Rationale and design of the randomized COmparison of Methods for Pulmonary blood flow Augmentation: Shunt versus Stent (COMPASS) trial: A Pediatric Heart Network study.

Neonates with congenital heart disease (CHD) and ductal-dependent pulmonary blood flow (DD-PBF) require early intervention. Historically, this intervention was most often a surgical systemic-to-pulmonary shunt (SPS; e.g., Blalock-Thomas-Taussig shunt). However, over the past two decades an alternative to SPS has emerged in the form of transcatheter ductal artery stenting (DAS). While many reports have indicated safety and durability of the DAS approach, few studies compare outcomes between DAS and SPS. The reports that do exist are comprised primarily of small-cohort single-center reviews. Two multicenter retrospective studies suggest that DAS is associated with similar or superior survival compared to SPS. These studies offer the best evidence to-date, and yet both have important limitations. The authors describe herein the rationale and design of the COMPASS (COmparison of Methods for Pulmonary blood flow Augmentation: Shunt vs. Stent) Trial (NCT05268094, IDE G210212). The COMPASS Trial aims to randomize 236 neonates with DD-PBF to either DAS or SPS across approximately 27 pediatric centers in North America. The goal of this trial is to compare important clinical outcomes between DAS and SPS over the first year of life in a cohort of neonates balanced by randomization to assess whether one method of palliation demonstrates therapeutic superiority.

Implementing Change: Sustaining Enhanced Recovery After Surgery Protocols in Pediatric Surgery Using Iterative Assessments.

INTRODUCTION: While Enhanced Recovery After Surgery (ERAS) protocols are becoming more common in pediatric surgery, there is still little published about protocol compliance and sustainability. METHODS: This is a prospective observational study to evaluate the compliance of an ERAS protocol for pectus repair at a large academic children's hospital. Our primary outcome was overall protocol compliance at 1-y postimplementation of the ERAS protocol. Our comparison group included all pectus repairs for 2 y before protocol implementation. RESULTS: Overall protocol compliance at 12 mo was 89%. Of the 16 pectus repairs included in the ERAS protocol group, 94% (n = 15) and 94% (n = 15) received preoperative acetaminophen and gabapentin, respectively, which was significantly greater than the historical control group (P < 0.001). For the intraoperative components analyzed, only the intrathecal morphine was significantly different than historical controls (100% versus 49%, P < 0.001). Postoperatively, the time from operating room to return to normal diet was shorter for the ERAS group (0.53 d versus 1.16 d, P < 0.001). There was no significant difference in readmission rates between the two groups. CONCLUSIONS: ERAS protocol compliance varies based on phase of care. Solutions to sustain protocols depend on the institution and the patient population. However, the utilization of implementation science fundamentals was invaluable in this study to identify and address areas for improvement in protocol compliance. Other institutions may adapt these strategies to improve protocol compliance at their centers.

Implementation Science Fundamentals: Pediatric Surgery Enhanced Recovery After Surgery Protocol for Pectus Repair.

INTRODUCTION: Surgical repair of pectus excavatum and carinatum in children has historically been associated with severe postoperative pain and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) is a multidisciplinary, multimodal approach designed to fast-track surgical care. However, obstacles to implementation have led to very few within pediatric surgery. The aim of this study is to outline the process of development and implementation of an ERAS protocol for pectus surgical repair using fundamental principles of implementation science. METHODS: A multidisciplinary team of providers worked collaboratively to develop an ERAS protocol for surgical repair of pectus excavatum and carinatum and methods for identifying eligible patients. The surgical champion collaborated with all end users to review and revise the ERAS protocol, assessing all foreseeable barriers and facilitators prior to implementation. RESULTS: Our entire pediatric surgery team, nurses at every stage (clinic/preoperative/recovery/floor), physical therapy, and information technology contributed to the creation and implementation of an ERAS protocol with seven phases of care. The finalized version was implemented by end users focusing on four main areas: pain control, ambulation, diet, and education. Barriers and facilitators were continually addressed with an iterative process to improve the success of implementation. CONCLUSIONS: This is one of the first studies in children which details the step-by-step process of developing and implementing an ERAS protocol for pectus excavatum and carinatum. The process of development and implementation of an ERAS protocol as outlined in this manuscript can serve as a model for future ERAS protocols in pediatric surgery.

