title: Cyclosporine A and pentosan polysulfate sodium for the treatment of interstitial cystitis: a randomized comparative study. Successful therapy of interstitial cystitis with pentosanpolysulfate. Psychometric validation of the O'leary-Sant interstitial cystitis symptom index in a clinical trial of pentosan polysulfate sodium. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. Cystoscopic findings consistent with interstitial cystitis in normal women undergoing tubal ligation. A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate. Safety and efficacy of hyperbaric oxygen therapy for the treatment of interstitial cystitis: a randomized, sham controlled, double-blind trial. A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis. Pentosan polysulfate sodium for therapy of interstitial cystitis. A double-blind placebo-controlled clinical study. Intravesical resiniferatoxin for the treatment of hypersensitive disorder: a randomized placebo controlled study. A randomized double‐blind placebo‐controlled crossover trial of the efficacy of l‐arginine in the treatment of interstitial cystitis A randomized controlled trial of intravesical bacillus calmette-guerin for treatment refractory interstitial cystitis. A prospective double-blind clinically controlled multicenter trial of sodium pentosanpolysulfate in the treatment of interstitial cystitis and related painful bladder disease. A prospective study of interstitial cystitis: results of longitudinal followup of the interstitial cystitis data base cohort. The Interstitial Cystitis Data Base Study Group. Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis. Prevalence of clinically confirmed interstitial cystitis in women: a population based study in Finland. The efficacy of intravesical Tice strain bacillus Calmette-Guerin in the treatment of interstitial cystitis: a double-blind, prospective, placebo controlled trial. Effect of isoniazid chemoprophylaxis on HIV-related mycobacterial disease. Effect Sizes for Interpreting Changes in Health Status Acquired rifamycin resistance with twice-weekly treatment of HIV-related tuberculosis. Intravesical bacillus Calmette-Guerin and dimethyl sulfoxide for treatment of classic and nonulcer interstitial cystitis: a prospective, randomized double-blind study. Pilot study of sequential oral antibiotics for the treatment of interstitial cystitis. Interstitial cystitis: bladder training with intravesical oxybutynin. Oral cimetidine gives effective symptom relief in painful bladder disease: a prospective, randomized, double‐blind placebo‐controlled trial A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. A controlled study of dimethyl sulfoxide in interstitial cystitis.
abstract: PURPOSE In a previous retrospective analysis , cyclosporine A ( CyA ) was highly efficient in treating patients with interstitial cystitis . A prospect i ve r and omized study with this immunosuppressive agent was warranted . We compared CyA to pentosan polysulfate sodium ( PPS ) in patients with interstitial cystitis . MATERIAL S AND METHODS A total of 64 patients with interstitial cystitis meeting the National Institute of Diabetes and Digestive and Kidney Diseases criteria were enrolled in a r and omized prospect i ve study . Patients were r and omized in a 1:1 ratio to 1.5 mg/kg CyA twice daily ( 27 women , 5 men ) or 100 mg PPS 3 times daily ( 26 women , 6 men ) for a period of 6 months . The primary end point was daily micturition frequency , and secondary end points were mean and maximal voided volume , number of nocturia episodes , O'Leary-Sant symptom and problem indexes , visual analogue scale for pain , and subjective global response assessment . RESULTS CyA was superior to PPS in all clinical outcome parameters measured at 6 months . Micturition frequency in 24 hours was significantly reduced in the CyA arm compared to the PPS arm ( -6.7 + /- 4.7 vs -2.0 + /- 5.1 times ) . The clinical response rate ( according to global response assessment ) was 75 % for CyA compared to 19 % for PPS ( p < 0.001 ) . Although there were more adverse events in the CyA arm than in the PPS arm , 29 patients completed the 6-month followup in both groups . CONCLUSIONS CyA is more effective than PPS in interstitial cystitis Sodium pentosanpolysulfate ( Elmiron ) is a synthetic , sulfated polysaccharide available in an oral form that is excreted into the urine . This drug was used in a double-blind fashion to evaluate its efficacy in the management of symptoms of interstitial cystitis . A dose of 100 mg . 3 times daily was used for a minimum of 4 months and was continued for longer than 18 months in some individuals . A total of 62 patients was evaluated from 2 different medical centers . Subjective improvements were greater in all parameters when the drug was compared to placebo therapy , with significant improvement in pain , urgency , frequency and nocturia . Objective improvement in average voided volumes was greater with the drug than with placebo ( p equals 0.009 ) . No significant difference was found between drug and placebo groups in the average number of daily voiding episodes The O'Leary-Sant Interstitial Cystitis Symptom Index ( ICSI ) has been proposed as a treatment outcome measure in interstitial cystitis ( IC ) . The psychometric properties of the ICSI were assessed for reliability and