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ObjectiveWithin a 2-way text messaging study in AYAs who recently completed treatment for cancer, we sought to evaluate text message responsivity across different types of text messages. MethodsAYAs who recently completed treatment for cancer (n=26; mean age=16 years; 62% female, 16/26 participants) received 2-way text messages about survivorship health topics over a 16-week period. Using participants’ text message log data, we coded responsivity to text messages and evaluated trends in responsivity to unprompted text messages and prompted text messages of varying content (eg, medication reminders, appointment reminders, and texts about personal experiences as a cancer survivor). ResultsAcross prompted and unprompted text messages, responsivity rapidly decreased (P ≤.001 and =.01, respectively) and plateaued by the third week of the intervention. However, participants were more responsive to prompted text messages (mean responsivity=46% by week 16) than unprompted messages (mean responsivity=10% by week 16). They also demonstrated stable responsivity to certain prompted content: medication reminders, appointment reminders, goal motivation, goal progress, and patient experience texts. ConclusionsOur methodology of evaluating text message responsivity revealed important patterns of engagement in a 2-way text message intervention for AYA cancer survivors.

Global dengue incidence has increased dramatically over the past few decades from approximately 500 000 reported cases in 2000 to over 5 million in 2019. This trend has been attributed to population growth in endemic areas, rapid unplanned urbanization, increasing global connectivity, and climate change expanding the geographic range of the Aedes spp. mosquito, among other factors. Reporting dengue surveillance data is key to understanding the scale of the problem, identifying important changes in the landscape of disease, and developing policies for clinical management, vector control and vaccine rollout. However, surveillance practices are not standardized, and data may be difficult to interpret particularly in low- and middle-income countries with fragmented health-care systems. The latest national dengue surveillance data for Cambodia was published in 2010. Since its publication, the country experienced marked changes in health policies, population demographics, climate and urbanization. How these changes affected dengue control remains unknown. In this article, we summarize two decades of policy changes, published literature, country statistics, and dengue case data collected by the Cambodia National Dengue Control Programme to: (i) identify important changes in the disease landscape; and (ii) derive lessons to inform future surveillance and disease control strategies. We report that while dengue case morbidity and mortality rates in Cambodia fell between 2002 and 2020, dengue incidence doubled and age at infection increased. Future national surveillance, disease prevention and treatment, and vector control policies will have to account for these changes to optimize disease control. Le taux d'incidence de la dengue dans le monde a considerablement augmente au cours des dernieres decennies, passant d'environ 500 000 cas notifies en 2000 a plus de 5 millions en 2019. Cette tendance est attribuee a la croissance demographique dans les zones d'endemie, a l'urbanisation rapide non planifiee, au developpement de la connectivite a l'echelle internationale, ainsi qu'au changement climatique, qui agrandit le territoire geographique du moustique Aedes spp, entre autres. La communication des donnees de surveillance de la dengue est essentielle pour comprendre l'etendue du probleme, identifier les principales variations de contexte entourant la maladie et mettre au point des politiques pour la prise en charge clinique, la lutte contre les vecteurs et le deploiement des vaccins. Les pratiques en matiere de surveillance ne sont toutefois pas standardisees et les donnees peuvent etre difficiles a interpreter, surtout dans les pays a revenu faible et intermediaire ou les systemes de soins de sante sont fragmentes. Les donnees de surveillance les plus recentes concernant la dengue au Cambodge ont ete publiees en 2010. Depuis leur publication, le pays a subi de profondes mutations au niveau des politiques de sante, de l'evolution demographique, du climat et de l'urbanisation. L'impact de ces mutations sur la lutte contre la dengue reste a etablir. Dans le present article, nous resumons deux decennies d'amendements politiques, de documentation, de statistiques nationales et d'informations collectees sur les cas par le programme cambodgien de lutte contre la dengue afin de: (i) definir les changements importants survenus dans le contexte entourant la maladie; mais aussi (ii) tirer des lecons en vue d'elaborer, a l'avenir, des strategies de surveillance et de lutte contre la maladie. Nous signalons qu'en depit d'une baisse des taux de morbidite et de mortalite lies aux cas de dengue entre 2002 et 2020 au Cambodge, son incidence a double et l'age des patients au moment de l'infection a augmente. Les futures politiques nationales de surveillance, de prevention et de traitement de la dengue, mais aussi de lutte contre ses vecteurs, devront tenir compte de ces changements de facon a mieux maitriser la maladie. La incidencia del dengue a nivel mundial ha aumentado considerablemente en las ultimas decadas, desde aproximadamente 500 000 casos notificados en el ano 2000 a mas de 5 millones en 2019. Esta tendencia se ha atribuido al crecimiento de la poblacion en zonas endemicas, a una urbanizacion rapida y no planificada, al aumento de la conectividad a nivel mundial y al cambio climatico, que esta permitiendo una distribucion geografica mas amplia del mosquito Aedes spp, entre otros factores. Para comprender la magnitud del problema resulta clave la notificacion de datos sobre vigilancia del dengue, la identificacion de cambios importantes dentro del escenario de la enfermedad, la creacion de politicas enfocadas a la gestion clinica, asi como el control de vectores y la implantacion de la vacuna. Sin embargo, las practicas sobre vigilancia no estan estandarizadas y es posible que sea dificil interpretar los datos, especialmente en paises con ingresos medios y bajos, que cuentan con sistemas fragmentados de atencion sanitaria. Los datos nacionales mas recientes sobre vigilancia del dengue en Camboya se publicaron en 2010. Desde su publicacion, el pais experimento cambios significativos en las politicas sanitarias, la demografia de la poblacion, el clima y la urbanizacion. Aun no se sabe como afectaron dichos cambios al control del dengue. En el presente articulo, resumimos dos decadas de cambios politicos, de bibliografia publicada, de datos estadisticos a nivel nacional y datos sobre casos de dengue recopilados por el programa nacional de control de dengue en Camboya, con el fin de: (i) identificar cambios importantes en el escenario de la enfermedad; y (ii) extraer conclusiones para orientar futuras estrategias sobre vigilancia y control de la enfermedad. Informamos de que, aunque las tasas de morbilidad y mortalidad de los casos de dengue en Camboya descendieron entre 2002 y 2020, la incidencia del dengue se duplico y la edad de infeccion aumento. Las futuras politicas nacionales sobre vigilancia, prevencion y tratamiento de la enfermedad y control de vectores deberan tener en cuenta estos cambios para optimizar el control de la enfermedad. [phrase omitted], Introduction The global incidence of reported dengue has increased by tenfold over the last two decades, from 505 430 cases in 2000 to 5.2 million in 2019. (1) To contain [...]

