***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: Summary : A single blind study of 1 % bifonazole cream applied once dalty and 2 % miconazole cream applied twice daily was canied out on 31 patients with tinea pedis proven by microscopy and culture . After three weeks treatment the mycological cure rate in the bifommle group was 73 % against 69 % in the miconazole group . This study indicates that bifonazole 1 % cream used once daily is as effective in treating tinea pedis as twice daily miconazole 2 % cream . Zusammenfassung : Ein einfach blinder klinischer Versuch mit 1-%-Bifonazol-Creme , die einmal taglrch adgelragen wurde , und mit 2-%-Miconazol-Creme , die meimal taglich aufgetragen wurde , wurde an 31 Patienten ansgeluhrt , die an mikroskopisch und kulturell nachgewiesener Fusmykose litten . Nach dreiwochiger Beh and hmg waren 73 Prozent in der Bifonazol-Gruppe gegenuber 69 Prozent in der Miconazol-Gruppe geheilt Dieser klinische Versuch deutet darauf hin , das 1-%-Bifonazol-Creme , einmal taglich aufgetragen , ebenso wirksam in der Beh and lung von Fusmykosen ist wie 2-%-Miconazol-Creme , zweimal taglich aufgetragen BACKGROUND Butenafine hydrochloride , a benzylamine derivative with potent antifungal activity , has been used in Japan to treat superficial fungal diseases . OBJECTIVE We evaluated the safety and efficacy of twice-daily butenafine versus its vehicle in the treatment of interdigital tinea pedis in a multicenter , r and omized , double-blind , parallel-group trial . METHODS A total of 402 patients with interdigital tinea pedis and a positive potassium hydroxide examination were enrolled . Of the 271 patients who had culture-confirmed tinea pedis and were assessed for efficacy , 132 applied butenafine and 139 applied vehicle twice daily for 1 week . Patients were assessed for mycologic cure , effective treatment , overall cure , and mycologic/ clinical cure . RESULTS The rates of all four end points were significantly higher with butenafine than with vehicle 5 weeks after treatment ended . Rates of mycologic cure and effective treatment with butenafine were significantly higher than with vehicle at cessation of treatment . Adverse events to treatment occurred in less than 1 % of patients treated with butenafine and 2 % of patients who applied vehicle . CONCLUSION Butenafine applied twice daily for 1 week is highly effective in treating interdigital tinea pedis Clotrimazole is a new antifungal agent which is effective topically in dermatophytosis , cutaneous c and idiasis , and tinea vesicolor . The authors performed a controlled double-blind clinical trial comparing topical clotrimazole with its vehicle in the treatment of 66 patients with dermatophytic infections of the skin of the feet .  Clotrimazole proved to be effective in the treatment of tinea pedis of both the interdigital and the plantar hyperkeratotic types Twenty-three patients were enrolled in a r and omized , double-blind trial of terbinafine 1 % cream compared with placebo vehicle in the treatment of tinea pedis . Of the 20 patients who were evaluated for efficacy , 10 received terbinafine and 10 received placebo . Except for the  terbinafine-treated patients being an average of 11 years older than the patients receiving placebo  and the median duration of disease being 6 weeks longer in the placebo group , the two groups were demographically and clinical ly similar . Results of mycologic tests and clinical findings showed terbinafine to be significantly more effective than placebo in the treatment of tinea pedis . Significantly more terbinafine-treated patients than placebo-treated patients showed conversion to negative culture and microscopy at end of therapy and a significant reduction in scored signs and symptoms . Overall efficacy at follow-up ( combined mycologic and clinical findings ) was also significantly greater in the terbinafine group ( 78 % ) than in the placebo group ( zero ) ( p less than 0.001 ) . Unexplained elevation of liver function test results was noted in three placebo-treated patients and in one terbinafine-treated patient , but these changes were not considered clinical ly relevant or drug related THE NEED FOR THERAPEUTIC OBSERVATIONS IN MAN Before any discussion of the value of clinical trials , it is worthwhile remembering why quantitative or numerical studies in man are necessary . That the need for such studies is not self evident is