The Perceived Usability of Virtual Visits Among Black Adults' Receiving Oncology Care: A Qualitative Analysis.

BACKGROUND: With the COVID-19 pandemic came rapid uptake in virtual oncology care. During this, sociodemographic inequities in access to virtual visits (VVs) have become apparent. To better understand these issues, we conducted a qualitative study to describe the perceived usability and acceptability of VVs among Black adults diagnosed with cancer. METHODS: Adults who self-identified as Black and had a diagnosis of prostate, multiple myeloma, or head and neck cancer were recruited from 2 academic medical centers, and their community affiliates to participate in a semi-structured interview, regardless of prior VV experience. A patient and family advisory board was formed to inform all components of the study. Interviews were conducted between September 2, 2021 and February 23, 2022. Transcripts were organized topically, and themes and subthemes were determined through iterative and interpretive immersion/crystallization cycles. RESULTS: Of the 49 adults interviewed, 29 (59%) had participated in at least one VV. Three overarching themes were derived: (1) VVs felt comfortable and convenient in the right contexts; (2) the technology required for VVs with video presented new challenges, which were often resolved by an audio-only telephone call; and (3) participants reported preferring in-person visits, citing concerns regarding gaps in nonverbal communication, trusting providers, and distractions during VV. CONCLUSION: While VVs were reported to be acceptable in specific circumstances, Black adults reported preferring in-person care, in part due to a perceived lack of interpersonal connectedness. Nonetheless, retaining reimbursement for audio-only options for VVs is essential to ensure equitable access for those with less technology savvy and/or limited device/internet capabilities.

Bladder Cancer Survivors Who Do Not Smoke Have Better Longitudinal Health-Related Quality of Life Measures: An Assessment of the Comparative Effectiveness and Survivorship Health in Bladder Cancer (CEASE-BC) Study.

PURPOSE: Cigarette smoking is the most common risk factor for the development of bladder cancer (BC), yet there is a paucity of data characterizing the relationship between smoking status and longitudinal health-related quality of life (HRQoL) outcomes in patients with BC. We examined the association between smoking status and HRQoL among patients with BC. MATERIALS AND METHODS: Data were sourced from a prospective, longitudinal study open between 2014 and 2017, which examined HRQoL in patients aged ≥ 18 years old diagnosed with BC across North Carolina. The QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core instrument) was administered at 3, 12, and 24 months after BC diagnosis. Our primary exposure of interest was current smoking status. Linear regression using generalized estimating equations was used to analyze the relationship between smoking status and various domains of the QLQ-C30. RESULTS: A total of 154 patients enrolled in the study. Eighteen percent were classified as smoking at 3 months from diagnosis, and packs per day ranged from < 0.5 to 2. When controlling for time from diagnosis, demographic covariates, cancer stage, and treatment type, mean differences for physical function (7.4), emotional function (5.6), and fatigue measures (-8.2) were significantly better for patients with BC who did not smoke. CONCLUSIONS: Patients with BC who do not smoke have significantly better HRQoL scores in the domains of physical function, emotional function, and fatigue. These results underscore the need to treat smoking as an essential component of BC care.

Feasibility, Acceptability, and Outcomes of a Mobile Health Tool for Radical Cystectomy Recovery.

PURPOSE: Postoperative education and symptom tracking are essential following cystectomy to reduce readmission rates and information overload. To address these issues, an internet-based tool was developed to provide education, alerts, and symptom tracking. We aimed to evaluate the tool's feasibility, acceptability, and impact on complication and readmission rates. MATERIALS AND METHODS: Thirty-three eligible patients over 18 years old scheduled for cystectomy were enrolled. Patients were asked to use the mobile health (mHealth) tool daily for the first 2 weeks, then less frequently up to 90 days after discharge. Descriptive statistics were used to summarize study variables. Feasibility was defined as at least 50% of patients using the tool once a week, and acceptability as patient satisfaction of > 75%. RESULTS: Use of the mHealth tool was feasible, with 90% of patients using it 1 week after discharge, but engagement declined over time to 50%, with technological difficulties being the main reason for nonengagement. Patient and provider acceptability was high, with satisfaction > 90%. Within 90 days, 36% experienced complications after discharge and 30% were readmitted. Engagement with the mHealth application varied but was not statistically associated with readmission (P = .21). CONCLUSIONS: The study showed that the electronic mobile health intervention for patients undergoing cystectomy was feasible, acceptable, and provided valuable educational content and symptom management. Future larger studies are needed to determine the tool's effectiveness in improving patient outcomes and its potential implementation into routine clinical care.

