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    To determine whether 24-hour urine testing in Veterans with USD (urinary stone disease) reduces or delays urinary stone recurrence.Cohort study of national health record data from Veterans Health Administration from 2007 through 2013. We utilized a study population of 130,129 Veterans with USD based on diagnostic or procedural codes and excluded those with USD claims in the two years before cohort entry. We then created a propensity-score matched cohort of 14,854 Veterans based on completion of 24-hour urine testing within 6 months of stone diagnosis. Primary outcome was time-to-next clinically significant stone event, defined as an emergency department visit, inpatient admission related to a urinary stone, or urologic stone procedure with 5-year follow up.Of 14,854 Veterans in the propensity-score matched cohort, 8,560 (57.6%) experienced a recurrent USD event. Completion of 24-hour urine testing was associated with a higher risk of developing a second stone event (hazard ratio (HR) 1.17, 95% confidence interval (95% CI) 1.12-1.22). Among Veterans with known recurrent disease, we examined time to a third stone event. In this cohort of 4,736 patients, completion of 24-hour urine testing was not associated with a higher risk of developing a third stone event (HR 1.06, 95% CI 0.99-1.12).Completion of 24-hour urine testing was not associated with a reduction in urinary stone recurrence. These findings challenge the validity of a longstanding recommendation in general medicine, nephrology, and urology practice.

    View details for Web of Science ID 000693688000745

    View details for PubMedID 34688771

  • Clinical laboratory tests associated with survival in patients with metastatic renal cell carcinoma: A Laboratory Wide Association Study (LWAS). Urologic oncology Velaer, K., Thomas, I. C., Yang, J., Kapphahn, K., Metzner, T. J., Golla, A., Hoerner, C. R., Fan, A. C., Master, V., Chertow, G. M., Brooks, J. D., Patel, C. J., Desai, M., Leppert, J. T. 2021


    Prognostic models for patients with metastatic renal cell carcinoma (mRCC) include select laboratory values. These models have important limitations, including reliance on a limited array of laboratory tests, and use of dichotomous ("high-low") cutoffs. We applied a Laboratory-Wide Association Study (LWAS) framework to systematically evaluate common clinical laboratory results associated with survival for patients diagnosed with mRCC.We used laboratory data for 3,385 patients diagnosed with mRCC from 2002 to 2017. We developed a LWAS framework, to examine the association with 53 common clinical laboratory tests results (641,712 measurements) and overall survival. We employed false-discovery rate to test the association of multiple laboratory tests with survival, and validated these results using 3 separate cohorts to generate a standardized hazard ratio (sHR), reported for a 1 standard deviation unit change in each laboratory test.The LWAS approach confirmed the association of laboratory values currently used in prognostic models with survival, including calcium (HR 1.35, 95%CI 1.24-1.48), leukocyte count (HR 1.40, 95%CI 1.30-1.51), platelet count (HR 1.36, 95%CI 1.27-1.51), and hemoglobin (HR 0.79, 95%CI 0.72-0.86). Use of these tests as continuous variables improved model performance. LWAS also identified acute phase reactants associated with survival not typically included in prognostic models, including serum albumin (HR 0.66, 95%CI 0.61-0.72), ferritin (HR 1.25, 95%CI 1.08-1.45), alkaline phosphatase (HR 1.31, 95%CI 1.23-1.40), and C-reactive protein (HR 1.70, 95%CI 1.14-2.53).Routinely measured laboratory tests can refine current prognostic models, facilitate comparisons across clinical trial cohorts, and match patients with specific systemic therapies.

    View details for DOI 10.1016/j.urolonc.2021.08.011

    View details for PubMedID 34580027

  • Time Burden of Bladder Management in Individuals With Spinal Cord Injury. Topics in spinal cord injury rehabilitation Velaer, K. N., Welk, B., Ginsberg, D., Myers, J., Shem, K., Elliott, C. 2021; 27 (3): 83-91


