Psychological And Methodological Issues In Substance Abu

在这个项目中，我们试图增加证明美沙酮维持的好处的文献，并加强这些好处。 我们已经完成了一项研究，以评估在美沙酮维持期间月经周期是否变得更规律。虽然海洛因？S的月经紊乱已经被证实，但关于美沙酮维持和月经功能的公开数据很少。我们回顾了来自两个临床试验的191名吸毒妇女的数据，持续了25-29周；每个妇女都服用了70-100毫克的美沙酮。收集每一次月经的开始/结束日期。月经类型可分为规律月经、不规律月经、一过性闭经、持续性闭经或重新开始月经。使用重复测量回归模型来确定周期长度与长周期(&gt；40天)和短周期(&lt；20天)的预测因子的相关性。出血发作(几天后？开始？去？停止？)被定义为一个或多个出血日，至少有两个非出血日。研究的相关/预测因素是体重指数、药物使用、美沙酮剂量和种族。在133名可确定月经类型的妇女中，月经周期长度不规律是常见的；周期不规律62例(46.7%)，规则37例(27.8%)，周期重新开始16例(12%)，持续性闭经11例(8.3%)，一过性闭经7例(5.3%)。美沙酮维持治疗每增加一周，发生长周期(OR=0.96p=0.001)和短周期(OR=0.92p=0.001)周期的风险降低。在27名研究前有继发性闭经的女性中，16名(59%)在服用美沙酮的情况下重新开始月经。阿片类药物或可卡因的阳性与短周期或长周期没有显著关联。因此，在美沙酮维持期间，周期长度开始正常化，可能会发生月经恢复。美沙酮的维持，尽管从绝对意义上说会干扰月经功能，但可能比非法海洛因滥用干扰更小。 我们还在进行方法学研究，以完善我们对药物使用和剂量充分性的监测。例如，我们正在研究美沙酮及其主要代谢物EDDP在血浆和唾液中的游离型和蛋白质结合型对映体浓度之间的关系。我们的合作者已经为这些目的开发了新的分析方法，现在正在分析我们完成的一项临床试验的样本。我们将确定分析物浓度、美沙酮剂量和治疗结果之间的关系。我们在这个项目中的发现可能有助于我们的治疗药物监测，因为我们正在开始另一项大型临床试验，在该试验中，灵活的、个性化的每日美沙酮剂量与固定的高剂量美沙酮进行双盲比较--这种比较从未被系统地进行过。

In this project, we seek to add to the body of literature demonstrating the benefits of methadone maintenance, and to enhance those benefits. We have completed a study to evaluate whether menstrual cycles become more regular during methadone maintenance. While heroin?s menstrual disruption has been demonstrated, there are few published data concerning methadone maintenance and menstrual function. We retrospectively examined data from 191 drug-using women from two clinical trials, lasting 25-29 weeks; each woman was maintained on 70-100 mg of methadone. Start/end dates of each menses were collected. Patterns of menstruation were classified as regular, irregular, transient amenorrhea, persistent amenorrhea, or cycle restart. Repeated-measures regression modeling was used to determine correlates of cycle length and predictors of long cycles (>40 days) and short cycles (<20 days). Bleeding episodes (days from ?start? to ?stop?) were defined as one or more bleeding days, bound by at least two non-bleeding days. Correlates/predictors examined were body mass index, drug use, methadone dose, and race. In the 133 women for whom menstrual patterns could be determined, cycle-length irregularity was common; the patterns seen were: irregular, 62 (46.7%); regular, 37 (27.8%); cycle restart, 16 (12%); persistent amenorrhea, 11 (8.3%); transient amenorrhea, 7 (5.3%). Each additional week on methadone maintenance was associated with decreased risk of long (OR=0.96, p=0.001 and short (OR=0.92, p=0.001) cycles. Of 27 women with secondary amenorrhea pre-study, 16 (59%) restarted menses while maintained on methadone. Positivity for opioids or cocaine was not significantly associated with short or long cycles. Thus, cycle length begins to normalize during methadone maintenance, and menses resumption may occur. Methadone maintenance, despite interfering with menstrual function in an absolute sense, may interfere less than illicit heroin abuse. We are also conducting methodological studies to refine our monitoring of drug use and dose adequacy. For example, we are investigating the relationships among the concentrations of free and protein-bound enantiomers of methadone and its major metabolite EDDP in plasma and saliva. Our collaborators have developed new assays for these purposes and are now analyzing specimens from one of our completed clinical trials. We will determine associations among analyte concentrations, methadone dose, and treatment outcome. Our findings in this project may contribute to our therapeutic drug monitoring as we begin another large clinical trial in which flexible, individualized daily methadone doses are compared double-blind to fixed high doses?a comparison that has never been systematically made.