validity in a r and omized , double-blind clinical study of 300 , 600 , and 900 mg daily dose of pentosan polysulfate sodium ( PPS ) in patients with IC . The ICSI contains 4 items that measure urgency and frequency of urination , nighttime urination , and pain or burning . The ICSI index score is the sum of the item scores ( range : 0 - 20 ) . ICSI scores were obtained at baseline , 4 , 8 , 12 , 16 , 24 , and 32 weeks of treatment . Patients ' overall ratings of improvement of symptoms ( PORIS ) scores evaluating improvements in pain , urgency , and overall IC symptoms were also collected except at baseline . A total of 376 patients were included in the analysis . Psychometric properties evaluated included variability ( range ) , test-retest reliability ( intraclass correlation coefficient [ ICC ] ) , internal consistency ( the Cronbach alpha ) , construct validity ( convergent , discriminant ) , responsiveness , and clinical ly meaningful change . The ICSI items and index score had good variability and test-retest reliability . The ICSI demonstrated internal consistency reliability and was responsive to change . Participants indicating a 75 % improvement in PORIS had a 48 % mean reduction in the ICSI score , while participants reporting 100 % improvement in PORIS had a 77 % mean reduction in the ICSI score . The ICSI is a valid , reliable , and responsive measure of change in IC symptoms . This outcome measure should be utilized in future treatment outcomes studies in IC PURPOSE This pilot study was design ed to evaluate the feasibility of a multicenter , r and omized , clinical trial in interstitial cystitis ( IC ) . Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium ( PPS ) , hydroxyzine , and the combination to consider their use in a larger r and omized clinical trial . MATERIAL S AND METHODS A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine .  Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry . The primary end point was a patient reported global response assessment . Secondary end points included vali date d symptom indexes and patient reports of pain , urgency and frequency . The target sample size was 136 participants recruited during 10 months . RESULTS A total of 121 ( 89 % of goal ) participants were r and omized over 18 months and 79 % provided complete followup data . The response rate for hydroxyzine was 31 % for those treated and 20 % for those not treated ( p = 0.26 ) . A nonsignificant trend was seen in the PPS treatment groups ( 34 % ) as compared to no PPS ( 18 % , p = 0.064 ) . There were no treatment differences for any of the secondary end points . Adverse events were mostly minor and similar to those in previous reports . CONCLUSIONS The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC . This trial demonstrated the feasibility of conducting a multicenter r and omized clinical trial in IC using uniform procedures and outcomes . However , slow recruitment underscored the difficulties of evaluating commonly available IC drugs PURPOSE We test the hypothesis that women without chronic pelvic pain or irritative voiding symptoms do not demonstrate petechial hemorrhages known as glomerulations that are characteristic of patients with interstitial cystitis . MATERIAL S AND METHODS A prospect i ve cohort design was used for examination with cystoscopy and bladder distention of 20 asymptomatic women undergoing tubal ligation . Cystoscopy with the patient under general anesthesia was performed to inspect the bladder mucosa before and after distention at 70 cm . of water pressure for 2 or 6 minutes . Photographs of the right , posterior and left of the bladder surfaces taken before and after the distention were scored on a scale of 1 to 5 using a panel of st and ards . Five urologists blinded to the source of individual photographs independently evaluated 120 research images interspersed with 46 other pictures from a library containing images from 19 symptomatic patients with and without interstitial cystitis . RESULTS A total of 20 normal women with a mean age plus or minus st and ard deviation of 29+/-6 years consented to participate in this trial during laparoscopic tubal ligation .  Photographs of bladder sites before and after distention with 890+/-140 ml . were scored as 1.4+/-0.3 ( before distention ) and 3.1+/-1.1 ( after distention ) on the scale of 1 to 5 . The increase in scores following distention in normal subjects was seen to the same degree and in the same proportion as in patients with symptoms of interstitial cystitis ( 8 of 19 symptomatic patients in this series met current diagnostic criteria for interstitial cystitis ) . Slight but significant differences were seen among sites in the bladder but not between 2 and 6-minute distention duration s. CONCLUSIONS Bladder mucosal lesions characteristically associated with irritative voiding symptoms and pelvic pain in patients diagnosed with interstitial cystitis were observed in asymptomatic women A r and omized , prospect i ve , double-blind , placebo-controlled study was conducted at 7 clinical centers on 148 patients . Patients received orally either 100 mg . pentosanpolysulfate ( a synthetic polysaccharide ) 3 times per day or a placebo . Of the patients on drug therapy 32 % showed significant improvement compared to 16 % of those on placebo ( p = 0.01 ) . This