Moderate- vs high-dose methadone for opioid dependence.
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Drug Administration Schedule↗
Biomedical subjects
J Grabowski
Publications and source records attributed to J Grabowski.
Smoking cessation in women with cardiac risk: a comparative study of two theoretically based therapies.
This gender-specific research study compares the relative effectiveness of two theory-based interventions targeting women who smoke. Women with coronary artery disease (CAD; n = 53) or CAD risk factors (n = 107) were randomly assigned to either coping-skills Relapse Prevention (RP) treatment or an educational/supportive treatment based on Health Belief Model (HBM) principles. RP was comparable, but not superior to HBM treatment, as indicated by the lack of differential smoking outcomes at 3 and 6 months. RP was more effective than HBM for women with low self-efficacy, as predicted. The presence of a smoking-related disease had a substantial effect on smoking status, in that the odds of being abstinent at 6 months were 2.2 times greater for non-diagnosed women when compared with CAD women. These findings indicate that more potent relapse prevention interventions are needed to increase cessation rates in women who smoke, especially those with established heart disease.
Adaptation, Psychological↗
Behavioral and emotional problems among children of cocaine- and opiate-dependent parents.
OBJECTIVE: To test associations between parental drug abuse and children's problems, children of cocaine- and opiate-dependent parents were compared with demographically matched referred and nonreferred children. METHOD: Cocaine- and opiate-dependent parents in treatment completed the Child Behavior Checklist for 410 children (218 boys, 192 girls) from ages 2 through 18 years (mean = 7.9 years). Children of drug abusers (CDAs) were demographically matched to referred (RCs) and nonreferred children (NRCs). RESULTS: RCs scored lower than CDAs and NRCs on most competence scales, and higher than CDAs and NRCs on all problem scales. CDAs scored lower than NRCs on most competence scales, and higher than NRCs on Withdrawn, Thought Problems, Delinquent Behavior, Aggressive Behavior, Internalizing, Externalizing, and Total Problems. Group status also predicted clinical range scores on most competence and all problem scales. CONCLUSIONS: CDAs showed more internalizing and externalizing psychopathology relative to matched NRCs, but they showed significantly less psychopathology than shown by matched RCs. CDAs are an important group to target for preventive interventions.
Adolescent↗
Medication take-home doses and contingency management.
Two studies examined contingent take-home medication doses during treatment of opiate or cocaine dependence. In the first study, methadone maintenance patients were randomly assigned to one of two 8-week baseline take-home (TH) conditions differing in frequency of clinic visits per week. This was followed by a 12-week contingency management (CM) procedure in which frequent THs resulted from drug-free urines. Participants receiving more frequent THs during baseline had lower illicit drug use during the first 6 weeks of CM. In the second study, fluoxetine (0-, 20-, 40-mg) TH doses were similarly contingent in treatment of cocaine dependence. The 40-mg group used less cocaine during contingency than did other groups. The combination of fluoxetine and environmental contingencies may produce benefit where neither alone is sufficient.
Adult↗
Retention, HIV risk, and illicit drug use during treatment: methadone dose and visit frequency.
OBJECTIVES: This study examined two major methadone treatment factors, visit frequency and methadone dose, posited to be important in reducing intravenous drug use and human immunodeficiency virus (HIV) transmission. METHODS: One hundred fifty opiate-dependent subjects randomly assigned to four groups received 50 or 80 mg of methadone and attended a clinic 2 or 5 days per week. RESULTS: Survival analysis indicated higher dropout rates for groups having five vs two visits per week (Chi2[1]=7.76). Higher proportions of opiate-positive results on urine screens were associated with lower methadone doses (F[1,91]=4.74). CONCLUSIONS: Receiving take-home doses early in treatment enhanced treatment retention. The 50-mg dose combined with five visits per week produced the worst outcome. Fewer visits enhanced retention at 50 mg, but opiate use rates were higher at this dose than they were for either 80-mg group. The HIV infection rate at entry was 9%. No subjects seroconverted during the study. Risk behaviors for acquired immunodeficiency syndrome declined over time regardless of group/dose assignment. These results have important implications for modification of regulatory and clinic policy changes.
Adult↗
Multiple outcome assessment in a study of the cost-effectiveness of clozapine in the treatment of refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.