    Background: While clean intermittent catheterization (CIC) is the gold standard for bladder management after spinal cord injury (SCI), many individuals with SCI, for reasons not fully understood, choose alternative bladder management. We hypothesized that CIC is associated with an increased time burden in individuals with SCI.Objectives: To investigate the time required to perform neurogenic bladder management in individuals with SCI.Methods: An electronic nonvalidated questionnaire was designed to determine the self-reported time spent performing bladder management. It was sent to participants in the Neurogenic Bladder Research Group SCI Registry, a national quality of life study of individuals with SCI.Results: Eighty-seven individuals responded to the survey. CIC was the most common bladder management (76%). Men and women performing independent CIC had similar average times with each catheterization episode (8.8 vs. 8.5 minutes, p = .864) as did women with a catheterizable stoma compared to women catheterizing per urethra (8.2 minutes, p = .913). Longer catheterization times were associated with cervical spine injury (mean 12.4 minutes per catheterization) and women requiring caregiver assistance (mean 20 minutes per catheterization). In addition, obese/overweight women had longer CIC times than normal weight women (14.5 minutes vs. 7 minutes; p = .036), while catheterization time was similar for all men regardless of body mass index. Individuals with indwelling catheters spent less than a third of the time on bladder management per day compared to those doing CIC (17 vs. 53 minutes per day, p < .001).Conclusion: Management of neurogenic bladder after SCI, especially in those performing CIC, is time consuming. This time burden may play a role in long-term bladder management decisions.

    View details for DOI 10.46292/sci20-00007

    View details for PubMedID 34456549

  • Laboratory-wide association study of survival with prostate cancer. Cancer Sohlberg, E. M., Thomas, I., Yang, J., Kapphahn, K., Velaer, K. N., Goldstein, M. K., Wagner, T. H., Chertow, G. M., Brooks, J. D., Patel, C. J., Desai, M., Leppert, J. T. 2020


    BACKGROUND: Estimates of overall patient health are essential to inform treatment decisions for patients diagnosed with cancer. The authors applied XWAS methods, herein referred to as "laboratory-wide association study (LWAS)", to evaluate associations between routinely collected laboratory tests and survival in veterans with prostate cancer.METHODS: The authors identified 133,878 patients who were diagnosed with prostate cancer between 2000 and 2013 in the Veterans Health Administration using any laboratory tests collected within 6 months of diagnosis (3,345,083 results). Using the LWAS framework, the false-discovery rate was used to test the association between multiple laboratory tests and survival, and these results were validated using training, testing, and validation cohorts.RESULTS: A total of 31 laboratory tests associated with survival met stringent LWAS criteria. LWAS confirmed markers of prostate cancer biology (prostate-specific antigen: hazard ratio [HR], 1.07 [95% confidence interval (95% CI), 1.06-1.08]; and alkaline phosphatase: HR, 1.22 [95% CI, 1.20-1.24]) as well laboratory tests of general health (eg, serum albumin: HR, 0.78 [95% CI, 0.76-0.80]; and creatinine: HR, 1.05 [95% CI, 1.03-1.07]) and inflammation (leukocyte count: HR, 1.23 [95% CI, 1.98-1.26]; and erythrocyte sedimentation rate: HR, 1.33 [95% CI, 1.09-1.61]). In addition, the authors derived and validated separate models for patients with localized and advanced disease, identifying 28 laboratory markers and 15 laboratory markers, respectively, in each cohort.CONCLUSIONS: The authors identified routinely collected laboratory data associated with survival for patients with prostate cancer using LWAS methodologies, including markers of prostate cancer biology, overall health, and inflammation. Broadening consideration of determinants of survival beyond those related to cancer itself could help to inform the design of clinical trials and aid in shared decision making.LAY SUMMARY: This article examined routine laboratory tests associated with survival among veterans with prostate cancer. Using laboratory-wide association studies, the authors identified 31 laboratory tests associated with survival that can be used to inform the design of clinical trials and aid patients in shared decision making.

    View details for DOI 10.1002/cncr.33341

    View details for PubMedID 33237577

  • Analysis of Primary Hyperparathyroidism Screening Among US Veterans With Kidney Stones. JAMA surgery Ganesan, C., Weia, B., Thomas, I., Song, S., Velaer, K., Seib, C. D., Conti, S., Elliott, C., Chertow, G. M., Kurella Tamura, M., Leppert, J. T., Pao, A. C. 2020


