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Available literature demonstrates that methadone is prone to moderate postmortem redistribution, but subject to high interindividual variability in the central to peripheral blood concentration ratios (C/P). In this case series, 10 cases of chronic methadone users displaying C/P < 1 (range 0.26–0.82) are described. Femoral, cardiac and ante-mortem blood concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) are reported for all cases, as well as sex, age, case history, results of the pathological investigation, other toxicological findings and cause and manner of death. EDDP blood concentrations, similar in both central and peripheral blood, as well as antemortem blood concentration results in Case 4, demonstrate that this atypical C/P < 1 finding is attributable to postmortem changes and not analytical or pre-analytical artifacts. Case 4 is a particularly instructive example, with femoral blood concentration (966 ng/mL) approximately twice as high as cardiac blood (499 ng/mL) and ante-mortem blood (418 ng/mL, collected 38 min prior to death)—clearly demonstrating that cardiac blood methadone concentration is more representative of the antemortem blood concentration in this case. In Case 4 and four others, toxicological interpretation based on femoral blood concentration alone would have been misleading. Based on these results and evidence from the literature, it is hypothesized that methadone bioaccumulates in the tissues of chronic users and redistributes from thigh tissues into femoral blood, increasing the concentration postmortem. This case series highlights how femoral blood is not always preserved from postmortem changes and that the analysis of multiple blood sources is necessary to avoid a misleading toxicological interpretation—particularly for cases of chronic methadone users. [ABSTRACT FROM AUTHOR]

Objective To investigate variation in drug poisoning mortality rates by drug type and occupation in Massachusetts. Methods Death certificates for deaths by drug poisonings occurring between 2010 and 2019 in Massachusetts were coded based on the decedent's occupation. Mortality rates and rate ratios (with all other occupations as the reference group) were calculated based on the occupation of the workers according to drug type. Poisson regression was used to determine significantly elevated mortality rates and trends in drug poisoning deaths by occupation and drug type. Results The rate of drug poisoning deaths increased from 2010 to 2016 after which they plateaued. With respect to specific substances, fentanyl- and cocaine-related deaths increased throughout the surveillance period. For drug poisoning deaths overall, workers in construction trades (3,017); food preparation and serving (1,116); transportation and material moving (1,062) occupations had the highest number of drug poisoning deaths. When adjusting for age, sex, race/ethnicity, and educational attainment, workers in 7 occupations had significantly elevated mortality rate ratios for drug poisonings overall: farming, fishing, and forestry (3.42, P < 0.001); construction trades (2.58, P < 0.001); health care support (1.61, P < 0.001); community and social service (1.60, P < 0.001); food preparation and serving related (1.54, P < 0.001); personal care and service (1.37, P < 0.001); and arts, design, entertainment, sports, and media (1.21, P = 0.010). In many cases, workers in these same occupations had elevated mortality rate ratios for poisonings from specific substances. Health care practitioners and technical occupation workers only had elevated rates for methadone-related poisonings (1.73, P = 0.010). Conclusions These findings highlight that workers in certain occupations have an elevated risk for drug poisonings and that the patterns differ with respect to the drug type. These findings can be useful for providing services to workers in high-risk occupations and in identifying occupational factors that may be related to the risk of drug poisoning death. While previous research has begun to uncover work-related factors that may contribute to opioid use, further work is needed to identify occupational factors that may contribute to psychostimulant and benzodiazepine use. [ABSTRACT FROM AUTHOR]

The article discusses the cases of two patients with endocarditis secondary to injection drug use. Topics discussed include signs and symptoms presented by the patients at the emergency room, disciplines involved in weekly social work-led interdisciplinary huddles for patients with substance use disorder (SUD) undergoing heart surgery, and extensive psychosocial support needed by patients with SUD.

Background Opioid deaths have increased in England and Wales. Coroners' Prevention of Future Deaths reports (PFDs) provide important insights that may enable safer use and avert harms, yet reports implicating opioids have not been synthesized. We aimed to identify opioid-related PFDs and explore coroners' concerns to prevent future deaths. Methods In this systematic case series, we screened 3897 coronial PFDs dated between 01 July 2013 and 23 February 2022, obtained by web scraping the UK's Courts and Tribunals Judiciary website. PFDs were included when an opioid was implicated in the death. Included PFDs were descriptively analysed, and content analysis was used to assess concerns reported by coroners. Results Opioids were involved in 219 deaths reported in PFDs (5·6% of PFDs), equating to 4418 years of life lost (median 33 years/person). Morphine (29%), methadone (23%) and diamorphine (16%) were the most common implicated opioids. Coroners most frequently raised concerns regarding systems and protocols (52%) or safety issues (15%). These concerns were most often addressed to National Health Service (NHS) organizations (51%), but response rates were low overall (47%). Conclusions Opioids could be used more safely if coroners' concerns in PFDs were addressed by national organizations such as NHS bodies, government agencies and policymakers, as well as individual prescribing clinicians. [ABSTRACT FROM AUTHOR]

Urine has been the preferred matrix for monitoring heroin and methadone adherence due to its large detection window. Drawbacks such as privacy concerns and adulteration however require other matrices. The study aims to determine if oral fluid and exhaled breath are suitable alternatives for heroin and methadone monitoring and to assess the detection time in exhaled breath. Forty-three participants, all on methadone and heroin-assisted treatment, were studied. Participants were monitored after the first and right before the second dosage of heroin. At both time points, oral fluid and exhaled breath samples were collected with urine at the second time point. All samples were screened for opiates, methadone and other drugs using immunoassay and LC–MS-MS. At the second time point, 98% of oral fluid samples and all exhaled breath samples tested positive for 6-monoacetylmorphine (6-MAM). Regarding morphine detection, the findings were reversed (100% in oral fluid, 98% in exhaled breath). Methadone-related results were 100% positive across all matrices, as expected. Notable is the detection of the heroin marker acetylcodeine in oral fluid and exhaled breath samples, which resulted in relatively low negative predictive value (average 54.6%). Oral fluid and exhaled breath are suitable alternatives for heroin and methadone maintenance monitoring. Clinicians should consider ease of collection, adulteration risk, costs, turn-around time and the substance of interest while choosing a matrix. In addition, even in cases when medicinal heroin is used, medical professionals should be aware of the presence of acetylcodeine in these alternate matrices. [ABSTRACT FROM AUTHOR]

Background Limited information exists about testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among Medicaid enrollees after starting medication for opioid use disorder (MOUD), despite guidelines recommending such testing. Our objectives were to estimate testing prevalence and trends for HIV, HBV, and HCV among Medicaid enrollees initiating MOUD and examine enrollee characteristics associated with testing. Methods We conducted a serial cross-sectional study of 505 440 initiations of MOUD from 2016 to 2019 among 361 537 Medicaid enrollees in 11 states. Measures of MOUD initiation; HIV, HBV, and HCV testing; comorbidities; and demographics were based on enrollment and claims data. Each state used Poisson regression to estimate associations between enrollee characteristics and testing prevalence within 90 days of MOUD initiation. We pooled state-level estimates to generate global estimates using random effects meta-analyses. Results From 2016 to 2019, testing increased from 20% to 25% for HIV, from 22% to 25% for HBV, from 24% to 27% for HCV, and from 15% to 19% for all 3 conditions. Adjusted rates of testing for all 3 conditions were lower among enrollees who were male (vs nonpregnant females), living in a rural area (vs urban area), and initiating methadone or naltrexone (vs buprenorphine). Associations between enrollee characteristics and testing varied across states. Conclusions Among Medicaid enrollees in 11 US states who initiated medications for opioid use disorder, testing for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and all 3 conditions increased between 2016 and 2019 but the majority were not tested. [ABSTRACT FROM AUTHOR]

Patients with opioid use disorder (OUD) tend to get assigned to one of 3 medications based on the treatment program to which the patient presents (e.g. opioid treatment programs tend to treat patients with methadone, while office-based practices tend to prescribe buprenorphine). It is possible that optimally matching patients with treatment type would reduce the risk of return to regular opioid use (RROU). We analyzed data from 3 comparative effectiveness trials from the US National Institute on Drug Abuse Clinical Trials Network (CTN0027, 2006–2010; CTN0030, 2006–2009; and CTN0051 2014–2017), in which patients with OUD (n  = 1,459) were assigned to treatment with either injection extended-release naltrexone (XR-NTX), sublingual buprenorphine-naloxone (BUP-NX), or oral methadone. We learned an individualized rule by which to assign medication type such that risk of RROU during 12 weeks of treatment would be minimized, and then estimated the amount by which RROU risk could be reduced if the rule were applied. Applying our estimated treatment rule would reduce risk of RROU compared with treating everyone with methadone (relative risk (RR) = 0.79, 95% confidence interval (CI): 0.60, 0.97) or treating everyone with XR-NTX (RR = 0.71, 95% CI: 0.47, 0.96). Applying the estimated treatment rule would have resulted in a similar risk of RROU to that of with treating everyone with BUP-NX (RR = 0.92, 95% CI: 0.73, 1.11). [ABSTRACT FROM AUTHOR]

