【作者】 谭俊；

【导师】 冯学山；

【作者基本信息】 复旦大学 ， 社会医学与卫生事业管理， 2012， 硕士

【摘要】 研究目的通过比较研究对象在社区戒毒康复治疗过程中服用中药济泰片与美沙酮后复吸和脱失的差异,评价中药济泰片预防复吸的效果：监测服药过程中的不良事件,以及研究对象在服药过程中的实验室指标,评价中药济泰片在服药过程中的安全性。研究方法采用队列研究,按照纳入与排除标准在上海市7个区65个社区筛选出合格的390例戒毒康复治疗对象,分为济泰片与美沙酮两个干预组,分别为208例,182例。两组同时合并实施心理咨询和社会支持干预。心理咨询由上海市自强总社的心理咨询师提供,社会支持包括自强总社根据研究对象实际情况,为其提供低保,就业培训,医疗费用减免等方式。随访分为服药后第8周,第26周,第52周共三次。实验室检查包括筛查及随访时点的生命体征,血常规,血生化,尿常规,尿毒品检查结果,尿妊娠试验,心电图等指标。安全性评定包括不良事件,实验室检测的异常结果及其改变情况。本次研究的主要评价指标为复吸率和不良事件发生率。研究结果1.经筛查进入研究队列的合格研究对象390人,其中完成基线数据采集的376人,完成8周访视的330人,完成26周访视的315人,完成52周访视的292人。2.完成基线数采集的376例对象中,两组在性别,年龄,婚姻状况,文化程度构成间的差别均无统计学意义,但职业构成的差别有统计学意义(P<0.0001)。男性318人,占84.57%,女性58人,占15.43%,男女性别比例为5.5：1；平均年龄为41.59岁；未婚149人,占39.63%；已婚106人,占28.19%：再婚11人,占2.93%；离异99人,占26.33%；分居4人,占1.06%；丧偶6人,占1.59%,1人信息缺失,占0.27%；小学文化程度14人,占3.72%；初中240人,占63.83%；高中112人,占29.79%；大专6人,占1.60%；本科及硕士2人,占0.53%,1人信息缺失,占0.27%。3.研究对象使用毒品主要为海洛因,济泰片组海洛因使用年限中位数为8.36年,美沙酮组海洛因使用年限中位数为9.48年,两组差别经Wilcoxon秩和检验有统计学意义；首次吸毒以来强制戒毒次数中位数两组都为3次,差别无统计学意义。4.实验室检测基线情况：生命体征指标中，脉搏和呼吸两组差别有统计学意义(P=0.0190,P<0.0001),身高,体重和血压差别无统计学意义：血红细胞,血红蛋白,淋巴细胞指标两组差别均有统计意义(P均<0.0001),血常规结果正常与否的卡方检验显示,淋巴细胞两组分布不一(P=0.0192),其他指标两组差别无统计学差异；两组血生化,尿素氮指标差别有统计意义(P=0.0192),两组其余指标差别均无统计学意义；两组尿毒品检测和尿妊娠试验结果均无统计学差异。济泰片组心电图检测结果结果异常29例,美沙酮组33例,差别无统计学意义(P=0.2184)。5.第一次随访,两组呼吸和脉搏频次间的差别经Wilcoxon秩和检验有统计学意义(P=0.0002,P=0.0079),其余指标间的差别无统计学意义。两组尿毒品检测和尿妊娠试验结果的差别也都无统计学差异。6.第二次随访,两组呼吸频率间的差别有统计学意义(P<0.0001),其余指标差别无统计学意义；两组红细胞,血红蛋白,淋巴细胞指标差别均有统计意义(P=0.0004,P<0.0001,P<0.0001)；血常规判定结果卡方检验统计学均无显著差异。血生化指标中,空腹血糖两组差别有统计意义(P=0.0091),其余指标两组差别均无统计学意义。尿常规检测两组差别均无统计学意义,其中尿糖,酮体,红细胞的比较采用了Fisher精确概率计算方法。尿毒品检测和尿妊娠试验结果两组差别都无统计学差异。心电图检测结果济泰片组结果异常27例,美沙酮组16例,卡方检验显示差别无统计学意义(P=0.2558)。7.第三次随访,呼吸和脉搏两组差别有统计学意义(P=0.0006,P=0.0165),血压和体重差别无统计学意义；血红细胞,血红蛋白,淋巴细胞两组差别有统计学意义(P=0.0021,P<0.0001,P=0.0193),其余指标差别无统计学意义,血常规的检测判定结果卡方检验两组均无统计学意义。血小板,白细胞,中性粒细胞,两组差别均有统计意义(P=0.0021,(P<0.0001,P<0.0193)；两组血生化指标实验室检测均无统计学意义；尿常规检测数值和结果判定均无统计学差异。两组尿毒品检测结果和尿妊娠试验差别都无统计学差异；心电图检测结果济泰片组结果异常20例,美沙酮组结果异常12例,卡方检验显示差别无统计学意义(P=0.3141)8.依从性：用药依从性,济泰片组用药依从性为99.8%：美沙酮组为100%。两组差异无统计学意义；团体心理干预依从性：济泰片组完成10次以上活动149人,10次以下的49人,美沙酮组完成10次以上活动137人,10次以下的41人,差别无统计学意义(P=0.6974)9.复吸情况：完成52周访视的济泰片组复吸人数22人,美沙酮组复吸人数20人,复吸率依次为11.24%,11.11%,卡方检验提示两组无统计学意义(P=0.9694)；三次随访济泰片组复吸人数依次为10人,3人,7人,复吸率依次为5.62%,1.69%,3.93%；美沙酮组复吸人数依次为9人,4人,9人,复吸率依次为4.55%,2.02%,4.55%,卡方检验提示三次随访复吸率差别无统计学意义(Fisher精确检验P=0.9508)。10.脱失情况：52周济泰片组脱失人数48人,美沙酮组脱失人数36人,脱失率依次为24.24%,20.22%,卡方检验提示两组复吸率无统计学意义(P=0.3504),三次随访济泰片组脱失人数依次为24人,8人,16人,脱失率依次为12.12%,4.04%,8.08%；美沙酮组脱失人数依次为22人,7人,7人,脱失率依次为12.36%,3.93%,3.93%,卡方检验提示三次随访脱失率差别无统计学意义(P=0.4172)。11.生存分析提示两组复吸生存曲线无统计学意义(log-rank test P=0.8205)。12.截止52周观测结束,本次研究中发生不良事件130例,其中济泰片组不良事件83例,美沙酮组47例,差别有统计学意义(P=0.0009)。未出现严重不良事件。实验室检测结果出现异常的有100例,其中济泰片组59例,美沙酮组41例；服用药物引起用药不适的临床事件为30例,其中济泰片组24例,主要表现为口干和嗜睡,胃口不适,美沙酮组为6例。研究结论在合并提供心理干预和社会支持的前提下,济泰片在社区戒毒康复治疗中预防复吸的效果与美沙酮相当；不良事件发生率济泰片组比美沙酮组高,在药物安全性方面还需进一步研究和改进。更多还原

【Abstract】 ObjectiveTo compare the relapse prevention effect and withdraw difference of Ji Taipian with methadone in the community rehabilitation process, monitor the laboratory indicator and the adverse event to evaluate the effect and safety of Ji Taipian.MethodsCohort study was conducted,390qualified subjects were selected from7districts and65communities in Shanghai,, Ji Taipian Group (n=208) and methadone group (n=182). The incidence of relapse was measured at the8th week,26th week and52th week. At the same time, subjects received physiology intervention and social support. psychological intervention was conducted by shanghai social self-support organization. Social support included low income insurance, staff