Topical corticosteroids in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial using fluticasone propionate aqueous nasal spray. Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne. Evaluation of the medical and surgical treatment of chronic rhinosinusitis: a prospective, randomised, controlled trial. Amphotericin B irrigation for the treatment of chronic rhinosinusitis without nasal polyps: a randomized, placebo-controlled, double-blind study. Preoperative therapeutic considerations in chronic suppurative otitis media. [Antimicrobial therapy in chronic suppurative otitis media].
Chronic rhinosinusitis (CRS) is a recalcitrant inflammatory process which has a marked detrimental impact on quality of life. At the present there is no cure for this condition, measures are taken to stop progression, and provide symptomatic relief. Topical corticosteroids are commonly prescribed in the management of CRS, but few trials show effectiveness in clinical settings. We set up a randomized, double-blind, placebo-controlled trial to study the effectiveness of a topical corticosteroid agent--fluticasone propionate aqueous nasal spray (FPANS) in patients with CRS. We measured symptoms, diary card, and rigid endoscopy scores, acoustic rhinometry, middle meatal swabs, blood tests--CRP, ESR, WBC, and eosinophil count. Measurements were done at the start of the trial, at 8 weeks, and 16 weeks where possible. Twenty-two patients completed the trial, 9 received FPANS, and 13 had placebo. There was no difference between the 2 groups on all counts. When patients were considered as one group, there was an improvement in the diary card scores (p = 0.054), comparing baseline to 8 or 16 weeks. There was no evidence that the regular use of topical corticosteroid increased the risk of developing an infection. An important observation was that the topical corticosteroid did not precipitate acute sinusitis. There is compelling evidence that topical corticosteroids down-regulate cytokine expression, and it is likely that a larger, and longer multi-centre trial may prove their efficacy in CRS. To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community; the propensity of each regimen to give rise to local and systemic adverse events; whether pre-existing bacterial resistance to the prescribed antibiotic resulted in reduced efficacy; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains.
                This was a parallel group randomised assessor-blind controlled clinical trial. It was a pragmatic design with intention-to-treat analysis. All treatments were given for 18 weeks, after a 4-week treatment free period. Outcomes were measured at 0, 6, 12 and 18 weeks.
                Primary care practices and colleges in and around Nottingham and Leeds, and one practice in Stockton-on-Tees, England.
                Participants were 649 people aged 12--39 years, all with mild to moderate inflammatory acne of the face.
                Study participants were randomised into one of five groups: 500 mg oral oxytetracycline (non-proprietary) twice daily (b.d.) + topical vehicle control b.d.; 100 mg oral Minocin MR (minocycline) once daily (o.d.) + topical vehicle control b.d.; topical Benzamycin (3% erythromycin + 5% benzoyl peroxide) b.d. + oral placebo o.d.; topical Stiemycin (2% erythromycin) o.d. + topical Panoxyl Aquagel (5% benzoyl peroxide) o.d. + oral placebo o.d., and topical Panoxyl Aquagel (5% benzoyl peroxide) b.d. + oral placebo o.d. (the active comparator group).
                The two primary outcome measures were: (1) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale, and (2) change in inflamed lesion count (red spots).
                The best response rates were seen with two of the topical regimens (erythromycin plus benzoyl peroxide administered separately o.d. or in a combined proprietary formulation b.d.), compared with benzoyl peroxide alone, oxytetracycline (500 mg b.d.) and minocycline (100 mg o.d.), although differences were small. The percentage of participants with at least moderate improvement was 53.8% for minocycline (the least effective) and 66.1% for the combined erythromycin/benzoyl peroxide formulation (the most effective); the adjusted odds ratio for these two treatments was 1.74 [95% confidence interval (CI) 1.04 to 2.90]. Similar efficacy rankings were obtained using lesion counts, acne severity scores and global rating by assessor. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen (ratio of means 12.3; difference in means -0.051 units/GBP, 95% CI -0.063 to -0.039). The efficacy of oxytetracycline was similar to that of minocycline, but at approximately one-seventh of the cost. For all regimens, the largest reductions in acne severity were recorded in the first 6 weeks. Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline. The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria, including antibiotic-resistant variants, and these were equally effective in participants with and without erythromycin-resistant propionibacteria. The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria. None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains. Systemic adverse events were more common with the two oral antibiotics. Local irritation was more common with the topical treatments, particularly benzoyl peroxide. Residual acne was present in most participants (95%) at the end of the study.
                The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal. Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period; extending treatment beyond 12 weeks increased overall benefit slightly. Around one-quarter dropped out when using such treatments, and 55% sought further treatment after 18 weeks. Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne. The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance. Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions. It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life. There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation, except that the former was nearly three times more cost-effective. The data on cost-effectiveness, and outcomes in patients with resistant propionibacterial floras, did not support the first line use of minocycline for mild to moderate inflammatory acne of the face. Three priority areas for clinical research in acne are: defining end-points in acne trials (i.e. what is a satisfactory outcome?); developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne; and exploring patient characteristics that may modify treatment effects (efficacy and tolerability). To conduct the first prospective, randomized, controlled trial evaluating and comparing the medical and surgical treatment of polypoid and nonpolypoid chronic rhinosinusitis (CRS).