Burn injury in children can cause severe and chronic physical and mental sequelae. Opioids are a mainstay in burn pain management but increasing utilization in this country has led to concern for their continued use and potential for dependence. Methadone is a long-acting analgesic that targets the N-methyl-D-aspartate (NMDA) receptor in addition to the mu opioid receptor and has benefit in adult burn patients. However, its use in the pediatric burn population has been less robustly studied. This is a retrospective cohort study at a single Level 1 Burn Center whose primary aim is to compare opioid utilization 36 hours postoperatively between pediatric burn patients who received intraoperative, intravenous methadone and those who did not. Secondary aim was to describe differences in methadone-related complications between the cohorts. There was decreased opioid utilization measured by median morphine equivalents per kilogram (ME/kg) postoperatively in the methadone cohort compared to the control cohort (0.54 vs 0.77 mg/kg, P = .18). No adverse events were noted upon chart review. The data suggest that methadone use is beneficial in pediatric burn patients, but further prospective studies are warranted on a larger population. [ABSTRACT FROM AUTHOR]

Opioid use has negative effects on immune responses and may impair immune reconstitution in persons living with HIV (PLWH) infection undergoing antiretroviral treatment (ART). The effects of treatment with μ opioid receptor (MOR) agonists (e.g., methadone, MET) and antagonists (e.g., naltrexone, NTX) on immune reconstitution and immune activation in ART‐suppressed PLWH have not been assessed in‐depth. We studied the effects of methadone or naltrexone on measures of immune reconstitution and immune activation in a cross‐sectional community cohort of 30 HIV‐infected individuals receiving suppressive ART and medications for opioid use disorder (MOUD) (12 MET, 8 NTX and 10 controls). Plasma markers of inflammation and immune activation were measured using ELISA, Luminex, or Simoa. Plasma IgG glycosylation was assessed using capillary electrophoresis. Cell subsets and activation were studied using whole blood flow cytometry. Individuals in the MET group, but no in the NTX group, had higher plasma levels of inflammation and immune activation markers than controls. These markers include soluble CD14 (an independent predictor of morbidity and mortality during HIV infection), proinflammatory cytokines, and proinflammatory IgG glycans. This effect was independent of time on treatment. Our results indicate that methadone‐based MOUD regimens may sustain immune activation and inflammation in ART‐treated HIV‐infected individuals. Our pilot study provides the foundation and rationale for future longitudinal functional studies of the impact of MOUD regimens on immune reconstitution and residual activation after ART‐mediated suppression. [ABSTRACT FROM AUTHOR]

Non-mineralized dental biofilm (plaque) has potential as a novel alternative matrix in forensic toxicology to prove drug use. The incorporation of illicit and medicinal drugs in dental plaque could take place through direct contact after oral or nasal intake, which can lead to high drug levels in the oral cavity, or indirectly via the secretion of drug-containing saliva, e.g. after intravenous application. Therefore, plaque samples from patients in opioid replacement therapy (ORT) and postmortem plaque samples were analyzed and the drug concentrations were compared. The study comprised 26 plaque samples from ORT patients with different daily doses, which were analyzed for methadone, morphine and their respective metabolites. Plaque samples were taken directly before the oral administration of the regular daily dose. Seventeen postmortem plaque samples were analyzed, either from cases of lethal drug intoxications or after pain therapy with morphine. Plaque analysis was performed using liquid chromatography--tandem mass spectrometry after liquid extraction with acetonitrile. Plaque concentrations in ORT for methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) ranged from 42 to approximately 49,000 pg/mg (median 1,300 pg/mg) and from below 10 to 610 pg/mg (median 31 pg/mg), respectively. Morphine plaque concentrations in ORT ranged from 120 to 480 pg/mg (median 400 pg/mg). In lethal intoxication cases, plaque concentrations were generally at least one order of magnitude higher than those in the study groups with therapeutic substance use. These data will help to interpret drug findings in plaque. Furthermore, the EDDP/methadone concentration ratio in plaque was lower after oral intake with contamination of the oral cavity (e.g. syrup) compared to cases with suspected intravenous application of methadone. Therefore, the EDDP/methadone concentration ratio could therefore indicate the drug administration route. [ABSTRACT FROM AUTHOR]

Peripheral blood (PB) concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to decomposition or large traumas, etc. In such cases, other tissues or bodily fluids must be sampled; however, limited information exists on postmortem concentrations in matrices other than blood. Pericardial fluid (PF), muscle and vitreous humor (VH) have been suggested as alternatives to blood, but only a few studies have investigated the detection of opioids in these matrices. In this study, we aimed to investigate the detection of methadone, buprenorphine, oxycodone, fentanyl and tramadol in postmortem samples of PF, skeletal muscle and VH, in addition to PB and cardiac blood and if drug concentrations in these alternative matrices were comparable to those in PB and thereby useful for interpretation. In most of the 54 included cases, only one opioid was detected. Methadone, oxycodone, fentanyl and tramadol were detected in all of the alternative matrices in almost all cases, while buprenorphine was detected less often. For methadone, the concentrations in the alternative matrices, except in VH, were relatively similar to those in PB. Larger variations in concentrations were found for buprenorphine, oxycodone and tramadol. Quantitative analyses appeared useful for fentanyl, in all of the alternative matrices, but only four cases were included. Toxicological analyses of opioids in these alternative postmortem matrices can be useful for detection, but quantitative results must be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background Serotonin toxicity (also referred to as serotonin syndrome) results from medications that affect the neurotransmitter serotonin. The antibiotic linezolid and the opioids methadone and buprenorphine are all reported to cause serotonin toxicity, but the degree of risk with use of linezolid in combination with methadone or buprenorphine is unknown. Methods We conducted a retrospective cross-sectional analysis of adult patients hospitalized from November 2015 to October 2019 who were administered linezolid in combination with methadone and/or buprenorphine within 24 hours and a subgroup that received the combination for ≥3 days. Cases of serotonin toxicity were identified from the clinical notes in the electronic medical record and were classified as possible or definite based on the clinical record. The Hunter diagnostic criteria were retrospectively applied. Results There were 494 encounters in which linezolid was administered concurrently with methadone and buprenorphine. The mean patient age was 42.5 years, and 52.4% of encounters were of female patients. The mean duration of concurrent administration was 1.9 days. There were 106 encounters with a duration of concurrent administration ≥3 days (mean, 5.4 days). Two cases of possible serotonin toxicity and 0 cases of definite serotonin toxicity occurred; neither possible case met the Hunter criteria from the available information. Possible cases occurred in 0.40% of all encounters and 1.89% of encounters with ≥3 days of overlap (upper 1-sided 95% CI, 0.87% and 4.06%). Conclusions Serotonin toxicity occurring during the administration of linezolid in combination with methadone and/or buprenorphine occurred rarely among 494 hospital encounters, including 106 encounters with ≥3 days of overlap. Limitations include potential missed diagnoses of serotonin toxicity and short durations of overlap. Further study evaluating the short-term risk of this combination is needed. [ABSTRACT FROM AUTHOR]

