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OBJECTIVES: Survivors of childhood B-acute lymphoblastic leukemia (B-ALL) are at risk for difficulties with attention and executive functioning (EF) as a late effect of treatment. The present study aimed to identify treatment and demographic factors associated with risk for difficulties with EF in youth treated for high-risk B-ALL. METHOD: Children and adolescents with B-ALL treated on Children's Oncology Group (COG) protocol AALL0232 were randomized to high-dose or escalating-dose methotrexate (MTX), and either dexamethasone or prednisone during the induction phase. Neuropsychological functioning was evaluated via protocol AALL06N1, including performance-based and parent-report measures, for 177 participants (57% female, 81% white; mean age at diagnosis = 8.4 years; SD = 5.0) 8-24 months following treatment completion. RESULTS: Mean scores for all attention and EF measures were within the average range, with no significant differences as a function of MTX delivery or steroid treatment (all p > 0.05). In multivariable models, participants with US public insurance exhibited significantly greater parent-reported EF difficulties than those with US private or non-US insurance (p ≤ 0.05). Additionally, participants diagnosed under 10 years of age performed significantly more poorly on measures of attention (i.e., continuous performance task, p ≤ 0.05) and EF (i.e., verbal fluency and tower planning task, p ≤ 0.05). CONCLUSIONS: For survivors of pediatric B-ALL, treatment-related factors were not associated with attention or EF outcomes. In contrast, outcomes varied by demographic characteristics, including age and insurance type, an indicator of economic hardship. Future research is needed to more directly assess the contribution of socioeconomic status on cognitive outcomes in survivors.
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BACKGROUND: Siblings of youth with cancer have heightened risk for poor long-term psychosocial outcomes. Although sibling psychosocial care is a standard in pediatric oncology, this standard is among those least likely to be met. To address barriers to providing sibling services, a blueprint for systematic psychosocial screening and support of siblings was developed based on feedback from a national sample of psychosocial providers. PROCEDURE: Semi-structured interviews were conducted with a purposive sample of psychosocial care providers (N = 27) of various disciplines working in US pediatric cancer centers, varied in size, type, and extent of sibling support. Interviews queried providers' suggestions for the future of sibling psychosocial care and impressions of a blueprint for sibling service delivery, which was iteratively refined based on respondents' feedback. Interviews were analyzed using applied thematic analysis. RESULTS: Based on existing literature and refined according to providers' recommendations, the Sibling Services Blueprint was developed to provide a comprehensive guide for systematizing sibling psychosocial care. The blueprint content includes: (i) a timeline for repeated sibling screening and assessment; (ii) a stepped model of psychosocial support; (iii) strategies for circumventing barriers to sibling care; and (iv) recommendations for how centers with varying resources might accomplish sibling-focused care. The blueprint is available online, allowing providers to easily access and individualize the content. Providers indicated enthusiasm and high potential utility and usability of the blueprint. CONCLUSIONS: The Sibling Services Blueprint may be a useful tool for systematizing sibling psychosocial care, promoting wider availability of sibling-focused services, and addressing siblings' unmet needs.
Subject(s)
Siblings , Humans , Siblings/psychology , Female , Male , Neoplasms/psychology , Neoplasms/therapy , Child , Adolescent , Social SupportABSTRACT
Steroid 5α reductase 2 (SRD5A2) converts testosterone to dihydrotestosterone and is crucial for prostatic development. 5α reductase inhibitors (5ARI) reduce prostate size in benign prostate hyperplasia (BPH) and ameliorate lower urinary tract symptoms secondary to BPH. However, the mechanisms of 5ARI functioning are still not fully understood. Here, we used a Srd5a2-/- mouse model and employed single-cell RNA sequencing to explore the impact of SRD5A2 absence on prostate cellular heterogeneity. Significant alterations in luminal epithelial cell (LE) populations were observed, alongside an increased proportion and proliferative phenotype of estrogen receptor 1 (ESR1)+ LE2 cells, following an SRD5A2-independent ESR1 differentiation trajectory. LE2 cells exhibited enhanced estrogen response gene signatures, suggesting an alternative pathway for prostate growth when SRD5A2 is absent. Human prostate biopsy analysis revealed an inverse correlation between the expressions of SRD5A2 and LE2 markers (ESR1/PKCα), and an inverse correlation between SRD5A2 and the clinical efficiency of 5ARI. These findings provide insights into 5ARI resistance mechanisms and potential alternative therapies for BPH-related lower urinary tract symptoms. © 2024 The Pathological Society of Great Britain and Ireland.
