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BACKGROUND: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. METHODS: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. FINDINGS: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. INTERPRETATION: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).
Assuntos
Mesotelioma , Neoplasias Pleurais , Humanos , Feminino , Masculino , Neoplasias Pleurais/cirurgia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/mortalidade , Pessoa de Meia-Idade , Idoso , Mesotelioma/cirurgia , Mesotelioma/tratamento farmacológico , Mesotelioma/mortalidade , Resultado do Tratamento , Reino Unido , Pleura/cirurgia , Mesotelioma Maligno/cirurgia , Mesotelioma Maligno/tratamento farmacológico , Terapia Combinada/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologiaRESUMO
Importance: Arginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma. Objective: To determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor. Design, Setting, and Participants: This was a phase 2-3, double-blind randomized clinical trial conducted at 43 centers in 5 countries that included patients with chemotherapy-naive nonepithelioid pleural mesothelioma from August 1, 2017, to August 15, 2021, with at least 12 months' follow-up. Final follow-up was on August 15, 2022. Data analysis was performed from March 2018 to June 2023. Intervention: Patients were randomly assigned (1:1) to receive weekly intramuscular pegargiminase (36.8 mg/m2) or placebo. All patients received intravenous pemetrexed (500 mg/m2) and platinum (75-mg/m2 cisplatin or carboplatin area under the curve 5) chemotherapy every 3 weeks up to 6 cycles. Pegargiminase or placebo was continued until progression, toxicity, or 24 months. Main Outcomes and Measures: The primary end point was overall survival, and secondary end points were progression-free survival and safety. Response rate by blinded independent central review was assessed in the phase 2 portion only. Results: Among 249 randomized patients (mean [SD] age, 69.5 [7.9] years; 43 female individuals [17.3%] and 206 male individuals [82.7%]), all were included in the analysis. The median overall survival was 9.3 months (95% CI, 7.9-11.8 months) with pegargiminase-chemotherapy as compared with 7.7 months (95% CI, 6.1-9.5 months) with placebo-chemotherapy (hazard ratio [HR] for death, 0.71; 95% CI, 0.55-0.93; P = .02). The median progression-free survival was 6.2 months (95% CI, 5.8-7.4 months) with pegargiminase-chemotherapy as compared with 5.6 months (95% CI, 4.1-5.9 months) with placebo-chemotherapy (HR, 0.65; 95% CI, 0.46-0.90; P = .02). Grade 3 to 4 adverse events with pegargiminase occurred in 36 patients (28.8%) and with placebo in 21 patients (16.9%); drug hypersensitivity and skin reactions occurred in the experimental arm in 3 patients (2.4%) and 2 patients (1.6%), respectively, and none in the placebo arm. Rates of poststudy treatments were comparable in both arms (57 patients [45.6%] with pegargiminase vs 58 patients [46.8%] with placebo). Conclusions and Relevance: In this randomized clinical trial of arginine depletion with pegargiminase plus chemotherapy, survival was extended beyond standard chemotherapy with a favorable safety profile in patients with nonepithelioid pleural mesothelioma. Pegargiminase-based chemotherapy as a novel antimetabolite strategy for mesothelioma validates wider clinical testing in oncology. Trial Registration: ClinicalTrials.gov Identifier: NCT02709512.
