A cost-benefit analysis of RSV prophylaxis in high-risk infants.

OBJECTIVE: To determine the cost and benefit of using RSV-IG and palivizumab as prophylactic therapy against respiratory syncytial virus (RSV)-associated illness in high-risk infants. METHODS: A nonrandomized, retrospective, cohort control study was conducted comparing the outcomes of patients who received either RSV-IG or palivizumab therapy against RSV during the 1998-1999 RSV season with patients identified from the 1994-1995 RSV season who would have been eligible to receive prophylaxis had either agent been available at that time. Medical record reviews were conducted to gather data regarding the costs associated with both the administration of the prophylactic drugs and the treatment of RSV-associated hospitalizations in both groups. Decision analysis was used to determine the average cost per patient for both groups. A cost-benefit analysis was then conducted to determine the return on investment, if any, for the use of these drugs. A sensitivity analysis was also conducted to determine the robustness of the data. RESULTS: Patients who received RSV-IG or palivizumab had a hospitalization rate of 1.6% compared with 25% for the group who did not receive prophylactic drugs. The average costs for the RSV prophylaxis group were less per patient $3,733 compared with $4,258 in the group who did not receive prophylaxis. The benefit is a 23.4% lower chance of hospitalization for each infant or, in dollar figures, $3,985 ($17,031 x 0.234). The benefit-cost ratio is 1.15:1 ($3,985:3,461). The benefits, therefore, exceed the costs associated with the prophylaxis program. The prophylaxis program saved healthcare dollars by preventing RSV-related hospital-izations. CONCLUSIONS: Results demonstrate that when used according to our institution's criteria, RSV prophylaxis is of benefit to our institution.

Sonographic appearance of appendicitis in a neutropenic pediatric patient after inversion appendectomy.

The technique of inversion-ligation appendectomy is used by some surgeons to eliminate the risk of peritoneal contamination as the result of incidental appendectomy during an otherwise clean surgical procedure. In most cases, the intussuscepted appendix necroses and sloughs into the cecum after several days. We present the first report of the ultrasonographic appearance of a retained, inflamed appendix, which occurred in a neutropenic pediatric patient 15 months after inversion appendectomy. Our case illustrates the importance of a complete surgical history for the interpretation of abnormal sonographic findings of the cecum.

Medication use evaluation: a work in progress.

The medication use evaluation (MUE) Program at the University of Iowa Hospitals and Clinics (UIHC) is a dynamic program that is constantly changing to meet the needs of this tertiary care institution. This article will provide an overview of the MUE process at UIHC as well as provide an example of a long-standing initiative that has evolved significantly since its inception in 1993. Examples of four other initiatives also will be provided to demonstrate the scope of this program. The examples to be covered in this article include: 5-HT3 receptor antagonists, alteplase, automatic substitution of cefotaxime, proton pump inhibitors, and COX-2 selective agents.

Cisplatin, etoposide, and paclitaxel in the treatment of patients with extensive small-cell lung carcinoma.

PURPOSE: The combination of cisplatin, etoposide, and paclitaxel was studied in patients with extensive small-cell lung cancer in a phase I component followed by a phase II trial to determine the maximum-tolerated dose (MTD), characterize toxicity, and estimate response and median survival rates. PATIENTS AND METHODS: Forty-one patients were treated between October 1993 and April 1997. Doses for the initial cohort were cisplatin 75 mg/m(2) on day 1, etoposide 80 mg/m(2)/d on days 1 to 3, and paclitaxel 130 mg/m(2) on day 1 over 3 hours. Cycles were repeated every 3 weeks for up to six cycles. The MTD was reached in the first six patients. In these six patients and in the next 35 patients, who were entered onto the phase II trial, response and survival were estimated. RESULTS: At the initial dose level, one of six patients developed febrile neutropenia, and five of six achieved targeted neutropenia (nadir absolute granulocyte count, 100 to 1,000/microL) without any other dose-limiting toxicity, defining this level as the MTD. Grade 4 neutropenia was observed in 88 (47%) of 188 total courses administered at or less than the MTD. Neutropenia was associated with fever in only 17 (9%) of 188 courses, but two patients experienced neutropenic sepsis that was fatal. Nonhematologic toxicity greater than grade 2 was observed in 10 (5%) of 188 total courses, with fatigue, peripheral neuropathy, and nausea/vomiting most common. The overall objective response rate was 90% of 38 assessable patients: six complete responses (16%) and 28 partial responses(74%). Median progression-free and overall survival durations were 31 and 47 weeks, respectively. CONCLUSION: The combination of cisplatin, etoposide, and paclitaxel produced response and survival rates similar to those of other combinations and was well tolerated.

The insulin-like growth factor type I receptor stimulates growth and suppresses apoptosis in prostatic stromal cells.

