Michael F. Rein

National Institutes of Health consensus development conference statement: management of hepatitis B.

National Institutes of Health (NIH) consensus and stateof-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ); 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session; 3) questions and statements from conference attendees during open discussion periods that are part of the public session; and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the U.S. government. The statement reflects the panel’s assessment of medical knowledge available at the time the statement was written. Thus, it provides a “snapshot in time” of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research. Hepatitis B is a major cause of liver disease worldwide, ranking as a substantial cause of cirrhosis and hepatocellular carcinoma. The development and use of a vaccine for hepatitis B virus (HBV) has resulted in a substantial decline in the number of new cases of acute hepatitis B among children, adolescents, and adults in the United States. However, this success has not yet been duplicated worldwide, and both acute and chronic HBV infection continue to represent important global health problems. Seven treatments are currently approved for adult patients with chronic HBV infection in the United States: interferon-, pegylated interferon-, lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate. Interferon- and lamivudine have been approved for children with HBV infection. Although available randomized, controlled trials (RCTs) show encouraging short-term results— demonstrating the favorable effect of these agents on such intermediate markers of disease as HBV DNA level, liver enzyme tests, and liver histology— limited rigorous evidence exists demonstrating the effect of these therapies on important long-term clinical outcomes, such as the development of hepatocellular carcinoma or a reduction in deaths. Questions therefore remain about which groups of patients benefit from therapy and at which point in the course of disease this therapy should be initiated.

National Institutes of Health Consensus Development Conference Statement: Management of Hepatitis B

Hepatitis B is a major cause of liver disease worldwide, ranking as a substantial cause of cirrhosis and hepatocellular carcinoma. The development and use of a vaccine for hepatitis B virus (HBV) has resulted in a substantial decline in the number of new cases of acute hepatitis B among children, adolescents, and adults in the United States. However, this success has not yet been duplicated worldwide, and both acute and chronic HBV infection continue to represent important global health problems. Seven treatments are currently approved for adult patients with chronic HBV infection in the United States: interferon, pegylated interferon, lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate. Interferonand lamivudine have been approved for children with HBV infection. Although available randomized, controlled trials (RCTs) show encouraging short-term results—demonstrating the favorable effect of these agents on such intermediate markers of disease as HBV DNA level, liver enzyme tests, and liver histology—limited rigorous evidence exists demonstrating the effect of these therapies on important long-term clinical outcomes, such as the development of hepatocellular carcinoma or a reduction in deaths. Questions therefore remain about which groups of patients benefit from therapy and at which point in the course of disease this therapy should be initiated.

Multicenter comparison of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine hydrochloride, and allantoin in the treatment of symptomatic trichomoniasis.

Background and Objectives: Trichomonas vaginalis is a common vaginal pathogen. Oral metronidazole is the drug of choice for the treatment of trichomoniasis. Oral metronidazole, however, may cause unpleasant side effects and is contraindicated during the first trimester of pregnancy. In vitro studies and preliminary clinical data have suggested that intravaginal clotrimazole may be effective against this pathogen. Goals: To compare the efficacy of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine, and allantoin (AVC suppositories) in the treatment of women with symptomatic trichomoniasis. Study Design: In a multicenter, open‐label trial conducted in 1982 and 1983, 168 symptomatic women with microscopically evident vaginal trichomoniasis were randomized to receive any of 2 g of metronidazole as a single oral dose, two 100‐mg clotrimazole vaginal tablets once a day for 7 days, or vaginal suppositories containing 1.05 g of sulfanilamide, 14 mg of aminacrine hydrochloride, and 140 mg of allantoin (AVC suppositories) twice a day for 7 days. Wet mounts and cultures were repeated at 1 to 2 and 4 to 6 weeks after completion of treatment. Results: The numbers of patients who had positive cultures after treatment were 40/45 (88.9%) in the clotrimazole group, 35/43 (81.4%) in the AVC suppository group, and 9/45 (20%) in the metronidazole group (P < 0.001). All treatments were associated with a reduction in reported symptoms. Oral metronidazole was more effective in reducing symptoms than either of the topical preparations. Adverse events, mostly mild or moderate in severity, were reported by 7 (14.6%) of 48 patients who had received oral metronidazole and 4 (7.8%) of 51 women who used AVC suppositories. There were no adverse events reported by the 50 women who used clotrimazole vaginal tablets. Conclusions: Oral metronidazole was more effective in eradicating T. vaginalis than clotrimazole vaginal tablets or AVC vaginal suppositories. All three regimens reduced symptoms; oral metronidazole was more effective in reducing symptoms than either topical preparation.