Decisional Conflict Among Patients Newly Diagnosed With Clinical T1 Renal Masses: A Prospective Study.

PURPOSE: Because multiple management options exist for clinical T1 renal masses, patients may experience a state of uncertainty about the course of action to pursue (ie, decisional conflict). To better support patients, we examined patient, clinical, and decision-making factors associated with decisional conflict among patients newly diagnosed with clinical T1 renal masses suspicious for kidney cancer. MATERIALS AND METHODS: From a prospective clinical trial, participants completed the Decisional Conflict Scale (DCS), scored 0 to 100 with < 25 associated with implementing decisions, at 2 time points during the initial decision-making period. The trial further characterized patient demographics, health status, tumor burden, and patient-centered communication, while a subcohort completed additional questionnaires on decision-making. Associations of patient, clinical, and decision-making factors with DCS scores were evaluated using generalized estimating equations to account for repeated measures per patient. RESULTS: Of 274 enrollees, 250 completed a DCS survey; 74% had masses ≤ 4 cm in size, while 11% had high-complexity tumors. Model-based estimated mean DCS score across both time points was 17.6 (95% CI 16.0-19.3), though 50% reported a DCS score ≥ 25 at least once. On multivariable analysis, DCS scores increased with age (+2.64, 95% CI 1.04-4.23), high- vs low-complexity tumors (+6.50, 95% CI 0.35-12.65), and cystic vs solid masses (+9.78, 95% CI 5.27-14.28). Among decision-making factors, DCS scores decreased with higher self-efficacy (-3.31, 95% CI -5.77 to -0.86]) and information-seeking behavior (-4.44, 95% CI -7.32 to -1.56). DCS scores decreased with higher patient-centered communication scores (-8.89, 95% CI -11.85 to -5.94). CONCLUSIONS: In addition to patient and clinical factors, decision-making factors and patient-centered communication relate with decisional conflict, highlighting potential avenues to better support patient decision-making for clinical T1 renal masses.

Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice.

Activity-induced muscle pain increases interleukin-1ß (IL-1ß) release from muscle macrophages and the development of hyperalgesia is prevented by blockade of IL-1ß in muscle. Brain derived neurotrophic factor (BDNF) is released from sensory neurons in response to IL-1ß and mediates both inflammatory and neuropathic pain. Thus, we hypothesize that in activity-induced pain, fatigue metabolites combined with IL-1ß activate sensory neurons to increase BDNF release, peripherally in muscle and centrally in the spinal dorsal horn, to produce hyperalgesia. We tested the effect of intrathecal or intramuscular injection of BDNF-Tropomyosin receptor kinase B (TrkB) inhibitors, ANA-12 or TrkB-Fc, on development of activity-induced pain. Both inhibitors prevented the hyperalgesia when given before or 24hr after induction of the model in male but not female mice. BDNF messenger ribonucleic acid (mRNA) and protein were significantly increased in dorsal root ganglion (DRG) 24hr after induction of the model in both male and female mice. Blockade of IL-1ß in muscle had no effect on the increased BNDF mRNA observed in the activity-induced pain model, while IL-1ß applied to cultured DRG significantly induced BDNF expression, suggesting IL-1ß is sufficient but not necessary to induce BNDF. Thus, fatigue metabolites, combined with IL-1ß, upregulate BDNF in primary DRG neurons in both male and female mice, but contribute to activity-induced pain only in males.