study provides a model to assess this disease quantitatively in a prospect i ve manner using a method whereby the patients globally assess their symptoms as either worse or improved by 0 , 25 , 50 , 75 or 100 % . Patients on drug therapy also experienced a significant decrease in pain and urgency ( p = 0.04 and 0.01 ) on analogue scales when compared to placebo and also more drug patients showed an average increase of more than 20 ml . in voided volume than did placebo patients ( p = 0.02 ) . All adverse effects were minor , with 7 in the drug group and 10 in the placebo group . The results support the concept that some patients with the interstitial cystitis syndrome may have abnormal bladder surface glycosaminoglycans PURPOSE We conducted a double-blind , sham controlled study to evaluate the safety , efficacy and feasibility of hyperbaric oxygenation for interstitial cystitis . MATERIAL S AND METHODS A total of 21 patients with interstitial cystitis were r and omized to 90 minutes treatment in a hyperbaric chamber pressurized with 100 % O2 to 2.4 atmosphere absolute for 30 treatments sessions or 1.3 atmosphere absolute , breathing normal air in the control group . Moderate or marked improvement in a global response assessment question naire was defined as treatment response ( primary outcomes ) . Secondary measurements included changes of pain and urgency evaluated by visual analog scales , functional bladder capacity and frequency . Changes in the O'Leary-Sant Interstitial Cystitis Index and rating of overall satisfaction with the therapeutic outcome were also reported . RESULTS There were 3 of 14 patients on verum and no control patients who were identified as responders ( p < 0.52 ) [ corrected ] At 12-month followup 3 patients ( 21.4 % ) still reported treatment response . Hyperbaric oxygenation result ed in a decrease of baseline urgency intensity from 60.2 + /- 15.0 to 49.9 + /- 35.2 mm at 3 months and decrease of pain intensity from 43.1 + /- 20.5 to 31.2 + /- 19.8 mm , respectively ( p < 0.05 ) . The Interstitial Cystitis Symptom Index score sum decreased from 25.7 to 19.9 points in patients on verum . Sham treatment did not result in improvement of the baseline parameters . CONCLUSIONS A total of 30 treatment sessions of hyperbaric oxygenation appear to be a safe , effective and feasible therapeutic approach to interstitial cystitis . In the treatment responders application of hyperbaric oxygenation result ed in a sustained decrease of interstitial cystitis symptoms with a discordant profile regarding the peak amelioration of the various interstitial cystitis symptoms compared with a normobaric , normoxic sham treatment OBJECTIVE To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate ( PPS ) compared with placebo in patients with interstitial cystitis ( IC ) . PATIENTS AND METHODS Twenty patients who fulfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study ; 10 received intravesical PPS ( 300 mg in 50 mL of 0.9 % sodium chloride ) applied twice a week for 3 months and the other 10 received a placebo .  Symptomatic relief and objective variables ( bladder capacity voiding volumes and urinary frequency ) were assessed after 3 months and the long-term outcome of those continuing treatment was determined . RESULTS Of the patients treated with PPS , four gained significant symptomatic relief compared with only two receiving placebo . Only the urodynamic bladder capacity showed a statistically significant increase in patients treated with PPS ( P = 0.047 ) . At 18 months from the start of the study , the symptoms were relieved in eight patients while still receiving PPS instillations and in four without treatment . CONCLUSIONS These results suggest that intravesical PPS is an effective option for the treatment of IC and shows that the intravesical application of PPS is a safe treatment with no important side-effects Pentosan polysulfate sodium ( PPS ) was compared with placebo for the symptomatic therapy of interstitial cystitis in a double-blind , multicenter study . A total of 110 patients were enrolled and treated for three months . In this study , overall improvement of greater than 25 percent was reported by 28 percent of the PPS-treated patients and by 13 percent of the placebo-treated patients ( p = 0.03 ) . The investigators ' overall evaluation provided similar results , 26 percent vs 11 percent in favor of PPS ( p = 0.04 ) . Improvement in pain and pressure to urinate also favored PPS over placebo and approached statistical significance ( p = 0.07 and 0.08 ) . The incidence of adverse reactions was 6 percent in the PPS-treated group and 13 percent in the placebo-treated group . All adverse reactions were minor , and treatment was discontinued by 1 patient in the PPS group and 2 in the placebo group . In this study , PPS was found to be significantly more effective than , and equally as safe as , placebo PURPOSE Present therapeutic approaches to control hypersensitive disorder of the lower urinary tract and bladder pain are clinical ly and scientifically unsatisfactory . We performed a r and omized placebo controlled study with followup after 1 and 3 months using intravesical resiniferatoxin to treat hypersensitive disorder and bladder pain . MATERIAL S AND METHODS We prospect ively r and omized 18 patients into 2 groups to receive a single dose of 10 nM. resiniferatoxin intravesically ( group 1 ) or a placebo saline solution only ( group 2 ) . All patients had at least a 6-month history of frequency , nocturia , urgency and symptoms of pelvic pain as well as no urinary tract infection within the last 3 months , functional disorders of the lower urinary tract , or other vesical or urethral pathology . Pretreatment voiding pattern and pain score were recorded . Patients were evaluated after 30 days ( primary end point ) and 3 months ( secondary end point ) . RESULTS The 2 groups were adequately homogeneous in regard to patient age , sex ratio , disease duration , voiding pattern and pain score . At the primary end point mean frequency plus or minus st and ard error of mean was decreased from 12 . 