Objectives: The prevalence of opioid use disorder (OUD) among pregnant women is increasing. Research consistently demonstrates the efficacy of medications for OUD (MOUD); however, researchers have called for additional studies evaluating the safety of MOUD during pregnancy, particularly the relative safety of two commonly used MOUD medications-methadone and buprenorphine. This study aimed to evaluate the consequences of MOUD exposure during pregnancy on risk for neonatal abstinence syndrome (NAS).Methods: In a clinical sample of infants born to women with OUD, we evaluated the risk of NAS among those exposed to (i) methadone and (ii) buprenorphine compared with those unexposed to MOUD, as well as the risk of NAS among those exposed to (i) methadone compared with those exposed to (ii) buprenorphine.Results: Compared with buprenorphine-exposed infants (n = 37), methadone-exposed infants (n = 27) were at increased risk for NAS (odds ratio [OR] = 4.67, 95% confidence interval [CI]: 1.03, 21.17). Compared with unexposed infants (n = 43), buprenorphine-exposed infants were at decreased risk for NAS (OR = 0.45, 95% CI: 0.14, 1.39) and methadone-exposed infants were at increased risk for NAS (OR = 2.64, 95% CI: 0.79, 8.76), though these associations were not statistically significant.Conclusions: Our study suggests that when methadone and buprenorphine are equally appropriate options for the treatment of OUD in pregnant women, buprenorphine may add the additional benefit of reduced risk of newborn NAS. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to assess the efficacy and adverse effects of methadone when used as first-line therapy in patients that are either receiving low doses of opioids or none. Methods Patients with advanced cancer were prospectively assessed. Opioid-naive patients (L-group) were started with methadone at 6 mg/day. Patients receiving weak or other opioids in doses of <60 mg/day of OME (H-group) were started with methadone at 9 mg/day. Methadone doses were changed according to the clinical needs to obtain the most favorable balance between analgesia and adverse effects. Edmonton Symptom Asssement Score (ESAS), Memorial Delirium Assessment Score (MDAS), doses of methadone, and the use of adjuvant drugs were recorded before starting the study treatment (T0), 1 week after (T7), 2 weeks after (T14), 1 month after (T30), and 2 months after (T60). Methadone escalation index percent (MEI%) and in mg (MEImg) were calculated at T30 and T60. Results Eighty-two patients were assessed. In both groups H and L, there were significant changes in pain and symptom intensity at the different times during the study. Adverse effects as causes of drop-out were minimal. Mean MEImg was 0.09 (SD 0.28) and 0.02 (SD 0.07) at T30 and T60, respectively. MEI% was 1.01 (SD 3.08) and 0.27 (SD 0.86) at T30 and T60, respectively. Conclusion Methadone used as a first-line opioid therapy provided good analgesia with limited adverse effects and a minimal opioid-induced tolerance. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of intraoperative methadone in comparison with those of standard-of-care intraoperative opioids, such as fentanyl and morphine, on pain scores, opioid consumption, and adverse effects in adults undergoing cardiothoracic surgery. Methods The literature was reviewed in PubMed, Embase, Cochrane Library, and Google Scholar, followed by a manual search of the reference lists of the identified articles. Search terms included a combination of "intraoperative methadone," "methadone," and "cardiac surgery." Our review includes four studies published between 2011 and 2020. Quality assessment of the studies was performed. Results The initial search identified 715 articles, from which 461 duplicates were removed and 236 were eliminated on the basis of inclusion and exclusion criteria. Eighteen articles underwent full-text review. Four studies evaluating a total of 435 patients with various cardiothoracic procedures were included in this review. We found that intraoperative methadone decreased acute postoperative pain and reduced postoperative opioid consumption in the first 24 postoperative hours in patients who received 0.1–0.3 mg/kg intraoperative methadone in comparison with morphine and fentanyl. No difference was found in adverse effects between the groups. Quality assessment of the studies showed a low risk of bias in three of the randomized controlled trials and a high risk of bias in the retrospective review because of the baseline confounding bias in the study design. Conclusions Intraoperative methadone use reduces acute postoperative pain and lowers opioid consumption in comparison with morphine and fentanyl. Initial results suggest that methadone may be an equivalent opioid to be administered during cardiothoracic procedures to reduce acute postsurgical pain, though further research is warranted. [ABSTRACT FROM AUTHOR]

The article presents case study of 52-year-old woman who presented to pain medicine clinic initially in 2012 due to painful lower extremity spasticity and increasing spasms in the upper extremities. It mentions diagnosis of neurosarcoidosis, a multi-organ system granulomatous disease that, when untreated, can cause significant morbidity and mortality.

Objective State prescription drug monitoring programs (PDMPs) identify controlled medications dispensed across providers and systems. Department of Veterans Affairs (VA) policy requires electronic health record documentation of PDMP queries at least annually for VA patients receiving controlled medications; however, queries are not uniformly conducted. We examined factors associated with PDMP queries for veterans receiving long-term opioid therapy. Methods Veterans with a VA provider who received long-term opioid therapy between August 2015 and August 2016 within a four-state region were identified; 9,879 were due for a PDMP query between August 2016 and February 2017. Likelihood of veterans' PDMP queries during this follow-up period was modeled as a function of patient, provider, and facility characteristics of interest in mixed-effects modified Poisson models estimating relative risk and 95% confidence intervals. Multivariable models controlled for potential confounders identified through the use of directed acyclic graphs. Results PDMP queries were documented for 62.1% of veterans that were due for a PDMP query. Veterans were more likely to be queried if they were Hispanic or if they received methadone, had average daily milligram morphine equivalents >20, or received urine drug screening during the studied period. Veterans were less likely to be queried if they had a rural address, mail order medication, or cancer diagnosis. Likelihood of PDMP queries was also lower for veterans whose opioid-prescribing provider was an oncologist or working in a low-complexity facility. Conclusions Adherence to PDMP query policy within the VA varied by patient, clinician, and facility factors. Mechanisms to standardize the conduct of PDMP queries may be needed. [ABSTRACT FROM AUTHOR]

Narcotic bowel syndrome is defined as worsening abdominal bloating and cramping with chronic opiate use, leading to paralytic ileus. This syndrome is common yet underreported in adults. However, there is no current evidence of such conditions in the newborn after exposure in utero to high doses of opiates. Our patient was a female indigenous preterm infant born to a mother on a high dose of methadone. On admission at the age of 12 h, she was found to have significant gastric distension. Initial abdominal X-ray showed a large gastric bubble with little evidence of rectal gas. Malrotation was suspected and surgical intervention was discussed. However, repeat abdominal X-ray, ultrasound and upper Gastrointestinal series were found to be normal and without acute findings. Thus, surgery was avoided. The gastric distension resolved spontaneously. She never required opiate therapy for neonatal abstinence syndrome. Given the pattern of gas seen on the initial abdominal X-ray and its spontaneous resolution after removal of maternal methadone, we suspect this baby had neonatal narcotic bowel syndrome. This has never been reported in the literature and is a unique finding. Given the lack of current reports, further observations for this syndrome should be conducted. [ABSTRACT FROM AUTHOR]

A microextraction by packed sorbent (MEPS) procedure for rapid concentration of methadone and its primary metabolite (EDDP) in hair samples was developed. The miniaturized approach coupled to gas chromatography with tandem mass spectrometry (GC–MS-MS) was successfully validated. Hair samples (50 mg) were incubated with 1 mL of 1 M sodium hydroxide for 45 min at 50°C, time after which the extract was neutralized by adding 100 μL of 20% formic acid. Subsequently, MEPS was applied using a M1 sorbent (4 mg; 80% C8 and 20% strong cation-exchange (SCX)), first conditioned with three 250-μL cycles of methanol and three 250-μL cycles of 2% formic acid. The extract load occurred with nine 150-μL cycles followed by a washing step involving three 50-μL cycles with 3.36% formic acid. For the elution of the analytes, six 100-μL cycles of 2.36% ammonium hydroxide in methanol were applied. The method was linear from 0.01 to 5 ng/mg, for both compounds, presenting determination coefficients greater than 0.99. Precision and accuracy were in accordance with the statements of international guidelines for method validation. This new miniaturized approach allowed obtaining recoveries ranging from 73 to 109% for methadone and 84 to 110% for EDDP, proving to be an excellent alternative to classic approaches, as well as other miniaturized procedures. [ABSTRACT FROM AUTHOR]

Methadone is an opioid commonly used for acute pain management in burn patients. One adverse effect of methadone is QTc interval prolongation, which may be associated with adverse cardiac outcomes. There is currently a paucity of data regarding risk of QTc prolongation in burn patients taking methadone and a lack of evidence-based recommendations for monitoring strategies in this population. The study objective was to determine the prevalence, risk factors, and cardiac outcomes related to methadone-associated QTc prolongation in adult burn patients. A total of 91 patients were included and were divided into groups according to maximum QTc. QTc prolongation was defined as greater than or equal to 470 ms (males) or 480 ms (females). There were no differences between groups regarding patient-specific risk factors, baseline QTc, or time to longest QTc. Patients in the prolonged QTc group had a higher rate of cardiac events (44% vs 9%; P < .001), higher median (IQR) change from baseline to longest QTc (61 ms [18,88] vs 23 ms [13,38]; P < .001), higher median (IQR) total daily dose of methadone (90 mg [53,98] vs 53 mg [30,75]; P = .004), and longer median (IQR) length of stay (53 [33,82] vs 35 [26,52] days; P = .008). QTc prolongation in burn patients was associated with increased methadone dose and resulted in a higher rate of cardiac events. This study was the first of its kind to look at risk factors and cardiac outcomes associated with methadone use in burn patients. [ABSTRACT FROM AUTHOR]

