationship between spiritual health and mental health in patients undergoing to methadone maintenance treatment (MMT dependent on the private and government sector in Sari. Method: This study was cross- sectional study. The target populations of this study were 123 women and men undergoing to methadone maintenance treatment (MMT. The data collected by spiritual and mental health questionnaire and were analyzed using two-sample t-test and spearman correlationin theSPSS (18 software. Findings: The grade average of spiritual health was 43/29 and mental health was 41/26.The results showed that a significant correlation between spiritual health with mental health. The highest correlation was between spiritual healthwith the social function and the lowestcorrelation was with physical problems. There was no significant relationshipbetween of marital status, number of children, sex and spiritual health. Conclusion: According to positive and significant role spiritual health in mental health, so, strengthen the spiritual dimension can to promote mental health and reduce mental disorders and the tendency to addiction.

Mother-child interaction and cognitive development in children prenatally exposed to methadone or buprenorphine.

Science.gov (United States)

Konijnenberg, Carolien; Sarfi, Monica; Melinder, Annika

2016-10-01

To assess the influence of mother-child interaction on children's cognitive development in a group of children prenatally exposed to methadone or buprenorphine. The study is part of a prospective longitudinal project investigating the development of children born to women in opioid maintenance therapy (OMT). The sample includes 67 children born between 2005 and 2007, 35 of which prenatally exposed to either methadone or buprenorphine and 32 non-exposed comparison children. Both groups scored within the normal range of development. However, the OMT group scored significantly lower on measures of cognitive development and mother-child interaction compared to the comparison group. Cognitive development was found to be affected by both group status, F(1,54)=5.65, p=0.02, η(2)=0.10 and mother-child interaction F(1,54)=5.26, p=0.03, η(2)=0.09. Behavioral inhibition (statue), sensorimotor function (imitating hand positions), and short-term memory (sentences) was influenced by group status while narrative memory and vocabulary were found to be more influenced by mother-child interaction. Different risk factors may influence different cognitive functions in children of women in OMT. Specifically, language-related cognitive skills may be more related to mother-child interaction while performance in higher cognitive functions requiring precise control over sensorimotor responses may be more sensitive to other factors such as prenatal OMT exposure, genetics, and/or prenatal exposure to other substances. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Current situation on new psychoactive substances abuse among methadone maintenance treatment patients in China].

Science.gov (United States)

Cheng, Z; Dai, M M; Cao, X B

2018-04-10

Methadone maintenance treatment (MMT) greatly contributed to the successful outcomes of prevention and control on both AIDS and drug abuse in China. However, the features on drug abuse changed in the past decades, and the prevalence of new psychoactive substances abuse potentially somehow offset the achievement of MMT. This paper concised the information on research and surveys of this issue that targeting on the current situation, characteristics, related factors and relevant public health problem on new psychoactive substances abuse, among patients who have been on MMT, in China.

Comparison of progress of patients with professional and paraprofessional counselors in a methadone maintenance program.

Science.gov (United States)

Connett, G E

1980-05-01

The progress of two groups of patients on methadone maintenance were compared by examining urine results for use or nonuse of illicit drugs, attaiment of a drug-free status, employment, continuous time in treatment, and take-out-clinic (TOC) medication (an assessment of a patient's overall progress as determined by the treatment team). Four paraprofessional counselors with an average education level of 12.7 years followed Group A patients (CGA) while five master's degree trained counselors followed Group B patients (CGB) (Table 1).

'Crisis' and 'everyday' initiators: A qualitative study of coercion and agency in the context of methadone maintenance treatment initiation.

Science.gov (United States)

Damon, Will; Small, Will; Anderson, Solanna; Maher, Lisa; Wood, Evan; Kerr, Thomas; McNeil, Ryan

2017-03-01

Patient attrition is common among people enrolled in methadone maintenance treatment (MMT) programs and most pronounced during the first year of treatment. However, the experiences of patients initiating MMT have been overlooked in the literature. This study explores experiences of MMT initiation among MMT patients, focusing on contextual influences on MMT initiation and perceptions of MMT and their subsequent influence on treatment retention. Semi-structured qualitative interviews were conducted with 39 MMT patients in Vancouver, Canada. Individuals reporting enrolment in MMT were recruited from within two ongoing cohort studies comprised of people who use drugs. Interview transcripts were analysed using an inductive and iterative approach. Two groups of MMT initiators were identified: (i) 'crisis initiators' prescribed methadone following critical transition events, such as incarceration or pregnancy; and (ii) 'everyday initiators' enrolled in MMT as part of routine healthcare utilisation. While most 'crisis initiators' and some 'everyday initiators' described experiencing coercion during MMT initiation, 'crisis initiators' were further subjected to the coercive leveraging of their vulnerability to motivate 'consent' for MMT. 'Crisis initiators' developed negative views towards MMT and were more likely to discontinue treatment. Long-standing patient-provider relationships and open dialogue were associated with more positive views regarding MMT, regardless of the circumstances of initiation. Findings underscore the need for clear and effective communication regarding treatment regimens and expectations during MMT initiation. Furthermore, training in trauma-informed care may help reduce perceptions of coercion and rates of early treatment termination. [Damon W, Small W, Anderson S, Maher L, Wood E, Kerr T, McNeil R. Crisis' and 'everyday' initiators: A qualitative study of coercion and agency in the context of methadone maintenance treatment initiation. Drug

Maternal propensity for infections and risk of childhood asthma

DEFF Research Database (Denmark)

Stokholm, Jakob; Sevelsted, Astrid; Bønnelykke, Klaus

2014-01-01

between maternal use of antibiotics and the risk of childhood asthma. METHODS: According to national registries, during the observation period (1997-2010), 910,301 children were born in Denmark and were included in the analysis. From these registries, data for cases of childhood asthma were obtained based...... that maternal use of antibiotics in pregnancy was associated with an increased risk of childhood asthma: the adjusted incidence rate ratio (aIRR) was 1·24 (95% CI 1·18-1·30) for inpatient admission, 1·22 (1·18-1·26) for outpatient attendance, and 1·18 (1·15-1·20) for inhaled corticosteroid use. A similar...... and independent association was also recorded for maternal antibiotic use in the 80 weeks before and after the pregnancy. A dose-related association occurred between the risk of childhood asthma and the number of maternal antibiotic treatments and was recorded separately for antibiotic treatment for respiratory...

Comparison of alexithymia scale and stress coping strategies in patients with methadone and addicts without treatment programs

Directory of Open Access Journals (Sweden)

Mehdi Madanifard

2017-08-01

Conclusion: The results showed that patients with methadone and addiction without treatment programs in the variables of alexithymia and coping strategies are flawed. However, the group was treated through the use of psychological and physical treatment and return relative to health conditions has fewer problems compared to untreated addicted individuals. In addition to the prescription drug treatment programs in these people who pay more attention to psychological interventions are proposed.

Physical compatibility of binary and ternary mixtures of morphine and methadone with other drugs for parenteral administration in palliative care.

Science.gov (United States)

Destro, Massimo; Ottolini, Luca; Vicentini, Lorenza; Boschetti, Silvia

2012-10-01

The parenteral administration of combinations of drugs is often necessary in palliative medicine, particularly in the terminal stage of life, when patients are no longer able to take medication orally. The use of infusers to administer continuous subcutaneous infusions is a well-established practice in the palliative care setting and enables several drugs to be given simultaneously, avoiding the need for repeated administrations and the effects of peaks and troughs in the doses of medication. The method is also appreciated by patients and caregivers in the home care setting because the devices and infusion sites are easy to manage. Despite their frequent use, however, the mixtures of drugs adopted in clinical practice are sometimes not supported by reliable data concerning their chemical and physical compatibility. The present study investigates the chemical compatibility of binary mixtures (morphine with ketorolac) and the physical compatibility of binary (morphine or methadone with ketorolac) or ternary mixtures (morphine with ketorolac and/or haloperidol, and/or dexamethasone, and/or metoclopramide, and/or hyoscine butylbromide) with a view to reducing the aleatory nature of the empirical use of such combinations, thereby increasing their safety and clinical appropriateness.

A randomized controlled trial of the therapeutic workplace for community methadone patients: a partial failure to engage.

Science.gov (United States)

Knealing, Todd W; Wong, Conrad J; Diemer, Karly N; Hampton, Jacqueline; Silverman, Kenneth

2006-08-01

The Therapeutic Workplace is an employment-based treatment for drug addiction that uses wages for work to reinforce drug abstinence. The Therapeutic Workplace has promoted abstinence from heroin and cocaine in treatment-resistant mothers in methadone treatment. This study attempted to replicate that effect in crack cocaine users recruited from community-based methadone programs. Participants were randomly assigned to a Therapeutic Workplace (n=22) or usual care control (n=25) group. Therapeutic Workplace participants were invited to work in the workplace and earn vouchers every weekday for 9 months contingent on documented opiate and cocaine abstinence. The two groups did not differ significantly on measures of cocaine or opiate use collected during study participation. Daily attendance and urinalysis results of the Therapeutic Workplace group were analyzed, and only 7 of the 22 participants initiated consistent periods of abstinence and workplace attendance. Two individuals gained access to the workplace on a few days, and 9 participants attempted to gain access to the workplace but never provided a drug-negative urine sample. Possible reasons for differences between the current study and the previous Therapeutic Workplace study are considered. Procedures that increase participant contact with the Therapeutic Workplace and its reinforcement contingencies might increase the likelihood of these individuals being successful in the treatment program.

Methadone-maintained patients in primary care have higher rates of chronic disease and multimorbidity, and use health services more intensively than matched controls

LENUS (Irish Health Repository)

O’Toole, John

2014-05-01

Background: Methadone maintenance treatment in primary care is cost-effective and improves outcomes for opiate-dependent patients. A more developed understanding of the evolving needs of this important cohort will facilitate further improvements in their integrated care within the community.\\r\

Maternal smoking during pregnancy and rapid weight gain from birth to early infancy

Directory of Open Access Journals (Sweden)

Tomosa Mine

2017-04-01

Full Text Available Background: Although several studies have focused on the association between maternal smoking during pregnancy and rapid weight gain (RWG during infancy, the dose-response relationship has not yet been confirmed, and very few studies have included Asian populations. Using a record-linkage method, we examined the association between maternal smoking during pregnancy and RWG in infants at around 4 months of age to clarify the dose-response relationship. Methods: Two databases were used: maternal check-ups during pregnancy and early infancy check-ups (between April 1, 2013 and March 31, 2014 in Okinawa, Japan were linked via IDs and provided to us after unlinkable anonymizing. For 10,433 subjects (5229 boys and 5204 girls, we calculated the change in infants' weight z-score by subtracting the z-score of their birth weight from their weight at early infancy check-ups. Smoking exposure was categorized into five groups. We used Poisson regression to examine the association of maternal smoking during pregnancy with RWG in early infancy. Results: Overall, 1524 (14.6% were ex-smoker and 511 (4.9% were current smoker. Compared with the reference category of non-smokers, the adjusted risk ratio of RWG was 1.18 (95% confidence interval [CI], 1.06–1.32 for ex-smokers, 1.18 (95% CI, 0.93–1.50 for those who smoked 1–5 cigarettes per day, 1.57 (95% CI, 1.24–2.00 for those who smoked 6–10 cigarettes per day, and 2.13 (95% CI, 1.51–3.01 for those who smoked ≥11 cigarettes per day. There was a clear dose-response relationship. Conclusion: Our study suggests that maternal smoking during pregnancy is associated in a dosedependent manner with increased risk of RWG in early infancy.

Methadone-maintenance outcomes for Hispanic and African-American men and women.

