The interactive effect of sustained sleep restriction and resistance exercise on skeletal muscle transcriptomics in young females.

Both sleep loss and exercise regulate gene expression in skeletal muscle, yet little is known about how the interaction of these stressors affects the transcriptome. The aim of this study was to investigate the effect of nine nights of sleep restriction (SR), with repeated resistance exercise (REx) sessions, on the skeletal muscle transcriptome of young, trained females. Ten healthy females aged 18-35 yr old undertook a randomized cross-over study of nine nights of SR (5 h time in bed) and normal sleep (NS; ≥7 h time in bed) with a minimum 6-wk washout. Participants completed four REx sessions per condition (days 3, 5, 7, and 9). Muscle biopsies were collected both pre- and post-REx on days 3 and 9. Gene and protein expression were assessed by RNA sequencing and Western blot, respectively. Three or nine nights of SR had no effect on the muscle transcriptome independently of exercise. However, close to 3,000 transcripts were differentially regulated (false discovery rate < 0.05) 48 h after the completion of three resistance exercise sessions in both NS and SR conditions. Only 39% of downregulated genes and 18% of upregulated genes were common between both conditions, indicating a moderating effect of SR on the response to exercise. SR and REx interacted to alter the enrichment of skeletal muscle transcriptomic pathways in young, resistance-trained females. Performing exercise when sleep restricted may not provide the same adaptive response for individuals as if they were fully rested.NEW & NOTEWORTHY This study investigated the effect of nine nights of sleep restriction, with repeated resistance exercise sessions, on the skeletal muscle transcriptome of young, trained females. Sleep restriction and resistance exercise interacted to alter the enrichment of skeletal muscle transcriptomic pathways in young, resistance-trained females. Performing exercise when sleep restricted may not provide the same adaptive response for individuals as if they were fully rested.

Bioavailable testosterone and androgen receptor activation, but not total testosterone, are associated with muscle mass and strength in females.

Testosterone, the major androgen, influences the reproductive and non-reproductive systems in males and females via binding to the androgen receptor (AR). Both circulating endogenous testosterone and muscle AR protein content are positively associated with muscle mass and strength in males, but there is no such evidence in females. Here, we tested whether circulating testosterone levels were associated with muscle mass, function, or the muscle anabolic response to resistance training in pre-menopausal females. Twenty-seven pre-menopausal, untrained females (aged 23.5 ± 4.8 years) underwent a 12-week resistance training programme. Muscle strength, size, power, and plasma and urine androgen hormone levels were measured. Skeletal muscle biopsies were collected before and after the training programme to quantify the effect of resistance training on AR content and nuclear localisation. Primary muscle cell lines were cultured from a subset (n = 6) of the participants' biopsies and treated with testosterone to investigate its effect on myotube diameter, markers of muscle protein synthesis and AR cellular localisation. Physiological levels of total testosterone were not associated with muscle mass or strength at baseline or with the changes in muscle mass and strength that occurred in response to resistance training in our cohort of pre-menopausal females. In contrast, bioavailable testosterone and the proportion of nuclear-localised AR were positively associated with skeletal muscle mass and strength in pre-menopausal females. In vitro, supra-physiological doses of testosterone increased myocyte diameter, but this did not occur via the Akt/mTOR pathway as previously suggested. Instead, we show a marked increase in AR nuclear localisation with testosterone administration in vitro. KEY POINTS: Total circulating testosterone was not related to muscle mass or strength before or after resistance training in pre-menopausal females. Bioavailable testosterone was positively related to exercise-induced muscle hypertrophy in pre-menopausal females. In vivo nuclear localisation of the androgen receptor was positively related to muscle mass in pre-menopausal females at baseline, but not to resistance training-induced hypertrophy. Testosterone treatment induced androgen receptor nuclear translocation but did not induce mTOR signalling in primary skeletal myocytes cultured from pre-menopausal female muscle.

Detection of OXA-181 Carbapenemase in Shigella flexneri.

We report the detection of OXA-181 carbapenemase in an azithromycin-resistant Shigella spp. bacteria in an immunocompromised patient. The emergence of OXA-181 in Shigella spp. bacteria raises concerns about the global dissemination of carbapenem resistance in Enterobacterales and its implications for the treatment of infections caused by Shigella bacteria.