Background Digital therapeutic tools (e.g. mobile applications) can be accessible, low-cost interventions that counter misconceptions about medication assisted treatment (MAT) and/or improve deficits in MAT knowledge that are common barriers to treatment entry among individuals with opioid dependence. The purpose of this pilot study was to examine the preliminary effectiveness of a mobile application, 'uMAT-R', that includes health information about OUD recovery supported by science and MAT benefits. Methods Twenty-six adult participants with OUD recruited via social media completed all modules and pre/post-assessments within uMAT-R. McNemar's test was used to compare interest in treatment before and after completing the app, and paired t tests were used to compare MAT attitude scores before and after completing the modules within uMAT-R. Results Before viewing uMAT-R, 32% agreed/strongly agreed that they were interested in starting treatment to recover from opioid misuse, compared to 48% after completing uMAT-R. The average scores on the MAT attitudes scale and its Aid to Behavior Change subscale improved from before to after viewing uMAT-R. Among the participants, 88% felt that uMAT-R would be useful to consult when making decisions about recovery. Conclusions Our encouraging pilot findings support the use of uMAT-R to help address the current opioid epidemic. [ABSTRACT FROM AUTHOR]

Background and Objectives: Substance use disorders are highly prevalent among individuals with psychotic disorders and are associated with negative outcomes. This study aims to explore differences in characteristics and treatment outcomes for individuals with psychotic disorders when compared with individuals with other nonpsychotic psychiatric disorders enrolled in treatment for opioid use disorder (OUD). Methods: Data were collected from a prospective cohort study of 415 individuals enrolled in outpatient methadone maintenance treatment (MMT). Psychiatric comorbidity was assessed using the Mini-International Neuropsychiatric Interview. Participants were followed for 12 months. Participant characteristics associated with having a psychotic disorder versus another nonpsychotic psychiatric disorder were explored by logistic regression analysis. Results: Altogether, 37 individuals (9%) with a psychotic disorder were identified. Having a psychotic disorder was associated with less opioid-positive urine drug screens (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.95, 0.99, P = .046). Twelve-month retention in treatment was not associated with psychotic disorder group status (OR = 0.73, 95% CI = 0.3, 1.77, P = .485). Participants with psychotic disorders were more likely to be prescribed antidepressants (OR = 2.12, 95% CI = 1.06, 4.22, P = .033), antipsychotics (OR = 3.57, 95% CI = 1.74, 7.32, P = .001), mood stabilizers (OR = 6.61, 95% CI = 1.51, 28.97, P = .012), and benzodiazepines (OR = 2.22, 95% CI = 1.11, 4.43, P = .024).Discussion and Conclusions: This study contributes to the sparse literature on outcomes of individuals with psychotic disorders and OUD-receiving MMT. Rates of retention in treatment and opioid use are encouraging and contrast to the widely held belief that these individuals do more poorly in treatment. Higher rates of coprescription of sedating and QTc-prolonging medications in this group may pose unique safety concerns. [ABSTRACT FROM AUTHOR]

Background Despite high hepatitis C virus (HCV) prevalence, opioid use disorder (OUD) patients on methadone rarely engage in HCV treatment. We investigated the effectiveness of HCV management via telemedicine in an opioid substitution therapy (OST) program. Methods OUD patients on methadone underwent biweekly telemedicine sessions between a hepatologist and physician assistant during the entire HCV treatment course. All pretreatment labs (HCV RNA, genotype, and noninvasive fibrosis assessments) were obtained onsite and direct-acting antivirals were coadministered with methadone using modified directly observed therapy. We used multiple correspondence analysis, least absolute shrinkage and selection operator, and logistic regression to identify variables associated with pursuit of HCV care. Results Sixty-two HCV RNA–positive patients (24% human immunodeficiency virus [HIV] infected, 61% male, 61% African American, 25.8% Hispanic) were evaluated. All patients were stabilized on methadone and all except 4 were HCV genotype 1 infected. Advanced fibrosis/cirrhosis was present in 34.5% of patients. Of the 45 treated patients, 42 (93.3%) achieved viral eradication. Of 17 evaluated patients who were not treated, 5 were discontinued from the drug treatment program or did not follow up after the evaluation, 2 had HIV adherence issues, and 10 had insurance authorization issues. Marriage and a mental health diagnosis other than depression were the strongest positive predictors of treatment pursuit, whereas being divorced, separated, or widowed was the strongest negative predictor. Conclusions HCV management via telemedicine integrated into an OST program is a feasible model with excellent virologic effectiveness. Psychosocial and demographic variables can assist in identification of subgroups with a propensity or aversion to pursue HCV treatment. [ABSTRACT FROM AUTHOR]

Aims To search for pharmaceutical additives in illicit alcoholic beverages referred to the laboratory of Legal Medicine Organization in Iran in 2017. Methods Hundred beverages were sampled. Ethanol content was determined by gas chromatography with flame ionization detection (GC–FID) and then a liquid-liquid extraction combined with reversed-phase high performance liquid chromatography equipped with a photodiode array detector (PAD) was employed for the qualitative analysis. The analysis was confirmed using gas chromatography coupled with mass spectroscopy (GC/MS). Results In 15% either one or more of the following were detected: tramadol, methadone, diazepam, oxazepam, flurazepam and alprazolam. Tramadol was found with highest frequency. Conclusions The wide availability of addictive pharmaceutical is leading to fortification of alcoholic beverages on some countries. The addition of such depressant additives should be better known because of the potentially fatal consequences of the combination with ethanol, as well as the potential for adverse effects on behavior. [ABSTRACT FROM AUTHOR]

Aims To search for pharmaceutical additives in illicit alcoholic beverages referred to the laboratory of Legal Medicine Organization in Iran in 2017. Methods Hundred beverages were sampled. Ethanol content was determined by gas chromatography with flame ionization detection (GC–FID) and then a liquid-liquid extraction combined with reversed-phase high performance liquid chromatography equipped with a photodiode array detector (PAD) was employed for the qualitative analysis. The analysis was confirmed using gas chromatography coupled with mass spectroscopy (GC/MS). Results In 15% either one or more of the following were detected: tramadol, methadone, diazepam, oxazepam, flurazepam and alprazolam. Tramadol was found with highest frequency. Conclusions The wide availability of addictive pharmaceutical is leading to fortification of alcoholic beverages on some countries. The addition of such depressant additives should be better known because of the potentially fatal consequences of the combination with ethanol, as well as the potential for adverse effects on behavior. [ABSTRACT FROM AUTHOR]

Background Although evidence from animal and human studies indicates opioid analgesics increase susceptibility to infections, it is unclear whether the risk varies by specific opioid. We compared the risk of serious infection among patients initiating long-acting opioid analgesics with and without previously reported immunosuppressive properties. Methods We conducted a retrospective cohort study of Tennessee Medicaid enrollees age ≥18 years initiating long-acting opioids (1995–2015). Hospitalizations for serious infection were identified using validated coding algorithms. We used multivariable Poisson regression models to calculate adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) to compare the infection risk among patients using long-acting opioids with known immunosuppressive properties (morphine, fentanyl, methadone) to the infection risk among patients using long-acting opioids without known immunosuppressive properties (oxycodone, oxymorphone, tramadol) accounting for demographics, opioid dose, comorbidities and pain conditions, medication use, frailty indicators, and healthcare encounter history using exposure propensity scores. We further compared users of individual long-acting opioids to long-acting morphine users (considered the prototypical immunosuppressive opioid). Results Among the 61 240 patients initiating opioids with immunosuppressive properties and 22 811 patients initiating opioids without immunosuppressive properties, we identified 1906 serious infections. Nonimmunosuppressive opioid users had a lower rate of infections than immunosuppressive opioid users (aIRR:0.78 [CI: 0.66–0.91]). Among individual opioids, oxycodone users had a lower rate of infection than morphine users (aIRR:0.73 [CI: 0.60–0.89]). There were no significant differences in the infection risk between other opioids and morphine. Conclusion The risk of serious infections among long-acting opioid users varies by opioid type. Providers should carefully consider the risk of serious infections when making pain management decisions. [ABSTRACT FROM AUTHOR]