Science.gov (United States)

Mulvaney, F D; Brown, L S; Alterman, A I; Sage, R E; Cnaan, A; Cacciola, J; Rutherford, M

1999-03-01

Six-month methadone-maintenance response and outcome were examined for African-American and Hispanic men and women in a large urban sample. A consistent pattern of improvement was indicated for both races and genders on the addiction severity index (ASI). There were virtually no statistically significant differences in ASI outcomes between Hispanics and African-Americans and men and women using conventional analysis of variance (ANOVA) procedures. Results from an additional equivalence analysis, however, indicated that baseline to 6-month changes for the different groups were generally not similar enough to consider them equivalent. Urine toxicologies obtained during the 6-month treatment period were also not statistically equivalent by race and gender. Evaluating outcomes by gender and race are discussed, as are the implications of using equivalence tests when examining group differences.

Design and implementation of a factorial randomized controlled trial of methadone maintenance therapy and an evidence-based behavioral intervention for incarcerated people living with HIV and opioid dependence in Malaysia.

Science.gov (United States)

Bazazi, Alexander R; Wickersham, Jeffrey A; Wegman, Martin P; Culbert, Gabriel J; Pillai, Veena; Shrestha, Roman; Al-Darraji, Haider; Copenhaver, Michael M; Kamarulzaman, Adeeba; Altice, Frederick L

2017-08-01

Incarcerated people living with HIV and opioid dependence face enormous challenges to accessing evidence-based treatment during incarceration and after release into the community, placing them at risk of poor HIV treatment outcomes, relapse to opioid use and accompanying HIV transmission risk behaviors. Here we describe in detail the design and implementation of Project Harapan, a prospective clinical trial conducted among people living with HIV and opioid dependence who transitioned from prison to the community in Malaysia from 2010 to 2014. This trial involved 2 interventions: within-prison initiation of methadone maintenance therapy and an evidence-based behavioral intervention adapted to the Malaysian context (the Holistic Health Recovery Program for Malaysia, HHRP-M). Individuals were recruited and received the interventions while incarcerated and were followed for 12months after release to assess post-release HIV transmission risk behaviors and a range of other health-related outcomes. Project Harapan was designed as a fully randomized 2×2 factorial trial where individuals would be allocated in equal proportions to methadone maintenance therapy and HHRP-M, methadone maintenance therapy alone, HHRP-M alone, or control. Partway through study implementation, allocation to methadone maintenance therapy was changed from randomization to participant choice; randomization to HHRP-M continued throughout. We describe the justification for this study; the development and implementation of these interventions; changes to the protocol; and screening, enrollment, treatment receipt, and retention of study participants. Logistical, ethical, and analytic issues associated with the implementation of this study are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Non-attendance at counselling therapy in cocaine-using methadone-maintained patients: lessons learnt from an abandoned randomised controlled trial.

LENUS (Irish Health Repository)

Darker, C

2012-12-01

Recently, the authors commenced a randomised controlled trial to study the effectiveness of cognitive behavioural coping skills (CBCS) to reduce cocaine usage in methadone-maintained patients\\' in a clinical setting by assessing attendance at treatment sessions and outcomes in terms of cocaine use. However, recruitment into the study stopped when it became apparent that attendance at counselling sessions was poor.

Matrix Model for Methamphetamine Dependence Among Iranian Female Methadone Patients: The First Report From the Most Populated Persian Gulf Country

Directory of Open Access Journals (Sweden)

Omid Massah

2017-09-01

Discussion: The results indicated that the Matrix Model is effective for treating MA dependence. However, the long length of the treatment, lack of cost-effectiveness, and intensive staff training are significant problems associated with providing MA treatment. Further studies are suggested to evaluate the role of brief interventions in reducing these problems in methadone treatment services.

The Comparison of the Effectiveness of Group Cognitive-Behavior Therapy and Methadone Maintenance Therapy on Changing Beliefs Related to Substance and Relapse Prevention

Directory of Open Access Journals (Sweden)

Taherh Ghorbani

2012-08-01

Full Text Available Introduction: This study was aimed to compare of the effectiveness of group cognitive-behavioral therapy and methadone maintenance therapy on changing beliefs toward substance abuse among addicted people. Method: The research method was a quasi-experimental pretest-posttest with witness group. 30 addicted people who were referred to the addiction treatment centers selected by available sampling, and they randomly assigned to three groups namely: cognitive-behavioral therapy, methadone maintenance therapy and witness groups. Substance abuse beliefs questionnaire was administered among all participants before and after intervention. Results: Results showed that in both experimental groups, beliefs toward drug was reduced significantly in comparison with witness group. Conclusion: Cognitive-behavioral therapy can be changed on cognitive mediator variables, like beliefs toward substance therefore, it can reduce the risk of relapse. However, the programs of treatment of substance abuse should be targeted this type of intermediate variables.

The efficacy of methadone maintenance interventions in reducing illicit opiate use, HIV risk behavior and criminality: a meta-analysis.

Science.gov (United States)

Marsch, L A

1998-04-01

To provide empirically based evaluation data regarding the efficacy of psychopharmacological interventions in opiate substance abuse, the present study employed meta-analytic statistical procedures to determine the effectiveness of methadone hydrochloride as a pharmacotherapeutic agent. Empirical research findings from 11 studies investigating the effect of methadone maintenance treatment (MMT) on illicit opiate use, and eight and 24 studies investigating the effect of MMT on HIV risk behaviors and criminal activities, respectively, by individuals in such treatment were addressed. Results demonstrate a consistent, statistically significant relationship between MMT and the reduction of illicit opiate use, HIV risk behaviors and drug and property-related criminal behaviors. The effectiveness of MMT is most apparent in its ability to reduce drug-related criminal behaviors. MMT had a moderate effect in reducing illicit opiate use and drug and property-related criminal behaviors, and a small to moderate effect in reducing HIV risk behaviors. Results clarify discrepancies in the literature and are useful in predicting the outcomes of individuals in treatment. The treatment's effectiveness is evident among opiate-dependent individuals across a variety of contexts, cultural and ethnic groups, and study designs.

Severe fetal and neonatal hyperthyroidism years after surgical treatment of maternal Graves' disease.

Science.gov (United States)

Dierickx, I; Decallonne, B; Billen, J; Vanhole, C; Lewi, L; De Catte, L; Verhaeghe, J

2014-02-01

Fetal/neonatal hyperthyroidism is a well-known complication of maternal Graves' disease with high concentrations of TSH-receptor antibodies (TRAb). Few data are available on the management of fetal hyperthyroidism in surgically treated Graves' disease. Clinical, ultrasound and biochemical data are reported in a fetus/neonate whose mother underwent a thyroidectomy > 10 years before and whose sibling was thin and hyperthyroid at birth. Maternal TRAb were persistently > 40 U/l; unequivocal signs of fetal hyperthyroidism were identified at 29 weeks gestational age (GA). The fetus was treated through maternal antithyroid drug (ATD) administration; the dose was reduced gradually once fetal tachycardia and valve dysfunction disappeared and normal T4 was confirmed by fetal blood sampling. Maternal euthyroidism was maintained. The neonate showed normal growth for GA and T4 concentration at birth but severe hyperthyroidism relapsed from day 13 until day 58. TSH remained strongly suppressed throughout the pre- and postnatal course. Prenatal ATD in a taper-off regime allowed normal T4 and growth in a hyperthyroid fetus from a thyroidectomised Graves' mother. Fetal TSH cannot be used to adjust the ATD dose. Prenatal ATD appears to postpone the onset but does not affect the severity or duration of the neonatal hyperthyroid flare.

Infant doses from the transfer of radionuclides in mothers' milk

International Nuclear Information System (INIS)

Harrison, J.D.; Smith, T.J.; Phipps, A.W.

2003-01-01

Assessments of potential internal exposures of the child following radionuclide intakes by the mother require consideration of transfers during lactation as well as during pregnancy. Current ICRP work on internal dosimetry includes the estimation of radiation doses to newborn infants from radionuclides ingested in mothers' milk. Infant doses will be calculated for maternal intakes by ingestion or inhalation of the radionuclides, radioisotopes of 31 elements, for which fetal dose coefficients have been published. In this paper, modelling approaches are examined, concentrating on models developed for iodine, caesium, polonium, alkaline earth elements and the actinides. Comparisons of model predictions show maximum overall transfer to milk following maternal ingestion during lactation of about 30% of ingested activity for 131 I, 20% for 45 Ca and 137 Cs, 10% for 90 Sr, 1% for 210 Po and low values of less than 0.01% for 239 Pu and 241 Am. The corresponding infant doses from milk consumption are estimated in preliminary calculations to be about two to three times the adult dose for 45 Ca and 131 I, 70-80% of the adult dose for 90 Sr, about 40% for 137 Cs, 20% for 210 Po, and 239 Pu and 241 Am. Infant doses from radionuclides in breast milk are compared with doses to the offspring resulting from in utero exposures during pregnancy. (author)

Effect of computerized cognitive behavioral therapy on acquisition of coping skills among cocaine-dependent individuals enrolled in methadone maintenance.

Science.gov (United States)

Kiluk, Brian D; DeVito, Elise E; Buck, Matthew B; Hunkele, Karen; Nich, Charla; Carroll, Kathleen M

2017-11-01

The acquisition of coping skills has long been considered one of the putative mechanisms of cognitive behavioral therapy (CBT) for substance use disorders, yet consistent statistical support is lacking. This study sought to replicate and extend prior findings regarding the quality of coping skills as a mediator of abstinence outcomes from a computerized CBT program for substance users. Participants were methadone-maintained, cocaine dependent individuals enrolled in a clinical trial evaluating the efficacy of computer-based training for CBT ('CBT4CBT') as an add-on to treatment as usual (TAU+CBT4CBT) compared to TAU only. A subsample (N=71) completed a role play assessment to measure coping skills, the Drug Risk Response Test (DRRT), which was administered before, during (week 4), and after the 8-week treatment period. Participants' verbal responses to various high-risk situations for cocaine use were recorded and independent evaluators rated the quality of the coping responses. Results of repeated measures analyses revealed a main effect of time for the quality of overall responses [F(1, 141.26)=4.29, pskills across groups, yet no differential effect of treatment. Despite the significant association between coping responses and abstinence outcomes, analyses did not support the quality of coping skills as a mediator of treatment effects. However, among the high-risk situations wherein individuals provided lower quality responses at baseline, those assigned to TAU+CBT4CBT showed greater improvement compared to those assigned to TAU only [F(1, 697.65)=6.47, p=0.01]. This study failed to replicate the quality of coping skills as a mediator of CBT4CBT's effect on reducing drug use previously shown in a mixed outpatient substance use sample. However, in this methadone maintained sample, those with poorer quality skills in response to certain high-risk situations at baseline appeared to improve their coping strategies following CBT4CBT compared to standard methadone

Synthesis and positron emission tomographic (PET) baboon studies of [{sup 11}C]methadone and R-(-)-[{sup 11}C]methandone

Energy Technology Data Exchange (ETDEWEB)

Ding, Y.S.; Fowler, J.S.; Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)] [and others

1996-05-01

Methadone (MET) maintenance has been used successfully for many years in the rehabilitation of heroin addicts. MET, a typical m{mu}-opioid receptor agonist, exists as two enantiomers and is used clinically as the racemic mixture. However, R-(-)-MET has a 10-fold higher affinity for m{mu} receptors than S-(+)-MET (IC{sub 50}: 3.0 nM and 26.4 nM, respectively) and R-(-)-MET is almost entirely responsible for the therapeutic actions of the racemate. In order to examine the pharmacokinetics and stereoselectivity of the drug, we have synthesized both [{sup 11}C]MET and R-(-)-[{sup 11}C]MET. Preparing the precursor by one-step approach to the N-demethylated methadone was precluded as other investigators cited problems with intramolecular cyclization. Therefore, a four-step synthesis using MET (or R-(-)-MET) as starting material was required to obtain the precursor, followed by a two-step radiolabeling synthesis (N-methylation followed by oxidation) to obtain [{sup 11}C]MET (or R-(-)-[{sup 11}C]MET). Comparative PET studies in the same baboon showed peak striatal uptake was 0.022%/cc at 5 minutes with a half time of clearance from peak of 100 minutes for R-(-)-[{sup 11}C]MET and a peak uptake of 0.013%/cc with a half time of 90 min for [{sup 11}C]MET. R-(-)-[{sup 11}C]MET also showed a slower disappearance in plasma. Both tracers showed higher C-11 in basal ganglia (BG), thalamus and midbrain relative to the cerebellum (CB) and occipital cortex (OC) but the BG/OC ratio was higher for R-(-)-[{sup 11}C]MET (1.3 vs 1.1). Pretreatment with naloxone (1 mg/kg, iv) increased R-(-)-[{sup 11}C]MET uptake in all brain regions whereas unlabeled MET slightly increased C-11 clearance in BG, OC and CB. These initial results show higher brain concentration and specificity of the pharmacologically active enantiomer of methadone along with significant non-specific binding.