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Hidrolases , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Polietilenoglicóis , Idoso , Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arginina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/etiologia , Neoplasias Pleurais/tratamento farmacológicoRESUMO
Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Animais , Humanos , Adolescente , Humor Irritável/fisiologia , Transtornos de Ansiedade/terapia , Transtornos de Ansiedade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Ansiedade/psicologia , Transtornos do Humor/terapia , Transtornos de Deficit da Atenção e do Comportamento DisruptivoRESUMO
OBJECTIVE: Irritability, typically defined as a proneness to anger, particularly in response to frustration, falls at the intersection of emotion and disruptive behavior. Despite well-defined translational models, there are few convergent findings regarding the pathophysiology of irritability. Most studies utilize computer-based tasks to examine neural responses to frustration, with little work examining stress-related responding to frustration in social contexts. The present study is the first to utilize the novel Frustration Social Stressor for Adolescents (FSS-A) to examine associations between adolescent irritability and psychological and physiological responses to frustration. METHOD: The FSS-A was completed by a predominantly male, racially, ethnically, and socioeconomically diverse sample of 64 12- to 17-year-olds, who were originally recruited as children with varying levels of irritability. Current irritability was assessed using the Multidimensional Assessment Profiles-Temper Loss scale (MAP-TL-Youth). Adolescents rated state anger and anxiety before and after the FSS-A, and usable salivary cortisol data were collected from 43 participants. RESULTS: Higher MAP-TL-Youth scores were associated with greater increases in anger during the FSS-A, but not increases in anxiety, or alterations in cortisol. Pre-task state anger negatively predicted the slope of the rise in cortisol observed in anticipation of the FSS-A. CONCLUSIONS: Results provide support for unique associations between adolescent irritability and anger during, and in anticipation of, frustrating social interactions. Such findings lay a foundation for future work aimed at informing physiological models and intervention targets.
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Ira , Ansiedade , Frustração , Hidrocortisona , Humor Irritável , Saliva , Humanos , Adolescente , Masculino , Feminino , Humor Irritável/fisiologia , Ira/fisiologia , Hidrocortisona/análise , Hidrocortisona/metabolismo , Saliva/química , Ansiedade/psicologia , Criança , Estresse Psicológico/psicologiaRESUMO
Neurocognitive models of pediatric irritability suggest a prominent role of anger; however, few studies have investigated anger-related biases and their neural correlates. Resting state functional connectivity (rsFC) of the amygdala was examined in relation to anger attribution bias (AAB) in a sample of young children (5-9 years old; N = 60; 55% White, 26.7% Hispanic) with clinically significant irritability characterized by impairing emotional outbursts (IEOs). Children completed a resting state functional magnetic resonance imaging scan as well as the assessment of children's emotional skills (ACES), which yields three measures of AAB in the context of social situations, social behaviors, and facial expressions. ACES scores were entered into a general linear model to examine associations with rsFC of the bilateral amygdalae. Children with IEOs exhibited significant biases in attributing anger to others across all three ACES domains. Greater biases toward attributing anger in social situations were associated with reduced rsFC of the bilateral amygdalae with the fusiform/lingual gyri and lateral occipital cortex. Alternatively, greater biases toward attributing anger to facial expressions positively predicted right amygdala-precuneus rsFC. Greater bias toward attributing anger to others based on their behaviors was associated with heightened rsFC of the right amygdala with the left middle frontal gyrus. Findings extend previous work implicating functional connections among regions of default mode and frontoparietal networks in pediatric irritability. Longitudinal studies are needed to further investigate the putative role of AAB in the etiology and long-term outcomes of pediatric irritability. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Tonsila do Cerebelo , Ira , Expressão Facial , Humor Irritável , Imageamento por Ressonância Magnética , Humanos , Ira/fisiologia , Masculino , Feminino , Criança , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiologia , Tonsila do Cerebelo/fisiopatologia , Pré-Escolar , Humor Irritável/fisiologia , Percepção Social , Conectoma , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologiaRESUMO
BACKGROUND: Few tissue biomarkers exist to date that could enrich patient with cancer populations to benefit from immune checkpoint blockade by programmed cell death protein 1/ligand-1 (PD-/L-1) inhibitors. PD-L1 expression has value in this context in some tumor types but is an imperfect predictor of clinical benefit. In malignant pleural mesothelioma, PD-L1 expression is not predictive of the benefit from PD-1 blockade. We aimed to identify novel markers in malignant pleural mesothelioma to select patients better. METHODS: We performed a multiplex-immune histochemistry analysis of tumor samples from the phase III PROMISE-meso study, which randomized 144 pretreated patients to receive either pembrolizumab or standard second-line chemotherapy. Our panel focused on CD8+T cell, CD68+macrophages, and the expression of PD-1 and PD-L1 on these and cancer cells. We analyzed single and double positive cells within cancer tissues (infiltrating immune cells) and in the stroma. In addition, we performed cell neighborhood analysis. The cell counts were compared with clinical outcomes, including responses, progression-free and overall survivals. RESULTS: We confirmed the absence of predictive value for PD-L1 in this cohort of patients. Furthermore, total CD8 T cells, CD68+macrophages, or inflammatory subtypes (desert, excluded, inflamed) did not predict outcomes. In contrast, PD-1-expressing CD8+T cells (exhausted T cells) and PD-1-expressing CD68+macrophages were both independent predictors of progression-free survival benefit from pembrolizumab. Patients with tumors simultaneously harboring PD1+T cells and PD-1+macrophages benefited the most from immune therapy. CONCLUSION: We analyzed a large cohort of patients within a phase III study and found that not only PD-1+CD8 T cells but also PD-1+CD68+ macrophages are predictive. This data provides evidence for the first time for the existence of PD-1+macrophages in mesothelioma and their clinical relevance for immune checkpoint blockade.
Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Humanos , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/metabolismo , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1 , Neoplasias Pulmonares/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Linfócitos T CD8-Positivos , MacrófagosRESUMO
OBJECTIVES: Characterize the dimensional spectrum of preadolescent (PA) irritability, a robust transdiagnostic vulnerability marker, using the youth version of the Multidimensional Assessment Profiles Temper Loss (MAPS-TL-Youth) scale including common and with developmentally specific items. Based on this, derive and validate a clinically optimized irritability screener to flag psychopathology risk in preadolescents. METHODS: The normal:abnormal irritability spectrum was modeled using MAPS-TL-Youth data from the Multidimensional Assessment of Preschoolers Study (MAPS) Study PA wave (n = 340) via item response theory. Both cross-cutting core items from the MAPS scales and developmentally specific items were used to generate this dimension. Stepwise logistic regression was then used to optimize MAPS-TL-Youth irritability items in relation to Kiddie Schedule of Affective Disorders and Schizophrenia impairment to generate a clinically optimized irritability screener. Receiver operator characteristic analysis identified the irritability threshold for the screener. For the first time, youth self-report of their own irritability on the MAPS-TL was also modeled via the MAPS-TL-Youth-Self-Report (MAPS-TL-Youth-SR). RESULTS: Irritability was unidimensional and ranged from mild and common to severe and rare behaviors. Developmentally specific items allowed detection of more severe irritability. Items for the screener were identified in relation to concurrent impairment. These included low frustration tolerance and pathognomonic severe behaviors. The clinically optimized screener demonstrated very good sensitively (87%) and specificity (81%) in regard to concurrent irritability-related DSM disorders. Modeling of the MAPS-TL-Youth-SR yielded similar results. CONCLUSION: Characterizing the normal: abnormal spectrum of irritability in preadolescence advances application of Research Domain Criteria methods to this developmental period. This foundational work yielded two developmentally specified tools for irritability characterization in preadolescence: a nuanced dimensional scale to precisely characterize the full normal-abnormal irritability spectrum, and a pragmatic, clinically optimized screener suitable for real world use. Future application in mechanistic and clinical studies will be important for establishing validity and incremental utility.
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Humor Irritável , Transtornos do Humor , Criança , Adolescente , Humanos , Humor Irritável/fisiologia , AutorrelatoRESUMO
Rigorous validation of the full developmentally sensitive normal:abnormal spectrum, including evaluating the incremental value of age-specific behaviors, is necessary for nuanced characterization of dimensional features of psychopathology. To maximize the clinical utility of transdiagnostic approaches to risk identification, derivation of psychometrically sound, pragmatic versions with empirically derived cutoffs is also key. This special section has a central focus on rigorous, developmentally-based measurement of irritability as an exemplar of this theory- and pragmatically-based approach. Elevated irritability is a robust transdiagnostic predictor of the common psychopathologies of childhood. The Multidimensional Assessment Profiles Temper Loss (MAPS-TL) Scales are the only irritability tool specifically designed to capture the normal:abnormal dimensional spectrum. These have been extensively investigated in preschool age but lack rigorous modeling at older and younger ages. In this special issue, (with three independent-and one longitudinal-set of samples), we test and improve measurement of irritability as a transdiagnostic phenotype of psychopathology risk as it unfolds across development, expanding the MAPS-TL scale in three important ways: (1) extending irritability dimensional modeling and the developmental specification approach to older ages, (2) advancing science to practice translation by generating pragmatic irritability screening tools across ages, and (3) extending the dimensional, developmental specification approach to other dimensions of behavior, that is, internalizing. Collectively, the special issue operationalizes and advances application of a neurodevelopmental, dimensional and transdiagnostic approach to psychopathology.
