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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 [...]

Our study characterized the neurodevelopmental spectrum of individuals with PTEN Hamartoma Tumor Syndrome (PHTS), a syndrome that predisposes to both neurodevelopmental phenotypes and cancer risk. We aim to better understand life‐impacting neurodevelopmental features of PHTS. Our study recruited 20 children/adolescents with PHTS, who were then administered assessments for autism spectrum disorder (ASD) and other neurocognitive measures, including assessment of IQ, executive and adaptive functioning, and health‐related quality of life. Thirteen individuals (65%) were identified as having ASD, of which five were newly diagnosed during the study. Of those, ASD symptom severity was in the mild–moderate range for 77%. Overall, IQ was in the average range, with a mean of 92.61 (SD 24.45, p = 0.5), though there was a non‐statistically significant trend toward individuals without ASD having a higher mean IQ (102.7 vs 82.3; p = 0.1). Subjects had significant impairment in processing speed (mean 75.38, SD 24.75, p < 0.05), decreased adaptive functioning skills across all domains, and a trend toward having more executive functioning problems. Individuals with PHTS are at increased risk of neurodevelopmental disorders, including ASD and impaired executive and adaptive functioning. Although clear guidelines exist for cancer surveillance for individuals with PHTS, additional guidelines and screening for neurodevelopmental disorders are warranted. [ABSTRACT FROM AUTHOR]

Self-oxidative degradation photosensitizers capable of bacterial agglutination and membrane insertion were fabricated based on a simple co-assembly strategy, for efficiently killing P. aeruginosa and rapidly deactivating their function post-treatment. [ABSTRACT FROM AUTHOR]

Multi-arm trials are increasingly of interest because for many diseases; there are multiple experimental treatments available for testing efficacy. Several novel multi-arm multi-stage (MAMS) clinical trial designs have been proposed. However, a major hurdle to adopting the group sequential MAMS routinely is the computational effort of obtaining stopping boundaries. For example, the method of Jaki and Magirr for time-to-event endpoint, implemented in R package MAMS, requires complicated computational efforts to obtain stopping boundaries. In this study, we develop a group sequential MAMS survival trial design based on the sequential conditional probability ratio test. The proposed method is an improvement of the Jaki and Magirr's method in the following three directions. First, the proposed method provides explicit solutions for both futility and efficacy boundaries to an arbitrary number of stages and arms. Thus, it avoids complicated computational efforts for the trial design. Second, the proposed method provides an accurate number of events for the fixed sample and group sequential designs. Third, the proposed method uses a new procedure for interim analysis which preserves the study power. [ABSTRACT FROM AUTHOR]

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]

Background Performance validity tests (PVTs) and symptom validity tests (SVTs) are essential to neuropsychological evaluations, helping ensure findings reflect true abilities or concerns. It is unclear how PVTs and SVTs perform in children who received radiotherapy for brain tumors. Accordingly, we investigated the rate of noncredible performance on validity indicators as well as associations with fatigue and lower intellectual functioning. Methods Embedded PVTs and SVTs were investigated in 98 patients with pediatric craniopharyngioma undergoing proton radiotherapy (PRT). The contribution of fatigue, sleepiness, and lower intellectual functioning to embedded PVT performance was examined. Further, we investigated PVTs and SVTs in relation to cognitive performance at pre-PRT baseline and change over time. Results SVTs on parent measures were not an area of concern. PVTs identified 0–31% of the cohort as demonstrating possible noncredible performance at baseline, with stable findings 1 year following PRT. Reliable digit span (RDS) noted the highest PVT failure rate; RDS has been criticized for false positives in pediatric populations, especially children with neurological impairment. Objective sleepiness was strongly associated with PVT failure, stressing need to consider arousal level when interpreting cognitive performance in children with craniopharyngioma. Lower intellectual functioning also needs to be considered when interpreting task engagement indices as it was strongly associated with PVT failure. Conclusions Embedded PVTs should be used with caution in pediatric craniopharyngioma patients who have received PRT. Future research should investigate different cut-off scores and validity indicator combinations to best differentiate noncredible performance due to task engagement versus variable arousal and/or lower intellectual functioning. [ABSTRACT FROM AUTHOR]