Ceftriaxone-resistant Neisseria gonorrhoeae detected in England, 2015-24: an observational analysis.

OBJECTIVES: Since June 2022, there has been a rise in the number of ceftriaxone-resistant Neisseria gonorrhoeae cases detected in England (n = 15), of which a third were XDR. We describe the demographic and clinical details of the recent cases and investigate the phenotypic and molecular characteristics of the isolates. For a comprehensive overview, we also reviewed 16 ceftriaxone-resistant cases previously identified in England since December 2015 and performed a global genomic comparison of all publicly available ceftriaxone-resistant N. gonorrhoeae strains with mosaic penA alleles. METHODS: All N. gonorrhoeae isolates resistant to ceftriaxone (MIC > 0.125 mg/L) were whole-genome sequenced and compared with 142 global sequences of ceftriaxone-resistant N. gonorrhoeae. Demographic, behavioural and clinical data were collected. RESULTS: All cases were heterosexual, and most infections were associated with travel from the Asia-Pacific region. However, some had not travelled outside England within the previous few months. There were no ceftriaxone genital treatment failures, but three of five pharyngeal infections and the only rectal infection failed treatment. The isolates represented 13 different MLST STs, and most had the mosaic penA-60.001 allele. The global genomes clustered into eight major phylogroups, with regional associations. All XDR isolates belonged to the same phylogroup, represented by MLST ST16406. CONCLUSIONS: Most cases of ceftriaxone-resistant N. gonorrhoeae detected in England were associated with travel from the Asia-Pacific region. All genital infections were successfully treated with ceftriaxone, but there were extragenital treatment failures. Ceftriaxone resistance continues to be associated with the penA-60.001 allele within multiple genetic backgrounds and with widespread dissemination in the Asia-Pacific region.

Healthcare professional perspectives following implementation of an infection management care pathway for pediatric patients with cancer: a qualitative study.

PURPOSE: The Pediatric Oncology Group of Ontario (POGO) supported an effort to implement infection management care pathways based on clinical practice guidelines, to improve the consistency of infection management in pediatric cancer patients. The objective of this qualitative study was to describe the perspective of healthcare professionals (HCPs) following implementation. METHODS: Four tertiary pediatric oncology centers in Ontario, Canada, implemented the pathways. We randomly identified three HCPs per group (clinical pharmacists; nurse case managers, educators or practitioners and physician assistants; pediatric oncology fellows; or pediatric oncology staff physicians) per site and invited them to participate in a qualitative interview. One-on-one interviews were conducted remotely, followed by thematic analysis of interview transcripts. RESULTS: A total of 66 invitations were extended and 42 HCPs participated. Identified themes were: (1) implementation approach, (2) access and navigation, (3) engagement, (4) concerns, (5) workplace benefits, (6) reception, and (7) provincial harmonization. HCPs preferred in-person implementation strategies over e-mail communication. They identified teaching/educational utility and benefits to non-oncology departments and non-tertiary centers participating in shared care of patients. Other positive aspects related to evidence-based practice, safety, supporting oncology HCPs, and benefits to patients and families. Concerns included need to ensure users applied clinical judgement and loss of autonomy. Provincial harmonization of practice was viewed positively, although potential logistical and institutional cultural barriers were raised. CONCLUSIONS: Following infection management care pathway implementation, HCPs described educational utility and benefits to non-oncology departments, oncology HCPs, patients, and families. Our findings may facilitate future infection management care pathway provincial harmonization.

Incidence Rates and Outcomes of Nodular and Superficial Spreading Melanoma along the Rural-Urban Continuum in Kentucky and Their Relationship to Provider Care Access.

OBJECTIVES: This study compared incidence rates, stage at presentation, and cause-specific mortality of nodular and superficial spreading melanoma along the rural-urban continuum in Kentucky. We compared resulting patterns in our data with sample demographic and other potential factors, including population by county and primary care provider rate. METHODS: Retrospective patient data were extracted from the Surveillance, Epidemiology, and End Results database from 2010 through 2017. These data were supplemented by environmental, demographic, and socioeconomic data derived from publicly accessible databases. Correlation and χ2 analyses were used to test for significant differences in outcome variables by US Department of Agriculture Rural-Urban Continuum Code (RUCC) categories and other potential predictor variables. RESULTS: Incidence rates by Kentucky county were not associated with RUCC or population; likewise, there was no relationship between stage at presentation and RUCC category. There was, however, a highly significant association between cause-specific mortality and RUCC; patients from rural areas were significantly more likely to die from melanoma than those in urban areas. This overall difference was due to differences in mortality for superficial spreading melanoma. CONCLUSIONS: Our results suggest that a disparity in patients' ability or tendency to access primary care and/or specialist providers postdiagnosis may be critical factors in determining the ultimate outcome of a melanoma diagnosis. Further studies should explore the availability of dermatologists and/or treatment options for melanoma in rural areas. Our data also provide additional support for inclusion of melanoma subtype in the American Joint Committee on Cancer guidelines.

Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children.

BACKGROUND: Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin's lymphoma are limited. METHODS: We conducted an open-label, international, randomized, phase 3 trial involving patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin's lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition of six doses of rituximab to standard lymphomes malins B (LMB) chemotherapy with standard LMB chemotherapy alone. The primary end point was event-free survival. Overall survival and toxic effects were also assessed. RESULTS: Analyses were based on 328 patients who underwent randomization (164 patients per group); 85.7% of the patients had Burkitt's lymphoma. The median follow-up was 39.9 months. Events were observed in 10 patients in the rituximab-chemotherapy group and in 28 in the chemotherapy group. Event-free survival at 3 years was 93.9% (95% confidence interval [CI], 89.1 to 96.7) in the rituximab-chemotherapy group and 82.3% (95% CI, 75.7 to 87.5) in the chemotherapy group (hazard ratio for primary refractory disease or first occurrence of progression, relapse after response, death from any cause, or second cancer, 0.32; 95% CI, 0.15 to 0.66; one-sided P = 0.00096, which reached the significance level required for this analysis). Eight patients in the rituximab-chemotherapy group died (4 deaths were disease-related, 3 were treatment-related, and 1 was from a second cancer), as did 20 in the chemotherapy group (17 deaths were disease-related, and 3 were treatment-related) (hazard ratio, 0.36; 95% CI, 0.16 to 0.82). The incidence of acute adverse events of grade 4 or higher after prephase treatment was 33.3% in the rituximab-chemotherapy group and 24.2% in the chemotherapy group (P = 0.07); events were related mainly to febrile neutropenia and infection. Approximately twice as many patients in the rituximab-chemotherapy group as in the chemotherapy group had a low IgG level 1 year after trial inclusion. CONCLUSIONS: Rituximab added to standard LMB chemotherapy markedly prolonged event-free survival and overall survival among children and adolescents with high-grade, high-risk, mature B-cell non-Hodgkin's lymphoma and was associated with a higher incidence of hypogammaglobulinemia and, potentially, more episodes of infection. (Funded by the Clinical Research Hospital Program of the French Ministry of Health and others; ClinicalTrials.gov number, NCT01516580.).

Brentuximab vedotin in combination with chemotherapy for pediatric patients with ALK+ ALCL: results of COG trial ANHL12P1.

Approximately 30% of pediatric patients with anaplastic large cell lymphoma (ALCL) relapse. Although brentuximab vedotin has demonstrated excellent activity in ALCL, it has not been used for newly diagnosed patients. Children's Oncology Group (COG) trial ANHL12P1 determined the toxicity and efficacy of brentuximab vedotin with chemotherapy in children with newly diagnosed nonlocalized anaplastic large cell lymphoma kinase (ALK)+/CD30+ ALCL. From 2013 to 2017, 68 children with ALK+ ALCL were enrolled and received brentuximab vedotin. All patients received 5-day prophase, followed by 6 cycles of chemotherapy. Brentuximab vedotin was given on day 1 of each of the 6 cycles. Of the 67 patients eligible for toxicity evaluation, 66 completed all 6 cycles of chemotherapy, resulting in 399 evaluable cycles. There were no toxic deaths, no case of progressive multifocal leukoencephalopathy syndrome, and no case of grade 3 or 4 neuropathy. The 2-year event-free survival (EFS) was 79.1% (95% confidence interval [CI], 67.2-87.1). The 2-year overall survival (OS) was 97.0% (95% CI, 88.1-99.2). Fourteen patients relapsed. Eleven of 14 (79%) relapses occurred within 10 months of diagnosis; only 1 patient (1.5%) relapsed during therapy. Quantitative reverse transcription polymerase chain reaction for NPM-ALK at baseline (minimal disseminated disease) demonstrated prognostic value for EFS (P = .0004). Overall, the addition of brentuximab vedotin to standard chemotherapy does not add significant toxicity or alter the desired interval between cycles. The addition of brentuximab vedotin prevented relapses during therapy, and the OS and EFS estimates compare favorably with results obtained using conventional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01979536.