444 + /- 0.70 voids to 7.111 + /- 0.67 and nocturia from 3.777 + /- 0 . 27 to 1.666 + /- 0.16 ( p < 0.01 ) . We observed a lesser significant improvement in mean frequency in group 1 at the secondary end point to 10.444 + /- 0.94 voids ( p < 0.05 ) . No significant modification was noted in patients assigned to placebo .  Mean pain score significantly decreased in group 1 at the primary end point from 5.555 + /- 0.29 to 2.666 + /- 0.23 ( p < 0.01 ) but not at the secondary end point ( 4.777 + /- 0.66 , p > 0.05 ) . No statistically significant improvement in mean pain score was observed in placebo group 2 . During resiniferatoxin infusion 4 group 1 patients noticed a light warm or burning sensation at the suprapubic and /or urethral level . CONCLUSIONS Intravesical resiniferatoxin may significantly improve the voiding pattern and pain score in patients with hypersensitive disorder and bladder pain . Because resiniferatoxin did not cause a significant warm or burning sensation at the suprapubic and /or urethral level , it may be considered a new strategy for treating hypersensitive disorder and bladder pain . However , further studies are necessary to confirm our results and define the resiniferatoxin mechanism of action , dose and necessary treatment schedule Objectives To determine , in a double‐blind placebo‐controlled crossover study , whether l‐arginine improves the symptoms of interstitial cystitis ( IC ) , a chronic condition in which nitric oxide ( NO ) may be important , as previous open pilot studies suggested that l‐arginine reduced the pain and frequency associated with IC PURPOSE We compared intravesical bacillus Calmette-Guerin ( BCG ) to placebo instillations in patients with treatment refractory interstitial cystitis ( IC ) . MATERIAL S AND METHODS Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC , and reported at least moderate pain and frequency for a minimum of 6 months before study entry , were r and omized to 6 weekly double-blinded intravesical instillations of either BCG or placebo , and then followed for a total of 34 weeks . The primary outcome was a patient reported global response assessment at week 34 , supplemented with medications for IC during weeks 31 to 34 . Secondary outcomes included a 24-hour voiding diary , pain , urgency , vali date d IC symptom indexes and adverse events . The target sample size was 260 participants , design ed to detect a difference in response rates between placebo and BCG of 30 % and 50 % , respectively . RESULTS A total of 265 participants were r and omized and 17 ( 6 % ) patients withdrew from study . The response rates for the primary outcome were 12 % for placebo and 21 % for BCG ( p = 0.062 ) . Small improvements were observed for all secondary outcomes , some more so with BCG , but these differences were of borderline statistical significance . Although a large number of adverse events were reported in the BCG arm , there was no statistically significant difference between the treatment arms in overall adverse event rates . CONCLUSIONS Although the BCG safety profile was acceptable , the response rate for the primary outcome was low . Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive Painful bladder disease , sensory bladder disease , chronic abacterial cystitis and interstitial cystitis are ill-defined conditions of unknown etiology and pathogenesis , and , therefore , they are without any rational therapy . Pathogenetic theories concerning defects in the epithelium and /or mucous surface coat ( including glycosaminoglycans ) of the bladder , and theories concerning immunological disturbances predominate . Sodium pentosanpolysulfate ( Elmiron ) acts by substituting a defective glycosaminoglycan layer and inhibits complement reactions in inflammatory processes . We compared sodium pentosanpolysulfate versus placebo in a prospect i ve double-blind , clinical ly controlled multicenter trial of 115 patients with painful bladder disease . Two protocol s were used . Protocol A included 43 patients with clinical ly and pathologically anatomically verified interstitial cystitis ( 28 or more mast cells per mm.2 ) , and protocol B included 72 patients with a painful bladder and unspecific histological findings . The patients were r and omized to receive either sodium pentosanpolysulfate ( 200 mg . twice daily ) or placebo capsules for 4 months . Before and after the trial the patients were evaluated with symptom grading , urodynamics and cystoscopy with distension and deep bladder biopsies . The results showed no difference between the