OBJECTIVE: To develop new methods for combining results from multiple outcome domains and to demonstrate their application in a study of the cost-effectiveness of clozapine in treating hospitalized patients with refractory schizophrenia. DATA SOURCES/STUDY SETTING: Interview assessments, and administrative utilization and cost data, concerning 423 patients with refractory schizophrenia who had been hospitalized for 30-364 days during the year before study entry, at 15 VA medical centers. STUDY DESIGN: A 12-month double-blind trial compared clozapine (n = 205) and haloperidol (n = 218) in the treatment of refractory schizophrenia. DATA COLLECTION/EXTRACTION METHODS: Data from standard assessment instruments, gathered at baseline and at 6 weeks, and at 3, 6, 9, and 12 months, were used to develop a Composite Health Index for Schizophrenia, a measure that addresses outcome in six domains, weighted by patient or provider preferences. Cumulative improvement was estimated by computing the area under the improvement curve. This measure was then combined with cost data, reflecting consumption of societal resources to estimate incremental cost-effectiveness ratios. PRINCIPAL FINDINGS: Clozapine was significantly more effective than haloperidol on measures of symptoms (p = .02) and side effects (p < .0001), with nonsignificant trends in the positive direction on community role functioning (p = .06), family relationships (p = .23), social relationships (p = .30), and daily activities (p = .20). Clozapine was also more effective than haloperidol on the one-year cumulative Composite Health Index for Schizophrenia (p < .0001 for all weighting schemes). After converting this measure to a 0-1 Worst Health-Good Health Scale analogous to Quality Adjusted Life Years, clozapine was found to yield a small improvement of .049 Worst Health-Good Health Units as compared to an improvement of only .027 Units for haloperidol (p < .0001). Average annual costs were $2,733 lower for clozapine (95% C.I. = -$9,220 to $3,754). Although clozapine was significantly more effective than haloperidol, the summary cost-effectiveness ratio had a wide 95 percent confidence interval ranging from -$431,585 to $177,352. CONCLUSIONS: Methods demonstrate an approach to using conventional disease-specific measures to evaluate the cumulative effectiveness of novel treatments for psychotic disorders and for expressing their economic effect as cost-effectiveness ratios. Among high hospital users with refractory schizophrenia, clozapine is more cost-effective than standard treatment, although the magnitude of its effect is small and there is considerable uncertainty about the cost estimates.
Clozapine↗
Fluorogenic compound hydrolysis as a measure of toxicity-induced cytoplasmic viscosity and pH changes.
If a fluorogenic compound, such as fluorescein diacetate, is added to a water solution containing living cells it becomes hydrolyzed by intracellular esterases into a fluorochrome whose fluorescence can be used to monitor the cytoplasmic pH and the cytoplasmic viscosity of the cells. In this paper we have used this technique to measure the effects of different concentrations of Co2+ and Cd2+ ions on the cytoplasmic pH and the cytoplasmic viscosity of a single cell culture. Our results indicate that the observed decrease in the efficiency of the intracellular hydrolyzation of fluorogenic substances in the presence of different concentrations of heavy metals could be caused by both a decrease in the cytoplasmic pH and an increase in the cytoplasmic viscosity. A decrease in cytoplasmic pH would decrease the effectiveness of the intracellular enzymes, whereas an increase in cytoplasmic viscosity would decrease diffusion which would also reduce the effectiveness of the reaction. The dependence of the reciprocal of the cytoplasmic viscosity on the concentration of these metals correlates well with published results on their toxicity.
Journal Article↗
Replacement medication for cocaine dependence: methylphenidate.
Agonists, or "replacement medications," are useful adjuncts in treatment of opiate and nicotine dependence. They have not been systematically examined in cocaine dependence. Results of early open trials with methylphenidate for treatment of cocaine dependence were equivocal. Twenty-four cocaine-dependent subjects were enrolled in an 11-week double-blind, placebo-controlled study of methylphenidate. Assignment was random. Intake included a 2-day human laboratory procedure in which subjects received initial doses of methylphenidate or placebo. Subjects attended the clinic Monday through Friday and received oral doses of methylphenidate (5 mg plus 20-mg sustained release) or placebo at 8:00 a.m., with afternoon and weekend take-home doses (20 mg sustained-release or placebo) provided in Medication Events Monitoring System bottles to monitor compliance. Clinic visits included therapy sessions, electrocardiograms, self-report measures, and twice-weekly urine screens. The two groups were equivalent in terms of retention (methylphenidate 48% and placebo 42%) and had similar cocaine use outcomes (40% benzoylecgonine-positive urine screens). There were no significant adverse effects. The doses were sufficient to permit detection of psychoactive effects ("stimulant," "more energy") and side effects ("jitteriness," "eating less") without increased "craving." Additional medications with different effects profiles are being studied to further evaluate the replacement model in cocaine dependence.
Adult↗
Baseline assessment, study entry, and stabilization: double-blind clinical trials in drug dependence.