    Importance: Approximately 3% to 5% of patients with kidney stones have primary hyperparathyroidism (PHPT), a treatable cause of recurrent stones. However, the rate of screening for PHPT in patients with kidney stones remains unknown.Objectives: To estimate the prevalence of parathyroid hormone (PTH) testing in veterans with kidney stones and hypercalcemia and to identify the demographic, geographic, and clinical characteristics of veterans who were more or less likely to receive PTH testing.Design, Setting, and Participants: This cohort study obtained Veterans Health Administration (VHA) health records from the Corporate Data Warehouse for veterans who received care in 1 of the 130 VHA facilities across the United States from January 1, 2008, through December 31, 2013. Historical encounters, medical codes, and laboratory data were assessed. Included patients had diagnostic or procedural codes for kidney or ureteral stones, and excluded patients were those with a previous serum PTH level measurement. Data were collected from January 1, 2006, to December 31, 2014. Data analysis was conducted from June 1, 2019, to January 31, 2020.Exposures: Elevated serum calcium concentration measurement between 6 months before and 6 months after kidney stone diagnosis.Main Outcomes and Measures: Proportion of patients with a serum PTH level measurement and proportion of patients with biochemical evidence of PHPT who underwent parathyroidectomy.Results: The final cohort comprised 7561 patients with kidney stones and hypercalcemia and a mean (SD) age of 64.3 (12.3) years. Of these patients, 7139 were men (94.4%) and 5673 were white individuals (75.0%). The proportion of patients who completed a serum PTH level measurement was 24.8% (1873 of 7561). Across the 130 VHA facilities included in the study, testing rates ranged from 4% to 57%. The factors associated with PTH testing included the magnitude of calcium concentration elevation (odds ratio [OR], 1.07 per 0.1 mg/dL >10.5 mg/dL; 95% CI, 1.05-1.08) and the number of elevated serum calcium concentration measurements (OR, 1.08 per measurement >10.5 mg/dL; 95% CI, 1.06-1.10) as well as visits to both a nephrologist and a urologist (OR, 6.57; 95% CI, 5.33-8.10) or an endocrinologist (OR, 4.93; 95% CI, 4.11-5.93). Of the 717 patients with biochemical evidence of PHPT, 189 (26.4%) underwent parathyroidectomy within 2 years of a stone diagnosis.Conclusions and Relevance: This cohort study found that only 1 in 4 patients with kidney stones and hypercalcemia were tested for PHPT in VHA facilities and that testing rates varied widely across these facilities. These findings suggest that raising clinician awareness to PHPT screening indications may improve evaluation for parathyroidectomy, increase the rates of detection and treatment of PHPT, and decrease recurrent kidney stone disease.

    View details for DOI 10.1001/jamasurg.2020.2423

    View details for PubMedID 32725208

  • Ultrasound in Hospitalized Children With First Febrile UTI: What Exactly Are We Looking For? Hospital pediatrics Velaer, K. N., Chang, P., Wu, H. 2020

    View details for DOI 10.1542/hpeds.2020-0049

    View details for PubMedID 32303563

  • The Urine Albumin-Creatinine Ratio and Kidney Function after Nephrectomy. The Journal of urology Sun, A. J., Thomas, I., Velaer, K. N., Ganesan, C., Song, S., Pao, A. C., Wagner, T. H., Brooks, J. D., Chertow, G. M., Leppert, J. T. 2020: 101097JU0000000000001005


    BACKGROUND: Patients with kidney cancer are at risk of developing chronic kidney disease (CKD) after radical and partial nephrectomy. We sought to determine if the urine albumin-creatinine ratio (UACR) is independently associated with progressive CKD after nephrectomy.METHODS: We performed a cohort study based within a large, integrated health care system. We identified patients who underwent radical or partial nephrectomy from 2004 to 2014 with UACR measured in the 12 months prior to surgery. We fit multivariable models to determine if the UACR was associated with the time to CKD progression (defined as reaching stage 4 or 5 CKD, eGFR <30 mL/min/1.73m2). We performed a parallel analysis measuring the time to stage 3b, 4 or 5 CKD (eGFR <45 mL/min/1.73m2) among patients with normal or near-normal preoperative kidney function (eGFR ≥60 mL/min/1.73 m2). We also examined the association between UACR and survival.RESULTS: 1930 patients underwent radical or partial nephrectomy and had preoperative UACR and pre- and post-operative eGFR. Of these, 658 (34%) and 157 (8%) had moderate (UACR 30-300mg/g) or severe albuminuria (UACR > 300mg/g), respectively. Albuminuria severity was independently associated with progressive CKD after radical (moderate albuminuria HR 1.7, 95%CI 1.4-2.2; severe albuminuria HR 2.3, 95%CI 1.7-3.1) and partial nephrectomy (moderate albuminuria HR 1.8, 95%CI 1.2-2.7; severe albuminuria HR 4.3, 95%CI 2.7-7.0). Albuminuria was also associated with survival following radical and partial nephrectomy.CONCLUSIONS: In patients undergoing radical or partial nephrectomy, the severity of albuminuria can stratify risk of progressive CKD.