Structurally silent peptide anchor modifications allosterically modulate T cell recognition in a receptor-dependent manner.

Presentation of peptides by class I MHC proteins underlies T cell immune responses to pathogens and cancer. The association between peptide binding affinity and immunogenicity has led to the engineering of modified peptides with improved MHC binding, with the hope that these peptides would be useful for eliciting cross-reactive immune responses directed toward their weak binding, unmodified counterparts. Increasing evidence, however, indicates that T cell receptors (TCRs) can perceive such anchor-modified peptides differently than wild-type (WT) peptides, although the scope of discrimination is unclear. We show here that even modifications at primary anchors that have no discernible structural impact can lead to substantially stronger or weaker T cell recognition depending on the TCR. Surprisingly, the effect of peptide anchor modification can be sensed by a TCR at regions distant from the site of modification, indicating a through-protein mechanism in which the anchor residue serves as an allosteric modulator for TCR binding. Our findings emphasize caution in the use and interpretation of results from anchor-modified peptides and have implications for how anchor modifications are accounted for in other circumstances, such as predicting the immunogenicity of tumor neoantigens. Our data also highlight an important need to better understand the highly tunable dynamic nature of class I MHC proteins and the impact this has on various forms of immune recognition.

Patient and Provider Perception of Transurethral Resection of Bladder Tumor vs Chemoablation for Nonmuscle-invasive Bladder Cancer Treatment.

PURPOSE: The aim of this mixed methods study was to investigate patient and provider perceptions of repeat transurethral resection of bladder tumors to improve counseling as new nonsurgical treatment modalities for nonmuscle-invasive bladder cancer emerge. MATERIALS AND METHODS: Quantitative data were collected via a web-based survey through the Bladder Cancer Advocacy Network of patients with nonmuscle-invasive bladder cancer who had undergone at least 1 transurethral resection of bladder tumor. Bivariable and multivariable analyses were performed to evaluate associations of patient demographics and clinical variables with treatment preference. Qualitative data were collected with 60 in-depth telephone interviews with patients (n=40) and urologists (n=20) to understand experiences with bladder cancer and transurethral resection of bladder tumor. Telephone interviews were conducted by trained qualitative experts. Transcripts were imported into Dedoose to facilitate analysis. RESULTS: Survey data of 352 patients showed 210 respondents (60%) preferred repeat transurethral resection of bladder tumor while 142 (40%) preferred intravesical chemoablation. Patients who preferred repeat transurethral resection of bladder tumor were more likely to prioritize initial treatment effectiveness (63%), whereas those who preferred chemoablation prioritized risk of recurrence (55%). Variables associated with a preference for intravesical chemoablation included U.S. residence (OR=2; 95% CI 1.1, 3.8), or if they expressed their reason for treatment preference as priority of recurrence risk over effectiveness (OR=14.6; 95% CI 7.4, 28.5). Predominant interview themes varied across participants, with patients but not urologists emphasizing the emotional toll of the procedure along with the need for improved counseling regarding recurrence, terminology, and cancer-related signs and symptoms. CONCLUSIONS: Differences exist in the way patients and urologists perceive repeat transurethral resection of bladder tumor for bladder cancer. Understanding transurethral resection of bladder tumor perception will aid in shared decision making as novel treatments emerge for nonmuscle-invasive bladder cancer.

Diagnosis and Management of Non-Metastatic Upper Tract Urothelial Carcinoma: AUA/SUO Guideline.

