The German linguistic validation of the Ureteral Stent Symptoms Questionnaire (USSQ).

PURPOSE: We developed and validated the German version of the Ureteral Stent Symptoms Questionnaire (USSQ) for male and female patients with indwelling ureteral stents. METHODS: The German version of the USSQ was developed following a well-established multistep process. A total of 101 patients with indwelling ureteral stents completed the German USSQ as well as the validated questionnaires International Prostate Symptom Score (IPSS) or International Consultation on Incontinence Questionnaire (ICIQ) and the Short Form Health Survey (SF-36). Patients completed questionnaires at 1 and 2-4 weeks after stent insertion and 4 weeks after stent removal. Statistical analyses were performed to assess the psychometric properties of the questionnaire. RESULTS: The German version of the USSQ showed good internal consistency (Cronbach's α = .72-.88) and test-retest reliability [intraclass correlation coefficient (ICC) = .81-.92]. Inter-domain associations within the USSQ showed substantial correlations between different USSQ domains, indicating a high conceptual relationship of the domains. Except from urinary symptoms and general quality of life, German USSQ showed good convergent validity with the corresponding validated questionnaires. All USSQ domains showed significant sensitivity to change (p ≤ .001). CONCLUSION: The new German version of the USSQ proved to be a reliable and robust instrument for the evaluation of ureteral stent-associated morbidity for both male and female patients. It is expected to be a valid outcome measure in the future stent research.

Evidence of Nonuniformity in Urothelium Barrier Function between the Upper Urinary Tract and Bladder.

PURPOSE: We compared the relative permeability of upper urinary tract and bladder urothelium to mitomycin C. MATERIALS AND METHODS: Ex vivo porcine bladder, ureters and kidneys were dissected out and filled with 1 mg ml(-1) mitomycin C. At 60 minutes the organs were emptied and excised tissue samples were sectioned parallel to the urothelium. Sectioned tissue was homogenized and extracted mitomycin C was quantified. Transurothelial permeation across the different urothelia was calculated by normalizing the total amount of drug extracted to the surface area of the tissue sample. Average mitomycin C concentrations at different tissue depths (concentration-depth profiles) were calculated by dividing the total amount of drug recovered by the total weight of tissue. RESULTS: Mitomycin C permeation across the ureteral urothelium was significantly greater than across the bladder and renal pelvis urothelium (9.07 vs 0.94 and 3.61 µg cm(-2), respectively). Concentrations of mitomycin C in the ureter and kidney were markedly higher than those achieved in the bladder at all tissue depths. Average urothelial mitomycin C concentrations were greater than 6.5-fold higher in the ureter and renal pelvis than in the bladder. CONCLUSIONS: To our knowledge we report for the first time that the upper urinary tract and bladder show differing permeability to a single drug. Ex vivo porcine ureter is significantly more permeable to mitomycin C than bladder urothelium and consequently higher mitomycin C tissue concentrations can be achieved after topical application. Data in this study correlate with the theory that mammalian upper tract urothelium represents a different cell lineage than that of the bladder and it is innately more permeable to mitomycin C.

An ex vivo investigation into the transurothelial permeability and bladder wall distribution of the nonsteroidal anti-inflammatory ketorolac.

Transurothelial drug delivery continues to be an attractive treatment option for a range of urological conditions; however, dosing regimens remain largely empirical. Recently, intravesical delivery of the nonsteroidal anti-inflammatory ketorolac has been shown to significantly reduce ureteral stent-related pain. While this latest development provides an opportunity for advancing the management of stent-related pain, clinical translation will undoubtedly require an understanding of the rate and extent of delivery of ketorolac into the bladder wall. Using an ex vivo porcine model, we evaluate the urothelial permeability and bladder wall distribution of ketorolac. The subsequent application of a pharmacokinetic (PK) model enables prediction of concentrations achieved in vivo. Ketorolac was applied to the urothelium and a transurothelial permeability coefficient (Kp) calculated. Relative drug distribution into the bladder wall after 90 min was determined. Ketorolac was able to permeate the urothelium (Kp = 2.63 × 10(-6) cm s(-1)), and after 90 min average concentrations of 400, 141 and 21 µg g(-1) were achieved in the urothelium, lamina propria and detrusor respectively. An average concentration of 87 µg g(-1) was achieved across the whole bladder wall. PK simulations (STELLA) were then carried out, using ex vivo values for Kp and muscle/saline partition coefficient (providing an estimation of vascular clearance), to predict 90 min in vivo ketorolac tissue concentrations. When dilution of the drug solution with urine and vascular clearance were taken into account, a reduced ketorolac concentration of 37 µg g(-1) across the whole bladder wall was predicted. These studies reveal crucial information about the urothelium's permeability to agents such as ketorolac and the concentrations achievable in the bladder wall. It would appear that levels of ketorolac delivered to the bladder wall intravesically would be sufficient to provide an anti-inflammatory effect. The combination of such ex vivo data and PK modeling provides an insight into the likelihood of achieving clinically relevant concentrations of drug following intravesical administration.