Challenges and Successes of Global Deprescribing Networks: A Qualitative Key Informant Study.

The landscape of deprescribing has been rapidly evolving and expanding globally with the formation of regional and national deprescribing networks. The work of these networks is primarily focused on older adults and high-risk medications. The purpose of the current qualitative study is to describe successes and challenges of deprescribing from thought-leaders across the world. Fourteen key informant interviews were conducted from various disciplines, levels of experiences, and regions around the globe. From the interviews, six major themes across two domains were identified: (a) network structure, (b) public perception, (c) policy implications, (d) implementation, (e) challenges, and (f) recommendations. These domains, themes, and insight provided by deprescribing leaders contribute to the advancement of deprescribing networks as global efforts continue to focus on optimizing medication management. Collaboration among interprofessional team members will be critical to the expansion as well as sustainability of this important work. [Journal of Gerontological Nursing, 48(1), 7-14.].

ftmsRanalysis: An R package for exploratory data analysis and interactive visualization of FT-MS data.

The high-resolution and mass accuracy of Fourier transform mass spectrometry (FT-MS) has made it an increasingly popular technique for discerning the composition of soil, plant and aquatic samples containing complex mixtures of proteins, carbohydrates, lipids, lignins, hydrocarbons, phytochemicals and other compounds. Thus, there is a growing demand for informatics tools to analyze FT-MS data that will aid investigators seeking to understand the availability of carbon compounds to biotic and abiotic oxidation and to compare fundamental chemical properties of complex samples across groups. We present ftmsRanalysis, an R package which provides an extensive collection of data formatting and processing, filtering, visualization, and sample and group comparison functionalities. The package provides a suite of plotting methods and enables expedient, flexible and interactive visualization of complex datasets through functions which link to a powerful and interactive visualization user interface, Trelliscope. Example analysis using FT-MS data from a soil microbiology study demonstrates the core functionality of the package and highlights the capabilities for producing interactive visualizations.

Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) peak intensity normalization for complex mixture analyses.

RATIONALE: Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) is a preferred technique for analyzing complex organic mixtures. Currently, there is no consensus normalization approach, nor an objective method for selecting one, for quantitative analyses of FT-ICR-MS data. We investigate a method to evaluate and score the amount of bias various normalization approaches introduce into the data. METHODS: We evaluate the ability of the Statistical Procedure for the Analysis of Normalization Strategies (SPANS) to guide the selection of appropriate normalization approaches for two different FT-ICR-MS data sets. Furthermore, we test the robustness of SPANS results to changes in SPANS parameter values and assess the impact of using various normalization approaches on downstream statistical analyses. RESULTS: The normalization approach identified by SPANS differed for the two data sets. Normalization methods impacted the statistical significance of peaks differently, underscoring the importance of carefully evaluating potential methods. More consistent SPANS scores resulted when at least 120 significant peaks are used, where larger sets of peaks were obtained by increasing the p-value threshold. Interestingly, we show that total sum scaling and highest peak normalization, used in previous studies, underperformed relative to SPANS-recommended normalization approaches. CONCLUSIONS: Although there is no single, best normalization method for all data sets, SPANS provides a mechanism to identify an appropriate normalization method for analyzing FT-ICR-MS data quantitatively. The number of peaks used in the background distributions of SPANS contributes more significantly to the reproducibility of results than the p-value thresholds used to obtain those peaks.

KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma.

BACKGROUND: Mast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma. METHODS: We conducted a randomized, double-blind, placebo-controlled, 24-week trial of imatinib in patients with poorly controlled severe asthma who had airway hyperresponsiveness despite receiving maximal medical therapy. The primary end point was the change in airway hyperresponsiveness, measured as the concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20% (PC20). Patients also underwent bronchoscopy. RESULTS: Among the 62 patients who underwent randomization, imatinib treatment reduced airway hyperresponsiveness to a greater extent than did placebo. At 6 months, the methacholine PC20 increased by a mean (±SD) of 1.73±0.60 doubling doses in the imatinib group, as compared with 1.07±0.60 doubling doses in the placebo group (P=0.048). Imatinib also reduced levels of serum tryptase, a marker of mast-cell activation, to a greater extent than did placebo (decrease of 2.02±2.32 vs. 0.56±1.39 ng per milliliter, P=0.02). Airway mast-cell counts declined in both groups. Muscle cramps and hypophosphatemia were more common in the imatinib group than in the placebo group. CONCLUSIONS: In patients with severe asthma, imatinib decreased airway hyperresponsiveness, mast-cell counts, and tryptase release. These results suggest that KIT-dependent processes and mast cells contribute to the pathobiologic basis of severe asthma. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01097694 .).

