Background:
There is a current crisis in children’s mental health. Defining social determinants of mental health (SDMH) facilitates investigations of social impact on mental health.
Aims:
To examine ...associations between nine SDMH and adolescent depression and anxiety in a U.S. nationally representative sample.
Methods:
Poor access to health care, caregiver underemployment, food insecurity, poorly built environment, housing insecurity, household dysfunction adverse childhood experiences (ACEs), racism, caregiver poor education, and poverty/income inequality were assessed from the 2018 to 2019 National Survey of Children’s Health (NSCH) (N = 24,817).
Results:
The likelihood of reporting adolescent depression and/or anxiety was assessed for each SDMH using multinomial logistic regressions. All SDMH, besides caregiver underemployment, were associated with increased odds of reporting adolescent anxiety, depression, or anxiety and depression. Only household dysfunction ACEs and racism had statistically significant associations for all three mental health outcomes.
Conclusions:
Interventions targeting ACEs and racism may be more impactful in mitigating mental health challenges associated with SDMH during adolescence. The NSCH may provide an important public health tool to investigate SDMH in children.
To assess the effect of treating pulmonary hypertension (PH) in infants younger than 1 year of age with systemic glucocorticoids while using echocardiographic and diagnostic biomarkers as measures of ...efficacy.
A retrospective chart review was performed on 17 hospitalized infants younger than 1 year of age at St Louis Children’s Hospital who received a 5- to 7-day course of systemic glucocorticoid treatment followed by a 3-week taper with no significant intracardiac shunts from January 1, 2017, to December 31, 2021. Quantitative echocardiographic indices for PH, N-terminal pro b-type natriuretic peptide, and/or b-type natriuretic peptide levels were collected before glucocorticoid treatment, after the glucocorticoid burst, and after the 21-day taper.
Mean (±SD) gestational age was 32.1 (±5.8) weeks, 5 infants were (29%) concomitantly treated with sildenafil, and 8 were male. Twelve were classified as World Health Organization group 3 PH (71%) and 5 as World Health Organization group 1 PH. There were significant improvements 30 days after glucocorticoid initiation in b-type natriuretic peptide levels (P = .008), PCO2 (P = .03), eccentricity index (P = .005), right ventricular ejection time (P = .04), pulmonary artery acceleration time (P = .002), and pulmonary artery acceleration time-to-right ventricular ejection time ratio (P = .02). Tricuspid regurgitation velocity was not able to be assessed. There were no mortalities during the study timeline.
In our retrospective study, systemic glucocorticoid therapy was well tolerated and appeared to be associated with significant improvement in cardiopulmonary function in infants with PH. Further prospective study in a larger sample is warranted.
The mammary gland extracellular matrix (ECM) is comprised of biopolymers, primarily collagen I, that are created and maintained by stromal fibroblasts. ECM remodeling by fibroblasts results in ...changes in ECM fiber spacing (pores) that have been shown to play a critical role in the aggressiveness of breast cancer. However, minimally invasive methods to measure the spatial distribution of ECM pore areas within tissues and in vitro 3D culture models are currently lacking. We introduce diffusion-sensitive optical coherence tomography (DS-OCT) to image the nanoscale porosity of ECM by sensing weakly constrained diffusion of gold nanorods (GNRs). DS-OCT combines the principles of low-coherence interferometry and heterodyne dynamic light scattering. By collecting co- and cross-polarized light backscattered from GNRs within tissue culture, the ensemble-averaged translational self-diffusion rate, DT, of GNRs is resolved within ∼3 coherence volumes (10 × 5 μm, x × z). As GNRs are slowed by intermittent collisions with ECM fibers, DT is sensitive to ECM porosity on the size scale of their hydrodynamic diameter (∼46 nm). Here, we validate the utility of DS-OCT using pure collagen I gels and 3D mammary fibroblast cultures seeded in collagen/Matrigel, and associate differences in artificial ECM pore areas with gel concentration and cell seed density. Across all samples, DT was highly correlated with pore area obtained by scanning electron microscopy (R2 = 0.968). We also demonstrate that DS-OCT can accurately map the spatial heterogeneity of layered samples. Importantly, DS-OCT of 3D mammary fibroblast cultures revealed the impact of fibroblast remodeling, where the spatial heterogeneity of matrix porosity was found to increase with cell density. This provides an unprecedented view into nanoscale changes in artificial ECM porosity over effective pore diameters ranging from ∼43 to 360 nm using a micron-scale optical imaging technique. In combination with the topical deposition of GNRs, the minimally invasive nature of DS-OCT makes this a promising technology for studying tissue remodeling processes.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood with an unmet clinical need for decades. A single oncogenic fusion gene is associated with treatment resistance and a 40 to ...45% decrease in overall survival. We previously showed that expression of this
