Interferon alfa in the treatment of chronic viral hepatitis B and C.

OBJECTIVE: To review the indications, efficacy, and toxicity of interferon alfa in the treatment of chronic hepatitis B and C. DATA SOURCES: English-language literature pertaining to chronic hepatitis B and C and their management with interferon reported between 1980 and June 1995 was identified through computer searches using MEDLINE and through extensive searching of bibliographies and identified articles. DATA SYNTHESIS: Two major causes of chronic hepatitis are hepatitis B virus and hepatitis C virus (HBV and HCV). Worldwide, HBV infection is a major cause of cirrhosis and hepatocellular carcinoma, but in the US it is mainly a disease of high-risk groups. In the US, and particularly the southern portion, HCV is more common. Like HBV, HCV also may cause cirrhosis and hepatocellular carcinoma. Except for interferon therapy, the ability to effectively treat chronic hepatitis is limited. Interferon has antiviral, antiproliferative, and immunomodulatory activity. This agent is indicated in patients who have histologic evidence of chronic hepatitis and ongoing viral replication. Thirty percent to 40% of patients with HBV achieve loss of serum HBV e antigen and HBV DNA after treatment with interferon alfa 5 million units/d or 10 million units three times weekly for 16 weeks. Fifty percent of patients with chronic HCV respond to interferon 3 million units three times weekly for 6 months, but half of these relapse within the next 6 months. Prolonged use (18 months) may provide longer term responses in HCV. Adverse effects are common, often dose-dependent, and usually transient. A flu-like syndrome occurs early in the treatment, but fatigue is the most common adverse effect and persists throughout therapy. Long-term interferon treatment has not been extensively evaluated and the impact on survival rates is not known. CONCLUSIONS: Interferon is the only agent to have shown a consistent therapeutic effect on chronic hepatitis. Response of HBV to interferon is usually sustained, while a recurrence of HCV occurs in 50% of those who initially respond. Despite the benefits of interferon, its adverse effects and impact on hepatitis must be considered before treatment can be freely advocated.

Inaccurate assessment of drug-induced thrombocytopenia: reason for concern.

OBJECTIVE: To report two cases in which patients were reputed to have exhibited thrombocytopenia secondary to the histamine-receptor blocking agent ranitidine. Evaluation and the associated time frame of events failed to confirm these observations. DESIGN: Two case studies. RESULTS: Ranitidine was ordered as part of the therapeutic course of two patients admitted to the medicine service. The development of thrombocytopenia in both patients was attributed to this agent and it was discontinued. In addition to ranitidine, both patients received several other agents with greater potential to cause thrombocytopenia, and had a time course of development of the adverse effect that would not support ranitidine as the offending agent. Both patients required histamine-receptor antagonists at some point following their discontinuation and, based on the available evidence, the pharmacy suggested that these agents be restarted. In neither case did restarting the histamine-receptor antagonist lead to recurrence of thrombocytopenia. CONCLUSIONS: Although ranitidine can cause thrombocytopenia, the reported incidence is very low. Spontaneous reporting of adverse effects is essential in establishing a true pattern of safety for a drug. However, reports need to be scrutinized before they are rolled into the collective intelligence. Overzealous or incomplete reporting will lead to cautions that are either unnecessary or, because they deny people necessary treatment, dangerous.

Aldose reductase inhibitors: an update.

OBJECTIVE: To update readers on research being conducted with the aldose reductase inhibitor (ARI) tolrestat in treating complications of diabetes mellitus. The article briefly describes early investigations with other ARIs and reviews the more recent studies of tolrestat. In addition, the article gives readers a simplified overview of the biochemical background pertinent to the use of these agents. DATA SOURCES: A MEDLINE search was performed to identify articles relating to the clinical use of, and research involving, the following ARIs: sorbinil, alrestatin, ponalrestat, and tolrestat. In addition, pharmaceutical manufacturers were contacted in an attempt to obtain data relating to ongoing investigations. STUDY SELECTION: Review articles and clinical trials of sorbinil, alrestatin, and ponalrestat were included. Articles dealing with clinical trials of tolrestat were selected from the MEDLINE search. As there were only a few trials, all studies identified were included. No additional written data were available from the manufacturers. DATA SYNTHESIS: ARIs, which when first introduced were proclaimed to be major advances in treating diabetic complications, have never produced the expected results. Problems with efficacy and toxicity relegated most of this class of agents to historical interest. One compound, tolrestat, has continued to be tested and has potential clinical application. To date, the extent of benefit that has been realized in tolrestat-treated patients is small to moderate. Improvements have occurred in paresthesia and neuropathy, but unfortunately, not in pain symptoms. Adverse effects have been minor and are primarily confined to elevations of hepatic alanine aminotransferase. Additional clinical trials are being conducted with this agent. CONCLUSION: Tolrestat is the only one of the original ARIs still undergoing clinical trials. Results so far have been encouraging, but by no means definitive, for improvement in some aspects of diabetic neuropathy. Information from ongoing investigations is necessary before the true usefulness of tolrestat therapy can be determined.

Translating mainframe computer data to spreadsheet format.

The translation of mainframe-stored information in ASCII into spreadsheet format for use in Lotus 1-2-3 is explained. Details are presented on how to use the Data Parse command to create a translation template that tells Lotus 1-2-3 how to interpret a file written in ASCII. Lotus 1-2-3 can also translate some files in formats other than ASCII. It can translate files in the Data Interchange Format directly into its own format. Translating mainframe computer data into spreadsheet format is relatively simple and obviates the rekeying of those data.

In-hospital anaerobic susceptibility testing: an aid to formulary decision making.

