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Biomedical subjects

Kenzie L Preston

Publications and source records attributed to Kenzie L Preston.

29 records · Page 2Linked to original sources

Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection.

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.

Administration, Oral↗

Cognitive-behavioral therapy plus contingency management for cocaine use: findings during treatment and across 12-month follow-up.

Contingency management (CM) rapidly reduces cocaine use, but its effects subside after treatment. Cognitive-behavioral therapy (CBT) produces reductions months after treatment. Combined, the 2 might be complementary. One hundred ninety-three cocaine-using methadone-maintained outpatients were randomly assigned to 12 weeks of group therapy (CBT or a control condition) and voucher availability (CM contingent on cocaine-negative urine or noncontingent). Follow-ups occurred 3, 6, and 12 months posttreatment. Primary outcome was cocaine-negative urine (urinalysis 3 times/week during treatment and once at each follow-up). During treatment, initial effects of CM were dampened by CBT. Posttreatment, there were signs of additive benefits, significant in 3- versus 12-month contrasts. Former CBT participants were also more likely to acknowledge cocaine use and its effects and to report employment.

Adult↗

Do noncontingent vouchers increase drug use?

Data from 2 contingency management trials, targeting opiate or cocaine use, were used to investigate whether noncontingent vouchers inadvertently reinforce drug use. The control group in each trial received noncontingent vouchers matched in value and frequency to those received by experimental groups, but independent of urinalysis. Vouchers were offered thrice weekly for 8 weeks (opiates) or 12 weeks (cocaine). Both dose-response and temporal associations of noncontingent voucher receipt with drug-positive urines were assessed. Drug use was unrelated to frequency of noncontingent voucher delivery and noncontingent voucher receipt when being drug positive was unassociated with risk of subsequent drug use, with one exception: cocaine use in the cocaine study (relative risk = 1.05, 95% confidence interval: 1.01-1.09). Overall, results do not indicate a causal relationship between noncontingent voucher receipt and increased drug use.

Adult↗

Methadone and metabolite urine concentrations in patients maintained on methadone.

As regulatory control over methadone maintenance relaxes, the need for methods of monitoring compliance will increase. In community clinics, monitoring would most likely involve immunoassays of outpatients' trough urine specimens. There are no published norms for such data. Therefore, we determined concentrations of methadone in 1093 urine specimens collected thrice weekly in 27 outpatients during up to 17 weeks of observed methadone ingestion (35 to 80 mg/day) using a semiquantitative homogeneous enzyme immunoassay (CEDIA). We used a separate CEDIA assay to measure methadone's main metabolite, 2-ethylidene-3,3-diphenylpyrrolidine (EDDP), which may help detect compliance in fast metabolizers or patients who adulterate samples to simulate compliance. Methadone concentrations were more variable than those of EDDP. Concentrations of methadone were < 100 ng/mL in one specimen, between 100 and 300 ng/mL in 27, and >or= 300 ng/mL in all others. EDPP concentrations were >or= 100 ng/mL in all specimens, suggesting that EDDP should be detectable in urine from compliant patients. Methadone and EDDP concentrations significantly increased with methadone dose and (in one participant with poor clinic attendance) significantly decreased following missed methadone doses. Nevertheless, variability was too great to permit estimation of methadone dose (or detect a single missed administration) from any single specimen.

Drug Monitoring↗

Methadone treatment induces attenuation of cerebrovascular deficits associated with the prolonged abuse of cocaine and heroin.

Opiate replacement therapy has been useful in reducing heroin use and in keeping patients in treatment programs. However, neuropsychological and neurophysiological effects of this treatment regimen have not been evaluated systematically. To determine whether methadone treatment reduces the magnitude of cerebral blood flow alternations in polysubstance (heroin and cocaine) abusers, we compared blood flow parameters in control subjects (n=26), polysubstance abusers (n=28) maintained on methadone for 24 weeks, and polysubstance abusers (n=22) who were not seeking treatment. Blood flow velocity was recorded from the anterior and middle cerebral arteries using transcranial Doppler sonography on an outpatient visit. The pulsatility index, a measure of cerebrovascular resistance, was significantly (p&<0.05) increased in both groups of polysubstance abusers compared to control subjects. Increased pulsatility in the two groups of substance abusers suggests constriction of the small cortical arteries. Nevertheless, the methadone-maintained polysubstance abusers had significantly lower pulsatility values than the nontreatment substance-abusing group. These findings suggest that maintenance on methadone might have significant beneficial neurovascular effects on this population of patients.

Adult↗

Abstinence reinforcement maintenance contingency and one-year follow-up.

BACKGROUND: Relapse to drug use is often seen when contingencies designed to reduce drug use are discontinued. This paper reports on a stepdown maintenance contingency and 1-year follow-up in 110 patients who were maintained on methadone (50 or 70 mg/day) and who had completed a contingency management trial targeted to decreasing their opiate use. In the prior study (induction phase, 8 weeks) participants received vouchers for each opiate-negative urine screen or noncontingently. METHODS: In this study (maintenance phase, 12 weeks), participants were rerandomized to receive vouchers and take-home methadone doses contingent on providing opiate-negative urine specimens (N=55) or noncontingently (N=55). Since participants had been rerandomized from induction-phase contingencies, most study data were analyzed as if from a 2 x 2 (inductionxmaintenance) design. Follow-up interviews were conducted at 3, 6, and 12 months after study participation. RESULTS: Patients who received the maintenance contingency following an 8-week induction contingency had better outcomes than those who received noncontingent incentives in either the maintenance or induction phases of the trial. Good outcome at follow-up was predicted by enrollment in methadone maintenance after the study. Significantly more participants in the maintenance contingency group transferred directly to another methadone program. CONCLUSION: These findings support the therapeutic value of extending the duration of contingency management and long-term methadone maintenance.