Assuntos
Humor Irritável , Humanos , Pré-EscolarRESUMO
OBJECTIVES: Heightened irritability in adolescence is an impairing symptom that can lead to negative outcomes in adulthood, but effective screening tools are lacking. This study aimed to derive clinically-optimized cutoff scores using the Multidimensional Assessment Profile Scales-Temper Loss (MAPS-TL) to pragmatically identify adolescents with impairing irritability. METHODS: A diverse sample of 79 adolescents and their parents completed the MAPS-TL-Youth version. Stepwise logistic regression analyses were used to determine the items associated with impairment, and receiver operator characteristic (ROC) analyses were conducted to derive optimal cutoff scores. RESULTS: Three parent-report items (become frustrated easily, angry/irritable/grouchy throughout the day, difficulty calming down when angry) and two youth-report items (hit/shove/kick when lost temper, difficulty calming down when angry) were strongly associated with impairment. Optimal cutoff scores garnered very good sensitivity (91%, 73%) and specificity (77%, 75%) for the parent- and youth-report versions respectively. Scores above these cutoffs were associated with increased internalizing and externalizing problems and lower overall quality of life. CONCLUSIONS: The MAPS-TL clinically optimized irritability scores show preliminary validity for implementation in practical settings to efficiently identify adolescents who need additional evaluation and/or intervention. Further research is important to validate these cutoff scores with larger population-based samples and real-world settings.
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Humor Irritável , Qualidade de Vida , Humanos , Adolescente , Ansiedade , PaisRESUMO
OBJECTIVES: Developmentally specified measures that identify clinically salient irritability are needed for early school-age youth to meaningfully capture this transdiagnostic risk factor for psychopathology. Thus, the current study modeled the normal:abnormal irritability spectrum and generated a clinically optimized screening tool for this population. METHODS: The irritability spectrum was modeled via the youth version of the Multidimensional Assessment Profile Scales-Temper Loss Scale (MAPS-TL-Youth) in children (n = 474; 6.0-8.9 years) using item response theory (IRT). Both cross-cutting core irritability items from the early childhood version and new developmentally specific items were included. Items uniquely associated with impairment were identified and used to derive a brief, clinically optimized irritability screener. Longitudinal data were then utilized to test the predictive utility of this clinically optimized screener in preadolescence (n = 348; 8.0-12.9 years). RESULTS: Most children exhibit irritability regularly, but daily occurrence was rare. Of the top 10 most severe items from the IRT analyses, 9 were from the developmentally specific items added for the MAPS-TL Youth version. Two items associated with concurrent impairment were identified for the clinically optimized irritability screener ("Become frustrated easily" and "Act irritable"). The MAPS-TL-Youth clinically optimized screener demonstrated good sensitivity (69%) and specificity (84%) in relation to concurrent DSM 5 irritability-related diagnoses. Youth with elevated scores on the screener at early school age (ESA) had more than 7x greater odds of irritability-related psychopathology at pre-adolescence. CONCLUSIONS: The MAPS-TL-Youth characterized the developmental spectrum of irritability at ESA and a clinically optimized screener showed promise at predicting psychopathology risk. Rigorous testing of clinical applications is a critical next step.