Quality Control Analysis in Real-time (QC-ART): A Tool for Real-time Quality Control Assessment of Mass Spectrometry-based Proteomics Data.

Liquid chromatography-mass spectrometry (LC-MS)-based proteomics studies of large sample cohorts can easily require from months to years to complete. Acquiring consistent, high-quality data in such large-scale studies is challenging because of normal variations in instrumentation performance over time, as well as artifacts introduced by the samples themselves, such as those because of collection, storage and processing. Existing quality control methods for proteomics data primarily focus on post-hoc analysis to remove low-quality data that would degrade downstream statistics; they are not designed to evaluate the data in near real-time, which would allow for interventions as soon as deviations in data quality are detected. In addition to flagging analyses that demonstrate outlier behavior, evaluating how the data structure changes over time can aide in understanding typical instrument performance or identify issues such as a degradation in data quality because of the need for instrument cleaning and/or re-calibration. To address this gap for proteomics, we developed Quality Control Analysis in Real-Time (QC-ART), a tool for evaluating data as they are acquired to dynamically flag potential issues with instrument performance or sample quality. QC-ART has similar accuracy as standard post-hoc analysis methods with the additional benefit of real-time analysis. We demonstrate the utility and performance of QC-ART in identifying deviations in data quality because of both instrument and sample issues in near real-time for LC-MS-based plasma proteomics analyses of a sample subset of The Environmental Determinants of Diabetes in the Young cohort. We also present a case where QC-ART facilitated the identification of oxidative modifications, which are often underappreciated in proteomic experiments.

pmartR: Quality Control and Statistics for Mass Spectrometry-Based Biological Data.

Prior to statistical analysis of mass spectrometry (MS) data, quality control (QC) of the identified biomolecule peak intensities is imperative for reducing process-based sources of variation and extreme biological outliers. Without this step, statistical results can be biased. Additionally, liquid chromatography-MS proteomics data present inherent challenges due to large amounts of missing data that require special consideration during statistical analysis. While a number of R packages exist to address these challenges individually, there is no single R package that addresses all of them. We present pmartR, an open-source R package, for QC (filtering and normalization), exploratory data analysis (EDA), visualization, and statistical analysis robust to missing data. Example analysis using proteomics data from a mouse study comparing smoke exposure to control demonstrates the core functionality of the package and highlights the capabilities for handling missing data. In particular, using a combined quantitative and qualitative statistical test, 19 proteins whose statistical significance would have been missed by a quantitative test alone were identified. The pmartR package provides a single software tool for QC, EDA, and statistical comparisons of MS data that is robust to missing data and includes numerous visualization capabilities.

Apneic Oxygenation As a Quality Improvement Intervention in an Academic PICU.

OBJECTIVES: To evaluate if the use of apneic oxygenation during tracheal intubation in children is feasible and would decrease the occurrence of oxygen desaturation. DESIGN: Prospective pre/post observational study. SETTING: A large single-center noncardiac PICU in North America. PATIENTS: All patients less than 18 years old who underwent primary tracheal intubation from August 1, 2014, to September 30, 2018. INTERVENTIONS: Implementation of apneic oxygenation for all primary tracheal intubation as quality improvement. MEASUREMENTS AND MAIN RESULTS: Total of 1,373 tracheal intubations (661 preimplementation and 712 postimplementation) took place during study period. Within 2 months, apneic oxygenation use reached to predefined adherence threshold (> 80% of primary tracheal intubations) after implementation and sustained at greater than 70% level throughout the postimplementation. Between the preimplementation and postimplementation, no significant differences were observed in patient demographics, difficult airway features, or providers. Respiratory and procedural indications were more common during preintervention. Video laryngoscopy devices were used more often during the postimplementation (pre 5% vs post 75%; p < 0.001). Moderate oxygen desaturation less than 80% were observed in fewer tracheal intubations after apneic oxygenation implementation (pre 15.4% vs post 11.8%; p = 0.049); severe oxygen desaturation less than 70% was also observed in fewer tracheal intubations after implementation (pre 10.4% vs post 7.2%; p = 0.032). Hemodynamic tracheal intubation associated events (i.e., cardiac arrests, hypotension, dysrhythmia) were unchanged (pre 3.2% vs post 2.0%; p = 0.155). Multivariable analyses showed apneic oxygenation implementation was significantly associated with a decrease in moderate desaturation less than 80% (adjusted odds ratio, 0.55; 95% CI, 0.34-0.88) and with severe desaturation less than 70% (adjusted odds ratio, 0.54; 95% CI, 0.31-0.96) while adjusting for tracheal intubation indications and device. CONCLUSIONS: Implementation of apneic oxygenation in PICU was feasible, and was associated with significant reduction in moderate and severe oxygen desaturation. Use of apneic oxygenation should be considered when intubating critically ill children.