Bacterial killing by bacteriostatic saline solutions--potential for diagnostic error.

IN recent years the technic of transtracheal aspiration of pulmonary secretions for microbiological examination has been increasingly used for ascertaining the cause of acute pulmonary infection. T...

Comparison of clindamycin phosphate vaginal cream with triple sulfonamide vaginal cream in the treatment of bacterial vaginosis.

Background Triple sulfonamide vaginal cream has been used to treat bacterial vaginosis for many years. There are few studies in which triple sulfonamide cream has been compared with newer regimens. Goal To compare the efficacy and safety of clindamycin phosphate vaginal cream with that of triple sulfonamide vaginal cream in the treatment of bacterial vaginosis. Study Design In this double-blind, randomized multicenter study, nonpregnant women 16 years of age or older with symptomatic bacterial vaginosis were assigned to receive either 2% clindamycin phosphate vaginal cream or triple sulfonamide vaginal cream for 7 days. Follow-up visits were conducted 5 to 10 days and 25 to 39 days after completion of treatment. Results Clinical cure or improvement at 25 to 39 days was noted in 55 (69.6%) of 79 assessable participants who received clindamycin vaginal cream and in 33 (41.8%) of 79 women who received triple sulfonamide vaginal cream (P < 0.0001). Most of the difference between the treatment groups was noted in women with a history of bacterial vaginosis. Among women without a history of bacterial vaginosis, clindamycin and triple sulfonamide creams had similar efficacy. Evaluation of Gram-stained vaginal smears correlated with clinical outcome. Most patients in both treatment groups reported an improvement in symptoms. No significant difference was observed between the treatment groups in the incidence of adverse events. Conclusion Clindamycin 2% vaginal cream is more effective than triple sulfonamide vaginal cream in the treatment of bacterial vaginosis.

The emotional experience of intercourse and sexually transmitted diseases: a decision-tree analysis.

Background Epidemiologic data document high risks for many sexually transmitted diseases (STDs) among US adolescents and young adults. Goal This case-control study used decision trees to investigate the relationship between STD incidence and emotional reactions to intercourse. Study Design For this study, 188 adolescents and young adults (mean age, 24.9 years [SD = 8.2]) at a regional public STD clinic completed a behavioral and psychological questionnaire and underwent a workup for STD. Results The prevalence of STD in this group was 44.8%. Decision-tree analysis identified emotional reactions to intercourse that were associated with STD diagnosis for some patients: feeling good about oneself after sex half the time or less (OR = 3.21; 95% CI = 1.73–5.95), feeling comfortable during sex half the time or less (OR = 2.17; 95% CI = 1.07–4.40), and feeling angry after sex (OR = 1.90; 95% CI = 0.91–3.99). Findings of a logistic regression model of emotional reactions to intercourse were significant (chi-square = 24.6; df = 8;P < 0.002), but adding behavioral variables did not improve prediction. Conclusions For some of these young adults at the time of life when they are at highest risk of STD, emotional factors have higher odds ratios for STD diagnosis than the traditionally assessed behavioral variables. This underscores the need for interventions targeted to specific subgroups and for readily available mental health services.