Children's Oncology Group's 2023 blueprint for research: Non-Hodgkin lymphoma.

Pediatric non-Hodgkin lymphoma (NHL) includes over 30 histologies (many with subtypes), with approximately 800 cases per year in the United States. Improvements in survival in NHL over the past 5 decades align with the overall success of the cooperative trial model with dramatic improvements in outcomes. As an example, survival for advanced Burkitt lymphoma is now >95%. Major remaining challenges include survival for relapsed and refractory disease and long-term morbidity in NHL survivors. Langerhans cell histiocytosis (LCH) was added to the NHL Committee portfolio in recognition of LCH as a neoplastic disorder and the tremendous unmet need for improved outcomes. The goal of the Children' Oncology Group NHL Committee is to identify optimal cures for every child and young adult with NHL (and LCH). Further advances will require creative solutions, including engineering study groups to combine rare populations, biology-based eligibility, alternative endpoints, facilitating international collaborations, and coordinated correlative biology.

Prospective Evaluation of the Fungitell® (1→3) Beta-D-Glucan Assay as a Diagnostic Tool for Invasive Fungal Disease in Pediatric Allogeneic Hematopoietic Cell Transplantation: A Report from the Children's Oncology Group.

BACKGROUND: Invasive fungal disease (IFD) is a major source of morbidity and mortality for hematopoietic cell transplant (HCT) recipients. Non-invasive biomarkers, such as the beta-D-glucan assay, may improve the diagnosis of IFD. The objective was to define the utility of surveillance testing using Fungitell® beta-D-glucan (BDG) assay in children receiving antifungal prophylaxis in the immediate post-HCT period. METHODS: Weekly surveillance blood testing with the Fungitell® BDG assay was performed during the early post-HCT period in the context of a randomized trial of children, adolescents, and young adults undergoing allogeneic HCT allocated to triazole or caspofungin prophylaxis. Positivity was defined at the manufacturer cutoff of 80 pg/ml. IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the Fungitell® BDG assay for the outcome of proven or probable IFD. RESULTS: A total of 51 patients (out of 290 patients in the parent trial) contributed blood specimens. In total, 278 specimens were evaluated. Specificity was 80.8% (95% confidence interval [CI]: 75.6%-85.3%), and NPV was over 99% (95% CI: 86.8%-99.9%). However, there were no true positive results, resulting in sensitivity of 0% (95% CI: 0.0%-84.2%) and PPV of 0% (95% CI: 0.0%-6.7%). CONCLUSIONS: Fungitell® BDG screening is of limited utility in diagnosing IFD in the post-HCT period, mainly due to high false-positive rates. Fungitell® BDG surveillance testing should not be performed in children during the early post-HCT period while receiving antifungal prophylaxis as the pretest probability for IFD is low.

Outcomes of Coronavirus Disease 2019 Infection in Children and Adolescents With Cancer in Canada: Population-based Study and Systematic Review.

Published outcomes for children with cancer with coronavirus disease 2019 (COVID-19) have varied. Outcome data for pediatric oncology patients in Canada, outside of Quebec, have not been reported. This retrospective study captured patient, disease, and COVID-19-related infectious episode characteristics and outcome data for children, 0 to 18 years, diagnosed with a first COVID-19 infection between January 2020 to December 2021 at 12 Canadian pediatric oncology centers. A systematic review of pediatric oncology COVID-19 cases in high-income countries was also undertaken. Eighty-six children were eligible for study inclusion. Thirty-six (41.9%) were hospitalized within 4 weeks of COVID-19; only 10 (11.6%) had hospitalization attributed to the virus, with 8 being for febrile neutropenia. Two patients required intensive care unit admission within 30 days of COVID-19 infection, neither for COVID-19 management. There were no deaths attributed to the virus. Of those scheduled to receive cancer-directed therapy, within 2 weeks of COVID-19, 20 (29.4%) experienced treatment delays. Sixteen studies were included in the systematic review with highly variable outcomes identified. Our findings compared favorably with other high-income country's pediatric oncology studies. No serious outcomes, intensive care unit admissions, or deaths, in our cohort, were directly attributable to COVID-19. These findings support the minimization of chemotherapy interruption after COVID-19 infection.

gcType: a high-quality type strain genome database for microbial phylogenetic and functional research.

