Pharmacokinetics of recombinant interleukin-2 in children with malignancies: a Pediatric Oncology Group study.

To develop effective interleukin-2 (IL-2) protocols for pediatric malignancies, it is important to define IL-2 pharmacokinetics in children. In a phase I trial, we studied IL-2 pharmacokinetics in seven children, aged 6-18, five with leukemia, one with neuroblastoma, and one with rhabdomyosarcoma. IL-2 was administered as a 15-min i.v. infusion of either 1 X 10(6) CU/m2/dose or 3 X 10(6) CU/m2/dose (every Monday, Wednesday, and Friday for 3 weeks). IL-2 levels were determined using an IL-2-dependent murine T lymphocyte cell line bioassay. Peak IL-2 levels of 120-426 and 330-740 CU/ml were achieved after the lower and higher doses, respectively. Pediatric IL-2 kinetics resembled data reported for adults, fitting a two-compartment model (least-squares-regression technique), with an alpha half-life of 14.0 +/- 5.6 min (range, 6.3-23.1) and a beta half-life of 51.4 +/- 10.7 min (range, 33.0-66.0). The volume of distribution approximated total extracellular fluid (mean, 0.18 L/kg). Further clinical trials are needed to identify which pediatric malignancies are sensitive to immunotherapy and to establish the optimal treatment regimens.

Intravenous immune globulin therapy. Treatment of a patient with severe immunodeficiency, chronic malabsorption, and fulminant septicemia.

Biweekly 200 mg/kg infusions of immune globulin (Gamimune) were given to a 46-year-old woman with severe common variable immunodeficiency, bronchiectasis, and chronic diarrhea with malabsorption. Failure to achieve therapeutically effective serum IgG concentrations in the face of fulminant sepsis was accompanied by a shortened serum IgG half-life of 10.6 days. Currently recommended doses of 200 mg/kg may prove inadequate in very ill patients with sepsis and malabsorption.

Behaviorally anchored ranking scale versus letters of recommendation for evaluating residency candidates.

A behavioral scale and traditional letters of recommendation were compared as tools for evaluating applicants for a hospital pharmacy residency program. In designing the behaviorally anchored ranking scale (BARS), a list of desirable characteristics of hospital pharmacy residents was compiled and descriptions were written of effective, average, and ineffective performance for these characteristics. Twelve characteristics in three categories (professionalism, special skills, and character attributes) were used. Each person who had written a letter of recommendation for the 1983-84 hospital pharmacy residency program at the University of Texas Medical Branch in Galveston was also asked to complete a BARS form. Pharmacy administrators involved in the resident-selection process used the BARS criteria to evaluate all letters of recommendation; responses on the BARS forms were then analyzed. For 18 applicants, 46 letters of recommendation and 39 BARS forms were completed. Many of the BARS characteristics were not addressed in letters of recommendation. None of the letters commented on leadership quality. Ability to work with others was the BARS characteristic most often mentioned in the letters (58.7%). Of characteristics that were mentioned in both the letters and the BARS, 82.4% were ranked equally in both. Of all the letters and scales, 59% were not in agreement with each other. The BARS provided a clearer picture of the characteristics and qualities of a hospital pharmacy residency candidate than did the letters of recommendation.

A utilization review of theophylline assays: sampling patterns and use.

Use of the theophylline assay was reviewed for two months in 121 hospital inpatients who received 426 evaluations at a university medical center. Clinicians adapted published audit criteria for the collection and use of theophylline assays. The charts of all patients receiving theophylline were examined daily, and the following data, among others, were collected: pulmonary function tests, arterial blood gases, liver function tests, vital signs, and physician assessments. Only 29.8 percent of the evaluations complied with all criteria. When the audit categories of rational indication, correct performance, and appropriate dosage adjustment were evaluated independently, compliance rates were 69.1, 72.3, and 67.2 percent, respectively. In 171 cases (48.6 percent), the physicians' instructions for the assay were inadequate to ensure proper collection time by the phlebotomist. Hospital laboratory charges for unnecessary, incorrectly performed, or inappropriately used theophylline assays were estimated to exceed +77000 annually. This audit demonstrates the need for a collaborative pharmacokinetics service with reimbursement through the physician billing charge.

Computer skills enhance a hospital pharmacy residency training program.

