Application of a Physiologically Based Pharmacokinetic Model to Study Theophylline Metabolism and Its Interactions With Ciprofloxacin and Caffeine.

Theophylline is a commonly used bronchodilator. However, due to its narrow therapeutic range, moderate elevation of serum concentration can result in adverse drug reactions (ADRs). ADRs occur because of interhuman pharmacokinetic variability and interactions with coprescribed medicines. We developed a physiologically based pharmacokinetic (PBPK) model of theophylline, caffeine, and ciprofloxacin metabolisms to: examine theophylline pharmacokinetic variability, and predict population-level outcomes of drug-drug interactions (DDIs). A simulation-based equation for personalized dosing of theophylline was derived. Simulations of DDI show that calculated personalized doses are safe even after cotreatment with large doses of strong inhibitors. Simulations of adult populations indicate that the elderly are most susceptible to ADRs stemming from theophylline-ciprofloxacin and theophylline-caffeine interactions. Females, especially Asians, due to their smaller average size, are more susceptible to DDI-induced ADRs following typical dosing practices. Our simulations also show that the higher adipose and lower muscle fractions in females significantly alter the pharmacokinetics of theophylline or ciprofloxacin.

Effects of a checklist on self-assessment of blood glucose level by a memory-impaired woman with diabetes mellitus.

This study evaluated effects of a checklist on the accuracy of self-assessment of blood glucose level by a diabetic woman with memory impairments caused by viral encephalitis. The checklist consisted of 54 steps for operating an electronic glucometer, which the subject performed in sequence and checked off when completed. Following introduction of the checklist, the percentage of steps completed correctly increased in simulated and actual blood glucose tests and yielded clinically useful information.

Applying a DRO schedule and compliance training to reduce aggressive and self-injurious behavior in an autistic man: a case report.

An autistic man who displayed aggressive, self-injurious, and destructive behavior in a psychiatric hospital ward despite administration of psychotropic medications and repeated application of physical restraints was treated with a differential reinforcement of other behavior (DRO) schedule and compliance training. These were employed in conjunction with ongoing medical interventions. After introduction of behavioral procedures, the frequency of applying restraints for violent behavior declined from an average of more than once per day to less than once per month. Data taken while the program was maintained over a 1-year period showed that violent behavior remained at a very low level.

Re-establishing conversational skills in overtly psychotic, chronic schizophrenic patients. Discrete trials training on the psychiatric ward.

A discrete trials procedure incorporating graduated prompts, social and consumable reinforcement, corrective feedback, delay of reinforcement, and a chaining procedure was used to teach four actively psychotic, chronic schizophrenic patients rudimentary conversational skills. In a multiple-baseline design, training was sequentially applied to the target conversational skills of giving a salutation, addressing the trainer by his or her name, making a personal inquiry, and asking a conversational question. Results showed systematic training effects in three of the four subjects. Training gains were reliable but slow, requiring over 70 trials to reach acquisition criterion on certain skills. The fourth subject exhibited only unstable gains on the first target response and minor improvements on the second target response, the latter of which disappeared when training procedures were withdrawn. All subjects displayed spontaneous recovery on the generalization measure of answering a personal inquiry.

Behavioral treatment of violent psychiatric patients.

This article reviewed major accelerative and decelerative behavioral treatments for aggressive and destructive behavior in psychiatric patients. Accelerative procedures supplant antagonistic behavior by teaching adaptive skills, and by strengthening competing responses; they are realized in token economies, social skills training, differential reinforcement of other behavior, and activity programming. Current decelerative procedures reduce violent behavior by decreasing reinforcement accessible to the patient following violent acts; they are exemplified by social extinction, response cost, time out from reinforcement, overcorrection, and contingent restraint. All behavioral interventions are applied within a philosophic framework that emphasizes observable behavior, measurement of treatment effects, and restructure of the social and physical environment to improve patients' response patterns. This approach extends beyond a problem-oriented model and presents proven techniques for developing and maintaining patients' adaptive functioning.

Training chronic mental patients to independently practice personal grooming skills.

Schizophrenic patients typically have poor grooming and self-care skills, which hinder their social relationships and their chances of successful adaptation in the community. A practical and inexpensive program for teaching grooming skills to hospitalized chronic mental patients has been developed in a California state hospital. Patients are also taught to evaluate their grooming behavior and to carry out grooming activities independently. Grooming deficits and improvements are rated on an 11-category performance checklist. Two small-scale pilot studies showed that the program is efficacious and that nursing staff can effectively apply the procedures; in another study, the program was implemented on a large psychiatric unit with minimal staffing and resources.

Providing independent recreational activities to reduce stereotypic vocalizations in chronic schizophrenics.

We evaluated the effects of minimally supervised, independent recreational activities on stereotypic vocal behavior in two chronic schizophrenic patients. In baseline sessions, subjects were observed during unstructured free time in the psychiatric ward. In treatment sessions, therapists presented preferred recreational materials (magazines, models, and art projects), verbally prompted on-task behavior every 20 min, and, in one condition, administered contingent tokens. Independent recreational activities reduced medium-rate self-talk in one subject and high-rate mumbling in a second subject by 60%-70%. Results were the same with or without contingent tokens. Apparent self-maintaining characteristics of these vocal responses are discussed.

Social skills training for chronic mental patients.

Social skills training has proved to be effective in increasing the social competence of chronic mental patients. The authors describe three models of social skills training, all of which involve role playing by the patient and modeling, prompting, feedback, and reinforcement by the therapist. Many patients can benefit from the basic training model. For patients functioning at a higher level, the problem-solving model provides general strategies for dealing with a variety of social situations. The attention-focusing model, designed for highly distractible and withdrawn patients, teaches skills through constant repetition of tasks and minimizes demands on cognitive abilities. The authors emphasize the importance of taking steps to ensure that the skills learned during training are generalized to other situations and settings.

Assessment and training of clinical interviewing skills: analogue analysis and field replication.

Two studies were conducted to assess the train clinical interviewing skills. In Experiment 1, eight university practicum students ("therapists") and either role played or volunteer "clients" were audiotaped during simulated interviews. Following the collection of baseline data on both therapist and client responses, training was provided by way of written materials, classroom instruction and practice, and quizzes. Results of a multiple baseline design across subjects showed improvements in therapists' interviewing skills and subsequent increases in client responding. Experiment 2 replicated and extended the research to a hospital outpatient clinic, in which therapists interviewed the parents of children with behavior problems. In addition, four months following the completion of Experiment 2, follow-up data collected during a maintenance condition showed continued high levels of therapist and client behavior. Finally, a panel of expert peers indicated that each response category was judged highly relevant to the behavioral assessment process.

Evaluation of staff training in group homes for retarded persons.

Staff in 12 group homes for mentally retarded persons were randomly assigned to either an experimental condition (N = 6), receiving eight 1.5-hour training sessions in behavior modification, or a waiting-list control condition (N = 6). Pre- to posttraining change scores showed that, compared to control home staff, experimental home staff increased significantly more in knowledge of behavioral techniques, had better evaluations of their residents, and indicated less decline in job satisfaction. Naturalistic observational data, collected with continuous real-time recording devices, showed trained staff superior in correctness and latency of their responses to residents. Trained homes also had significantly greater increases in the frequency and duration of positive staff and resident behavior.