Stromal cells derived from benign prostatic hyperplasia synthesize and secrete measurable levels of insulin-like growth factor (IGF). Seventy-two-hour conditioned medium obtained from these cells contains IGF-II at levels ranging from 125-177 ng/mL.10(6) cells. IGF-I is almost undetectable. RT-PCR analysis has demonstrated that the genes for both the type I IGF receptor (IGF-IR) and the type II IGF receptor (IGF-IIR) are expressed by benign stromal cells in vitro. Competition binding analysis for IGF-I and IGF-II confirmed the existence of binding sites for both ligands with respective Kd and binding capacities of 4.9 x 10(-9) mol/L and 6.6 x 10(5) sites/cell and 4.7 x 10(-9) mol/L and 3.8 x 10(6) sites/cell. Under serum-free conditions, IGF-I and IGF-II at 500 ng/mL induce 80% and 113% increases in stromal cell density, respectively, over a 96-h period. Incubation with the IGF-IR-neutralizing antibody alpha IR3 (50 micrograms/mL) reduces the rate of stromal cell proliferation by approximately 60-80% even in the presence of stimulatory concentrations of IGFs. Camptothecin-induced apoptosis is inhibited by the addition of IGF-I and -II (500 ng/mL). alpha IR3 suppresses these survival signals and itself induces cell death in the prostatic stroma. The data suggest that IGF-IR is a pivotal molecule in prostatic stromal cell maintenance, and that specific antagonism may offer a novel means of controlling the fibromuscular expansion characteristic of benign prostatic hyperplasia.

An assessment of patients' attitudes to day-case general anaesthesia for removal of mandibular third molars.

Day-case surgery is used extensively in many hospital departments including departments of oral surgery. In this study, the preoperative attitudes of 170 patients to, and postoperative satisfaction with, surgical removal of third molar teeth under general anaesthesia as day cases were evaluated. A 69% response to the questionnaire (n = 110) indicated that 102 (96%) of the 106 that had been satisfactorily completed were satisfied with the prospect of afternoon, day-case removal of their third molar teeth, and 96 (91%) remained satisfied postoperatively. Only two patients did not like the idea beforehand and had their opinions confirmed. Patients' comments included satisfaction with the support they received (n = 29) and with pain control (n = 5) and amount of information given (n = 5). However, five complained of the long wait and two who were last on the list thought that they should have been kept in overnight.

Increased adverse drug reaction reporting through wall-mounted ADR reporting cards.

To increase adverse drug reaction reporting, the Pharmacy Department Quality Assessment and Improvement Committee at the University of Iowa Hospitals and Clinics created an abbreviated wall-mounted adverse drug reaction card on "tear-off" pads. This report discusses strategies the Committee identified in order to attain its goal.

Influencing prescribing practices and associated outcomes utilizing the drug use evaluation process.

Influencing prescribing practices and the implementation of pharmaceutical care utilizing the drug use evaluation (DUE) process at a 891-bed teaching hospital are described. The DUE program has been structured to provide for significant pharmacy involvement while maintaining medical staff responsibility as outlined by the Joint Commission on Accreditation of Healthcare Organizations. A multidisciplinary approach is used to identify problems and develop prescribing criteria and educational initiatives. Pharmacists provide drug therapy monitoring and engage in clinical interventions and documentation of outcomes on a daily basis. DUE program pharmacists help target possible interventions, assure monitoring and outcome documentation, and compile results of all initiatives for reporting purposes to the medical staff and quality assessment program. Specific performance compliance and problems are identified and incorporated into the credentialing process. Corrective measures are determined by the Pharmacy and Therapeutics (P&T) Subcommittee with subsequent actions carried out by peer physicians. The net result is a positive influence on prescribing practices that improves the appropriate and effective use of drugs and improves patient outcomes.

Use and sterility of multidose ophthalmic medications.

Liquid ophthalmic products in opened multidose containers were studied to determine whether the date of opening was marked on the container and whether the drugs were contaminated. Pharmacy personnel collected opened containers for four months from a hospital's eye center clinic and outpatient surgery area. Half of the containers were randomly selected and the contents tested for bacterial and fungal contamination. The ophthalmic products were dripped from the containers' dropper tips into nutrient broth. Broth samples that became turbid after incubation were to be tested in the microbiology laboratory. Of 166 opened containers collected, 118 were marked with dates. The dates indicated that 97 had been opened within 30 days before collection; nursing policy dictated that containers be discarded 30 days after being opened. Acquisition cost for the undated, opened containers, which should have been discarded by nurses, was $182. In incubated samples from 81 opened containers, 61 of them dated and 52 dated within the past 30 days, no turbidity was seen. Although no bacterial or fungal contamination was detected in these ophthalmic products from opened containers, the absence of dates on some containers indicated deviation from institutional policy and probable avoidable waste of undated products.