training, medical fees waiver. Follow-up was carried out at8th weeks,26th weeks, and52th weeks. Laboratory examination included physics examination, blood test, blood chemical test, urine test, human chorionic gonad hormone test and electrocardiogram test. Adverse effect included switched results from normal laboratory examination to abnormal and medical events during the whole process. The main indicator of this evaluation was relapse rate. The research would include the physical indictor examination and physical sample, the whole research plan was approved by shanghai mental hospital ethics committee.Results1.390subjects entered the cohort study,376subjects finished the baseline screening information collection,330subjects finished the8weeks interview,315subjects finished the26weeks interview and292subjects finished the52weeks interview.2.Among376subjects, the demographic test found no significance between two groups except job information (P<0.0001), details as follows:318male and58female, the percent was84.57and15.43for each, sex ratio was5.5:1; the mean age was41.59:The marriage situation:149unmarried,106married,11remarriage,99devoiced,6widowed.1missing, the percent was as follows:39.63%,28.19%,2.93%,26.33%,1.06%.1.59%,0.27%for each segment; the education background:14with primary school experience,240with middle school background,112high school or junior college,2with undergraduate or higher degree.1missing, the percent was as follows:3.72%,63.83%,29.79%,1.60%,0.53%.0.27%.3. Heroin was the main kind of drug which the population had used. The median time of drug using of Ji Taipian group was8.36and9.48in methadone group. Wilcoxon test found the significant difference; the rehabilitation times was3in both groups without significance.4.The baseline result of laboratory examination:physics examination:pulse and breath has significant difference in two groups(P=0.0190, P<0.0001), height and weight has no significant difference; blood test found red blood cell, globin and lymphocyte has significant difference among each group,(P values were P<0.0001, P<0.0001, P<0.0001); the dichotomous blood result has no significant difference between two groups. Blood chemistry test:the blood urea nitrogen had significant difference between two groups (P=0.0192), ALT, AST, Fasting plasma glucose had no significant difference; Urine drug test and human chorionic gonad hormone test had no statistical significance. ECG test found Ji Taipian group had29abnormal results and methadone group22abnormal ones, Chi-square test had no significant difference.5. The first follow up, physical examination had no significance except breath and pulse indicators (P=0.0002, P=0.0079). The drug test of urine and HCG test had no significance.6.The second follow up, physics examination only found breath had significant difference (P<0.0001); Blood wtest found red blood cell, globin and lymphocyte test has significance of each group,(P value were as follows:P<0.0004, P<0.0001, P<0.0001). the dichotomous result of blood had no significance between two groups. Blood chemistry test: Fasting plasma glucose indicator had significance between two groups, ALT, AST. Fasting plasma glucose, has no significance. Urine test had no significance in two groups, urine glucose, ketone and red blood cell test used Fisher exact probability method. Urine drug test and human chorionic gonad hormone test had no significant difference. ECG test shows that Ji Taipian group has27abnormal results and methadone group16abnormal results, Chi-square test had no