An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era.

The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with aggressive non-Hodgkin lymphoma (NHL) for the past 20 years. Using raw clinical data from the National Comprehensive Cancer Network (NCCN) database collected during the rituximab era, we built an enhanced IPI with the goal of improving risk stratification. Clinical features from 1650 adults with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed from 2000-2010 at 7 NCCN cancer centers were assessed for their prognostic significance, with statistical efforts to further refine the categorization of age and normalized LDH. Five predictors (age, lactate dehydrogenase (LDH), sites of involvement, Ann Arbor stage, ECOG performance status) were identified and a maximum of 8 points assigned. Four risk groups were formed: low (0-1), low-intermediate (2-3), high-intermediate (4-5), and high (6-8). Compared with the IPI, the NCCN-IPI better discriminated low- and high-risk subgroups (5-year overall survival [OS]: 96% vs 33%) than the IPI (5 year OS: 90% vs 54%), respectively. When validated using an independent cohort from the British Columbia Cancer Agency (n = 1138), it also demonstrated enhanced discrimination for both low- and high-risk patients. The NCCN-IPI is easy to apply and more powerful than the IPI for predicting survival in the rituximab era.

High Body Mass Index in Elderly Patients With DLBCL Treated With Rituximab-Containing Therapy Compensates for Negative Impact of Male Sex.

BACKGROUND: The impact of patient body habitus and sex on outcomes in diffuse large B-cell lymphoma (DLBCL) remains controversial. We investigated the impact of body mass index (BMI), body surface area (BSA), age, and sex on clinical outcomes in patients with DLBCL treated in the rituximab era. PATIENTS AND METHODS: Patients with de novo DLBCL (n=1,386) diagnosed between June 2000 and December 2010 treated with rituximab-containing chemotherapy were identified from the NCCN Oncology Outcomes Database for Non-Hodgkin's Lymphoma. Progression-free survival (PFS) and overall survival (OS) at 3 years were analyzed based on sex, age, and baseline BMI/BSA. RESULTS: High BMI was associated with a lower risk of disease progression or death than low or normal BMI, whereas male sex was associated with poor clinical outcomes, especially among elderly patients (age >60 years). Compared with elderly women, elderly men experienced worse PFS (3-year hazard ratio [HR], 1.5) and OS (3-year HR, 1.6), but these differences diminished with increases in BMI and BSA. In multivariable analysis, normal BMI compared with high BMI was independently associated with poor outcomes (3-year PFS HR, 1.5; OS HR, 1.6) after adjusting for sex. Notably, only 13% of elderly men had BMI less than 25 kg/m2 and only 26% had BSA less than 2 m2 CONCLUSIONS: Analysis of unselected patients with DLBCL treated with rituximab-containing chemotherapy confirmed an age-dependent disadvantage to male sex in treatment outcomes, but this effect is abrogated by higher levels of BMI and BSA in most North American men.

Radiation for diffuse large B-cell lymphoma in the rituximab era: analysis of the National Comprehensive Cancer Network lymphoma outcomes project.