Hospital pharmacy residents participated in a program designed to introduce them to computer systems useful in pharmacy practice and to provide them with access to a variety of computer resources that could be helpful in completing their residency projects. Using existing computer facilities, various short courses and individual tutorials were employed to train residents in a variety of computer skills. These courses provided a useful vehicle for recent pharmacist graduates to acquire necessary computer skills not obtained during their academic training. Because the program provided residents with the tools needed for the management and analysis of large data sets, a marked increase occurred in the number of residency projects acceptable for publication in peer-reviewed pharmacy journals. Thus, residency projects improved in quality and faculty preceptors were more motivated to get involved in such projects.

A utilization review of digoxin assays: sampling patterns and use.

A review of digoxin assay utilization concurrent with patient hospitalization was conducted at the University of Texas Medical Branch. An interdepartmental committee of clinicians adapted audit criteria for the collection and use of digoxin assays. This included rational indications, correct performance (i.e., collection and processing of serum sample) and appropriate dose adjustment. The charts of all patients receiving digoxin were examined daily, whether or not the physician had ordered a drug assay. Contributory data were collected and analyzed, including serum electrolyte concentrations, arterial blood gases, renal function tests, vital signs, physician assessments, and other information relating to pertinent and concomitant diseases or drug therapy. The 2-month review included 104 hospital inpatients who received 245 evaluations. Only 38.4% of the evaluations were determined to be compliant with all criteria. When the audit categories of rational indication, correct performance, and appropriate dosage adjustment were evaluated independently, compliance rates were 66%, 73% and 86%, respectively. In 108 cases (52%), the physicians provided inadequate instructions in their request for the digoxin assay to insure proper collection time by the phlebotomist. Approximately 94% of all assay results were verbally communicated to the physician or returned to the patients' charts for use in patient management within a minimum of 24 hours. Hospital laboratory charges for unnecessary, incorrectly performed, or inappropriately used digoxin assays were estimated to exceed $100,900 annually. The audit was used to demonstrate the need for changes in hospital procedures and house staff training. A collaborative pharmacokinetics service was organized with reimbursement accomplished through the physician billing charge.

The feasibility of barcode-based dispensing quality assurance programs.

A study was conducted to evaluate the feasibility of using barcodes in an outpatient pharmacy quality assurance program. In the first step of this study, adhesive labels containing a barcode representation of the National Drug Code (NDC) identification for the hospital's formulary medications were printed for each stock bottle or drug package used in dispensing. When an outpatient prescription was presented to the pharmacist, a label containing a barcode representation of the NDC identification for the prescribed medication was generated on-line and attached to the back of the prescription form. After the prescription item was filled by the pharmacist, an automated check was performed with a scanning wand by comparing the barcode on the prescription with the previously generated barcode on the stock bottle or drug packaging. A match indicated that the correct medication had been dispensed. Elaborations on this basic automated system for a barcode-based dispensing quality assurance program are suggested.

Effect of a triplicate prescription law on prescribing of Schedule II drugs.

Prescribing of Schedule II drugs for outpatients before and after enactment of a triplicate prescription law (TPL) was examined at a 1200-bed teaching hospital in Texas. Four pharmacists reviewed all prescriptions for Schedule II drugs during 1981 (before TPL) and 1982 (after TPL). The name of the drug product, quantity, and prescriber's training classification were recorded. Prescribing of non-Schedule II analgesics was also analyzed. Finally, prescribing by 280 resident physicians was examined for six months before and six months after enactment of TPL. The total number of prescriptions received for Schedule II drugs decreased by 60.4% from 1981 to 1982 (total outpatient prescriptions increased by 12.7%). The number of Schedule II prescriptions received from first-year residents decreased by 44.5%, more than for any other category of prescribers. In each year, nine of the ten most frequently prescribed Schedule II medications were analgesics. The numbers of prescriptions for several non-Schedule II analgesics increased in 1982 at a rate greater than that for all outpatient drugs. The medical residents wrote 2958 Schedule II prescriptions in 1981 and 834 in 1982. At this hospital, a TPL discouraged prescribing of Schedule II drugs.

Review of bupropion.

