Real-World Effectiveness of Preventive Pharmacological Therapy in Patients With Urolithiasis: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Data supporting the efficacy of preventive pharmacological therapy (PPT) to reduce urolithiasis recurrence are based on clinical trials with composite outcomes that incorporate imaging findings and have uncertain clinical significance. This study evaluated whether the use of PPT leads to fewer symptomatic stone events. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Medicare enrollees with urolithiasis who completed 24-hour urine collections that revealed hypercalciuria, hypocitraturia, low urine pH, or hyperuricosuria. EXPOSURE: PPT (thiazide diuretics for hypercalciuria, alkali for hypocitraturia or low urine pH, or uric acid lowering drugs for hyperuricosuria) categorized as (1) adherent to guideline-concordant PPT, (2) nonadherent to guideline-concordant PPT, or (3) untreated. OUTCOME: Symptomatic stone event occurrence (emergency department [ED] visit or hospitalization for urolithiasis or stone-directed surgery). ANALYTICAL APPROACH: Cox proportional hazards regression. RESULTS: Among 13,942 patients, 31.0% were prescribed PPT. Compared with no treatment, concordant/adherent PPT use was associated with a significantly lower hazard of symptomatic stone events for patients with hypercalciuria (HR, 0.736 [95% CI, 0.593-0.915]) and low urine pH (HR, 0.804 [95% CI, 0.650-0.996]) but not for patients with hypocitraturia or hyperuricosuria. These associations were largely driven by significantly lower rates of ED visits after initiating PPT among the concordant/adherent group versus untreated patients. Patients with hypercalciuria had adjusted 2-year predicted probabilities of a visit of 3.8% [95% CI, 2.5%-5.2%%] and 6.9% [95% CI, 6.0%-7.7%] for the concordant/adherent PPT and no-treatment groups, respectively. Among patients with low urine pH, these probabilities were 4.3% (95% CI, 2.9%-5.7%) and 7.3% (95% CI, 6.5%-8.0%) for the concordant/adherent PPT and no-treatment groups, respectively. LIMITATIONS: Potential bias from the possibility that patients prescribed PPT had more severe disease than untreated patients. CONCLUSIONS: Patients with urolithiasis and hypercalciuria who were adherent to treatment with thiazide diuretics as well as those with low urine pH adherent to prescribed alkali therapy had fewer symptomatic stone events than untreated patients. PLAIN-LANGUAGE SUMMARY: Despite multiple clinical trials demonstrating the efficacy of thiazide diuretics and alkali for secondary prevention of kidney stones, they are infrequently prescribed due in part to a lack of data about their effectiveness in real-world settings. We analyzed medical claims from older adults with kidney stones for whom urine chemistry data were available. We found that patients who took prescribed thiazide diuretics for elevated urine calcium levels or alkali for low urinary pH were less likely to experience symptomatic stone recurrences than untreated patients. This benefit was expressed as lower rates of emergency department visits after initiating therapy. Our findings should inform the prescription of and adherence to treatment with thiazide diuretics and alkali for the prevention of recurrent kidney stones.

Understanding the Barriers to Preventive Pharmacological Therapy Use in Older Patients With Urinary Stone Disease.

INTRODUCTION: Despite compelling clinical trial evidence and professional society guideline recommendations, prescription rates of preventative pharmacological therapy (PPT) for urinary stone disease are low. We sought to understand how patient- and clinician-level factors contribute to the decision to prescribe PPT after an index stone event. METHODS: We identified Medicare beneficiaries with urinary stone disease who had a 24-hour urine collection processed by a central laboratory. Among the subset with a urine chemistry abnormality (ie, hypercalciuria, hypocitraturia, hyperuricosuria, or low urine pH), we determined whether PPT was prescribed within 6 months of their collection. After assigning patients to the clinicians who ordered their collection, we fit multilevel models to determine how much of the variation in PPT prescription was attributable to patient vs clinician factors. RESULTS: Of the 11,563 patients meeting inclusion criteria, 33.6% were prescribed PPT. There was nearly sevenfold variation between the treating clinician with the lowest prescription rate (11%) and the one with the highest (75%). Nineteen percent of this variation was attributable to clinician factors. After accounting for measured patient differences and clinician volume, patients had twice the odds of being prescribed PPT if they were treated by a nephrologist (odds ratio [OR], 2.15; 95% CI, 1.79-2.57) or a primary care physician (OR, 1.78; 95% CI, 1.22-2.58) compared to being treated by a urologist. CONCLUSIONS: These findings suggest that the type of clinician whom a patient sees for his stone care determines, to a large extent, whether PPT will be prescribed.