BACKGROUND: The role of consolidation radiotherapy was examined for patients with diffuse large B-cell lymphoma who were treated at institutions of the National Comprehensive Cancer Network during the rituximab era. METHODS: Failure-free survival (FFS) and overall survival (OS) were analyzed in terms of patient and treatment characteristics. Potential associations were investigated with univariate and multivariate survival analysis and matched pair analysis. RESULTS: There were 841 patients, and most (710 or 84%) received 6 to 8 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); 293 (35%) received consolidation radiation therapy (RT). Failure occurred for 181 patients: 126 patients (70%) who did not receive RT and 55 patients (30%) who did. At 5 years, both OS and FFS rates were better for patients who had received RT versus those who did not (OS, 91% vs 83% [P = .01]; FFS, 83% vs 76% [P = .05]). A matched pair analysis (217 pairs matched by age, stage, International Prognostic Index [IPI] score, B symptoms, disease bulk, and response to chemotherapy) showed that the receipt of RT improved OS (hazard ratio [HR], 0.53 [P = .07]) and FFS (HR, 0.77 [P = .34]) for patients with stage III/IV disease, but too few events took place among those with stage I/II disease for meaningful comparisons (HR for OS, 0.94 [P = .89]; HR for FFS, 1.81 [P = .15]). A multivariate analysis suggested that the IPI score and the response to chemotherapy had the greatest influence on outcomes. CONCLUSIONS: There was a trend of higher OS and FFS rates for patients who had received consolidation RT after R-CHOP (especially for patients with stage III/IV disease), but the difference did not reach statistical significance.

From placement to prison revisited: Do mental health services disrupt the delinquency pipeline among Latino, African American and Caucasian youth in the child welfare system?

Racial and ethnic disparities in delinquency among child welfare-involved youth are well documented. However, less is known about the mechanisms through which these disparities occur. This study explores the extent to which sets of variables predict the occurrence of juvenile delinquency and whether race/ethnicity moderates the strength of the relationships between (1) social, emotional, and behavioral (SEB) problems and delinquency and (2) mental health service use and delinquency. We used a nationally representative sample of 727 African American, Caucasian, and Latino youth between the ages of 12-17 who were referred to the child welfare system. Controlling for age, gender, placement instability, maltreatment history, poverty, and urbanicity, linear regression analyses revealed that African American and Latino youth engaged in more delinquent acts than Caucasian youth did. However, service use decreased the likelihood of engaging in more delinquent acts for African Americans. Additional efforts are needed to illuminate and address the contextual and organizational barriers to delivering effective mental health services as a strategy to reduce racial disparities in delinquent behavior.

Comparison of referring and final pathology for patients with T-cell lymphoma in the National Comprehensive Cancer Network.

BACKGROUND: T-cell lymphomas (TCLs) are uncommon in the United States. The accurate diagnosis of TCL is challenging and requires morphologic interpretation, immunophenotyping, and molecular techniques. The authors compared pathologic diagnoses at referring centers with diagnoses from expert hematopathology review to determine concordance rates and to characterize the usefulness of second-opinion pathology review for TCL. METHODS: Patients in the National Comprehensive Cancer Network non-Hodgkin lymphoma database with peripheral TCL, not otherwise specified (PTCL-NOS), angioimmunoblastic TCL (AITL), and anaplastic lymphoma kinase (ALK)-positive and ALK-negative anaplastic large cell lymphoma (ALCL) were eligible if they had prior tissue specimens examined at a referring institution. Pathologic concordance was evaluated using available pathology and diagnostic testing reports and provider progress notes. The etiology of discordance and the potential impact on treatment were examined. RESULTS: Among 131 eligible patients, 57 (44%) had concordant results, totaling 64% of the 89 patients who were referred with a final diagnosis. Thirty-two patients (24%) had discordant results, representing 36% of those who were referred with a final diagnosis. The rates of discordance among patients with of PTCL-NOS, AITL, ALK-negative ALCL, and ALK-positive ALCL were 19%, 33%, 34%, and 6%, respectively. In 14 patients (44% of discordant results), pathologic reclassification could have resulted in a different therapeutic strategy. Forty-two patients (32%) were referred for classification with a provisional diagnosis. CONCLUSIONS: In a large cohort of patients with TCL who were referred to National Comprehensive Cancer Network centers, the likelihood of a concordant final diagnosis at a referring institution was low. As current and future therapies target TCL subsets, these data suggest that patients with suspected TCLs would benefit from evaluation by an expert hematopathologist.

