human
***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: The conventional treatment of  chronic anal fissure  is lateral sphincterotomy ( LAS ) . The alternative options of tailored sphincterotomy ( TS ) and ‘ chemical sphincterotomy ’ using medication such as nifedipine have recently become available BACKGROUND Anal fissure is a frequent proctologic disease . There are many and various treatments adopted to cure this disease . In this study we applied radiofrequencies to the subcutaneous lateral internal sphincterotomy and we compared the techniques in a r and omised trial . METHODS Patients have been r and omized in two groups : in group A 18 patients underwent subcutaneous lateral internal sphincterotomy using radiofrequency bistoury while in group B 17 patients underwent the conventional lateral internal sphincterotomy described by Parks .  RESULTS The mean values for operative time were 6.6 min for group A and 9.1 min for group B. According to pain score , patients ' mean values were 1.8 for group A and 1.9 for group B. Healing of the wound was faster in group A than group B , while healing of the anal fissure was approximately the same . CONCLUSION Lateral subcutaneous sphincterotomy is the most advantageous operation for the treatment of the idiopathic anal fissure . The radiofrequency bistoury easies the procedure , lessens operating times and healing process of the surgical wounds Purpose The objective of this study was to compare the efficacy of 0.25 percent glycerin trinitrate ointment in association with cryothermal anal dilators with 0.25 percent glycerin trinitrate ointment only and cryothermal anal dilators only . Methods A total of 48 patients suffering from chronic anal fissure were enrolled in this prospect i ve , r and omized study between January 2002 and December 2003 : Group A , 16 patients were treated with 0.25 percent glycerin trinitrate ointment and also used cryothermal anal dilators ; Group B , 16 patients were treated with 0.25 percent glycerin trinitrate ointment only ; Group C , 16 patients were treated with cryothermal anal dilator use only . All patients in each group followed the specified treatment protocol for six weeks . Results After seven weeks of treatment , the symptoms complained of were resolved in 15 patients ( 93.7 percent ) in Group A , 12 patients ( 75 percent ) in Group B , and 12 patients ( 78 percent ) in Group C. After two years of follow-up , 14 patients ( 87.5 percent ) in Group A , 9 patients ( 56.2 percent ) in Group B , and 10 patients ( 62.5 percent ) in Group C presented no recurrence of symptoms . No patient in any group reported serious side effects of the treatment proposed , and treatment did not have to be withdrawn in any of the r and omized patients . No episodes of anal incontinence of gas or feces were recorded in the patients who had used the anal dilators . Conclusions The combined treatment for chronic anal fissure proved to be efficacious , safe , and with statistically significant better results than the other treatments analyzed Background There is common belief among some medical research ers that if a potential surrogate endpoint is highly correlated with a true endpoint , then a positive ( or negative ) difference in potential surrogate endpoints between r and omization groups would imply a positive ( or negative ) difference in unobserved true endpoints between r and omization groups . We investigate this belief when the potential surrogate and unobserved true endpoints are perfectly correlated within each r and omization group . Methods We use a graphical approach . The vertical axis is the unobserved true endpoint and the horizontal axis is the  potential surrogate endpoint  . Perfect correlation within each r and omization group implies that , for each r and omization group , potential surrogate and true endpoints are related by a straight line . In this scenario the investigator does not know the slopes or intercepts . We consider a plausible example where the slope of the line is higher for the experimental group than for the control group . Results In our example with unknown lines , a decrease in mean potential surrogate endpoints from control to experimental groups corresponds to an increase in mean true endpoint from control to experimental groups . Thus the potential surrogate endpoints give the wrong inference . Similar results hold for binary potential surrogate and true outcomes ( although the notion of correlation does not apply ) . The potential surrogate endpointwould give the correct inference if either ( i ) the unknown lines for the two group coincided , which means that the distribution of