Comparison of Class-Specific Side Effects Across Preventative Pharmacologic Therapies for Kidney Stone Disease.

INTRODUCTION: Clinical guidelines recommend monitoring for metabolic derangements while on preventive pharmacologic therapy for kidney stone disease. The study objective was to compare the frequency of side effects among patients receiving alkali citrate, thiazides, and allopurinol. METHODS: Using claims data from working-age adults with kidney stone disease (2008-2019), we identified those with a new prescription for alkali citrate, thiazide, or allopurinol within 12 months after their index stone-related diagnosis or procedure. We fit multivariable logistic regression models, adjusting for cohort characteristics like comorbid illness and medication adherence, to estimate 2-year measured frequencies of claims-based outcomes of acute kidney injury, falls/hip fracture, gastritis, abnormal liver function tests/hepatitis, hypercalcemia, hyperglycemia/diabetes, hyperkalemia, hypokalemia, hyponatremia, and hypotension. RESULTS: Our cohort consisted of 1776 (34%), 2767 (53%), and 677 (13%) patients prescribed alkali citrate, thiazides, or allopurinol, respectively. Comparing unadjusted rates of incident diagnoses, thiazides compared to alkali citrate and allopurinol were associated with the highest rates of hypercalcemia (2.3% vs 1.5% and 1.0%, respectively, P = .04), hypokalemia (6% vs 3% and 2%, respectively, P < .01), and hyperglycemia/diabetes (17% vs 11% and 16%, respectively, P < .01). No other differences with the other outcomes were significant. In adjusted analyses, compared to alkali citrate, thiazides were associated with a higher odds of hypokalemia (OR=2.01, 95% CI 1.44-2.81) and hyperglycemia/diabetes (OR=1.52, 95% CI 1.26-1.83), while allopurinol was associated with a higher odds of hyperglycemia/diabetes (OR=1.34, 95% CI 1.02-1.75). CONCLUSIONS: These data provide evidence to support clinical guidelines that recommend periodic serum testing to assess for adverse effects from preventive pharmacologic therapy.

Associations Between Provider Specialty and Use of Follow-up Testing Among Patients on Preventive Pharmacological Therapy for Urinary Stone Disease.

INTRODUCTION: The AUA Medical Management of Kidney Stones guideline outlines recommendations on follow-up testing for patients prescribed preventive pharmacological therapy. We evaluated adherence to these recommendations by provider specialty. METHODS: Using claims data from working-age adults with urinary stone disease (2008-2019), we identified patients prescribed a preventive pharmacological therapy agent (a thiazide diuretic, alkali citrate therapy, allopurinol, or a combination thereof) and the specialty of the prescribing physician (urology, nephrology, and general practice). Next, we identified patients who completed a 24-hour urine collection prior to their prescription fill. We then measured adherence to 3 recommendations outlined in the AUA guideline. Finally, we fit multivariable logistic regression models evaluating associations between prescribing provider specialty and adherence to recommended follow-up testing. RESULTS: Among 2,600 patients meeting study criteria, 1,523 (59%) adhered to ≥1 follow-up testing recommendation, with a significant increase over the study period. Nephrologists had higher odds of adherence to ≥1 follow-up test compared to urologists (odds ratio, 1.52; 95% confidence interval, 1.19-1.94; P < .01). Significant differences in adherence to the 3 individual guideline recommendations were also observed by specialty. CONCLUSIONS: Following initiation of preventive pharmacological therapy, adherence to guideline-recommended follow-up testing was low overall. There exist meaningful specialty-specific differences in the use of this testing.

Potential for Urolithiasis-related Research Using the Novel Medicare-Litholink Database.

