***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Current treatment of onychomycosis of the toenail is poor and relapse is common . OBJECTIVE Our purpose was to assess the efficacy and safety of oral terbinafine and placebo in onychomycosis of the toenail with the use of a novel treatment protocol . METHODS This was a r and omized , double-blind , 48-week study . Twelve weeks of terbinafine ( 250 mg daily ) or placebo was followed by 12 weeks of observation . Responders received no further treatment and nonresponders were offered 12 weeks of terbinafine ( 250 mg daily ) from week 28 . RESULTS Of 111 evaluable patients , 88 % ( 49 of 56 ) of the patients given terbinafine and 29 % ( 16 of 55 ) of the patients given placebo had a negative mycologic culture at week 24 ( p < 0.001 ) , 57 % ( 32 of 56 ) of the terbinafine group and 6 % ( 3 of 55 ) of the placebo group were responders ( p < 0.001 ) . By week 48 , after the terbinafine nonresponders were given a second 12-week course of terbinafine , the overall mycologic cure rate for the patients given terbinafine was 94 % . CONCLUSION High mycologic cure rates in onychomycosis of the toenail can be achieved by terbinafine by this novel treatment regimen BACKGROUND Many patients with chronic dermatophytosis and onychomycosis have depressed cell-mediated immunity ( CMI ) to trichophytin . OBJECTIVE The fungicidal properties of oral terbinafine provide a unique opportunity to explore whether elimination of antigen could restore CMI response in these patients . METHODS A double-blind , placebo-controlled study evaluated the effect of terbinafine ( 250 mg/d for 12 weeks ) on skin immunoreactivity to intradermal trichophytin antigen ( TRIPA ) , mycologic status of the nail , and nail growth in patients with toenail onychomycosis .  RESULTS Skin reactivity , in an optimized , dose response challenge series to TRIPA was inversely related to disease chronicity . Mycologic/ clinical response rates were 72%/84 % for terbinafine and 0%/7 % for placebo . Terbinafine increased the number of TRIPA reactors 2-fold and the mean TRIPA reaction area 4-fold ; responses in placebo-treated patients were relatively unchanged . Of the 7 ( of 25 ) patients receiving  terbinafine  who still had positive mycology 6 months after treatment , all were anergic to TRIPA at baseline and all but one remained so after treatment . CONCLUSION Terbinafine treatment enhances and restores CMI to TRIPA in patients with Trichophyton rubrum onychomycosis and may thereby reduce susceptibility to reinfection . Terbinafine reversal of immunologic anergy may be an important model of microbial tolerance in chronic dermatophyte infections BACKGROUND Griseofulvin has been used in the treatment of toenail onychomycosis with limited success . Evidence suggests that terbinafine may be more effective . OBJECTIVE In a double-blind , parallel-group study we compared 250 mg/day terbinafine for 16 weeks with 500 mg/day griseofulvin for 52 weeks ( or for shorter periods in cured patients ) in patients with toenail onychomycosis . METHODS Eighty-nine patients with culture-proved tinea unguium were included , and 43 in the terbinafine group and 41 in the griseofulvin group were assessable for efficacy . Patients who had not improved after 16 weeks were entered into an open study and were given 250 mg/day terbinafine for 16 weeks with the study code still blinded and were then followed up for 20 weeks . RESULTS Terbinafine was significantly more effective than griseofulvin , with 42 % being completely cured and 84 % mycologically cured compared with only 2 % with total cure and 45 % with mycologic cure in the griseofulvin-treated group . The number of side effects was significantly lower in the terbinafine group ( 11 % ) compared with the griseofulvin group ( 29 % ) . CONCLUSION Terbinafine is significantly more effective than griseofulvin in the treatment of toenail onychomycosis A new method for assessing drug effectiveness in onychomycosis is presented . It is based on the clinical experience when three systemic antifungal drugs ( griseofulvin , thiabendazole , and ketoconazole ) are used against onychomycosis . These drugs act clinical ly as a barrier to the invasion of the fungus