Systemic antifungal therapy for tinea capitis in children

BACKGROUND: Tinea capitis is a common contagious fungal infection of the scalp in children. Systemic therapy is required for treatment and to prevent spread. This is an update of the original Cochrane review. OBJECTIVES: To assess the effects of systemic antifungal drugs for tinea capitis in children. SEARCH METHODS: We updated our searches of the following databases to November 2015: the Cochrane Skin Group Specialised Register, CENTRAL (2015, Issue 10), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), and CINAHL (from 1981). We searched five trial registers and checked the reference lists of studies for references to relevant randomised controlled trials (RCTs). We obtained unpublished, ongoing trials and grey literature via correspondence with experts in the field and from pharmaceutical companies. SELECTION CRITERIA: RCTs of systemic antifungal therapy in children with normal immunity under the age of 18 with tinea capitis confirmed by microscopy, growth of fungi (dermatophytes) in culture or both. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 25 studies (N = 4449); 4 studies (N = 2637) were new to this update. Terbinafine for four weeks and griseofulvin for eight weeks showed similar efficacy for the primary outcome of complete (i.e. clinical and mycological) cure in three studies involving 328 participants with Trichophyton species infections (84.2% versus 79.0%; risk ratio (RR) 1.06, 95% confidence interval (CI) 0.98 to 1.15; low quality evidence). Complete cure with itraconazole (two to six weeks) and griseofulvin (six weeks) was similar in two studies (83.6% versus 91.0%; RR 0.92, 95% CI 0.81 to 1.05; N = 134; very low quality evidence). In two studies, there was no difference between itraconazole and terbinafine for two to three weeks treatment (73.8% versus 78.8%; RR 0.93, 95% CI 0.72 to 1.19; N = 160; low quality evidence). In three studies, there was a similar proportion achieving complete cured with two to four weeks of fluconazole or six weeks of griseofulvin (41.4% versus 52.7%; RR 0.92, 95% CI 0.81 to 1.05; N = 615; moderate quality evidence). Current evidence for ketoconazole versus griseofulvin was limited. One study favoured griseofulvin (12 weeks) because ketoconazole (12 weeks) appeared less effective for complete cure (RR 0.76, 95% CI 0.62 to 0.94; low quality evidence). However, their effects appeared to be similar when the treatment lasted 26 weeks (RR 0.95, 95% CI 0.83 to 1.07; low quality evidence). Another study indicated that complete cure was similar for ketoconazole (12 weeks) and griseofulvin (12 weeks) (RR 0.89, 95% CI 0.57 to 1.39; low quality evidence). For one trial, there was no significant difference for complete cure between fluconazole (for two to three weeks) and terbinafine (for two to three weeks) (82.0% versus 94.0%; RR 0.87, 95% CI 0.75 to 1.01; N = 100; low quality evidence). For complete cure, we did not find a significant difference between fluconazole (for two to three weeks) and itraconazole (for two to three weeks) (82.0% versus 82.0%; RR 1.00, 95% CI 0.83 to 1.20; low quality evidence). This update provides new data: in children with Microsporum infections, a meta‐analysis of two studies found that the complete cure was lower for terbinafine (6 weeks) than for griseofulvin (6‐12 weeks) (34.7% versus 50.9%; RR 0.68, 95% CI 0.53 to 0.86; N = 334; moderate quality evidence). In the original review, there was no significant difference in complete cure between terbinafine (four weeks) and griseofulvin (eight weeks) in children with Microsporum infections in one small study (27.2% versus 60.0%; RR 0.45, 95% CI 0.15 to 1.35; N = 21; low quality evidence). One study provides new evidence that terbinafine and griseofulvin for six weeks show similar efficacy (49.5% versus 37.8%; RR 1.18, 95% CI 0.74 to 1.88; N = 1006; low quality evidence). However, in children infected with T. tonsurans, terbinafine was better than griseofulvin (52.1% versus 35.4%; RR 1.47, 95% CI 1.22 to 1.77; moderate quality evidence). For children infected with T. violaceum, these two regimens have similar effects (41.3% versus 45.1%; RR 0.91, 95% CI 0.68 to 1.24; low quality evidence). Additionally, three weeks of fluconazole was similar to six weeks of fluconazole in one study in 491 participants infected with T. tonsurans and M. canis (30.2% versus 34.1%; RR 0.88, 95% CI 0.68 to 1.14; low quality evidence). The frequency of adverse events attributed to the study drugs was similar for terbinafine and griseofulvin (9.2% versus 8.3%; RR 1.11, 95% CI 0.79 to 1.57; moderate quality evidence), and severe adverse events were rare (0.6% versus 0.6%; RR 0.97, 95% CI 0.24 to 3.88; moderate quality evidence). Adverse events for terbinafine, griseofulvin, itraconazole, ketoconazole, and fluconazole were all mild and reversible. All of the included studies were at either high or unclear risk of bias in at least one domain. Using GRADE to rate the overall quality of the evidence, lower quality evidence resulted in lower confidence in the estimate of effect. AUTHORS' CONCLUSIONS: Newer treatments including terbinafine, itraconazole and fluconazole are at least similar to griseofulvin in children with tinea capitis caused by Trichophyton species. Limited evidence suggests that terbinafine, itraconazole and fluconazole have similar effects, whereas ketoconazole may be less effective than griseofulvin in children infected with Trichophyton. With some interventions the proportion achieving complete clinical cure was in excess of 90% (e.g. one study of terbinafine or griseofulvin for Trichophyton infections), but in many of the comparisons tested, the proportion cured was much lower. New evidence from this update suggests that terbinafine is more effective than griseofulvin in children with T. tonsurans infection. However, in children with Microsporum infections, new evidence suggests that the effect of griseofulvin is better than terbinafine. We did not find any evidence to support a difference in terms of adherence between four weeks of terbinafine versus eight weeks of griseofulvin. Not all treatments for tinea capitis are available in paediatric formulations but all have reasonable safety profiles