INTRODUCTION: To overcome the data availability hurdle of observational studies on urolithiasis, we linked claims data with 24-hour urine results from a large cohort of adults with urolithiasis. This database contains the sample size, clinical granularity, and long-term follow-up needed to study urolithiasis on a broad level. METHODS: We identified adults enrolled in Medicare with urolithiasis who had a 24-hour urine collection processed by Litholink (2011 to 2016). We created a linkage of their collections results and paid Medicare claims. We characterized them across a variety of sociodemographic and clinical factors. We measured frequencies of prescription fills for medications used to prevent stone recurrence, as well as frequencies of symptomatic stone events, among these patients. RESULTS: In total, there were 11,460 patients who performed 18,922 urine collections in the Medicare-Litholink cohort. The majority were male (57%), White (93.2%), and lived in a metropolitan county (51.5%). Results from their initial urine collections revealed abnormal pH to be the most common abnormality (77.2%), followed by low volume (63.8%), hypocitraturia (45.6%), hyperoxaluria (31.1%), hypercalciuria (28.4%), and hyperuricosuria (11.8%). Seventeen percent had prescription fills for alkali monotherapy, and 7.6% had prescription fills for thiazide diuretic monotherapy. Symptomatic stone events occurred in 23.1% at 2 years of follow-up. CONCLUSIONS: We successfully linked Medicare claims with results from 24-hour urine collections performed by adults that were processed by Litholink. The resulting database is a unique resource for future studies on the clinical effectiveness of stone prevention strategies and urolithiasis more broadly.

Financial Toxicity of Nephrolithiasis: The First Assessment of the Economic Stresses of Kidney Stone Treatment.

OBJECTIVE: To investigate the financial toxicity (FT) related to kidney stone treatment. METHODS: We performed a cross-sectional cohort study with multi-institutional in-person and online cohorts of stone formers.  Participants were surveyed using the validated COST tool (COmprehensive Score for financial Toxicity). The maximum score is 44 and lower scores indicate increased FT. "Moderate FT" was defined by COST scores between 25 and 14 points and "severe FT" for scores <14. Descriptive statistics, X2 tests, T tests, Spearman correlation, and logistic regression were performed using SPSS v28. RESULTS: Two hundred and forty-one participants were surveyed, including 126 in-person participants and 115 online. A total of 60% of participants reported at least moderate FT (COST score <26) and 26% reported severe FT (COST score <14). Patients who reported moderate to severe FT were younger than those with low FT by a median difference of 8 years (95%CI = 4, 12). There was a significant correlation between out-of-pocket expense and COST scores, such that as out-of-pocket expenses increased, COST scores decreased, (Spearman's rho =-0.406, P = <.001). Participants with moderate to severe FT tended to miss more workdays (P = .002), and their caretakers tended to miss more workdays (P = .007) due to their stone disease. CONCLUSION: Most participants reported moderate to severe FT. As prior studies have shown that patients with "moderate FT" employ cost-coping strategies (i.e., medication rationing) and those with "severe FT" have worse health outcomes, urologists need to be sensitive to the financial burdens of treatment experienced by such patients undergoing kidney stone treatment.

Associations of Obesity and Neighborhood Factors With Urinary Stone Parameters.

INTRODUCTION: Obesity is associated with kidney stone disease, but it is unknown whether this association differs by SES. This study assessed the extent to which obesity and neighborhood characteristics jointly contribute to urinary risk factors for kidney stone disease. METHODS: This was a retrospective analysis of adult patients with kidney stone disease evaluated with 24-hour urine collection (2001-2020). Neighborhood-level socioeconomic data were obtained for a principal component analysis, which identified 3 linearly independent factors. Associations between these factors and 24-hour urine measurements were assessed using linear regression as well as groupings of 24-hour urine results using multivariable logistic regression. Finally, multiplicative interactions were assessed testing effect modification by obesity, and analyses stratified by obesity were performed. Analyses were performed in 2021. RESULTS: In total, 1,264 patients met the study criteria. Factors retained on principal component analysis represented SES, family structure, and housing characteristics. On linear regression, there was a significant inverse correlation between SES and 24-hour urine sodium (p=0.0002). On multivariable logistic regression, obesity was associated with increased odds of multiple stone risk factors (OR=1.61; 95% CI=1.15, 2.26) and multiple dietary factors (OR=1.33; 95% CI=1.06, 1.67). No significant and consistent multiplicative interactions were observed between obesity and quartiles of neighborhood SES, family structure, or housing characteristics. CONCLUSIONS: Obesity was associated with the presence of multiple stone risk factors and multiple dietary factors; however, the strength and magnitude of these associations did not vary significantly by neighborhood SES, family structure, and housing characteristics.