Methadone maintenance therapy is a cost-effective, evidence-based treatment for heroin dependence. In the USA, a majority of heroin-dependent offenders are forced to detox from methadone when incarcerated. Recent research published in The Lancet has demonstrated the negative health and economic outcomes associated with such policies (Rich, J. D. McKenzie, M. Larney, S. Wong, J. B. Tran, L. Clarke, J. et al. (2015). Methadone Continuation Versus Forced Withdrawal on Incarceration in a Combined US Prison and Jail: A Randomised, Open Label Trial. The Lancet, 386, 350–359). This novel evidence raises questions as to the justification for current policies of forced detox in American prisons. Opponents of methadone provision in prisons might offer arguments from retributivism, resource allocation and curative effectiveness to justify their position. This article contends that these arguments do not stand up to ethical scrutiny. In light of this, we hold that American policymakers should reform criminal justice policies to allow the initiation and continuation of methadone treatment in correctional settings. This would be consistent with both international recommendations and the example set by a number of other Western countries. [ABSTRACT FROM AUTHOR]

Background There is no countable biomarker for opioid dependence treatment responses thus far. In this study, we recruited Taiwanese methadone maintenance treatment patients to search for genes involving the regulatory mechanisms of methadone dose by genome-wide association analyses. Methods A total of 344 Taiwanese methadone maintenance treatment patients were included in a genome-wide association study. The involvement of GRK5 in opioid dependence was then further confirmed by gene expression study on lymphoblastoid cell lines derived from 3 independent age- and gender-matched groups: methadone maintenance treatment patients, medication-free former heroin abusers, and normal controls. Results The results indicated that GRK5, the gene encoding an enzyme related to μ-opioid receptor desensitization, is associated with methadone dose by additive model of gene-based association analysis (P =6.76×10-5). We found that 6 of the 55 single nucleotide polymorphisms from the genome-wide genotype platform and 2 single nucleotide polymorphisms from the 29 additionally selected single nucleotide polymorphisms were significantly associated with methadone maintenance dose in both genotype and allele type (P ≤.006), especially in patients who tested negative in the urine morphine test. The levels of GRK5 gene expression were similar between methadone maintenance treatment patients and medication-free former heroin abusers. However, the normal controls showed a significantly lower level of GRK5 gene expression than the other groups (P=.019). Conclusions The results suggested an important role for GRK5 in the regulatory mechanisms of methadone dose and course of heroin dependence. [ABSTRACT FROM AUTHOR]

In forensic toxicology, when extended time has elapsed before discovery of the body, the most commonly analyzed specimens are often degraded or not available at all due to decomposition. In this case, skeletal tissue may be the only specimen left. Nevertheless, very limited research is found on the drug disposition in bone, making toxicological interpretation very difficult. Since methadone is linked to almost 50% of drug abuse fatalities in Belgium, an easy extraction and quantification method was developed and validated to investigate the distribution pattern of methadone and its metabolites in skeletal tissue after chronic dosing. In this study, Wistar rats were administered a subcutaneous daily methadone dose of 3 mg/kg for 139 days. After dissection, single whole bones or bone parts underwent a methanolic extraction. The final extract was analyzed using LC-ESI(+)--MS-MS for methadone, EDDP and EMDP. Methadone and its metabolites were proven to be detectable and quantifiable in skeletal tissue of chronically dosed rats using a fast and easy methanol extraction. Within bone, comparison showed that bone marrow yields the highest concentration. Trabecular bone also showed to be the best type of bone tissue for sampling. Between bone comparison, proved the humerus to be the best bone type for sampling. The concentrations found in tibiae and humeri appeared to be dose dependent for methadone with a variance of <9%. However, for other bones the variance in methadone concentration ranged from 24 to 32%. A possible explanation is seen in the lower vascularization of these bones. For the metabolites, no correlation was seen. This could be explained by the highly inter-individual metabolism of methadone. However, skeletal tissue concentration showed no correlation to blood for methadone nor its metabolites. Using the developed method, quantitative information about methadone after chronic administration was only found in the humeri and tibiae. [ABSTRACT FROM AUTHOR]

Confounding may account for the apparently improved infant outcomes after prenatal exposure to buprenorphine versus methadone. We used Massachusetts Medicaid Analytic eXtract (MAX) data to identify a cohort of opioid-dependent mother-infant pairs (2006-2011), supplemented with confounder data from an external Boston, Massachusetts, cohort (2015-2016). Associations between prenatal buprenorphine exposure versus methadone exposure and infant outcomes in the MAX cohort were adjusted for measured MAX confounders and were additionally adjusted for unmeasured confounders with bias analysis using external cohort data. A total of 477 women in MAX were treated with methadone and 543 with buprenorphine. More buprenorphine users than methadone users were white and used psychotropic medications. After adjustment forMAX confounders, risk ratios among infants exposed to buprenorphine versus those exposed tomethadone were 0.45 (95% confidence interval (CI): 0.34, 0.61) for preterm birth (birth at <37 weeks) and 0.75 (95%CI: 0.51, 1.11) for low birth weight for gestational age. The mean difference in infant hospitalization was -7.35 days (95% CI: -9.16, -5.55). After further adjustment with bias analysis, the risk ratios were 0.53 (95%CI: 0.39, 0.71) for preterm birth and 1.14 (95%CI: 0.77, 1.69) for low birth weight for gestational age, and the mean difference in infant hospitalization was -3.66 days (95% CI:-5.46,-1.87). External confounder data can be used to adjust for unmeasured confounding in studies of prenatal outcomes among women on opioid agonist therapy based on administrative databases. [ABSTRACT FROM AUTHOR]

The quantification of drugs of abuse in keratinized matrices is becoming of special relevance for monitoring consumption and for post-mortem investigations. We aimed to implement an analytical method for the simultaneous detection of morphine (MORF), 6-monoacetylmorphine (6-MAM), methadone (MET), 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrrolidine (EMDP) in nails. After decontamination, the nail samples (30 mg) were submitted to an alkaline digestion followed by a two-step liquid--liquid and SPE extraction using mixed-mode cation exchange cartridges. The analytes were eluted with 5% NH4OH/methanol. After derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide, the analytes were quantified by gas chromatography-mass spectrometry. The method was optimized and fully validated only for MET, EDDP and EMDP, since for MOR and 6-MAM it was not possible to obtain adequate recovery rates after extraction, although detection of MOR was still possible. The method was selective, accurate and precise. Regression analysis demonstrated linearity over a concentration range of 20.8-333.3 ng/mg for MET and 10.4-166.7 ng/mg for EDDP and EMDP. Limits of detection and quantification values ranged from 3.3 to 6.0 ng/mg and 10.4 to 20.8 ng/mg, respectively, and recovery rates ranged from 82% to 98%. The applicability of the method was demonstrated by analyzing nail and urine samples obtained from heroin consumers under substitution therapy with MET. [ABSTRACT FROM AUTHOR]

Objective. Sharp increases in opioid prescriptions, and associated increases in overdose deaths in the 2000s, evoked widespread calls to change perceptions of opioid analgesics. Medical literature discussions of opioid analgesics began emphasizing patient and public health hazards. Repetitive exposure to this information may influence physician assumptions. While highly consequential to patients with pain whose function and quality of life may benefit from opioid analgesics, current assumptions about prescription opioid analgesics, including their role in the ongoing opioid overdose epidemic, have not been scrutinized. Methods. Information was obtained by searching PubMed, governmental agency websites, and conference proceedings. Results. Opioid analgesic prescribing and associated overdose deaths both peaked around 2011 and are in long-term decline; the sharp overdose increase recorded in 2014 was driven by illicit fentanyl and heroin. Nonmethadone prescription opioid analgesic deaths, in the absence of co-ingested benzodiazepines, alcohol, or other central nervous system/respiratory depressants, are infrequent. Within five years of initial prescription opioid misuse, 3.6% initiate heroin use. The United States consumes 80% of the world opioid supply, but opioid access is nonexistent for 80% and severely restricted for 4.1% of the global population. Conclusions. Many current assumptions about opioid analgesics are ill-founded. Illicit fentanyl and heroin, not opioid prescribing, now fuel the current opioid overdose epidemic. National discussion has often neglected the potentially devastating effects of uncontrolled chronic pain. Opioid analgesic prescribing and related overdoses are in decline, at great cost to patients with pain who have benefited or may benefit from, but cannot access, opioid analgesic therapy. [ABSTRACT FROM AUTHOR]

The article profiles the American Academy of Pain Medicine (AAPM) president Steven P. Santos who has been serving the AAPM members and an advocate for patients suffering with pain. He states that he treated his patients with care and misunderstanding especially the patients with stigma and lack of compassion. He also states that he reevaluated their current opioid treatment and has helped improve their quality of life and decrease the patients' risk for harm.

