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1
Roberts DT, Taylor WD, Boyle J. Guidelines for treatment of onychomycosis. Brit J Dermatol 2003;148: 402–410. RATIONALE: Confirmation of diagnosis: only 50% of cases of nail dystrophy are fungal, and it is not easy to identify these clinically. The length of treatment needed (6-12 months) is too long for a trial of therapy.

2
Chung CH, Young-Xu Y, Kurth T, Orav JE, Chan AK. The safety of oral antifungal treatments for superficial dermatophytosis and onychomycosis: a meta-analysis. Am J Med 2007; 120: 791-798. RATIONALE: Pooled data from about 20,000 participants found that both continuous and pulse therapy with terbinafine, itraconazole, or fluconazole were well tolerated. The risk of having asymptomatic raised liver transaminases was less than 2% for all treatments. The risk of having raised liver transaminases that required treatment discontinuation with continuous treatment ranged from 0.11% (itraconazole 100mg/day) to 1.22% (fluconazole 50mg/day). The risk with pulse treatment ranged from 0.39% (itraconazole 400mg/day) to 0.85% (fluconazole 300-450mg/week).

3
CKS. Fungal nail infection (onychomycosis) Clinical Knowledge Summaries 2009.
http://cks.nice.org.uk/fungal-nail-infection#azTab Accessed 23.09.14. RATIONALE: Non-dermatophyte nail infection: there is limited evidence that both terbinafine and itraconazole are effective. Candidal nail infection: there is evidence that itraconazole is effective for candidal nail infection. There is weak evidence that terbinafine is also effective. Specialist advice for children: this is because fungal nail infection is rare in children, and the preferred treatments are not licensed for use in children.

4
Public Health England Mycology Reference Laboratory recommends itraconazole for non-dermatophyte infections because although some of the infecting organisms are not particularly susceptible to this agent in vitro, it does reach high concentrations in nail tissue. It can be given as a pulse therapy regimen rather than continuous treatment.

5
Reinel, D. Topical treatment of onychomycosis with amorolfine 5% nail lacquer: comparative efficacy and tolerability of once and twice weekly use. Dermatology. 1992;184(Suppl 1): 21-24. RATIONALE: One RCT (n = 456) without a placebo control found that 46% of those randomized to amorolfine applied once a week for 6 months achieved mycological cure of dermatophyte infection compared with 54% of those who applied topical amorolfine twice a week.

6
Crawford F & Ferrari J. Fungal toenail infections. In Clinical Evidence Concise. London. BMJ Publishing Group. 2006; 15: 561-63. RATIONALE: Terbinafine vs itraconazole: one systematic review pooled data from two randomized controlled trials (n = 501). At 1-year follow-up, the cure rate following 12 weeks of treatment was greater for people with dermatophyte onychomycosis treated with oral terbinafine 250mg once a day (69%) compared with oral itraconazole 200mg daily (48%). Absolute risk reduction 21%, 95% CI 13% to 29%. Pulsed vs continuous itraconazole: four small RCTs were identified that found no statistically significant difference between continuous and pulsed itraconazole for dermatophyte onychomycosis.

The POCAST project is funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London and by the Imperial College Healthcare Charity (Grant Ref No:7006/P36U).