Subject(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase , Epithelial Cells , Estrogen Receptor alpha , Membrane Proteins , Mice, Knockout , Prostate , Prostatic Hyperplasia , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , Male , Animals , Estrogen Receptor alpha/metabolism , Estrogen Receptor alpha/genetics , Prostate/pathology , Prostate/metabolism , Humans , Prostatic Hyperplasia/pathology , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/genetics , Epithelial Cells/metabolism , Epithelial Cells/pathology , Membrane Proteins/metabolism , Membrane Proteins/genetics , Mice , 5-alpha Reductase Inhibitors/pharmacology , Cell Proliferation , Disease Models, Animal , Cell Differentiation , Lower Urinary Tract Symptoms/pathology , Lower Urinary Tract Symptoms/metabolismABSTRACT
Recent advances in single-cell and multicellular microfluidics technology have provided powerful tools for studying cancer biology and immunology. The ability to create controlled microenvironments, perform high-throughput screenings, and monitor cellular interactions at the single-cell level has significantly advanced our understanding of tumor biology and immune responses. We discuss cutting-edge multicellular and single-cell microfluidic technologies and methodologies utilized to investigate cancer-immune cell interactions and assess the effectiveness of immunotherapies. We explore the advantages and limitations of the wide range of 3D spheroid and single-cell microfluidic models recently developed, highlighting the various approaches in device generation and applications in immunotherapy screening for potential opportunities for point-of-care approaches.
Subject(s)
Microfluidics , Neoplasms , Point-of-Care Systems , Single-Cell Analysis , Humans , Single-Cell Analysis/methods , Microfluidics/methods , Tumor Microenvironment , Immunotherapy/methods , Spheroids, Cellular , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Cell Communication , Animals , Lab-On-A-Chip DevicesABSTRACT
BACKGROUND: Sickle cell disease (SCD) pain is associated with functional impairment, and treatment is often limited to pharmacological approaches with unwanted side effects. Although behavioral interventions exist for non-SCD pain populations, interventions designed to address pain-related impairment in SCD are lacking. METHODS: Twenty youth (9-17 years) with SCD completed a four-week telemedicine pain intervention (NCT04388241). Participants and caregivers completed baseline and post-intervention PROMIS pain measures and the Treatment Evaluation Inventory-Short Form (TEI-SF). Descriptive analyses assessed feasibility and acceptability. Reliable Change Index analyses assessed for significant post-intervention changes in pain functioning. Paired t test analyses compared baseline and post-intervention opioid prescription fills. RESULTS: All participants completed at least one treatment session. Eighteen (90%) youth completed all sessions. Youth (100%) and caregivers (94%) rated the intervention as moderately or highly acceptable on the TEI-SF. Forty-seven percent of caregivers and 44% of youth reported reliably significant improvements in pain interference after the intervention (median T-score differences: 24.8 and 23.5, respectively). Sixty-five percent of caregivers (T-score improvement difference: 19.3) and 31% of youth (T-score improvement difference: 32) reported improvements in pain behaviors. There was no significant difference in opioid prescription fills pre- and post-intervention (P > 0.05). CONCLUSIONS: The Balance Program is feasible, highly acceptable, and can be delivered remotely to reduce barriers to care. Approximately half of youth and caregivers reported significant declines in pain interference following the intervention, with substantial improvements in functioning for treatment responders. Behavioral pain interventions are important adjunctive treatments to uniquely address functional impairment associated with acute and chronic pain in SCD.
