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.

医护-社工联动康复模式对美沙酮维持治疗患者心理状况的影响

目的 探究医护-社工联动康复模式对美沙酮维持治疗患者心理状况的影响。方法 纳入94例美沙酮维持治疗服务的患者,随机分为观察组(48例)和对照组(46例)。对观察组运用医护-社工联动康复模式进行个体化干预,对照组则运用常规美沙酮治疗服务模式进行干预。分别在干预前、干预3个月及6个月三个时间点对两组受试者的焦虑状态、抑郁状态及生活质量进行评估。结果 观察组受试者在接受医护-社工联动康复模式干预6个月后在抑郁状态和焦虑状态方面均较干预前显著改善,并且无论是BDI评分和BAI评分均显著低于对照组(P <0.05)。同时,观察组受试者中“有抑郁”的人数占比和“有焦虑”的人数占比均显著低于对照组(P <0.05)。干预6个月后,观察组受试者的生活质量评分(183.77±8.90)显著高于对照组(174.76±11.14)(P <0.01)。结论 医护-社工联动康复模式在改善美沙酮维持治疗患者的心理状态方面具有一定的优越性,值得被推广应用。

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.

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.

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.

美沙酮按需转换法治疗癌痛的临床研究

目的:探讨美沙酮按需转换法(Ad libitum,AL)治疗癌痛的有效性和安全性。方法:选取南京大学医学院附属金陵医院疼痛科2022年11月至2023年9月全身大剂量使用阿片类药物疼痛控制不佳的癌痛病人31例,采用每次20 mg(间隔≥2 h)按需口服美沙酮转换,观察并记录美沙酮转换前、转换第1~7天和第14天病人平均疼痛数字分级评分法(numerical rating scale,NRS)评分;记录转换前、转换第1天、第3天及第7天不良反应;转换第1天至第5天补救次数;评估转换前和转换第7、14天病人生活质量(quality of life,QOL);评价并计算病人满意度和转换成功率(NRS评分降低50%,且无不能耐受的不良反应)。结果:与转换前相比,转换第1~7天及第14天病人平均NRS评分均降低(P<0.05),生活质量明显改善(P<0.001)。补救次数随滴定时间的延长而降低。病人均未出现不能耐受的药物不良反应,总体满意度为4.0(1.0),美沙酮转换成功率为93.5%。结论:全身大剂量阿片类药物使用病人,采用每次20 mg口服美沙酮按需转换效果确切、不良反应少,病人生活质量获得改善且满意度高,适合中国人群,可供临床参考。

美沙酮维持治疗对海洛因依赖者大脑度中心性影响的静息态fMRI研究

目的探索美沙酮维持治疗(methadone maintenance treatment,MMT)对海洛因依赖(heroin dependence,HD)患者大脑拓扑特性度中心性(degree centrality,DC)的影响及其与心理行为学的相关性。材料与方法回顾性分析2016年1月至2017年12月于西安市灞桥区美沙酮门诊招募的41名正在接受MMT的HD患者,采集静息态功能磁共振成像(functional magnetic resonance imaging,fMRI)数据,评估稽延性戒断症状与渴求评分,纵向随访一年。对影像数据进行DC分析,并采用配对样本t检验进行纵向比较,差异脑区与心理学指标进行相关分析。结果HD患者入组时与MMT一年后稽延性戒断症状评分差异存在统计学意义(Z=3.004,P=0.003),渴求评分差异无统计学意义(Z=0.872,P=0.383)。与基线相比,HD患者经过MMT一年后,双侧丘脑、尾状核、壳核与左侧苍白球的DC降低;右侧舌回与距状回的DC值升高(Gaussian random field校正,单体素水平P<0.001,团块体素水平P<0.01,团块体素>95)。双侧尾状核及左侧苍白球DC值与戒断症状呈负相关性(r=-0.417,P=0.030;r=-0.392,P=0.043;r=-0.383,P=0.049),双侧壳核及左侧苍白球DC值的变化量与渴求的变化量呈正相关性(r=0.410,P=0.008;r=0.332,P=0.034;r=0.395,P=0.011)。结论美沙酮可能通过降低HD患者纹状体在成瘾奖赏脑网络中的中心性,从而调节HD患者戒毒后的稽延性戒断症状与心理渴求;同时可能抑制了冲动性,增强了视觉核心脑区的活动。该研究结果可以为美沙酮对HD患者治疗的神经机制提供影像学依据。

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%.

