Reliability and Validity of Addiction Severity Index in Drug Users with Methadone Maintenance Treatment in Guizhou Province, China

Objective To evaluate the reliability and validity of the Chinese version of addiction severity index （ASI）-5th version （ASI-C-5）, in illegal drug users receiving methadone maintenance treatment （MMT） in China. Methods One hundred and eighty-six heroin addicts （144 men and 42 women） receivihg MMT at three clinics in Guizhou province, southwest China, were recmited. They were all interviewed with a questionnaire of ASI-C-5 and 35 were re-interviewed at an interval of seven days to assess its test-retest reliability. Results Cronbach＇s alpha for internal consistency of CSs varied from 0.60 to 0.81 in all domains. Test-retest reliability of composite scores （CSs） of ASI-C-5 were satisfactory （r=0.38-0.97）. Based on item analysis and expert＇s suggestions, five items were deleted and one item was modified in ASI-C-5. Criterion validity of ASI-C-5 was found acceptable, as compared to addicts＇ self-rating anxiety scale （SAS） and self-rating depression scale （SDS） （r=0.59 and 0.45） except for social support rating scale （SSRS）. Conclusions ASI-C-5 can be used for heroin addicts receiving MMT with acceptable reliability and validity.

Conversion from prolonged intravenous fentanyl infusion to enteral methadone in critically ill children

AIM To describe our institutional experience with conversion from intravenous(IV) fentanyl infusion directly to enteral methadone and occurrence of withdrawal in critically ill mechanically ventilated children exposed to prolonged sedation and analgesia.METHODS With Institutional Review Board approval,we retrospectively studied consecutively admitted invasively mechanically ventilated children(0-18 years) sedated with IV fentanyl infusion > 5 d and subsequently converted directly to enteral methadone.Data were obtained onsubject demographics,illness severity,daily IV fentanyl and enteral methadone dosing,time to complete conversion,withdrawal scores(WAT-1),pain scores,and need for rescue opioids.Patients were classified as rapid conversion group(RCG) if completely converted ≤ 48 h and slow conversion group(SCG) if completely converted in > 48 h.Primary outcome was difference in WAT-1 scores at 7 d.Secondary outcomes included differences in overall pain scores,and differences in daily rescue opioids.RESULTS Compared to SCG(n = 21),RCG(n = 21) had lower median WAT-1 scores at 7 d(2.5 vs 5,P = 0.027).Additionally,RCG had lower overall median pain scores(3 vs 6,P = 0.007),and required less median daily rescue opioids(3 vs 12,P = 0.003) than SCG.The starting daily median methadone dose was 2.3 times the daily median fentanyl dose in the RCG,compared to 1.1 times in the SCG(P = 0.049).CONCLUSION We observed wide variation in conversion from IV fentanyl infusion directly to enteral methadone and variability in withdrawal in critically ill mechanically ventilated children exposed to prolonged sedation.In those children who converted successfully from IV fentanyl infusion to enteral methadone within a period of 48 h,a methadone:fentanyl dose conversion ratio of approximately 2.5:1 was associated with less withdrawal and reduced need for rescue opioids.

Effects of Methadone Exposure during Development on Avian Brain and Blood Cells

Maintenance with methadone is standard treatment for opioid-addicted patients, including pregnant women. Cellular effects of methadone exposure during development are investigated by using an avian model, which is free of confounding maternal variables. In the first study, which explored dose by duration interactions, methadone was administered at one of two doses (0.458 mg/kg or 1.75 mg/kg) for one of three durations of exposure: late in development (Incubation Days 12 to 19), middle to late (Days 9 to 19), or early to late (Days 5 to 19). In the second study, 1.00 mg/kg of methadone was administered from days 8 to 18 and compared with controls (0.00 mg/kg). Brain tissue and blood samples were harvested for all dose conditions from the two studies. Increased methadone exposure was associated with subependymal anomalies, subependymal hemorrhaging, edema, monocytic infiltration, an increase in disintegrating red blood cells, an increase in white blood cells, and a decrease in neurons. Significant differences in variance for cell counts by condition were observed. Exposed specimens had significantly more thrombocytes (t = - 2.66, p < 0.05). The anomalies suggest that methadone exposure may be harmful to develop organisms at the cellular level.