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Background: College students experience increased responsibility for healthcare transition. They are at increased risk for depressive symptoms and cannabis use (CU), potentially modifiable predictors of successful healthcare transition. This study investigated how depressive symptoms and CU related to transition readiness, and if CU moderated the association between depressive symptoms and transition readiness for college students. Methods: College students (N = 1,826, Mage=19.31, SD = 1.22) completed online measures of depressive symptoms, healthcare transition readiness, and past-year CU. Regression identified 1) the main effects of depressive symptoms and CU on transition readiness and 2) examined if CU moderated the relationship between depressive symptoms and transition readiness with chronic medical conditions (CMC) status as a covariate. Results: Higher depressive symptoms were correlated with past-year CU (r=.17, p<.001) and lower transition readiness (r=-0.16, p<.001). In the regression model, higher depressive symptoms were related to lower transition readiness (ß=-0.02, p<.001); CU was not related to transition readiness (ß=-0.10, p=.12). CU moderated the relationship between depressive symptoms and transition readiness (B=.01, p=.001). The negative relationship between depressive symptoms and transition readiness was stronger for those with no past-year CU (B=-0.02, p<.001) relative to those with a past-year CU (ß=-0.01, p<.001). Finally, having a CMC was related to CU and higher depressive symptoms and transition readiness. Conclusions: Findings highlighted that depressive symptoms may hinder transition readiness, supporting the need for screening and interventions among college students. The finding that the negative association between depressive symptoms and transition readiness was more pronounced among those with past-year CU was counterintuitive. Hypotheses and future directions are provided.
Subject(s)
Cannabis , Transition to Adult Care , Humans , Depression/diagnosis , StudentsABSTRACT
PURPOSE/OBJECTIVE: The stressors experienced by parents of children admitted for inpatient rehabilitation likely place parents at high risk for poor psychosocial adjustment; however, no research to date has described parent adjustment during the acute phase of a child's inpatient rehabilitation hospitalization. The present study evaluates parent adjustment processes through the lens of the transactional stress and coping model by assessing a specific cognitive process (i.e., illness uncertainty) and coping methods (i.e., self-care), which may influence parent adjustment during the inpatient rehabilitation. RESEARCH METHOD/DESIGN: Forty-two parents (47.6% White, 86% female) of children newly admitted to a pediatric inpatient rehabilitation hospital were recruited. Parents completed self-report measures of demographics, illness uncertainty, self-care, and depressive, anxious, and posttraumatic stress symptoms. RESULTS: Sixty-six percent of parents reported clinically significant symptoms in at least one domain of distress. Illness uncertainty accounted for 22.2%-42.4% of the variance in parent distress symptoms, after controlling for parent and child age, parent trauma history, and income. Self-care accounted for 35.1%-51.9% of the variance in parent distress symptoms, when accounting for parent and child age, parent trauma history, and income. CONCLUSIONS/IMPLICATIONS: More than half of parents endorsed clinical elevations in anxiety, depression, and/or posttraumatic stress. Illness uncertainty and self-care are likely very important clinical topics to discuss with parents. Future research should seek to not only assess how parent distress changes across time, but also how other cognitive processes, as well as environmental and family factors influence the parent adjustment process. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Subject(s)
Inpatients , Self Care , Child , Humans , Female , Male , Uncertainty , Parents/psychology , Anxiety/psychology , Stress, PsychologicalABSTRACT
BACKGROUND: Although providing sibling psychosocial services is a standard of care in pediatric oncology, initial survey research suggests that this standard is rarely achieved and siblings' support needs remain unmet. Which sibling psychosocial services are available and how centers provide such services is unknown. To identify targetable services gaps, this qualitative study characterizes current sibling psychosocial care practices at select pediatric cancer centers across the United States. PROCEDURE: Semi-structured interviews were conducted with a purposive sample of psychosocial care providers (N = 27) working across the United States in pediatric oncology centers of varied sizes. Interviews queried providers regarding sibling-focused parent psychoeducation, psychosocial screening, comprehensive assessment, and psychosocial support offerings. Interview data were analyzed using Applied Thematic Analysis. RESULTS: Across cancer centers, sibling care practices did not align with consensus-based recommendations. The nature and availability of sibling-focused psychoeducation, screening, assessment, and support were variable between and within centers. Siblings themselves were largely absent from sibling psychosocial care, and care was rarely sibling-specific. The flow of information about siblings was discontinuous and uncoordinated across the care continuum, resulting in psychosocial care provided reactively, typically in response to parental concerns. CONCLUSIONS: Sibling psychosocial care provision falls short of established care recommendations, leaving sibling psychosocial needs unmet. Findings highlight the need for tools and strategies to facilitate the implementation of sibling psychosocial care across the care continuum, to support siblings' psychosocial functioning across the life course.