Relief of stent related symptoms: review of engineering and pharmacological solutions.

PURPOSE: We review the recent publications on developing engineering and pharmaceutical agents to alleviate stent related symptoms, and examine basic science studies that may support a particular approach. MATERIALS AND METHODS: Data on randomized controlled trials for relief of stent related symptoms were analyzed. Studies involving engineering and pharmacological agents to resolve stent related morbidity were assessed separately. RESULTS: A variety of physical characteristics of stents, including materials, diameter, length and shape, have been modified to reduce stent related symptoms. Numerous studies have been conducted to engineer the ideal stent without clear and definite conclusions. There are mixed results with materials and negative results with shape. Appropriate stent length appears to be important but decreased diameter has not been shown to help. A recent study using a ketorolac eluting stent showed no significant benefit. Even with the best material and length it appears that patients still have significant stent related symptoms. To relieve stent related symptoms several classes of oral medications have been proposed for off-label use based on intuition or experience. Recently prospective, randomized, placebo controlled trials have been performed, along with basic science studies regarding the pharmacology of the ureter. They showed a clear and consistent beneficial effect of alpha1-blockers in patients with indwelling ureteral stents. CONCLUSIONS: Although there have been many advances in stent composition, construction geometry and design, the ideal stent has yet to be engineered. By contrast, the oral administration of alpha-blockers has shown the greatest reduction in stent morbidity.

The impact of urinary stone disease and their treatment on patients' quality of life: a qualitative study.

Urinary stone disease is a common, often recurrent disease, that can have a negative impact on patients' health-related quality of life (HRQoL), often effecting working, productive members of society. The literature lacks data from structured, qualitative research which could give unique insight into patients' HRQoL. The objective is to understand the impact of urinary stone disease and treatments on patients' HRQoL, from patients' and their relatives' perspective using qualitative and quantitative methodologies. Semi-structured interviews and a focus group were used to understand the HRQoL issues of patients with urinary stones disease, covering the American Urology Association index stone categories. Thematic analysis was performed (using qualitative data analysis software). Familial impact was assessed using the family-related outcome measure (FROM-16©). 62 patients with stone disease and interventions (mean age 51, range 19-92) participated. Data collection stopped when data saturation was achieved. Analysis revealed negative impact of stone disease and interventions on the patients' HRQoL, affecting domains of pain, physical symptoms, outlook on life, work/career, change in lifestyle/diet, social life, difficulties of daily living, travel/holiday problems, relationships and family member impact (106 themes grouped under ten broad headings). Sub-group analyses revealed similar impact in either sex, ureteric and renal stone groups. Recurrent stones were associated with work/financial concerns and treatment preferences varied accordingly. Our qualitative study presents detailed insights into the multidimensional impact of urinary calculi and their treatments on various domains of the HRQoL, confirming previous findings and adding new observations. The findings are expected to help in the development of patient-centric measures and communication tools.

The Italian linguistic validation of the ureteral stent symptoms questionnaire.

PURPOSE: We validated the Italian version of the Ureteral Stent Symptoms Questionnaire in male and female patients with an indwelling ureteral stent. MATERIALS AND METHODS: A double-back translation of the original Ureteral Stent Symptoms Questionnaire was performed by 3 urologists and 4 professional translators. A total of 78 patients (cases) with and 35 healthy subjects without (controls) an indwelling ureteral stent were asked to complete the Italian version of the Ureteral Stent Symptoms Questionnaire and a visual analog scale for pain as well as the International Prostate Symptom Score (men) and Urogenital Distress Inventory-6 plus Incontinence Impact Questionnaire-7 (women). Cases were evaluated at weeks 1 and 4 after stent placement, and at week 4 after removal, while controls were evaluated once. The psychometric properties of the questionnaire were analyzed. RESULTS: A total of 66 cases and 30 controls were suitable for analysis. The questionnaire showed good internal consistency in all domains except global quality of life compared with that of the International Prostate Symptom Score (Cronbach's alpha >0.75). Test-retest reliability was good except for the sexual matters domain (Pearson's coefficient >0.7). Relatively high correlation coefficients (greater than 0.65) were found for the visual analog scale for pain, the International Prostate Symptom Score, the Urogenital Distress Inventory-6 and the Incontinence Impact Questionnaire-7 with the corresponding Ureteral Stent Symptoms Questionnaire domains, suggesting good convergent validity. Sensitivity to change and discriminant validity were also good (p <0.001). CONCLUSIONS: The Italian version of the Ureteral Stent Symptoms Questionnaire is a reliable and robust instrument that can be self-administered to male and female Italian patients with an indwelling ureteral stent in the clinical and research settings.