fusion oncogene in alveolar RMS (aRMS) mediates tolerance to chemotherapy and radiotherapy and that the class I-specific histone deacetylase (HDAC) inhibitor entinostat reduces PAX3:FOXO1 protein abundance. Here, we established the antitumor efficacy of entinostat with chemotherapy in various preclinical cell and mouse models and found that HDAC3 inhibition was the primary mechanism of entinostat-induced suppression of PAX3:FOXO1 abundance. HDAC3 inhibition by entinostat decreased the activity of the chromatin remodeling enzyme SMARCA4, which, in turn, derepressed the microRNA miR-27a. This reexpression of miR-27a led to
mRNA destabilization and chemotherapy sensitization in aRMS cells in culture and in vivo. Furthermore, a phase 1 clinical trial (ADVL1513) has shown that entinostat is tolerable in children with relapsed or refractory solid tumors and is planned for phase 1B cohort expansion or phase 2 clinical trials. Together, these results implicate an HDAC3-SMARCA4-miR-27a-PAX3:FOXO1 circuit as a driver of chemoresistant aRMS and suggest that targeting this pathway with entinostat may be therapeutically effective in patients.
Abstract
Objective
The primary aim of this study was to apply a novel technology acceptance model (TAM) for virtual reality (VR) in healthcare. The secondary aim was to assess reliability of this ...model to evaluate factors that predict the intentions of pediatric health providers’ use of VR as an anxiolytic for hospitalized pediatric patients.
Materials and Methods
Healthcare providers that interacted with pediatric patients participated in a VR experience available as anxiolysis for minor procedures and then completed a survey evaluating attitudes, behaviors, and technology factors that influence adoption of new technologies.
Results
Reliability for all domain measurements were good, and all confirmatory factor analysis models demonstrated good fit. Usefulness, ease of use, curiosity, and enjoyment of the VR experience all strongly predict intention to use and purchase VR technologies. Age of providers, past use, and cost of technology did not influence future purchase or use, suggesting that VR technologies may be broadly adopted in the pediatric healthcare setting.
Discussion
Previous VR-TAM models in non-healthcare consumers formulated that age, past use, price willing to pay, and curiosity impacted perceived ease of use. This study established that age, past use, and cost may not influence use in healthcare. Future studies should be directed at evaluating the social influences and facilitating conditions within healthcare that play a larger influence on technology adoption.
Conclusion
The VR-TAM model demonstrated validity and reliability for predicting intent to use VR in a pediatric hospital.
Lay Summary
Acceptance of virtual reality (VR) in healthcare has been evaluated by a technology acceptance model (TAM) known as VR TAM, but these studies were limited to nursing students and psychiatrists. This study explored the validity and reliability of a VR TAM to predict the intentions of 270 pediatric health providers to use VR as an anxiolytic for hospitalized pediatric patients. Usefulness, ease of use, curiosity, and enjoyment of the VR experience strongly predicted intention to use and purchase VR technologies. Age of providers, past use, and cost of technology did not influence future purchase or use, suggesting that VR technologies may be broadly adopted in the pediatric healthcare setting. Future studies should evaluate the social influences and facilitating conditions that influence technology adoption.
Cancer patients with advanced disease routinely exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments ...options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates molecular sequencing data with functional assay data to develop patient-specific combination cancer treatments.
Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the primary murine tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient's epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient's primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay.
Our computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model).
These proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.