Introduction: Childhood cancer survivors (CCS) are at risk for radiotherapy (RT) late effects, including second malignancies. Optimal screening for differentiated thyroid cancer (DTC) in CCS post-RT remains controversial. We assessed the outcome of thyroid ultrasound (US) surveillance in CCS exposed to RT. Methods: 306 CCS were surveilled with thyroid US between 2002–2021. Surveillance was dependent on age at the time of primary diagnosis, interval from receipt of RT, and individual provider. Thyroid US, clinicopathologic features, and outcomes were described. Cutpoints of CCS RT age associated with varying risk of nodule presentation were explored. The selected cutpoints were used to define age categories, which were then used to compare thyroid nodule-related outcomes. Risk factors for thyroid nodule(s) were evaluated using multivariate logistic regression (odds ratio [OR] [95% confidence interval]). Results: The most common CCS diagnoses were leukemia (32%), CNS tumor (26%), and neuroblastoma (18%). Patients received TBI (45%) and/or RT to craniospinal (44%), chest (11%), and neck regions (6%). About 49% (n = 150) of patients had thyroid nodule(s). Forty-four patients underwent surgery, and 28 had DTC: 19 with American Thyroid Association (ATA) low-risk classification, 2 with ATA intermediate-risk, and 7 with ATA high-risk disease. Age cutpoint analyses identified cutpoints 3 and 10; hence, ≤3, >3 to ≤10, and >10 years were used. Of the 9 patients with intermediate- or high-risk disease, 8 were ≤10 years and 1 was >10 years at the time of RT. Female sex (OR = 1.62 [1.13–2.12] p = 0.054) and greater interval between RT and first US (OR = 1.10 [1.04–1.16] p = 0.001) were independent risk factors for nodule presentation. Conclusions: Thyroid US surveillance may be beneficial for CCS exposed to RT at younger ages (≤10 years) for earlier detection of DTC, prior to developing advanced metastatic disease. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common cancer after non-melanoma skin cancer and the second leading cause of cancer deaths in US men. Its incidence and mortality rates vary substantially across geographical regions and over time, with large disparities by race, geographic regions (i.e., Appalachia), among others. The widely used Cox proportional hazards model is usually not applicable in such scenarios owing to the violation of the proportional hazards assumption. In this paper, we fit Bayesian accelerated failure time models for the analysis of prostate cancer survival and take dependent spatial structures and temporal information into account by incorporating random effects with multivariate conditional autoregressive priors. In particular, we relax the proportional hazards assumption, consider flexible frailty structures in space and time, and also explore strategies for handling the temporal variable. The parameter estimation and inference are based on a Monte Carlo Markov chain technique under a Bayesian framework. The deviance information criterion is used to check goodness of fit and to select the best candidate model. Extensive simulations are performed to examine and compare the performances of models in different contexts. Finally, we illustrate our approach by using the 2004-2014 Pennsylvania Prostate Cancer Registry data to explore spatial-temporal heterogeneity in overall survival and identify significant risk factors. [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]

Background: Pediatric acute myeloid leukemia (AML) chemotherapy increases the risk of life‐threatening complications, including septic shock (SS). An area‐based measure of social determinants of health, the social disorganization index (SDI), was hypothesized to be associated with SS and SS‐associated death (SS‐death). Methods: Children treated for de novo AML on two Children's Oncology Group trials at institutions contributing to the Pediatric Health Information System (PHIS) database were included. The SDI was calculated via residential zip code data from the US Census Bureau. SS was identified via PHIS resource utilization codes. SS‐death was defined as death within 2 weeks of an antecedent SS event. Patients were followed from 7 days after the start of chemotherapy until the first of end of front‐line therapy, death, relapse, or removal from study. Multivariable‐adjusted Cox regressions estimated hazard ratios (HRs) comparing time to first SS by SDI group. Results: The assembled cohort included 700 patients, with 207 (29.6%) sustaining at least one SS event. There were 233 (33%) in the SDI‐5 group (highest disorganization). Adjusted time to incident SS did not statistically significantly differ by SDI (reference, SDI‐1; SDI‐2: HR, 0.84 [95% confidence interval (CI), 0.51–1.41]; SDI‐3: HR, 0.70 [95% CI, 0.42–1.16]; SDI‐4: HR, 0.97 [95% CI, 0.61–1.53]; SDI‐5: HR, 0.72 [95% CI, 0.45–1.14]). Nine patients (4.4%) with SS experienced SS‐death; seven of these patients (78%) were in SDI‐4 or SDI‐5. Conclusions: In a large, nationally representative cohort of trial‐enrolled pediatric patients with AML, there was no significant association between the SDI and time to SS. Time to first septic shock event was not associated with the social disorganization index (SDI), an area‐based measure of social determination of health, in children with acute myeloid leukemia treated on two Children's Oncology Group trials. Septic shock–associated mortality is rare in children with acute myeloid leukemia, and differences by SDI were not able to be detected. [ABSTRACT FROM AUTHOR]

In this paper, we develop an estimation and testing procedure for comparing matched-pair ordinal outcomes in studies with confounding factors. The classification method for the categories of ordinal outcomes that is accessible for all units may be prone to mis-classification, and thus another error-free classification method that can only be affordable for a fraction of the units are used, resulting in a dataset with partial validation. The distribution of categorical variables is modelled using correlated bivariate Gaussian latent variables, and the confounding factors are adjusted as covariates. The mis-classification of ordinal outcomes is addressed by estimating the mis-classification probabilities through the partial validation structure of the dataset. The mis-classification probabilities and the other parameters are estimated by a two-stage maximum likelihood estimator, and the difference between the matched-pair ordinal outcomes are assessed by a Wald test statistic. Simulation studies were conducted to investigate the accuracy of the estimates of the model parameters, and the type I error rates and power of the proposed testing procedure. The motivating dataset from the Garki Project was analysed to demonstrate the applicability of the proposed approach. [ABSTRACT FROM AUTHOR]