John B. Forrest

AUA Guideline for the Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome

PURPOSE To provide a clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS A systematic review of the literature using the MEDLINE® database (search dates 1/1/83-7/22/09) was conducted to identify peer reviewed publications relevant to the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Insufficient evidence-based data were retrieved regarding diagnosis and, therefore, this portion of the Guideline is based on Clinical Principles and Expert Opinion statements. The review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. These publications were used to create the majority of the treatment portion of the Guideline. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). Additional treatment information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. See text and algorithm for definitions, and detailed diagnostic management, and treatment frameworks. RESULTS The evidence-based guideline statements are provided for diagnosis and overall management of interstitial cystitis/bladder pain syndrome as well as for various treatments. The panel identified first through sixth line treatments as well as developed guideline statements on treatments that should not be offered. CONCLUSIONS Interstitial cystitis/bladder pain syndrome is best identified and managed through use of a logical algorithm such as is presented in this Guideline. In the algorithm the panel identifies an overall management strategy for the interstitial cystitis/bladder pain syndrome patient. Diagnosis and treatment methodologies can be expected to change as the evidence base grows in the future.

AUA Best Practice Statement for the Prevention of Deep Vein Thrombosis in Patients Undergoing Urologic Surgery

Summary of VTE prophylaxis recommendations Level of risk Prophylactic treatmentLow Risk ● No prophylaxis other than early ambulationModerate Risk ● Heparin 5000 units every 12 hours subcutaneous starting after surgery ● OR *Enoxaparin 40 mg. (Cr Cl 30 ml/min. 30 mg.) subcutaneous daily ● OR Pneumatic compression device if risk of bleeding is highHigh Risk ● Heparin 5000 units every 8 hours subcutaneous starting after surgery ● OR *Enoxaparin 40 mg. (Cr Cl 30 ml/min. 30 mg.) subcutaneous daily ● OR Pneumatic compression device if risk of bleeding is highVery High Risk ● *Enoxaparin 40 mg. (Cr Cl 30 ml/min. 30 mg.) subcutaneous daily and adjuvant pneumatic compression device, or ● Heparin 5000 units every 8 hours subcutaneous starting after surgery and adjuvant pneumatic compression device* Guidelines and Cautions for Enoxaparin Use ● In patients with a body weight 150 Kg. consider increasing prophylaxis dose of Enoxaparin to 40 mg. subcutaneous every 12 hours. ● Withhold Enoxaparin generally for at least 2 to 3 days after major trauma, and then only consider use after review of current patient condition and risk benefit ratio.

Pentosan Polysulfate Sodium for Treatment of Interstitial Cystitis/Bladder Pain Syndrome: Insights from a Randomized, Double-Blind, Placebo Controlled Study

PURPOSE We compared the efficacy and safety of the currently recommended dose of pentosan polysulfate sodium with a third of the daily dose and with placebo. MATERIALS AND METHODS In this multicenter, double-blind, randomized, placebo controlled study 368 adults with interstitial cystitis/bladder pain syndrome, defined as an ICSI total score of 8 or greater and a score of greater than 0 on the 4 ICSI component items, received pentosan polysulfate sodium 100 mg once daily or 3 times daily, or matching placebo for 24 weeks. Study eligibility was not based on cystoscopy findings. ICSI was administered at baseline, and at weeks 4, 8, 12, 18 and 24. Unblinded interim analysis performed at 6 years with 54% of the target number of 645 patients enrolled resulted in early study termination. RESULTS There was no statistically significant difference between the pentosan polysulfate sodium group and the placebo group or between the 2 pentosan polysulfate sodium groups for the primary end point, defined as responder achieving a 30% or greater reduction from the baseline ICSI total score at study end. This primary end point was achieved by 48 of 118 patients (40.7%) in the placebo group, and by 51 of 128 (39.8%) and 52 of 122 (42.6%) in the pentosan polysulfate sodium 100 mg once daily and 3 times daily groups, respectively. Pentosan polysulfate sodium was well tolerated with a similar percent of patients (range 10.2% to 13.3%) across the groups discontinuing due to an adverse event. CONCLUSIONS Results of this study in a broad population of patients with symptoms consistent with interstitial cystitis revealed no treatment effect vs placebo for pentosan polysulfate sodium at the currently established dose or at a third of the daily dose.

Cyclosporine A for refractory interstitial cystitis/bladder pain syndrome: experience of 3 tertiary centers.

PURPOSE Cyclosporine A is a fifth-tier treatment option in the American Urological Association guidelines for interstitial cystitis/bladder pain syndrome. It was more effective than pentosanpolysulfate in a Finnish trial, but experience elsewhere is limited. Some centers use cyclosporine A off label for carefully selected patients but the number of patients in each center is small. We performed a retrospective review combining data from 3 tertiary centers that focus on interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS Charts were reviewed for patients with interstitial cystitis/bladder pain syndrome who received cyclosporine A. Response was defined as markedly improved on the 7-point global response assessment (2 centers) or as at least a 50% decrease in Interstitial Cystitis Symptom Index score (1 center). RESULTS The study included 14 men and 30 women. Mean patient age was 55.5 years (range 27 to 75) and mean followup was 20.8 months (range 3 to 81). A total of 34 patients had Hunner lesions. Of these patients 29 (85%) responded but 6 eventually stopped cyclosporine A for adverse events, resulting in a success rate of 68% (23 of 34) for patients with Hunner lesions. In contrast, only 3 of 10 patients without Hunner lesions responded (30%). For all responders, the response occurred within 4 months. CONCLUSIONS Cyclosporine A had a high success rate for patients with Hunner lesions in whom more conservative options, including endoscopic treatment, had failed. The success rate was low for patients without Hunner lesions. A 3 to 4-month trial is sufficient time to assess response. Adverse events were common and led to discontinuation of cyclosporine A for some patients. Close monitoring is needed, especially for blood pressure and renal function.