Subject(s)
Neoplasms , Psychiatric Rehabilitation , Humans , Child , Siblings/psychology , Neoplasms/therapy , Neoplasms/psychology , Medical Oncology , Parents/psychologyABSTRACT
INTRODUCTION: Adolescents and young adults (AYA) with a chronic medical condition (CMC) attending college must learn to manage their own healthcare (i.e., transition readiness). Maturity has been linked to positive outcomes in AYAs. Research has established a positive relationship between transition readiness and quality of life. The current study aimed to examine a model of perceived maturityàtransition readinessàmental and physical quality of life. METHOD: AYA (N = 153) with a CMC completed self-report questionnaires. RESULTS: The perceived maturityâtransition readinessâmental quality of life indirect path was significant (ab = 1.96, 95% CI = 0.53 to 3.62). The perceived maturityâtransition readinessâphysical quality of life direct and indirect paths were not significant. DISCUSSION: Results showed that maturity and transition readiness are positively associated. Transition readiness may be one mechanism by which maturity results in enhanced quality of life. PRACTICE IMPLICATIONS: Findings highlight the value of enhancing strengths such as maturity to promote AYA independence/autonomy.
Subject(s)
Quality of Life , Transition to Adult Care , Young Adult , Adolescent , Humans , Surveys and Questionnaires , Chronic DiseaseABSTRACT
Introduction: Canine diabetes mellitus (CDM) is a relatively common endocrine disease in dogs. Many CDM clinical features resemble human type 1 diabetes mellitus (T1DM), but lack of autoimmune biomarkers makes calling the disease autoimmune controversial. Autoimmune biomarkers linking CDM and T1DM would create an alternative model for drug development impacting both human and canine disease. Methods: We examined peripheral blood of diagnosed CDM dog patients comparing it to healthy control (HC) dogs. Dogs were recruited to a study at the Colorado State University Veterinary Teaching Hospital and blood samples collected for blood chemistry panels, complete blood counts (CBC), and immunologic analysis. Markers of disease progression such as glycated albumin (fructosamine, the canine equivalent of human HbA1c) and c-peptide were addressed. Results: Significant differences in adaptive immune lymphocytes, innate immune macrophages/monocytes and neutrophils and differences in platelets were detected between CDM and HC based on CBC. Significant differences in serum glucose, cholesterol and the liver function enzyme alkaline phosphatase were also detected. A systemic immune inflammation index (SII) and chronic inflammation index (CII) as measures of dynamic changes in adaptive and innate cells between inflammatory and non-inflammatory conditions were created with highly significant differences between CDM and HC. Th40 cells (CD4+CD40+ T cells) that are demonstrably pathogenic in mouse T1DM and able to differentiate diabetic from non-diabetic subjects in human T1DM were significantly expanded in peripheral blood mononuclear cells. Conclusions: Based on each clinical finding, CDM can be categorized as an autoimmune condition. The association of significantly elevated Th40 cells in CDM when compared to HC or to osteoarthritis, a chronic but non-autoimmune disease, suggests peripheral blood Th40 cell numbers as a biomarker that reflects CDM chronic inflammation. The differences in SII and CII further underscore those findings.
