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Context: Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza.Objective: To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection.Design: Randomized, placebo-controlled, double-blind study conducted January through March 1998.Setting: Sixty primary care and university health centers throughout the United States.Participants: A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom.Interventions: Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209).Main Outcome Measures: Duration and severity of illness in individuals infected with influenza.Results: Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P < or = .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P < .001).Conclusions: Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications. [ABSTRACT FROM AUTHOR]

Objective and Study Design: This multicentre, randomised, double-blind clinical trial compared the clinical and bacteriological efficacy and safety of cefuroxime axetil and amoxicillin/clavulanic acid in the treatment of secondary bacterial infections of acute bronchitis (SBIAB). Patients and Methods: 312 patients with signs and symptoms of acute bronchitis were enrolled at 16 centres and randomised to receive either 5 days of treatment with cefuroxime axetil 250mg twice daily (n = 156) or 10 days of treatment with amoxicillin/clavulanic acid 875/125mg twice daily (n = 156). Patients were assessed once during treatment (3 to 5 days) and twice post-treatment (1 to 4 days and 11 to 14 days post-treatment). Results: Organisms were isolated from pretreatment sputum specimens of 294 of 312 (94%) patients, common pathogens being Haemophilus parainfluenzae, H. influenzae, Moraxella catarrhalis and Streptococcus pneumoniae (39, 23, 9 and 8% of isolates, respectively). 33% of H. influenzae isolates and 88% of M. catarrhalis isolates produced β-lactamase. A satisfactory clinical outcome was achieved in 86% (114 of 133) and 90% (128 of 142) of the clinically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanic acid, respectively (p = 0.27), at the 11- to 14-day follow-up visit. A satisfactory bacteriological outcome was obtained in 89% (110 of 123) and 92% (123 of 134) of bacteriologically and clinically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanic acid, respectively (p = 0.516), at the 11- to 14-day follow-up visit. Amoxicillin/clavulanic acid treatment was associated with a greater incidence of drug-related adverse events (32 vs 12%, p < 0.001), particularly gastrointestinal adverse events (23 vs 4%, p < 0.001), than was cefuroxime axetil treatment. Conclusions: Cefuroxime axetil 250mg twice daily for 5 days has similar efficacy to amoxicillin/clavulanic acid 875/125mg twice daily for 10 days in the treatment of acute bronchitis, and produces fewer drug-related adverse events. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia.Background: Despite the availability of statins, many patients do not achieve lipid targets. Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals.Methods: After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =145 mg/dl to < or =250 mg/dl and triglycerides (TG) < or =350 mg/dl were randomized to one of the following 10 groups administered daily for 12 consecutive weeks: ezetimibe 10 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg plus simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups.Results: Ezetimibe plus simvastatin significantly improved LDL-C (p < 0.01), high-density lipoprotein cholesterol (HDL-C) (p = 0.03), and TG (p < 0.01) compared with simvastatin alone. Ezetimibe plus simvastatin (pooled doses) provided an incremental 13.8% LDL-C reduction, 2.4% HDL-C increase, and 7.5% TG reduction compared with pooled simvastatin alone. Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44% to 57%, TG reductions of 20% to 28%, and HDL-C increases of 8% to 11%, depending on the simvastatin dose. Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44% LDL-C reduction. The coadministration of ezetimibe with simvastatin was well tolerated, with a safety profile similar to those of simvastatin and of placebo.Conclusions: When coadministered with simvastatin, ezetimibe provided significant incremental reductions in LDL-C and TG, as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone. [ABSTRACT FROM AUTHOR]