Sickle cell disease (SCD) decreases the oxygen-carrying capacity of red blood cells. Children with SCD have reduced/restricted cerebral blood flow, resulting in neurocognitive deficits. Hydroxyurea is the standard treatment for SCD; however, whether hydroxyurea influences such effects is unclear. A key area of SCD-associated neurocognitive impairment is working memory, which is implicated in other cognitive and academic skills. The neural correlates of working memory can be tested using n-back tasks. We analyzed functional magnetic resonance imaging (fMRI) data of patients with SCD (20 hydroxyurea-treated patients and 11 controls, aged 7–18 years) while they performed n-back tasks. Blood-oxygenation level–dependent (BOLD) signals were assessed during working memory processing at 2 time points: before hydroxyurea treatment and ~1 year after treatment was initiated. Neurocognitive measures were also assessed at both time points. Our results suggested that working memory was stable in the treated group. We observed a treatment-by-time interaction in the right cuneus and angular gyrus for the 2- >0-back contrast. Searchlight-pattern classification of the 2 time points of the 2-back tasks identified greater changes in the pattern and magnitude of BOLD signals, especially in the posterior regions of the brain, in the control group than in the treated group. In the control group at 1-year follow-up, 2-back BOLD signals increased across time points in several clusters (e.g., right inferior temporal lobe, right angular gyrus). We hypothesize that these changes resulted from increased cognitive effort during working memory processing in the absence of hydroxyurea. In the treated group, 0- to 2-back BOLD signals in the right angular gyrus and left cuneus increased continuously with increasing working memory load, potentially related to a broader dynamic range in response to task difficulty and cognitive effort. These findings suggest that hydroxyurea treatment helps maintain working memory function in SCD. [ABSTRACT FROM AUTHOR]

