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

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 contractio

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

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

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

We developed and validated the German version of the Ureteral Stent Symptoms Questionnaire (USSQ) for male and female patients with indwelling ureteral stents. 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. The German version of the USSQ showed good internal consistency (Cronbach's alpha = .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 ae .001). 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

An <i>ex Vivo</i> 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 <i>ex vivo</i> 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 <i>in vivo</i>. Ketorolac was applied to the urothelium and a transurothelial permeability coefficient (<i>K</i>_p) calculated. Relative drug distribution into the bladder wall after 90 min was determined. Ketorolac was able to permeate the urothelium (<i>K</i>_p = 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 <i>ex vivo</i> values for <i>K</i>_p and muscle/saline partition coefficient (providing an estimation of vascular clearance), to predict 90 min <i>in vivo</i> 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 <i>ex vivo</i> data and PK modeling provides an insight into the likelihood of achieving clinically relevant concentrations of drug following intravesical administration

Current process and outcomes of the surgical management of LUTS due to benign prostatic enlargement: how consistent are we? - results from the multi-institutional audit of surgical management of BPE (AuSuM BPE) in the United Kingdom.

OBJECTIVE In view of changing landscape of surgical treatment for LUTS secondary to BPE, this audit was undertaken to assess key aspects of the processes and outcomes of the current interventional treatments for BPE, across different units in the UK. MATERIALS AND METHOD A multi-institutional snapshot audit was conducted for patients undergoing interventions for LUTS/BPE over 8-week period. Using Delphi process two-part proforma was designed to capture data. RESULTS 529 patients were included across 20 NHS trusts in England and Wales. Median age was 73 years. Indications for surgery were acute retention (47%) and LUTS (45%). 80% of patients had prior medical therapy. TURP formed the commonest procedure. 27% patients had <23 hour hospital stay. Immediate (21%) and delayed (18%) complications were Clavien-Dindo <2 category. High proportion of patients reported residual symptoms. Type and indication of surgery were significant predictor of complications, length of stay and failure of TWOC outcomes, on multivariate analyses. There were variations in departmental processes, 50% centres used PROMs. CONCLUSION Monopolar TURP still remains the commonest intervention for BPE. Most departments are adopting newer technologies. The audit identified opportunities for development of consistent, effective and patient centric practices as well as need for large-scale focused studies

An ex Vivo

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