Paid maternity leave and childhood vaccination uptake: Longitudinal evidence from 20 low-and-middle-income countries.

Science.gov (United States)

Hajizadeh, Mohammad; Heymann, Jody; Strumpf, Erin; Harper, Sam; Nandi, Arijit

2015-09-01

The availability of maternity leave might remove barriers to improved vaccination coverage by increasing the likelihood that parents are available to bring a child to the clinic for immunizations. Using information from 20 low-and-middle-income countries (LMICs) we estimated the effect of paid maternity leave policies on childhood vaccination uptake. We used birth history data collected via Demographic and Health Surveys (DHS) to assemble a multilevel panel of 258,769 live births in 20 countries from 2001 to 2008; these data were merged with longitudinal information on the number of full-time equivalent (FTE) weeks of paid maternity leave guaranteed by each country. We used Logistic regression models that included country and year fixed effects to estimate the impact of increases in FTE paid maternity leave policies in the prior year on the receipt of the following vaccines: Bacillus Calmette-Guérin (BCG) commonly given at birth, diphtheria, tetanus, and pertussis (DTP, 3 doses) commonly given in clinic visits and Polio (3 doses) given in clinic visits or as part of campaigns. We found that extending the duration of paid maternity leave had a positive effect on immunization rates for all three doses of the DTP vaccine; each additional FTE week of paid maternity leave increased DTP1, 2 and 3 coverage by 1.38 (95% CI = 1.18, 1.57), 1.62 (CI = 1.34, 1.91) and 2.17 (CI = 1.76, 2.58) percentage points, respectively. Estimates were robust to adjustment for birth characteristics, household-level covariates, attendance of skilled health personnel at birth and time-varying country-level covariates. We found no evidence for an effect of maternity leave on the probability of receiving vaccinations for BCG or Polio after adjustment for the above-mentioned covariates. Our findings were consistent with the hypothesis that more generous paid leave policies have the potential to improve DTP immunization coverage. Further work is needed to understand the health effects of

Metadon

DEFF Research Database (Denmark)

Nielsen, Mette Odegaard; Hetmar, Ole

2008-01-01

A woman with schizophrenia in methadone treatment was admitted for treatment of psychotic symptoms and cocaine addiction. Her prescribed medication was a 400 mg daily dose of methadone. It became evident during her hospitalisation that she was only taking a small part of the medication herself...... and she sold the rest of the methadone to finance her addiction of cocaine. To address this kind of misuse of prescribed medication, this paper examines the importance of following guidelines put forward by the NBH (National Board of Health)....

Integrated internist - addiction medicine - hepatology model for hepatitis C management for individuals on methadone maintenance.

Science.gov (United States)

Martinez, A D; Dimova, R; Marks, K M; Beeder, A B; Zeremski, M; Kreek, M J; Talal, A H

2012-01-01

Despite a high prevalence of hepatitis C virus (HCV) among drug users, HCV evaluation and treatment acceptance are extremely low among these patients when referred from drug treatment facilities for HCV management. We sought to increase HCV treatment effectiveness among patients from a methadone maintenance treatment program (MMTP) by maintaining continuity of care. We developed, instituted and retrospectively assessed the effectiveness of an integrated, co-localized care model in which an internist-addiction medicine specialist from MMTP was embedded in the hepatitis clinic. Methadone maintenance treatment program patients were referred, evaluated by the internist and hepatologist in hepatitis clinic and provided HCV treatment with integration between both sites. Of 401 evaluated patients, anti-HCV antibody was detected in 257, 86% of whom were older than 40 years. Hepatitis C virus RNA levels were measured in 222 patients, 65 of whom were aviremic. Of 157 patients with detectable HCV RNA, 125 were eligible for referral to the hepatitis clinic, 76 (61%) of whom accepted and adhered with the referral. Men engaged in MMTP <36 months were significantly less likely to be seen in hepatitis clinic than men in MMTP more than 36 months (odds ratio = 7.7; 95% confidence interval 2.6-22.9) or women. We evaluated liver histology in 63 patients, and 83% had moderate to advanced liver disease. Twenty-four patients initiated treatment with 19 completing and 13 (54%) achieving sustained response. In conclusion, integrated care between the MMTP and the hepatitis clinic improves adherence with HCV evaluation and treatment compared to standard referral practices. © 2010 Blackwell Publishing Ltd.

Effects of Maternal Valium Administration on Fetal MRI Motion Artifact: A Comparison Study at High Altitude.

Science.gov (United States)

Meyers, Mariana L; Mirsky, David M; Dannull, Kimberly A; Tong, Suhong; Crombleholme, Timothy M

2017-01-01

Fetal MRI is performed without sedation. In cases of maternal claustrophobia or when reduction of fetal motion is critical, benzodiazepines may help. The purpose of this study was to evaluate the effects of low-dose benzodiazepine on fetal motion MRI and its effect on maternal oxygen levels at higher elevation. A total of 131 fetal MRI scans performed from March 2012 through December 2013 were studied. Nineteen of the cases were performed following Valium administration. Images were graded with a 5-point Likert scale. Using pulse oximetry, maternal oxygen levels were recorded. Results were analyzed for each category combining 3 readers' interpretations. Using a 2-sample t test model, the average imaging scores were better for the control than the Valium group (p = 0.0139). Maternal oxygen levels at different times and positions were compared using independent 2-sample t test between the Valium and control groups showing no change in O2 saturation, except when controlling for altitude and gestational age (p = 0.0326). Administration of low-dose Valium did not decrease fetal motion on MRI. Valium did not pose any risk of maternal hypoxemia, except when controlling for altitude and gestational age on supine position. Thus, caution should be exercised to prevent the risk of fetal hypoxemia. © 2016 S. Karger AG, Basel.

Opiate Users' Perceived Barriers Against Attending Methadone Maintenance Therapy: A Qualitative Study in China

Science.gov (United States)

Lin, Chunqing; Wu, Zunyou; Detels, Roger

2012-01-01

Methadone maintenance therapy (MMT) in China is facing challenges such as high relapse rates and low coverage. The study assessed factors influencing MMT utilization among opiate users. In-depth interviews were conducted among 30 opiate users in 2008 to ascertain the barriers against seeking MMT. Data were analyzed using ATLAS.ti. Barriers to the treatment included requirement of registration with police, perceived discrimination, logistic difficulties, side effects, fear of being addicted to another drug, lack of additional services, and economic burden. The result suggests the need for structural changes such as improving comprehensive services, simplifying application procedure, and enhancing referral system. The study's limitations are noted. PMID:21417558

Cost of provision of opioid substitution therapy provision in Tijuana, Mexico.

Science.gov (United States)

Burgos, Jose Luis; Cepeda, Javier A; Kahn, James G; Mittal, Maria Luisa; Meza, Emilio; Lazos, Raúl Rafael Palacios; Vargas, Psyché Calderón; Vickerman, Peter; Strathdee, Steffanie A; Martin, Natasha K

2018-05-23

Mexico recently enacted drug policy reform to decriminalize possession of small amounts of illicit drugs and mandated that police refer identified substance users to drug treatment. However, the economic implications of drug treatment expansion are uncertain. We estimated the costs of opioid substitution therapy (OST) provision in Tijuana, Mexico, where opioid use and HIV are major public health concerns. We adopted an economic health care provider perspective and applied an ingredients-based micro-costing approach to quantify the average monthly cost of OST (methadone maintenance) provision at two providers (one private and one public) in Tijuana, Mexico. Costs were divided by type of input (capital, recurrent personnel and non-personnel). We defined "delivery cost" as all costs except for the methadone and compared total cost by type of methadone (powdered form or capsule). Cost data were obtained from interviews with senior staff and review of expenditure reports. Service provision data were obtained from activity logs and senior staff interviews. Outcomes were cost per OST contact and cost per person month of OST. We additionally collected information on patient charges for OST provision from published rates. The total cost per OST contact at the private and public sites was $3.12 and $5.90, respectively, corresponding to $95 and $179 per person month of OST. The costs of methadone delivery per OST contact were similar at both sites ($2.78 private and $3.46 public). However, cost of the methadone itself varied substantially ($0.34 per 80 mg dose [powder] at the private site and $2.44 per dose [capsule] at the public site). Patients were charged $1.93-$2.66 per methadone dose. The cost of OST provision in Mexico is consistent with other upper-middle income settings. However, evidenced-based (OST) drug treatment facilities in Mexico are still unaffordable to most people who inject drugs.

High-dose versus low-dose local anaesthetic for transversus abdominis plane block post-Caesarean delivery analgesia: a meta-analysis.

Science.gov (United States)

Ng, S C; Habib, A S; Sodha, S; Carvalho, B; Sultan, P

2018-02-01

The optimal local-anaesthetic (LA) dose for transversus-abdominis-plane (TAP) block is unclear. In this meta-analysis, we aimed to determine whether TAP blocks for Caesarean delivery (CD) with low-dose (LD) LA demonstrated non-inferiority in terms of analgesic efficacy, compared with high-dose (HD) LA. A literature search was performed for randomised controlled trials examining the analgesic efficacy of TAP blocks vs control after CD. The different dosing used in these studies was classified as HD or LD (bupivacaine equivalents >50 or ≤50 mg per block side, respectively). The pooled results of each dose group vs control were indirectly compared using the Q test. The primary outcome was 24 h opioid consumption. Secondary outcomes included 6 and 24 h postoperative pain scores, time to first analgesia, 6 h opioid consumption, opioid-related side-effects, and maternal satisfaction. Fourteen studies consisting of 770 women (389 TAP and 381 control) were included. Compared with controls, the 24 h opioid consumption (milligram morphine equivalents) was lower in HD [mean difference (MD) 95% confidence interval (CI) -22.41 (-38.56, -6.26); P=0.007; I 2 =93%] and LD [MD 95% CI -16.29 (-29.74, -2.84); P=0.02; I 2 =98%] TAP groups. However, no differences were demonstrated between the HD and LD groups (P=0.57). There were also no differences between the HD and LD groups for the 6 h opioid consumption, time to first analgesia, 6 and 24 h pain scores, postoperative nausea and vomiting, pruritus, and maternal satisfaction. Low-dose TAP blocks for Caesarean delivery provide analgesia and opioid-sparing effects comparable with the high-dose blocks. This suggests that lower doses can be used to reduce local anaesthetic toxicity risk without compromising the analgesic efficacy. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Attendance Rates in A Workplace Predict Subsequent Outcome of Employment-Based Reinforcement of Cocaine Abstinence in Methadone Patients

OpenAIRE

Donlin, Wendy D; Knealing, Todd W; Needham, Mick; Wong, Conrad J; Silverman, Kenneth

2008-01-01

This study assessed whether attendance rates in a workplace predicted subsequent outcome of employment-based reinforcement of cocaine abstinence. Unemployed adults in Baltimore methadone programs who used cocaine (N  =  111) could work in a workplace for 4 hr every weekday and earn $10.00 per hour in vouchers for 26 weeks. During an induction period, participants provided urine samples but could work independent of their urinalysis results. After the induction period, participants had to prov...