Evaluation of the suicide risk factors among methadone maintenance treatment of opiate dependent individuals: A six month assessment

Background: Opiate abuse is a universal socio-medical problem and one of the most important risk factors for suicide, especially in accordance with other psychological disorders. This study designed to evaluate four important suicide risk factors in methadone maintenance therapy clinics within six months treatment. Method: In this cross-sectional study, a psychologist performed interviews with 82 patients who attended in methadone maintenance therapy (MMT) center of Hejazi and Ebnesina hospitals’ clinics, Mashhad, Iran. Five questionnaires including demographic characteristics, Beck Anxiety Inventory (BAI), Beck Hopelessness Scale (BHS), Beck Scale for Suicide Ideation (BSS), Beck Depression Inventory (BDI) were completed at first visit and after six months treatment. Results: Eighty two individuals (68 male and 14 female) ranged between 20 to 44 years old (31.68 ± 4.93) abused mostly crystal (crystal heroein) (79.3%), opium (15.9%) then Shishe (methamphetamine) (4.9%). All studied characteristics of the patients decreased significantly after six month follow up (P 0.05), while BHS after MMT period decreased significantly in men (P = 0.028). Conclusion: The positive effect of methadone maintenance therapy on reduction of four important risk factors for suicide imply on another benefits of this treatment method and it is useful for reduction of suicide risk, among substance abusers.

Methadone Maintenance Treatment Program in Portuguese Community Pharmacies

MMT （Methadone maintenance treatment） is an effective way to treat opioid dependence. In Portugal, an MMT program has been available in pharmacies since January 1998, when a formal agreement was signed by the IDT, I.P. （Institute on Drugs and Drug Addiction）, the PPS （Portuguese Pharmaceutical Society）, and the ANF （National Association of Pharmacies）. In January 2004, the INFARMED （National Authority of Medicine and Health Products） became a partner of the program. The possibility of continuing the treatment at a community pharmacy was restricted to patients receiving a stabilized dose of methadone at IDT, I.P. treatment centers. Pharmacists joining the MMT were given mandatory training. Patients on the MMT program received daily doses of methadone solution under directly observed therapy, and were followed up by trained pharmacists. From January 1998 to January 2013, 3,090 patients underwent MMT in Portuguese community pharmacies. The delivery of MMT at community pharmacy level is feasible. This strategy improves access and adherence to methadone treatment, thus helping to reduce the use of illegal opioids. Community pharmacists fully demonstrated their ability to perform extended roles in public health and harm-reduction strategies. Interaction and close cooperation between the different health professionals and organizations involved were crucial to achieve adequate support to the patients.

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

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 χ 2 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 need for repeat colonoscopy(32.8% vs 12.5%,P = 0.004) were significantly higher in MD group compared to C,respectively.Under univariate analysis,factors significantly associated with MD group were presence of fecal particulate [odds ratio(OR),3.89,95% CI:1.33-11.36,P = 0.01] and solid stool(OR,13.5,95% CI:4.21-43.31,P < 0.001).Fair(OR,3.82,95% CI:1.63-8.96,P = 0.002) and poor(OR,8.10,95% CI:3.05-21.56,P < 0.001) assessment of bowel preparation were more likely to be associated with MD patients.Requirement for repeat colonoscopy was also significant higher in MD group(OR,3.42,95% CI:1.44-8.13,P = 0.01).In the multivariate analyses,the only variable independently associated with MD group was presence of solid stool(OR,7.77,95% CI:1.66-36.47,P = 0.01).Subgroup analysis demonstrated a general trend towards poorer bowel visualization with higher methadone dosage.ANOVA analysis demonstrated that mean methadone dose associated with presence of solid stool(poor visualization) was significantly higher compared to mean dosage for clean colon(excellent visualization,P = 0.02) or for those with liquid stool only(good visualization,P = 0.01).CONCLUSION:Methadone dependence is a risk factor for poor bowel visualization and leads to more repeat colonoscopies.More aggressive bowel preparation may be needed in MD patients.

Cardiovascular Risk of Opioids: A Real-World Study Based on FAERS

Objective:This research utilizes the FAERS for data mining to identify heart-related side effects caused by opioids,ensuring the safe use of these medications.Methods:Data from 79 quarters(Q12004 to Q32023)involving adverse event(AE)reports for opioids like morphine and oxycodone was reviewed.We applied the MedDRA system to categorize events and used statistical tools,ROR and BCPNN,for signal detection.These findings were cross-checked with drug labels and SIDER 4.1 for accuracy.Identified risks were then categorized by severity using DME and IME classifications.Results:Analysis of adverse events(AEs)for the five examined drugs(35359,14367,144441,10592,and 28848)identified 33,6,12,37,and 34 cardiovascular AEs,and 16,5,7,25,and 21 instances of important medical events(IMEs)respectively.Each drug was linked to cases of cardiac and cardiopulmonary arrest.The cardiovascular AEs varied widely in occurrence and severity,with methadone notably presenting diverse and potent risks,including sudden cardiac death as a distinct medical event(DME).A comparison with SIDER 4.1 showed 11 opioid-related cardiovascular AEs in line with our findings.Standardized MedDRA Queries(SMQs)confirmed these results,indicating stronger signals for methadone and tramadol,while morphine,hydromorphone,and oxycodone exhibited fewer and weaker signals.Conclusion:The study revealed numerous heart-related adverse effects(AEs)not listed on drug labels and identified new AE patterns.Recognizing these differences in AE profiles and risks across different opioids is crucial for safer prescription practices to minimize cardiac complications.