To summarize, perhaps most important, but most difficult to achieve will be commonalties and standardization across trials so that rigorous comparison is possible. Researchers will do well to examine clinical trials in other areas, mimicking those elements that are compatible, avoiding those that are not, and above all, avoiding costly reinvention.
Clinical Trials as Topic↗
Evaluation of the expert system for respiratory therapy of newborns on archival data.
The aim of this study was to evaluate the artificial ventilation expert system for neonates (AVES-N) using archival data. The recommendations of the system were compared to the decisions made by the expert-physician in the same clinical situation (patient condition, respirator settings). In our retrospective study we used data of 320 newborns which were ventilated in the Neonatal Intensive Care Unit of the Vanderbilt University Hospital in Nashville (USA). Best agreement between the recommendations of the system and the decisions of the experts was found for positive end expiratory pressure (PEEP), inspired oxygen fraction (FiO2) and peak inspiratory pressure (PIP)--about 70%. Worse agreement was found for time related parameters: respiratory frequency (f) - 54%, time of inspiration (ti) - 46%, time of next blood gas analysis - 15%. The expert system advised lower FiO2 PEEP and f. The differences were smaller in a group of patients who survived than in a group of patients who died. The overall agreement of the AVES-N advice and real therapeutic actions leads to the clinical evaluation of the expert system. The differences can be attributed to a) different therapeutic strategies at 2 NICU's, b) missing data regarding complications in the data base which were not taken into account by the expert system.
Archives↗
A method for determination of the anisotropic properties of biomembranes.
A methodology was developed for potential determination of the anisotropic properties of biomembranes. This method is based on the theoretical discretization of a continuous membrane used for finite element analysis and the simultaneous measurement of the displacement of nodes on the surface of a membrane. From the given loads and measured nodal displacements, one can assemble the resulting stiffness matrix and approximate the material properties associated with the membrane. Mathematical estimations and computer simulations were performed to determine the perturbation of load and displacement errors on the resulting material properties. The results indicated that the material properties are particularly sensitive to displacement errors. The displacement measurements may require an accuracy of 20 microns for a 4 x 4 cm2 specimen. Significant inaccuracies occur close to the points of load application.
Anisotropy↗
Orally delivered methadone as a reinforcer in rhesus monkeys.
Methadone usually is taken orally for drug abuse treatment in humans but oral methadone self-administration by laboratory animals has not been investigated extensively. The present study examines acquisition and maintenance of oral methadone maintained responding in four adult male rhesus monkeys. Drug solution was available from one liquid delivery system and water from a second system during daily 3-h sessions. Locations of liquids were reversed each session, and liquid (0.65 ml per delivery) was delivered according to a fixed-ratio reinforcement schedule. Initially a test for the reinforcing effects of 0.00625-0.4 mg/ml methadone solutions was carried out but a consistent preference for drug over water was not seen. To establish methadone as a reinforcer, a fading procedure was used in which responding was first maintained by solutions of methadone (0.00625-0.4 mg/ml) combined with ethanol (0.0325-2.0% w/v). Subsequently, the concentration of the ethanol in the combination was gradually reduced to zero. Methadone-maintained responding (0.4 mg/ml) persisted when ethanol was no longer present. To confirm that the drug was serving as a reinforcer, the dose was varied: (a) by changing the volume delivered while the concentration was held constant and (b) by changing the concentration of the methadone while the volume per delivery was held constant. Over a wide range of doses, deliveries of methadone solution usually exceeded deliveries of concurrently available water. Orderly relationships were observed among methadone dose, response rate, and drug intake. The study of oral self-administration of opioid drugs by nonhuman primates may be a useful strategy for the development and evaluation of new drug substitution or replacement therapies.
Administration, Oral↗
Fluoxetine is ineffective for treatment of cocaine dependence or concurrent opiate and cocaine dependence: two placebo-controlled double-blind trials.
