Cindy J. Wordell

Use of Intravenous Immune Globulin Therapy: An Overview

The intravenous immune globulin (IGIV) preparations are reviewed with respect to method of preparation, pharmacokinetics, clinical uses (with emphasis on the labeled indications), and adverse reactions; a brief review of the immune system also is provided. IGIV preparations are approved for the treatment of hypogammaglobulinemia, recurrent bacterial infections due to B-cell chronic lymphocytic leukemia, and idiopathic thrombocytopenic purpura (ITP). The mechanism of action in the first two indications is passive replacement of antibodies, but in ITP the mechanism is not clearly established. The clinical literature on the use of IGIV for these indications is summarized. In patients with ITP, platelet counts return to safe levels and the number of infections is reduced in patients with primary humoral immunodeficiency treated with IGIV. The use of IGIV in pregnant women and premature infants is controversial. Adverse reactions are primarily related to infusion rate, activation of complement, and anaphylactic reactions to a component of the product. There is minimal to no risk of viral transmission with IGIV therapy. IGIV also has been administered safely on an outpatient or homecare basis. This has led to a feeling of greater control by patients over their chronic illness. Other uses of IGIV are under investigation. As our understanding of the immune system and the pharmacology of immune globulin increases, the uses of IGIV will expand.

Alternatives to Sodium Amobarbital in the Wada Test

Objective: To review the literature and identify alternatives to sodium amobarbital for use in the Wada test. Data Sources: A search of PubMed (1960-October 2010) was performed using the following key words alone or in combination: Wada test, intracarotid amobarbital procedure, intracarotid, intraarterial, sodium amobarbital, methohexital, Brevital, pentobarbital, etomidate, propofol, and alternative anesthetics. References of the identified articles were reviewed for relevant information. Study Selection and Data Extraction: All articles in English identified from the data sources were evaluated. Review included comparative, prospective, and retrospective studies along with case series and case reports. Data Synthesis: Methohexital, pentobarbital, etomidate, and propofol have all been studied as alternatives to sodium amobarbital in the Wada test. Four controlled experimental trials, 1 uncontrolled experimental trial, 6 retrospective chart reviews, and 2 case reports were reviewed. Methohexital, pentobarbital, and propofol required a second injection due to their short duration of action. Etomidate was studied as a bolus injection followed by a continuous infusion until the critical speech and memory tests were administered, which differed from the standard Wada test procedure. Patients had an increased risk of seizures with methohexital, whereas 1 patient developed transient respiratory depression immediately after receiving pentobarbital. Furthermore, propofol caused increased tone with twitching and rhythmic movements, which interfered with the completion of the Wada test for 1 patient. All authors concluded that these agents were equivalent to amobarbital for the Wada test. Conclusions: Methohexital, pentobarbital, etomidate, and propofol are viable alternatives to sodium amobarbital for use in the Wada test, but each has shortcomings.

The Formulary Decision-Making Process in a US Academic Medical Centre

SummaryThis article reviews and describes the formulary decision-making process in an academic medical centre. The pharmacy and therapeutics (P & T) committee is the organisational nucleus of the drug use control process in the institutional environment. Thomas Jefferson University Hospital (TJUH). a 720-bed academic medical centre in an urban locality in the US, is used as a model representative of how most of these committees function. Survey responses collected from 29 peer academic medical centres arc presented to compare and contrast the structure and function of the P & T committee at TJUH with corresponding procedures in other university hospitals in the US.TJUH is typical of the institutions which comprise the University Hospital Consortium (UHC). The P & T committee of TJUH is composed of 29 members, meets once per month for 10 months of the year, and has a network of 13 subcommittees. TJUH has an intermediately controlled (mixed) formulary, and uses both restricted drugs and treatment guidelines. Of the 29 UHC member institutions responding to the survey. the average P & T membership is 18, the average meeting frequency is 11 times per year, and 83% of these committees have a network of subcommittees, None describe their formulary system as open, 86% have a closed formulary and 14% have a mixed formulary system. There is a restricted drug programme in 76% of the institutions, 79% utilise treatment guidelines, 76% practice therapeutic interchange and all employ generic substitution.Specific areas addressed in this review include the history of the formulary system, the structure and function of the P & T committee, types of formularies, cost containment and the formulary decision-making process. the impact of organisational culture on physician decision making. the role of the pharmacy department, the role of pharmaceutical sales representatives and their impact on prescribing habits, the impact of the Joint Commission on Accreditation of Healthcare Organisations (JCAHO) Agenda for Change on the formulary process, and future challenges.

