Protocol of the Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) study: a pragmatic, prospective multicenter observational cohort study of recurrent high-grade non-muscle invasive bladder cancer.

BACKGROUND: Bladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians. The CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options) Study aims to address this critical knowledge gap by comparing outcomes between patients undergoing BST and radical cystectomy. METHODS: The CISTO Study is a pragmatic, prospective observational cohort trial across 36 academic and community urology practices in the US. The study will enroll 572 patients with a diagnosis of recurrent high-grade NMIBC who select management with either BST or radical cystectomy. The primary outcome is health-related quality of life (QOL) at 12 months as measured with the EORTC-QLQ-C30. Secondary outcomes include bladder cancer-specific QOL, progression-free survival, cancer-specific survival, and financial toxicity. The study will also assess patient preferences for treatment outcomes. Statistical analyses will employ targeted maximum likelihood estimation (TMLE) to address treatment selection bias and confounding by indication. DISCUSSION: The CISTO Study is powered to detect clinically important differences in QOL and cancer-specific survival between the two treatment approaches. By including a diverse patient population, the study also aims to assess outcomes across the following patient characteristics: age, gender, race, burden of comorbid health conditions, cancer severity, caregiver status, social determinants of health, and rurality. Treatment outcomes may also vary by patient preferences, health literacy, and baseline QOL. The CISTO Study will fill a crucial evidence gap in the management of recurrent high-grade NMIBC, providing evidence-based guidance for patients and clinicians in choosing between BST and radical cystectomy. The CISTO study will provide an evidence-based approach to identifying the right treatment for the right patient at the right time in the challenging clinical setting of recurrent high-grade NMIBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03933826. Registered on May 1, 2019.

Patient and public involvement in the design and conduct of a large, pragmatic observational trial to investigate recurrent, high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Patient-centered approaches to research design are particularly important for diseases with complex treatment decision-making, such as recurrent, high-grade non-muscle-invasive bladder cancer (NMIBC). The objective of this article is to describe patient and public involvement (PPI) in designing a large, pragmatic observational trial and to articulate barriers, challenges, and lessons learned for future design. METHODS: Through multistakeholder involvement, a large, pragmatic observational trial was designed to investigate the outcomes of high-risk, recurrent NMIBC, and it was titled Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO). CISTO's design used the Guidance for Reporting Involvement of Patients and the Public 2 reporting checklist for PPI and built on prior engagement infrastructure in partnership with the Bladder Cancer Advocacy Network. RESULTS: CISTO's PPI began with research prioritization to identify the highest priority questions facing patients with NMIBC. A pragmatic observational study design was selected and refined through stakeholder input. PPI included patients and caregivers organized into an advocate advisory board and clinicians, researchers, payers, and industry representatives organized into an external advisory board. An engagement plan was created to define the stages of PPI and the level and nature of the involvement of each group. PPI was measured quantitatively and qualitatively through evaluation surveys and iterative feedback from board members, with changes made for continuous improvement. CONCLUSIONS: Through intentional PPI, CISTO aims to produce pragmatic and generalizable results that will allow patients to make informed decisions for recurrent, high-risk NMIBC based on their personal experiences. LAY SUMMARY: Involving patients and other stakeholders in research ensures that it reflects the outcomes that matter most to them. This is especially important when research focuses on conditions in which patients face difficult decisions about treatment options. This article describes the key role that stakeholders played in shaping the Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer (CISTO) study. It compares treatments for recurrent noninvasive bladder cancer and describes how stakeholders were engaged to design and develop the study and the practices that supported their involvement.

Randomized Clinical Trial of Lidocaine Analgesia for Transurethral Bladder Catheterization Delivered via Blunt Tipped Applicator in Young Children.

