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The Cochrane Database of Systematic... May 2015Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy.
OBJECTIVES
To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults.A secondary objective is to assess whether the same interventions are effective in the management of seborrhoeic dermatitis in patients with HIV/AIDS.
SEARCH METHODS
We searched the following databases up to December 2014: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 11), MEDLINE (from 1946), EMBASE (from 1974) and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982). We also searched trials registries and checked the bibliographies of published studies for further trials.
SELECTION CRITERIA
Randomised controlled trials of topical antifungals used for treatment of seborrhoeic dermatitis in adolescents and adults, with primary outcome measures of complete clearance of symptoms and improved quality of life.
DATA COLLECTION AND ANALYSIS
Review author pairs independently assessed eligibility for inclusion, extracted study data and assessed risk of bias of included studies. We performed fixed-effect meta-analysis for studies with low statistical heterogeneity and used a random-effects model when heterogeneity was high.
MAIN RESULTS
We included 51 studies with 9052 participants. Of these, 45 trials assessed treatment outcomes at five weeks or less after commencement of treatment, and six trials assessed outcomes over a longer time frame. We believe that 24 trials had some form of conflict of interest, such as funding by pharmaceutical companies.Among the included studies were 12 ketoconazole trials (N = 3253), 11 ciclopirox trials (N = 3029), two lithium trials (N = 141), two bifonazole trials (N = 136) and one clotrimazole trial (N = 126) that compared the effectiveness of these treatments versus placebo or vehicle. Nine ketoconazole trials (N = 632) and one miconazole trial (N = 47) compared these treatments versus steroids. Fourteen studies (N = 1541) compared one antifungal versus another or compared different doses or schedules of administration of the same agent versus one another. KetoconazoleTopical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low-quality evidence) at four weeks of follow-up, but the effect on side effects was uncertain because evidence was of very low quality (RR 0.97, 95% CI 0.58 to 1.64, six studies); heterogeneity between studies was substantial (I² = 74%). The median proportion of those who did not have clearance in the placebo groups was 69%.Ketoconazole treatment resulted in a remission rate similar to that of steroids (RR 1.17, 95% CI 0.95 to 1.44, six studies, low-quality evidence), but occurrence of side effects was 44% lower in the ketoconazole group than in the steroid group (RR 0.56, 95% CI 0.32 to 0.96, eight studies, moderate-quality evidence).Ketoconozale yielded a similar remission failure rate as ciclopirox (RR 1.09, 95% CI 0.95 to 1.26, three studies, low-quality evidence). Most comparisons between ketoconazole and other antifungals were based on single studies that showed comparability of treatment effects. CiclopiroxCiclopirox 1% led to a lower failed remission rate than placebo at four weeks of follow-up (RR 0.79, 95% CI 0.67 to 0.94, eight studies, moderate-quality evidence) with similar rates of side effects (RR 0.9, 95% CI 0.72 to 1.11, four studies, moderate-quality evidence). Other antifungalsClotrimazole and miconazole efficacies were comparable with those of steroids on short-term assessment in single studies.Treatment effects on individual symptoms were less clear and were inconsistent, possibly because of difficulties encountered in measuring these symptoms.Evidence was insufficient to conclude that dose or mode of delivery influenced treatment outcome. Only one study reported on treatment compliance. No study assessed quality of life. One study assessed the maximum rash-free period but provided insufficient data for analysis. One small study in patients with HIV compared the effect of lithium versus placebo on seborrhoeic dermatitis of the face, but treatment outcomes were similar.
AUTHORS' CONCLUSIONS
Ketoconazole and ciclopirox are more effective than placebo, but limited evidence suggests that either of these agents is more effective than any other agent within the same class. Very few studies have assessed symptom clearance for longer periods than four weeks. Ketoconazole produced findings similar to those of steroids, but side effects were fewer. Treatment effect on overall quality of life remains unknown. Better outcome measures, studies of better quality and better reporting are all needed to improve the evidence base for antifungals for seborrhoeic dermatitis.
Topics: Adolescent; Adult; Antifungal Agents; Ciclopirox; Clotrimazole; Dermatitis, Seborrheic; Facial Dermatoses; Humans; Ketoconazole; Lithium Compounds; Miconazole; Pyridones; Randomized Controlled Trials as Topic; Scalp Dermatoses; Solanum; Steroids
PubMed: 25933684
DOI: 10.1002/14651858.CD008138.pub3 -
The Cochrane Database of Systematic... Apr 2015Fungal keratitis is a fungal infection of the cornea. It is common in lower income countries, particularly in agricultural areas but relatively uncommon in higher income... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fungal keratitis is a fungal infection of the cornea. It is common in lower income countries, particularly in agricultural areas but relatively uncommon in higher income countries. Although there are medications available, their effectiveness is unclear.
OBJECTIVES
To assess the effects of different antifungal drugs in the management of fungal keratitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2015), EMBASE (January 1980 to March 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 16 March 2015.
SELECTION CRITERIA
We included randomised controlled trials of medical therapy for fungal keratitis.
