| ObjectiveAccording to the concept of integrated evidence chains in clinical research,firstly,we carry out a network meta-analysis to explore the better therapeutic intervention measures of acupuncture and moxibustion in treating opioid dependence,which may obtain high-quality evidence that can guide clinical practice.Secondly,through clinical prospective randomized controlled study,we aim to examin the effectiveness and safety of Jin’s three needles technique(JTN)in opioid dependence.Thirdly,basic on the result clinical research of Jin’s three needles technique in opioid dependence,we conduct health economics evaluation to explore the cost in treating this disease.MethodsWe conducted a comprehensive search of Medline,EMBASE,Cochrane Library,CNKI,VIP from inception to December 15,2018 by using terms such as "acupuncture","electro-acupuncture","warm needle","fire needle","bleeding","auricular acupuncture","moxibustion","cupping","heroin","opioid dependence","withdrawal symptoms","drug addiction","substance use disorder".The evaluation form is designed in advance with the data extraction spreadsheet,in which the quality evaluation of each study is carried out independently by two researchers during the data extraction process.Stata(Version:14.0)was used to draw the network diagram and the network-meta analysis based on Bayesian framework is calculated by using the "gemtc"(Version:0.8-2)package under R(Version:3.5.2)software,and the Monte Carlo simulation of Markov chain is carried out by calling JAGS(Version:4.3.0)through"gemtc",which was used to compare the curative effect of different acupuncture and moxibustion intervebtions in the literature by direct and indirect comparison and the best interventions were selected by quantitative sequencing.2.All of 135 Patients who met the inclusion and exclusion criteria were recruited from June 2019 to December 2019 in Guangzhou huiai hospital.All eligible participants will be randomly assigned to the JTN group or control group in a 1:1 allocation ratio by SAS9.0 software.Participants who are enrolled into the JTN group will receive methadone maintenance therapy(MMT)and JTN treatment for 30-min per session.Meanwhile,those who are assigned to the control arm will receive MMT only.All of 18 sessions of JTN treatment will be delivered over 6 weeks(3 per week)and followed by 4 weeks follow-up period.The primary outcome measure is the visual analog scale for drug craving(VAS)and the daily consumption of methadone.Secondary outcome measure include the urine test for heroin use,the 36-Item Short Form Survey(SF-36),the Beck Anxiety Inventory(BAI),the Beck Depression Inventory Ⅱ(BDI-Ⅱ)and Pittsburgh sleep quality index(PSQI).VAS,the daily consumption of methadone,BAI,BDI-Ⅱ and the urine test will be evaluated at baseline,the second week,the fourth week,the sixth week and the tenth weeks.SF-36 and PSQI will be assessed at baseline,the fourth week,the sixth week and the tenth weeks.3.According to the result clinical research of Jin’s three needles technique in opioid dependence,compare the the daily consumption of methadone,VAS for drug craving and the total scores of PSQI resulte with cost to evaluate the cost-effectiveness Ratio.We use SF-36 based British SF-6D to calculate the QALYs.Then compare QALY with cost to evaluate the Cost-Utility Ratio and Incremental Cost-Utility Ratio.The sensitivity was conducted to test the result whether reliability or not.Results1.By searching the databases of Chinese and foreign country,2514 results were identified.The number of hits in each database is as follows:Medline 204,EMBASE 108,Cochrane Library 279,CNKI 549,VIP 366,Wanfang 1008,of which 1923 are Chinese and 591 are English Acorrding to inclusion and exclusion criteria,we identified 21 eligible randomised controlled trials,which published in 1997-2010 and basic information,subjects,sample size,intervention measures,treatment course and outcome indicators of RCTs were extracted.All of 21 eligible studies were conducted in China and published in Chinese.A total of 7 studies were funded,while 14 studies were not.The bias risk assessment result showed that only 2 studies described the randomization in detail and the rest only mentioned it,that 2 studies were high risk of bias and the rest were not clear in allocation concealment,that only 3 studies were described blinding in detail,that only 2 studies may report incomplete data and one study may have selective reporting.Interventions under the Bayesian framework the overall response rate ranked as follows:acupuncture,electro-acupuncture,Chinese medicine,ear acupuncture,western medicine,Transcutaneous acupoint electrical stimulation(TAES);The withdrawal symptom score ranked as follows:acupuncture,electro-acupuncture,Chinese medicine,western medicine,TAES.2.All of 135 patients were included in clinical research and 12 patients were dropout.There were 123 patients finished the trials,including 62 patients in JTN group and 61 patients in control group,which were comparable in baseline.The results showed that the daily dose of methadone of JTN group have dropped obviously from zero week to six week and have significant time effect,while the control group