OBJECTIVE: Transurethral bladder catheterization (TUBC) is a painful, frequently performed procedure for collecting sterile urine. We sought to determine if administration of intraurethral lidocaine before TUBC using a blunt tipped syringe decreases procedural pain in young children in the pediatric emergency department. METHODS: Randomized clinical trial of children 0 to 36 months old requiring TUBC for collection of urine in a pediatric emergency department was performed. Patients received intraurethral 2% lidocaine jelly or usual care (no analgesia). Randomization was stratified by sex. Intraurethral lidocaine jelly was administered via Uro-Jet, 5 minutes before TUBC. Baseline child state, lidocaine application, TUBC, and child state 1 minute post-TUBC were videotaped. Neither providers nor parents were blinded to study arm. Videos were scored by a trained, independent, blinded reviewer using the Faces, Legs, Arms, Cry, and Consolability (FLACC) and Modified Behavioral Pain Score scales. Pain scores were compared using the Wilcoxon rank sum test. Our primary outcome was difference in FLACC scores between groups. RESULTS: Eighty children were enrolled in the study, and 73 had analyzable data. No differences were detected in pain by mean FLACC score between intervention (8; 95% confidence interval, 7-9) and control (9; 95% confidence interval, 8-10) groups. There were no differences between groups in mean FLACC score when stratified by age or sex or in mean Modified Behavioral Pain Score. CONCLUSIONS: Intraurethral lidocaine for TUBC for urine collection using a blunt tipped applicator did not improve procedural pain scores. Pain scores were high across groups. Further study should be performed to improve analgesia for this highly painful procedure.

Disposable Autonomous Device for Swab-to-Result Diagnosis of Influenza.

A prototype of a self-contained, automated, disposable device for chemically amplified protein-based detection of influenza virus from nasal swab specimens was developed and evaluated in a clinical setting. The device required only simple specimen manipulation without any dedicated instrumentation or specialized training by the operator for interpretation. The device was based on a sandwich immunoassay for influenza virus nucleoprotein; it used an enzyme-labeled antibody and a chromogenic substrate to provide an amplified visible signal, in a two-dimensional paper network format. All reagents were stored within the device. Device performance was assessed at Seattle Children's Hospital; clinical staff collected nasal swab samples from 25 patients and then operated test devices on site to detect influenza A and B in those specimens. The total test time from device initiation to result was approximately 35 min. Device performance for influenza A detection was ∼70% accurate using in-house qRT-PCR influenza A as a gold-standard comparison. The ratio of valid to total completed device runs yielded a success rate of 92%, and the negative predictive value for both the influenza A and B assay was 81%. The ability to diagnose respiratory infections rapidly and close to the patient was well received by hospital staff, inspiring further optimization of device function.

Interruptions in bladder cancer care during the COVID-19 public health emergency.

BACKGROUND: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. METHODS: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. RESULTS: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. CONCLUSIONS: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic.

Deficiencies in Provider-Reported Interpreter Use in a Clinical Trial Comparing Telephonic and Video Interpretation in a Pediatric Emergency Department.

BACKGROUND: Professional interpretation improves health care quality and outcomes for limited English proficient (LEP) patients, yet interpreter use remains low even when interpretation is available remotely. The researchers analyzed the effect of remote interpretation (telephone or video) on pediatric emergency provider attitudes and behaviors around professional interpretation. METHODS: A cross-sectional questionnaire of pediatric emergency providers was conducted as part of a randomized trial of telephone vs. video interpretation with Spanish speaking LEP families. Providers recalled lapses of professional interpretation for medical communication (use of an ad hoc or no interpreter), if they had delayed or deferred communication due to the need for professional interpretation, and were asked about their satisfaction with the interpretation modality. Bivariate and multivariate analysis of professional interpreter use and communication behaviors were analyzed by self-report of study group assignment. RESULTS: One third of providers reported lapses of professional interpretation and many reported less frequent (45.6%) and deferred (34.6%) communication due to the need for interpretation. There was no significant difference in these outcomes between telephone and video assignment. Interpreter skill and technical difficulties were similar between groups. Providers assigned to telephone, compared to video, were more likely to be dissatisfied (p < 0.001) and to report that interpretation was ineffective (p = 0.002). CONCLUSION: Despite access to interpretation, providers caring for patients enrolled in a study of professional interpreter modalities reported frequent lapses in professional interpretation and deferring or delaying communication because an interpreter was needed. Addressing barriers to remote interpreter use will improve quality of care and health equity for LEP patients.