DATA COLLECTION AND ANALYSIS
Two review authors selected studies for inclusion in the review, assessed trials for risk of bias and extracted data. The primary outcome was clinical cure at two to three months. Secondary outcomes included best-corrected visual acuity, time to clinical cure, compliance with treatment, adverse outcomes and quality of life.
MAIN RESULTS
We included 12 trials in this review; 10 trials were conducted in India, one in Bangladesh and one in Egypt. Seven of these trials were at high risk of bias in one or more domains, two of these studies were at low risk of bias in all domains. Participants were randomised to the following comparisons: topical 5% natamycin compared to topical 1% voriconazole; topical 5% natamycin compared to topical 2% econazole; topical 5% natamycin compared to topical chlorhexidine gluconate (0.05%, 0.1% and 0.2%); topical 1% voriconazole compared to intrastromal voriconazole 50 g/0.1 mL (both treatments combined with topical 5% natamycin); topical 1% voriconazole combined with oral voriconazole compared to both oral voriconazole and oral itraconazole (both combined with topical 5% natamycin); topical 1% itraconazole compared to topical 1% itraconazole combined with oral itraconazole; topical amphotericin B compared to topical amphotericin B combined with subconjunctival injection of fluconazole; intracameral injection of amphotericin B with conventional treatment compared to conventional treatment alone (severe fungal ulcers); topical 0.5% and 1% silver sulphadiazine compared to topical 1% miconazole. Overall the results were inconclusive because for most comparisons only one small trial was available. The exception was the comparison of topical natamycin and topical voriconazole for which three trials were available. In one of these trials clinical cure (healed ulcer) was reported in all 15 people allocated to natamycin and in 14/15 people allocated to voriconazole (risk ratio (RR) 1.07; 95% confidence interval (CI) 0.89 to 1.28, low quality evidence). In one trial people randomised to natamycin were more likely to have a microbiological cure at six days (RR 1.64; 95% CI 1.38 to 1.94, 299 participants). On average, people randomised to natamycin had better spectacle-corrected visual acuity at two to three months compared to people randomised to voriconazole but the estimate was uncertain and the 95% confidence intervals included 0 (no difference) (mean difference -0.12 logMAR, 95% CI -0.31 to 0.06, 434 participants; 3 studies, low quality evidence) and a decreased risk of corneal perforation or therapeutic penetrating keratoplasty, or both (RR 0.61; 95% CI 0.40 to 0.94, 434 participants, high quality evidence). There was inconclusive evidence on time to clinical cure. Compliance with treatment and quality of life were not reported. One trial comparing natamycin and voriconazole found the effect of treatment greater in Fusarium species, but this subgroup analysis was not prespecified by this review.
AUTHORS' CONCLUSIONS
The trials included in this review were of variable quality and were generally underpowered. There is evidence that natamycin is more effective than voriconazole in the treatment of fungal ulcers. Future research should evaluate treatment effects according to fungus species.
Topics: Antifungal Agents; Eye Infections, Fungal; Humans; Keratitis; Natamycin; Randomized Controlled Trials as Topic; Voriconazole
PubMed: 25855311
DOI: 10.1002/14651858.CD004241.pub4 -
The Cochrane Database of Systematic... Sep 2014Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever.
OBJECTIVES
To assess whether commonly used antifungal drugs decrease mortality in cancer patients with neutropenia.
SEARCH METHODS
We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.
SELECTION CRITERIA
Randomised clinical trials of amphotericin B, fluconazole, ketoconazole, miconazole, itraconazole or voriconazole compared with placebo or no treatment in cancer patients with neutropenia.
DATA COLLECTION AND ANALYSIS
The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.
MAIN RESULTS
Thirty-two trials involving 4287 patients were included. Prophylactic or empirical treatment with amphotericin B significantly decreased total mortality (relative risk (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.96), whereas the estimated RRs for fluconazole, ketoconazole, miconazole, and itraconazole were close to 1.00. No eligible trials were found with voriconazole. Amphotericin B and fluconazole decreased mortality ascribed to fungal infection (RR 0.45, 95% CI 0.26 to 0.76 and RR 0.42, 95% CI 0.24 to 0.73, respectively). The incidence of invasive fungal infection decreased significantly with administration of amphotericin B (RR 0.41, 95% CI 0.24 to 0.73), fluconazole (RR 0.39, 95% CI 0.27 to 0.57) and itraconazole (RR 0.53, 95% CI 0.29 to 0.97), but not with ketoconazole or miconazole. Effect estimates were similar for those 13 trials that had adequate allocation concealment and were blinded. The reporting of harms was far too variable from trial to trial to allow a meaningful overview. For the 2011 and 2014 updates no additional trials were identified for inclusion.
AUTHORS' CONCLUSIONS
Intravenous amphotericin B was the only antifungal agent that reduced total mortality. It should therefore be preferred when prophylactic or empirical antifungal therapy is introduced in cancer patients with neutropenia.
Topics: Antifungal Agents; Humans; Immunocompromised Host; Mycoses; Neoplasms; Neutropenia; Opportunistic Infections; Randomized Controlled Trials as Topic
PubMed: 25188768
DOI: 10.1002/14651858.CD000026.pub2