pre-trial and post-trial values in the sodium pentosanpolysulfate and placebo groups in both protocol s in regard to symptoms , urodynamic parameters , cystoscopic appearance and mast cell counts . A significant increase in the cystoscopically determined bladder capacity in the sodium pentosanpolysulfate group in protocol A was found . We conclude that no statistically or clinical ly significant effect of sodium pentosanpolysulfate was found compared to placebo in patients with painful bladder disease PURPOSE We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study , a prospect i ve cohort study of patients with interstitial cystitis . MATERIAL S AND METHODS A total of 637 eligible patients were entered into the study and followed for symptoms of pain , urgency and urinary frequency . Median followup was 31 months . RESULTS More than 90 % of patients were white women with a median age of 43 years . Using the overall pain-urgency-frequency score 7 % of participants presented with mild , 44 % with moderate and 49 % with severe symptoms . Severe urgency in 41 % of cases and severe 24-hour frequency in 41 % were more common than severe pain in 29 % . Of the patients 51 % reported nighttime frequency of 2 or more voids . Median duration of interstitial cystitis symptoms was 8 years and 68 % of participants were previously diagnosed with the condition . The 36 % of patients who withdrew from study or were lost to followup were more likely to have had more severe symptoms at baseline . Patterns of change with time suggest initial symptom improvement due to regression to the mean , and an intervention effect associated with the increased followup and care of cohort participants . Although all symptoms fluctuated , there was no evidence of significant long-term change in overall disease severity . CONCLUSIONS Our observations support the clinical observation that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time . These results provide a foundation for the design and performance of future clinical trials in interstitial cystitis using these end points in a similar patient population OBJECTIVES To compare the current recommended dose of pentosan polysulfate sodium ( PPS ) with doses two to three times higher . METHODS We evaluated three dosages ( 300 , 600 , and 900 mg ) of PPS in a r and omized , double-blind , double-dummy , parallel-group , multicenter , 32-week study . Adults ( n = 380 ) with a diagnosis of interstitial cystitis ( IC ) as determined by a positive cystoscopic examination combined with bladder pain and urgency or a history of IC symptoms for at least 6 months were enrolled . Participants completed the Patient 's Overall Rating of Symptom Index ( PORIS ) and the O'Leary-Sant Interstitial Cystitis Symptom Index ( ICSI ) at baseline ( ICSI only ) and during follow-up visits at 4 , 8 , 12 , 16 , 24 , and 32 weeks . RESULTS Mean ICSI scores improved significantly during the 32 weeks for all dosages ( baseline 11.2 , 11.9 , and 11.9 to endpoint 8.2 , 8.1 , 8.6 for 300 , 600 , and 900 mg , respectively ; P < 0.001 ) but the response to treatment was not dose dependent ( no statistically significant difference in response among the three dosages ) . At baseline , 3.2 % , 62.2 % , and 34.6 % reported mild , moderate , and severe symptoms , respectively , as assessed by the ICSI . At study end , 27.5 % , 56.9 % , and 15.7 % reported mild , moderate , and severe symptoms , respectively . The PORIS scores improved within 4 weeks with 15.8 % to 21.1 % of all patients classified as responders ( 50 % or greater improvement on PORIS ) . At 32 weeks , 49.6 % , 49.6 % , and 45.2 % of all patients were responders at a dose of 300 , 600 , and 900 mg , respectively . Most adverse events were mild and resolved without intervention . CONCLUSIONS For all three dosages of PPS , a clinical ly significant but similar response was demonstrated . The duration of therapy appears to be more important than the dosage PURPOSE Interstitial cystitis ( IC ) is a clinical condition occurring predominantly in women that is characterized by irritative voiding symptoms , including urinary frequency , urgency and pain . To our knowledge its etiology is unknown and little is known about its occurrence . We evaluated the prevalence of  IC in women in Finl and . MATERIAL S AND METHODS A total of 2,000 participants were r and omly selected from the Finnish population register . Urinary symptoms were evaluated using the vali date d O'Leary-Sant IC symptom and problem index question naire . Women with moderate or severe symptom scores ( 7 or higher ) without any urinary tract infection during the last month were invited to undergo clinical examination . RESULTS Of the 1,331 respondents 32 had moderate or severe symptoms involving a suspicion of IC , of whom 21 underwent clinical evaluation . Three women were found to have probable IC and 4 had possible IC . Thus , the prevalence of clinical ly confirmed probable IC in women was 230/100.000 ( 95 % CI 100 to 360 ) and that of possible/probable IC was 530/100.000 ( 95 % CI 140 to 910 ) . Considering the lack of information on 8 patients with urinary symptoms the corrected estimates were 300/100,000 ( 95 % CI 120 to 770 ) and 680/100,000 women ( 95 % CI 360 to 1,300 ) , respectively . CONCLUSIONS Our results based on a large and representative population , and clinical ly confirmed diagnoses indicate that IC is substantially more common than previously thought PURPOSE Interstitial cystitis is a debilitating bladder disease of unknown etiology with no cure . A recent report suggested that bacillus Calmette-Guerin ( BCG ) may be effective in the treatment of interstitial cystitis . A r and omized , prospect i ve , double-blind , placebo controlled trial to evaluate the safety and efficacy of intravesical BCG in treating interstitial cystitis was done . MATERIAL S AND METHODS Patients meeting the National Institute of Arthritis , Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis received 6 weekly instillations of Tice strain BCG or placebo .  