Adult↗

A dose response study of cognitive behavioral therapy in cocaine abusers.

In order to evaluate the effect of frequency of counseling sessions, we studied retention, cocaine use and craving, and psychiatric symptoms of 68 cocaine-dependent outpatients randomly assigned to twice weekly, once weekly, or biweekly sessions in a 12-week treatment program that utilized manual-based, individual cognitive behavioral psychotherapy. All participants were tested and monitored twice a week. Retention was comparable among treatment groups, and improvement was found regardless of counseling frequency. Cocaine use (urine toxicology and self-report), cocaine craving (VAS), and total psychiatric symptoms (SCL-90) decreased by modest but statistically significant (p < 0.05) amounts in all treatment groups. Findings suggest that cognitive behavioral therapy is effective in reducing cocaine use even if a less intensive schedule is used.

Adult↗

Open-label pilot study of bupropion plus bromocriptine for treatment of cocaine dependence.

Combinations of medications are often used in neuropsychiatry to enhance treatment efficacy. This 8-week, open-label study tested the combination of bupropion (< or =300 mg) and bromocriptine (< or =7.5 mg) daily in 34 cocaine-dependent (DSM-IIIR) outpatients also receiving weekly individual counseling. The first 18 subjects spent one week at maximum dose; the next 16 spent three weeks. Both groups showed significant reductions in self-reported cocaine use, with no significant change in proportion of urine toxicology tests positive for cocaine. There were no significant differences in outcome between groups. These results suggest that the combination of bupropion and bromocriptine is safe in cocaine addicts, but provide ambiguous evidence of its efficacy.

Adolescent↗

Urinary elimination of cocaine metabolites in chronic cocaine users during cessation.

We previously showed that chronic cocaine use by active illicit users produced a longer plasma half-life than expected based on acute low-dose cocaine studies. Here we report urinary excretion patterns of cocaine metabolites as benzoylecgonine (BE) equivalents from 18 of the same individuals, housed for up to 14 days on a closed research unit. In addition, we evaluated whether creatinine normalization of BE equivalents increased mean detection time and reduced mean within-subject variability. All urine voids (N = 953) were individually assayed; BE equivalents were determined semi-quantitatively by FPIA. Compared to concentration in first void after admission, BE equivalents decreased to approximately 33%, 8%, and 4% at 24, 48, and 72 h, respectively. Mean +/- SD (range) time to first negative specimen (BE equivalents < 300 ng/mL) was 43.6 +/- 17.1 (16-66) h. BE equivalents fluctuated considerably across successive specimens; 69% of participants tested positive at least once after testing negative, and the mean time to last positive specimen was 57.5 +/- 31.6 (11-147) h after the first specimen. Thus, mean cocaine metabolite detection times were consistent with prolonged elimination, with 63% of participants testing positive longer than the expected 48-h window of detection after admission to the unit. Mean time to last positive after last use of cocaine, known by self-report only, was approximately 81 +/- 34 (34-162) h. Creatinine normalization, with the cut-off of 300 ng BE equivalents/mg creatinine, increased detection time: mean time to first negative specimen was 54.8 +/- 20.7 (20-100) h, and mean time to last positive specimen was 88.4 +/- 51.0 (35.6-235) h. Compared with the concentration in the first void after admission, BE equivalents/creatinine decreased to approximately 56%, 6%, and 5% at 24, 48, and 72 h. However, creatinine normalization did not reduce the fluctuation of BE equivalents across successive specimens. Thus, creatinine normalized values may be useful when the goal is to maximize the probability or duration of cocaine metabolite detection, but may be less useful in determining whether an individual has used cocaine since a previous specimen collection.

Adult↗

Toxicologic aspects of heroin substitution treatment.

Heroin abuse is an international problem with which all countries must continually cope. Many countries have implemented heroin substitution therapy as an effective means of decreasing illicit heroin use, crime, HIV risk, and death, and in improving employment and social adjustment. Although methadone is the most commonly used medication for heroin substitution, other agonists in current use include levomethadyl acetate (LAAM), buprenorphine, and pharmaceutical-grade heroin. This report reviews toxicologic issues that arise in these programs. A broad array of testing methodologies are available that allow selection of on-site testing or laboratory-based methodology. Urine specimens may be monitored for nonprescribed drugs on a qualitative or semiquantitative basis. Methods for differentiating opiate sources by urinalysis have been proposed to distinguish poppy seed consumption from heroin abuse and for distinguishing pharmaceutical-grade heroin from illicit heroin. Therapeutic drug monitoring for methadone in plasma continues to be evaluated for use in establishing adequate dosing and detecting diversion, and new methods have been devised for measurement of the optical isomers of methadone in plasma. Biologic specimens, in addition to plasma and urine, have been evaluated for use in drug monitoring, including sweat, hair, and oral fluid, with promising results. Overall, the many recent developments in testing methodology provide more effective means to assess patients in heroin substitution programs and should contribute to improvements in public health.

Buprenorphine↗

Gender differences in indices of opioid dependency and medical comorbidity in a population of hospitalized HIV-infected African-Americans.

We examined gender differences in drug use patterns and in medical presentation among 520 hospitalized, HIV-infected African-Americans. Substance abuse history was self-reported, and medical data were obtained by chart review. Overall, 321 (65%) reported ever having used heroin, with equivalent rates in men and women. Women were more likely to report current use, to have sought treatment, and tended to feel more dependent on heroin than men. Among heroin users, women were more likely to be admitted for conditions related to drug use, rather than AIDS, and to have CD4 counts > 200/mm3. These gender differences in opioid dependency and medical comorbidity may indicate a need for alternative treatment approaches for men and women.

Adult↗