    View details for DOI 10.1097/JU.0000000000001005

    View details for PubMedID 32125227

  • The time burden of bladder management in individuals with spinal cord injury Velaer, K., Welk, B., Ginsberg, D., Myers, J., Shem, K., Elliott, C. WILEY. 2020: S195–S196
  • Deep learning enabled prediction of 5-year survival in pediatric genitourinary rhabdomyosarcoma. Surgical oncology Bhambhvani, H. P., Zamora, A. n., Velaer, K. n., Greenberg, D. R., Sheth, K. R. 2020; 36: 23–27


    Genitourinary rhabdomyosarcoma (GU-RMS) is a rare, pediatric malignancy originating from embryonic mesenchyme. Current approaches to prognostication rely upon conventional statistical methods such as Cox proportional hazards (CPH) models and have suboptimal predictive ability. Given the success of deep learning approaches in other specialties, we sought to develop and compare deep learning models with CPH models for the prediction of 5-year survival in pediatric GU-RMS patients.Patients less than 20 years of age with GU-RMS were identified within the Surveillance, Epidemiology, and End Results (SEER) database (1998-2011). Deep neural networks (DNN) were trained and tested on an 80/20 split of the dataset in a 5-fold cross-validated fashion. Multivariable CPH models were developed in parallel. The primary outcomes were 5-year overall survival (OS) and disease-specific survival (DSS). Variables used for prediction were age, sex, race, primary site, histology, degree of tumor extension, tumor size, receipt of surgery, and receipt of radiation. Receiver operating characteristic curve analysis was conducted, and DNN models were tested for calibration.277 patients were included. The area under the curve (AUC) for the DNN models was 0.93 for OS and 0.91 for DSS. AUC for the CPH models was 0.82 for OS and 0.84 for DSS. The DNN models were well-calibrated: OS model (slope = 1.02, intercept = -0.06) and DSS model (slope = 0.79, intercept = 0.21).A deep learning-based model demonstrated excellent performance, superior to that of CPH models, in the prediction of pediatric GU-RMS survival. Deep learning approaches may enable improved prognostication for patients with rare cancers.

    View details for DOI 10.1016/j.suronc.2020.11.002

    View details for PubMedID 33276260

  • Contemporary multicenter outcomes of continent cutaneous ileocecocystoplasty in the adult population over a 10-year period: A Neurogenic Bladder Research Group study. Neurourology and urodynamics Cheng, P. J., Keihani, S. n., Roth, J. D., Pariser, J. J., Elliott, S. P., Bose, S. n., Khavari, R. n., Crescenze, I. n., Stoffel, J. T., Velaer, K. N., Elliott, C. S., Raffee, S. M., Atiemo, H. O., Kennelly, M. J., Lenherr, S. M., Myers, J. B. 2020


    Evidence is sparse on the long-term outcomes of continent cutaneous ileocecocystoplasty (CCIC). We hypothesized that obesity, laparoscopic/robotic approach, and concomitant surgeries would affect morbidity after CCIC and aimed to evaluate the outcomes of CCIC in adults in a multicenter contemporary study.We retrospectively reviewed the charts of adult patients from sites in the Neurogenic Bladder Research Group undergoing CCIC (2007-2017) who had at least 6 months of follow-up. We evaluated patient demographics, surgical details, 90-day complications, and follow-up surgeries. the Mann-Whitney U test was used to compare continuous variables and χ² and Fisher's Exact tests were used to compare categorical variables.We included 114 patients with a median age of 41 years. The median postoperative length of stay was 8 days. At 3 months postoperatively, major complications occurred in 18 (15.8%), and 24 patients (21.1%) were readmitted. During a median follow-up of 40 months, 48 patients (42.1%) underwent 80 additional related surgeries. Twenty-three patients (20.2%) underwent at least one channel revision, most often due to obstruction (15, 13.2%) or incontinence (4, 3.5%). Of the channel revisions, 10 (8.8%) were major and 14 (12.3%) were minor. Eleven patients (9.6%) abandoned the catheterizable channel during the follow-up period. Obesity and laparoscopic/robotic surgical approach did not affect outcomes, though concomitant surgery was associated with a higher rate of follow-up surgeries.In this contemporary multicenter series evaluating CCIC, we found that the short-term major complication rate was low, but many patients require follow-up surgeries, mostly related to the catheterizable channel.