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Humor Irritável , Saúde Mental , Criança , Adolescente , Humanos , Pré-Escolar , Humor Irritável/fisiologiaRESUMO
OBJECTIVE: Although emotion dysregulation has been defined as a maladaptive process of emotional experiences, there is no specific reference to the emotional valence of the dysregulation. To date, child psychiatry has focused primarily on dysregulation of negative affect. Here, we suggest that positive emotion dysregulation requires additional clinical and research attention. METHOD: First, we present a developmental approach to the study of positive emotion regulation within a temperament framework. Second, we describe emerging research findings regarding dysregulation of positive emotion in early childhood. Third, we integrate neuroscientific approaches to positive emotion regulation and introduce a framework for future investigations and clinical applications. RESULTS: Dysregulation in positive affect can be examined from temperamental, developmental, clinical, and neuroscientific perspectives. Both temperamental surgency, which includes positive affect, and the proposed clinical extension, excitability, are associated with increased risk of externalizing symptoms and clinical impairment in youth. CONCLUSION: Studying the role of both temperamental surgency and clinically impairing positive affect, or excitability, in developmental psychopathology will help to elucidate the full spectrum of emotion dysregulation and to clarify the neural basis of dysregulation. A more comprehensive conceptualization of positively valanced emotion dysregulation will provide a more nuanced understanding of developmental risk and potential targets for intervention. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science.
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Emoções , Transtornos do Humor , Criança , Adolescente , Humanos , Pré-Escolar , Emoções/fisiologia , Sintomas Afetivos , Temperamento , PsicopatologiaRESUMO
This study aimed to examine changes in depression and anxiety symptoms from before to during the first 6 months of the COVID-19 pandemic in a sample of 1,339 adolescents (9-18 years old, 59% female) from three countries. We also examined if age, race/ethnicity, disease burden, or strictness of government restrictions moderated change in symptoms. Data from 12 longitudinal studies (10 U.S., 1 Netherlands, 1 Peru) were combined. Linear mixed effect models showed that depression, but not anxiety, symptoms increased significantly (median increase = 28%). The most negative mental health impacts were reported by multiracial adolescents and those under 'lockdown' restrictions. Policy makers need to consider these impacts by investing in ways to support adolescents' mental health during the pandemic.
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COVID-19 , Adolescente , Feminino , Humanos , Criança , Masculino , Pandemias , Depressão/epidemiologia , Ansiedade/epidemiologia , EtnicidadeRESUMO
Humans are reliant on their caregivers for an extended period of time, offering numerous opportunities for environmental factors, such as parental attitudes and behaviors, to impact brain development. The default mode network is a neural system encompassing the medial prefrontal cortex, posterior cingulate cortex, precuneus, and temporo-parietal junction, which is implicated in aspects of cognition and psychopathology. Delayed default mode network maturation in children and adolescents has been associated with greater general dimensional psychopathology, and positive parenting behaviors have been suggested to serve as protective mechanisms against atypical default mode network development. The current study aimed to extend the existing research by examining whether within- default mode network resting-state functional connectivity would mediate the relation between parental acceptance/warmth and youth psychopathology. Data from the Adolescent Brain and Cognitive Development study, which included a community sample of 9,366 children ages 8.9-10.9 years, were analyzed to test this prediction. Results demonstrated a significant mediation, where greater parental acceptance/warmth predicted greater within- default mode network resting-state functional connectivity, which in turn predicted lower externalizing, but not internalizing symptoms, at baseline and 1-year later. Our study provides preliminary support for the notion that positive parenting behaviors may reduce the risk for psychopathology in youth through their influence on the default mode network.
