Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial.

BACKGROUND: Recurrent herpes simplex labialis (HSL) occurs in 20% to 40% of the US population. Although the disease is self-limiting in persons with a healthy immune response, patients seek treatment because of the discomfort and visibility of a recurrent lesion. OBJECTIVE: Our purpose was to determine whether docosanol 10% cream (docosanol) is efficacious compared with placebo for the topical treatment of episodes of acute HSL. METHODS: Two identical double-blind, placebo-controlled studies were conducted at a total of 21 sites. Otherwise healthy adults, with documented histories of HSL, were randomized to receive either docosanol or polyethylene glycol placebo and initiated therapy in the prodrome or erythema stage of an episode. Treatment was administered 5 times daily until healing occurred (ie, the crust fell off spontaneously or there was no longer evidence of an active lesion) with twice-daily visits. RESULTS: The median time to healing in the 370 docosanol-treated patients was 4.1 days, 18 hours shorter than observed in the 367 placebo-treated patients (P =.008; 95% confidence interval [CI]: 2, 22). The docosanol group also exhibited reduced times from treatment initiation to (1) cessation of pain and all other symptoms (itching, burning, and/or tingling; P =.002; 95% CI: 3, 16.5); (2) complete healing of classic lesions (P =.023; 95% CI: 1, 24.5); and (3) cessation of the ulcer or soft crust stage of classic lesions (P <.001; 95% CI: 8, 25). Aborted episodes were experienced by 40% of the docosanol recipients versus 34% of placebo recipients (P =.109; 95% CI for odds ratio: 0.95, 1.73). Adverse experiences with docosanol were mild and similar to those with placebo. CONCLUSION: Docosanol applied 5 times daily is safe and effective in the treatment of recurrent HSL. Differences in healing time compared favorably with those reported for the only treatment of HSL that has been approved by the Food and Drug Administration.

Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection. Results of an international, multicenter, double-blind, randomized clinical trial. The Valaciclovir International Herpes Simplex Virus Study Group.

BACKGROUND AND OBJECTIVES: Valaciclovir, the L-valine ester prodrug of acyclovir, is much better absorbed than acyclovir and produces acyclovir exposures three to five times those attainable with the parent drug. GOALS: To determine whether the improved bioavailability of valaciclovir and a more convenient, less frequent dose regimen can maintain the clinical efficacy previously demonstrated for acyclovir. STUDY DESIGN: This was an international, multicenter, randomized, double-blind clinical trial comparing 10-day regimens of valaciclovir (1000 mg, twice daily) and acyclovir (200 mg, 5 times daily) in the treatment of 643 otherwise healthy adults (> or = 18 years of age) with first-episode genital herpes. Patients were evaluated clinically and lesions were staged and cultured on days 1, 2, 3, 5, 7, 10, 14, and then twice weekly until healed. Blood for herpes serology tests was obtained on days 1 and 14; hematology and chemistry toxicity screening was done on days 1 and 7. RESULTS: Valaciclovir and acyclovir did not differ significantly in efficacy with respect to duration of viral shedding (hazard ratio, 1.00; 95% confidence interval [CI], 0.84-1.18), time to healing (hazard ratio, 1.08; 95% CI, 0.92-1.27), duration of pain (hazard ratio, 1.0; 95% CI, 0.85-1.18), and time to loss of all symptoms (hazard ratio, 1.02; 95% CI, 0.85-1.22). Patients with primary genital herpes (no preexisting antibody to either herpes simplex virus type at enrollment with seroconversion at day 14) had longer times to healing and longer duration of viral shedding and pain than patients with nonprimary first genital episodes. Adverse experiences were generally infrequent and mild and were comparable in the two treatment groups. CONCLUSIONS: Twice-daily valaciclovir proved as effective and well tolerated in the treatment of first-episode genital herpes as five-times-daily acyclovir. Valaciclovir provides a useful alternative to acyclovir with the advantage of a more convenient dosing regimen and the potential for improved compliance.

The Deaconess Informed Consent Comprehension Test: an assessment tool for clinical research subjects.