significance between groups.7.The third follow up:physics examination show breath and pulse had significance (P=0.0165, P=0.0006), other indicators had no significance; blood test found red blood cell, globin and lymphocyte had significance among each group,(P value were as follows: P<0.0004, P<0.0001, P<0.0001), other indicators had no significance. The dichotomous result of blood result had no significance between two groups. Blood chemistry test had no significance, either the laboratory data or dichotomous classified results. Urine test shows that glucose, protein, ketone, alt, white blood cell, red blood cell had no significance. Fisher exact probability method was used to test the glucose, ketone, red blood cell. Urine drug test and human chorionic gonad hormone test had no statistical significance. ECG test shows that Ji Taipian group has20abnormal results, methadone group12abnormal, Chi-square test show no significance between two groups (P=0.3141).8.The drug compliance:in Ji Taipian group, the drugs compliance of this group was99.8%and100%in the methadone group, no significance between these groups.9.Relapse:among the subject who finished52weeks interview, there are22subjects relapse in Ji Taipian group and20in methadone group. Relapse rate were11.24%and11.11%, Chi-square test had no significance between these two groups (P=0.9694). The relapse subject of each interview was10,3,7and relapse rate were5.62%,1.69%and3.93%in Ji Taipian group; the relapse subject of methadone group was9,4,9and the relapse rate were4.55%,2.02%,4.55%. Exact Fisher probability shows the relapse rate of three follow up had no significance (Exact Fisher probability was0.9508).10.Withdraw:among the subject who finished52weeks interview:48subjects withdrawer in Ji Taipian group and36in methadone group. Withdraw rates were24.24%,20.22%, Chi-square test shows no significance of these two groups (P=0.3504).The drop-out subject of each interview was24,8,16and the drop rates were12.12%,4.04%,8.08%in Ji Taipian group. The drop-out subjects of each interview was22,7,7and the rates of drop-out were12.36%,3.93%,3.93%, Chi-square test show the withdraw rate of these three follow up had no significance (P=0.4172)11.Life test indicated that the relapse curve had no significance (log-rank test P=0.8205)12.Adverse effect:until the final52weeks interview,130adverse events were found in total,83in Ji Taipian group and47in methadone group, Chi-square test shows significance of this situation (P=0.0009), the adverse effect rate of Ji Taipian group was41.92%, which is higher than26.40%in methadone group. There is no serve adverse event in this research.100subjects had the Lab result switched from normal to abnormal,59in Ji Taipian group and41in methadone group. The number of Subjects who had uncomfortable experience because of drug using were30in total,24in Ji Taipian group, mainly symptoms included feeling thirty. sleepy, and loss of appetite, the number of uncomfortable symptoms in methadone group was6. The adverse effects in two groups had significance.Conclusion In the condition of psychology and social support, Ji Taipian had the similar function of relapse prevention with methadone in community rehabilitation process. There is no significance of laboratory monitor process results between Ji Taipian and methadone group. The adverse event monitor process in this research found that the adverse event rate of Ji Taipian group was a little higher than the methadone group, the component of Ji Taipian could be improved in new research.更多还原