true endpoint conditional on potential surrogate endpoint does not depend on treatment group , which is called the Prentice Criterion or ( ii ) if one could accurately predict the lines based on data from prior studies . Conclusion Perfect correlation between potential surrogate and unobserved true outcomes within r and omized groups does not guarantee correct inference based on a potential surrogate endpoint . Even in early phase trials , investigators should not base conclusions on potential surrogate endpoints in which the only validation is high correlation with the true endpoint within a group Abstract . Mean maximum anal resting pressure is directly related to the activity of the smooth muscles of the internal and external sphincters and has been found to be increased in the patients of anal fissure . It has been shown that blood flow at the posterior midline of anoderm is inversely related to the mean maximum anal resting pressure , and topical application of glyceryl trinitrate ( GTN ) ointments is a very successful treatment . This r and omized study was design ed to evaluate the relative value of a nitroglycerin patch applied at a distance from the fissure site in healing anal fissure compared to GTN ointment and compared to surgical treatment .  Forty-two consecutive patients with chronic anal fissure of more than 4 months ' duration were r and omized into two equally sized groups : those in group A received 0.2 % GTN ointment while those in group B received a 10-mg nitroglycerin patch for 8 weeks . Patients were also asked to rate their pain intensity on a scale of 0–10 . Five patients were excluded for various reasons ; results were analyzed for the remaining 37 patients ( group A , n=18 ; group B , n=19 ) . A control group C consisted of 12 patients who underwent surgical treatment . Fissures healed completely in 12 of 18 ( 66.7 % ) patients in group A , 12 of 19 ( 63.2 % ) in group B and 11/12 ( 91.7 % ) in group C. The healing rates in groups A and B did not differ significantly ( P=0.7 ) , nor was there a difference between these and surgical group C ( P=0.13 ) . The local application of GTN ointment and the nitroglycerin patch are both effective , economical , and alternative treatment options for most patients with anal fissures Aim The present study aims to evaluate and compare the efficacy of two nitrate gels , containing isosorbide-5-mononitrate ( ISMN ) or glyceryl trinitrate ( GTN ) , in the therapy of chronic anal fissure . Material s and methods The patients were r and omly assigned to three groups : 0.1 % ISMN gel ( 21 patients ) , 0.1 % GTN gel ( 21 patients ) and a placebo group ( ten patients ) . The ethic committee of our hospital approved the protocol and informed consent was obtained from all participants . All patients underwent clinical examination , visual inspection of the fissure and anal manometry prior to and after therapy . Results The chronic anal fissure was completely healed in 71 % of the patients treated with ISMN , 67 % with GTN and in 30 % from the placebo group . One patient in the ISMN group reported mild headache . Three patients in the GTN group had anal burning . Conclusion Both topical nitrate treatments ( ISMN and GTN ) were effective for chronic anal fissures . The reduction of the anal pressure was slightly higher after ISMN treatment ( 28 % ) than the treatment with GTN ( 23 % ) . However , the statistical difference was not significant ( p > 0.05 ) Abstract . Background The surgical approach in chronic anal fissures ( CAF ) may , occasionally result in anal incontinence . The aim of this investigation was to study feasibility , effectiveness , and safety of hydropneumatic anal dilation ( HAD ) in conservative treatment of CAF and to compare it with local nitroglycerin ( GTN ) treatment . Methods Efficacy of HAD was evaluated in 109 patients ( 65 male , 44 female ; mean age , 53.3 years ) , following anal dilation using Microvasive Rigiflex instrument ( Otw 40 mm ) . Thereafter , 36 patients were r and omly divided into two groups to undergo treatment with 0.25 % GTN or HAD . Results Recovery rate with HAD was 79.8 % after 10 days and 94.5 % after 30 days . An immediate ( within 24 hours ) drop was observed in the level of pain ; no significant complications or recurrence were reported within 2 years . Healing rate was 94.5 % following HAD vs. 38.9 % after GTN . Conclusion HAD should be considered a new safe option in CAF treatment Objective The aim of this study was to compare prospect ively diltiazem with GTN ointment in the treatment of anal fissure One hundred and three patients with an acute first episode of posterior anal fissure