Adjuvant Corticosteroid Therapy for Pneumocystis Carinii Pneumonia in Aids Patients

OBJECTIVE: To review published abstracts, case reports, and journal articles and evaluate data examining the use of systemic corticosteroids as adjuvant treatment for Pneumocystis carinii pneumonia (PCP) in patients with AIDS. DATA SOURCES: Computerized online databases, peer-reviewed journals from January 1986 through September 1991, and personal communication with a National Institutes of Health correspondent. STUDY SELECTION: The authors identified 13 reports pertinent to this review. By author consensus, five studies were selected for analysis based on sample size, controlled study design, and clinical outcome measures. Recommendations of an expert panel from the National Institutes of Health and the University of California also are discussed. DATA EXTRACTION: Data are presented based on the methodologic strength of the studies reviewed. Studies are assessed on sample size, inclusion criteria, comparative cohort populations, specific patient outcome measures, and statistical analysis. DATA SYNTHESIS: Results of the study analysis support the use of systemic corticosteroids as early adjunctive therapy for AIDS patients with moderate-to-severe PCP who have an initial arterial oxygen partial pressure of <70 mm Hg or an alveolar-arterial gradient >35 mm Hg on room air. Improved outcomes included decreased mortality, respiratory failure, and deterioration of oxygenation. Data evaluated have shown that adjuvant corticosteroid therapy is most effective when initiated within 72 hours of beginning specific antipneumocystis therapy. A small, but sometimes significant, increased rate of infection in steroid-treated patients was noted. CONCLUSIONS: Based on the literature reviewed, early systemic adjuvant corticosteroid therapy can benefit patients with moderate-to-severe AIDS-related PCP. The steroid regimen used in the largest controlled trial and recommended by the expert panel is prednisone 40 mg bid (days 1–5), then 40 mg/d (days 6–10), then 20 mg/d (days 1–21).

Management of Pneumocystis carinii Pneumonia in Patients with AIDS and Other Conditions: Experience in a Philadelphia University Teaching Hospital

We reviewed the records of 49 patients who had 55 episodes of Pneumocystis carinii pneumonia (PCP) from January 1984 to January 1987. Thirty‐three patients had acquired immunodeficiency syndrome (AIDS), with the risk groups being homosexual/bisexual practices (26), hemophilia (6), and blood transfusion (1). Fourteen patients had a history of malignancy or chemotherapy and two underwent organ transplantation. Overall response to therapy of PCP was 75% (77% of patients with AIDS, 68% of those with other conditions). All six relapses occurred in patients with AIDS. Both trimethoprim‐sulfamethoxazole (TMP‐SMX) and pentamidine were associated with a higher rate of toxicity in those patients than in patients with other conditions. A 30% rate of failure due to side effects occurred when TMP‐SMX was used as initial therapy, but the combination is considered effective and should be given an adequate therapeutic trial. Pentamidine was an effective alternative for patients who failed with TMP‐SMX and for those who failed therapy due to side effects, but was associated with serious toxicities. Our experience was similar in some respects to previous published results from New York and California.

INTERNET UTILIZATION AMONG MEDICAL INFORMATION SPECIALISTS IN THE PHARMACEUTICAL INDUSTRY AND ACADEMIA

The Drug Use Policy and Medical Information Service of Thomas Jefferson University Hospital conducted a survey of industry- and academic-based drug information centers to examine the types of Internet-based resources provided and used, demographics of the centers, and electronic mail and World Wide Web usage. A total of 464 surveys were sent (293 to industry sites and 171 to academic sites), with a response rate of 29%. Results indicated that medical information specialists in industry- and academic-based drug information centers use the Internet daily. Most centers have access to e-mail and the World Wide Web. Fewer that 25% of the respondents provided a homepage for their center. Internet usage in many centers has increased from the previous year.

Hyperkalemia and High-Dose Trimethoprim/Sulfamethoxazole

Evidence from the literature strongly supports that high doses of TMP, as used in the treatment of PCP in AIDS patients, have the propensity to cause hyperkalemia by inhibiting sodium channels in the distal nephron, thereby impairing potassium secretion. The mechanism of TMP-induced hyperkalemia is believed to be similar to that of triamterene and amiloride because of the structural similarity of these agents. It is also possible that declining renal function, which is a natural progression of HIV disease, may contribute to the hyperkalemia seen in this patient population. In addition, patients with AIDS also may exhibit a defect in adrenal function, potentiating the hyperkalemic effect of TMP therapy. Therefore, it is crucial for clinicians to monitor closely the serum potassium concentration in this patient population, especially during therapy with high doses of TMP.