Economic Impact of Bladder Cancer in the USA.

INTRODUCTION: Incidence and mortality for bladder cancer has changed very little over the past 20 years. Approximately 40% of patients with high-risk nonmuscle invasive bladder cancer eventually recur/progress. It is important to understand the economic impact of disease recurrence/progression in bladder cancer. Our aim was to estimate and understand the direct costs associated with the treatment of bladder cancer from the payer's perspective in the USA, in the year of 2021, including costs for both newly diagnosed bladder cancer (stages 0a-IV) and recurrent patients. METHODS: An economic model was constructed to calculate the number of patients receiving each treatment modality at every stage of disease and their respective costs. Epidemiological data were based on the CancerMPact Patient Metrics (PM) database and treatment modality data retrieved from CMP Treatment Architecture (TA), 2021 version. Resource utilization and costs were obtained from medical literature and public data sources. Only direct costs were considered. RESULTS: There were an estimated 83,532 newly diagnosed patients with bladder cancer of all stages in 2021 with a projected total cost of treatment of ~$2.6 billion. Average cost per newly diagnosed patient varied from $19,521 (stage 0a) to $169,533 (metastatic disease). Cost profile differed substantially among the stages of disease. For the 75,760 patients that were expected to have a recurrence in 2021, an additional cost of ~$3.9 billion was estimated at an average cost per patient of $52,179. The expected total cost to treat newly diagnosed and newly recurrent patients is reported in this model, with the total cost in 2021 estimated to exceed $6.5 billion. CONCLUSIONS: Treatment and resource costs increase for bladder cancer as the disease recurs/progresses. More effective treatments that can delay recurrence/progression may reduce the economic burden associated with bladder cancer.

The costs of treating bladder cancer in the USA are high, expected to have exceeded $6.5 billion in the year 2021. The average cost for newly diagnosed patients ranges from $19,521 for the earliest stage of disease to $169,533 for metastatic disease. Average costs per patient increase upon disease recurrence and more effective initial treatments to delay disease recurrence or progression may reduce the costs associated with bladder cancer.

Patient experience and unmet needs in high-risk nonmuscle-invasive bladder cancer: Insights from qualitative interviews and a cross-sectional survey.

OBJECTIVES: To evaluate patient experience, unmet needs, and burden among patients with high-risk nonmuscle-invasive bladder cancer (HR-NMIBC) treated with Bacillus Calmette-Guérin (BCG). METHODS: This cross-sectional study included HR-NMIBC patients who received BCG treatment in the past 3 years. The study, preceded by a focused literature review, was conducted in 2 phases: 1) qualitative interviews with 32 patients in the United States (US), France, Germany, and United Kingdom (UK) and 2) quantitative survey of 150 patients in the US. Both phases of the study assessed patient characteristics, treatment history, experience, and perceptions, as well as side effects, pain, discomfort, and time burden associated with BCG treatment. The quantitative survey included additional items related to BCG treatment satisfaction, health-related quality of life (HRQoL), productivity, and healthcare resource utilization. Descriptive statistics and bivariate subgroup comparisons were reported. RESULTS: All patients in both study phases received transurethral resection of the bladder tumor (TURBT). Nearly all patients reported keeping their bladder/avoiding radical cystectomy (RC) was important (99%). Results from the quantitative survey reported a substantial impact to cancer-specific HRQoL of patients, with lower mean scores on physical (64.7), social (62.8), and role functioning (56.7) as measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30). Most patients (69%) were satisfied overall with BCG treatment, although satisfaction declined with increased number of side effects, higher numbers of BCG administrations, and greater discomfort (all P < 0.05). CONCLUSIONS: Most HR-NMIBC patients were satisfied overall with BCG treatment. Approximately half of the patients had stopped BCG treatment, notably, most during the induction phase, suggesting nonadherence to guidelines which recommend maintenance treatment after induction. Future treatments should focus on delaying or avoiding recurrence and cystectomy while reducing patient discomfort and discontinuation prior to completing the recommended course of treatment.

A Phase Three Study of the Safety and Immunogenicity of a Four-dose Series of 20-Valent Pneumococcal Conjugate Vaccine in Healthy Infants.