Subject(s)
Autoimmune Diseases , Diabetes Mellitus, Type 1 , Humans , Dogs , Animals , Mice , Leukocytes, Mononuclear/metabolism , Hospitals, Animal , Hospitals, Teaching , CD4-Positive T-Lymphocytes , Biomarkers , Autoimmune Diseases/metabolism , Inflammation/metabolismABSTRACT
PURPOSE: As men age, the prostate continues to grow on average 2.5% per year. While the variable growth rate of the total prostate gland is recognized, the growth rate of different prostate zones remains largely unclear. We evaluated the growth patterns of the prostate zones and identified clinical parameters contributing to the zonal growth rates. MATERIALS AND METHODS: Prostate magnetic resonance imaging (MRI) data and clinical information were obtained retrospectively on 156 patients who had at least 3 prostate MRIs between 2003 and 2018. Different prostate zonal volumes were measured and analyzed. The outcome was analyzed using linear regression. RESULTS: We observed that prostate growth rates vary depending on body mass index (BMI), transition zone index (TZI), the prostate zone and 5-alpha reductase inhibitor (5ARI) use. The peripheral zone volume growth rates increased with age and peaked at 60-70 years of age (p=0.047), while the transition zone volume demonstrates continuous growth without a peak through all ages. BMI and TZI are associated with the growth rate of the peripheral zone (p=0.026, p <0.001, respectively) but not the transition zone growth rate. 5ARI use is significantly associated with the reduction in the transition zone growth rate (p=0.033), not the peripheral zone. In addition, patients with TZI greater than 60% had the most significant reduction in the transition zone growth rate while taking 5ARI (p <0.001). CONCLUSIONS: Transition and peripheral zones of the prostate grow at variable rates. BMI and TZI affect peripheral zone growth rate, while 5ARI use reduces the transition zone growth rate.
Subject(s)
Aging/physiology , Body Mass Index , Prostate/growth & development , Prostatic Hyperplasia/drug therapy , 5-alpha Reductase Inhibitors/therapeutic use , Aged , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Organ Size , Prostate/diagnostic imaging , Prostate/drug effects , Prostatic Hyperplasia/pathology , Retrospective StudiesABSTRACT
OBJECTIVE: Neurocognitive impairments and psychological distress are among the most common difficulties experienced by children treated for cancer. Elevated rates of suicidal ideation (SI) are documented among cancer survivors, and a link between neurocognitive deficits and SI is evident, yet the relationship between SI and pediatric cancer-related neurocognitive effects has not yet been studied. PARTICIPANTS AND METHODS: Participants were 166 pediatric cancer patients (57.8% Brain Tumor, 31.3% leukemia, 10.8% other cancers) aged 6-23 (M = 11.57, SD = 3.82; 45.8% female) referred for neuropsychological surveillance. SI prevalence was measured by parent, teacher, or patient endorsement of self-harm related items on informant-report measures (e.g., the Child Behavior Checklist). Executive functioning (Behavior Rating Inventory of Executive Function), ADHD symptoms (ADHD Rating Scale), and performance-based measures were compared between those with SI and those without. RESULTS: 17.5% of pediatric cancer patients experienced SI, of which 44.7% had self-endorsement only, 58.5% parent-endorsement only, 20.6% teacher-endorsement only, and 24.1% had two endorsements. Those with SI had significantly greater impairments in global executive composite scores by both parent- and teacher-report (ps < 0.05). Parents of children with SI endorsed significantly more inattention symptoms (M = 6.10, SD = 15.48) than those without SI (M = 50.56, SD = 8.70; p < 0.01), but hyperactivity symptoms did not differ. Intellectual and executive function performance did not differ between those with and without SI (ps > 0.1). CONCLUSIONS: An elevated number of children treated for cancer experience SI and related neurocognitive problems. Screening for SI and further assessment of the connection between executive functioning and SI in pediatric cancer populations is needed.