PURPOSE: The purpose of this guideline is to provide a useful reference on the effective evidence-based diagnoses and management of non-metastatic upper tract urothelial carcinoma (UTUC). MATERIALS/METHODS: The Pacific Northwest Evidence-based Practice Center of Oregon Health & Science University (OHSU) team conducted searches in Ovid MEDLINE (1946 to March 3rd, 2022), Cochrane Central Register of Controlled Trials (through January 2022), and Cochrane Database of Systematic Reviews (through January 2022). The searches were updated August 2022. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (Table 1).[Table: see text]Results:This Guideline provides updated, evidence-based recommendations regarding diagnosis and management of non-metastatic UTUC including risk stratification, surveillance and survivorship. Treatments discussed include kidney sparing management, surgical management, lymph node dissection (LND), neoadjuvant/adjuvant chemotherapy and immunotherapy. CONCLUSION: This standardized guideline seeks to improve clinicians' ability to evaluate and treat patients with UTUC based on available evidence. Future studies will be essential to further support these statements for improving patient care. Updates will occur as the knowledge regarding disease biology, clinical behavior and new therapeutic options develop.

Immediate and Ongoing Impact of COVID-19 on Chlamydia Treatment in Australia.

BACKGROUND: The COVID-19 pandemic has impacted the sexual health and well-being of individuals, directly through risk of contracting COVID-19, and indirectly through government lockdowns. Government restrictions were especially strict and long-lasting in Australia, they also varied by state, offering an interesting opportunity to study the impacts of varying restrictions. This study compares the impact of the COVID-19 pandemic and resulting restrictions on chlamydia treatment prescriptions during 2020, through to July 2021 between different states and demographic groups in Australia. METHODS: The rate of prescriptions per 100,000 population filled each month from January 2017 to July 2021 from Australia's Pharmaceutical Benefits Scheme for Azithromycin with a restricted indication to treat Chlamydia trachomatis was used to measure chlamydia treatment. The impact of COVID-19 lockdowns was modeled using an interrupted time-series Poisson regression model. RESULTS: The data included 520,025 prescriptions to treat chlamydia, averaging 37.5 prescriptions per month per 100,000 population. Prescriptions declined 26% in April to May 2020 when initial COVID-19 lockdowns began in Australia; prescriptions increased in the following months but remained on average 21% below prepandemic (2017-2019) levels through to July 2021. Prescriptions declined the most in 1 Australian state, Victoria, both in the initial lockdown and the following period; generally, states with more COVID-19 cases saw bigger reductions in prescriptions. CONCLUSIONS: This is the first study to examine how treatment for chlamydia in Australia was impacted by the COVID-19 pandemic and restrictions not only in the immediate-term, but also ongoing up to July 2021, providing important information for planning for sexual health services in future pandemics.

An eHealth symptom and complication management program for cancer patients with newly created ostomies and their caregivers (Alliance): a pilot feasibility randomized trial.

BACKGROUND: Cancer patients with newly created ostomies face complications that reduce quality of life (QOL) and increase morbidity and mortality. This proof-of-concept study examined the feasibility, usability, acceptability, and initial efficacy of an eHealth program titled the "Patient Reported Outcomes-Informed Symptom Management System" (PRISMS) during post-ostomy creation care transition. METHODS: We conducted a 2-arm pilot randomized controlled trial among 23 patients who received surgical treatment with curative intent for bladder and colorectal cancer and their caregivers. After assessing QOL, general symptoms, and caregiver burden at baseline, participants were randomly assigned to PRISMS (n = 16 dyads) or usual care (UC) (n = 7 dyads). After a 60-day intervention period, participants completed a follow-up survey and post-exit interview. We used descriptive statistics and t-tests to analyze the data. RESULTS: We achieved an 86.21% recruitment rate and a 73.91% retention rate. Among the PRISMS participants who used the system and biometric devices (n = 14, 87.50%), 46.43% used the devices for ≥ 50 days during the study period. Participants reported PRISMS as useful and acceptable. Compared to their UC counterparts, PRISMS patient social well-being scores decreased over time and had an increased trend of physical and emotional well-being; PRISMS caregivers experienced a greater decrease in caregiver burden. CONCLUSIONS: PRISMS recruitment and retention rates were comparable to existing family-based intervention studies. PRISMS is a useful and acceptable multilevel intervention with the potential to improve the health outcomes of cancer patients needing ostomy care and their caregivers during post-surgery care transition. A sufficiently powered RCT is needed to test its effects. TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT04492007. Registration date: 30/07/2020.