Cocaine dependence has proved difficult to treat, whether occurring alone or in combination with opiate dependence. No medication has been demonstrated to be uniquely effective. Fluoxetine was examined as a candidate in two randomized, double-blind, placebo-controlled trials, one with cocaine-dependent patients (study 1) and the other with patients both cocaine and opiate dependent (study 2). It was selected for known specific action, antidepressant effects, minimum side effects, and data showing reduced cocaine effect and self-administration. Clinic visit frequency requirement, a variable with implications for treatment and cost, was also examined in study 1. A total of 228 patients in study 1 and 21 patients in study 2 completed consent and intake procedures. Patients with serious medical or DSM-III-R diagnoses other than cocaine dependence (study 1) or opiate and cocaine dependence (study 2) were excluded. Study 1 patients were assigned to one of two visit frequency schedules (2 or 5 days/week) and one of three medication doses (0, 20, or 40 mg of fluoxetine/day). Study 2 patients received placebo or 20 mg of fluoxetine and 65 to 80 mg of methadone and attended the clinic 5 days/week. All patients participated in individual therapy sessions. Urine screens were conducted twice weekly. A fluoxetine dose response relationship emerged in study 1 for retention with groups from best to worst being placebo, 20 mg, and 40 mg. Dose effect order was the same for both visit conditions. Cocaine use persisted in all groups. The two visits/week condition was correlated with better retention than the five visits/week condition. A significant interaction emerged between intake urine and visit frequency; patients with benzoylecognine screens at intake used cocaine significantly less in the 5 days/week condition, while exhibiting no reduction in the 2 days/week condition. Patients cocaine positive at intake were better retained with infrequent visits. In study 2, a transient reduction in benzoylecognine-positive drug screens emerged for the fluoxetine group. These complementary studies demonstrate that fluoxetine is ineffective in reducing cocaine use or craving. Study 1 also points to setting conditions modulating treatment outcome.
Adult↗
[Control processes in speech production: flexibility and determination of event related speech planning].
The issue of our study is the flexibility of high level adjustments for the process of relating events. Our assumptions are based on the Mannheim Regulation Theory of Speech Production, in which three modes of central control are distinguished: stimulus control, schema control, and ad hoc control. Our first experiment shows that verbal accounts of an event (due to selection and construction processes) as well as the interindividual variability of this accounts (due to the control mode being less or more restricted) are strongly determined by the situational characteristics in which they are produced. In our second experiment, pressure of time is introduced into the speech production task as a disturbance factor to put some load on the attentional resources thus uncovering the flexibility vs. automaticity of the speech production process. A comparison of the results favors the assumption of verbal accounts of an event being produced by strong schematic control in a highly institutionalized situation, whereas verbal accounts of the same event in an unofficial, private situation are produced by more ad hoc planning. The results permit to psychologically reconstruct the narrating of events and the reporting of events as speech production processes which are guided by different control modes with respect to their flexibility and to their attentional demands.
Adult↗
Effects of ethanol on human free-operant cooperative responding.
The effects of ethanol (0.5, 0.75 and 1.00 g/kg) on human cooperative behavior were examined. Ethanol or placebo was administered 30 min before the second of five trials. During the first of two alternating schedule components, button presses were maintained by a random interval (RI) 60-s schedule of point additions to a counter marked 'Your Earnings'. During the second, Choice, component a concurrent RI 60-s schedule maintained button presses on two manipulanda. Subjects randomly assigned to the social group were instructed that they were paired with another person and could earn points working with or independently of this person. Working together, the cooperative response, simultaneously produced points on counters marked 'Other's Earnings' and 'Your Earnings'. Working independently, the independent response produced points only on the counter marked 'Your Earnings'. The other person was fictitious. The instructions for the non-social group did not mention another subject and the counter marked 'Other's Earnings' was not visible but schedule contingencies were identical to those for the social instruction group. For the social instructions group, 1.00 g/kg ethanol increased the proportion of cooperative responses and time allocated the cooperative option. For the non-social instruction group, time allocated to the topographically identical but non-social equivalent of the cooperative response decreased at the same dose. No significant between-group effects were observed following acute administration of 0.50 and 0.75 g/kg ethanol. These results suggest that the instructions established a functionally distinct social, cooperative, response which was differentially affected by ethanol.
Adolescent↗
The effects of high and low doses of methadone on cigarette smoking.
The effect of methadone dose on the cigarette smoking of five methadone maintenance subjects was studied in a clinical setting. Following a two-week baseline period, daily doses of methadone were either increased (50-80 mg) or decreased (80-50 mg) every two weeks according to an A-B-A-B study design. Continuous self-monitoring was used to collect data on natural smoking behavior, and expired air carbon monoxide (CO) levels were measured at each clinic visit. The predicted methadone dose-related changes in smoking were found in three of the five subjects. Fine-grained analysis of self-monitoring records showed that the proportion of total daily smoking was highest within 4 h after taking methadone for three subjects. CO levels were not significantly associated with smoking rate. The results further support and extend previous reports that methadone may produce dose-related increases in smoking. No reactive effects of self-monitoring were observed, and compliance with this procedure was extremely high, supporting the usefulness of this method for assessing natural smoking behavior in this population.
Adult↗
Methadone dosage, cocaine and opiate abuse.
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Cocaine↗
[American Indian inhabitants in Saint Lawrence Valley, 1608-1765].
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Canada↗