Comparison of Empiric Preventative Pharmacologic Therapies on Stone Recurrence Among Patients with Kidney Stone Disease.

OBJECTIVE: To compare the frequency of stone-related events among patients receiving thiazides, alkali citrate, and allopurinol without prior 24 h urine testing.  It is unknown whether 1 preventative pharmacological therapy (PPT) medication class is more beneficial for reducing kidney stone recurrence when prescribed empirically. MATERIALS AND METHODS: Using medical claims data from working-age adults with kidney stone disease diagnoses (2008-2018), we identified those prescribed thiazides, alkali citrate, or allopurinol. We excluded those who received 24 h urine testing prior to initiating PPT and those with less than 3 years of follow-up. We fit multivariable regression models to estimate the association between the occurrence of a stone-related event (emergency department visit, hospitalization, or surgery for stones) and PPT medication class. RESULTS: Our cohort consisted of 1834 (60%), 654 (21%), and 558 (18%) patients empirically prescribed thiazides, alkali citrate, or allopurinol, respectively. After controlling for patient factors including medication adherence and concomitant conditions that increase recurrence risk, the adjusted rate of any stone event was lowest for the thiazide group (14.8%) compared to alkali citrate (20.4%) or allopurinol (20.4%) (each P < .001). Thiazides, compared to allopurinol, were associated with 32% lower odds of a subsequent stone event by 3 years (OR 0.68, 95% CI 0.53-0.88). No such association was observed when comparing alkali citrate to allopurinol (OR 1.00, 95% CI 0.75-1.34). CONCLUSION: Empiric PPT with thiazides is associated with significantly lower odds of subsequent stone-related events. When 24 h urine testing is unavailable, thiazides may be preferred over alkali citrate or allopurinol for empiric PPT.

Comparison of Selective vs Empiric Pharmacologic Preventive Therapy of Kidney Stone Recurrence With High-Risk Features.

OBJECTIVE: To compare the frequency of stone-related events among subgroups of high-risk patients with and without 24-hour urine testing before preventive pharmacological therapy (PPT) prescription. While recent studies show, on average, no benefit to a selective approach to PPT for urinary stone disease (USD), there could be heterogeneity in treatment effect across patient subgroups. MATERIALS AND METHODS: Using medical claims data from working-age adults and their dependents with USD (2008-2019), we identified those with a prescription fill for a PPT agent (thiazide diuretic, alkali therapy, or allopurinol). We then stratified patients into subgroups based on the presence of a concomitant condition or other factors that raised their stone recurrence risk. Finally, we fit multivariable regression models to measure the association between stone-related events (emergency department visit, hospitalization, and surgery) and 24-hour urine testing before PPT prescription by high-risk subgroup. RESULTS: Overall, 8369 adults with USD had a concomitant condition that raised their recurrence risk. Thirty-three percent (n = 2722) of these patients were prescribed PPT after 24-hour urine testing (median follow-up, 590 days), and 67% (n = 5647) received PPT empirically (median follow-up, 533 days). Compared to patients treated empirically, those with a history of recurrent USD had a significantly lower hazard of a subsequent stone-related event if they received selective PPT (hazard ratio, 0.83; 95% confidence interval, 0.71-0.96). No significant associations were noted for selective PPT in the other high-risk subgroups. CONCLUSION: Patients with a history of recurrent USD benefit from PPT when guided by findings from 24-hour urine testing.