BACKGROUND: The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13). METHODS: This phase 3, double-blind study conducted in the United States/Puerto Rico evaluated PCV20 safety and immunogenicity. Healthy infants were randomized to receive a 4-dose series of PCV20 or PCV13 at 2, 4, 6 and 12-15 months old. Objectives included demonstrating noninferiority (NI) of PCV20 to PCV13 immunoglobulin G (IgG) geometric mean concentrations after doses 3 and 4 and percentages of participants with predefined IgG concentrations after dose 3, with 7 additional PCV20 serotypes compared with the lowest result among vaccine serotypes in the PCV13 group. Safety assessments included local reactions, systemic events, adverse events, serious adverse events and newly diagnosed chronic medical conditions. RESULTS: Overall, 1991 participants were vaccinated (PCV20, n = 1001; PCV13, n = 990). For IgG geometric mean concentrations 1 month after both doses 3 and 4, all 20 serotypes met NI criteria (geometric mean ratio lower 2-sided 95% confidence interval > 0.5). For percentages of participants with predefined IgG concentrations after dose 3, NI (percentage differences lower 2-sided 95% confidence interval > -10%) was met for 8/13 matched serotypes and 6/7 additional serotypes; 4 serotypes missed the statistical NI criterion by small margins. PCV20 also elicited functional and boosting responses to all 20 serotypes. The safety profile of PCV20 was similar to PCV13. CONCLUSION: A 4-dose series of PVC20 was well tolerated and elicited robust serotype-specific immune responses expected to help protect infants and young children against pneumococcal disease due to the 20 vaccine serotypes. Clinical trial registration: NCT04382326.

Rationale and Design of the Randomized COmparison of Methods for Pulmonary Blood Flow Augmentation: Shunt Versus Stent (COMPASS) Trial: A Pediatric Heart Network Study.

Neonates with congenital heart disease and ductal-dependent pulmonary blood flow (DD-PBF) require early intervention. Historically, this intervention was most often a surgical systemic-to-pulmonary shunt (SPS; eg, Blalock-Thomas-Taussig shunt). However, over the past two decades, an alternative to SPS has emerged in the form of transcatheter ductal artery stenting (DAS). While many reports have indicated safety and durability of the DAS approach, few studies compare outcomes between DAS and SPS. The reports that do exist are comprised primarily of small-cohort single-center reviews. Two multicenter retrospective studies suggest that DAS is associated with similar or superior survival compared with SPS. These studies offer the best evidence to-date, and yet both have important limitations. The authors describe herein the rationale and design of the COMPASS (COmparison of Methods for Pulmonary blood flow Augmentation: Shunt vs Stent [COMPASS]) Trial (NCT05268094, IDE G210212). The COMPASS Trial aims to randomize 236 neonates with DD-PBF to either DAS or SPS across approximately 27 pediatric centers in North America. The goal of this trial is to compare important clinical outcomes between DAS and SPS over the first year of life in a cohort of neonates balanced by randomization in order to assess whether one method of palliation demonstrates therapeutic superiority.

Transformed non-Hodgkin lymphoma in the rituximab era: analysis of the NCCN outcomes database.

Histological transformation (HT) is a major cause of morbidity and mortality in patients with indolent non-Hodgkin lymphoma (NHL). The multicentre National Cancer Comprehensive Network database for NHL provides a unique opportunity to investigate the natural history of HT in the rituximab era. 118 patients with biopsy-confirmed indolent lymphoma and subsequent biopsy-confirmed HT were identified. Treatments for HT included autologous stem-cell transplant (auto-SCT) (n = 50), allogeneic SCT (allo-SCT) (n = 18), and treatment without transplant (n = 50). The 2-year overall survival (OS) for the entire cohort was 68%. For auto-SCT patients aged ≤ 60 years (n = 24), the 2-year OS was 74%. For non-transplanted patients aged ≤ 60 years (n = 19), the 2-year OS was 59%. The 2-year OS of patients naïve to chemotherapy prior to HT was superior to patients who were exposed to chemotherapy prior to HT (100% vs. 35%, P = 0.03). In this largest prospective cohort of patients of strictly defined HT in the rituximab era, the natural history of HT appears more favourable than historical studies. Younger patients who were not exposed to chemotherapy prior to HT experienced a prolonged survival even without transplantation. This study serves as a benchmark for future trials of novel approaches for HT in the Rituximab era.