Clinical practice guidelines to inform evidence-based clinical practice.

BackgroundWith the volume of medical research currently published, any one practitioner cannot independently review the literature to determine best evidence-based medical care. Additionally, non-specialists usually do not have the experience to know best practice for all of the frequent clinical circumstances for which there is no good evidence. Clinical practice guidelines (CPGs) help clinicians to address these problems because they are systematically created documents that summarize knowledge and provide guidance to assist in delivering high-quality medicine. They aim to improve health care by identifying evidence that supports the best clinical care and making clear which practices appear to be ineffective.MethodsNon-structured literature review.ResultsCPGs combine evidence-based medicine (on topics for which evidence exists) with expert opinion (on topics for which there is no evidence). The optimal CPG applies structured and transparent judgments, from an unbiased and diverse panel which includes both clinical experts and non-physicians, to a systematic evidence review. It includes decisions in areas in which clinical data are both available and unavailable. The resulting guideline statements should be clearly linked to the quality of the available evidence and the target patient(s) should be clearly defined, so that the reader can assess strength and applicability of the statements to an individual patient.ConclusionsThe application of high-quality CPGs improves patient care, but all too often CPGs are not used to the greatest advantage because of inadequate dissemination and incorporation into practice. This article provides an overview of CPGs, focusing on their justification, creation, improvement, and use.

The Relationship Among Symptoms, Sleep Disturbances and Quality of Life in Patients With Interstitial Cystitis

PURPOSE We conducted a retrospective analysis to determine associations among symptoms, sleep disturbances and quality of life in responder and nonresponder groups of patients with interstitial cystitis. MATERIALS AND METHODS Patients in a multidose pentosan polysulfate sodium clinical trial with a diagnosis of interstitial cystitis who were randomized to 300 mg pentosan polysulfate sodium per day (128) completed the Interstitial Cystitis Symptom Index, an adapted Medical Outcomes Study Sleep scale and the Medical Outcomes Study Short Form-12 Health Survey at baseline, and at weeks 8, 16, 24 and 32. Responders were defined as those achieving a 30% or greater reduction in Interstitial Cystitis Symptom Index score from baseline to study end point (week 32 or last observation carried forward). RESULTS A positive correlation at baseline was observed between sleep scores and Short Form-12 physical and mental components (r = 0.43 and 0.37, respectively, p <0.0001). Patients showed statistically significant improvement in Interstitial Cystitis Symptom Index and sleep scores by week 32. Responders (48, 43%) had a mean change in sleep score of 11.8 +/- 22.4 while nonresponders (64, 57%) had a mean change of 1.6 +/- 15.7 (p = 0.0055 between groups). The reduction in Interstitial Cystitis Symptom Index score correlated with improvement in sleep score from baseline to study end point (r = -0.33, p = 0.0003). At the study end point responders demonstrated a significant improvement in the Short Form-12 physical component compared with baseline (p <0.0001). CONCLUSIONS Reduction in interstitial cystitis symptoms may be associated with patient reported improvement in sleep and quality of life.

First dose efficacy of alfuzosin once daily in men with symptomatic benign prostatic hyperplasia

OBJECTIVES To evaluate the onset of action of alfuzosin once daily (OD) as determined by uroflowmetry early after initial dosing. Alfuzosin OD is an extended-release formulation of a uroselective, alpha1-adrenoreceptor-blocking agent (alpha-blocker) used in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS This was a randomized, placebo-controlled, two-way Latin square crossover study. Forty-nine patients were selected for this study on the basis of their symptomatic improvement during previous treatment with alpha-blockers and significant decreases in urinary flow rate when that treatment was withdrawn. RESULTS Our analysis showed that significant increases in the maximal urinary flow rate (Qmax) in 34 assessable patients occurred as soon as 8 hours after the initial dose of medication and persisted for at least 4 days. The DeltaQmax for alfuzosin 10 mg OD was 3.2 mL/s and for placebo it was 1.1 mL/s. The difference of means for the assessable population was 2.1 (95% confidence interval 0.8 to 3.4, P = 0.002). The overall incidence of adverse events was low. Only dizziness, experienced by 3 patients treated with alfuzosin compared with 1 patient treated with placebo, appeared to be related to the study drug. CONCLUSIONS Together, our findings suggest that alfuzosin OD exhibits a urodynamically measurable effect on bladder outlet obstruction due to benign prostatic hyperplasia in men with lower urinary tract symptoms within hours of the first administration.

810 CYCLOSPORINE A FOR REFRACTORY INTERSTITIAL CYSTITIS: EXPERIENCE OF TWO TERTIARY CENTERS

cells from cystitis model only express the ER , with co-locating with androgen receptor by immunofluorescence. CONCLUSIONS: Our data suggest that estrogen receptor is expressed in bladder tissue from IC patients. Estrogen has a role in mast cell activation. ER may mediate the mast cell function in cystitis development. In summary, estrogen may be essential to the pathogenesis of interstitial cystitis.