toward the proximal areas of the nail plate . A monthly quantity of normal nail plate should be produced by a given subject after the administration of an effective dose of the antifungal being tested . This quantity is best measured at monthly intervals , and this in fact reflects the normal monthly nail plate growth for the individual . Although there is a slight variation among individuals , most normal healthy subjects grow 1.5 to 2 mm of nail plate per month from their large toenails and 3 to 4 mm of nail plate per month from their fingernails . Utilizing this quantitative system , ketoconazole and griseofulvin ultramicrosize were compared in the treatment of distal subungual onychomycosis by Trichophyton rubrum . In a double-blind study , sixteen patients were treated . It appears that both griseofulvin and ketoconazole can eradicate the episode of onychomycosis . One-year use of a topical antifungal cream after clinical cure of onychomycosis prevented reinfection in the 12-month follow-up period . The use of ketoconazole in long-term therapy may result in serious side effects and should be considered carefully prior to treatment BACKGROUND Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes . Fluconazole is active in vitro against the most common pathogens , penetrates into the nail bed , and is clinical ly effective in the treatment of a wide variety of fungal infections . OBJECTIVE The purpose of this study was to assess the safety and efficacy of oral fluconazole 150 , 300 , and 450 mg administered once weekly compared with placebo in the treatment of distal subungual onychomycosis of the fingernail caused by dermatophytes . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled study enrolling 349 patients with onychomycosis of the fingernails .  Clinical and mycologic efficacy as well as measures of safety were assessed monthly for a maximum of 9 months of treatment , with additional safety visits occurring at weeks 2 and 6 . For inclusion , patients were required to have clinical ly and mycologically documented onychomycosis of the fingernail caused by dermatophytes with at least 25 % involvement of the target fingernail . After end of therapy , patients with improved or cured fingernails entered a blinded 6-month follow-up without drug treatment during which efficacy was assessed every 2 months . Efficacy was assessed by clinical ( visual ) and mycologic ( microscopic and culture ) measures . Clinical measures included assessment s of the percentage of target nail involvement , measurement of the distance from the nail fold to the proximal onychomycotic border , and signs and symptoms of onychomycosis . RESULTS Fluconazole was significantly superior to placebo in eradicating clinical and mycologic symptoms of onychomycosis , both at the end of active treatment and at 6 months after treatment ( p=0.0001 for all efficacy measures ) . At the end of therapy , 91 % to 100 % of patients in the fluconazole groups were judged clinical successes , defined as reduction of the affected area of the target nail to less than 25 % or cure , compared with 8 % for placebo .  Clinical cure rates at end of therapy were 76 % , 85 % , and 90 % for fluconazole 150 , 300 , and 450 mg , respectively , compared with 3 % for placebo . These clinical success and cure rates were largely maintained or improved during follow-up . Clinical relapse in cured patients during the follow-up period was very low ( 1.5 % to 3.3 % ) . Fluconazole demonstrated mycologic eradication rates of 89 % to 100 % at the end of treatment and 90 % to 99 % at the end of follow-up ; for placebo the rates were 8 % and 12 % , respectively . CONCLUSION Fluconazole administered once weekly is safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes Background : Itraconazole given in pulse therapy has become popular for onychomycosis treatment since it results in less plasma exposure to the drug while maintaining an effective drug concentration in the nail plate and also increasing patient compliance . Objective : The current study aims to evaluate two different regimens of itraconazole for toenail onychomycosis , looking at both the immediate post‐therapy cure rate and the relapse rate after 2 years . Methods : Two