Clinical and radiographic outcomes following salvage intervention for ureteropelvic junction obstruction

ABSTRACT Purpose: We aimed to assess failure rates of salvage interventions and changes in split kidney function (SKF) following failed primary repair of ureteropelvic junction obstruction (UPJO). Materials and Methods: A retrospective review of adult patients at an academic medical center who underwent salvage intervention following primary treatment for UPJO was performed. Symptomatic failure was defined as significant flank pain. Radiographic failure was defined as no improvement in drainage or a decrease in SKF by ≥7%. Overall failure, the primary outcome, was defined as symptomatic failure, radiographic failure, or both. Results: Between 2008-2017, 34 patients (median age 38 years, 50% men) met study criteria. UPJO management was primary pyeloplasty/secondary endopyelotomy for 21/34 (62%), primary pyeloplasty/secondary pyeloplasty for 6/34 (18%), and primary endopyelotomy/secondary pyeloplasty for 7/34 (21%). Median follow-up was 3.3 years following secondary intervention. Patients undergoing primary pyeloplasty/secondary endopyelotomy had significantly higher overall failure than those undergoing primary pyeloplasty/secondary pyeloplasty (16/21 [76%] vs. 1/6 [17%], p=0.015). Among patients undergoing secondary endopyelotomy, presence of a stricture on retrograde pyelogram, stricture length, and SKF were not associated with symptomatic, radiographic, or overall failure. Serial renography was performed for 28/34 (82%) patients and 2/28 (7%) had a significant decline in SKF. Conclusions: Following failed primary pyeloplasty, secondary endopyelotomy had a greater overall failure rate than secondary pyeloplasty. No radiographic features assessed were associated with secondary endopyelotomy failure. Secondary intervention overall failure rates were higher than reported in the literature. Unique to this study, serial renography demonstrated that significant functional loss was overall infrequent.

Clinical and radiographic outcomes following salvage intervention for ureteropelvic junction obstruction.

PURPOSE: We aimed to assess failure rates of salvage interventions and changes in split kidney function (SKF) following failed primary repair of ureteropelvic junction obstruction (UPJO). MATERIALS AND METHODS: A retrospective review of adult patients at an academic medical center who underwent salvage intervention following primary treatment for UPJO was performed. Symptomatic failure was defined as significant flank pain. Radiographic failure was defined as no improvement in drainage or a decrease in SKF by ≥7%. Overall failure, the primary outcome, was defined as symptomatic failure, radiographic failure, or both. RESULTS: Between 2008-2017, 34 patients (median age 38 years, 50% men) met study criteria. UPJO management was primary pyeloplasty/secondary endopyelotomy for 21/34 (62%), primary pyeloplasty/secondary pyeloplasty for 6/34 (18%), and primary endopyelotomy/secondary pyeloplasty for 7/34 (21%). Median follow-up was 3.3 years following secondary intervention. Patients undergoing primary pyeloplasty/secondary endopyelotomy had significantly higher overall failure than those undergoing primary pyeloplasty/secondary pyeloplasty (16/21 [76%] vs. 1/6 [17%], p=0.015). Among patients undergoing secondary endopyelotomy, presence of a stricture on retrograde pyelogram, stricture length, and SKF were not associated with symptomatic, radiographic, or overall failure. Serial renography was performed for 28/34 (82%) patients and 2/28 (7%) had a significant decline in SKF. CONCLUSIONS: Following failed primary pyeloplasty, secondary endopyelotomy had a greater overall failure rate than secondary pyeloplasty. No radiographic features assessed were associated with secondary endopyelotomy failure. Secondary intervention overall failure rates were higher than reported in the literature. Unique to this study, serial renography demonstrated that significant functional loss was overall infrequent.

Disparities in Kidney Stone Disease: A Scoping Review.

PURPOSE: We reviewed the available evidence regarding health disparities in kidney stone disease to identify knowledge gaps in this area. MATERIALS AND METHODS: A literature search was conducted using PubMed®, Embase® and Scopus® limited to articles published in English from 1971 to 2020. Articles were selected based on their relevance to disparities in kidney stone disease among adults in the United States. RESULTS: Several large epidemiological studies suggest disproportionate increases in incidence and prevalence of kidney stone disease among women as well as Black and Hispanic individuals in the United States, whereas other studies of comparable size do not report racial and ethnic demographics. Numerous articles describe disparities in imaging utilization, metabolic workup completion, analgesia, surgical intervention, stone burden at presentation, surgical complications, followup, and quality of life based on race, ethnicity, socioeconomic status and place of residence. Differences in urinary parameters based on race, ethnicity and socioeconomic status may be explained by both dietary and physiological factors. All articles assessed had substantial risk of selection bias and confounding. CONCLUSIONS: Health disparities are present in many aspects of kidney stone disease. Further research should focus not only on characterization of these disparities but also on interventions to reduce or eliminate them.

