***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: OBJECTIVE --To compare patient tolerance and treatment efficacy of subcutaneous interferon ( IFN ) alpha 2a plus cryotherapy versus cryotherapy alone in treatment of primary anogenital ( AG ) warts .  DESIGN --R and omised placebo controlled observer blind study . Statistical analysis was by chi square and Mann Whitney U tests . PATIENTS --60 patients with newly diagnosed AG warts . INTERVENTION--29 and 31 patients were treated with subcutaneous IFN alpha 2a plus cryotherapy or placebo injections plus cryotherapy , respectively . MAIN OUTCOME MEASURES -- Clinical presence or absence of AG warts . Patients wart-free at 8 weeks were asked to re-attend at 12 weeks ; those with persistent warts at 8 weeks were withdrawn from the study . RESULTS --At 8 weeks 60.7 % ( 17/28 patients ) of the IFN group and 67.9 % ( 19/28 patients ) of the placebo group were clinical ly wart-free ( not significant ) ; corresponding figures at 12 week review were 29.6 % ( 8/27 patients ) and 40 % ( 10/25 patients ) respectively ( not significant ) . There was no difference in treatment response between males and females . Recurrence of warts at three month review , in patients cleared of warts at 8 weeks , was seen in 50 % ( 8/16 ) and 37.5 % ( 6/16 ) of patients in the IFN and placebo groups respectively ( not significant ) . Multiple warts and the presence of perianal/anal canal warts , either alone or concurrent with warts on the genitalia , at first clinic attendance , were adverse prognostic indicators ( p less than 0.001 , and p = 0.05 respectively ) . Cervical human papilloma virus ( HPV ) infection , exophytic or sub clinical , was present in 58.3 % and 77.2 % of females in the IFN and placebo groups respectively , at trial entry . Although these lesions were not directly treated , colposcopic resolution was seen in 12.5 % of affected women , in both treatment groups , by the end of the 7 week treatment period . Systemic side effects were significantly more common in the IFN than in the placebo group , 50 % versus 10.7 % of patients ( p less than 0.01 ) . Severe influenza like symptoms occurred , after the first three injections only , in one patient treated with IFN ; all other reported side effects were mild . CONCLUSIONS --Subcutaneous IFN alpha 2a combined with cryotherapy is no more effective than cryotherapy alone in the treatment of primary AG warts . The presence of multiple warts and perianal/anal canal warts are adverse prognostic indicators OBJECTIVE : To determine whether the combination of systemically administered interferon alpha-2a and ablative surgery for the treatment of genital and /or perianal warts produces a 30 % or greater improvement in lasting response rate compared with a control group receiving a combination of placebo and ablative therapy . DESIGN : R and omised , triple-blind , placebo-controlled trial using 1 or 3 MIU of interferon alpha-2a or placebo administered subcutaneously three times weekly for 10 weeks in combination with ablative surgery . SETTING : International , multicentre study in 10 genitourinary medicine clinics . PATIENTS : Two hundred and fifty patients with anogenital warts . MAIN OUTCOME MEASURES : Lasting response at week 38 . RESULTS : St and ard efficacy analysis at week 38 showed a lasting response in 51 % ( 35/68 ) of 3 MIU interferon-treated patients , 48 % ( 30/63 ) of 1 MIU interferon-treated patients and 43 % ( 29/67 ) of placebo-treated patients . CONCLUSIONS : With the doses and regime described , treatment with interferon alpha-2a in combination with ablative therapy is not significantly superior in the treatment of anogenital warts than placebo and ablative therapy In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES --The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a ( IFN ) and podophyllin 25 % W/V administered twice per week , preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule . The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups . DESIGN --R and omised , double-blind parallel group study . SETTING --Multicentre study in six genitourinary clinics within the U.K. PATIENTS --One hundred and twenty-four patients with primary anogenital warts . MAIN OUTCOME MEASURES --Complete response rate at week 10 , and recurrence rate at week 26 in complete responders . RESULTS --At week 10 analysis of the efficacy population showed complete response in 36 % ( 15/42 patients ) of IFN-treated group and 26 % ( 11/43 patients ) in the placebo group ( no significant difference ) . Analysis of the safety population at week 26 showed persistence of the complete response in 57 % ( 8/14 patients ) of the IFN-treated group and 80 % ( 12/15 patients ) of the placebo group ( no significant difference ) . Adverse effects were more common in IFN-treated patients , involved particularly application site reaction and malaise but were generally mild . CONCLUSIONS --At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events Sexually transmitted diseases caused by human papilloma viruses , such as condylomata acuminata , are increasing in incidence and are often difficult to treat because of their tendency to recur . Many reports in the literature document the usefulness of interferons topically or systemically in these diseases . A r and omized study was conducted to evaluate interferon Alfa-2b ( Intron A ) as adjuvant therapy following CO2 laser surgery of condylomata acuminata . A low-dose regimen was administered ( two courses with 1 million I.U. s.c . daily for 