Pregnancy Complications Associated With Maternal Hypothyroidism: A Systematic Review.

Science.gov (United States)

Shinohara, Danielle Rosani; Santos, Thais da Silva; de Carvalho, Hayalla Corrêa; Lopes, Laíza Cristina Bahls; Günther, Luciene Setsuko Akimoto; Aristides, Sandra Mara Alessi; Teixeira, Jorge Juarez Vieira; Demarchi, Izabel Galhardo

2018-04-01

Hypothyroidism is one of the most prevalent diseases in pregnancy, but there is no consensus about its management in pregnant women. In this systematic review, we evaluated the association between pregnancy complications and treated or untreated maternal hypothyroidism. PubMed and reference lists were searched for the Medical Subject Headings terms "pregnancy complications" and "hypothyroidism." The eligibility criteria for inclusion in the study were an original study published between 2002 and 2013. Six reviewers independently selected the studies, and 3 extracted the data. Two reviewers assessed the risk of bias and quality of the studies. Eighteen studies were included in the systematic review. The most prevalent complications associated with maternal hypothyroidism were abortion, intrauterine fetal death, preterm delivery, and preeclampsia. The pregnancy outcome depended on the treatment that was received by the patient. Strong evidence indicates that maternal hypothyroidism is associated with maternal-fetal complications, but no consensus was found among the studies reviewed herein. The dose of levothyroxine that is required to maintain euthyroidism is still questioned, but studies have suggested that levothyroxine should be adjusted according to the gestational period and laboratory profile.

Severe acute maternal morbidity and maternal death audit - a rapid ...

African Journals Online (AJOL)

Severe acute maternal morbidity and maternal death audit - a rapid diagnostic tool for evaluating maternal care. L Cochet, R.C. Pattinson, A.P. Macdonald. Abstract. Objective. To analyse severe acute maternal morbidity (SAMM) and maternal mortality in the Pretoria region over a 2-year period (2000 - 2001). Setting.

Maternal characteristics and hospital policies as risk factors for nonreceipt of hepatitis B vaccine in the newborn nursery.

Science.gov (United States)

O'Leary, Sean T; Nelson, Christina; Duran, Julie

2012-01-01

A birth dose of hepatitis B vaccine (HBV) is a primary focus of the Advisory Committee on Immunization Practices' strategy to eliminate transmission of hepatitis B virus in the United States. We sought to assess the impact of maternal characteristics and hospital policy on the receipt of a birth dose of HBV. A retrospective cohort study was performed using data from the 2008 Colorado birth registry. Hospital policy was assessed by state health department personnel. Univariate and multivariate logistic regression analyses were used to examine the association of maternal characteristics and hospital policy with nonreceipt of HBV. A total of 64,425 infants were identified in the birth cohort, of whom 61.6% received a birth dose of HBV. Higher maternal education and income were associated with nonreceipt of HBV (master's degree vs. eighth grade or less: adjusted odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.49-1.85; >$75,000 vs. risk of perinatal hepatitis B transmission, hospitals should stipulate that all infants are offered HBV and ensure that these policies are implemented and followed.

Maternal vitamin D supplementation to meet the needs of the breastfed infant: a systematic review.

Science.gov (United States)

Thiele, Doria K; Senti, Jeanine L; Anderson, Cindy M

2013-05-01

Maternal vitamin D insufficiency during lactation, related to lack of sun exposure and minimal intake of vitamin D from the diet, contributes to low breast milk vitamin D content and, therefore, infant vitamin D deficiency. The objective of this review was to examine the literature regarding evidence for achieving maternal vitamin D status that promotes sufficient vitamin D transfer from mother to infant exclusively from breast milk. PubMed and CINAHL databases were searched using the terms lactation or breastfeeding or milk, human and vitamin D. The resulting articles were further limited to those written in English, published within the last 10 years, and involving clinical or randomized controlled trials of humans. The search yielded 13 studies, 3 of which provide evidence for maternal intake of vitamin D and the correlation with exclusively breastfed infants' serum 25-hydroxyvitamin D level. A strong positive correlation exists between maternal vitamin D intake during exclusive breastfeeding and infant serum 25-hydroxyvitamin D levels. There is support to conclude that when maternal vitamin D intake is sufficient, vitamin D transfer via breast milk is adequate to meet infant needs. In the reviewed studies, doses up to 10 times the current recommended daily intake of vitamin D were needed to produce sufficient transfer from mother to breastfed infant. Further research is needed to refine the dose and gestational timing of maternal vitamin D supplementation. Due to the high rates of vitamin D deficiency during lactation and the correlations between vitamin D deficiency and multiple diseases, providers should consider monitoring lactating mothers' vitamin D status.

Inter-individual variation of selenium in maternal plasma, cord plasma and placenta

International Nuclear Information System (INIS)

Lee, Anne M.; Huel, Guy; Godin, Jean; Hellier, Georgette; Sahuquillo, Josiane; Moreau, Thierry; Blot, Phillipe

1994-01-01

Selenium (Se) in high doses has been known to cause injury to the fetus and newborn. The major difficulty in assessing the effects of selenium on human reproduction stems from the need for a suitable means of estimating maternal and fetal exposure. The present investigation, therefore, examines the respective reliability of maternal plasma, cord plasma and placenta as epidemiological indicators as well as inter-individual variation of this trace element. An unselected population of 128 pregnancies was studied. Obstetrical characteristics were noted. Selenium concentrations were determined for maternal plasma, cord plasma, and placental tissue by fluorometric analysis. Maternal plasma selenium concentrations (Se-Bm) were significantly greater than fetal concentrations (Se-Bc). Placental selenium (Se-Pl) levels were four times that of fetal levels. Variability of Se-Bc is best explained by placental concentrations. Maternal weight and ethnic origin are significantly correlated with Se-Bc. Female newborn have higher selenium levels than male newborn. The present study demonstrates the significance of the placenta as an indicator of fetal selenium exposure

Cost-effectiveness of methadone maintenance therapy as HIV prevention in an Indonesian high-prevalence setting: a mathematical modeling study.

Science.gov (United States)

Wammes, Joost J G; Siregar, Adiatma Y; Hidayat, Teddy; Raya, Reynie P; van Crevel, Reinout; van der Ven, André J; Baltussen, Rob

2012-09-01

Indonesia faces an HIV epidemic that is in rapid transition. Injecting drug users (IDUs) are among the most heavily affected risk populations, with estimated prevalence of HIV reaching 50% or more in most parts of the country. Although Indonesia started opening methadone clinics in 2003, coverage remains low. We used the Asian Epidemic Model and Resource Needs Model to evaluate the long-term population-level preventive impact of expanding Methadone Maintenance Therapy (MMT) in West Java (43 million people). We compared intervention costs and the number of incident HIV cases in the intervention scenario with current practice to establish the cost per infection averted by expanding MMT. An extensive sensitivity analysis was performed on costs and epidemiological input, as well as on the cost-effectiveness calculation itself. Our analysis shows that expanding MMT from 5% coverage now to 40% coverage in 2019 would avert approximately 2400 HIV infections, at a cost of approximately US$7000 per HIV infection averted. Sensitivity analyses demonstrate that the use of alternative assumptions does not change the study conclusions. Our analyses suggest that expanding MMT is cost-effective, and support government policies to make MMT widely available as an integrated component of HIV/AIDS control in West Java. Copyright © 2012 Elsevier B.V. All rights reserved.

[Trend in buprenorphine and methadone shopping behavior in France from 2004 to 2014].

Science.gov (United States)

Kernisant, Mélanie; Delorme, Jessica; Kabore, Jean-Luc; Brousse, Georges; Laporte, Catherine; Zenut, Marie; Chenaf, Chouki; Authier, Nicolas

2016-12-01

The opioid maintenance treatments (OMT) are widely misused and diverted in many countries. Doctor shopping represented the main way to obtain high quantities of opioids in abuse/diversion. The aim of this study was to assess the trends in the prevalence of doctor shopping for high dosage buprenorphine (HDB) and methadone (MTD) from 2004 to 2014 by using the French Health Insurance claims. This was a cross-sectional study of patients treated by OMT (High Dosage Buprenorphine or Methadone) between 2004 and 2014 from a representative sample of the French Health Insurance claims. Doctor shopping was defined as at least 1 day of overlapping prescriptions, written by at least 2 different prescribers and filled in at least 3 different pharmacies. HDB patients were more likely men (77.9 % in 2014) with a mean age ranged from 33.4±7.6 years in 2004 to 39.5±9.3 years in 2014, Pshopping for HDB decreased from 2004 to 2014 (12.6 % versus 3.9 %, Pshopping for MTD was very low during the period study (0.2 % to 0.5 %). Overall, the prevalence of doctor shopping was higher for HDB than for MTD whatever the year (Pshopping for HDB decreased significantly during the last decade while doctor shopping for MTD remained nearly inexistent even if it could be underestimated because of dispensations in specialized centers and in hospitals not comprised in the insurance claims. The low rates of doctor shopping reported in these last years could result from the guidelines for good practices in OMT use made in 2004 and the adjustments of ANSM (French National Agency for Medicines and Health Products Safety) for HDB best use made in 2011. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Evaluation of CF/CM, concentration ratios for elements in fetus to mother, using cord blood and maternal blood

International Nuclear Information System (INIS)

Watanabe, Y.; Yukawa, M.; Kim, H.S.; Nishimura, Y.; Osada, H.; Sekiya, S.

2000-01-01

ICRP recommends age-dependent dose evaluation for intakes of radionuclides by inhalation and ingestion, and gave age-specific biokinetic models and dose coefficients (doses per unit intake) for infants, children and adults in the publications. Dose coefficients are also needed for the assessment of exposures received in utero and after birth by the offspring of the woman who has received intakes of radionuclides. In the model that has been adopted by ICRP, the doses to the developing fetus are calculated using CF/CM values, concentration ratios for radionuclides in the fetus and the maternal tissues. The purpose of this study is to evaluate the CF/CM of each radionuclide by the measurement of element concentration in cord blood and maternal blood. Blood samples were obtained from 35 mothers who delivered in Department of Obstetrics and Gynecology of Chiba University. Just after the delivery, unbiblical cord blood was sampled. Maternal blood was also obtained from the arm vein within 30 minutes after the delivery. The serum was separated from the blood sample with centrifugation. About 50 mg of freezer-dried whole blood and serum were digested with 0.5 ml of 65% ultra-pure nitric acid and 0.2 ml of 30% hydrogen peroxide in a microwave digester. The diluted solutions were used for the determination of elements by ICP-MS (Inductively Coupled Plasma Mass Spectrometry) and ICP-AES (Inductively Coupled Plasma Atomic Emission Spectrometry). The elements determined in these samples included Mg, K, Ca, Mn, Fe, Cu, Zn, Se, Rb, Sr and Cs. The concentration of Cu was higher in the maternal blood than in the cord blood in both whole blood and serum. On the other hand, Mn and Fe were higher in the cord blood. The differences of concentration ratios among elements and the differences among tissues will be discussed. (author)

Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.