In this study, the susceptibility of 116 recent anaerobic isolates, including the Bacteroides fragilis group (n = 22), Bacteroides spp (n = 65), gram-positive cocci (n = 13), Clostridium spp (n = 10), and Fusobacterium spp (n = 6) were tested by agar dilution against a variety of agents suggested for prophylaxis or therapy. These agents included ampicillin sodium and sulbactam sodium, cefotaxime, cefoxitin, ceftizoxime, clindamycin, imipenem-cilastatin, metronidazole, and ticarcillin and clavulanate potassium. All anaerobes demonstrated 100% susceptibility to imipenem-cilastatin, metronidazole, ampicillin sodium and sulbactam sodium, and ticarcillin and clavulate potassium. Varying degrees of susceptibility (ranging from 60% to 100%) of Bacteroides spp to the selected panel of antibiotics were seen. Fusobacterium spp and the gram-positive cocci were inhibited by all agents tested. Clostridium spp was 90% susceptible to cefoxitin, 80% susceptible to clindamycin, and 100% susceptible to the other six agents. Due to the varying activity of these agents, local susceptibility patterns, antimicrobic spectrum, and cost effectiveness must be considered in the choice of agents used for empiric therapy.

Hostility and hallucinations as a consequence of midazolam administration.

A 74-year-old woman experienced an apparent psychotic reaction several hours after administration of iv midazolam as a premedicant for gastroscopy. The reaction included confusion, hallucinations, and hostility and required administration of haloperidol to calm her. The woman subsequently underwent colonoscopy with meperidine as a premedication and experienced no behavioral changes. Although other causes cannot be completely ruled out, the evidence points strongly to midazolam as the precipitating agent for the psychotic reaction.

Facilitating drug-use evaluation with spreadsheet software.

The use of a personal computer spreadsheet program, Lotus 1-2-3, as an aid in drug-use evaluation is described. Dipyridamole was chosen for review because the drug is widely prescribed and often given for questionable indications. Developing criteria that could be translated into conditional logic statements made possible the use of the spreadsheet program for determining appropriateness of drug use. As data are entered into spreadsheet cells, the program simultaneously determines if the criteria for appropriate drug use are met. The program is not particularly difficult to apply to drug-use evaluation and is faster, more accurate, and more consistent than manual processing of data. In addition, the program allows the user to extract subsets of data for more detailed examination of drug-use patterns. Because decisions by the operator are unnecessary during data entry, this step can be performed by secretarial or technical personnel rather than pharmacists. A commercially available spreadsheet software program was faster and more accurate than a manual system for determining appropriate drug use.

Altering aminoglycoside selection in a community hospital.

The aminoglycoside antibiotics make up a large part of the pharmacy budget. A method developed by the pharmacy department in conjunction with the P & T Committee for implementing usage guidelines at a community hospital is presented. The program was designed to promote cost-effective therapy while maintaining safety and efficacy. After the program was implemented, both aminoglycoside use and expenditures were altered. The data indicate that by incorporating current medical information into an institution-specific program, it is possible to bring about a decrease in the cost of antibiotic therapy. This study suggests that interventions may be effective in community hospitals as well as in large teaching institutions.

Sepsis from Flavobacterium meningosepticum, an uncommon pathogen with unusual susceptibility patterns.

Flavobacterium meningosepticum, because of its unusual susceptibility patterns and predilection for debilitated or immunocompromised hosts, can be a dangerous pathogen. Identification of the organism and proper susceptibility studies, which are essential in designing antibiotic therapy, helped in the selection of a regimen that proved curative in this case.

Pelvic inflammatory disease: a review with emphasis on antimicrobial therapy.

Pelvic inflammatory disease accounts for 5%-20% of hospital admissions for gynecologic problems and is associated with health care costs of more than 1 billion dollars annually. This article reviews the epidemiology, polymicrobial etiology, and diagnosis of this disease state. Special consideration is given to in vivo and in vitro studies of antimicrobial therapy, including both established regimens and expanded-spectrum beta-lactam antibiotics. The adjunctive modalities reviewed include treatment of sexual contacts, removal of intrauterine devices, use of alternative contraceptive methods associated with a reduced risk of disease, and surgery. Although understanding of pelvic inflammatory disease has increased markedly, investigation of its various aspects is both necessary and ongoing. In particular, well-designed, controlled, comparative clinical trials of new treatment regimens must be performed to verify a true advantage of these therapies.

PIP: This state-of-the-art review focuses on the epidemiology, etiology, diagnosis, and treatment of pelvic inflammatory disease (PID). 5-20% of hospital admissions for gynecologic problems are secondary to PID; the condition itself is associated with health care costs of about $1.25 billion each year in the US. Special consideration is given in this article to in vivo and in vitro studies of antimicrobial therapy, including both established regimens and expanded spectrum beta-lactam antibiotics. Early treatment of PID can reduce the effects of the infection on the fallopian tubes; however, microbe-related inflammation and tubal necrosis can precede the manifestation of symptoms, especially in cases where Chlamydia is the infecting agent. The 2nd-generation cephalosporins seem to offer advantages in the treatment of PID because of an expanded spectrum that includes many of the major pathogens. In vitro tests have demonstrated considerable activity against penicillinase-producing strains of N gonorrhoeae resistant to both penicillin and 1st-generation cephalosporins. Cefoxitin is currently considered the most attractive such cephalosporin and has shown cure rates of 95-100% in the treatment of uncomplicated gonorrhea. Also reviewed in this article are adjunctive methods of treatment, including treatment of sexual contacts, removal of IUDs, use of alternate methods of contraception associated with a reduced risk of disease and surgery. Oral contraceptives are the logical alternative when a switch in contraception is indicated given the lower risk of PID incidence and severity, infertility, and ectopic pregnancy in pill users. There remains a need for well-designed, prospective, comparative studies of new treatment regimens.