Rhinovirus Disease in Children Seeking Care in a Tertiary Pediatric Emergency Department.

BACKGROUND: Rhinovirus is the most common cause of viral respiratory tract infections in children. Virologic predictors of lower respiratory tract infection (LRTI), such as viral load and the presence of another respiratory virus (coinfection), are not well characterized in pediatric outpatients. METHODS: Mid-nasal turbinate samples were collected from children presenting for care to the Seattle Children's Hospital emergency department (ED) or urgent care with a symptomatic respiratory infection between December 2011 and May 2013. A subset of samples was tested for rhinovirus viral load by real-time polymerase chain reaction. Clinical data were collected by chart reviews. Multivariate logistic regression was used to evaluate the relationship between viral load and coinfection and the risk for LRTI. RESULTS: Rhinovirus was the most frequent respiratory virus detected in children younger than 3 years. Of 445 patients with rhinovirus infection, 262 (58.9%) had LRTIs, 231 (51.9%) required hospital admission and 52 (22.5%) were hospitalized for 3 days or longer. Children with no comorbidities accounted for 142 (54%) of 262 rhinovirus LRTIs. Higher viral load was significantly associated with LRTI among illness episodes with rhinovirus alone (OR, 2.11; 95% confidence interval [CI], 1.24-3.58). Coinfection increased the risk of LRTI (OR, 1.83; 95% CI, 1.01-3.32). CONCLUSIONS: Rhinovirus was the most common pathogen detected among symptomatic young children in a pediatric ED who had respiratory viral testing performed, with the majority requiring hospitalization. Higher rhinovirus viral load and coinfection increased disease severity. Virologic data may assist clinical decision making for children with rhinovirus infections in the pediatric ED.

Parental vaccine hesitancy and acceptance of seasonal influenza vaccine in the pediatric emergency department.

BACKGROUND: Providing influenza vaccine to patients in the pediatric emergency department (PED) is one strategy to increase childhood influenza vaccine uptake. The Parent Attitudes about Childhood Vaccines (PACV) survey is a new tool to identify vaccine-hesitant parents that may facilitate influenza vaccine uptake in the PED. OBJECTIVE: To assess the feasibility of administering the PACV modified for influenza vaccination in the PED setting and to determine whether parental PACV scores are associated with patient receipt of influenza vaccine in the PED. METHODS: We conducted a cross-sectional study in the PED of a tertiary pediatric hospital in Seattle, WA during the 2013-2014 influenza season. English-speaking parents of children aged 6 months to 7 years who were afebrile, medically stable to be discharged home from the PED, and had not already received an influenza vaccine this season were administered a modified version of the PACV. PACV scores (0-100, higher score=higher hesitancy) were dichotomized (<50 and ≥50) consistent with previous validation studies. Feasibility was assessed by determining time to complete the PACV. Our primary outcome was influenza vaccine refusal in the PED. We used multivariable logistic regression to estimate unadjusted and adjusted odds ratios for association between vaccine refusal and dichotomized PACV scores. RESULTS: 152 parent participants were included in the analysis. The median time for administering the PACV was 7 min. The median PACV score was 28, with 74% scoring <50. Parents who scored ≥50 on the PACV had increased odds of refusing the influenza vaccine compared to parents who scored <50 (adjusted OR [95% CI]: 6.58 [2.03-21.38]). CONCLUSION: Administration of the PACV in the PED is feasible, and higher PACV scores in this setting are associated with increased influenza vaccine refusal.