5种阿片受体激动剂不良反应信号的数据挖掘与分析

目的基于美国食品药品管理局不良事件报告系统(FAERS)对5种阿片受体激动剂(吗啡、可待因、哌替啶、芬太尼、美沙酮)相关不良反应进行挖掘分析,为阿片受体激动剂的临床安全用药提供参考依据。方法利用美国食品药品管理局公共数据开放项目(OpenFDA)平台,收集2004年第1季度至2021年第4季度FAERS数据库中5种阿片受体激动剂的不良反应报告数据,采用报告比值比(reporting odds ratio,ROR)法对5种阿片受体激动剂的药品不良反应(ADR)进行信号挖掘,分析ADR报告中的安全警告信号。结果最终得到吗啡165572份,可待因79574份,哌替啶9838份,芬太尼145819份,美沙酮43433份ADR报告。这些ADR报告中女性207657份多于男性156810份,主要集中于18~60岁年龄段病人,且美国地区的上报数最多为282820份,严重ADR报告中以住院或住院时间延长的上报数最多为129454份。在上报数前20位的ADR中,药物依赖、过量、新生儿戒断综合征、怀孕期间胎儿暴露相关ADR在5种药物的说明书中均有提及,各类神经系统疾病及精神病类相关ADR在说明书较为常见。经ROR法检测发现,常见有精神障碍相关ADR,吗啡和可待因信号强度最为显著,药物依赖性吗啡信号最强,除芬太尼外其余学习障碍和发育迟缓高危信号均较强,自杀身亡美沙酮信号最强。结论通过对吗啡、可待因、哌替啶、芬太尼和美沙酮等阿片受体激动剂的严重和其他重要ADR信号的挖掘与分析,可更深入了解此类药物的ADR特征和潜在风险,促进临床安全用药。

青少年特发性脊柱侧凸后路融合术后以美沙酮为基础的多模式镇痛效果

目的探讨美沙酮为基础的多模式镇痛模式对青少年特发性脊柱侧凸患儿术后疼痛和阿片类药物用量的影响。方法选择2018年1月~2020年12月在本院实施PSF的102例患儿作为研究对象,采用随机数字表法分为A组和B组各51例。对照组采用常规自控镇痛为主的多模式镇痛,B组给予美沙酮为基础的多模式镇痛。观察两组患儿术后每日阿片类药物消耗量(吗啡毫克当量,MME)、视觉VAS评分、阿片类药物相关副作用和术后住院时间。结果术后当天,B组疼痛VAS评分和阿片类药物用量显著高于A组(P<0.05);术后第1天,两组患儿疼痛VAS评分和阿片类药物用量差异无统计学意义(P>0.05);术后第2、3天,B组疼痛VAS评分和阿片类药物用量显著低于A组(P<0.05)。A组患者住院时间和首次排便时间均显著长于B组(P<0.05),两组患儿均未观察到呼吸抑制等严重不良反应。结论美沙酮为基础的多模式镇痛可改善AIS患儿PSF术后疼痛控制,降低阿片类药物消耗量。

盐酸美沙酮片剂用于慢性癌症疼痛治疗中国专家共识解读

美沙酮是世界卫生组织(WHO)癌痛三阶梯治疗中的第三阶梯强阿片药物,具有独特的镇痛效果,但在国内相关领域美沙酮并未得到充分应用。为了指导美沙酮在中国慢性癌痛病人中的临床应用,中国麻醉药品协会组织国内相关领域专家撰写盐酸美沙酮片剂用于慢性癌症疼痛治疗中国专家共识(简称《共识》)。本文对《共识》中的重点内容进行解读,旨在加深医护人员对《共识》的认识,促进美沙酮规范应用于慢性癌痛的镇痛治疗。