COVID-19 vaccination rates among pregnant women remain low, despite increased risk of COVID-19-related illness and death and demonstrated vaccine safety and efficacy in this population. The objective ...of this study is to identify sociodemographic predictors of COVID-19 vaccine hesitancy and elucidate important concerns among the pregnant population in light of evolving conversations regarding COVID-19.
A prospective survey of pregnant women at a single urban clinic in South Texas was conducted August to September 2021 to identify predictors of COVID-19 vaccine hesitancy among the pregnant population. Collected variables included demographics, COVID-19 beliefs, tetanus-diphtheria-pertussis (Tdap)/influenza vaccine hesitancy, and primary vaccine concerns. Statistical analyses included Fisher's exact test, asymptotic two-sample Brown-Mood median test, and multinomial logistic regression.
One hundred and nine participants completed the survey, 35 vaccinated and 74 unvaccinated, with a response rate of 91.6%. Women who were COVID-19 vaccine hesitant were more likely to be younger (28.0 vs. 31.0 years, p < .004) and further along in pregnancy (30.0 vs. 20.0 weeks, p = .001). They were also more likely to report influenza (odds ratio (OR) 6.3; 95% confidence interval (CI) 2.5-17.1) and Tdap (OR 4.1; 95% CI 1.75-10.7) vaccine hesitancy. Furthermore, women who were vaccine hesitant were more likely to believe they did not have enough information to confidently make their decision (OR 4.0; 95% CI 1.4-11.4). Primary concerns with COVID-19 vaccines included: short- and long-term side effects on the pregnancy, personal long-term side effects, and harmful ingredients.
COVID-19 vaccine hesitant pregnant women were more likely to be younger, hesitant toward other vaccines, and concerned with pregnancy impact and harmful ingredients. Personal knowledge of other vaccinated pregnant women was associated with significantly higher vaccine acceptance rates. Access to vaccines and concerns about quality control were not cited as reasons for vaccine hesitancy, in contrast to earlier studies on this topic.
The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1–2 week) in the clinical, public health, and health systems fields.
We ...conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group.
A request for developing recommendations within 2 week is the usual trigger for an urgent response. Although the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of the 4 potential approaches: adopt existing recommendations, adapt existing recommendations, develop new recommendations using existing adequate systematic review, or develop new recommendations using expert panel input; and (8) consider an updating plan.
An urgent response for developing recommendations requires building a cohesive, skilled, and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise; adapting to shifting needs; complying with the principles of transparency; and properly managing conflicts of interest.
•The proposed approach for developing trustworthy recommendations as part of urgent responses (1–2 week) builds on the general principles of trustworthy guideline development.•The approach proposes the following steps: (1) assess the level of urgency; (2) clarify and focus the scope of question(s); (3) prioritize and collect the information needed; (4) assess the adequacy of identified information; and then (5) develop recommendations;•Developing recommendations can consist of (1) adopting existing recommendations; (2) adapting existing recommendations; (3) developing new recommendations using existing systematic reviews; or (4) developing new recommendations using identified information and panel input.
Nonrhabdomyosarcoma soft-tissue sarcomas (STSs) are a class of 50+ cancers arising in muscle and soft tissues of children, adolescents, and adults. Rarity of each subtype often precludes ...subtype-specific preclinical research, leaving many STS patients with limited treatment options should frontline therapy be insufficient. When clinical options are exhausted, personalized therapy assignment approaches may help direct patient care. Here, we report the results of an adult female STS patient with relapsed undifferentiated pleomorphic sarcoma (UPS) who self-drove exploration of a wide array of personalized Clinical Laboratory Improvement Amendments (CLIAs) level and research-level diagnostics, including state of the art genomic, proteomic, ex vivo live cell chemosensitivity testing, a patient-derived xenograft model, and immunoscoring. Her therapeutic choices were also diverse, including neoadjuvant chemotherapy, radiation therapy, and surgeries. Adjuvant and recurrence strategies included off-label and natural medicines, several immunotherapies, and N-of-1 approaches. Identified treatment options, especially those validated during the in vivo study, were not introduced into the course of clinical treatment but did provide plausible treatment regimens based on FDA-approved clinical agents.
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