Subject(s)
Attention Deficit Disorder with Hyperactivity/complications , Brain Neoplasms/psychology , Cancer Survivors/psychology , Neurocognitive Disorders/complications , Suicidal Ideation , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/psychology , Brain Neoplasms/therapy , Child , Cognition , Executive Function , Female , Humans , Male , Neurocognitive Disorders/psychology , Neuropsychological Tests , Prevalence , Young AdultABSTRACT
BACKGROUND: Siblings of children with cancer are at increased risk for poor long-term psychosocial outcomes. The standard of psychosocial care in pediatric oncology calling for sibling support is not routinely implemented, often leaving siblings with unmet psychosocial needs. Barriers to implementing the sibling standard may exist at multiple levels. This study addresses research gaps regarding multilevel barriers to supporting siblings at the health care system, oncology center, and family levels. PROCEDURE: Qualitative interviews were conducted with psychosocial care providers (N = 27; 18 psychologists, five social workers, three psychiatrists, and one child life specialist) employed at oncology centers within hospitals across the United States, varying in extent of sibling programming and center size. Interviews included questions about providers' roles, oncology center characteristics, existing psychosocial sibling services, barriers to providing systematic sibling assessment, and ideas about how to overcome barriers. Data were analyzed using applied thematic analysis. RESULTS: Qualitative analysis revealed (a) barriers to providing sibling services occur at multiple levels (health care system, oncology center, family); (b) barriers at multiple levels frequently interact with one another; and (c) interacting barriers maintain a cycle: barriers to providing services contribute to limited provision of services, low service provision leads to limited utilization of existing services and underprioritization of siblings, and together this leads to siblings being off the radar, which further limits sibling service provision. CONCLUSION: Addressing health care system and oncology center barriers to implementing sibling assessment and support may be important potential targets for interventions to help ensure that siblings receive needed psychosocial assessment and support.
Subject(s)
Neoplasms , Psychiatric Rehabilitation , Child , Humans , Medical Oncology , Needs Assessment , Neoplasms/psychology , Neoplasms/therapy , Siblings/psychologyABSTRACT
OBJECTIVE: Adolescents and young adults in the college setting often report poor sleep hygiene and quality. These sleep difficulties may be related to emotion dysregulation, which is highly relevant to broader adjustment. The current study aimed to empirically identify latent groups of healthy college students with distinct subjective sleep patterns and examine differences in emotion dysregulation between subgroups. METHODS: College students (N = 476; Mage=19.38) completed the Adolescent Sleep-Wake Scale-Revised, Adolescent Sleep Hygiene Scale-Revised, and Difficulties in Emotion Dysregulation Scale. Most participants were White (78%), non-Hispanic/Latinx (85%), and female (77%). Latent profile analysis identified patterns of sleep with maximum likelihood estimation. Bolck-Croon-Hagenaars procedure evaluated differences in emotion dysregulation by class. RESULTS: A three-class model had optimal fit, Bayesian information criterion = 11,577.001, Bootstrapped Parametric Likelihood Ratio Test = -5,763.042, p < .001, entropy = .815. The three profiles identified were good sleep (overall high sleep quality and hygiene; n = 219), moderate sleep (low sleep quality with mix of low and high sleep hygiene; n = 221), and poor sleep (very low sleep quality and hygiene; n = 36). Those in the good sleep group (M = 68.06, SE = 1.5) reported significantly less emotion dysregulation than the moderate sleep group (M = 92.12, SE = 1.67; X2(2) = 98.34, p = .001) and the poor sleep group (M = 99.51, SE = 4.10; p < .001). The moderate and poor sleep groups did not significantly differ, X2(2) = 2.60, p = .11. CONCLUSIONS: Emotion dysregulation differed across three sleep profiles, with participants classified in the good sleep group reporting, on average, the lowest emotion dysregulation, compared to the moderate and poor sleep groups. These findings highlight contextual factors of sleep that may be clinically targeted to promote emotion regulation.
Subject(s)
Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders , Adolescent , Bayes Theorem , Emotions , Female , Humans , Sleep , Sleep Wake Disorders/psychology , Universities , Young AdultABSTRACT
INTRODUCTION: The present study aimed to evaluate the feasibility and efficacy of CogmedRM, a computerized, home-based working memory (WM) training program, in children with NF1. METHOD: A pre-post design was used to evaluate changes in performance-based measures of attention and WM, and parent-completed ratings of executive functioning. Children meeting eligibility criteria completed CogmedRM over 9 weeks. Primary outcomes included compliance statistics and change in attention and WM scores. RESULTS: Thirty-one children (52% male; M age = 10.97 ± 2.51), aged 8-15, were screened for participation; 27 children (87%) evidenced WM difficulties and participated in CogmedRM training. On average, participants completed 19.7 out of 25 prescribed sessions, with an adherence rate of 69%. Participants demonstrated improvements in short-term memory, attention, and executive functioning (all Ps < .05). CONCLUSION: Results suggest that computerized, home-based WM training programs may be both feasible and efficacious for children with NF1 and cognitive deficits.