Objective. To examine how drug counselors with no prior training in pain management respond to their patients' reports of chronic pain. Design, Setting, Subjects, and Methods. We conducted individual interviews with 30 drug counselors in methadone maintenance treatment. Interviews were audiotaped, transcribed, and systematically coded using the constant comparative method. Results. Participants identified counselor, patient, and logistical factors that serve as a barrier or facilitate their treatment of patients with chronic pain. Counselor barriers included lack of expertise in managing co-occurring chronic pain and opioid use disorder, complexity of patients' treatment needs, concerns about medication regimens, reliance on patient self-report, and absence of patient improvement. Counselor barriers facilitators included empathy, attending to small changes, and self-reflection. Counselors' perceptions of patientrelated barriers included prior negative interactions with medical providers, diminished social roles, attenuated motivation, and negative attitudes toward opioid use disorder. Logistical barriers included lack of appropriate pain management referrals, limited counselor time, and attenuated treatment adherence; a logistical facilitator was consulting with medical providers. Conclusions. Perceived barriers to treating patients with chronic noncancer pain are common among drug counselors. Addressing these barriers in drug counselor training and in methadone maintenance treatment programs may benefit both methadonemaintained patients with chronic pain and their providers. [ABSTRACT FROM AUTHOR]

Objectives: Patient satisfaction can provide a measure of service quality and serve as a predictor of health-related behaviors. Little is known about how patients' satisfaction with clinician-patient interactions affects their adherence to taking analgesics. The purposes of this study were to (1) investigate the predictors of patients' satisfaction with clinicians, and (2) examine whether patients' satisfaction with their clinicians can improve adherence to analgesic use.Design: A cross-sectional and descriptive design was used.Setting: Outpatient oncology clinic at a medical center in Taiwan.Participants: A convenience sample (N = 309) was recruited.Main Outcome Measures: The Medical Interview Satisfaction Scale 21 - Chinese Version, Short Version of the Barriers Questionnaire - Taiwan Form, Taiwanese version of the Morisky Medication Adherence Measure, and Interpersonal Physician Trust Scale - Chinese version, and Brief Pain Inventory Chinese Version.Results: Variables that could significantly predict patients' satisfaction were patient age and trust in clinicians, which together accounted for 33% of the total variance. Patients' satisfaction with their clinicians significantly predicted patients' adherence to medication use (OR = 3.10, P < 0.05). There was an interactive effect (OR = 0.12, P < 0.05) between patients' satisfaction and barriers to analgesic use. Correlation coefficients between barriers to analgesic use and patients' adherence are -0.52 (P < 0.001) and -0.13 (P = 0.20) in the higher satisfaction and lower satisfaction patients, respectively.Conclusions: Patients' satisfaction with their clinicians can have a positive effect on changing analgesics adherence behaviors when patients hold incorrect beliefs about analgesics. Patients' satisfaction has an important role in enhancement of analgesics adherence behaviors. [ABSTRACT FROM AUTHOR]

Background Poisoning has become the leading cause of injury death in the USA--with opioid analgesic involved in more fatal poisonings than any other drug, including cocaine and heroin. The epidemic of prescription drug poisonings is a public health concern. This study aimed to define potential high-risk groups for unintentional prescription drug poisoning by methadone, opioid analgesics, antidepressants or benzodiazepines. Methods A hospital-based retrospective case series analysis of admissions related to prescription drug poisonings associated with methadone, opioid analgesics, antidepressants or benzodiazepines for hospitals in Clark County, Nevada between 2009 and 2013 was employed. Results There were 7414 admissions with a primary diagnosis of an unintentional poisoning due to methadone, opioid analgesics, antidepressants or benzodiazepines. Women had the highest rate of admissions particularly in the 45-54 age group. Higher rates of admissions were also found among non-Hispanic whites, single and uninsured populations. There were concerning increases in admissions among 65+ and Native American/Alaskan Native subgroups in 2013. Benzodiazepines and opioid analgesics were the most prevalent drug categories for prescription drug poisoning admissions. Conclusion Public health professionals can utilize hospital data to identify populations at risk and in need of targeted interventions. [ABSTRACT FROM AUTHOR]

Cytochrome P450 (CYP) enzyme 2B6 plays a significant role in the stereo-selective metabolism of (S)-methadone to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine, an inactive methadone metabolite. Elevated (S)-methadone can cause cardiotoxicity by prolonging the QT interval of the heart's electrical cycle. Large inter-individual variability of methadone pharmacokinetics causes discordance in the relationship between dose, plasma concentrations and side effects. The purpose of this study was to determine if one or more single nucleotide polymorphisms (SNPs) located within the CYP2B6 gene contributes to a poor metabolizer phenotype for methadone in these fatal cases. The genetic analysis was conducted on 125 Caucasian methadone-only fatalities obtained from the West Virginia and Kentucky Offices of the Chief Medical Examiner. The frequency of eight exonic and intronic SNPs (rs2279344, rs3211371, rs3745274, rs4803419, rs8192709, rs8192719, rs12721655 and rs35979566) was determined. The frequencies of SNPs rs3745274 (*9, c516G > T, Q172H), and rs8192719 (21563 C > T) were enhanced in themethadone-only group. Higher blood methadone concentrations were observed in individuals who were genotyped homozygous for SNP rs3211371 (*5, c1459C > T, R487C). These results indicate that these three CYP2B6 SNPs are associated with methadone fatalities. [ABSTRACT FROM AUTHOR]

Driving after illicit drug use is a worldwide growing concern requiring rapid and sensitive screening at the roadside. It is noteworthy that the sampling method used to collect oral fluid (OF) may significantly influence drug concentrations in the collected sample and thus alter the accuracy of the measurement. We evaluated two OF collection devices, Quantisal® and Certus® collectors, for their suitability for collecting samples to allow laboratory confirmation of driving after illicit drug use. Four parameters were studied including (i) the collected OF volume; (ii) the recovery efficiency using OFs spiked with opiates, cannabinoids, amphetamines, cocaine and its metabolites; (iii) drug stability after storage for 1, 7 and 14 days at -20°C, +4°C and room temperature; and (iv) the impact of mouth cells present in the collected OF on drug stability. Drug concentrations were measured using gas and liquid chromatography-mass spectrometry. Certus® collector allowed the collection of significantly larger (0.94 ± 0.18 mL vs. 0.84 ± 0.06mL, P = 0.08) but less reproducible OF volumes (19 vs. 6.7%) compared with Quantisal® collector. Drug recovery was significantly better with Quantisal® than with Certus® collector, especially when used to detect cannabinoids (0.94 vs. 0.54, P < 0.001 for Δ9-tetrahydrocannabinol (THC)). For both OF collectors, storage at 4°C was preferable except for methadone, the stability of which was altered by adherence to the collector device. In the presence of mouth cells in the OF sample, THC concentrations were significantly decreased at Day 7 in comparison with Day 1 with both collection devices (P = 0.001 with Quantisal® collector and P = 0.01 with Certus® collector). In conclusion, Quantisal® collector is more reliable than Certus® collector although the practicability of both devices remains to be determined at the roadside. [ABSTRACT FROM AUTHOR]

Introduction. Most clinical reports on methadone rotation describe outcomes in hospitalized patients. The few studies that have included outpatients are retrospective. The aim of this study was to assess the efficacy and safety of methadone as a second-line opioid in adult patients with advanced cancer after rotation in routine clinical practice at a palliative care outpatient clinic. Patients and Methods. This was a prospective, open-label study of 145 patients whose treatment was rotated from other opioids to methadone. Informed consent was obtained in all cases. The main outcome measure was change in the variable "worst pain" at day 28. Pain and pain interference were assessed with the Brief Pain Inventory, with side effects evaluated according to the Common Terminology Criteria for Adverse Events version 3.0. Pain levels were evaluated at study entry and at days 3, 7, 9,14, 21, and 28. Results. Rotation to methadone was performed for the following reasons: poor pain control (77.9%), opioid side effects (2.1%), or both (20%). The mean daily oral morphine equivalent dose before rotation was 193.7 mg. The median worst and average pain scores decreased significantly (p < .0001) from baseline to day 28: The median worst pain score decreased from 9 (interquartile range [IQR]: 8-10) to 6 (IQR: 3-8), and the median average pain score decreased from 6 (IQR: 5-7) to 4 (IQR: 2-5). The proportions of patients with moderate to severe worst and average pain decreased by 30.3% and 47.5%, respectively, by day 28. No increase in opioid toxicity was observed during the study. Conclusion. In outpatients with advanced cancer, rotation to methadone as a second-line opioid was efficacious and safe when using a tiered scheme with close follow-up by experienced health professionals. [ABSTRACT FROM AUTHOR]