Taxonomic and functional research of microorganisms has increasingly relied upon genome-based data and methods. As the depository of the Global Catalogue of Microorganisms (GCM) 10K prokaryotic type strain sequencing project, Global Catalogue of Type Strain (gcType) has published 1049 type strain genomes sequenced by the GCM 10K project which are preserved in global culture collections with a valid published status. Additionally, the information provided through gcType includes >12 000 publicly available type strain genome sequences from GenBank incorporated using quality control criteria and standard data annotation pipelines to form a high-quality reference database. This database integrates type strain sequences with their phenotypic information to facilitate phenotypic and genotypic analyses. Multiple formats of cross-genome searches and interactive interfaces have allowed extensive exploration of the database's resources. In this study, we describe web-based data analysis pipelines for genomic analyses and genome-based taxonomy, which could serve as a one-stop platform for the identification of prokaryotic species. The number of type strain genomes that are published will continue to increase as the GCM 10K project increases its collaboration with culture collections worldwide. Data of this project is shared with the International Nucleotide Sequence Database Collaboration. Access to gcType is free at http://gctype.wdcm.org/.

Superior outcomes with paediatric protocols in adolescents and young adults with aggressive B-cell non-Hodgkin lymphoma.

Survival disparities by locus of care (LOC; paediatric versus adult) among adolescents and young adults (AYA) with acute lymphoblastic leukaemia (ALL) are well documented. Whether similar disparities exist among AYA with aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) is unknown. We identified all Ontario, Canada AYA aged 15-21 years at diagnosis of B-NHL between 1992 and 2012. Demographic, disease, treatment and outcome data were chart abstracted. The impact of LOC on event-free (EFS) and overall survival (OS) were determined, adjusted for patient and disease covariates. Among 176 AYA with B-NHL, 62 (35·2%) received therapy at paediatric centres. The 5-year EFS and OS [± standard error (SE)] for the overall cohort were 72·2 [3·4]% and 76·1 [3·2]% respectively. Both EFS and OS were superior among paediatric centre AYA [EFS (± SE) 82·2 (4·9)% vs. 66·7 (4·4)%, P = 0·02; OS 85·5 (4·5)% vs. 71·1 (4·3)%, P = 0·03]. Adjusted for histology, stage and time period, adult centre AYA had inferior EFS [hazard ratio (HR) 2·4, 95% confidence interval (CI) 1·1-4·9, P = 0·02] and OS (HR 2·5, 95% CI 1·1-5·7, P = 0·03). Sensitivity analyses restricted to the latest time period, when most adult centre AYA received rituximab, demonstrated similar disparities. Similar to AYA with ALL, AYA with B-NHL may benefit from being treated with paediatric protocols. Studies prospectively validating these results are warranted.

The mSteps pilot study: Analysis of the distance walked using a novel smartphone application in multiple sclerosis.

BACKGROUND: Clinical studies in multiple sclerosis (MS) often require accurate measurement of walking distance. Utilisation of electronic devices could theoretically improve this. Mobile devices have the potential to continuously monitor health by collecting movement data. Popular fitness trackers record steps taken and distance travelled, typically using a fixed-stride length. However, applications using fixed-stride length may be less accurate in those with altered gait patterns. While useful for everyday purposes, medical monitoring requires greater accuracy. OBJECTIVE: Our aim was to determine the agreement and reliability of using a smartphone application to measure distance walked. METHOD: A phone application (mSteps) was developed and tested in a pilot study and then a validation study, looking at an indoor and outdoor setting with people with multiple sclerosis (PwMS) and a control cohort. RESULTS: In the pilot study, the 95% limits of agreement (LOA) for outdoor tracking in control cohort lay within the a priori defined limit; however, the indoor tracking in both cohorts did not meet the defined limit. The app was then successfully validated outdoors in PwMS. CONCLUSION: mSteps could be used to accurately measure distance outdoors in PwMS. There is still a need for solutions to accurately and reliably measure distance walked indoors.