The chemistry, pharmacokinetics, pharmacology, clinical efficacy, adverse effects, and dosage of bupropion hydrochloride, an aminoketone antidepressant, are reviewed. Bupropion is rapidly absorbed after oral administration and demonstrates a first-order absorptive phase. Bupropion has biphasic elimination with a redistribution half-life of about one hour and an elimination half-life of 11-14 hours. Bupropion is widely distributed to tissues and extensively metabolized by oxidation and reduction to at least six metabolites, some of which may be active. Bupropion does not inhibit monoamine oxidase, exerts no effect on serotonin uptake, and minimally alters the reuptake of norepinephrine at presynaptic sites. It does not appear to exert action leading to postsynaptic beta-adrenergic down-regulation, and it has minimal inhibitory effects on presynaptic dopamine uptake. Bupropion has been shown to be as effective as tricyclic antidepressants (TCAs), with particularly well-documented efficacy in depressed patients with manic-depressive illness in several controlled clinical trials. Bupropion causes fewer anticholinergic, orthostatic, and cardiac conductive side effects than TCAs. Elderly patients may be given full adult doses of bupropion, and preliminary experience with overdoses suggests that it is a relatively safe drug for patients with suicidal ideation. The usual adult daily dose of bupropion hydrochloride is 300-750 mg, depending on the severity of the depression. In all cases, bupropion should be given in three doses daily. Bupropion is an effective antidepressant with a good side-effect profile; it is a useful alternative for patients unresponsive to or intolerant of therapeutic doses of TCAs.

Pharmacists' dispensing accuracy in a high-volume outpatient pharmacy service: focus on risk management.

A 12-day peer-review audit was performed in the outpatient pharmacy of a large teaching hospital. The audit process was not masked, that is, the pharmacists were aware of the peer-review evaluation. During the 12-day period, 9394 prescription forms and their corresponding pharmaceutical products were examined manually before being delivered to the patient. A total of 1165 (12.4 percent) dispensing errors were detected, with 141 (1.5 percent) of these considered potentially serious. Seventy-six prescriptions contained two errors and four prescriptions contained three. A linear relationship (r2 = 0.78; p less than 0.001) existed between the number of potentially serious errors and the total number of prescriptions filled. There were no statistically significant differences in the dispensing-error rate for the eight pharmacists audited. There was a trend for the number of pharmacist-hours containing at least one potentially serious dispensing error to increase as the prescription-filling rate accelerated. Outpatient pharmacies with high volumes should set a limit to the number of prescriptions filled by their pharmacists and should experiment with quality assurance systems to reduce dispensing errors and subsequent legal liabilities.

A data base management system for the administration of hospital pharmacy personnel.

A data base management system (System 2000) was utilized to develop a pharmacy personnel inventory that would allow the pharmacy and hospital administrators to quickly and easily obtain biographic and demographic information about employees in a large pharmacy department. The inventory provides personal information about each employee and administrative data such as previous employment and salary histories, benefits packages, and special skills. In addition, the personnel inventory provides other administrative functions including: 1) a tally of vacation or sick days accrued; 2) salary and merit increase information for pay evaluations; 3) a personnel telephone directory; 4) the immediate access to employee emergency contact information; 5) a tally of continuing education credits accrued by each pharmacist; 6) a list of languages, other than English, spoken by pharmacy personnel; 7) pharmacist licensure information; and 8) a list of the ethnic groups represented in the department for use in equal opportunity employment. Computer-prompted instructions allow use of the system by individuals with little or no computer background. Implementation of the system required less than 200 hours and maintenance costs have been relatively minimal. Recent advances in computer technology have made data base management systems similar to that described in this report, a realistic investment for the administrative needs of even the smaller hospital pharmacy.

Physician noncompliance with prescription-writing requirements.

Prescriptions processed in an outpatient pharmacy department (OPD) were audited retrospectively for physician noncompliance with prescription-writing requirements, and the estimated cost in pharmacist and patient time attributable to the errors made was assessed. During a 14-day period, 7858 prescriptions written by 451 physicians and taken to the OPD of a large teaching hospital were examined. When the patient's name, physician's signature, drug quantity, or directions for use were omitted, patients were asked to return the prescription in person for correction. In a follow-up study, the time spent at the clinic for this purpose was recorded for 50 patients. For another sample of 52 prescriptions corrected by a pharmacist's telephone call to the physician, pharmacist time spent was recorded. Errors were found in 1070 prescriptions. The total number of errors was 1130, for a noncompliance rate of 14.38%. The most frequent errors were ordering of nonformulary drugs and erroneous or unspecified dosage strength. There was no difference in noncompliance among physicians with various levels of training. An average of 25 patients per day were asked to return to the clinic for correction of their prescriptions; more than half did not return to the OPD. For the 50 patients whose return visits were monitored, time spent in the clinic area was 15.0 +/- 9.1 minutes. For the 52 prescriptions corrected by telephone calls to physicians, the pharmacist spent 10.3 +/- 11.0 minutes. Under these study conditions, pharmacists spent 16.3 hours per day correcting prescription errors; if asked to return all unfillable prescriptions, patients would have spent 23.7 hours per day. Pharmacy departments might reduce these time expenditures by conducting periodic reviews of prescription errors and apprising physicians of frequent areas of noncompliance.