Science.gov (United States)

Wu, Pingsheng; Feldman, Amy S; Rosas-Salazar, Christian; James, Kristina; Escobar, Gabriel; Gebretsadik, Tebeb; Li, Sherian Xu; Carroll, Kecia N; Walsh, Eileen; Mitchel, Edward; Das, Suman; Kumar, Rajesh; Yu, Chang; Dupont, William D; Hartert, Tina V

2016-01-01

Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma. We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma) cohort. The individual and cumulative impact of maternal urinary tract infections (UTI) during pregnancy, maternal colonization with group B streptococcus (GBS), mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated. Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI) and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course) were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling) was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal delivery, C

Relative Importance and Additive Effects of Maternal and Infant Risk Factors on Childhood Asthma.

Directory of Open Access Journals (Sweden)

Pingsheng Wu

Full Text Available Environmental exposures that occur in utero and during early life may contribute to the development of childhood asthma through alteration of the human microbiome. The objectives of this study were to estimate the cumulative effect and relative importance of environmental exposures on the risk of childhood asthma.We conducted a population-based birth cohort study of mother-child dyads who were born between 1995 and 2003 and were continuously enrolled in the PRIMA (Prevention of RSV: Impact on Morbidity and Asthma cohort. The individual and cumulative impact of maternal urinary tract infections (UTI during pregnancy, maternal colonization with group B streptococcus (GBS, mode of delivery, infant antibiotic use, and older siblings at home, on the risk of childhood asthma were estimated using logistic regression. Dose-response effect on childhood asthma risk was assessed for continuous risk factors: number of maternal UTIs during pregnancy, courses of infant antibiotics, and number of older siblings at home. We further assessed and compared the relative importance of these exposures on the asthma risk. In a subgroup of children for whom maternal antibiotic use during pregnancy information was available, the effect of maternal antibiotic use on the risk of childhood asthma was estimated.Among 136,098 singleton birth infants, 13.29% developed asthma. In both univariate and adjusted analyses, maternal UTI during pregnancy (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.18, 1.25; adjusted OR [AOR] 1.04, 95%CI 1.02, 1.07 for every additional UTI and infant antibiotic use (OR 1.21, 95%CI 1.20, 1.22; AOR 1.16, 95%CI 1.15, 1.17 for every additional course were associated with an increased risk of childhood asthma, while having older siblings at home (OR 0.92, 95%CI 0.91, 0.93; AOR 0.85, 95%CI 0.84, 0.87 for each additional sibling was associated with a decreased risk of childhood asthma, in a dose-dependent manner. Compared with vaginal delivery, C

Effects of maternal acrolein exposure during pregnancy on testicular testosterone production in fetal rats.

Science.gov (United States)

Yang, Yuzhuo; Zhang, Zhe; Zhang, Hongliang; Hong, Kai; Tang, Wenhao; Zhao, Lianming; Lin, Haocheng; Liu, Defeng; Mao, Jiaming; Wu, Han; Jiang, Hui

2017-07-01

Acrolein has been reported to have diverse toxic effects on various organs, including the reproductive system. However, little is known regarding the effects of maternal acrolein exposure on testicular steroidogenesis in male offspring. The present study investigated the effects of acrolein on fetal testosterone production and associated genes. Pregnant Sprague‑Dawley rats were intraperitoneally injected with vehicle (normal saline) or 1, 2 or 5 mg/kg acrolein from gestational day (GD) 14‑20, and fetal testes were examined on GD 21. Fetal body and testicular weights were markedly reduced in pups following exposure to high doses of acrolein (5 mg/kg) in late pregnancy. Notably, in utero exposure of 5 mg/kg acrolein significantly decreased the testicular testosterone level and downregulated the expression levels of steroidogenic acute regulatory protein (StAR) and 3β‑hydroxysteroid dehydrogenase (3β‑HSD), whereas the levels of other steroidogenic enzymes, including scavenger receptor class B, cholesterol side‑chain cleavage enzyme and steroid 17 alpha‑hydroxylase/17,20 lyase, were unaffected. Furthermore, the 3β‑HSD immunoreactive area in the interstitial region of the fetal testes was reduced at a 5 mg/kg dose, whereas the protein expression levels of 4‑hydroxynonenalwere dose‑dependently increased following maternal exposure to acrolein. mRNA expression levels of insulin‑like factor 3, a critical gene involved in testicular descent, were unaltered following maternal acrolein exposure. Taken together, the results of the present study suggested that maternal exposure to high doses of acrolein inhibited fetal testosterone synthesis, and abnormal expression of StAR and 3β‑HSD may be associated with impairment of the steroidogenic capacity.

Localization of radioactivity from 2-methoxy[1,2-14C]ethanol in maternal and conceptus compartments of CD-1 mice

International Nuclear Information System (INIS)

Sleet, R.B.; John-Greene, J.A.; Welsch, F.

1986-01-01

2-Methoxyethanol (ME) induces paw malformations in CD-1 mice when given by gavage on gestation day (gd) 11 (vaginal plug + day = gd 0). The distribution of radioactivity originating from 2-methoxy[1,2- 14 C]ethanol ([ 14 C]ME) was examined by liquid scintillation spectrophotometry and whole body autoradiography in pregnant (gd 11) CD-1 mice from 5 min to 48 hr after oral administration. Each dam received either a trace dose of [ 14 C]ME (0.92 mumol; 13 muCi) combined with an unlabeled teratogenic dose (187 mumol). By 5 min after the trace dose was administered, 14 C had distributed throughout the maternal and conceptus compartments. Radioactivity in the maternal compartment was most concentrated in the liver, blood and gastrointestinal tract. Conceptus 14 C was associated with the placenta, yolk sac, and embryonal structures such as limb buds, somites, and neuroepithelium. The concentration of blood 14 C plateaued within 30 min after administration of the trace or combined trace/teratogenic dose. It remained stable for 1.5 hr and then gradually declined, reaching 2 to 10% of the maximal concentration by 48 hr. 14 C content in the maternal liver, conceptuses, and embryos per se was always greater than that of the blood and was inversely related to ME dose at 6 hr but not 48 hr. At 6 hr after administration of the trace dose, 69% of total liver and 33% of embryonal 14 C were acid insoluble. Tissue-specific interaction with [ 14 C]ME was demonstrated by the distribution of acid insoluble radioactivity among various cellular components of the maternal liver and embryo. The findings indicate that the embryo is readily susceptible to blood borne ME and/or its metabolites. In addition, the chemical characteristics of the labeled molecule(s) apparently favored label incorporation into macromolecules by the liver and embryo

The US EPA reference dose for methylmercury: sources of uncertainty

International Nuclear Information System (INIS)

Rice, D.C.

2004-01-01

The US Environmental Protection Agency (EPA) derived a reference dose for methylmercury in 2001, based on an extensive analysis by the National Research Council (NRC) of the National Academy of Sciences. The NRC performed benchmark dose analysis on a number of endpoints from three longitudinal prospective studies: the Seychelles Islands, the Faroe Islands, and the New Zealand studies. Adverse effects were reported in the latter two studies, but not in the Seychelles study. The NRC also performed an integrative analysis of all three studies. Dose conversion from cord blood or maternal hair mercury concentration was performed by EPA using a one-compartment pharmacokinetic model. A total uncertainty factor of 10 was applied for intrahuman pharmacokinetic and pharmacodynamic variability. There are numerous decisions made by the NRC/EPA that could greatly affect the value of the reference dose (RfD). Some of these include the choice of a linear model for the relationship between mercury body burden and neuropsychological performance, the choice of values of P 0 and the benchmark response, the use of the 'critical study/critical endpoint' approach in the interpretation of the maternal body burden that corresponds to the RfD, the use of central tendencies in a one-compartment pharmacokinetic model rather than the inclusion of the distributions of variables for the population of reproductive-age women, the assumption of unity for the ratio of fetal cord blood to maternal blood methylmercury concentrations, the choice of a total of 10 as an uncertainty factor, and the lack of dose-response analysis for other health effects such as cardiovascular disease. In addition, it may be argued that derivation of a RfD for methylmercury is inappropriate, given that there does not appear to be a threshold for adverse neuropsychological effects based on available data

Cost-effectiveness of maternal GBS immunization in low-income sub-Saharan Africa.

Science.gov (United States)

Russell, Louise B; Kim, Sun-Young; Cosgriff, Ben; Pentakota, Sri Ram; Schrag, Stephanie J; Sobanjo-Ter Meulen, Ajoke; Verani, Jennifer R; Sinha, Anushua

2017-12-14

A maternal group B streptococcal (GBS) vaccine could prevent neonatal sepsis and meningitis. Its cost-effectiveness in low-income sub-Saharan Africa, a high burden region, is unknown. We used a decision tree model, with Markov nodes to project infants' lifetimes, to compare maternal immunization delivered through routine antenatal care with no immunization. 37 countries were clustered on the basis of economic and health resources and past public health performance. Vaccine efficacy for covered serotypes was ranged from 50% to 90%. The model projected EOGBS (early-onset) and LOGBS (late-onset) cases and deaths, disability-adjusted life years (DALYs), healthcare costs (2014 US$), and cost-effectiveness for a representative country in each of the four clusters: Guinea-Bissau, Uganda, Nigeria, and Ghana. Maximum vaccination costs/dose were estimated to meet two cost-effectiveness benchmarks, 0.5 GDP and GDP per capita/DALY, for ranges of disease incidence (reported and adjusted for under-reporting) and vaccine efficacy. At coverage equal to the proportion of pregnant women with≥4 antenatal visits (ANC4) and serotype-specific vaccine efficacy of 70%, maternal GBS immunization would prevent one-third of GBS cases and deaths in Uganda and Nigeria, where ANC4 is 50%, 42-43% in Guinea-Bissau (ANC4=65%), and 55-57% in Ghana (ANC4=87%). At a vaccination cost of $7/dose, maternal immunization would cost $320-$350/DALY averted in Guinea-Bissau, Nigeria, and Ghana, less than half these countries' GDP per capita. In Uganda, which has the lowest case fatality ratios, the cost would be $573/DALY. If the vaccine prevents a small proportion of stillbirths, it would be even more cost-effective. Vaccination cost/dose, disease incidence, and case fatality were key drivers of cost/DALY in sensitivity analyses. Maternal GBS immunization could be a cost-effective intervention in low-income sub-Saharan Africa, with cost-effectiveness ratios similar to other recently introduced vaccines

Prenatal drug exposure: infant and toddler outcomes.

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Bandstra, Emmalee S; Morrow, Connie E; Mansoor, Elana; Accornero, Veronica H

2010-04-01

This manuscript provides an overview of the current scientific literature on the impact of maternal drug use, specifically opioids and cocaine, during pregnancy on the acute and long-term outcomes of infants and toddlers from birth through age 3 years. Emphasis with regard to opioids is placed on heroin and opioid substitutes used to treat opioid addiction, including methadone, which has long been regarded as the standard of care in pregnancy, and buprenorphine, which is increasingly being investigated and prescribed as an alternative to methadone. Controlled studies comparing methadone at high and low doses, as well as those comparing methadone with buprenorphine, are highlighted and the diagnosis and management of neonatal abstinence syndrome is discussed. Over the past two decades, attention of the scientific and lay communities has also been focused on the potential adverse effects of cocaine and crack cocaine, especially during the height of the cocaine epidemic in the United States. Herein, the findings are summarized from prospective studies comparing cocaine-exposed with non-cocaine-exposed infants and toddlers with respect to anthropometric growth, infant neurobehavior, visual and auditory function, and cognitive, motor, and language development. The potentially stigmatizing label of the so-called "crack baby" preceded the evidence now accumulating from well-designed prospective investigations that have revealed less severe sequelae in the majority of prenatally exposed infants than originally anticipated. In contrast to opioids, which may produce neonatal abstinence syndrome and infant neurobehavioral deficits, prenatal cocaine exposure appears to be associated with what has been described as statistically significant but subtle decrements in neurobehavioral, cognitive, and language function, especially when viewed in the context of other exposures and the caregiving environment which may mediate or moderate the effects. Whether these early findings may

Characterizing fentanyl use in methadone-maintained clients.