Background: Influenza can cause significant morbidity and mortality in subjects at high risk for complications, including the elderly (age >or=65 years) and those with chronic respiratory, cardiovascular, or metabolic conditions. Effective prophylaxis can significantly reduce the disease burden in this population. Previous studies conducted primarily in non-high-risk subjects have reported the efficacy of inhaled zanamivir in preventing influenza., Objective: This study investigated the efficacy and safety of zanamivir in preventing influenza in community-dwelling adult and adolescent subjects at high risk for complications of influenza., Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in community-dwelling subjects aged >or=12 years who were at high risk for developing complications of influenza, were able to use the Diskhaler device (Glaxo Group Limited, Research Triangle Park, North Carolina), and were able to take the first dose of study medication within 5 days of laboratory-confirmed local influenza activity. Eligible subjects were randomized to receive inhaled zanamivir 10 mg or placebo once daily for 28 days. The primary end point was the proportion of randomized subjects who developed symptomatic influenza during prophylaxis, as confirmed by culture and/or serology. All adverse events (AEs) occurring after the first dose of study medication were recorded., Results: The study enrolled 3363 subjects, of whom 58% were female and 93% were white; the mean age of participants was 60.4 years (range, 12-94 years), and 4% were adolescents. Significantly fewer zanamivir-treated subjects developed symptomatic, laboratory- confirmed influenza during prophylaxis compared with placebo recipients (4/1678 vs 23/1685, respectively), representing a relative risk (RR) of 0.17 (95% CI, 0.07-0.44; P < 0.001) and a protective efficacy of 83%. The incidence of complications was reduced in zanamivir-treated subjects compared with placebo recipients (1/1678 and 8/1685), representing an RR of 0.12 (95% CI, 0.02-0.73; P = 0.042) and a protective efficacy of 88%. The numbers of zanamivir recipients (151/1678 [9%]) and placebo recipients (169/1685 [ 10 % ] ) who developed symptomatic influenza-like illness regardless of laboratory confirmation did not differ significantly (RR = 0.86; 95% CI, 0.70-1.06), indicating that zanamivir was not effective in preventing influenza-like illness that was not caused by influenza infection. Similarly, there was no significant difference in the numbers of zanamivir and placebo recipients who developed laboratory-confirmed infection regardless of symptoms (39/1678 [2%] and 52/1685 [3%], respectively; RR = 0.76; 95% CI, 0.50-1.15). Of these, 64 subjects (35 and 29) were asymptomatic; seroconversion occurred in all but 1 subject, indicating that zanamivir prophylaxis did not prevent asymptomatic seroconversion. During prophylaxis, 51% of subjects in both treatment groups reported at least 1 AE. There were no major differences in the frequency or nature of AEs between groups. The most commonly reported AEs (>or=3% of subjects in each treatment group) were consistent with upper respiratory viral infection (headache: 17% zanamivir, 18% placebo; cough: 14% and 15%, respectively; throat and tonsil discomfort/pain: 13% and 14%). There were no differences between groups in the overall incidence of viral respiratory infections (5% in both groups) or ear, nose, and throat infections (2% in both groups). None of the analyzed isolates from confirmed cases of influenza exhibited reduced susceptibility to zanamivir or genotypic evidence of resistance., Conclusions: Zanamivir, administered once daily for 28 days, was efficacious in preventing infection with the predominant circulating strains in the 2000- 2001 influenza season in the Northern Hemisphere (influenza A/New Calendonia/20/99-1ike and influenza B/ Sichuan/379/99-like) in these high-risk community- dwelling subjects aged >or=12 years. Zanamivir was well tolerated, with a safety profile comparable to that of placebo. No emergence of resistant virus was detected., (Copyright 2007 Excerpta Medica, Inc.)

Objective: To determine the effect of oseltamivir (75mg twice daily) on time to return to baseline health, sleep and activity in patients with laboratory-confirmed influenza infection., Patients and Methods: Data from 1642 otherwise healthy adults (aged 13-64 years), who had experienced a febrile influenza-like illness (>38 degrees C) of up to 36 hours' duration together with at least one respiratory and one systemic/constitutional symptom, were pooled from four randomised, double-blind, placebo-controlled clinical trials. Patients in these trials had been randomised to receive either oseltamivir or placebo for 5 days and had been allowed unlimited use of symptom-relief medications. The primary analysis examined the effect of oseltamivir treatment on patients' general health status, sleep and normal activities as measured by visual analogue scales. Secondary analyses examined the possible effects of gender, influenza type, smoking, employment status and time to treatment (< or = or >24 hours) on these endpoints., Results: Oseltamivir significantly reduced the time taken to return to baseline health, sleep and activity across all pooled patients (p < 0.0001) and increased the proportion of patients returning to full activity within the first 7 days following treatment start. Gender, smoking status, time to treatment, influenza subtype and employment status had no appreciable effect on the effectiveness of oseltamivir., Conclusions: In otherwise healthy adults, oseltamivir reduces the time to return to pre-illness levels of health, sleep and activity, and may help to decrease the overall burden of influenza on society. This provides an important rationale for the early use of antiviral treatment, such as oseltamivir, for the treatment of influenza in otherwise healthy adults and adolescents.

Three hundred eighty-nine patients were enrolled in a double-masked, multicenter, randomized clinical trial comparing the clinical and bacteriologic efficacies and safety of a 5-day course (n = 195) versus a 10-day course (n = 194) of grepafloxacin 400 mg once daily in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB). Patients in the 5-day treatment group received placebo on days 6 through 10. Bacteriologic assessments were based on cultures of sputum specimens obtained before and, when possible, during and after treatment. Organisms were isolated from the pretreatment sputum specimens of 332 of 388 (86%) patients, the primary pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus (29%, 19%, 4%, 5%, and 5% of isolates, respectively). Among isolates tested for beta-lactamase production, results were positive in 25% of H influenzae isolates and 90% of M catarrhalis isolates. Forty-two percent of S pneumoniae isolates demonstrated reduced susceptibility (intermediate or high-level resistance) to penicillin. A satisfactory clinical outcome (cure or improvement) was achieved in 83% (128 of 155) and 81% (122 of 150) of clinically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. Pathogens were eradicated or presumed eradicated in 77% (106 of 138) and 80% (98 of 123) of bacteriologically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. The 2 treatment groups were equivalent with respect to both clinical and bacteriologic efficacy, and no statistically significant differences in the incidence of drug-related adverse events were seen between the 2 groups. Substantial symptom relief was evident with both treatment regimens by the first during-treatment measurement, which occurred between days 3 through 5. These results indicate that treatment with 400 mg grepafloxacin once daily for 5 days is as well tolerated and effective as treatment for 10 days in patients with ABECB. The lower cost compared with a 10-day regimen and the increased likelihood that patients will complete the entire shorter, once-daily regimen make the 5-day grepafloxacin regimen a useful therapeutic option in the treatment of ABECB.