Objective: Examine the influence of household income on health‐related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). Design: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. Exposure: Household income was self‐reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. Outcome: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. Result: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2–20.2). Seven percent of enrolled patients presented with high acuity (ICU‐level care in the first 72 h), and 16% had high toxicity (any ICU‐level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. Conclusions: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy enables the delivery of a high radiation dose to tumors while sparing surrounding normal tissues. Inaccurate patient positioning may lead to underdosing of the targeted tumor and overdosing of nearby healthy tissues. Before a course of proton therapy, a CT scan is acquired for treatment planning with the patient in the treatment position, and this image dataset is used as a reference for patient localization at each treatment fraction. Radiation therapists perform daily cone-beam CT (CBCT) image guidance to align the patient to closely match the planning CT and minimize inaccuracies in radiation delivery. In this study, CBCT scans were systematically collected with clinical and treatment information to investigate questions related to image guidance, setup uncertainty, and patient motion during the treatment of pediatric brain tumors. Knowledge gained from this study provides a basis for designing safe and optimal proton treatments. This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1–1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients ( p = 0.0016 ). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort. [ABSTRACT FROM AUTHOR]

Spinal bulbar muscular atrophy (SBMA) is a motor neuron disease caused by toxic gain of function of the androgen receptor (AR). Previously, we found that co-regulator binding through the activation function-2 (AF2) domain of AR is essential for pathogenesis, suggesting that AF2 may be a potential drug target for selective modulation of toxic AR activity. We screened previously identified AF2 modulators for their ability to rescue toxicity in a Drosophila model of SBMA. We identified two compounds, tolfenamic acid (TA) and 1-[2-(4-methylphenoxy)ethyl]-2-[(2-phenoxyethyl)sulfanyl]-1H-benzimidazole (MEPB), as top candidates for rescuing lethality, locomotor function and neuromuscular junction defects in SBMA flies. Pharmacokinetic analyses in mice revealed a more favorable bioavailability and tissue retention of MEPB compared with TA in muscle, brain and spinal cord. In a preclinical trial in a new mouse model of SBMA, MEPB treatment yielded a dose-dependent rescue from loss of body weight, rotarod activity and grip strength. In addition, MEPB ameliorated neuronal loss, neurogenic atrophy and testicular atrophy, validating AF2 modulation as a potent androgen-sparing strategy for SBMA therapy., Author(s): Nisha M Badders [1]; Ane Korff [1, 2]; Helen C Miranda [3]; Pradeep K Vuppala [4]; Rebecca B Smith [1]; Brett J Winborn [1]; Emmanuelle R Quemin [1]; Bryce [...]

Simple Summary: Limited effective therapies exist for the treatment of neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN). The aim of our prospective clinical trial was to evaluate the activity and safety of vinblastine and methotrexate (conventional cytotoxic chemotherapies) given on a metronomic schedule in children and young adults with NF1 and PN. Of the 23 participants evaluable for treatment outcomes and toxicities, 14 completed all protocol therapy. There were no participants that discontinued therapy due to dose-limiting toxicities. In addition, there were no participants that demonstrated a partial response. VBL/MTX was well-tolerated but did not result in objective volumetric responses. Limited therapies exist for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN). For this reason, the activity of vinblastine (VBL) and methotrexate (MTX) was evaluated in children and young adults with NF1 and PN. Patients ≤ 25 years of age with progressive and/or inoperable NF1-PN received VBL 6 mg/m2 and MTX 30 mg/m2 weekly for 26 weeks, followed by every 2 weeks for 26 weeks. Objective response rate was the primary endpoint. Of 25 participants enrolled, 23 were evaluable. The median age of participants was 6.6 years (range 0.3–20.7). The most frequent toxicities were neutropenia and elevation of transaminases. On two-dimensional (2D) imaging, 20 participants (87%) had stable tumor, with a median time to progression of 41.5 months (95% confidence interval 16.9, 64.9). Two of eight participants (25%) with airway involvement demonstrated functional improvements including decreased positive pressure requirements and apnea-hypopnea index. A post hoc three-dimensional (3D) analysis of PN volumes was completed on 15 participants with amenable imaging; 7 participants (46%) had progressive disease on or by the end of therapy. VBL/MTX was well-tolerated but did not result in objective volumetric response. Furthermore, 3D volumetric analysis highlighted the lack of sensitivity of 2D imaging for PN response evaluation. [ABSTRACT FROM AUTHOR]

