PURPOSE: The STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS) sought to identify risk factors for pain and urinary symptoms, as well as how these symptoms interfere with daily activities after ureteroscopy for stone treatment.

MATERIALS AND METHODS: This prospective observational cohort study enrolled patients aged ≥12 years undergoing ureteroscopy with ureteral stent for stone treatment at 4 clinical centers. Participants reported symptoms at baseline; on postoperative days (POD) 1, 3, 5; at stent removal; and day 30 post-stent removal. Outcomes of pain intensity, pain interference, urinary symptoms, and bother were captured with multiple instruments. Multivariable analyses using mixed-effects linear regression models were identified characteristics associated with increased stent-associated symptoms (SAS).

RESULTS: A total of 424 participants were enrolled. Mean age was 49 years (SD 17); 47% were female. Participants experienced a marked increase in SAS on POD 1. While pain intensity decreased ∼50% from POD 1 to POD 5, interference due to pain remained persistently elevated. In multivariable analysis, older age was associated with lower pain intensity(p=0.004). Having chronic pain conditions(p<0.001), prior severe stent pain(p=0.021), and depressive symptoms at baseline(p<0.001) were each associated with higher pain intensity. Neither sex, stone location, ureteral access sheath use, nor stent characteristics were drivers of SAS.

CONCLUSIONS: In this multicenter cohort, interference persisted even as pain intensity decreased. Patient factors (e.g., age, depression) rather than surgical factors were associated with symptom intensity. These findings provide a foundation for patient-centered care and highlight potential targets for efforts to mitigate the burden of SAS.

<p><strong>BACKGROUND: </strong>Our objective was to describe day-to-day evolution and variations in patient-reported stent-associated symptoms (SAS) in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS), a prospective multicenter observational cohort study, using multiple instruments with conceptual overlap in various domains.</p>

<p><strong>METHODS: </strong>In a nested cohort of the STENTS study, the initial 40 participants having unilateral ureteroscopy (URS) and stent placement underwent daily assessment of self-reported measures using the Brief Pain Inventory short form, Patient-Reported Outcome Measurement Information System measures for pain severity and pain interference, the Urinary Score of the Ureteral Stent Symptom Questionnaire, and Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index. Pain intensity, pain interference, urinary symptoms, and bother were obtained preoperatively, daily until stent removal, and at postoperative day (POD) 30.</p>

<p><strong>RESULTS: </strong>The median age was 44&nbsp;years (IQR 29,58), and 53% were female. The size of the dominant stone was 7.5&nbsp;mm (IQR 5,11), and 50% were located in the kidney. There was consistency among instruments assessing similar concepts. Pain intensity and urinary symptoms increased from baseline to POD 1 with apparent peaks in the first 2&nbsp;days, remained elevated with stent in situ, and varied widely among individuals. Interference due to pain, and bother due to urinary symptoms, likewise demonstrated high individual variability.</p>

<p><strong>CONCLUSIONS: </strong>This first study investigating daily SAS allows for a more in-depth look at the lived experience after URS and the impact on quality of life. Different instruments measuring pain intensity, pain interference, and urinary symptoms produced consistent assessments of patients' experiences. The overall daily stability of pain and urinary symptoms after URS was also marked by high patient-level variation, suggesting an opportunity to identify characteristics associated with severe SAS after URS.</p>

<p><strong>RATIONALE &amp; OBJECTIVE: </strong>Although maintaining high fluid intake is an effective, low-risk intervention for the secondary prevention of urinary stone disease (USD), many stone patients do not increase their fluid intake.</p>

<p><strong>STUDY DESIGN: </strong>We describe the rationale and design of the Prevention of Urinary Stones with Hydration (PUSH) study, a randomized trial of a multi-component behavioral intervention program to increase and maintain high fluid intake. Participants are randomized (1:1 ratio) to intervention or control arm. The target sample size is 1642 participants.</p>

<p><strong>SETTING &amp; PARTICIPANTS: </strong>Adults and adolescents ≥12 years of age with a symptomatic stone history and low urine volume are eligible. Exclusion criteria include infectious or monogenic causes of USD and comorbid conditions precluding increased fluid intake.</p>

<p><strong>INTERVENTIONS: </strong>All participants receive usual care and a smart water bottle and smartphone application. Participants in the intervention arm receive a fluid intake prescription and an adaptive program of behavioral interventions, including financial incentives, structured problem solving, and other automated adherence interventions. Control arm participants receive guideline-based fluid instructions.</p>

<p><strong>OUTCOMES: </strong>The primary endpoint is recurrence of a symptomatic stone over 24-months of follow-up. Secondary endpoints include changes in radiographic stone burden, 24-hour urine output, and urinary symptoms.</p>

<p><strong>LIMITATIONS: </strong>Periodic 24-hour urine volumes may not fully reflect daily behavior.</p>

<p><strong>CONCLUSIONS: </strong>With its highly novel features, the PUSH study will address an important healthcare problem.</p>

<p>Ureteral stents are commonly employed after ureteroscopy to treat urinary stone disease, but the devices impose a substantial burden of stent-associated symptoms (SAS), including pain and urinary side effects. The NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) Urinary Stone Disease Research Network sought to develop greater understanding of SAS causes and severity among individuals treated ureteroscopically for ureteral or renal stones. We designed a prospective, observational cohort study comprising adolescents and adults undergoing ureteroscopic intervention for ureteral or renal stones. Participants will undergo detailed symptom assessment using validated questionnaires, a psychosocial assessment, and detailed collection of clinical and operative data. Quantitative sensory testing will be utilized to assess pain sensitization. In addition, a small cohort (∼40 individuals) will participate in semi-structured interviews to develop more granular information regarding their stent symptoms and experience. Biospecimens (blood and urine) will be collected for future research. The Study to Enhance Understanding of sTent-associated Symptoms (STENTS) enrolled its first participant in March 2019 and completed nested qualitative cohort follow-up in August 2019. After a planned pause, enrollment for the main study cohort resumed in September 2019 and is expected to be completed in 2021. STENTS is expected to provide important insights into the mechanisms and risk factors for severe ureteral SAS after ureteroscopy. These insights will generate future investigations to mitigate the burden of SAS among individuals with urinary stone disease.</p>