Periodic question naires , voiding diaries and cystometrograms were obtained . A total of 30 evaluable subjects was enrolled in the study with a mean followup of 8 months ( range 6 to 13 ) . Based on an exit question naire a responder was defined as one who rated the interstitial cystitis symptoms as moderately improved or better . RESULTS A 60 % BCG response rate was noted , compared to a 27 % placebo response rate . Minimum voided volume and quality of life improved in the BCG group compared to placebo .  Adverse events were similar in each group , mostly irritative in nature , and no significant systemic events were noted . CONCLUSIONS Intravesical Tice strain BCG appears to be safe and efficacious in the treatment of interstitial cystitis . Additional studies must be performed to confirm the results of this pilot study OBJECTIVES The aims of this study were to ( 1 ) identify trends and risk factors for mycobacterial disease and ( 2 ) determine the effect of exp and ed access to isoniazid chemoprophylaxis on tuberculosis incidence . METHODS A prospect i ve observational cohort study was conducted among community-based injecting drug users ( IDUs ) ; 2960 IDUs ( 942 human immunodeficiency virus [ HIV ] seropositive ) were followed up from January 1988 to June 1994 .  Directly observed chemoprophylaxis with twice-weekly isoniazid ( 10 to 15 mg/kg ) was offered to purified protein derivative ( PPD ) tuberculin-positive ( > or = 5-mm in duration diameter in HIV-seropositive subjects and > or = 10-mm diameter in HIV-seronegative subjects ) individuals but not to those with cutaneous anergy . Overall and annual incidence rates of disease due Mycobacterium tuberculosis , Mycobacterium avium complex , and other atypical mycobacteria were estimated using Poisson regression . RESULTS HIV seropositivity was the strongest risk factor for tuberculosis , M avium complex , and other mycobacterial disease ( relative risk [ RR ] , 3.8 , 17.2 , and 6.9 , respectively ) . Median CD4 lymphocyte cell counts for the three groups of mycobacterial disease were 0.17 , 0.03 , and 0.02 x 10(9)/L ( 167/microL , 30/microL , 18/microL ) within 6 months of diagnosis ( before or after ) . Overall incidence rates of tuberculosis , M avium complex disease , and other mycobacterial disease were 1.9 , 8.8 , and 2.7 per 1000 person-years , respectively . Tuberculosis incidence peaked in 1991 at six per 1000 person-years . However , after access to directly observed preventive therapy was exp and ed for tuberculin-positive subjects , incidence fell to only one case in 1992 and zero cases for 24 months from mid-1992 to mid-1994 . During this period the number of PPD-positive patients who completed at least 26 weeks of therapy ( or were still receiving isoniazid ) more than tripled ( from 21 to 70 ) . None of the 12 patients with tuberculosis diagnosed during follow-up had received any preventive therapy . In addition , no tuberculosis developed among participants with cutaneous anergy . Calendar trends in risk for M avium complex and tuberculosis diverged after exp and ed access to isoniazid prophylaxis . Compared with 1988 - 1989 , risk of M avium complex increased sevenfold . Tuberculosis risk fell 83 % from the peak risk in 1990 - 1991 . CONCLUSIONS Exp and ed access to directly observed isonazid therapy for tuberculin-positive IDUs with and without HIV infection was associated with an 83 % drop in tuberculosis incidence , while in the same period M avium complex incidence significantly increased . These population -based data are consistent with those obtained from clinical trials of isoniazid prophylaxis and were obtained without offering chemoprophylaxis to HIV-infected patients with cutaneous energy Health status measures are being used with increasing frequency in clinical research . Up to now the emphasis has been on the reliability and validity of these measures . Less attention has been given to the sensitivity of these measures for detecting clinical change . As health status measures are applied more frequently in the clinical setting , we need a useful way to estimate and communicate whether particular changes in health status are clinical ly relevant . This report considers effect sizes as a useful way to interpret changes in health status . Effect sizes are defined as the mean change found in a variable divided by the st and ard deviation of that variable . Effect sizes are used to translate “ the before and after changes ” in a “ one group ” situation into a st and ard unit of measurement that will provide a clearer underst and ing of health status results . The utility of effect