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.

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.

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%.

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.

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.

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.

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.

Characteristics of Heroin Users in Lomé(Togo)

Introduction: Opioid use is a public health problem today. The aim of this study was to describe the socio-demographic characteristics, judicial aspects, addictive behaviours and medical aspects of heroin users placed on methadone (HUM) at the Integrated Addiction Care Centre of Kodjoviakopé (CEPIAK). Framework and Method: This was a descriptive cross-sectional study conducted at the CEPIAK in Lomé, Togo, from December 1st, 2020 to January 31, 2021. Results: A total of 200 HUM were included in this study. They were Togolese in 89.0% of cases. Their mean age was 43.4 ± 9.6 years with extremes ranging from 16 to 66 years. Males accounted for 90.5% of the HUM, i.e. a sex ratio of 9.5. Primary education accounted for 39.0% of cases. Single people accounted for 44.0% of cases. One hundred and nineteen HUM (59.5%) had a history of incarceration. Cannabis, tobacco and cocaine were the other drugs associated with heroin use in 79.5%, 74.5% and 59.5% of cases respectively. A history of overdose accounted for 18.0% of the HUM in our sample. Suicide attempts accounted for 19.5% of the HUM. Tuberculosis was detected in 5.5% of the HUM. HIV accounted for 3.0% of the HUM. Conclusion: It is important for the Togolese health system to give more importance to this issue, which is shared by the medical and social sectors, in order to effectively reduce and prevent these social ills.