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.

Psychological Stress Management and Stress Reduction Strategies for Stroke Survivors: A Scoping Review.

BACKGROUND: Stroke can be a life-changing event, with survivors frequently experiencing some level of disability, reduced independence, and an abrupt lifestyle change. Not surprisingly, many stroke survivors report elevated levels of stress during the recovery process, which has been associated with worse outcomes. PURPOSE: Given the multiple roles of stress in the etiology of stroke recovery outcomes, we aimed to scope the existing literature on stress management interventions that have been trialed in stroke survivors. METHODS: We performed a database search for intervention studies conducted in stroke survivors which reported the effects on stress, resilience, or coping outcome. Medline (OVID), Embase (OVID), CINAHL (EBSCO), Cochrane Library, and PsycInfo (OVID) were searched from database inception until March 11, 2019, and updated on September 1, 2020. RESULTS: Twenty-four studies met the inclusion criteria. There was significant variation in the range of trialed interventions, as well as the outcome measures used to assess stress. Overall, just over half (13/24) of the included studies reported a benefit in terms of stress reduction. Acceptability and feasibility were considered in 71% (17/24) and costs were considered in 17% (4/24) of studies. The management of stress was rarely linked to the prevention of symptoms of stress-related disorders. The overall evidence base of included studies is weak. However, an increase in the number of studies over time suggests a growing interest in this subject. CONCLUSIONS: Further research is required to identify optimum stress management interventions in stroke survivors, including whether the management of stress can ameliorate the negative impacts of stress on health.

Optimising the management of children with concomitant bladder dysfunction and behavioural disorders.

Bladder dysfunction and behavioural disorders in children are commonly concomitant; hence, it is difficult to treat each in isolation. Pharmacotherapy is common treatment for behavioural disorders, and these medications may have intended or unintended positive or negative bladder sequelae. This review identifies the literature regarding the effects of behavioural pharmacotherapy on bladder functioning and possible bladder management strategies in children with concomitant behaviour and bladder disorders to enable clinicians to better manage both conditions. A PROSPERO registered PRISMA-guided review of three major databases was performed. After an initial scoping study revealed significant heterogeneity, a narrative approach was undertaken to discuss the results of all relevant cases relating to children being treated with pharmacotherapy for behaviour disorders and outcomes related to bladder function. Studies were screened to identify those that described effects of commonly prescribed medications in children with behavioural disorders such as stimulants, alpha 2 agonists, tricyclic antidepressants (TCA), serotonin and noradrenergic reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI) and antipsychotics, and the findings and implications were summarised. The review identified 46 studies relevant to behavioural pharmacotherapy and bladder function (stimulants (n = 9), alpha 2 agonists (n = 2), TCAs (n = 7), SNRIs (n = 8), SSRIs (n = 8) and antipsychotics (n = 6). Six studies focused specifically on bladder management in children with behavioural disorders with concurrent behavioural pharmacotherapy. This review identifies useful factors that may assist clinicians with predicting unintended bladder effects following initiation of behavioural pharmacotherapy to facilitate the best approach to the treatment of bladder dysfunction in children with behavioural disorders. With this evidence, we have provided a useful decision-making algorithm to aide clinicians in the management of these dual pathologies.

Ohio Coronavirus Wastewater Monitoring Network: Implementation of Statewide Monitoring for Protecting Public Health.