were stable.The daily dose of methadone decreased 17.24±1.41mg/d in JTN group(P<0.001)and 1.05±2.03mg/d in control group(P=0.609).The daily dose of methadone of JTN group were lower than control group at 2th,4th,6th week respectively and the difference between two groups have statistical significance(<0.001).The VAS for craving scores of JTN group have dropped noticeably from zero week to six week and have significant time effect,while the control group were stable.The VAS for craving scores decreased 36.19±2.88(P<0,001))and 1.94±1.59 in control group(P=0.226).The VAS for craving scores of JTN group were lower than control group at 2th,4th,6th week respectively and the difference between two groups have statistical significance(P<0.001).After six weeks treatment,sleep duration,habitual sleep efficiency,subjective sleep quality and total scores have dereased and have significant time effect.The sleep duration,habitual sleep efficiency,subjective sleep quality and total scores of JTN group respectively decreased 0.63±0.13,0.78±0.17,0.31±0.11、0.24±0.10 and 2.18±0.52(P<0.05),while only habitual sleep efficiency of the control group increased 0.36±0.16 and have statistical significance(P=0.029).Sleep duration score of JTN group were lower than control group at 6th week and habitual sleep efficiency scores of JTN group were lower than control group at 4th,6th week and the difference between two groups have statistical significance(P<0.05).After six weeks treatment,physical functioning(PF),bodily pain(BP),general mental health(MH),vitality(VT)and general health(GH)scores have increased and have significant time effect(P<0.05).The PF,RP,RE,MH,VT,SF and GH scores of JTN group respectively increased 12.35±3.85,6.25±5.25,6.86±5.44,6.35±2.15,7.79±2.02,7.35±3.32 and 6.40±2.08(P<0.05),while only MH and VT scores of the control group increased 5.79±2.30 and 6.64±1.97 and have statistical significance(P<0.05).The PF score of JTN group were higher than control group at 4th,6th week and the RP,RE,MH and GH scores of JTN group were higher than control group at 4th week and the difference between two groups have statistical significance(P<0.05).The BAI scores of two group have dropped from zero week to six week and have significant time effect(P=0.011).The BAI scores decreased 2.18±1.10 in JTN group(P=0.051)and 2.15±0.97 in control group(P=O.030).The difference of BAI scores between two groups have non statistical significance(P>0.05)at 2th,4th,6th week.The BDA-Ⅱ scores of JTN group have dropped from zero week to six week and have significant time effect(P<0.001),while the control group were stable.The BDA-Ⅱ scores decreased 4.15±1.30 in JTN group(P<0.001)and 1.67±0.93 in control group(P=0.076).The difference of BDA-Ⅱ scores between two groups have non statistical significance(P>0.05)at 2th,4th,6th week.After six weeks treatment,the difference of positive urine test between two groups have non statistical significance(P>0.05)and there were non statistical significance difference of positive urine test for two groups befor and after treatment(P<0.05).3.Results of health economic evaluation showed that total costs of JTN group and control group were ￥2869.50 and ￥2186.04,which were statistical significance difference between two groups.Direct medical costs were ￥1303.94 in JTN group and ￥729.66 in control group.Direct non-medical costs were ￥112.35 in JTN group and ￥105.05 in control group.Indirect costs were ￥1453.21 in JTN group and ￥1351.33 in control group.Cost-effectiveness analysis demonstrated that when the daily dose of methadone decreased one milligram,the cots of JTN group and control group were ￥162.30 and ￥2043.03,that when the VAS for craving scores decreased one point,the cots of JTN group and control group were ￥74.98 and ￥828.05,that when the PSQI scores decreased one point,the cots of JTN group and control group were ￥1316.28 and ￥7286.8.Therefor,the JTN group was costs less than control group in cost-effectiveness.Cost-utility analysis show that the cost-utility ratio(CUR)of JTN group and control group were 36600.77 per QALY and 28688.19 per QALY.Compared with control group,incremental-cost-utility ratio(ICUR)of JTN group was ￥310663.64 per QALY,which was higher than the societal threshold(￥141600).Sensitivity analysis showed that the results were stable.Conclusion1.According to the results of network meta-analysis,patients with acupuncture treatment was better than that of western medicine alone in the overall response rate and the withdrawal symptom score and found that it was a better therapeutic intervention for opioid dependence.2.Patients with methadone maintain therapy plus Jin’ s three-needle therapy may safetively reduce the daily dose of methadone and lower the craving for drug,as well as improve sleep quality,depression and some part of life quality.However,there was nothing improve in patients with anxiety.3.On health economic evaluation,compared with methadone maintain therapy only,patents received MMT plus Jin’ s three-needle therapy are cost less,which indicated Jin’ s three-needle therapy is more optimal,but ICUR higher than the societal threshold. |
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