                Ninety patients with CRS were equally randomized either to medical or surgical therapy. All patients underwent pre- and posttreatment assessments of visual analogue score (VAS), the Sinonasal Outcome Test-20 (SNOT-20), the Short Form 36 Health Survey (SF-36), nitric oxide (NO), acoustic rhinometry, saccharine clearance time (SCT), and nasal endoscopy. Each patient had three assessments: before starting the treatment, after 6 months, and, finally, after 1 year.
                Both the medical and surgical treatment of CRS significantly improved almost all the subjective and objective parameters of CRS (P <.01), with no significant difference being found between the medical and surgical groups (P >.05), except for the total nasal volume in CRS (P <.01) and CRS without polyposis (P <.01) groups, in which the surgical treatment demonstrated greater changes.
                CRS should be initially targeted with maximal medical therapy (e.g., a 3 month course of a macrolide antibiotic, douche, and topical steroid), with surgical treatment being reserved for cases refractory to medical therapy. The presence of nasal polyps is not a poor prognostic factor for the efficacy of CRS therapy, either surgical or medical. Fungus-driven inflammation is proposed to play an important role in the pathogenesis of chronic rhinosinusitis (CRS). Previous studies tested the efficacy of intranasal antifungal agents for patients with nasal polyps. The purpose of this study was to evaluate the efficacy of intranasal amphotericin B (AMB) in patients who have CRS without nasal polyps (CRSsNP).
                Patients diagnosed with CRSsNP were enrolled in this study. They were assigned randomly to receive irrigation with AMB solution (20 mg of AMB in 500 mL of normal saline) or placebo (yellowish dye in 500 mL of normal saline) for 4 weeks. The outcome measures included the Chinese version of the Rhinosinusitis Outcome Measure 31 (CRSOM-31), nasal endoscopy, and bacterial and fungal cultures.
                Seventy patients were enrolled and 64 patients completed this study. There was significant improvement in the AMB group (n = 32) both in endoscopic (p = 0.013) and CRSOM-31 scores (p < 0.0001). The placebo group (n = 32) showed significant improvement in CRSOM-31 scores (p < 0.0001). CRSOM-31 scores were significantly lower in the AMB group than in the placebo group after 2-week treatment (p = 0.018) and remained lower after 4-week treatment, although the difference was not significant (p = 0.091). There were no significant differences in endoscopic scores and bacterial or fungal culture rates between two groups after treatment.
                Our results showed that AMB irrigation improved symptoms and endoscopic scores but did not show superiority to saline irrigation alone in patients who have CRSsNP. The present randomized, prospective study of 119 cases of chronic suppurative otitis media compares the effectiveness of inexpensive, atoxic, nonallergenic disinfectants applied locally, to that of a number of occasionally toxic antimicrobial chemotherapeutic agents, administered systemically. Systemic treatment resulted in a cure rate of 53.5% (SEp = 5.9%) while ototopical treatment resulted in a 39.5% cure rate (SEp = 7%). Eradication of pathogens or colonization by a nonpathogen occurred in 50.7% (SEp = 5.9%) with systemic treatment, and in 39.5% (SEp = 7%) with ototopical treatment. Bacteriological modification was 2.5 times more frequent with systemic treatment than with ototopical treatment. No recurrences were noted with ototopical treatment, while 13% to 36% recurrence rates were noted in various subgroups of cases treated systemically. Cure rates achieved with particular drug regimens (administration based on sensitivity tests in vitro) were: Azactam 25% (5%-57% confidence limits), sulfamethoxazole plus trimethoprim 58.6% (38%-76%), ciprofloxacin 87.5% (47%-99%), ciprofloxacin plus metronidazole 90% (55%-99%). Cure rates with other drugs were inconclusive because of the limited number of observations. A randomized study was made of 125 patients with chronic middle ear infection. The most frequently isolated microorganisms were: Pseudomonas aeruginosa, Staphylococcus aureus and Enterobacteriaceae. Ciprofloxacin is very active against the microorganisms usually isolated and it has been shown to provide effective therapy in ear infections. In order to study the effectiveness of ciprofloxacin in chronic otitis media, we selected four different treatment groups: oral ciprofloxacin (500 mg/12 h); 0.5 and 0.2% topical solutions of ciprofloxacin (3 drops/8 h), and oral ciprofloxacin plus 0.2% topical solution. Topical polymyxin and neomycin were used as controls. Topical ciprofloxacin (0.2%) was the most effective regimen of those tested for the treatment of chronic otitis media.
On the basis of this meta-analysis, there is no evidence to support the use of either topical or systemic antifungal treatment in the management of CRS.