Vesicular Cystitis: A Chronic Cystitis Variant Often Unresponsive to Antibiotics and Electrofulguration.

OBJECTIVE: The aim of the study was to report on the presentation and outcomes of vesicular cystitis (VC), a chronic cystitis exhibiting translucent bladder mucosal vesicles, among women with antibiotic-refractory recurrent urinary tract infections (RUTIs). METHODS: An analysis of our Institutional Review Board-approved series on antibiotic-refractory RUTIs was performed, selecting for documented VC lesions on cystoscopy. All patients had RUTIs defined as ≥3 urinary tract infections/year with positive urine culture. All patients were extensively treated with antibiotics with no resolution of RUTIs and were offered electrofulguration (EF) of VC lesions under anesthesia as a last resort. All patients had a 6-month post-EF office cystoscopy documenting persistence or resolution of the lesions, and a clinical outcome assessment based on RUTI frequency. RESULTS: Of 482 patients, 18 (3.7%) treated during 2011-2017 met the study criteria. VC was most commonly found over the dome/anterior wall (7/18, 38%) and as pancystitis (7/18, 38%). There was often concomitant cystitis cystica of the trigone (8/18, 44%). At post-EF cystoscopy, persistence of VC was noted in 10/18 (56%) patients; 6/18 (33%) underwent repeat EF and an additional 3/18 (17%) were retreated due to new lesions after initial resolution. Two (11%) patients required simple cystectomy and urinary diversion due to RUTIs refractory to all interventions. Within a median follow-up of 2.8 years after EF, clinical cure was observed in 5/18 (28%), improvement in 10/18 (56%), and failure in 3/18 (17%) patients. CONCLUSIONS: Among women with antibiotic-refractory RUTIs, VC is an infrequent and persistent form of cystitis with a predilection for non-trigonal bladder surfaces, whose management is challenging.

Contribution of Dietary Oxalate and Oxalate Precursors to Urinary Oxalate Excretion.

Kidney stone disease is increasing in prevalence, and the most common stone composition is calcium oxalate. Dietary oxalate intake and endogenous production of oxalate are important in the pathophysiology of calcium oxalate stone disease. The impact of dietary oxalate intake on urinary oxalate excretion and kidney stone disease risk has been assessed through large cohort studies as well as smaller studies with dietary control. Net gastrointestinal oxalate absorption influences urinary oxalate excretion. Oxalate-degrading bacteria in the gut microbiome, especially Oxalobacter formigenes, may mitigate stone risk through reducing net oxalate absorption. Ascorbic acid (vitamin C) is the main dietary precursor for endogenous production of oxalate with several other compounds playing a lesser role. Renal handling of oxalate and, potentially, renal synthesis of oxalate may contribute to stone formation. In this review, we discuss dietary oxalate and precursors of oxalate, their pertinent physiology in humans, and what is known about their role in kidney stone disease.

Electrofulguration in the advanced management of antibiotic-refractory recurrent urinary tract infections in women.

