Faculty Bibliography

Chemical tracers are thought to be a desirable means of measuring patient compliance with medication. However, no compound has emerged as a standard. To explain this observation, the authors explored the mathematics of simulated tracers with half-lives 5 to 140 days over a month of daily dosing. To model assay variability, they added random 'noise' to calculated tracer serum levels. They then fitted those altered levels to the dosing pattern most likely to have produced them, given known kinetics of the tracers. The large number of possible dosing patterns over a month (268,435,456) magnified uncertainty in interpreting noise-altered levels. At best, with an assay variability of 5%, compliance could be estimated only within 4 to 8 doses per month. The tracer with a half-life of 30 days performed best. Pairing tracers did not improve uncertainty. The authors found that even a model neglecting many real-world variables suggests a limited role for tracers in measuring compliance

AIMS: We aimed to determine whether simultaneous use of two tracer compounds with long and differing elimination half-lives may permit more precise recognition of percent compliance and discrimination among remote, intermediate, and recent patterns of daily dosing. METHODS: We have derived, through computer modelling, the potential utility of digitoxin and phenobarbitone as simultaneous tracers. From kinetic data on these reliably measured compounds with long half-lives we defined the percentage error below which this pair of tracers can be expected to discern the precise, and the approximate, pattern and number of daily doses taken over a mouth. RESULTS: The longer the half-lives of the tracers the greater the sensitivity of our model to percentage compliance. At extremely long half-lives, relative to the period of dosing being monitored, sensitivity approaches 100% if measurement error is in the 1-2% range. The ratio of the half-lives between the two tracers that is optimal for detection of percentage compliance is 0.2 to 0.8. The detection of pattern does not depend importantly either on the tracer half-lives or on their ratio to each other. The greater the percentage compliance, the more accurately our two-tracer model determines the pattern of dosing. CONCLUSIONS: Precise characterization of compliance using tracers must probably await the development of compounds with half-lives measured in weeks or months. The probability of compliance of a given degree can be derived from our two-tracer technique with best-fit analysis such as we describe

HIV infection cannot be treated nor can its spread among those who use drugs be contained unless physicians diagnose and treat drug dependence. Recent changes in the DSM-III definitions simplify diagnosis. It is primarily by the presence and extent of the dependence syndrome that decisions are made regarding early HIV counseling and testing, medical management, referral for drug dependence treatment, and the approach to minimizing disease spread by the patient

We screened inpatient and outpatient parenteral drug users with no clinical evidence of AIDS for immunodeficiency and antibodies to HTLV-III by ELISA. Among 20 outpatient drug users, 5 (25%) were seropositive. Three of these (and 2 who were seronegative) had low T-cell ratios. Over 6 months, 1 seropositive patient with a low ratio developed oral thrush and weight loss. We also studied 13 parenteral drug users hospitalized for conditions other than AIDS. Eight had low T-cell ratios, and at least 6 of these developed AIDS or ARC within 4 months. Serum from 8 of 13 inpatients was available for HTLV-III testing: 6/8 were seropositive and 3 of these 6 were among those developing AIDS or ARC. Abnormal T-cell ratios among all patients were associated with abnormal HTLV-III serology (p = .02). Of the 7 patients who developed AIDS or ARC, 4 were tested for both antibodies and T-cell ratios: all 4 were seropositive and had low ratios. A low ratio (p = .0004), a positive ELISA (p = .014), and abnormalities of both tests (p = .001) were associated with the development of AIDS or ARC. Of the 26 patients without AIDS or ARC, 3 were lost to follow-up and 23 did not develop AIDS or ARC. Six of these 26 had abnormal ratios. Of the 21 patients who did not develop AIDS or ARC and who were tested for HTLV antibodies, 2 were lost to follow-up. Seven of 21 were seropositive and 2/21 were both seropositive and had a low ratio. One of these 2 seropositive patients with low ratios also had lymphadenopathy, but he was lost to follow-up. The other had no adenopathy and remained well until her death from trauma a year later. This study found two populations with very different risks. Six of 13 hospitalized parenteral drug users and only 1 of 20 healthy outpatients developed AIDS or ARC

Acquired Immune Deficiency Syndrome (AIDS) is a clinical entity that is part of a spectrum of immune dysfunction found in specific high risk groups, among them intravenous drug users. In drug users AIDS almost always presents as an opportunistic infection, usually Pneumocystis carinii. The leading etiologic hypothesis is of a viral agent acting, it is possible, on a previously immunocompromised host. Recent research at hospitals affiliated with The Albert Einstein College of Medicine, where an unusually large proportion of AIDS patients are drug users, is described. Suggestions are advanced for the management of IV drug users with immune dysfunction

We studied the demographic characteristics, drug use patterns, and sexual habits of intravenous (IV) drug abusers to further define this population at risk for acquired immunodeficiency syndrome (AIDS). Sixteen IV drug abuser patients with AIDS, 24 IV drug abuser patients with AIDS-related complex (ARC), and 14 IV drug abuser controls without evidence of AIDS or ARC were evaluated. The subjects in each group were similar demographically, in drug use practice, and in sexual orientation and experience. Of the AIDS and ARC patients, 34 (88%) of 40, including all seven homosexual men, shared needles, as did all drug abusers without AIDS or ARC. Seventy-four percent of patients, including all homosexual men, attended 'shooting galleries,' where anonymous multiple-partner needle sharing took place. Needle sharing supports the hypothesis of AIDS transmission by a blood-borne route, can explain the spread of AIDS and the high rate of seropositivity to the putative AIDS agent among IV drug abusers, and is a logical link between IV drug abusers and male homosexuals, the two largest groups with AIDS

A questionnaire concerning knowledge of opiate abuse and attitudes about abusers was administered to 94 randomly selected physicians and medical students at a large urban teaching hospital. Physicians from four clinical departments and at each level of residency training and medical students in the final year were represented. The mean knowledge score was 3.3 out of a possible 12. Neither the level of training nor specialty was related to test score for the group as a whole. However, family practitioners gained knowledge with increasing experience, while medical and surgical specialists scored lower as they advanced in training. On the attitude section, physicians had strong but individualistic views about drug abuse. Level of training, specialty, and knowledge test score were on the whole unrelated to attitude. The results indicated that physicians at every level of training might benefit from improved teaching in the area of opiate abuse

To determine the reliability of the laboratory in detecting drugs taken by overdosed patients, we evaluated laboratory performance on an unbiased sample of actual clinical specimens. Replicate serum and urine samples from a series of 20 consecutive clinically overdosed patients were sent to three commercial laboratories and one academic research laboratory for identification and quantification of intoxicating agents. All laboratories used the advance analytical techniques of gas chromatography-mass spectrometry. The results suggest that laboratories do not reliably identify drugs in the serum of overdosed patients, partly because of technical limitation, partly because of laboratory error, and possibly because of inadequate specimens. Drugs judged responsible for the overdose were identified in only 50% to 70% of the cases, depending on the laboratory. Reported concentrations sometimes varied over a 10-fold range