Studies on Coordinative Effect of Electroacupuncture and Methadone on Heroin Withdrawal Syndrome

Eight six heroin addicts were randomly divided into the treatment group by electroacupuncture plus Methadone and the control group by single Methadone for comparison of the therapeutic effects. Statistically there was no significant difference in the therapeutic effect （score reduction rate） between the treatment group and the control group （P〉 0.05）, In the treatment group, the dose of Methadone was half of routine dose, but the therapeutic effect was similar and side effect was less, in comparison with full dose in the control group.

Traditional Chinese Medicine-facilitated switch from methadone to buprenorphine-naloxone for treatment of heroin dependence: a case report

The switch from methadone to buprenorphine-naloxone for individuals with heroin dependence is associated with several obstacles and challenges.Such patients may experience discomfort from discontinuing methadone, precipitated withdrawal symptoms induced by buprenorphine-naloxone,and poor psychosocial adjustments such as anticipatory anxiety regarding severe opioid withdrawal.We herein describe a 46-year-old man with a history of heroin dependence who underwent Traditional Chinese Medicine(TCM)-facilitated switching from methadone to buprenorphine-naloxone. No precipitated withdrawal was induced by buprenorphine-naloxone. The drug-switching process was successful and smooth. He maintained abstinence from heroin for the following year. In this case, we applied TCM for enhancement of methadone metabolism and detoxification, analgesic effects, and anxiolytic and hypnotic effects during the drug switch. We observed that TCM effectively facilitated the switch from methadone to buprenorphine-naloxone in our case. Further studies regarding TCM-facilitated treatment for heroin dependence should be conducted.

Dose,Plasma Level,and Treatment Outcome Among Methadone Patients in Shanghai,China

Abstract The purpose of this study was to investigate the blood levels of methadone in participants receiving methadone for the treatment of opioid dependence. After stabilization on methadone for four weeks, blood samples from 95 participants were collected between treatment weeks 4 and 12, before and after receiving doses of methadone, and its blood levels were measured. A multiple linear regression model was used to examine the associa- tion between methadone blood levels and the outcomes of methadone maintenance treatment （MMT）. Outcome dif- ferences between participants who had high （≥2） or low （〈2） peak-to-trough ratios were also compared using an independent sample t-test. The blood level of methadone was not correlated with the clinical outcome of MMT with the moderate range of doses given. However, the retention of patients who had a free peak-to-trough ratio 〉2 was significantly poorer than those whose ratio was 〈2. Thus, monitoring plasma methadone levels is unlikely to be effective for guiding dosing decisions in situations where compliance with MMT is already very high or when themethadone dose is no longer the dominant factor in determining the clinical outcome. However, monitoring plasma methadone levels is still helpful for guiding the dosage for patients with a rapid metabolism.

Clinical Observation on Improvement of Heroin Withdrawal Syndrome by Acupuncture plus Methadone

Purpose： To observe therapeutic effect of acupuncture plus Methadone on improvement of heroin withdrawal syndrome. Methods： Sixty cases of heroin dependence patients were divided into the treatment group and the control group. The treatment group was given acupuncture plus Methadone, and the control group was treated with Methadone. Results： The score of the withdrawal symptoms was lower in the treatment group than in the control group （P〈 0.05）. The improvement of withdrawal symptoms was significantly better in the treatment group than in the control group （P〈 0.05）. Conclusion： Acupuncture plus Methadone can significantly improve heroin withdrawal syndrome.

Prenatal and postnatal drug exposure:focus on persistent central effects

Clinical studies indicate significant use of prescription,nonprescription and social/recreational drugs by women during pregnancy;however,limited knowledge exists about the detrimental effects that this practice may have on the developing central nervous system of the fetus.Importantly,few experimental and clinical data are available on how gestational exposure could exacerbate the effects of the same or a different drug consumed by the offspring later in life.The present review summarizes recent findings on the central toxicity elicited by several classes of drugs,administered prenatally and postnatally in experimental animals and humans,focusing on prescription and nonprescription analgesics,anti-inflammatory agents,alcohol and nicotine.