We developed an instrument to assess comprehension of informed consent information among 275 adults entering one of four ambulatory trials. At the conclusion of trial enrollment, subjects rated their understanding of the information presented and completed the Deaconess Informed Consent Comprehension Test (DICCT). Subjects completed the vocabulary subtest of the revised Weschler Adult Intelligence Scale (WAIS-R) and the reading subtest of the revised Wide Range Achievement Test (WRAT-R). The DICCT for 50 subjects was scored by 2 blinded investigators. Interrater agreement was 0.84 (df = 49, p < 0.001). To investigate the DICCT's potential validity, its scores were correlated with WAIS-R vocabulary scores (r = 0.44, df = 199, p < 0.01) and WRAT-R reading scores (r = 0.39, df = 268, p < 0.01). Understanding of consent information was rated as thorough by 70% of subjects. The mean +/- SD DICCT score was 20.4 +/- 3.9. The DICCT is a reliable instrument to assess comprehension of informed consent information. There is preliminary evidence for the scale's validity. The subjects believed that they had greater understanding of study information than was shown by the DICCT.

Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group.

OBJECTIVE: To document the effects of treatment with famciclovir on the acute signs and symptoms of herpes zoster and postherpetic neuralgia. DESIGN: A randomized, double-blind, placebo-controlled, multicenter trial. SETTING: 36 centers in the United States, Canada, and Australia. PATIENTS: 419 immunocompetent adults with uncomplicated herpes zoster. INTERVENTION: Patients were assigned within 72 hours of rash onset to famciclovir, 500 mg; famciclovir, 750 mg; or placebo, three times daily for 7 days. MEASUREMENTS: Lesions were assessed daily for as long as 14 days until full crusting occurred and then weekly until the lesions healed. Viral cultures were obtained daily while vesicles were present. Pain was assessed at each of the visits at which lesions were examined and then monthly for 5 months after the lesions healed. Safety was assessed throughout the study. RESULTS: Famciclovir was well tolerated, with a safety profile similar to that of placebo. Famciclovir accelerated lesion healing and reduced the duration of viral shedding. Most importantly, famciclovir recipients had faster resolution of postherpetic neuralgia (approximately twofold faster) than placebo recipients; differences between the placebo group and both the 500-mg famciclovir group (hazard ratio, 1.7 [95% CI, 1.1 to 2.7]) and the 750-mg famciclovir group (hazard ratio, 1.9 [CI, 1.2 to 2.9]) were statistically significant (P = 0.02 and 0.01, respectively). The median duration of postherpetic neuralgia was reduced by approximately 2 months. CONCLUSIONS: Oral famciclovir, 500 mg or 750 mg three times daily for 7 days, is an effective and well-tolerated therapy for herpes zoster that decreases the duration of the disease's most debilitating complication, postherpetic neuralgia.

Informed consent: clinical and legal issues in family practice.

While patient informed consent is an important clinical and legal dimension of specialty medical care, many important issues arise in primary care. Family physicians are in a unique position to implement informed consent discussions in the ethical spirit in which the doctrine was intended. Because of their long-term relationships with patients and sensitivity to psychosocial issues, family physicians can engage patients in collaborative health care decision making. Primary care physicians are optimally suited to assess patients' understanding of medical information and their competence. Instead of viewing the informed consent process simply as a necessary legal requirement, it should be a method for educating patients and allowing them to participate in their health care decision making.

Mechanical ventilation.

Among the many advances made in intensive care therapeutics in recent years, few have rivaled the impact of mechanical ventilators. Their expanded use affects all who practice in the critical care setting. This article reviews the physiologic basis for mechanical ventilation, how ventilators are classified, the various modes, and specific indications. A basic introduction is made into ventilator set up, weaning techniques, adjunctive drug therapy, and complications. The pharmacotherapy specialist who understands interactions between patients and ventilators, and the effects of mechanical ventilation on cardiopulmonary function will be best equipped to individualize drug therapy.

Near-total reduction in verapamil bioavailability by rifampin. Electrocardiographic correlates.

We evaluated the significance of the interaction between rifampin and verapamil in six volunteers who received single doses of verapamil, 10 mg intravenously (IV), then 120 mg orally two days later. Subjects were then given rifampin, 600 mg orally every day for 15 days. After 13 and 15 days of rifampin therapy, the IV and oral doses of verapamil were repeated. Electrocardiograms (ECG) were done and serum verapamil and norverapamil concentrations measured before and for 12 h after each dose. For IV verapamil, there was a small decrease in area under the serum concentration-time curve and an increase in clearance after rifampin therapy (p less than 0.05). There were no changes in elimination half-life, volume of distribution, or AUC for percentage of change in P-R interval-time curve (AUCPR). For oral verapamil, there were marked decreases in peak concentration, AUC, oral bioavailability (all p less than 0.005), and AUCPR (p less than 0.001) after rifampin treatment. There were no changes in time to peak concentration or elimination half-life. For oral verapamil, significant P-R interval prolongation occurred only before treatment with rifampin. The decrease in oral bioavailability and the abolition of ECG response confirm that a highly significant drug interaction exists between rifampin and verapamil given orally but not intravenously.