sizes is demonstrated from four different perspectives using three health status data sets derived from arthritis population s administered the Arthritis Impact Measurement Scales ( AIMS ) . The first perspective shows how general and instrument-specific benchmarks can be developed and how they can be used to translate the meaning of clinical change . The second perspective shows how effect sizes can be used to compare traditional clinical measures with health status measures in a st and ard clinical drug trial . The third application demonstrates the use of effect sizes when comparing two drugs tested in separate drug trials and shows how they can facilitate this type of comparison . Finally , our health status results show how effect sizes can supplement st and ard statistical testing to give a more complete and clinical ly relevant picture of health status change . We conclude that effect sizes are an important tool that will facilitate the use and interpretation of health status measures in clinical research in arthritis and other chronic diseases RATIONALE Rifabutin was recommended in place of rifampin during treatment of HIV-related tuberculosis ( TB ) to facilitate concomitant potent antiretroviral therapy , but this approach has not been evaluated in a prospect i ve study . OBJECTIVE To evaluate the activity of intermittent rifabutin-based therapy . METHODS Patients with culture-confirmed TB were treated under direct supervision with 2 mo of rifabutin , isoniazid , pyrazinamide , and ethambutol ( given daily , thrice-weekly , or twice-weekly per the local tuberculosis control program ) , followed by 4 mo of twice-weekly rifabutin plus isoniazid . MEASUREMENTS Culture-positive treatment failure or relapse . MAIN RESULTS A total of 169 eligible patients were enrolled . Most had advanced HIV disease ; the median CD4 cell count and HIV-RNA level were 90 cells/mm3 ( interquartile range , 35 - 175 ) and 5.3 log10 copies/ml ( interquartile range , 4.8 - 5.7 ) , respectively . Nine ( 5.3 % ) patients had culture-positive treatment failure ( n = 3 ) or relapse ( n = 6 ) . Eight of these nine ( 89 % ) cases had isolates with acquired rifamycin resistance . Treatment failure or relapse was associated with baseline CD4 lymphocyte count , being 12.3 % ( 9/73 ; 95 % confidence interval , 6.5 - 22.0 % ) among patients with CD4 < 100 cells/mm3 versus 0 % ( 0/65 ; 95 % confidence interval , 0.0 - 4.5 % ) among those with higher CD4 lymphocyte counts ( p < 0.01 ) . One hundred thirty-seven ( 81 % ) patients received antiretroviral therapy during TB treatment . Adverse events were common , but only two patients ( 1 % ) permanently discontinued study drugs . CONCLUSIONS Intermittent rifabutin-based therapy for HIV-related TB was well tolerated , but there was a high risk of treatment failure or relapse with acquired rifamycin resistance among patients with low CD4 lymphocyte counts PURPOSE We conducted a prospect i ve , double-blind study with a crossover design of intravesical bacillus Calmette-Guerin ( BCG ) and dimethyl sulfoxide to determine whether patients with classic and nonulcer interstitial cystitis , respectively , might benefit from either regimen . MATERIAL S AND METHODS A total of 21 patients , including 11 with classic and 10 with nonulcer interstitial cystitis , r and omly underwent treatments with intravesical BCG or dimethyl sulfoxide and , if not improved , were treated with the other substance after a washout period . All 21 patients were evaluated with symptom question naires , including a visual analog pain scale and voiding diaries . RESULTS Regardless of regimen , there was no improvement in maximal functional capacity . There was a reduction in urinary frequency following dimethyl sulfoxide treatment but only in the classic subtype ( p < 0.05 ) , whereas no reduction was seen following BCG in either subtype . A substantial pain decrease was noted in classic ( p < 0.05 ) as well as nonulcer ( p < 0.05 ) interstitial cystitis following dimethyl sulfoxide . CONCLUSIONS Intravesical BCG has been presented as a promising new option for treatment of interstitial cystitis . We failed to demonstrate benefit from this treatment . Dimethyl sulfoxide had no positive effect on maximal functional capacity but result ed in a significant reduction in pain and urinary frequency , although only in patients with classic interstitial cystitis PURPOSE Interstitial cystitis is a chronic disease of unknown etiology characterized by bladder pain , urgency and frequency . Although a single microbe has not been implicated as a cause of interstitial cystitis , several groups noted various organisms in the urine of some women with interstitial cystitis and some patients reported that antibiotics decrease symptoms . Consequently we performed a prospect i ve , r and omized , double-blinded , placebo controlled pilot study of sequential oral antibiotics . MATERIAL S AND METHODS We r and omized 50 patients with interstitial cystitis to receive 18 weeks of placebo or antibiotics , including rifampin plus a sequence of doxycycline , erythromycin , metronidazole , clindamycin , amoxicillin and ciprofloxacin for 3 weeks each . RESULTS Intent to treat analysis demonstrated that 12 of 25 patients ( 48 % ) in the antibiotic and 6 of 25 ( 24 % ) in the placebo group reported overall