Pilot randomized psychosocial trial of a screening intervention in pediatric oncology.

OBJECTIVE: Psychosocial screening is a standard of care in pediatric oncology, but there is limited information about how to intervene after screening. This pilot trial aimed to determine feasibility of the novel Enhanced Psychosocial Screening Intervention (EPSI) and explore its preliminary efficacy outcomes. We examined rates of recruitment, retention, intervention acceptability, and monthly distress screening completion, as well as exploratory efficacy outcomes (Patient-Reported Outcomes Measurement Information System: depression, anxiety and fatigue; distress thermometer, pain and sleep). METHODS: Parallel-group randomized pilot trial: Caregiver-youth (10-17 years at enrollment, newly diagnosed with cancer) dyads were randomly allocated to either EPSI or standard care with 1:1 ratio allocation. EPSI consists of having a Psychosocial Navigator who shares screening results conducted near diagnosis and monthly for one year with treating teams and families, and provides recommendations tailored to screening results. RESULTS: Enrollment rate was 54% (38 dyads); retention was 90% and acceptability 86% (caregivers) and 76% (youth). Exploratory symptoms of depression, anxiety, distress and fatigue outcomes consistently improved mainly for caregivers. CONCLUSIONS: Results suggest EPSI is feasible and acceptable and exploratory mental and physical efficacy outcomes are promising for use in a future confirmatory multisite efficacy trial.

A qualitative examination of the benefits and challenges of a psychosocial screening intervention in pediatric oncology: "Support comes to us".

BACKGROUND: Pediatric cancer diagnosis and treatment can have detrimental mental health effects on parents (caregivers) and their children/adolescents (youth). Psychosocial screening and intervention have been recognized as standards of care in pediatric oncology. The most effective psychosocial interventions to support those in need post screening have not been determined. AIMS: This qualitative study aimed to investigate the perceived benefits and challenges for caregiver and youth participants in the screening-intervention arm of an Enhanced Psychosocial Screening Intervention (EPSI) pilot study. METHODS: EPSI consists of a psychosocial navigator (PSN) who shares screening results conducted near diagnosis (T1) and monthly for 1 year (T2) with treating teams and families. All 17 caregiver-youth dyads who had completed EPSI were invited to participate in a semi-structured interview. RESULTS: Ten caregivers and nine youth participated. Identified themes were grouped into benefits and challenges of EPSI: feeling supported and cared for (support comes to us regularly, having someone to talk to); and feeling empowered through knowledge of resources and services were perceived as benefits. Caregivers were challenged by feeling overwhelmed, and youth by screening questions perceived as too repetitive. CONCLUSIONS: Regular monthly contacts for a year by the PSN with screening results and recommendations were perceived as beneficial by youth newly diagnosed with cancer and their caregivers who participated in EPSI. Feeling that support came to them and they had someone to talk to was a critical component. While information about psychosocial resources was not always used right away, it did evoke feelings of being empowered.

Perceptions of parents of pediatric patients with acute lymphoblastic leukemia on oral chemotherapy administration: A qualitative analysis.

OBJECTIVE: To describe the experiences and perspectives of parents of pediatric patients with acute lymphoblastic leukemia (ALL) regarding oral chemotherapy administration during maintenance therapy. METHODS: English-speaking parents of patients 4 to <18 years who were receiving ALL maintenance oral chemotherapy were eligible to participate in this mixed methods study. Using semi-structured interviews, we asked participants how difficult they found oral chemotherapy administration. We also probed regarding barriers and facilitators of oral chemotherapy administration and strategies used to overcome challenges. Lastly, we asked participants for their advice to future parents giving oral chemotherapy to their children. RESULTS: Twenty-three participants were interviewed. One-fifth of participants stated that oral chemotherapy administration at home was hard or very hard. Common factors influencing oral chemotherapy administration were product-related (e.g., formulation) and treatment-related adverse effects (e.g., nausea), lifestyle adjustment (e.g., fitting in with family schedule), and attitudes (e.g., onus of medication administration). Strategies to address oral chemotherapy administration included several administration techniques, scheduling of medication administration, and normalization of medication taking. CONCLUSIONS: Oral chemotherapy administration during ALL maintenance therapy was hard for some parents. Identification of these parents and discussion of strategies to facilitate adherence to oral chemotherapy regimens may optimize patient outcomes.