were r and omised to receive a three week trial of lignocaine ointment ( n = 33 ) versus hydrocortisone ointment ( n = 35 ) or warm sitz baths combined with an intake of unprocessed bran ( n = 35 ) . Seven patients were withdrawn owing to failure to adhere to the trial protocol . After one and two weeks of treatment symptomatic relief was significantly better among patients treated with sitz baths and bran than among patients treated with lignocaine ointment or hydrocortisone ointment . After three weeks there was no difference in symptomatic relief among the three groups . Patients treated with lignocaine , however , had significantly fewer healed fissures ( 60 % ) than patients treated with hydrocortisone ( 82.4 % ) or warm sitz baths and bran ( 87 % ) . In this study warm sitz baths plus an intake of unprocessed bran came out as the treatment of choice for an acute first episode of posterior anal fissure . This treatment is cheap , has no potential serious side effects , and brings the best and quickest relief of symptoms The effect of unprocessed bran in a dose of 5 g three times daily and a dose of 2.5 g three times daily for one year on the recurrence rate of anal fissures was studied in a double-blind , placebo-controlled trial in 90 patients with recently healed acute posterior anal fissures . Fifteen patients ( 16.6 % ) were withdrawn before the code was broken due to failure to follow the trial protocol for various reasons . Significantly fewer recurrences occurred in patients receiving bran 5 g throe times daily ( recurrence rate 16 % , 95 % confidence limits , 4.54 to 36.08 ) when compared with patients receiving bran 2.5 g three times daily ( 60 % ; 38.67 to 78.87 ) ( P<0.01 ) and with patients receiving placebo three times daily ( 68 % ; 46.50 to 85.05 ) ( P<0.01 ) . No significant difference in recurrences was found between patients on bran 2.5 g and those on placebo BACKGROUND Anal fissure is most commonly treated surgically by internal anal sphincterotomy . However , there is some concern over the effects of this procedure on continence . Nitric oxide donors such as glyceryl trinitrate ( GTN ) have been shown to cause a reversible chemical sphincterotomy capable of healing fissures in a small series of cases . This study reports a prospect i ve , r and omised , double-blind , placebo-controlled trial to test the hypothesis that topical GTN is the best first-line treatment for chronic anal fissure . METHODS 80 consecutive patients were r and omised to receive treatments with topical 0.2 % GTN ointment or placebo .  Maximum anal resting pressure ( MARP ) was measured with a constantly perfused side-hole catheter before and after the first application of trial ointment . Anodermal blood flow was measured during manometry by laser Doppler flowmetry . After initial treatments , patients were given a supply of ointment ( either GTN or placebo ) to be applied to the lower anal canal twice daily . Patients were review ed 2-weekly . At the initial and follow up visits patients were asked to record pain experienced on defaecation on a linear analogue pain score . Endpoints were healing of the fissure or condition after 8 weeks of treatment . FINDINGS After 8 weeks , healing was observed in 26/38 ( 68 % ) patients treated with GTN and in 3/39 ( 8 % ) patients treated with placebo ( p < 0.0001 , chi 2 test ) . Linear analogue pain score fell significantly in both groups after 2 weeks of treatment . This fall was maintained in those treated with GTN but pain scores returned to pre-treatment values by 4 weeks on treatment with placebo .  MARP fell significantly from a mean of 115.9 ( SD 31.6 ) to 75.9 ( 30.1 ) cm H2O ( p < 0.001 , Student 's paired t-test ) in patients treated with GTN but no change was seen in MARP after placebo .  Anodermal blood flow measured by laser Doppler flowmetry significantly increased after application of GTN ointment but was unaffected by placebo . INTERPRETATION Topical GTN provides rapid , sustained relief of pain in patients with anal fissure . Over two-thirds of patients treated in this way avoided surgery which would otherwise have been required for healing . Long-term follow up is needed to assess the risk of recurrent fissure in patients with GTN PURPOSE : This was a multicenter , r and omized , controlled trial to compare the effectiveness of topical nitroglycerin with internal sphincterotomy in the treatment 
    Output:
    
agent
Botox and CCBs were equivalent to GTN in efficacy with fewer adverse events .
No medical therapy came close to the efficacy of surgical sphincterotomy , though none in these RCTs was associated with the risk of incontinence .