Science.gov (United States)

Arfken, Cynthia L; Suchanek, Jessica; Greenwald, Mark K

2017-04-01

Deaths attributed to fentanyl have increased in the United States. However, little is known about fentanyl use among substance abuse treatment clients. To fill this gap, we assessed prevalence of fentanyl exposure, characteristics of clients testing positive for fentanyl, other substances detected concurrently or simultaneously with fentanyl, and clients' perception of how many people are actively seeking to use fentanyl. A retrospective chart review was conducted of all clients at one methadone maintenance treatment clinic between January 2015 and May 2016 in Wayne County, Michigan. Urine drug screens (UDS) including fentanyl (and its metabolite norfentanyl) were conducted clinically. To obtain additional data, 113 clients in this clinic subsequently completed an anonymous survey. Of 368 unique clients with UDS, 38.0% had at least one and 26.1% had ≥2 fentanyl-positive UDS results. None had a fentanyl prescription. Clients ever testing positive for fentanyl were significantly (pFentanyl-positive UDS results coincided most commonly with metabolites of cocaine- and heroin-positive UDS results. Of the anonymously surveyed clients, most (67.3%) reported they did not know anyone seeking fentanyl, a proportion significantly higher than for heroin, cocaine, alprazolam, hydrocodone and morphine. Fentanyl was commonly detected during this period with some clients having multiple fentanyl-positive UDS. Most clients did not know anyone seeking to obtain fentanyl. Regardless, the high exposure underscores that naloxone training and distribution is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Maternal correlates of maternal child feeding practices: a systematic review.

Science.gov (United States)

McPhie, Skye; Skouteris, Helen; Daniels, Lynne; Jansen, Elena

2014-01-01

Establishing healthy eating habits early in life is one important strategy to combat childhood obesity. Given that early maternal child feeding practices have been linked to child food intake and weight, identifying the maternal correlates of maternal child feeding practices is important in order to understand the determinants of childhood obesity; this was the overall aim of the current review. Academic databases were searched for studies examining the relationship between maternal child feeding practices and parenting, personal characteristics and psychopathology of mothers with preschoolers. Papers were limited to those published in English, between January 2000 and June 2012. Only studies with mothers of normally developing children between the ages of 2 and 6 years were included. There were no restrictions regarding the inclusion of maternal nationality or socioeconomic status (SES). Seventeen eligible studies were sourced. Information on the aim, sample, measures and findings of these was summarised into tables. The findings of this review support a relationship between maternal controlling parenting, general and eating psychopathology, and SES and maternal child feeding practices. The main methodological issues of the studies reviewed included inconsistency in measures of maternal variables across studies and cross-sectional designs. We conclude that the maternal correlates associated with maternal child feeding practices are complex, and the pathways by which maternal correlates impact these feeding practices require further investigation. © 2012 John Wiley & Sons Ltd.

Impact of Maternal Diet on Offspring Bone Fracture Risk During Childhood

DEFF Research Database (Denmark)

Petersen, Sesilje Elise Bondo

, including maternal diet and vitamin D status. However, few studies have investigated whether these factors during pregnancy impact offspring bone health in short as well as in the long term. The overall objective of this thesis was to investigate epidemiologically whether maternal vitamin D status...... and dietary patterns in two prospective pregnancy cohorts, were associated with offspring risk of bone fractures in childhood. Overall, our studies provided limited support to the hypothesis that fetal bone health is programmed by the maternal vitamin D status and overall diet during pregnancy. However......, there were some indications of an increased risk for fractures when the mother consumed a Western diet and had high consumption of artificially sweetened soft drinks. Further, our results indicated that mid-pregnancy use of dietary supplements with high doses of vitamin D increased the risk for offspring...

Design of pediatric oral formulations with a low proportion of methadone or phenobarbital for the treatment of neonatal abstinence syndrome.

Science.gov (United States)

Provenza, Nora; Calpena, Ana C; Mallandrich, Mireia; Pueyo, Blanca; Clares, Beatriz

2016-09-01

Elaboration of oral liquid formulations is the best alternative when no marketed forms are available for pediatrics. The development, characterization and stability evaluation of methadone (MI, MII, MIII) and phenobarbital (PI, PII) can be used for the treatment of neonatal abstinence syndrome (NAS). A standard operating procedure was established and parameters such as appearance, pH, rheological behavior and drug content were evaluated at three temperatures for 90 days. Changes in color of phenobarbital made necessary the storage below 25 °C. pH did not change in methadone solutions and was able to maintain phenobarbital solubilized. Degradation data at 4 °C fitted to Plateau equation followed by one phase decay. MI was stable for 60 days at the three temperatures; MII for 90 days at 4 and 25 °C and 60 days at 40 °C; MIII for 60 days at 4 °C, 15 days at 25 °C and 7 days at 4 °C. PI was stable for 60 days at 4 °C and 30 days at 25 °C. PII was stable for 7 days at 4 and 25 °C. All solutions met microbial specifications. A correct dosage for the treatment of NAS was guaranteed.

Maternal Mortality in a Nigerian Maternity Hospital | Olopade ...

African Journals Online (AJOL)

Despite recent focus on maternal mortality in Nigeria, its rates remain unacceptably high in Nigeria. A retrospective case-control study was carried out at Adeoyo Maternity Hospital, Ibadan between January 2003 and December 2004. This was to determine the maternal mortality ratio in a secondary health facility, to identify ...

[Maternal phenylketonuria].

Science.gov (United States)

Bókay, János; Kiss, Erika; Simon, Erika; Szőnyi, László

2013-05-05

Elevated maternal phenylalanine levels during pregnancy are teratogenic, and may result in embryo-foetopathy, which could lead to stillbirth, significant psychomotor handicaps and birth defects. This foetal damage is known as maternal phenylketonuria. Women of childbearing age with all forms of phenylketonuria, including mild variants such as hyperphenylalaninaemia, should receive detailed counselling regarding their risks for adverse foetal effects, optimally before contemplating pregnancy. The most assured way to prevent maternal phenylketonuria is to maintain the maternal phenylalanine levels within the optimal range already before conception and throughout the whole pregnancy. Authors review the comprehensive programme for prevention of maternal phenylketonuria at the Metabolic Center of Budapest, they survey the practical approach of the continuous maternal metabolic control and delineate the outcome of pregnancies of mothers with phenylketonuria from the introduction of newborn screening until most recently.

Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos

International Nuclear Information System (INIS)

Moreira, Estefania G.; Yu Xiaozhong; Robinson, Joshua F.; Griffith, Willian; Hong, Sung Woo; Beyer, Richard P.; Bammler, Theo K.; Faustman, Elaine M.

2010-01-01

Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles across doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10 mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system.

An investigation into techniques for reducing doses from neo-natal radiographic examinations

Energy Technology Data Exchange (ETDEWEB)

Wraith, C.M.; Martin, C.J. [Aberdeen Royal Hospitals NHS Trust (United Kingdom). Dept. of Bio-Medical Physics and Bio-Engineering; Stockdale, E.J.N.; McDonald, S.; Farquhar, B. [Royal Aberdeen Children`s Hospital (United Kingdom)

1995-10-01

A survey of radiation doses received by infants having radiography in a neo-natal unit was undertaken at Aberdeen Maternity Hospital. Options for dose reduction recommended by the CEC Lake Starnberg Group were investigated. Techniques were implemented for clinical evaluation after assessments of image quality with test objects and phantoms. Clinical image quality of radiographs was evaluated by paediatric radiologists using CEC criteria. Results revealed a clear relationship between entrance dose and patient weight, indicating that reference doses for infants could be linked to weight. (author).

Assessment of fetal radiation dose to patients and staff in diagnostic radiology

International Nuclear Information System (INIS)

Osei, E.K.

2000-07-01

A major source of uncertainty in the estimation of fetal absorbed radiation dose is the influence of fetal size and position as these change with gestational age. Consequently, dose to the fetus is related to gestational age. Most studies of fetal dose estimation during pregnancy assume that the uterus dose is equal to fetal dose. These dose estimates do not take account of gestational age and individual fetal depth, factors which are significant when calculating dose. To establish both positional and size data for estimation of fetal absorbed dose from radiological examinations, the depths from the mother's anterior surface to the mid-line of the fetal head and abdomen were measured from ultrasound scans in 215 pregnant women. Depths were measured along a ray path projected in the anterior-posterior direction from the mother's abdomen. The fetal size was estimated from measurements of the fetal abdominal and head circumference, femur length and the biparietal diameter. The effects of fetal presentation, maternal bladder volume, placenta location, gestational age and maternal AP thickness on fetal depth and size were analysed. A Monte Carlo (MC) model was developed, and used to derive factors for converting dose-area product and free-in-air entrance surface dose from medical exposure of a pregnant patient to absorbed dose to the uterus/embryo, and for converting uterus dose to fetal dose in the later stages of pregnancy. Also presented are factors for converting thermoluminescence dosimeter reading from occupational exposure of a pregnant worker to equivalent dose to the fetus. The MC model was verified experimentally by direct measurement of uterus depth dose in a female Rando phantom, and also by comparison with other experimental work and MC results in the literature. The application of the various conversion factors is demonstrated by a review of the dose estimation process in 50 cases of fetal irradiation from medical exposures. (author)

Reconfiguring Maternity Care?

DEFF Research Database (Denmark)

Johannsen, Nis

This dissertation constitutes a reflection on two initiatives seeking to reconfigure maternity care. One initiative sought to digitalise maternity records and included a pilot run of an electronic maternity record in a Danish county. The other consisted of a collaboration between a maternity ward...... at a hospital and a group of researchers which included me. Both initiatives involved numerous seemingly different interests that were held together and related to reconfiguring maternity care. None of the initiatives can unequivocally be labelled a success, as neither managed to change maternity care, at least...... experimental designs are constructed. The consequences and the politics of the proposed changes are engaged with in laboratory manner through collaborative development of the designs and through exposing them to members of field of maternity care...

[The relationship between early neo-maternal exposure, and maternal attachment, maternal self-esteem and postpartum depression in the mothers of NICU infants].

Science.gov (United States)

Ahn, Young-Mee; Kim, Mi-Ran

2005-08-01

This study was performed to investigate the quantities of three neo-maternal exposures; visiting frequency, auditory contact and physical contact, and to examine the relationship between the quantities of each exposure and maternal attachment, maternal self-esteem and postpartum depression in 40 mothers of NICU babies during the first week in the NICU. Each neo-maternal exposure was counted at every mother's visit to the newborn and maternal attachment, maternal self-esteem and postpartum depression were measured using the maternal attachment inventory, the maternal self-report inventory and Edinburgh Postpartum Depression Scale (EPDS) on the first and seventh day in the NICU. The Mean of each neo-maternal exposure was 8.77(2.81) for the visiting frequency, 5.82(3.66) for the auditory contact and 5.60(2.89) for the physical contact during 7 days in the NICU. No significant changes were found in the scores of maternal attachment, maternal self-esteem and postpartum depression between the first and the seventh day in the NICU. The quantities of neo-maternal exposures were positively related to the scores of maternal attachment and maternal self-esteem but not related to postpartum depression. The results of the study suggest the lack of early neo-maternal exposure in cases of NICU hospitalization negate its beneficial effects on maternal psychological well-being in increasing maternal attachment and self-esteem. More efforts are needed for the neo-maternal interaction and the reevaluation of NICU visitation hours in order to promote maternal-infant interaction.

Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial.