reflected by the fact that it is only relatively recently that numerical based arguments have achieved preeminence over insights based solely on pathophysiologic mechanisms ( for review s see V and enbroucke1,2 ) . Science is reductionist : science ’s explanatory approach is to attempt to explain phenomena at one level of description by analysis of those forces acting at a different ( “ lower ” ) level of description . This epistemic paradigm is phenomenally successful , and despite cl aims to the contrary , there seems little alternative . It is equally true , but apparently not obvious , that the ability to make precise quantitative predictions from a more basic level to a higher one is often poor . It is therefore the inadequacy of the reductionist enterprise that justifies the need for collecting the results of clinical interventions . A topical example may help . We may “ underst and ” the details of how  ultraviolet radiation ( UVR ) interferes with cell membranes , how UVR induces changes in gene expression , and how UVR induces particular forms of DNA damage , but our insights do not allow us to make sufficiently precise predictions in the clinical arena : should we use UVB twice or three times a week ; what is the risk of melanoma for patients with red hair treated with PUVA ; what dosing regimen of UVR should we use for particular diseases ? There is an enormous gap , and a gap that can not be closed , between explanatory pathways of the sort popular in fields such as cell biology and the sort of quantitative predictive models we require in the clinic . An important corollary of this line of reasoning is easily neglected . Once we accept the limits on our ability to predict with sufficient rigor from a more basic level to a patient , by the same logic the idea of translational research —from bench to clinic , to use the cliche — can only provide a partial view of reality . In many instances a more fruitful approach is in the reverse direction , from clinic to bench . Ironically , because it is often thought as showing quite the opposite , the rise of human molecular genetics over the past 10 years has provided the best example of clinic to bench . The whole of positional cloning has relied on the definition of a disease at a higher level of explanation guiding the search for the respective “ disease gene . ” The starting point is clinical description and syndrome identification . Only once this is in place can you identify a putative genetic cause . By contrast , if all research were translational in origin we would be left trying to r and omly mutate the 50,000 or so genes in the human genome and attempting to delineate particular clinical phenotypes ; a task even beyond the National Institutes of Health and the most zealous enthusiasts for knock-out mouse strategies . The underlying message and rationale is quite simple : just as we ca n’t explain behavior on the basis of an individual synapse , we ca n’t explain much disease or the effects of our interventions on a particular disease without extremely accurate predictive causal pathways , which for most of molecular and cell biology we simply do not have . Clinical medicine is both complex and complicated . Instead , we need to rely on studies in humans under conditions that we can manipulate or at least reason about . Although this latter approach is often described as clinical epidemiology or “ trials , ” it forms the core of what has been the long-st and ing method of clinical discovery : the comparison of those with a particular state and those without a particular state and an inquiry into either the causal antecedents for the current state or examination of the changes in the status after intervention . The rest of this article seeks to critically appraise this approach using psoriasis as an example . From the Grant Chair of Dermatology , University of Edinburgh . Reprint requests : Professor Jonathan Rees , Systems Group , Dermatology , University of Edinburgh , First Floor , Lauriston Buildings , Lauriston Place , EH3 9YW , United Kingdom . E-mail : jonathan.rees@ed.ac.uk . J Am Acad Dermatol 2003;48:135 - 43 . Copyright © 2003 by the American Academy of Dermatology , Inc. 0190 - 9622/2003/$30.00 0 Twenty-seven patients with chronic tinea pedis , athlete 's foot type , were enrolled in a r and omized , double-blind trial of topical treatment with terbinafine 1 % cream versus its vehicle ( placebo ) . Patients were examined weekly during 4 weeks of twice-daily treatment and at follow-up 2 weeks after the conclusion of therapy . No adverse events were reported in either treatment group . Drug efficacy was evaluated in 22 patients , of whom nine ( 41 % ) were treated with terbinafine and 13 ( 59 % ) with placebo . Analysis of combined mycologic and clinical results showed that terbinafine was significantly more effective than placebo at the end of therapy ( 78 % vs zero ) and at the 2-week follow-up ( 89 % vs zero ) ( p less than or equal to 0.001 at both intervals Sulconazole nitrate 1 % cream applied twice daily was compared with its vehicle in the treatment of 229 patients with chronic moccasin-type tinea pedis confirmed by positive results of a potassium hydroxide preparation . At admission in this r and omized , double-blind , parallel multicenter trial , 131 patients had positive dermatophyte cultures ; Trichophyton rubrum was identified in 121 ( 92 % ) . After 4 weeks of treatment , patients were examined and , if necessary , were treated for an additional 2 weeks . Sulconazole cream was significantly more effective than the vehicle in the treatment of chronic T. rubrum tinea pedis ; 57 % of patients were cured by sulconazole , compared with 13 % cured with the vehicle .  Relapse rates , assessed 2 weeks after the end of treatment , were significantly lower in patients treated with sulconazole than in those receiving vehicle ( 27 % vs 71 % ) . The 103 patients with moccasin-type tinea pedis whose cultures were not positive for T. rubrum achieved similar results BACKGROUND Patients with tinea pedis often discontinue treatment before eradication of the fungus when their symptoms improve . The result is an incomplete cure/recurrence . OBJECTIVE Terbinafine , a topical fungicidal agent , was evaluated in double-blind , placebo-controlled trials ( 159 patients ) for its ability to achieve cure and relief of symptoms in the same time frame , that is , before compliance wanes . METHODS Mycologic characteristics ( with potassium hydroxide examination and culture ) and clinical signs and symptoms were assessed at baseline , at the end of a 1-week , twice-daily treatment and at 1 , 3 , and 5 weeks after the completion of therapy . RESULTS Both terbinafine and vehicle provided early relief of symptoms . However , only terbinafine gave progressive mycologic improvement such that at 5 weeks after treatment , 88 % of the patients receiving terbinafine had converted from positive to negative mycology compared with 23 % of the patients treated with vehicle . CONCLUSION The rapid and potent fungicidal action of terbinafine results in a high cure rate in interdigital tinea pedis with 1 week of treatment and may avoid failures caused by non-compliance I. Dicken CH , Carrington SG , Winkelmann RK . Generalized granulomaannulare . Arch DermatolI969;99:556 - 63 . 2 . Mobacken H , Gisslen H , Johannisson G. Granuloma annulare : cortisone-glucose tolerancetest in a non-diabetic group . Acta Derm Venereal ( Stockh ) 1970;50:440 - 4 . 3 . Williamson DM , Dykes JRW . Carbohydrate metabolism in granuloma annulare . J InvestDermatol 1972;58:400 - 4 . 4 . BlohmeG , MobackenH , WaldenstromJ. Early insulinresponseto glucoseinjectedintravenously in patients with 10calizedgranulomaannulare . ActaDerm Venereal(Stockh ) 1974;54:259 - 63 . 5 . H aim S , Friedman-BirnbaumR , Shafir A , et al. Generalized granulomaannulare : relationshipto diabetes mellitus as revealed in 8 cases . Br J DermatoI1970;83:302 - 5 . 6 . Hammond R , DyessK , Castro A. Insulin production and glucosetolerancein  patients with granuloma annulare . Br J DermatoI1972;87:540 - 7 . 7 . And ersen BL , VerdichJ. Granuloma annulare and diabetes mellitus . Clin Exp Dermatol 1979;4:31 - 7 . 8 . Muhlemann MF , Williams DDR . Localized granuloma Briefcommunications Tea tree oil ( an essential oil derived primarily from the Australian native Melaleuca alternifolia ) has been used as a topical antiseptic agent since the early part of this century for a wide variety of skin infections ; however , to date , the evidence for its efficacy in fungal infections is still largely anecdotal . One hundred and four patients completed a r and omized , double‐bl 
    Output:
    
Data from patients treated with allylamines  have shown their superior effects relative to vehicle controls since 1991 for even short-term outcomes .