Subject(s)
Computer-Assisted Instruction/methods , Memory, Short-Term/physiology , Neurofibromatosis 1/physiopathology , Neurofibromatosis 1/therapy , Therapy, Computer-Assisted/methods , Adolescent , Child , Executive Function , Feasibility Studies , Female , Humans , Male , Neuropsychological Tests , Pilot Projects , Treatment OutcomeABSTRACT
INTRODUCTION: Pediatric brain tumor survivors (PBTS) are at risk for both neurocognitive impairments and psychological difficulties, yet these two domains have historically been discretely examined, with assessment of psychosocial outcomes rarely included in studies of cognitive outcomes. Taking a person-centered approach, the current study aimed to more comprehensively evaluate PBTS late effect profiles, including both neurocognitive and psychological sequelae, and predictors of these profiles. METHOD: PBTS (N = 89) were assessed in a pediatric neuropsychological clinic between May 2009 and May 2018, diagnosed at least 1 year prior, and off-treatment for at least 3 months (Mage = 6.57 years, SD = 4.53; 46.1% female). Parent- and teacher-report of psychological symptoms, and performance-based measures of neurocognitive functioning were examined using latent profile analysis. The R3STEP procedure identified predictors of class membership. RESULTS: The optimal model identified four classes characterized by: (1) average functioning across all measures ("Average," n = 47), (2) average psychosocial functioning and impaired neurocognitive functioning ("Cognitive Deficit," n = 25), (3) elevated social problems and significant neurocognitive impairments ("Social/Cognitive Deficit," n = 9), and (4) impaired visual planning and problem-solving and elevated parent-reported psychosocial problems, but average processing speed, working memory, and teacher-reported psychosocial outcomes ("Discrepant," n = 8). Ethnicity, race, radiation treatment, and diagnoses of neurofibromatosis 1, hydrocephalus, and cerebellar mutism syndrome were significant predictors of class membership (ps < 0.05). CONCLUSION: The present study identified distinct phenotypes with unique patterns of relations among neurocognitive and psychological domains. These findings are a vital first step toward identifying those at highest risk for poor outcomes and informing interventions that effectively address interrelated treatment targets for specific groups.
Subject(s)
Brain Neoplasms , Cognition Disorders , Child , Female , Humans , Male , Memory, Short-Term , Neuropsychological Tests , Phenotype , SurvivorsABSTRACT
OBJECTIVE: To identify possible subgroups of health care utilization (HCU) patterns among adolescents and young adults (AYAs) with a chronic medical condition (CMC), and examine how these patterns relate to transition readiness and health-related quality of life (HRQoL). METHODS: Undergraduates (N = 359; Mage=19.51 years, SD = 1.31) with a self-reported CMC (e.g., asthma, allergies, irritable bowel syndrome) completed measures of demographics, HCU (e.g., presence of specialty or adult providers, recent medical visits), transition readiness, and mental HRQoL (MHC) and physical HRQoL (PHC). Latent class analysis identified four distinct patterns of HCU. The BCH procedure evaluated how these patterns related to transition readiness and HRQoL outcomes. RESULTS: Based on seven indicators of HCU, a four-class model was found to have optimal fit. Classes were termed High Utilization (n = 95), Adult Primary Care Physician (PCP)-Moderate Utilization (n = 107), Family PCP-Moderate Utilization (n = 81), and Low Utilization (n = 76). Age, family income, and illness controllability predicted class membership. Class membership predicted transition readiness and PHC, but not MHC. The High Utilization group reported the highest transition readiness and the lowest HRQoL, while the Low Utilization group reported the lowest transition readiness and highest HRQoL. CONCLUSIONS: The present study characterizes the varying degrees to which AYAs with CMCs utilize health care. Our findings suggest poorer PHC may result in higher HCU, and that greater skills and health care engagement may not be sufficient for optimizing HRQoL. Future research should examine the High Utilization subgroup and their risk for poorer HRQoL.