CONTEXT: Prior to the COVID-19 pandemic, wastewater influent monitoring for tracking disease burden in sewered communities was not performed in Ohio, and this field was only on the periphery of the state academic research community. PROGRAM: Because of the urgency of the pandemic and extensive state-level support for this new technology to detect levels of community infection to aid in public health response, the Ohio Water Resources Center established relationships and support of various stakeholders. This enabled Ohio to develop a statewide wastewater SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) monitoring network in 2 months starting in July 2020. IMPLEMENTATION: The current Ohio Coronavirus Wastewater Monitoring Network (OCWMN) monitors more than 70 unique locations twice per week, and publicly available data are updated weekly on the public dashboard. EVALUATION: This article describes the process and decisions that were made during network initiation, the network progression, and data applications, which can inform ongoing and future pandemic response and wastewater monitoring. DISCUSSION: Overall, the OCWMN established wastewater monitoring infrastructure and provided a useful tool for public health professionals responding to the pandemic.

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.

Minimal Patient-Reported Side Effects for a Chemoablative Gel (UGN-102) Used as Frontline Treatment in Adults with Nonmuscle-Invasive Bladder Cancer.

PURPOSE: Optima II ("OPTimized Instillation of Mitomycin for Bladder Cancer Treatment," clinicaltrials.gov: NCT03558503) was a phase 2b trial evaluating a nonsurgical alternative as a primary treatment for nonmuscle-invasive bladder cancer (NMIBC). Patients received 6 weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel. This is the first study to report on patient-reported side effects of UGN-102. MATERIALS AND METHODS: Sixty-three patients enrolled in Optima II from 20 sites. Of these 63 patients, 44 were in the cohort completing a quarterly patient-reported outcome measure assessing side effects. Changes in side effects were evaluated using the Wilcoxon signed-rank test. Associations of 3-month outcomes with demographic and clinical characteristics were examined with regression, controlling for baseline values. Ten of 44 patients (23%) were interviewed after the trial to understand tolerability for future patients making treatment decisions. Transcripts were double-coded using standard methods. RESULTS: In the patient-reported outcome measure cohort (44), 61% were men, 57% aged 65+ years and 89% were non-Hispanic White. UGN-102 did not cause decrements in patient-reported urinary symptoms, bloating/flatulence or malaise at the primary endpoint of 3 months. Sexual function mildly worsened. Future health worries improved. Demographics were not correlated with changes. Clinically, sexual function was correlated with new NMIBC and bloating/flatulence was associated with transurethral resection of bladder tumor within 12 months. In interviews, patients appreciated a nonsurgical alternative, would recommend the gel to other patients and would choose the gel over surgery. CONCLUSIONS: A nonsurgical, chemoablative gel (UGN-102) used as a primary treatment for NMIBC offers a more patient-centered therapeutic approach than standard treatments.

A Patient-Centered Approach to Research Prioritization in Prostate Cancer.

PURPOSE: Research priorities are often set by expert clinicians and researchers. We sought to apply an established process in patient-centered research to engage survivors and their caregivers in prioritizing research topics in prostate cancer. MATERIALS AND METHODS: A prostate cancer patient survey network, formed in partnership with Us TOO and the National Alliance of State Prostate Cancer Coalitions, engaged in a series of mixed-methods studies to prioritize comparative effectiveness research questions. This was accomplished through an iterative process that included 2 survey rounds and multidisciplinary working groups. RESULTS: There were 591 and 706 survey respondents in the first and second rounds, respectively, with most having had localized prostate cancer (58.1%). Survey participants represented 45 states in the U.S. Five of the top 11 prioritized research questions related to treatment decision making and/or survivorship care. The following had the highest overall importance ratings: What is the comparative effectiveness of different 1) strategies to improve counseling regarding the side effects of prostate cancer treatment, 2) tools for decision making in localized prostate cancer and 3) sequences of treatments for metastatic prostate cancer? CONCLUSIONS: We present a unique, patient-centered list of prioritized research questions among prostate cancer patients and their caregivers. These research questions may inform funding decisions for organizations that support research, and should be considered as priorities for clinicians, researchers and institutions conducting prostate cancer research. Prostate cancer is a common disease that affects 1 in 9 men over their lifetime. Researchers usually identify questions to study without asking men with prostate cancer. We asked survivors of prostate cancer and their caregivers to help us. They identified research questions and topics that are important to them. Researchers can focus on this list of questions to help men with prostate cancer. Groups who pay for research studies can make these questions their priority.