Systemic absorption of tetracycline and lidocaine following intrapleural instillation.

Seven patients with symptomatic pleural effusions (six) and recurrent pneumothorax (one) underwent attempted pleurodesis using tetracycline. Lidocaine (150 mg), followed immediately by tetracycline (20 mg/kg), was instilled into the pleural space through a chest tube. Venous blood was obtained at 0, 15, 30, 60, and 120 minutes following instillation in order to determine concentrations of lidocaine and tetracycline. The mean peak serum concentration of lidocaine was 1.3 mu/ml +/- 0.4 microgram/ml (mean +/- SE) (range, 0.3 microgram/ml to 3.2 microgram/ml), and the mean time to peak serum concentration of lidocaine was 86 +/- 13 minutes. The mean peak serum concentration of tetracycline was 3.6 microgram/ml +/- 0.9 microgram/ml (range, 1.0 microgram/ml to 5.0 micrograms/ml), and the mean time to peak serum concentration of tetracycline was 96 +/- 16 minutes. Therapeutic serum concentrations of lidocaine were found in four of the seven patients and therapeutic serum levels of tetracycline in four of five patients. With systemic absorption of lidocaine and tetracycline following intrapleural instillation, patients are at risk for potential toxic effects. If lidocaine is used in a dosage of less than 3 mg/kg, toxic levels of the drug are unlikely to occur. Furthermore, use of tetracycline or lidocaine in pleurodesis is contraindicated in patients with known sensitivity to the drugs.

Lidocaine concentrations in bronchoscopic specimens.

We measured lidocaine concentrations in bronchoscopic specimens and found that bronchoalveolar lavage (BAL) concentrations (16 +/- 7 micrograms/ml) were lower than those in bronchial washings (967 +/- 379 micrograms/ml [p less than 0.001]). Lidocaine concentrations in bronchial washings obtained "early" (991 +/- 505 micrograms/ml) compared with "late" (943 +/- 580 micrograms/ml) in the procedure did not differ (p = NS). High lidocaine concentrations sufficient to inhibit growth in culture of mycobacterial and fungal pathogens (greater than 5,000 micrograms/ml) occurred in one early and two late bronchial washings but no BAL specimens. No correlation between lidocaine dose and measured concentrations was noted in any specimen category; however, highest bronchial washing concentrations occurred with the use of greater than 250 mg of lidocaine. We conclude that BAL specimens are suitable for culturing pathogens that may be inhibited by lidocaine. Furthermore, collecting bronchial washings late in the procedure or limiting the lidocaine dosage do not reliably decrease measured lidocaine concentrations.

Verapamil infusions in the treatment of atrial tachyarrhythmias.

Ten patients with symptomatic atrial tachyarrhythmias were treated with an iv verapamil bolus (mean 8.5 mg) followed by a continuous verapamil infusion (mean dose 9.4 mg/h). The infusions were titrated to ventricular rate and continued for an average of 20 h, until oral therapy could be instituted. All patients had a significant, sustained reduction in ventricular rate during the infusion, without a significant reduction in mean arterial pressure. Although one patient complained of dizziness after 8 h of infusion therapy, the regimen was generally well tolerated and no patient had clinical worsening of heart failure. These preliminary data suggest that continuous verapamil infusions can safely and effectively control ventricular rate in patients with rapid atrial tachyarrhythmias, until oral medications can be started.

Verapamil-rifampin interaction.

A case of verapamil-rifampin interaction is presented in a patient receiving verapamil for supraventricular tachycardia (SVT) and rifampin for pulmonary tuberculosis. The patient experienced recurrent symptomatic SVT, despite receiving verapamil 480 mg po q6h. Serum verapamil concentrations were determined to be extremely low. Discontinuation of rifampin and substitution of ethambutol resulted in an almost four-fold increase in verapamil levels with concurrent control of SVT. Rifampin may have increased the metabolism of verapamil by inducing hepatic microsomal enzymes resulting in low verapamil levels and failure to control SVT.