Background: Opiates such as morphine are the most powerful analgesics, but their protracted use is restrained by the development of tolerance to analgesic effects. Recent works suggest that tolerance to morphine might be due to its inability to promote mu opioid receptor endocytosis, and the co-injection of morphine with a mu opioid receptor internalizing agonist like [D-Ala²,N-Me-Phe4,Gly-ol5]enkephalin reduces tolerance to morphine. So far, no studies have been conducted to evaluate the ability of methadone to reduce morphine tolerance in morphine-pretreated animals, a treatment sequence that could be encountered in opiate rotation protocol. We investigated the ability of methadone (a mu opioid receptor internalizing agonist used in therapy) to reverse morphine tolerance and the associated cellular mechanisms in the periaqueductal gray matter, a region involved in pain control. Methods: We measured analgesic response following a challenge dose of morphine in the hot plate test and investigated regulation of mu opioid receptor (coupling and endocytosis) and some cellular mechanisms involved in tolerance such as adenylate cyclase superactivation and changes in N-methyl-d-aspartate receptor subunits expression and phosphorylation state. Results: A chronic treatment with morphine promoted tolerance to its analgesic effects and was associated with a lack of mu opioid receptor endocytosis, adenylate cyclase overshoot, NR2A and NR2B downregulation, and phosphorylation of NR1. We reported that a methadone treatment in morphine-treated mice reversed morphine tolerance to analgesia by promoting mu opioid receptor endocytosis and blocking cellular mechanisms of tolerance. Conclusions: Our data might lead to rational strategies to tackle opiate tolerance in the frame of opiate rotation. [ABSTRACT FROM AUTHOR]

Introduction: Smoking cessation pharmacotherapies tested in persons with opioid use disorder have produced low quit rates. Electronic cigarettes (e-cigarettes) have been used by many methadone-maintained (MMT) smokers, but controlled trials evaluating cessation and reduction outcomes have not been performed in this population with deleterious tobacco-related health consequences.Methods: In this open trial of NJOY e-cigarettes, MMT smokers received 6 weeks of treatment and were instructed to use only e-cigarettes. Outcomes included carbon monoxide confirmed 7-day point smoking cessation prevalence at week 7 (end of treatment) and self-reported change in mean cigarettes per day (CPD) at each 2-week assessment. The final assessment was 2 weeks after treatment ended (week 9).Results: The 12 participants averaged 46 years old and 50% were male. On average, participants reported smoking 17.8 (±5.3) CPD. One person had a biochemically confirmed quit at week 7. Participants tended to report marked reductions in mean CPD between quit day (week 1) and the week 3 assessment. Relative to baseline, statistically significant reductions in mean CPD were observed at all follow-up assessments. Mean reductions in CPD were -12.4 (95% confidence interval [CI]: -15.0, -9.9; P < .001), -14.8 (95% CI: -17.4, -12.2; P < .001), -13.9 (95% CI: -16.6, -11.2), and -10.8 (95% CI: -13.4, -8.2; P < .01) at the 3-, 5-, 7-, and 9-week assessments, respectively. Adherence to e-cigarettes was 89.1% during the 6 treatment weeks.Conclusions: E-cigarettes were associated with reductions in cigarette use. Smoking cessation rates in MMT smokers are low and whether long-term smoking reductions can persist and produce health benefits should be studied.Implications: E-cigarettes were associated with reduced tobacco use in MMT smokers. Adherence to e-cigarettes is high among methadone smokers. Week-7 smoking quit rates are similar to pharmacotherapies tested in this population. [ABSTRACT FROM AUTHOR]

Introduction: Addiction treatment clients are more likely to die of tobacco-related diseases than of alcohol or illicit drug-related causes. We aimed to assess smoking behavior, and smoking-related attitudes and services, in New York addiction treatment programs before a statewide smoking ban in treatment facilities was implemented (2008), 1 year (2009) and 5 years after implementation (2013).Methods: We conducted surveys at each time point with clients (N = 329, 341, and 353, respectively) and staff (N = 202, 203, and 166, respectively) from five residential and two methadone maintenance programs in New York State. At each data collection wave, questionnaires measured smoking behavior as well as smoking-related knowledge, attitudes, and experiences with tobacco cessation services as part of addiction treatment.Results: Staff smoking prevalence decreased from 35.2% in 2008 to 21.8% in 2013 (P = .005) while client smoking prevalence over the same period was unchanged (68.1% vs. 66.0%, P = .564). Among clients who smoked, mean cigarettes per day decreased from 13.7 (SD = 8.38) to 10.2 (SD = 4.44; P < .001). There were significant time-by-treatment-type interactions for client tobacco-related attitudes and cessation services received; and for staff self-efficacy and cessation services provided. In residential programs, scores for most items decreased (became less positive) in 2009 followed by a partial rebound in 2013. Methadone program scores tended to rise (become more positive) throughout the study period.Conclusions: Staff and clients may respond differentially to tobacco-free policies depending on type of treatment program, and this finding may help to inform the implementation of tobacco-free policies in other statewide addiction treatment systems. [ABSTRACT FROM AUTHOR]

Objective. Equianalgesic conversion methods are commonly used to switch patients from one opioid to another due to suboptimal pain relief or adverse events. There is no universally accepted opioid conversion method, however, and there is often significant variability between conversion resources. As a result, patients are at risk for undertreated pain and serious adverse events. The purpose of this survey was to compare the equianalgesic conversion estimates between nurse practitioners, pharmacists, and physicians for commonly prescribed opioids. Methods. A survey form was developed using Survey Monkey. Participation was solicited by providing a link to the survey via social media (e.g., Facebook, Twitter, LinkedIn, etc.) and emailing professional organizations for sharing with their members and followers. Data collected included demographics and estimated morphine equivalents (MEQs) of hydrocodone 80 mg, fentanyl transdermal patches 1,800 mcg (as 75 mcg/hour), methadone 40 mg, oxycodone 120 mg, and hydromorphone 48 mg. Participants were also asked to provide their choice of reference utilized to complete the conversions, including personal knowledge. Descriptive analyses were performed using measures of central tendency. Hypothesis testing was performed using Pearson's chi-squared and Fisher's Exact Test for categorical data and the Kruskal--Wallis equality of populations rank test for continuous data to assess differences between median opioid doses by professional groups. Results. The total number of respondents included in the analysis was 319. Physicians, pharmacists, and nurse practitioners/physician assistants comprised 25.4%, 56.7%, and 16.3%, respectively, of respondents. The overall mean (6 standard deviation) MEQ doses for fentanyl, hydrocodone, hydromorphone, methadone, and oxycodone were: 176 (6117) mg, 88 (642) mg, 192 (655) mg, 193 (6201) mg, and 173 (639) mg, respectively. For fentanyl, the mean (6standard deviation) MEQ doses were 180 (6122) mg, 178 (6128) mg, and 157 (668) mg, for physicians, pharmacists, and nurse practitioners/physician assistants, respectively. For all three groups of clinicians, the median MEQ dose for fentanyl was 150 mg. The mean (6 standard deviation) MEQ doses of methadone for physicians, pharmacists, and nurse practitioners/physician assistants were: 214 (6142) mg, 171 (6107) mg, and 185 (6129) mg, respectively. The median MEQ dose for methadone was 160 mg for each of the clinician groups. Conclusions. As evidenced by large standard deviations, there was significant variation in mean opioid conversions to MEQ doses within each profession type, particularly for fentanyl and methadone. The median MEQ doses provided for opioid conversions were the same among each profession. No universal method exists that allows each of the five studied opioids to be accurately and consistently converted to another opioid (i.e., morphine). [ABSTRACT FROM AUTHOR]

Objective. The subject of this publication has been focused on local considerations for facilitating regional best practice, including identifying and uniformly adopting the most relevant international guidelines on opioid use (OU) in chronic pain management. Design and Setting. The Change Pain Latin America (CPLA) Advisory Panel conducted a comprehensive, robust, and critical analysis of published national and international reviews and guidelines of OU, considering those most appropriate for Latin America. Methods. A PubMed search was conducted using the terms "opioid," "chronic," and "pain" and then refined using the filters "practice guidelines" and "within the last 5 years" (2007-2012). Once the publications were identified, they were selected using five key criteria: "Evidence based," "Comprehensive," "From a well-recognized source," "Current publications," and "Based on best practice" and then critically analyzed considering 10 key criteria for determining the most relevant guidelines to be applied in Latin America. Results. The initial PubMed search identified 177 reviews and guidelines, which was reduced to 16 articles using the five preliminary criteria. After a secondary analysis according to the 10 key criteria specific to OU in Latin America, 10 publications were selected for critical review and discussion. Conclusions. The CPLA advisory panel considered the "Safe and effective use of opioids for chronic non-cancer pain" (published in 2010 by the NOUGG of Canada) to be valid, relevant to Latin America, practical, evidence-based, concise, unambiguous, and sufficiently educational to provide clear instruction on OU and pain management and, thus, recommended for uniform adoption across the Latin America region. [ABSTRACT FROM AUTHOR]