How Do Urinary Calculi Influence Health-Related Quality of Life and Patient Treatment Preference: A Systematic Review.

INTRODUCTION: Urinary stone disease is a common and often recurrent condition that can affect kidney function and requires a range of medical and surgical treatments, all of which can have a significant impact on patients' health-related quality of life (HRQoL) and treatment preferences. OBJECTIVE: To review the literature systematically for all studies that include HRQoL measurement or patient preferences in the context of urinary stone disease. METHODS: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process, EMBASE, SCOPUS, EconLit, and Web of Science were searched from inception to January 2016. All study designs with adult participants were included. Narrative synthesis was performed. RESULTS: Thirty-five studies met the inclusion criteria (six randomized controlled trials and 29 observational studies) from 15 countries, including 5472 patients. Eleven studies showed that stone formers had worse HRQoL than the general population; it was noted that stone formers were more likely to suffer from depression. Women have significantly lower HRQoL than men. Twenty-six studies used a generic HRQoL measure and six were nonvalidated disease specific. Studies concerning patient preference were heterogeneous and showed that extracorporeal shock wave lithotripsy is still favored above other interventions and that a large number of patients would prefer the treatment pathway to be decided upon by their clinician. CONCLUSION: Urinary calculi and its treatment can have significant negative patient impact and influence patient preferences. Patients with stone disease tend to have worse physical and mental HRQoL, quantified using generic measures. Structured research with disease-specific measures underpinned by sound methodology would be beneficial and aid in development of patient-centric management. SYSTEMATIC REVIEW REGISTRATION: This review was prospectively registered with the international prospective register of systematic reviews-PROSPERO 2013:CRD42013006084.

Investigating detrusor muscle concentrations of oxybutynin after intravesical delivery in an ex vivo porcine model.

Intravesical oxybutynin is highly effective in the treatment of overactive bladder. Traditionally the mechanism of action was explained by antagonism of muscarinic receptors located in the detrusor, however evidence now suggests antimuscarinics may elicit their effect by modifying afferent pathways in the mucosal region. This study aimed to investigate the bladder wall distribution of oxybutynin in an ex vivo setting providing tissue - layer specific concentrations of drug achieved after intravesical delivery. Whole ex vivo porcine bladders were intravesically instilled with 0.167 mg mL(-1) oxybutynin solution. After 60 min, tissue samples were excised, serially sectioned parallel to the urothelial surface and extracted drug quantified. Drug distribution into the urothelium, lamina propria and detrusor was determined. Oxybutynin permeated into the bladder wall at a higher rate than other drugs previously investigated (apparent transurothelial Kp = 1.36 × 10(-5) cm s(-1) ). After 60 min intravesical instillation, concentrations achieved in the urothelium (298.69 µg g(-1) ) and lamina propria (43.65 µg g(-1) ) but not the detrusor (0.93 µg g(-1) ) were greater than reported IC50 values for oxybutynin. This work adds to the increasing body of evidence suggesting antimuscarinics elicit their effects via mechanisms other than direct inhibition of detrusor contraction.

Endoluminal ultrasonography with reusable probe: preliminary results.