Medical therapy for chronic anal fissure , acute fissure and fissure in children may be applied with a chance of cure that is marginally better than placebo , and , for chronic fissure in adults , far less effective than surgery
***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: The conventional treatment of  chronic anal fissure  is lateral sphincterotomy ( LAS ) . The alternative options of tailored sphincterotomy ( TS ) and ‘ chemical sphincterotomy ’ using medication such as nifedipine have recently become available BACKGROUND Anal fissure is a frequent proctologic disease . There are many and various treatments adopted to cure this disease . In this study we applied radiofrequencies to the subcutaneous lateral internal sphincterotomy and we compared the techniques in a r and omised trial . METHODS Patients have been r and omized in two groups : in group A 18 patients underwent subcutaneous lateral internal sphincterotomy using radiofrequency bistoury while in group B 17 patients underwent the conventional lateral internal sphincterotomy described by Parks .  RESULTS The mean values for operative time were 6.6 min for group A and 9.1 min for group B. According to pain score , patients ' mean values were 1.8 for group A and 1.9 for group B. Healing of the wound was faster in group A than group B , while healing of the anal fissure was approximately the same . CONCLUSION Lateral subcutaneous sphincterotomy is the most advantageous operation for the treatment of the idiopathic anal fissure . The radiofrequency bistoury easies the procedure , lessens operating times and healing process of the surgical wounds Purpose The objective of this study was to compare the efficacy of 0.25 percent glycerin trinitrate ointment in association with cryothermal anal dilators with 0.25 percent glycerin trinitrate ointment only and cryothermal anal dilators only . Methods A total of 48 patients suffering from chronic anal fissure were enrolled in this prospect i ve , r and omized study between January 2002 and December 2003 : Group A , 16 patients were treated with 0.25 percent glycerin trinitrate ointment and also used cryothermal anal dilators ; Group B , 16 patients were treated with 0.25 percent glycerin trinitrate ointment only ; Group C , 16 patients were treated with cryothermal anal dilator use only . All patients in each group followed the specified treatment protocol for six weeks . Results After seven weeks of treatment , the symptoms complained of were resolved in 15 patients ( 93.7 percent ) in Group A , 12 patients ( 75 percent ) in Group B , and 12 patients ( 78 percent ) in Group C. After two years of follow-up , 14 patients ( 87.5 percent ) in Group A , 9 patients ( 56.2 percent ) in Group B , and 10 patients ( 62.5 percent ) in Group C presented no recurrence of symptoms . No patient in any group reported serious side effects of the treatment proposed , and treatment did not have to be withdrawn in any of the r and omized patients . No episodes of anal incontinence of gas or feces were recorded in the patients who had used the anal dilators . Conclusions The combined treatment for chronic anal fissure proved to be efficacious , safe , and with statistically significant better results than the other treatments analyzed Background There is common belief among some medical research ers that if a potential surrogate endpoint is highly correlated with a true endpoint , then a positive ( or negative ) difference in potential surrogate endpoints between r and omization groups would imply a positive ( or negative ) difference in unobserved true endpoints between r and omization groups . We investigate this belief when the potential surrogate and unobserved true endpoints are perfectly correlated within each r and omization group . Methods We use a graphical approach . The vertical axis is the unobserved true endpoint and the horizontal axis is the  potential surrogate endpoint  . Perfect correlation within each r and omization group implies that , for each r and omization group , potential surrogate and true endpoints are related by a straight line . In this scenario the investigator does not know the slopes or intercepts . We consider a plausible example where the slope of the line is higher for the experimental group than for the control group . Results In our example with unknown lines , a decrease in mean potential surrogate endpoints from control to experimental groups corresponds to an increase in mean true endpoint from control to experimental groups . Thus the potential surrogate endpoints give the wrong inference . Similar results hold for binary potential surrogate and true outcomes ( although the notion of correlation does not apply ) . The potential surrogate endpointwould give the correct inference if either ( i ) the unknown lines for the two group coincided , which means that the distribution of true endpoint conditional on potential surrogate endpoint does not depend on treatment group , which is called the Prentice Criterion or ( ii ) if one could accurately predict the lines based on data from prior studies . Conclusion Perfect correlation between potential surrogate and unobserved true outcomes within r and omized groups does not guarantee correct inference based on a potential surrogate endpoint . Even in early phase trials , investigators should not base conclusions on potential surrogate endpoints in which the only validation is high correlation with the true endpoint within a group Abstract . Mean maximum anal resting pressure is directly related to the activity of the smooth muscles of the internal and external sphincters and has been found to be increased in the patients of anal fissure . It has been shown that blood flow at the posterior midline of anoderm is inversely related to the mean maximum anal resting pressure , and topical application of glyceryl trinitrate ( GTN ) ointments is a very successful treatment . This r and omized study was design ed to evaluate the relative value of a nitroglycerin patch applied at a distance from the fissure site in healing anal fissure compared to GTN ointment and compared to surgical treatment .  Forty-two consecutive patients with chronic anal fissure of more than 4 months ' duration were r and omized into two equally sized groups : those in group A received 0.2 % GTN ointment while those in group B received a 10-mg nitroglycerin patch for 8 weeks . Patients were also asked to rate their pain intensity on a scale of 0–10 . Five patients were excluded for various reasons ; results were analyzed for the remaining 37 patients ( group A , n=18 ; group B , n=19 ) . A control group C consisted of 12 patients who underwent surgical treatment . Fissures healed completely in 12 of 18 ( 66.7 % ) patients in group A , 12 of 19 ( 63.2 % ) in group B and 11/12 ( 91.7 % ) in group C. The healing rates in groups A and B did not differ significantly ( P=0.7 ) , nor was there a difference between these and surgical group C ( P=0.13 ) . The local application of GTN ointment and the nitroglycerin patch are both effective , economical , and alternative treatment options for most patients with anal fissures Aim The present study aims to evaluate and compare the efficacy of two nitrate gels , containing isosorbide-5-mononitrate ( ISMN ) or glyceryl trinitrate ( GTN ) , in the therapy of chronic anal fissure . Material s and methods The patients were r and omly assigned to three groups : 0.1 % ISMN gel ( 21 patients ) , 0.1 % GTN gel ( 21 patients ) and a placebo group ( ten patients ) . The ethic committee of our hospital approved the protocol and informed consent was obtained from all participants . All patients underwent clinical examination , visual inspection of the fissure and anal manometry prior to and after therapy . Results The chronic anal fissure was completely healed in 71 % of the patients treated with ISMN , 67 % with GTN and in 30 % from the placebo group . One patient in the ISMN group reported mild headache . Three patients in the GTN group had anal burning . Conclusion Both topical nitrate treatments ( ISMN and GTN ) were effective for chronic anal fissures . The reduction of the anal pressure was slightly higher after ISMN treatment ( 28 % ) than the treatment with GTN ( 23 % ) . However , the statistical difference was not significant ( p > 0.05 ) Abstract . Background The surgical approach in chronic anal fissures ( CAF ) may , occasionally result in anal incontinence . The aim of this investigation was to study feasibility , effectiveness , and safety of hydropneumatic anal dilation ( HAD ) in conservative treatment of CAF and to compare it with local nitroglycerin ( GTN ) treatment . Methods Efficacy of HAD was evaluated in 109 patients ( 65 male , 44 female ; mean age , 53.3 years ) , following anal dilation using Microvasive Rigiflex instrument ( Otw 40 mm ) . Thereafter , 36 patients were r and omly divided into two groups to undergo treatment with 0.25 % GTN or HAD . Results Recovery rate with HAD was 79.8 % after 10 days and 94.5 % after 30 days . An immediate ( within 24 hours ) drop was observed in the level of pain ; no significant complications or recurrence were reported within 2 years . Healing rate was 94.5 % following HAD vs. 38.9 % after GTN . Conclusion HAD should be considered a new safe