Primary Chemoablation of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer Using UGN-102, a Mitomycin-Containing Reverse Thermal Gel (Optima II): A Phase 2b, Open-Label, Single-Arm Trial.

PURPOSE: Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC. MATERIALS AND METHODS: This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. RESULTS: A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue. CONCLUSIONS: Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.

Durability of Response to Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma Using UGN-101, a Mitomycin-Containing Reverse Thermal Gel: OLYMPUS Trial Final Report.

PURPOSE: Our goal was to evaluate long-term safety and durability of response to UGN-101, a mitomycin-containing reverse thermal gel, as primary chemoablative treatment for low-grade upper tract urothelial carcinoma. MATERIALS AND METHODS: In this open-label, single-arm, multicenter, phase 3 trial (NCT02793128), patients ≥18 years of age with primary or recurrent biopsy-proven low-grade upper tract urothelial carcinoma received 6 once-weekly instillations of UGN-101 via retrograde catheter to the renal pelvis and calyces. Those with complete response (defined as negative ureteroscopic evaluation, negative cytology and negative for-cause biopsy) 4-6 weeks after the last instillation were eligible for up to 11 monthly maintenance instillations and were followed for ≥12 months with quarterly evaluation of response durability. Durability of complete response was determined by ureteroscopic evaluation; duration of response was estimated by the Kaplan-Meier method. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Of 71 patients who initiated treatment, 41 (58%) had complete response to induction therapy and consented to long-term followup; 23/41 patients (56%) remained in complete response after 12 months (95% CI 40, 72), comprising 6/12 (50%) who did not receive any maintenance instillations and 17/29 (59%) who received ≥1 maintenance instillation. Kaplan-Meier analysis of durability was estimated as 82% (95% CI 66, 91) at 12 months. Ureteric stenosis was the most frequently reported TEAE (31/71, 44%); an increasing number of instillations appeared to be associated with increased incidence of urinary TEAEs. CONCLUSIONS: Durability of response to UGN-101 with or without maintenance treatment is clinically meaningful, offering a kidney-sparing therapeutic alternative for patients with low-grade disease.

Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report.

Wiskott-Aldrich syndrome (WAS) is an X-linked disease caused by mutations in the WAS gene, leading to thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is the primary curative approach, with the goal of correcting the underlying immunodeficiency and thrombocytopenia. HCT outcomes have improved over time, particularly for patients with HLA-matched sibling and unrelated donors. We report the outcomes of 129 patients with WAS who underwent HCT at 29 Primary Immune Deficiency Treatment Consortium centers from 2005 through 2015. Median age at HCT was 1.2 years. Most patients (65%) received myeloablative busulfan-based conditioning. With a median follow-up of 4.5 years, the 5-year overall survival (OS) was 91%. Superior 5-year OS was observed in patients <5 vs ≥5 years of age at the time of HCT (94% vs 66%; overall P = .0008). OS was excellent regardless of donor type, even in cord blood recipients (90%). Conditioning intensity did not affect OS, but was associated with donor T-cell and myeloid engraftment after HCT. Specifically, patients who received fludarabine/melphalan-based reduced-intensity regimens were more likely to have donor myeloid chimerism <50% early after HCT. In addition, higher platelet counts were observed among recipients who achieved full (>95%) vs low-level (5%-49%) donor myeloid engraftment. In summary, HCT outcomes for WAS have improved since 2005, compared with prior reports. HCT at a younger age continues to be associated with superior outcomes supporting the recommendation for early HCT. High-level donor myeloid engraftment is important for platelet reconstitution after either myeloablative or busulfan-containing reduced intensity conditioning. (This trial was registered at www.clinicaltrials.gov as #NCT02064933.).