BACKGROUND AND PURPOSE: Endoluminal ultrasound probes have been disposable, making their regular use costly. We describe the technique and preliminary results of a reusable endoluminal ultrasound probe for examining ureteral anatomy. PATIENTS AND METHODS: The 2.4-mm (7.2F) or 3-mm (9F) probe (Olympus, Tokyo) is passed up the ureter after a retrograde ureteropyelogram has been obtained. No intraoperative preparation of the probe is needed. An axial image as little as 1 cm or as much as 10 cm around the ureter can be obtained. Over the last 20 months, 50 procedures using endoluminal ultrasonography were performed in our unit: 36 (72%) for uretero-pelvic junction (UPJ) obstruction, 10 (20%) for upper-tract filling defects, and the remaining 4 (8%) for ureteral strictures. RESULTS: Endoluminal ultrasonography detected crossing vessels at the UPJ in 19 (53%) and a septum in 9 (25%) of the 36 renal units with UPJ obstruction. In eight of the 36 renal units with UPJ obstruction (22%), endopyelotomy was not done because of the presence of crossing vessels. A further 4 renal units (11%) had the direction of the incision modified because of the ultrasound findings. In the cases with upper-tract transitional-cell carcinoma, images correlated well with the nephroureterectomy specimen. The probe had to be replaced twice. CONCLUSIONS: This endoluminal ultrasound system produces clear images of the ureteral and periureteral anatomy. The reusable aspect of the probe removes an important obstacle to its common use for evaluating a variety of upper urinary tract abnormalities.

The Spanish linguistic validation of the ureteral stent symptom questionnaire.

BACKGROUND AND PURPOSE: Ureteral Stent Symptoms Questionnaire (USSQ) is an intervention-specific health-related quality-of-life (HrQoL) measure. We describe development and validation of the Spanish version. MATERIALS AND METHODS: We followed established methods to develop the Spanish version of the original USSQ. After pilot testing, we conducted a formal validation study; 70 patients, undergoing placement of ureteral stents, successfully completed the Spanish USSQ as well as the EuroQoL-5D (male and female), the ICIQ male and female lower urinary tract symptoms questionnaires at weeks 1 and 4 after stent insertions, and at week 4 after their removal. In addition, 40 healthy people acted as a control group and completed the same questionnaires twice at 3-week intervals. Statistical analyses were performed to evaluate reliability, validity, and sensitivity to change of the Spanish USSQ. RESULTS: After revision of the initial two drafts after translation, back translation, and pilot testing, a final draft was developed that underwent field testing. Psychometric analyses revealed satisfactory internal consistencies (Cronbach alpha coefficients: 0.73-0. 85) and test-retest reliability (Spearman correlation coefficient: >0.6) for the domains of urinary symptom, body pain, and general health. It demonstrated satisfactory discriminant validity (sensitivity to change, p<0.01), convergent validity (good correlations between the domains of the USSQ and existing validated questionnaires), and test-retest reliability (p<0.001). Analysis of the domains of the sexual matter (21.4%) and work performance (35.7%) were limited because of the small proportion of the study population for whom it was applicable. CONCLUSIONS: Results of our development and validation study demonstrate that the new Spanish version of the USSQ is a psychometrically valid intervention-specific measurer for use in the second most common language in the world. It is a reliable outcome measure that could be used for both clinical and research purposes.

Cross-cultural application of the Korean version of Ureteral Stent Symptoms Questionnaire.

PURPOSE: We validated the Korean version of the Ureteral Stent Symptoms Questionnaire (USSQ) in patients with an indwelling ureteral stent. MATERIALS AND METHODS: Linguistic validation of the original USSQ was performed through a standard process including translation, back translation, and pilot study. A total of 65 patients who underwent ureteroscopic surgery were asked to complete the Korean USSQ as well as EuroQOL (male and female), the International Prostate Symptom Score (male), and Urogenital Distress Inventory-6 (female). Patients were evaluated at weeks 1 and 2 after stent placement and at week 4 after removal. Sixty-four healthy subjects without a ureteral stent were also asked to complete the Korean USSQ once. The psychometric properties of the questionnaire were analyzed. RESULTS: Internal consistencies (Cronbach α coefficients: 0.73-0.83) and test-retest reliability (Spearman correlation coefficient: ≥0.6) were satisfactory for urinary symptom, body pain, general health, and work performance domains. Most USSQ domains showed moderate correlations with each other. Convergent validity determined by correlation between other instruments and corresponding USSQ domain was satisfactory. Sensitivity to change and discriminant validity were also good in most domains (P<0.01). Only a small proportion of the study population had an active sexual life, with the stent in situ, limiting its analysis. CONCLUSIONS: The Korean version of the USSQ is a reliable and valid instrument that can be self-administered by Korean patients with a ureteral stent in the clinical and research settings. Further clinical studies in the Korean settings would be useful to provide robust data on sensitivity to change.