Identifying drivers of viral diversity is key to understanding the evolutionary as well as epidemiological dynamics of the COVID-19 pandemic. Using rich viral genomic data sets, we show that periods of steadily rising diversity have been punctuated by sudden, enormous increases followed by similarly abrupt collapses of diversity. We introduce a mechanistic model of saltational evolution with epistasis and demonstrate that these features parsimoniously account for the observed temporal dynamics of inter-genomic diversity. Our results provide support for recent proposals that saltational evolution may be a signature feature of SARS-CoV-2, allowing the pathogen to more readily evolve highly transmissible variants. These findings lend theoretical support to a heightened awareness of biological contexts where increased diversification may occur. They also underline the power of pathogen genomics and other surveillance streams in clarifying the phylodynamics of emerging and endemic infections. In public health terms, our results further underline the importance of equitable distribution of up-to-date vaccines. Author summary: The coronavirus responsible for the COVID-19 pandemic, SARS-CoV-2, has shown a remarkable ability to evolve novel, increasingly transmissible variants. Using large amounts of viral sequences sampled during the pandemic, we map the genomic diversity over time. We find that the pathogen has followed a clear pattern of punctuated evolution, where periods of genetic drift are interrupted by sudden large increases in diversity followed by similarly abrupt collapses. This is in contrast to the pattern previously identified for influenza, which does not show similarly sudden increases in diversity. Using a mathematical model, we show that the observed pattern can result from rare evolutionary jumps (saltations) occurring within some hosts, in combination with epistasis. One possible explanation for such jumps is accelerated evolution within immunocompromised hosts, underscoring the importance of equitable vaccine distribution. Furthermore, a simple modification of the model to include incomplete cross immunity offers an explanation for recently observed patterns of variant co-circulation. [ABSTRACT FROM AUTHOR]

Objective: Fewer than one-third of childhood cancer survivors receive follow-up from an adult provider, and adolescent and young adults (AYAs) from structurally minoritized sociodemographic groups often face health disparities that can impact transition to adult-oriented care. The primary aim of this study was to determine the relation among sociodemographic factors, cumulative effects, and transition beliefs/expectations and goals, and the moderating role of health competence beliefs in AYA survivors of childhood cancer.Methods: A total of 195 AYAs (aged 15-29) reported sociodemographic information, completed the Transition Readiness Inventory assessing positive beliefs/expectations and goals related to transition, and completed the Health Competence Beliefs Inventory assessing health perceptions, healthcare satisfaction, cognitive competence, and autonomy. A cumulative sociodemographic factor variable was computed to investigate the potential additive effects of multiple sociodemographic factors associated with disparities. T-tests, Pearson correlations, and multivariate linear regressions were used.Results: Cumulative sociodemographic factors were not related to transition readiness, and insurance type was the only factor associated with health competence beliefs and transition readiness, such that AYAs with public insurance reported lower healthcare satisfaction, cognitive competence, and transition goals relative to those with private insurance. There were no interaction effects; however, health competence beliefs were significantly associated with transition beliefs/expectations and goals.Conclusion: Public insurance is a barrier to holding positive beliefs/expectations and goals about transition, yet other sociodemographic factors associated with risks for poor transfer were not related to transition readiness. Multi-level interventions to reduce disparities and improve transition readiness should target health competence beliefs and barriers created by insurance. [ABSTRACT FROM AUTHOR]