option in CAF treatment Objective The aim of this study was to compare prospect ively diltiazem with GTN ointment in the treatment of anal fissure One hundred and three patients with an acute first episode of posterior anal fissure were r and omised to receive a three week trial of lignocaine ointment ( n = 33 ) versus hydrocortisone ointment ( n = 35 ) or warm sitz baths combined with an intake of unprocessed bran ( n = 35 ) . Seven patients were withdrawn owing to failure to adhere to the trial protocol . After one and two weeks of treatment symptomatic relief was significantly better among patients treated with sitz baths and bran than among patients treated with lignocaine ointment or hydrocortisone ointment . After three weeks there was no difference in symptomatic relief among the three groups . Patients treated with lignocaine , however , had significantly fewer healed fissures ( 60 % ) than patients treated with hydrocortisone ( 82.4 % ) or warm sitz baths and bran ( 87 % ) . In this study warm sitz baths plus an intake of unprocessed bran came out as the treatment of choice for an acute first episode of posterior anal fissure . This treatment is cheap , has no potential serious side effects , and brings the best and quickest relief of symptoms The effect of unprocessed bran in a dose of 5 g three times daily and a dose of 2.5 g three times daily for one year on the recurrence rate of anal fissures was studied in a double-blind , placebo-controlled trial in 90 patients with recently healed acute posterior anal fissures . Fifteen patients ( 16.6 % ) were withdrawn before the code was broken due to failure to follow the trial protocol for various reasons . Significantly fewer recurrences occurred in patients receiving bran 5 g throe times daily ( recurrence rate 16 % , 95 % confidence limits , 4.54 to 36.08 ) when compared with patients receiving bran 2.5 g three times daily ( 60 % ; 38.67 to 78.87 ) ( P<0.01 ) and with patients receiving placebo three times daily ( 68 % ; 46.50 to 85.05 ) ( P<0.01 ) . No significant difference in recurrences was found between patients on bran 2.5 g and those on placebo BACKGROUND Anal fissure is most commonly treated surgically by internal anal sphincterotomy . However , there is some concern over the effects of this procedure on continence . Nitric oxide donors such as glyceryl trinitrate ( GTN ) have been shown to cause a reversible chemical sphincterotomy capable of healing fissures in a small series of cases . This study reports a prospect i ve , r and omised , double-blind , placebo-controlled trial to test the hypothesis that topical GTN is the best first-line treatment for chronic anal fissure . METHODS 80 consecutive patients were r and omised to receive treatments with topical 0.2 % GTN ointment or placebo .  Maximum anal resting pressure ( MARP ) was measured with a constantly perfused side-hole catheter before and after the first application of trial ointment . Anodermal blood flow was measured during manometry by laser Doppler flowmetry . After initial treatments , patients were given a supply of ointment ( either GTN or placebo ) to be applied to the lower anal canal twice daily . Patients were review ed 2-weekly . At the initial and follow up visits patients were asked to record pain experienced on defaecation on a linear analogue pain score . Endpoints were healing of the fissure or condition after 8 weeks of treatment . FINDINGS After 8 weeks , healing was observed in 26/38 ( 68 % ) patients treated with GTN and in 3/39 ( 8 % ) patients treated with placebo ( p < 0.0001 , chi 2 test ) . Linear analogue pain score fell significantly in both groups after 2 weeks of treatment . This fall was maintained in those treated with GTN but pain scores returned to pre-treatment values by 4 weeks on treatment with placebo .  MARP fell significantly from a mean of 115.9 ( SD 31.6 ) to 75.9 ( 30.1 ) cm H2O ( p < 0.001 , Student 's paired t-test ) in patients treated with GTN but no change was seen in MARP after placebo .  Anodermal blood flow measured by laser Doppler flowmetry significantly increased after application of GTN ointment but was unaffected by placebo . INTERPRETATION Topical GTN provides rapid , sustained relief of pain in patients with anal fissure . Over two-thirds of patients treated in this way avoided surgery which would otherwise have been required for healing . Long-term follow up is needed to assess the risk of recurrent fissure in patients with GTN PURPOSE : This was a multicenter , r and omized , controlled trial to compare the effectiveness of topical nitroglycerin with internal sphincterotomy in the treatment 
    Output:
    