6 days with a 2-week interval between the courses ) and had hardly any side-effects . The recurrence rate in the therapy group was significantly reduced ( 42 % vs 81 % ) , so routine prophylaxis of recurrence with interferons in condylomata acuminata should be discussed Systemic treatment modalities for eradication of multiple therapy resistant genital warts  are so far not available . In this study laser treated patients with multiple genital warts received postoperatively either interferon alpha-2b subcutaneously ( s.c . ) 5 x 10(6 ) IU or matching placebo three times weekly for four weeks . At the conclusion of the study , 6 - 8 weeks after discontinuation of therapy , a significantly higher cure rate was found in the group of interferon-treated patients ( 14 of 27 ( 52 % ) patients cured ) than among placebo treated patients ( 5 of 22 ( 23 % ) patients cured ) ( p less than 0.05 ) . The side effects of fever , chills , myalgia , headache and leukopenia occurred more commonly in the interferon treated group than in the placebo group . However , only three of 32 patients discontinued interferon therapy because of side effects . We conclude that the addition of s.c . administered interferon alpha-2b to laser treated patients with chronic therapy resistant genital warts is fairly well tolerated and that it significantly enhances the chance of eliminating the disease Skillful laser ablation can remove any volume of human papillomavirus-associated vulvar disease but can not prevent reactivation of the surrounding latent viral reservoir during postoperative healing . Conversely , interferon and 5-fluorouracil are relatively ineffective as primary therapies in clearing bulky lesions . In this study of 71 assessable patients , topical 5-fluorouracil and systemic interferon injections were used postoperatively . Success rates within the adjuvant 5-fluorouracil and laser alone arms were essentially the same ( 9 of 18 vs 8 of 20 ) . In contrast , outcome in the interferon group was significantly better than that for the other two arms combined ( 27 of 33 [ 82 % ] vs 17 of 38 [ 45 % ] ; chi 2 10.31 ; p less than 0.002 ) . Moreover , 18 of 21 failures ( 86 % ) in the first two arms and 3 of 6 failures ( 50 % ) in the interferon arm were " rescued " from the need for a second laser surgical procedure by crossover to either the 1 or 3 MIU interferon regimen . Results from this open-label , r and omized clinical trial suggest that even a relatively low dose of recombinant interferon , used in combination with effective surgical debulking , can markedly reduce the risk of postoperative recurrence Forty-nine subjects were enrolled in a study comparing two dosages of parenterally administered interferon (IFN)-beta in combination with cryotherapy for the treatment of  anogenital warts . Subjects were r and omized to receive subcutaneous injections of either 2 x 10(6 ) or 4 x 10(6 ) IU/m2 of IFN-beta ( Biogen ) three times a week for a total of 6 weeks . Cryotherapy was administered concomitantly by aerosolization of liquid nitrogen at 10-day intervals . Systemic side- effects were modest in intensity and included fever , chills , myalgia , and headaches ( flu-like symptoms ) . During the first 2 weeks of therapy , they were more common in the high dose group than in the low dose group ( P = 0.02 ) . Using survival analysis , there was no significant difference between the two groups in rates of resolution of warts present at baseline ( P = 0.62 ) . However , the rate of new lesion formation during the study was significantly lower in the high dose group ( P = 0.04 ) In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted OBJECTIVE --To determine whether interferon alpha-2a , when utilised as adjuvant chemotherapy following ablation of condylomata acuminata ( genital warts ) by cryotherapy , is effective in the prevention of recurrences . DESIGN --R and omised , placebo-controlled , double-blind study . Statistical analysis was by 2-tailed Fisher 's Exact Test . PATIENTS --97 patients with recurrent condylomata acuminata . INTERVENTION--49 patients were treated with cryotherapy plus subcutaneously administered interferon alpha-2a , and 48 received cryotherapy plus placebo . Of these , 36 and 37 patients , respectively , completed the study and were evaluable . MAIN OUTCOME MEASURE-- Clinical eradication of condylomata for six months following adjuvant chemotherapy .  RESULTS --By completion of the adjuvant chemotherapy , 10 ( 28 % ) interferon recipients and 16 ( 43 % ) placebo recipients experienced recurrences . At six months follow-up , 25 ( 69 % ) interferon and 27 ( 73 % ) placebo recipients experienced recurrences . In the six months following interferon therapy , only 31 % of interferon and 27 % of placebo recipients remained free of recurrences ( p = 0.99 ) . CONCLUSIONS --Interferon alpha-2a administered subcutaneously offers no benefit as a chemotherapeut 
    Output:
    
Compared with placebo , adjuvant alpha- , beta- and gamma-interferon were generally not significantly superior in terms of complete clearance over the short , intermediate or long term , nor with regard to intermediate- or long-term recurrence .
However , the low-dose subgroup of adjuvant alpha-interferon was significantly superior compared with placebo regarding intermediate-term complete clearance and recurrence .
No significant differences were seen in these comparisons regarding efficacy .
Overall , we found no reliable evidence favouring the systemic use of interferon after ablative treatment of AGW