Science.gov (United States)

Paridaans, Noortje P; Kamphuis, Marije M; Taune Wikman, Agneta; Tiblad, Eleonor; Van den Akker, Eline S; Lopriore, Enrico; Challis, Daniel; Westgren, Magnus; Oepkes, Dick

2015-01-01

Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e., 0.5 g/kg. This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 10(9)/l (range 8-269) in the 0.5 g/kg group versus 110 × 10(9)/l (range 11-279) in the 1 g/kg group (p = 0.644). The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

Placental transfer and pharmacokinetics of a single oral dose of [14C] p-nitrophenol in rats

International Nuclear Information System (INIS)

Abu-Qare, A.W.; Brownie, C.F.; Abou-Donia, M.B.

2000-01-01

The pharmacokinetics and placental transfer of a single oral dose of 100 mg/kg (10 μCi/kg, 16% of acute oral LD 50 ) of uniformly phenyl-labeled [ 14 C]p-nitrophenol were investigated in pregnant Sprague-Dawley rats at 14-18 days of gestation. Three animals were killed on gestation day 18, at 0.5, 1, 2, 4, 12, 24, and 48 h after dosing. Radioactivity was rapidly absorbed and distributed throughout the maternal and fetal tissues. The gastrointestinal tract contents retained 20% and 2% of the dose at 0.5 h and 4 h after dosing. The peak maternal plasma concentration of radioactivity (μg p-nitrophenol equivalent/ml) was 7.17 compared with 0.37 for fetal plasma at 0.5 h. Maximum concentration of radioactivity (μg p-nitrophenol equivalent/g fresh tissue) was detected in most tissues 0.5 h after dosing and was in descending order: kidney 23.27, liver 12.37, placenta 3.56, fetus 2.17, and brain 1.99. Radioactivity was eliminated from plasma and all tissues beiexponentially. The half-lives of elimination of 14 C were 34.65 h and 69.30 h for maternal and fetal plasma, respectively. p-Nitrophenol, detected by HPLC, was the major compound identified in plasma and tissues. While p-nitrophenol disappeared biphasically from maternal plasma and kidney, it was eliminated monophasically from brain, placenta, and liver. p-Nitrocatechol and p-aminophenol were detected in the liver with peak concentrations at 0.5 h of 1.13 and 1.00 μg/g fresh tissue, respectively. While the change in the concentration of p-nitrocatechol with time was monophasic, that of p-aminophenol showed a biphasic pattern with elimination half-lives of 1.93 h and 4.95 h, respectively. Radioactivity was rapidly excreted in the urine mostly as polar metabolites, while only 3% of the dose was recovered in the feces. Radioactive materials excreted in the urine comprised: glucuronides 4%, sulfates 8%, hot-acid hydrolysates 11%, nonconjugated compounds 16%, and water-soluble metabolites 61%. This study demonstrated

Is Internet Addiction Prevalent Among Methadone Maintenance Treatment Patients? Data from Las Vegas and Tel Aviv.

Science.gov (United States)

Peles, Einat; Linzy, Shirley; Sason, Anat; Tene, Oren; Adelson, Miriam

2015-01-01

Internet addiction is known to be associated with depression. The Internet Addiction Test (IAT) and the Center for Epidemiologic Studies Depression scale (CES-D) for depression were studied among non-selective methadone maintenance treatment patients from the United States (n = 164) and Israel (n = 113). Thirty percent were not exposed to the internet, and 2.9% (n = 8) had an "occasional/frequent problem." The IAT and CES-D scores correlated significantly (p = .03). The non-exposed group was older, less educated, and had more benzodiazepine abusers. Unlike other behavioral addictions that characterized these patients, the internet addiction problem is rare, but should not be ignored.

Regional homogeneity changes between heroin relapse and non-relapse patients under methadone maintenance treatment: a resting-state fMRI study

OpenAIRE

Chang, Haifeng; Li, Wei; Li, Qiang; Chen, Jiajie; Zhu, Jia; Ye, Jianjun; Liu, Jierong; Li, Zhe; Li, Yongbin; Shi, Ming; Wang, Yarong; Wang, Wei

2016-01-01

Background Methadone maintenance treatment (MMT) is recognized as one of the most effective treatments for heroin addiction but its effect is dimmed by the high incidence of heroin relapse. However, underlying neurobiology mechanism of heroin relapse under MMT is still largely unknown. Here, we took advantage of a resting-state fMRI technique by analysis of regional homogeneity (ReHo), and tried to explore the difference of brain function between heroin relapsers and non-relapsers in MMT. Met...

Maternal anxiety, maternal sensitivity, and attachment

NARCIS (Netherlands)

Stevenson-Hinde, Joan; Chicot, Rebecca; Shouldice, Anne; Hinde, Camilla A.

2016-01-01

Previous research has related maternal anxiety to insecurity of attachment. Here we ask whether different aspects of maternal sensitivity mediate this link. From a community sample of intact families with 1-3 children, mothers with 4.5-year-olds were selected for low, medium, or high anxiety

Maternal anxiety, maternal sensitivity, and attachment

NARCIS (Netherlands)

Stevenson-Hinde, J.; Chicot, R.; Schouldice, A.; Hinde, C.A.

2013-01-01

Previous research has related maternal anxiety to insecurity of attachment. Here we ask whether different aspects of maternal sensitivity mediate this link. From a community sample of intact families with 1-3 children, mothers with 4.5-year-olds were selected for low, medium, or high anxiety levels

Long-term effects of environmentally relevant doses of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153 on neurobehavioural development, health and spontaneous behaviour in maternally exposed mice

Directory of Open Access Journals (Sweden)

Heegaard Einar

2011-01-01

Full Text Available Abstract Background Polychlorinated biphenyls (PCBs are widespread in the environment, human food and breast milk. Seafood is known to contain nutrients beneficial for the normal development and function of the brain, but also contaminants such as PCBs which are neurotoxic. Exposure to non-coplanar PCBs during brain development can disrupt spontaneous behaviour in mice and lead to hyperactive behaviour. Humans are chronically exposed to the highest relative levels of organochlorines in early childhood during brain development, though usually at doses which do not give clinical symptoms of toxicity. This study aimed to elucidate the developmental and behavioural effects of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153 in mice, mimicking human exposure during gestation and lactation. Methods Environmentally relevant doses of PCB153 were added to the experimental diets. Feed concentrations were approximately 0.5, 6.5, and 1500 μg PCB153/kg feed, representing a realistic and a worst case scenario of frequent consumption of contaminated fish. The study also investigated the effects of maternal nutrition, i.e. a standard rodent diet versus a high inclusion of salmon. Mice pups were examined for physical- and reflex development, sensorimotor function and spontaneous behaviour from five days after birth until weaning. A selection of pups were followed until 16 weeks of age and tested for open field behaviour and the acoustic startle response (ASR with prepulse inhibition (PPI. Blood thyroid hormones and liver enzymes, blood lipids and PCB153 content in fat were examined at 16 weeks. Statistical analyses modelled the three way interactions of diet, PCB exposure and litter size on behaviour, using generalized linear models (GLM and linear mixed effect models (LME. The litter was used as a random variable. Non-parametric tests were used for pair wise comparisons of biochemical analyses. Results Litter size consistently influenced pup development and behaviour

Long-term effects of environmentally relevant doses of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153) on neurobehavioural development, health and spontaneous behaviour in maternally exposed mice.

Science.gov (United States)

Haave, Marte; Bernhard, Annette; Jellestad, Finn K; Heegaard, Einar; Brattelid, Trond; Lundebye, Anne-Katrine

2011-01-13

Polychlorinated biphenyls (PCBs) are widespread in the environment, human food and breast milk. Seafood is known to contain nutrients beneficial for the normal development and function of the brain, but also contaminants such as PCBs which are neurotoxic. Exposure to non-coplanar PCBs during brain development can disrupt spontaneous behaviour in mice and lead to hyperactive behaviour. Humans are chronically exposed to the highest relative levels of organochlorines in early childhood during brain development, though usually at doses which do not give clinical symptoms of toxicity. This study aimed to elucidate the developmental and behavioural effects of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153) in mice, mimicking human exposure during gestation and lactation. Environmentally relevant doses of PCB153 were added to the experimental diets. Feed concentrations were approximately 0.5, 6.5, and 1500 μg PCB153/kg feed, representing a realistic and a worst case scenario of frequent consumption of contaminated fish. The study also investigated the effects of maternal nutrition, i.e. a standard rodent diet versus a high inclusion of salmon. Mice pups were examined for physical- and reflex development, sensorimotor function and spontaneous behaviour from five days after birth until weaning. A selection of pups were followed until 16 weeks of age and tested for open field behaviour and the acoustic startle response (ASR) with prepulse inhibition (PPI). Blood thyroid hormones and liver enzymes, blood lipids and PCB153 content in fat were examined at 16 weeks. Statistical analyses modelled the three way interactions of diet, PCB exposure and litter size on behaviour, using generalized linear models (GLM) and linear mixed effect models (LME). The litter was used as a random variable. Non-parametric tests were used for pair wise comparisons of biochemical analyses. Litter size consistently influenced pup development and behaviour. Few lasting PCB153 related changes were observed

Effects of maternal confidence and competence on maternal parenting stress in newborn care.

Science.gov (United States)

Liu, Chien-Chi; Chen, Yueh-Chih; Yeh, Yen-Po; Hsieh, Yeu-Sheng

2012-04-01

This paper is a report of a correlational study of the relations of maternal confidence and maternal competence to maternal parenting stress during newborn care. Maternal role development is a cognitive and social process influenced by cultural and family contexts and mother and child characteristics. Most knowledge about maternal role development comes from western society. However, perceptions of the maternal role in contemporary Taiwanese society may be affected by contextual and environmental factors. A prospective correlational design was used to recruit 372 postpartum Taiwanese women and their infants from well-child clinics at 16 health centres in central Taiwan. Inclusion criteria for mothers were gestational age >37 weeks, ≥18 years old, and healthy, with infants maternal confidence, maternal competence and self-perceived maternal parenting stress. After controlling for maternal parity and infant temperament, high maternal confidence and competence were associated with low maternal parenting stress. Maternal confidence influenced maternal parenting stress both directly and indirectly via maternal competence. To assist postpartum women in infant care programmes achieve positive outcomes, nurses should evaluate and bolster mothers' belief in their own abilities. Likewise, nurses should not only consider mothers' infant care skills, but also mothers' parity and infant temperament. Finally, it is crucial for nurses and researchers to recognize that infant care programmes should be tailored to mothers' specific maternal characteristics. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

Allopathic, complementary, and alternative medical treatment utilization for pain among methadone-maintained patients.

Science.gov (United States)

Barry, Declan T; Beitel, Mark; Cutter, Christopher J; Garnet, Brian; Joshi, Dipa; Schottenfeld, Richard S; Rounsaville, Bruce J

2009-01-01

We surveyed 150 methadone maintenance treatment program (MMTP) patients about pain, pain treatment utilization, perceived efficacy of prior pain treatment, and interest in pursuing pain treatment at the MMTP. Respondents with chronic severe pain (CSP) (ie, pain lasting at least six months with moderate to severe pain intensity or significant pain interference) and "some pain" (ie, pain reported in the previous week but not CSP) endorsed similar rates of past-week and lifetime allopathic or standard medical (with the exception of lifetime medical use of non-opiate medication) and complementary and alternative medicine (CAM) utilization for pain reduction. Prior pain treatments were perceived to be less effective by CSP than SP patients but both groups had equivalent high rates of interest in pain treatment associated with the MMTP. These findings may have implications for resource and program planning in MMTPs.

Non-invasive in situ identification and band assignments of diazepam, flunitrazepam and methadone hydrochloride with FT-near-infrared spectroscopy.