Nylon 6-cellulose composite hosted in a hypodermic needle: Biofluid extraction and analysis by ambient mass spectrometry in a single device

This study proposes a hypodermic needle(HN)as a sorbent holder and an electrospray(ESI)emitter,thus combining extraction and analysis in a single device.A novel nylon 6-cellulose(N6-Cel)composite sorbent is proposed to extract methadone from oral fluid samples.The cellulosic substrate provides the composite with high porosity,permitting the flow-through of the sample,while the polyamide contributes to the extraction of the analyte.The low price of the devices(considering the holder and the sorbent)contributes to the affordability of the method,and their small size allows easy transportation,opening the door to on-site extractions.Under the optimum conditions,the analyte can be determined by high-resolution ambient ionization mass spectrometry at a limit of detection(LOD)as low as 0.3 mg/L and precision(expressed as relative standard deviation,RSD)better than 9.3%.The trueness,expressed as relative recovery(RR),ranged from 90%to 109%.As high-resolution mass spectrometers are not available in many laboratories,the method was also adapted to low-resolution spectrometers.In this sense,the direct infusion of the eluates in a triple quadrupole-mass spectrometry provided an LOD of 2.2 mg/L.The RSD was better than 5.3%,and the RR ranged from 96%to 121%.

Injection drug use and HIV/AIDS transmission in China

After nearly three decades of being virtually drug free, use of heroin and other illicit drugs has re-emerged in China as a major public health problem. One result is that drug abuse, particularly heroin injection, has come to play a predomi- nant role in fueling China’s AIDS epidemic. The first outbreak of HIV among China’s IDUs was reported in the border area of Yunnan province between China and Myanmar where drug trafficking is heavy. Since then drug-related HIV has spread to all 31 provinces, autonomous regions and municipalities. This paper provides an overview to HIV/AIDS transmission through injection drug use in China. It begins with a brief history of the illicit drug trade in China, followed by a discussion of the emergence of drug related AIDS, and a profile of drug users and their sexual partners who have contracted the virus or who are vulnerable to infection. It ends by summarizing three national strategies being used by China to address both drug use and AIDS as major health threats.

Eligibility of persons who inject drugs for treatment of hepatitis C virus infection

In this decade, an increase is expected in end-stageliver disease and hepatocellular carcinoma, most commonly caused by hepatitis C virus(HCV) infection.Although people who inject drugs(PWID) are the ma-jor source for HCV infection, they were excluded fromantiviral treatments until recently. Nowadays there isincontrovertible evidence in favor of treating these patients, and substitution therapy and active substanceuse are no longer contraindications for antiviral treatment. The viral clearance in PWID after HCV antiviraltreatment with interferon or pegylated interferon combined with ribavirin is comparable to the viral clearancein non-substance users. Furthermore, multidisciplinary approaches to delivering treatment to PWID are advised, and their treatment should be considered on anindividualized basis. To prevent the spread of HCV inthe PWID community, recent active PWID are eligiblefor treatment in combination with needle exchange programs and substitution therapy. As the rate of HCV reinfection is low after HCV antiviral treatment, there is no need to withhold HCV treatment due to concerns about reinfection alone. Despite the advances in treatment efficacies and data supporting their success, HCV assessment of PWID and initiation of antiviral treatment remains low. However, the proportion of PWID assessed and treated for HCV is increasing, which can be further enhanced by understanding the barriers to and facilitators of HCV care. Removing stigmatization and implementing peer support and group treatment strategies, in conjunction with greater involvement by nurse educators/practitioners, will promote greater treatment seeking and adherence by PWID. Moreover, screening can be facilitated by noninvasive methods for detecting HCV antibodies and assessing liver fibrosis stages. Recently, HCV clearance has become a major endpoint in the war against drugs for the Global Commission on Drug Policy. This review highlights the most recent evidence concerning HCV infection and treatment strategies in PWID.

Recent advances in the treatment of opioid use disorders–focus on long-acting buprenorphine formulations

Oral methadone or sublingual buprenorphine are first-line medications for pharmacotherapy of opioid use disorders(OUDs).Three long-acting buprenorphine depot or implant formulations are currently available for the treatment of OUDs:(1)CAM 2038(Buvidal)for subcutaneous weekly and monthly application;(2)RBP-6000(Sublocade^(TM))as a monthly depot formulation;and(3)A six-month buprenorphine implant[Probuphine^(TM)].The pharmacology,clinical efficacy and prospects of these medications are discussed.