Delivering enhanced cardiovascular (Hypertension) disease care through private health facilities in Pakistan

Background: Cardiovascular diseases (CVDs) are one of the leading causes of death and disability in the world. Over 80% of CVD deaths take place in low-and middle-income countries. One-third of the population aged above 40 years suffers from Hypertension (HTN) and this is largely unreported as there is no registry for CVDs. No guidelines are available for use in health care facilities, especially private health facilities where practice among GPs varies considerably. We aim to conduct a Cluster Randomized Controlled trial delivering a quality HTN-CVD care package at strengthened private health facilities as compared to current practice at private health facilities.Methods/Design: A pragmatic cluster randomized trial, with qualitative and economic studies, will be conducted in Sargodha district of Punjab, Pakistan, from January 2012 to December 2016. At least 912 hypertensives will be registered in the two arms, six clusters per arm. The proposed cluster randomized controlled trial will evaluate the effects of delivering quality HTN-CVD care, through enabled private health care facilities, to achieve better case registration, adherence and hypertension control also blood glucose and serum cholesterol control. The trial will be conducted through the doctors and paramedics at private health facilities. Main outcomes are mean difference in Systolic blood pressure among the two arms. Secondary outcomes are mean change in total serum cholesterol levels and mean change in glycaemic control achieved in the adult hypertensive patients. Individual and Cluster level analysis will be done according to intention-to-treat.Discussion: Due to the high burden of disease where 1 in 3 individuals aged above 45 suffers from hypertension, topped with the fact that there is a dearth of a set of available, standardised guidelines for management, the disease is constantly on a hike in Pakistan. The government has made no effort to issue a set of guidelines adapted specifically for our population and this becomes more of a problem when managing CVD in urban population through private practitioners whose practices vary widely.If our set of context sensitive guidelines show an effectiveness in the proposed intervention districts it will be replicated in other such settings.Trial registration: Current Controlled Trials ISRCTN34381594