Science.gov (United States)

Ali, Hassan Refat H

2011-03-20

Near-infrared spectroscopy (NIR) has evolved into an important rapid, direct and non-invasive technique in drugs analysis. In this study, the suitability of NIR spectroscopy to identify two benzodiazepine derivatives, diazepam and flunitrazepam, and a synthetic opiate, methadone hydrochloride, inside USP vials and probe the solid-state form of diazepam presents in tablets has been explored. The results show the potential of NIR spectroscopy for rapid, in situ and non-destructive identification of drugs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Maternal Depression and Youth Internalizing and Externalizing Symptomatology: Severity and Chronicity of Past Maternal Depression and Current Maternal Depressive Symptoms

Science.gov (United States)

O’Connor, Erin E.; Langer, David A.; Tompson, Martha C.

2017-01-01

Maternal depression is a well-documented risk factor for youth depression, and taking into account its severity and chronicity may provide important insight into the degree of risk conferred. This study explored the degree to which the severity/chronicity of maternal depression history explained variance in youth internalizing and externalizing symptoms above and beyond current maternal depressive symptoms among 171 youth (58% male) ages 8 to 12 over a span of three years. Severity and chronicity of past maternal depression and current maternal depressive symptoms were examined as predictors of parent-reported youth internalizing and externalizing symptomatology, as well as youth self-reported depressive symptoms. Severity and chronicity of past maternal depression did not account for additional variance in youth internalizing and externalizing symptoms at Time 1 beyond what was accounted for by maternal depressive symptoms at Time 1. Longitudinal growth curve modeling indicated that prior severity/chronicity of maternal depression predicted levels of youth internalizing and externalizing symptoms at each time point when controlling for current maternal depressive symptoms at each time point. Chronicity of maternal depression, apart from severity, also predicted rate of change in youth externalizing symptoms over time. These findings highlight the importance of screening and assessing for current maternal depressive symptoms, as well as the nature of past depressive episodes. Possible mechanisms underlying the association between severity/chronicity of maternal depression and youth outcomes, such as residual effects from depressive history on mother–child interactions, are discussed. PMID:27401880

Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally.

Science.gov (United States)

Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

2014-03-01

Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg·d) from gestational days (GD) 11 to 20, or 180 mg/kg·d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose-effect study and on GD11, 14 and 17 in the time-course study were analyzed by ¹H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. Copyright © 2014 Elsevier Inc. All rights reserved.

Contribution of maternal radionuclide burdens to prenatal radiation doses

International Nuclear Information System (INIS)

Sikov, M.R.; Hui, T.E.; Meznarich, H.K.; Thrall, K.D.

1992-03-01

This report discusses approaches to calculating and expressing radiation doses to the embryo/fetus from internal radionuclides. Information was obtained for selected, occupationally significant radionuclides in chemical forms that provided a spectrum of metabolic and dosimetric characteristics. Fractional placental transfer and/or ratios of concentration in the embryo/fetus to that in the woman were estimated for these materials, and were combined with data from biokinetic transfer models to predict radioactivity levels in the embryo/fetus as a function of stage of pregnancy and time after entry into the transfer compartment or blood of the pregnant woman. Medical Internal Radiation Dosimetry (MIRD) methodologies were extended to formalize and describe details for calculating radiation absorbed doses to the embryo/fetus. Calculations were performed for representative situations; introduction of 1 μCi into a woman's blood at successive months of pregnancy was assumed to accommodate the stage dependence of geometric relationships and biological behaviors. Summary tables of results, correlations, and dosimetric relations, and of tentative generalized categorizations, are provided in the report

Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro

DEFF Research Database (Denmark)

Fanoe, Søren; Jensen, Gorm Boje; Sjøgren, Per

2008-01-01

with the use of these drugs. WHAT THIS PAPER ADDS: This study is the first to show that oxycodone dose is associated with QT prolongation and in vitro blockade of hERG channels expressed in HEK293. Neither morphine nor tramadol doses are associated with the QT interval length. AIMS: During recent years some...... and TdP could be a more general problem associated with the use of these drugs. The aims of this study were to evaluate the association between different opioids and the QTc among patients and measure hERG activity under influence by opioids in vitro. METHODS: One hundred chronic nonmalignant pain...... patients treated with methadone, oxycodone, morphine or tramadol were recruited in a cross-sectional study. The QTc was estimated from a 12-lead ECG. To examine hERG activity in the presence of oxycodone, electrophysiological testing was conducted using Xenopus laevis oocytes and HEK293 cells expressing h...

Child Health, Maternal Marital and Socioeconomic Factors, and Maternal Health

OpenAIRE

Garbarski, Dana; Witt, Whitney P.

2012-01-01

While maternal socioeconomic status and health predict in part children’s future health and socioeconomic prospects, it is possible that the intergenerational association flows in the other direction such that child health affects maternal outcomes. Previous research demonstrates that poor child health increases the risk of adverse maternal physical and mental health outcomes. We hypothesize that poor child health may also increase the risk of poor maternal health outcomes through an interact...

The WHO maternal near-miss approach and the maternal severity index model (MSI: tools for assessing the management of severe maternal morbidity.

Directory of Open Access Journals (Sweden)

Joao Paulo Souza

Full Text Available OBJECTIVES: To validate the WHO maternal near-miss criteria and develop a benchmark tool for severe maternal morbidity assessments. METHODS: In a multicenter cross-sectional study implemented in 27 referral maternity hospitals in Brazil, a one-year prospective surveillance on severe maternal morbidity and data collection was carried out. Diagnostic accuracy tests were used to assess the validity of the WHO maternal near-miss criteria. Binary logistic regression was used to model the death probability among women with severe maternal complications and benchmark the management of severe maternal morbidity. RESULTS: Of the 82,388 women having deliveries in the participating health facilities, 9,555 women presented pregnancy-related complications, including 140 maternal deaths and 770 maternal near misses. The WHO maternal near-miss criteria were found to be accurate and highly associated with maternal deaths (Positive likelihood ratio 106.8 (95% CI 99.56-114.6. The maternal severity index (MSI model was developed and found to able to describe the relationship between life-threatening conditions and mortality (Area under the ROC curve: 0.951 (95% CI 0.909-0.993. CONCLUSION: The identification of maternal near-miss cases using the WHO list of pregnancy-related life-threatening conditions was validated. The MSI model can be used as a tool for benchmarking the performance of health services managing women with severe maternal complications and provide case-mix adjustment.

The maternal health outcomes of paid maternity leave: a systematic review.

Science.gov (United States)

Aitken, Zoe; Garrett, Cameryn C; Hewitt, Belinda; Keogh, Louise; Hocking, Jane S; Kavanagh, Anne M

2015-04-01

Paid maternity leave has become a standard benefit in many countries throughout the world. Although maternal health has been central to the rationale for paid maternity leave, no review has specifically examined the effect of paid maternity leave on maternal health. The aim of this paper is to provide a systematic review of studies that examine the association between paid maternity leave and maternal health. We conducted a comprehensive search of electronic databases (Medline, Embase, CINAHL, PsycINFO, Web of Science, Sociological Abstracts) and Google Scholar. We searched websites of relevant organisations, reference lists of key papers and journals, and citation indices for additional studies including those not in refereed journals. There were no language restrictions. Studies were included if they compared paid maternity leave versus no paid maternity leave, or different lengths of paid leave. Data were extracted and an assessment of bias was performed independently by authors. Seven studies were identified, with participants from Australia, Sweden, Norway, USA, Canada, and Lebanon. All studies used quantitative methodologies, including cohort, cross-sectional, and repeated cross-sectional designs. Outcomes included mental health and wellbeing, general health, physical wellbeing, and intimate partner violence. The four studies that examined leave at an individual level showed evidence of maternal health benefits, whereas the three studies conducting policy-level comparisons reported either no association or evidence of a negative association. The synthesis of the results suggested that paid maternity leave provided maternal health benefits, although this varied depending on the length of leave. This has important implications for public health and social policy. However, all studies were subject to confounding bias and many to reverse causation. Given the small number of studies and the methodological limitations of the evidence, longitudinal studies are

Progeny of male rats treated with methadone: physiological and behavioural effects.

Science.gov (United States)

Joffe, J M; Peruzović, M; Milković, K

1990-04-01

Male rats were injected with methadone HCl (METH) at 5 mg/kg s.c. for 4 days prior to mating with drug-free females. Offspring resulting from these matings were compared with offspring of drug-free males. The progeny of METH-treated males gained less weight after weaning and had lighter thymuses as adults (but not in infancy). Gonadal weights did not differ in infancy or adulthood, and adrenal weights were heavier in female offspring in adulthood. In adulthood METH offspring were significantly different from controls on all behavioural tests used (open field activity, activity cage activity, passive avoidance latencies, shuttle box avoidances, and rotarod latencies), with the differences frequently affected by test order, days of testing, or sex of offspring. The effects in progeny of METH-treated males in the absence of differences in litter size or neonatal mortality indicate that paternal drug ingestion prior to mating can produce physiological and behavioural changes in progeny that are not dependent on detectable effects on early viability or growth.

Severe maternal morbidity for 2004-2005 in the three Dublin maternity hospitals.

LENUS (Irish Health Repository)

Murphy, Cliona M

2012-02-01

OBJECTIVE: To assess the prevalence and causes of severe maternal morbidity in Dublin over a two year period from 2004 to 2005. STUDY DESIGN: A prospective cohort study from January 2004 to December 2005 was undertaken in the three large maternity hospitals in Dublin, which serve a population of 1.5 million people. All are tertiary referral centres for obstetrics and neonatology and have an annual combined delivery rate of circa 23,000 births. Cases of severe maternal morbidity were identified. A systems based classification was used. The primary cause of maternal morbidity and the number of events experienced per patient was recorded. RESULTS: We identified 158 women who fulfilled the definition for severe maternal morbidity, giving a rate of 3.2 per 1000 maternities. There were two maternal deaths during the time period giving mortality to morbidity ratio of 1:79. The commonest cause of severe morbidity was vascular dysfunction related to obstetric haemorrhage. Eclampsia comprised 15.4% of cases. Intensive care or coronary care admission occurred in 12% of cases. CONCLUSION: The prevalence of severe maternal morbidity in this population is 3.2\\/1000 maternities. Obstetric haemorrhage was the main cause of severe maternal morbidity.

Bisphenol S (BPS) Alters Maternal Behavior and Brain in Mice Exposed During Pregnancy/Lactation and Their Daughters.

Science.gov (United States)

Catanese, Mary C; Vandenberg, Laura N

2017-03-01

Estrogenic endocrine disrupting chemicals have been shown to disrupt maternal behavior in rodents. We investigated the effects of an emerging xenoestrogen, bisphenol S (BPS), on maternal behavior and brain in CD-1 mice exposed during pregnancy and lactation (F0 generation) and in female offspring exposed during gestation and perinatal development (F1 generation). We observed different effects in F0 and F1 dams for a number of components of maternal behavior, including time on the nest, time spent on nest building, latency to retrieve pups, and latency to retrieve the entire litter. We also characterized expression of estrogen receptor α in the medial preoptic area (MPOA) and quantified tyrosine hydroxylase immunoreactive cells in the ventral tegmental area, 2 brain regions critical for maternal care. BPS-treated females in the F0 generation had a statistically significant increase in estrogen receptor α expression in the caudal subregion of the central MPOA in a dose-dependent manner. In contrast, there were no statistically significant effects of BPS on the MPOA in F1 dams or the ventral tegmental area in either generation. This work demonstrates that BPS affects maternal behavior and brain with outcomes depending on generation, dose, and postpartum period. Many studies examining effects of endocrine disrupting chemicals view the mother as a means by which offspring can be exposed during critical periods of development. Here, we demonstrate that pregnancy and lactation are vulnerable periods for the mother. We also show that developmental BPS exposure alters maternal behavior later in adulthood. Both findings have potential public health implications. Copyright © 2017 by the Endocrine Society.

Psychometric properties of the medical outcomes study: social support survey among methadone maintenance patients in Ho Chi Minh City, Vietnam: a validation study.