OBJECTIVE: To evaluate the long-term efficacy of electrofulguration in women with recurrent urinary tract infections. METHODS: After institutional review board approval, a retrospective study of women who underwent electrofulguration alone was carried out. All patients had recurrent urinary tract infections defined as three or more urinary tract infections/year, and a preoperative office cystoscopy showing inflammatory lesions, categorized by location: urethra, bladder neck, trigone and beyond the trigone. All lesions were cauterized during outpatient electrofulguration under anesthesia. On 6-month postoperative office cystoscopy, endoscopic success was defined as resolution of all lesions previously seen and no new lesions. The primary outcome was urinary tract infections/year, with urinary tract infection defined as antibiotic treatment for urinary tract infection-like symptoms and/or for positive urine culture. Clinical cure was defined as no further urinary tract infections, clinical improvement as less than three urinary tract infections/year, and clinical failure as three or more urinary tract infections/year. RESULTS: Of 95 women who met the study criteria between 2004 and 2016, 62 (65%) were endoscopically successful, and 33 (35%) were endoscopic failures based on postoperative cystoscopy. Among all patients, over a median follow-up period of 4.9 years, the median number of urinary tract infections/year was 0.8. Endoscopically successful patients had fewer urinary tract infections/year compared with endoscopic failures (0.6 vs 0.9, P = 0.03). Clinically, 14 (15%) patients were cured, 69 (73%) were improved and 12 (13%) failed. Compared with clinically improved patients, clinical failures were more likely to have infections with multiple organisms (92% vs 35%, P < 0.001) and highly resistant organisms (92% vs 23%, P < 0.001). CONCLUSIONS: In our experience, nearly two-thirds of women with recurrent urinary tract infection can be successfully treated with electrofulguration, and >80% experience long-term clinical cure or improvement in urinary tract infections.

Comparison of the EORTC tables and the EAU categories for risk stratification of patients with nonmuscle-invasive bladder cancer.

PURPOSE: To characterize outcomes of patients with TaT1 urothelial carcinoma of the bladder stratified by the European Association of Urology (EAU) categories and to compare them with European Organization for Research and Treatment of Cancer (EORTC) risk groups to assess the rate and effect of reclassification. PATIENTS AND METHODS: A multi-institutional database of 5,122 patients with TaT1 urothelial carcinoma of the bladder who underwent transurethral resection of the bladder with or without adjuvant therapy at 8 institutions between 1996 and 2007. Multivariable Cox-regression analyses addressed factors associated with disease recurrence and progression. The net reclassification index was used to compare the performance of the EAU categories with the EORTC scoring system. RESULTS: Of 5,122 patients, 632 (12.3%), 2,302 (45.0%), and 2,188 (42.7%) were assigned to the low-, intermediate-, and high-risk EAU category, respectively. Within a median follow-up of 62 months (interquartile range: 27-97), 2,365 (46.2%) and 516 (10.1%) patients experienced disease recurrence and progression, respectively. In multivariable Cox-regression analyses, EAU intermediate- and high-risk categories were associated with a higher risk of disease recurrence (P<0.001) and progression (P<0.001) compared to low-risk patients. Application of the EAU categories reclassified 1,940 (37.9%) patients into a higher risk group for recurrence. Likewise, 602 (11.8%) patients were reclassified to a higher and 278 (5.4%) to a lower risk group for progression. The net reclassification index of the EAU risk stratification was 0.1% (95% CI: -3.1% to 3.2%) for recurrence and 10.1% (95% CI: -8.0% to 12.0%) for progression, respectively. CONCLUSIONS: Compared to EORTC risk stratification, the EAU categories reclassifies 37.9% patients into a higher risk group of recurrence and 11.8% into a higher risk of progression. However, the novel risk stratification assigns most patients to the same treatment as the more complex EORTC tables and can be regarded as an alternative tool for treatment decision-making.

Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing virus therapeutics.

The past century's description of oncolytic virotherapy as a cancer treatment involving specially-engineered viruses that exploit immune deficiencies to selectively lyse cancer cells is no longer adequate. Some of the most promising therapeutic candidates are now being engineered to produce immunostimulatory factors, such as cytokines and co-stimulatory molecules, which, in addition to viral oncolysis, initiate a cytotoxic immune attack against the tumor. This study addresses the combined effects of viral oncolysis and T-cell-mediated oncolysis. We employ a mathematical model of virotherapy that induces release of cytokine IL-12 and co-stimulatory molecule 4-1BB ligand. We found that the model closely matches previously published data, and while viral oncolysis is fundamental in reducing tumor burden, increased stimulation of cytotoxic T cells leads to a short-term reduction in tumor size, but a faster relapse. In addition, we found that combinations of specialist viruses that express either IL-12 or 4-1BBL might initially act more potently against tumors than a generalist virus that simultaneously expresses both, but the advantage is likely not large enough to replace treatment using the generalist virus. Finally, according to our model and its current assumptions, virotherapy appears to be optimizable through targeted design and treatment combinations to substantially improve therapeutic outcomes.