Individuals with opioid use disorder experiencing a non-fatal opioid-overdose (OOD) are at heightened risk for future OODs; there are no interventions to facilitate treatment enrollment for these patients. Our goal was to develop and initially test the 'tailored telephone intervention delivered by peers to prevent recurring opioid-overdoses' (TTIP-PRO), a computer-facilitated, peer-delivered, individually tailored secondary prevention intervention designed to: (i) encourage patients to initiate medication-assisted treatment (MAT) and (ii) increase OOD knowledge. A pre-post-study assessed TTIP-PRO-content acceptability and software performance. Two Peer Interventionists, who were abstinent from illicit opioids, enrolled in MAT and had experience with OOD, were recruited from a MAT clinic. Recruitment letters were sent to patients treated for OOD in a hospital emergency department within the prior 8 months. Eight patients received TTIP-PRO and completed pre-/post-assessment. Peer Interventionists completed training within 4 h and reported high satisfaction with TTIP-PRO. There were no performance issues with the software. All participants rated TTIP-PRO as 'very helpful'. Participants' OOD knowledge increased significantly, with 69.9% correct responses pre-TTIP-PRO and 93.6% post-TTIP-PRO. Interest in receiving MAT, measured on a 10-point scale, increased from 8.1 to 9.5, but this change was not statistically significant. Further development and testing of TTIP-PRO appears warranted. [ABSTRACT FROM AUTHOR]

Current methods of methadone analysis in untreated urine are traditionally limited to enzyme immunoassays (EIA) while confirmation techniques require specimen processing (i.e., sample clean-up) before analyzing by gas or liquid chromatography coupled with mass spectrometry (GC-MS or LC-MS-MS). EIA and traditional confirmation techniques can be costly and, at times inefficient. As an alternative approach, we present Direct Analysis in Real Time (DART™) coupled with both time-of-flight and triple quadrupole linear ion trap (Q-TRAP™) mass spectrometers for screening and confirming methadone in untreated urine specimens. These approaches require neither expensive kits nor sample clean-up for analysis. More importantly, the total combined analysis time for both screening and confirmation methods was <5 min per sample; in contrast to the 3-5day process required by traditional EIA, GC-MS and LC-MS-MS techniques. To examine the fundamental protocol and its applicability for routine drug screening, studies were performed that included limits of detection, precision, selectivity and specificity, sample recovery and stability and method robustness. The methods described in this report were determined to be highly specific and selective; allowing for detection of methadone at 250 ng/mL, consistent with cutoffs for current EIA techniques (300 ng/mL). The results reported here demonstrate the DART™ MS platform provides rapid and selective methadone analysis and the potential for providing savings of both time and resources compared with current analysis procedures. [ABSTRACT FROM AUTHOR]

Objective. Despite unknown risks, prescription opioid use (POU) for nonmalignant chronic pain has grown in the US over the last decade. The objective of this study was to examine associations between POU and coronary heart disease (CHD), stroke, and cardiovascular disease (CVD) death in a large cohort. Design, Setting, Subjects. POU was assessed in the prospective cohort study of 29,025 participants of the REasons for Geographic and Racial Differences in Stroke study, enrolled between 2003 and 2007 from the continental United States and followed through December 31, 2010. CHD, stroke, and CVD death were expert adjudicated outcome measures. Methods. Cox proportional hazards models adjusted for CVD risk factors were used. Results. Over a median (SD) of 5.2 (1.8) years of follow- up, 1,362 CHD events, 749 strokes, and 1,120 CVD death occurred (105, 55, and 104, respectively, in the 1,851 opioid users). POU was not associated with CHD (adjusted hazard ratio [aHR]) 1.03 [95% CI 0.83-1.26] or stroke (aHR 1.04 [95% CI 0.78-1.38]), but was associated with CVD death (aHR 1.24 [95% CI 1.00-1.53]) in the overall sample. In the sexstratified analyses, POU was associated with increased risk of CHD (aHR 1.38 [95% CI 1.05-1.82]) and CVD death (aHR 1.66 [95% CI 1.27-2.17]) among females but not males (aHR 0.70 [95% CI 0.50-0.97] for CHD and 0.78 [95% CI 0.54-1.11] for CVD death). Conclusion. Female but not male POU were at higher risk of CHD and CVD death. POU was not associated with stroke in overall or sex-stratified analyses. [ABSTRACT FROM AUTHOR]

Objective Patients with chronic pain frequently experience concomitant sleep disorders. There has been controversy on whether opioids have a beneficial or deleterious effect on sleep quality, duration and efficiency. There is also concern regarding the association between chronic opioid therapy (COT) and sleep disordered breathing (SDB) and the increased risk for unintentional opioid related overdose. This article provides a narrative review of the literature on the effect of opioids on sleep disorders and discusses risk assessment and mitigation strategies. Design A narrative review of the current literature on the effect of prescription opioids on sleep quality and efficiency, the relationship between opioids and sleep disorders and potential risk factors in patients with chronic pain. Results There is conflicting evidence regarding the benefit of opioids in improving sleep quality, duration and efficiency with several studies and reviews suggesting a beneficial effect of opioids on sleep and other studies demonstrating the opioids can cause sleep disturbance leading to hyperalgesia. There was credible evidence of a strong relationship between opioids and SDB with noted risk factors including use of methadone, high opioid dosing (>200 mg MED) and combining opioids with benzodiazepines. Conclusions Further research is required to elucidate the effect of prescription opioids on sleep quality and pain intensity and the risks associated with opioids and SDB. The risk of SDB should be routinely assessed in patients on COT. [ABSTRACT FROM AUTHOR]

Objective The burgeoning rate of prescription opioid misuse, abuse, addiction, and opioid related overdose deaths has gained substantial professional and national media attention. This manuscript provides a narrative review and critique of the literature on prescription opioid misuse, abuse, addiction and opioid-related mortality and discusses future research needs in this area. Design Current literature on misuse, abuse, addiction and opioid related fatalities was reviewed in patients with chronic noncancer pain receiving long-term prescription opioid therapy. Results There have been inconclusive results on the efficacy of long-term opioid therapy in patients with chronic pain but moderate level evidence of dose-dependent risk of harm. The estimated prevalence of prescription opioid abuse and opioid use disorders ranges from <1% to 40% due to the paucity of uniform definitions of what constitutes misuse, abuse, and addiction but several recent studies have developed unique methodology to more accurately assess these states in the pain population. The rate of opioid-related overdose deaths is not inconsequential and a number of patient related and medication specific risk factors have been identified that may provide a basis for risk mitigation strategies. Conclusions Accurately assessing the prevalence of misuse, abuse, and addiction in the pain population has been challenging due to inconsistent definitions between studies. Additional high-quality research is needed in this area utilizing consistent definitions and in reducing the risk of opioid-related overdose fatalities. [ABSTRACT FROM AUTHOR]

Objective To determine if patients receiving chronic opioid therapy can be tapered to lower opioid doses without a subsequent increase in pain. Design Retrospective and prospective chart review at a VA Medical Center. Methods Patients were included in the review if they were prescribed opioids chronically for at least 90 consecutive days and if a plan to taper opioid doses was agreed upon. Patients 89 years of age and older, patients with cancer, and patients exhibiting aberrant behavior were excluded. The primary endpoint was to determine the percent reduction of morphine equivalents (ME) over a 12-month period. Secondary endpoints included percent reduction of ME at 3 and 6 months, change in pain perception at 3, 6, and 12 months, and change in the number of adjuvant medications prescribed at 3, 6, and 12 months. Data were analyzed utilizing descriptive statistics. Results A total of 50 patient charts were included in the study. The average percent reduction of opioid doses was 46% over a 12-month period. Seventy percent of patients either experienced no change in pain or had less pain when comparing baseline to 12 months. An equal percentage of patients either had no change in the number of adjuvant medications prescribed or had more adjuvant medications prescribed when comparing baseline to 12 months. Conclusions Patients in the population studied can be successfully tapered to lower opioid doses and may not necessarily experience more pain. [ABSTRACT FROM AUTHOR]