Improving infectious adverse event reporting for children and adolescents enrolled in clinical trials for acute lymphoblastic leukemia: A report from the Children's Oncology Group.

Infections cause substantial morbidity for children with acute lymphoblastic leukemia (ALL). Therefore, accurate characterization of infectious adverse events (AEs) reported on clinical trials is imperative to defining, comparing, and managing safety and toxicity. Here, we describe key processes implemented to improve reporting of infectious AEs on two active phase III Children's Oncology Group (COG) ALL trials. Processes include: (a) identifying infections as a targeted toxicity, (b) incorporation of infection-specific case report form questions, and (c) physician review of AEs with real-time data cleaning. Preliminary assessment of these processes suggests improved reporting, as well as opportunities for further improvement.

Answers to common questions about COVID-19 vaccines in children with cancer.

BACKGROUND: The SARS-CoV-2 outbreak in 2020 evolved into a global pandemic, and COVID-19 vaccines became rapidly available, including for pediatric patients. However, questions emerged that challenged vaccine acceptance and use. We aimed to answer these questions and give recommendations applicable for use in pediatric patients with cancer by healthcare professionals and the public. METHODS: A 12-member global COVID-19 Vaccine in Pediatric Oncology Working Group made up of physicians and nurses from all world regions met weekly from March to July 2021. We used a modified Delphi method to select the top questions. The Working Group, in four-member subgroups, answered assigned questions by providing brief recommendations, followed by a discussion of the rationale for each answer. All Working Group members voted on each recommendation using a scale of 1 to 10, 10 being complete agreement. A "pass" recommendation corresponded to an agreement ≥7.5. RESULTS: We selected 15 questions from 173 suggested questions. Based on existing published information, we generated answers for each question as recommendations. The overall average agreement for the 24 recommendations was 9.5 (95% CI 9.4-9.6). CONCLUSION: Top COVID-19 vaccine-related questions could be answered using available information. Reports on COVID-19 vaccination and related topics have been published at record speed, aided by available technology and the priority imposed by the pandemic; however, all efforts were made to incorporate emerging information throughout our project. Recommendations will be periodically updated on a dedicated website.

A qualitative study of the acceptability of remote electronic bednet use monitoring in Uganda.

BACKGROUND: Distribution of long-lasting insecticide treated nets (LLINs) is the most widely used intervention for the prevention of malaria but recall and social desirability biases may lead to challenges in accurately measuring use of bednets. SmartNet is a remote electronic monitor that provides objective measurements of bednet use over weeks at a time. Assessing local acceptability is important when implementing innovative global health technologies such as SmartNet. This study draws on established models such as the Technology Acceptance Model (TAM) and Theoretical Framework of Acceptability (TFA) to assess acceptability of SmartNet in Ugandan households. METHODS: Semi-structured qualitative interviews were conducted at weeks one and six following installation of SmartNet in ten households in Western Uganda. Heads-of-households answered open-ended questions addressing the main acceptability domains of the TFA and TAM models (i.e. perceived ease of use, ethicality, etc.). Responses were digitally recorded, transcribed, coded and analyzed using a thematic analysis approach. RESULTS: Seven out of ten households interviewed reported no difference in use between SmartNet and a standard LLIN. Households stated the large size, soft fabric, and the efficacy of SmartNet relative to a standard LLIN contributed to perceived usefulness and perceived ease of use. Opportunity costs of the novel monitoring system expressed by households included difficulty washing nets and dislike of blinking lights on the device. Barriers to SmartNet use focused on questions of the ethics of bednet use monitoring, discomfort with technical aspects of the device and a poor understanding of its function amongst others in the community. However, explaining SmartNet to other community members resolved these concerns and often resulted in interest and acceptance among peers. CONCLUSION: Objective monitoring of bednet use with SmartNet appears acceptable to these households in Uganda. Use of SmartNet seems to be similar to behaviors around use of standard LLINs. Viewpoints on many aspects of SmartNet were generally favorable. Concerns around ethicality of bednet monitoring are present and indicate the need for continuing community education. The device will continue to be optimized to make it more acceptable to users and to accurately reflect standard LLIN use to improve our understanding of prevention behaviors in malaria endemic settings.