groups of 52 patients each were given either ‘ st and ard ’ oral itraconazole pulse therapy for 3 months ( 200 mg × 2/day for 1 week/month ) followed by an additional single course ( 200 mg/day for 7 days ) after 3 months ( regimen A ) or ‘ modified ’ ( 6‐week interval ) itraconazole pulse therapy ×3 followed by an additional single course ( 200 mg × 2/day for 7 days ) after 3 months . All patients were followed‐up for 24 months from the beginning of treatment . Results : Regimen A : 37 patients were available for examination after 24 months , of whom 22 patients ( 59.5 % ) had total cure and two patients ( 5.5 % ) had marked improvement . Regimen B : 38 patients were available for examination after 24 months , of whom 29 patients ( 76.3 % ) had total cure and three patients ( 7.9 % ) had marked improvement . There were no statistical differences in cure rates between the two groups at the end of treatment , after 12 months and after 24 months . None of the patients ( in both treatment groups ) who had total cure at the end of the treatment period had onychomycosis recurrence after 12 or 24 months . Conclusion : The results at the end of the 24‐month period are encouraging , where 64.9 % ( regimen A ) and 84.2 % ( regimen B ) of the patients had total cure or marked improvement in their toenail condition . Therefore , those two regimens are acceptable alternatives to the current treatment regimen BACKGROUND Effective treatments for onychomycosis are expensive . Previous studies suggest that less costly , pulsed doses of antifungal medications may be as effective as st and ard , continuous doses . Terbinafine is the current treatment of choice for toenail onychomycosis . OBJECTIVE Our purpose was to determine whether pulse-dose terbinafine is as effective as st and ard continuous-dose terbinafine for treatment of toenail onychomycosis . METHODS We conducted a double-blind , r and omized , noninferiority , clinical intervention trial in the Minneapolis Veterans Affairs Medical Center . The main inclusion criteria for participants were a positive dermatophyte culture and at least 25 % distal subungual clinical involvement . Six hundred eighteen volunteers were screened ; 306 were r and omized .  Terbinafine , 250 mg daily for 3 months ( continuous ) or terbinafine , 500 mg daily for 1 week per month for 3 months ( pulse ) was administered . The primary outcome measure was mycological cure of the target toenail at 18 months . Secondary outcome measures included clinical cure and complete ( clinical plus mycological ) cure of the target toenail and complete cure of all 10 toenails . RESULTS Results of an intent-to-treat analysis did not meet the prespecified criterion for noninferiority but did demonstrate the superiority of continuous-dose terbinafine for : mycological cure of the target toenail ( 70.9 % [ 105/148 ] vs 58.7 % [ 84/143 ] ; P = .03 , relative risk [ RR ] of 1.21 [ 95 % confidence interval ( CI ) , 1.02 - 1.43 ] ) ; clinical cure of the target toenail ( 44.6 % [ 66/148 ] vs 29.3 % [ 42/143 ] ; P = .007 , RR = 1.52 [ 95 % CI , 1.11 - 2.07 ) ; complete cure of the target toenail ( 40.5 % [ 60/148 ] vs 28.0 % [ 40/143 ] ; P = .02 , RR=1.45 [ 95 % CI , 1.04 - 2.01 ) ; and complete cure of all 10 toenails ( 25.2 % [ 36/143 ] vs 14.7 % [ 21/143 ] ; P = .03 , RR = 1.71 [ 95 % CI , 1.05 - 2. 
    Output:
    
AUTHORS ' CONCLUSIONS We found high- quality evidence that compared to placebo , terbinafine and azoles are effective treatments for the mycological and clinical cure of onychomycosis , with moderate- quality evidence of excess harm .
However , terbinafine probably leads to better cure rates than azoles with the same risk of adverse events ( moderate- quality evidence ) .Azole and griseofulvin were shown to probably have a similar effect on cure , but more adverse events appeared to occur with the latter ( moderate- quality evidence ) .
Terbinafine may improve cure and be associated with fewer adverse effects when compared to griseofulvin ( low- quality evidence ) .Only four comparisons assessed recurrence rate : low- quality evidence found that terbinafine or azoles may lower the recurrence rate when compared to placebo , but there may be no difference between them .