    View details for DOI 10.1002/nau.24420

    View details for PubMedID 32506711

  • Diabetes Medications, Prostate-Specific Antigen Values, and the Chemoprevention of Prostate Cancer. JAMA network open Velaer, K. N., Leppert, J. T. 2019; 2 (11): e1914644

    View details for DOI 10.1001/jamanetworkopen.2019.14644

    View details for PubMedID 31693117

  • Quadruple immunotherapy of Bacillus Calmette-Guerin, interferon, interleukin-2, and granulocyte-macrophage colony-stimulating factor as salvage therapy for non muscle-invasive bladder cancer UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Steinberg, R. L., Nepple, K. G., Velaer, K. N., Thomas, L. J., O'Donnell, M. A. 2017; 35 (12)
  • Quadruple immunotherapy of Bacillus Calmette-Guérin, interferon, interleukin-2, and granulocyte-macrophage colony-stimulating factor as salvage therapy for non-muscle-invasive bladder cancer. Urologic oncology Steinberg, R. L., Nepple, K. G., Velaer, K. N., Thomas, L. J., O'Donnell, M. A. 2017; 35 (12): 670.e7-670.e14


    Bacillus Calmette-Guérin (BCG) is the most effective initial intravesical therapy for high-grade non-muscle invasive bladder cancer, but many patients still fail. Combination intravesical BCG and interferon (IFN) will salvage some patients but results remain suboptimal.We hypothesized that further immunostimulation with intravesical interleukin-2 and subcutaneous granulocyte-macrophage colony-stimulating factor may improve response to intravesical BCG and IFN in patient with prior BCG failure(s).A retrospective review was performed. Patients received 6 treatments of quadruple immunotherapy (intravesical solution with one-third dose BCG, 50 million units IFN, and 22 million units interleukin-2, along with a 250-mcg subcutaneous sargramostim injection). Surveillance began 4 to 6 weeks after treatment completion. Patients received maintenance if recurrence-free. Success was defined as no recurrence (bladder or extravesical) and bladder preservation. Analysis was performed by Kaplan-Meier method (P<0.05).Fifty-two patients received treatment with a median recurrence follow-up of 16.3 months and overall follow-up of 41.8 months. All patients had at least 1 prior BCG failure and 13% had 2 or more prior failures. Only 3 patients (6%) were unable to tolerate full induction. Treatment success was 55% at 1 year, and 53% at 2 years. Thirteen patients (25%) underwent cystectomy at a median time of 17.3 months with disease progression to T2 in 1 patient and T3 in 2 patients. No patients had positive surgical margins or positive lymph nodes.In patients with non-muscle-invasive bladder cancer with prior BCG failure, quadruple immunotherapy demonstrated good treatment success in some patients and warrants further evaluation.

    View details for DOI 10.1016/j.urolonc.2017.07.024

    View details for PubMedID 28801026

  • Experience with Sequential Intravesical Gemcitabine and Docetaxel as Salvage Therapy for Non-Muscle Invasive Bladder Cancer CURRENT UROLOGY REPORTS Velaer, K. N., Steinberg, R. L., Thomas, L. J., O'Donnell, M. A., Nepple, K. G. 2016; 17 (5): 38


    Patients with high-grade muscle invasive bladder cancer (NMIBC) receive intravesical therapy with bacillus Calmette-Guérin (BCG) as the well-established standard-of-care. However, even with prompt induction of intravesical therapy, approximately 40 % of patients will recur within 2 years. For patients who fail BCG, options include radical cystectomy, repeat BCG therapy, or alternative intravesical salvage therapy. In this review, we will discuss the most recent published evidence on salvage intravesical therapy with an emphasis on a more in-depth report of our therapeutic strategy with sequential gemcitabine and docetaxel intravesical therapy for this treatment-refractory population. In addition, we will provide practical advice on our approach to this challenging patient population including the use of operative staging to aid early identification of treatment failures.

    View details for DOI 10.1007/s11934-016-0594-2

    View details for Web of Science ID 000372232400003

    View details for PubMedID 26968418