improvement ( p = 0.14 ) , while 10 and 5 , respectively , noticed improvement in pain and urgency ( p = 0.22 ) . In the antibiotic group 20 participants ( 80 % ) had adverse effects compared with 10 ( 40 % ) in the placebo group ( p = 0.009 ) . CONCLUSIONS Our findings suggest that these antibiotics alone or in combination may sometimes be associated with decreased symptoms in some patients but they do not represent a major advance in therapy for interstitial cystitis PURPOSE We assess the efficacy of intravesical administration of oxybutynin chloride in patients with interstitial cystitis . MATERIAL S AND METHODS The study included 36 women with a mean age of 45 years with a diagnosis of interstitial cystitis . Patients were treated with gradual intravesical instillation of saline oxybutynin solution ( oxybutynin group ) or gradual filling of simple saline ( control group ) . Evaluation parameters consisted of symptom problem index , voids per day , volume per void , functional bladder capacity , volume at first sensation , cystometric bladder capacity and cystometric volume at first sensation . RESULTS Statistically significant improvement of all evaluated parameters was found in both groups . When comparing the outcomes statistically significant improvement of parameters favored the oxybutynin group . CONCLUSIONS Bladder training alone produces a satisfactory result by gradually exp and ing the bladder , and an additional statistically significant improvement is evident with intravesical oxybutynin Objective To evaluate the efficacy of oral cimetidine as a treatment for  painful bladder disease ( PBD , variously described as a ‘ symptom complex ’ of suprapubic pain , frequency , dysuria and nocturia in the absence of overt urine infection ) by assessing symptom relief and histological changes in the bladder wall tissue components , compared with placebo PURPOSE Nitric oxide synthase activity is decreased in the urine of patients with interstitial cystitis compared to the urine of controls . In a preliminary trial oral L-arginine , the substrate for nitric oxide synthase , increased urinary nitric oxide synthase activity and improved interstitial cystitis symptoms . This r and omized , double-blind , placebo controlled study further investigates the efficacy of L-arginine treatment for interstitial cystitis . MATERIAL S AND METHODS A total of 53 interstitial cystitis patients were assigned to receive daily 1,500 mg . L-arginine or placebo orally for 3 months . Interstitial cystitis symptoms were assessed by interviews at 2 weeks , and 1 , 2 and 3 months . RESULTS The trial was completed by 21 of 27 patients in the L-arginine group and 25 of 26 in the placebo group . Using per protocol analysis 29 % ( 6 of 21 patients ) in the L-arginine group and 8 % ( 2 of 25 ) in the placebo group were clinical ly improved by the end of the trial ( p = 0.07 ) . A Likert scale showed greater global improvement in the L-arginine group ( 48 % , 10 of 21 ) compared to the placebo group ( 24 % , 6 of 25 ) at 3 months ( p = 0.05 ) with a decrease in pain intensity ( p = 0.04 ) , and tendency toward improvement in urgency ( p = 0.06 ) and frequency of pain ( p = 0.09 ) . Using an intention to treat approach to analysis there were no differences between groups . CONCLUSIONS Oral L-arginine ( 1,500 mg . daily ) may decrease pain and urgency in a subset of interstitial cystitis patients To evaluate the effectiveness of dimethyl sulfoxide in the treatment of patients with biopsies suggestive of interstitial cystitis , 33 patients underwent a controlled crossover trial . Patients were allocated r and omly to receive 50 per cent dimethyl sulfoxide or placebo ( saline ) . The medication was administered intravesically every 2 weeks for 2 sessions of 4 treatments each . Response was assessed urodynamically and symptomatically . Thirty women and 3 men ( mean age 48 years and mean duration of symptoms 5.5 years ) were entered into the study . No significant side effects to dimethyl sulfoxide were noted . When assessed subjectively , 53 per cent of dimethyl sulfoxide treated patients were markedly improved compared to 18 per cent of the placebo treated patients . Of the dimethyl sulfoxide group 93 per cent had objective improvement versus 35 per cent of the placebo group . Thus , dimethyl sulfoxide proved to be superior to placebo in the objective and subjective improvement of patients with interstitial cystitis
target: Current evidence also suggests the efficacy of  dimethyl sulfoxide and amitryptyline therapy .
  Hydroxyzine , intravesical bacille Calmette-Guérin  , and  resiniferatoxin therapy  failed to demonstrate efficacy , but evidence was inconclusive owing to method ological limitations .
  Pentosan polysulfate may be modestly beneficial for symptoms of PBS/IC .
  There is insufficient evidence for other pharmacologic treatments .
background: BACKGROUND More than 180 different types of therapy have been used in the treatment and management of  painful bladder syndrome/interstitial cystitis ( PBS/IC ) , yet evidence from clinical trials remains inconclusive .
  This study aim ed to evaluate the efficacy of pharmacologic approaches to PBS/IC , to quantify the effect size from r and omized controlled trials , and to begin to inform a clinical consensus of treatment efficacy for PBS/IC .