Failure of the Treponema pallidum lmmobilization Test to Provide Additional Diagnostic Information about Contemporary Problem Sera

Two hundred forty-five sera submitted to the Center for Disease Control, Atlanta, Ga., (CDC) were analyzed serologically in an attempt to demonstrate the diagnostic value of the Treponema pallidum immobilization (TPI) test when performed in addition to the fluorescent treponemal antibody-absorption (FTA-Abs) test. Diagnoses for the patients whose sera were tested were based on information supplied by the referring physicians. Fifty-four per cent of the diagnostic problems were resolved merely by the finding of a negative result with the FTA-Abs test. There was agreement between the serologic results of the referring laboratory and those of the CDC for 76% of sera tested by the Venereal Disease Research Laboratory test and for 71% of sera tested by the FTA-Abs test. For patients with treponemal disease, the sensitivity of the TPI test was 56% and that of the FTA-Abs test was 78%. When the FTA-Abs test was reactive, a negative TPI test was not significantly associated with systemic lupus erythematosus (P > 0.6) or other collagen vascular disease (P > 0.6), nor was a positive TPI test associated with treponemal disease (P > 0.09). It is concluded that once the result of the FTA-Abs test is known, the TPI test does not provide additional diagnostic information.

Auxotypes and antibiotic susceptibility patterns of Neisseria gonorrhoeae from disseminated and local infections.

The arginine-hypoxanthine-uracil auxotype has been linked with the propensity of gonococci to cause disseminated infections. Gonococci recovered from 25 patients with disseminated gonococcal infections were compared with gonococci recovered from matched controls, patients with uncomplicated gonorrhea selected during the same month. Minimal inhibitory concentrations of penicillin, tetracycline, crythromycin, and ampicillin, and the nutritional requirements (auxotypes) for prolinc alone, arginine alone, arginine, hypoxanthine and uracil together, serine alone and cysteine-cystine (wild type) were analyzed by discriminant analysis. Significant susceptibility to penicillin characterized strains causing disseminated infections, and a proline requirement was the most common auxotype (48%) among strains isolated in Atlanta. Together the minimal inhibitory concentration of penicillin and the proline auxotype best separated the strains causing disseminated gonococcal infections from those causing gonorrhea. The arginine-hypoxanthine-uracil auxotype was found in only 24% of strains causing disseminated infections. A trait other than auxotype must determine the capacity of the organisms to disseminate.

Increase in CD4 Lymphocyte Counts After Splenectomy in HIV-infected Patients

The records were reviewed of five human immunodeficiency virus (HIV) type 1-infected patients who underwent splenectomy, four for HIV-associated thrombocytopenia and one for gastric compression secondary to splenomegaly. After splenectomy, the four adult patients all had marked, sustained increases in their absolute CD4 lymphocyte counts; greater increases were observed in CD8 lymphocyte counts, accounting for decreases in the CD4:CD8 ratios. In patients 5 (one of triplets, all of whom were infected with HIV after a blood transfusion), absolute CD4 lymphocyte counts were stabilized after splenectomy; the other siblings manifested a decline in CD4 counts, which was associated with a delay in physical development and recurrent episodes of varicella. Immunohistochemical staining of spleen sections demonstrated significantly higher numbers of CD4 cells in splenic tissue from HIV-infected patients than from patients splenectomized secondary to trauma (2,070 +/- 284 vs. 962 +/- 296; p = 0.025). In addition, the HIV-infected patients had significantly higher percentages of CD4 lymphocytes in splenic tissue than in peripheral blood (49.3 +/- 11.0 vs. 20.3 +/- 7.9; p = 0.005), suggesting that CD4 cells were sequestered in the spleens of these patients. These findings have implications for the management of splenectomized HIV-infected patients with regard to optimal timing of initiation of zidovudine therapy and for prophylaxis of Pneumocystis carinii pneumonia.

A comparison of rosoxacin with ampicillin and probenecid in the treatment of uncomplicated gonorrhea.

Rosoxacin, a β-lactamase-resistant, pyridyl quinolone derivative with in vitro activity against Neisseria gonorrhoeae, was compared to an oral regimen of ampicillin plus probenecid for the treatement of uncomplicated gonococcal infection. Fifty-seven patients were evaluated for the effectiveness of the two antibiotics. Thirty (97%) of 31 patients receiving rosoxacin were cured of their infection as were 25 (96%) of 26 patients who received the oral regimen of ampicillin plus probenecid. Both drug regimens were associated with a significant number of side effects. Of the ampicillin-treated group, 29% had diarrhea and/or abdominal cramping. Of the rosoxacin-treated patients, 52% had reactions classified as central nervous system effects; these included headaches, dizziness, euphoria, and drowsiness.