Subject(s)
Patient Acceptance of Health Care , Quality of Life , Adolescent , Chronic Disease , Humans , Latent Class Analysis , Surveys and Questionnaires , Young AdultABSTRACT
Objective: Obesity resulting from high-fat diets has a close relationship with the morbidity and mortality associated with Prostate cancer (PCa) in males. The anti-cancer role of Icaritin (ICT, a traditional Chinese herbal medicine) has been reported in several types of cancer including PCa. Adipokines are novel adipocyte-specific secretory protein, which plays a key role in the development of various diseases including obesity, diabetes, atherosclerosis, and cancer. However, the function of ICT and the molecular mechanisms underlying its role in PCa regression through modulation of adipokines have not been studied. Here, we assessed the anti-cancer properties of ICT under the influence of human epidermal growth factor receptor type 2 (HER2) pathway modulating adipokines in obese PCa models. Materials and Methods: In this study, we used transgenic adenocarcinoma of mouse prostate (TRAMP), a well-established animal model for the study of PCa pathogenesis. All the animals were fed on a high-fat diet (HFD with 40% fat) and divided into two groups, one received ICT solution of 30 mg/kg body bwt (i.p) while the other group served as control without any ICT treatment. The mortality rate, tumor formation and fat ratio were assessed by histopathological and magnetic resonance analysis at different time points of 20th, 24th and 28th weeks. The protein expression of HER2 and serum levels of adipokines were measured using western blotting, IHC and multiplex immunoassays. The PCa grade in 12 TRAMP mice were longitudinally evaluated to visualize PCa development and progression upon post-surgery using PET/CT scanning. Results: We observed that ICT treatment significantly reduces the total mortality rate of TRAMP mice (p = 0.045) and the percentage of prostate intraepithelial neoplasia (PIN) or PCa (p = 0.029). Interestingly, significantly decreased levels of leptin (p = 0.006 @20th wk) and the elevated levels of adiponectin (p = 0.030 @20th wk) were observed in different subgroups upon ICT treatment in a time-dependent manner. In addition, a decrease level of HER2 (p = 0.032 @28th wk) and an elevated level of PEA3 (p = 0.014 @28th wk) were also detected in ICT treated group. The PET/CT-based imaging showed that ICT vs non-ICT treated mice had different standard uptake value and metastasis. Discussion and Conclusion: Our results showed potent anti-cancer properties of ICT through the modulation of adipokine secretion may alter the expression and activation of HER2 pathway as an alternative mechanism to prevent PCa progression. Altogether, our findings indicate that ICT could be a promising cancer preventive agent with the potential to target and eradicate tumor cells in obese PCa patients.
ABSTRACT
OBJECTIVE: A subset of parents of children with disorders/differences of sex development (DSD) including ambiguous genitalia experience clinically elevated levels of anxious and depressive symptoms. Research indicates that uncertainty about their child's DSD is associated with parent psychosocial distress; however, previous studies have been cross-sectional or correlational in nature. The current study is the first to examine the longitudinal trajectory of the relationship between caregiver-perceived uncertainty about their child's DSD and caregiver anxious and depressive symptoms across the first 12 months following genital surgery in young children, or if surgery was not performed, the first 12 months following study entry. METHODS: One hundred and thirteen caregivers (Mage = 32.12; 57.5% mothers; 72.6% Caucasian) of children (N = 70; Mage = 9.81 months; 65.7% female) with DSD were recruited from 12 DSD specialty clinics in the United States. Caregivers completed psychosocial measures at baseline, 6 and 12 months following genitoplasty, or study entry if parents elected not to have surgery for their child. RESULTS: Caregiver illness uncertainty and both anxious and depressive symptoms were highest at baseline and decreased over time (ps < .05). Caregiver illness uncertainty predicted symptoms of anxious and depressive symptoms across all time points (ps < .05). CONCLUSIONS: Caregivers' perceptions of uncertainty about their child's DSD are highest soon after diagnosis, and uncertainty continues to predict both anxious and depressive symptoms across time. Thus, the initial diagnostic period is a critical time for psychological assessment and intervention, with parent illness uncertainty being an important clinical target.