Life after Addiction—Post-Operative Pain Management in an Obstetrical Patient on Long-Term Buprenorphine Therapy

A G6P2032 female, prior cesarean x3 with history of opioid addiction maintained on buprenorphine presented for scheduled repeat cesarean section. Pre-operatively, her maintenance dose of medication was held secondary to concerns for partial agonist effect. Post-operative pain control was suboptimal with the patient ultimately proceeding to withdrawal. Doses of hydromorphone were titrated to 10 mg every 3 hours to avoid further withdrawal. Review of expert opinion after discharge recommended against holding buprenorphine therapy in the post-operative period. Pain management options include maintenance therapy with additional doses of opioid and non-opioid pain relieving medications.

Neonatal opioid exposure:public health crisis and novel neuroinflammatory disease

Substance use,specifically the use of prescription and non-prescription opioids among pregnant women,is a major public health issue and chief contributor to the opioid crisis.The prevalence of Neonatal Opioid Withdrawal Syndrome has risen 5-fold in the past decade,and is a well-recognized consequence of perinatal opioid exposure.By contrast,the long-term damage to the developing brain from opioid medications is just beginning to be recognized as a serious concern.Published data suggest that opioid exposure commencing in utero negatively affects the maturation of the neural-immune system,and trajectory of central nervous system development.Methadone induces peripheral immune hyper-reactivity,lasting structural and microstructural brain injury,and significant deficits in executive function and cognitive control in adult animals following in utero exposure.Thus,to address the cascading public health crisis stemming from the multitude of infants with in utero opioid exposure who will grow up with altered neurodevelopmental trajectories,rigorous preclinical,mechanistic studies are required.Such studies will define the long-term sequelae of prenatal opioid exposure in an effort to develop appropriate and targeted interventions.Specifically,the development of novel fluid,neuroimaging and biobehavioral biomarkers will be the most useful to aid in early identification and treatment of opioid exposed infants with the greatest risk of poor clinical outcomes.These studies will be essential to understand how in utero insults determine brain structure and function in adulthood,and what targeted interventions will be required to improve longterm outcomes in the countless children being born exposed to opioids each year.

Advancing Service Integration in Opioid Treatment Progams for the Care and Treatment of Hepatitis C Infection

It is estimated that approximately 200 million people globally are infected with the hepatitis C virus and that roughly half of these people live in Asia. Without treatment, it is estimated that roughly twenty percent of those infected with hepatitis C virus progress to chronic liver disease, then subsequently, end-stage liver disease. Thus, access to hepatitis C testing and subsequent care and treatment of chronic hepatitis C infection are essential to address the global burden of disease. In the United States, the Center for Disease Control and Prevention estimates that 60% of new cases of hepatitis infection are due to injection drug use. Opioid Treatment Programs (OTP’s) dispense methadone and buprenorphine under specific federal regulations to injection drug users diagnosed with opioid dependence. OTPs are developing comprehensive care and treatment model programs that integrate general medical and infectious disease-related medical care with substance abuse and mental health services. Integrating hepatitis care services and treatment in the substance abuse treatment settings foster access to care for patients with hepatitis C infection, many who otherwise would not receive needed care and treatment. This may serve as a national model for highly cost-efficient healthcare that has a measurable outcome of improved public health with reduced hepatitis C prevalence.

Establishment of Human Neuroblastoma Cell-Line (SK-N-SH) as an In Vitro Model of Morphine Addiction

Morphine is a schedule II-controlled substance that used to allow the diminution of intra-operative, post-operative orchronic pain. However, its usage is limited due to addiction and overdose liabilities. Morphine was observed to cause tolerance,dependence and withdrawal in human. Justification: to date lack of scientific evidence of morphine addiction was carried out byusing specific single human neuroblastoma cell-line (SK-N-SH). Therefore, this study was performed to establish the morphineaddiction model in this cell line. The cells were exposed to morphine for 24 hrs before treatment with methadone, as ananti-withdrawal drug for subsequence 24 hours. The cytosolic fraction of the cell was used in different objectives including receptoraffinity, withdrawal properties, endocytic machinery, desensitisation or internalisation and cellular adaptation. The result shows thatmorphine and methadone bind to the μ-opioid receptor. The morphine-treated cells were observed to increase the expression ofaddiction markers, have a low rate of the endocytic machinery, cause desensitisation of receptor and reduce cellular adaptation.Those changes by morphine were normalised by the treatment of methadone. As a whole, it is postulated that neuroblastoma cell line,SK-N-SH, can be used as an in-vitro model to demonstrate morphine addiction before animal and human testing.