Ethnic sensitivity study of fingolimod in white and Asian subjects.

OBJECTIVE: The authors compared the pharmacokinetics and pharmacological effects of the immunomodulator fingolimod in healthy white and Asian subjects for potential ethnic differences. METHODS: White and Asian (Japanese) healthy subjects were demographically matched for sex, age and weight. Subjects received single 1.25 mg doses of fingolimod (6 ethnic pairs), 2.5 mg (7 pairs), 5 mg (6 pairs) or 5 mg/day for 7 days (6 pairs). The pharmacokinetics of fingolimod, major metabolites, peripheral blood lymphocyte counts and heart rate were characterized over 1 month after single-dose and 2 months after multiple-dose administration. RESULTS: There were no clinically relevant differences in the fingolimod dose Cmax or dose AUC relationships between Asian subjects (slopes 0.84 and 1.05) versus white subjects (slopes 1.13 and 1.26) after single-dose administration. During multiple-dose administration, there were no clinically relevant interethnic differences in fingolimod accumulation ratios (6.6 +/- 0.4 for whites, 7.0 +/- 0.7 for Asians), area under the concentration-time curve (390 +/- 73 versus 382 +/- 106 ng x h/ml), or elimination half-life (7.4 +/- 0.8 versus 7.9 +/- 2.0 days). The acute decrease in lymphocyte counts after single- and multiple-dose fingolimod were similar in the two ethnic groups. The lymphocyte recovery rate to baseline after a 5 mg single dose and 5 mg/day multiple dose was reduced by 36 and 15% in Asian subjects compared with white subjects. The transient, acute decrease in heart rate after the first dose of fingolimod and the subsequent return to baseline was similar in the two ethnic groups. CONCLUSION: There were no marked differences between healthy white and Asian subjects in fingolimod single-dose and multiple-dose pharmacokinetics, lymphocyte trafficking and heart rate responses.

Rethinking patient placement: the human service matrix model for matching services to needs.

The improvements in both clinical and fiscal outcomes necessary for prosperity in the current healthcare environment require a rethinking of our conceptual approaches to patient assessment, treatment planning, and service delivery. Conventional practice rests in part on the Level of Care concept, which assigns intensities of both clinical services and treatment settings in a linked manner according to impairment severity. Although this approach has resulted in more efficient matching of resources to needs, it is overly restrictive, and does not speak directly to the need to match both healthcare and social services (including treatment setting) to human needs for treatment to be successful. The Human Service Matrix model presented in this article delinks clinical from social services and creates a conceptual framework for integrating social and healthcare services in the cure of patients with addictions. Our experience with this model suggests it has heuristic value in promoting cost and outcome effective treatment.

The effect of managed care on the treatment outcome of substance use disorders.

This study examined the effect of managed care and other reimbursement mechanisms on the outcome of substance abuse treatment at a single treatment facility. A retrospective review of 1594 patient records yielded treatment utilization, diagnostic, and demographic data. Recidivism rates for intensive managed care, traditional managed care, private pay, and state-funded groups of patients were compared. Results showed that, contrary to expectations, recidivism rates were not different for managed vs nonmanaged care patients. In addition, recidivist patients had significantly more ICD-9 diagnoses than nonrecidivist patients. A discussion of future research suggests that other outcome measures need to be examined in addition to recidivism rate, such as psychosocial functioning following treatment and indicator(s) of severity of illness, to better determine the effect of managed care and other reimbursement mechanisms on treatment outcome.

Discriminating placebo and drug in generalized anxiety disorder (GAD) trials: single vs. multiple clinical raters.

A multisite, double-blind, placebo-controlled study was made of 177 patients with the diagnosis of generalized anxiety disorder. After a 1-week placebo lead-in, they were randomized to 4 weeks of treatment by placebo or one of two doses of a novel, nonsedating compound that had demonstrated reduction of fear-avoidance behavior in animals. Efficacy was not demonstrated at a significant level. A further analysis of 142 patients who completed the treatment was undertaken to test the hypothesis that efficacy might be demonstrated by the single-rater procedure (SRP), which eliminates interrater error variance. The 80 patients who were examined by the same clinical rater for all six visits were compared with the 62 patients who had the multiple-rater procedure (MRP), ratings by two or more clinicians sequentially over the six visits. A two-way analysis of variance showed significantly greater discrimination of placebo and drug for the MRP group. The results provided no support for the frequent preference for the SRP. The MRP may include less psychotherapeutic interaction with the patient and less researcher bias in ratings.

Treatment Issues in Adolescent Substance Use and Addictions: Options, Outcome, Effectiveness, Reimbursement, and Admission Criteria.

Cost-reduction strategies and a lack of overall perspective have created a potentially dangerous climate for the treatment of the various forms of adolescent substance abuse. The authors argue for a holistic approach that focuses on demographics, family issues, school functioning, and other related problems as well as on careful evaluation of treatment outcome and criteria for admission, continued stay, and discharge from treatment programs.

The first shall be last; but can the last be first?

The State of Hawaii has long prided itself on being a leader in the nation in its provision of mental health and other social and health services. In 1986, and again in 1988, the Public Citizen Health Research Group, a Ralph Nader affiliated entity, ranked Hawaii 51st among the states and the District of Columbia in its care of the seriously mentally ill. Initial reaction within the mental health community in Hawaii was primarily one of perplexity and disbelief. Although it quickly realized that this report was based on the cursory opinion of one principal individual, drawing upon very little data and solid comparable information, the impact of these rankings has been to focus much more attention upon what really is happening to the seriously disabled mentally ill (SDMI) in this state. Hopefully, the eventual results will conform to the original intent of the report's authors, Drs. Fuller Torrey and Sidney Wolfe, namely a new, enhanced and broadbased commitment to improving services to this special and often forgotten population in need.

An instrument for treatment progress and matching: the recovery attitude and treatment evaluator (RAATE).

Clinicians are under increasing pressure to contain costs and to justify their triage decisions and addiction treatment settings to third party payors. Treatment-effectiveness research points to the need for better patient/treatment matching decisions and systems of care. The Recovery Attitude and Treatment Evaluator (RAATE) is an instrument to develop a profile of the severity of the patient's illness. It is a clinically useful, chemical-dependency-specific, comprehensive but efficient instrument to help classify patients, define admission and utilization review criteria, match patients to the appropriate level of care, and measure treatment progress. The RAATE can be used by clinicians, health care managers and researchers in the chemical dependency treatment field, which lacks a common "language" for comparing patient populations, describing treatment progress, and communicating across disciplines.