***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 Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes . Fluconazole is active in vitro against the most common pathogens of onychomycosis , penetrates into the nail bed , and is clinical ly effective in the treatment of a wide variety of superficial fungal infections . OBJECTIVE The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole ( 150 , 300 , and 450 mg ) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes . METHODS In this multicenter , double-blind study , 362 patients with mycologically confirmed onychomycosis were r and omized to treatment with fluconazole , 150 , 300 , or 450 mg once weekly , or placebo once weekly for a maximum of 12 months . To enter the study , patients were required to have at least 25 % involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border . Patients who were clinical ly cured or improved at the end of treatment were further evaluated over a 6 month follow-up period . At both the end of therapy and the end of follow-up , clinical success of the target nail was defined as reduction of the affected area to less than 25 % or cure . RESULTS At the end of therapy , 86 % to 89 % of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8 % of placebo-treated patients . Clinical cure ( completely healthy nail ) was achieved in 28 % to 36 % of fluconazole-treated patients compared with 3 % of placebo-treated patients . Fluconazole demonstrated mycologic eradication rates of 47 % to 62 % at the end of therapy compared with 14 % for placebo . The rates at the end of follow-up were very similar , indicating that eradication of the dermatophyte was maintained over the 6-month period . All efficacy measures for the fluconazole groups were significantly superior to placebo ( p=0.0001 ) ; there were no significant differences between the fluconazole groups on these efficacy measures . The clinical relapse rate among cured patients over 6 months of follow-up was low at 4 % . Fluconazole was well tolerated at all doses over the 12-month treatment period , with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups . Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months . This time frame may be used as a guideline for fluconazole treatment duration . CONCLUSION The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes . Doses between 150 to 450 mg weekly for 6 months were clinical ly and mycologically effective as well as safe and well tolerated In a multicentre , r and omised , double-blind , 48-week clinical trial , 118 patients with toe-nail onychomycosis were given terbinafine ( 250 mg daily ) or placebo for 12 weeks , followed by 12 weeks of observation . Non-responders were offered 12 further weeks of terbinafine ( 250 mg daily ) from week 28 . Each patient had 8 - 12 consecutive nail specimens collected from the same nail , allowing for an assessment of the fungal nail flora from 1,321 nail specimens . By week 48 , the overall mycological cure rate for terbinafine patients was 94 % . 64 % of patients had an underlying dermatophyte infection with at least 1 non-dermatophyte mould or yeast isolated from at least 1 specimen . These contaminants often overgrow or mask the presence of a dermatophyte . In only 2.5 % of all patients was the same non-dermatophyte isolated from 2 or more consecutive specimens , probably representing secondary colonisation which exploits nutrients released by the underlying dermatophyte . The presence of incidental non-dermatophyte contaminants or secondary colonisers did not affect treatment outcome , and in this study treatment of the primary dermatophyte pathogen with terbinafine  cleared the nails from infection in all cases . 80 % of patients remained mycologically negative after 2 years 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 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 BACKGROUND Dermatophyte infections of the toenail have been difficult to treat , requiring long courses of therapy and having high recurrence rates . New oral antifungal agents with better outcomes and minimal adverse events are needed . OBJECTIVE The purpose of this study was to compare two newer antifungal compounds , terbinafine and itraconazole , for efficacy and safety in toenail onychomycosis caused by dermatophytes . METHODS The study was r and omized and double-blind . It compared 12 weeks of continuous oral treatment with terbinafine 250 mg/day or itraconazole 200 mg/day for confirmed toenail dermatophyte onychomycosis . Clinical symptoms and mycologic outcome were assessed at weeks 4 , 8 , 12 , 24 , 36 , and 48 . A total of 372 patients ( 186 in each group ) with dermatophyte infection confirmed by microscopy and culture were included in the intent-to-treat analysis . RESULTS At week 48 , a statistically significantly greater percentage of the terbinafine group than itraconazole group showed negative mycology ( 73 % [ 119 of 163 ] vs 45.8 % [ 77 of 168 ] ; p < 0.0001 ) ( difference = 27.2 % ; 95 % CI = [ 17.0 % , 37.3 % ] ) . The difference was also confirmed clinical ly ( p = 0.001 ) in the patients who were clinical ly cured or had only minimal symptoms at the end of the study ( 76.2 % [ 125 of 164 ] vs 58.1 % [ 100 of 172 ] ) ( difference = 18.1 % ; 95 % CI = [ 8.24 % , 27.9 % ] ) . The geometric mean length of healthy nail of the big toe was significantly greater in the terbinafine than itraconazole group ( 8.1 vs 6.4 mm ; p = 0.026 ) . Tolerability was good to very good in almost 90 % of patients in both groups , and all reported adverse events were known for these compounds . CONCLUSION Terbinafine produced higher rates of clinical and mycologic cure at follow-up than did itraconazole Toenail tinea is a very recalcitrant dermatosis . Griseofulvin at > or = 500 mg/day is the current medication of choice , but it is minimally successful . In a controlled open trial ultramicrosize griseofulvin ( UMSG ) at doses of 660 and 990 mg/day was compared with itraconazole at 100 mg/day in 109 patients . At 4-week intervals , the patients were evaluated for their clinical and mycological statuses and adverse reactions . Treatment was given for up to 18 months . Compliance was checked by tablet counting . Response ( cure , partial cure , marked improvement ) was analyzed by the intent-to-treat method . Cured and partially cured patients were followed up . Except for one early dropout , the toenails ( mean , 6 to 7 ) were involved . Cure or partial cure was found in 6 % ( UMSG at 660 mg ) , 14 % ( UMSG at 990 mg ) , and 19 % ( itraconazole at 100 mg ) of patients ( P = 0.2097 ) ; marked improvement was found in 36 , 44 , and 39 % of patients in the three treatment groups , respectively . Most patients had to be treated for 18 months . Failure was related to short medication periods ( adverse drug reactions , dropout ) . While stable cure was not obtained with UMSG at 660 mg , the higher dose of UMSG and itraconazole gave stable cures in the other patients . Side effects of nausea , diarrhea , and headache were found in 20 , 26 , and 11 patients , respectively ( P = 0.0028 ) , and the numbers in whom medication had to be discontinued differed , too ( P = 0.0137 ) . While there was no major difference with glutamic-pyruvic transaminase and gamma-GT , total and low-density lipoprotein cholesterol levels declined slightly in the itraconazole group ( P = 0.0357 and P = 0.0639 , respectively , at 3 months ) . More than 70 % of the patients had an average compliance of > or = 90 % ; four patients ( two dropouts ) were poor compliers . In conclusion , it appears question able whether griseofulvin can continue to be considered the " gold st and ard " in the treatment of toenail tinea . At present , itraconazole at 100 mg shows better efficacy and is better tolerated Lamisil ® ( terbinafine ) 250 mg daily and itraconazole 200 mg daily were compared in the treatment of dermalophyte toe onychomycosis over 12 weeks in a double‐blind r and omized clinical trial . At the end of follow‐up ( week 48 ) treatment with Lamisil ® led to negative mycology in 7 3 % of patients compared with 45–8 % in the itraconazole group ( P < 00001 ) , Globally the clinical symptoms of the target nail improved , a response which was in favour of Lamisil ® ( P=0·001 ) , The percentages of patients who were clinical ly totally cured or who presented with only minimal symptoms were 76′3 ' ) ( ) for the Lamisil ® ‐treated group compared with 58–1 % in the itraconazole group . The unaffected nail length for big toes was significantly higher in the Lamisil ® ‐treated group ( 9·1 mm vs , 7·7 mm ; P= 0·0298 ) . Onycholysis was also less in the Lamisil ® group ( P = 0·001 ) . We conclude that 12 weeks ” conlinitous oral therapy leads to higher cure rates  with Lamisil ® than with itraconazole and that both drugs are equally well toler 
    Output:
    
There is good evidence that a continuous regimen of terbinafine ( 250 mg/d ) for 3 months is the most effective oral treatment for fungally infected toenails .