Impact of a pharmacist education program on nonformulary drug use.

The effect of an educational program for pharmacists that included instructions for handling nonformulary drug requests and determining suitable formulary alternatives for frequently prescribed nonformulary drug requests was measured. Results indicate a significant increase in the number of appropriate nonformulary drug dispensings when the postintervention phase was compared with the preintervention phase. Other values, including the financial impact per nonformulary drug request, did not differ significantly between the two phases. Since all nonformulary drug requests require pharmacist time, a more cost-effective nonformulary drug policy might focus the pharmacist's efforts on nonformulary drug products that are more costly than their formulary alternatives.

A double-blind, placebo-controlled study of the efficacy of Lactinex in the prophylaxis of amoxicillin-induced diarrhea.

The disruption of the natural flora of the gastrointestinal tract (especially Lactobacillus acidophilus) may occur during antibiotic therapy. This may lead to diarrhea, dehydration, and electrolyte imbalances. It has been suggested that replacement of the lactobacilli with a commercially available product may prevent the diarrhea. The efficacy and safety of prophylactically administered Lactinex (culture of L. acidophilus and L. bulgaricus) was compared with placebo for the prevention of amoxicillin-induced diarrhea in pediatric patients. Lactinex or placebo was administered four times a day for ten days to coincide with the antibiotic therapy. The Lactobacillus preparation did not appear to consistently prevent diarrhea in this patient population. Patients' age, diet, and parental definition of diarrhea were factors that may have influenced the results.

Status of generic substitution: problematic drug classes reviewed.

The Drug Price Competition and Patent Term Restoration Act of 1984 enticed numerous manufacturers to enter the generic drug market. Even though products marketed under this act must be bioequivalent to brand name products and must meet the same FDA standards for quality, reports of inequivalence have appeared in the literature. However, cases of inequivalence and lack of efficacy have also been reported with brand name drugs. Discussed in this article are current data on the use of brand name versus generic products of several problematic drugs and drug classes--thyroid preparations, conjugated estrogens, digoxin, phenothiazines, theophylline, and anticonvulsants. Also included in this article is an explanation of the terms used in discussions of brand name and generic drugs, a review of recent changes in legislation that pertain to the development of brand name and generic drugs, and recommendations of steps to take (in-house and federal) when problems with medications are discovered.

Retrospective evaluation of piperacillin use in a university hospital.

A retrospective review was conducted to evaluate the appropriateness of empiric and definitive piperacillin use and to determine if less expensive, more appropriate antibiotics could have been used. The criteria were approved by the chief of infectious diseases and the drug utilization review committee at this institution. One hundred courses of piperacillin use in adult patients were reviewed. Therapy was categorized as appropriate in 78 of the 100 courses: 21 were appropriate empiric, 32 were appropriate empiric changed to definitive due to culture and sensitivity reports, and 25 were appropriate definitive. Reasons for this high percentage of appropriate use include: 1) 40% of the infections involved Pseudomonas aeruginosa; 2) 18% of the organisms that were sensitive to piperacillin were resistant to ticarcillin and mezlocillin; and 3) 64% of the courses of therapy involved critically ill patients with diagnoses such as neutropenia secondary to cancer chemotherapy, burns, sepsis, and hospital-acquired pneumonia. Although only 19.7% of the 11,845 grams of piperacillin used were categorized as inappropriate, the cost is relatively high (annualized to $19,648) and cost savings could be realized if piperacillin use were monitored more closely.

Compliance with a restricted antimicrobial agent policy in a university hospital.

Compliance with a policy for use of antimicrobial agents that requires both oral approval from the infectious diseases service and completion of a restricted antimicrobial agent use form was evaluated in a 950-bed teaching hospital. The charts of patients for whom a restricted antimicrobial agent was ordered during four one-week periods between January 1987 and April 1987 were audited to determine whether completed use forms had accompanied orders for restricted antimicrobial agents. The validity of the information on completed forms was determined by comparing the information on the form with notes in patients' charts and through discussions with infectious diseases physicians. Two infectious diseases physician reviewers evaluated the appropriateness of prescribing of piperacillin and ceftazidime by analyzing data collected by pharmacists. Forms were submitted with 132 of 154 orders written for restricted agents; incomplete forms were received and accepted by pharmacists for 39 courses of therapy. The infectious disease service had not been contacted to approve use of a restricted agent in 25 cases. Eight of the 48 courses of piperacillin or ceftazidime therapy were deemed inappropriate despite initial infectious diseases approval. Compliance with a formal antimicrobial agent restriction policy at this institution has been good, but periodic re-education and follow-up monitoring appear to be necessary to ensure optimal use of restricted agents.