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Mapeamento Encefálico , Transtornos Mentais , Criança , Humanos , Adolescente , Imageamento por Ressonância Magnética , Rede de Modo Padrão , Encéfalo/diagnóstico por imagem , Transtornos Mentais/diagnóstico por imagem , PaisRESUMO
INTRODUCTION: Clinical and laboratory parameters associated with response for patients with advanced pre-treated malignant pleural mesothelioma (MPM) are lacking. We aimed to identify prognostic and predictive markers among patients with relapsed MPM who were randomised into the ETOP 9-15 PROMISE-meso phase III trial, evaluating pembrolizumab and chemotherapy. METHODS: Baseline clinical and laboratory parameters were investigated for prognostic or predictive value on progression-free survival (PFS) and overall survival (OS) in a retrospective analysis, based on the full cohort of 144 MPM patients. These consisted of immune-inflammatory indexes (neutrophil-lymphocyte ratio [NLR], systemic immune-inflammatory index [SII], lactate dehydrogenase [LDH]) along with other already known prognostic baseline characteristics and laboratory values. Cut-offs were chosen independently of outcome. Based on Cox multivariable analysis for PFS in the whole cohort, a risk factor model was built to illustrate the prognostic stratification of patients by the combination of the derived independent prognostic factors, taking into account the EORTC score, a validated prognostic score in MPM. All models were stratified by histology and adjusted by treatment. RESULTS: In the stratified multivariable analysis in the whole cohort, high SII (hazard ratio (HR) 2.06; 95%CI 1.39-3.05) and low haemoglobin (HR 1.62; 95%CI 1.06-2.50) were associated with worse PFS. Based on these two prognostic factors, a mesothelioma risk score (MRS) was constructed with three PFS risk prognosis categories: favourable, intermediate and poor with 0, 1 and 2 risk factors, respectively (corresponding percent of cohort: 24%, 34% and 42% and median PFS: 5.8, 4.2 and 2.1 months). The derived MRS stratified the prognosis for PFS and OS, overall and within each of the EORTC groups. No significant predictors of treatment benefit were identified. CONCLUSIONS: The proposed MRS is prognostic of patient outcome and it fine-tunes the prognosis of patients with pre-treated MPM alone or when used with the already established EORTC score.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Imunoterapia , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Neoplasias Pleurais/patologia , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To test whether parental factors including internalizing symptoms, parenting style, and confidence in assisting with remote learning conferred risk/resilience for children with/without ADHD's learning and emotional outcomes during the COVID-19 pandemic. METHOD: 291 parents of children (ages 6-13; n = 180 males) with (n = 148) and without ADHD completed questionnaires online (April-July 2020). RESULTS: Structural equation modeling identified parental risk/resilience factors. Across groups, risk predicted greater difficulties with learning, internalizing and externalizing symptoms, while parent confidence in educating their child predicted better outcomes. A positive association was observed between parental involvement and child difficulties, which was stronger in families of children with ADHD. Children with/without ADHD did not differ in remote learning difficulties. CONCLUSION: Parent factors impacted child emotional and learning outcomes during the pandemic. With increases in remote learning practices, there is a need for improved understanding of how parent factors impact outcomes of children with/without ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , COVID-19 , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Humanos , Masculino , Pandemias , Poder Familiar/psicologia , Pais/psicologiaRESUMO
Emotion dysregulation (ED) is prevalent among youth with Attention-Deficit/Hyperactivity Disorder (ADHD) and significantly impacts functioning. Nuanced measurement of ED is central to understanding its role in this disorder and informing treatment approaches. The present study examined the factor structure of the Emotion Regulation Checklist (ERC) among children with ADHD with and without Oppositional Defiant Disorder (ODD). Exploratory factor analysis (EFA) conducted in a sample of 328 youth (mean ageâ¯=â¯6.08) with ADHD indicated a four-factor solution, comprised of the following factors: Negative Emotion Lability, Positive Emotion Lability, Socially Appropriate Affect, and Socially Incongruent Affect. The Negative and Positive Emotion Lability subscales assess the reactivity of negatively and positively valenced emotions, respectively. The Socially Appropriate and Socially Incongruent Affect subscales provide an assessment of social-emotional functioning. All subscales discriminated between children with ADHD only and ADHD with co-morbid ODD, such that children with ODD had greater emotional lability and social-emotional difficulties. This revised factor structure of the ERC facilitates a uniquely brief, yet multifaceted and specific, assessment of emotional difficulties in children with ADHD that can inform treatment planning and operationalize emotional reactivity and social-emotional functioning in future research efforts.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Regulação Emocional , Adolescente , Sintomas Afetivos/complicações , Sintomas Afetivos/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo , Lista de Checagem , Criança , Emoções/fisiologia , HumanosRESUMO
Among the many impacts of the Coronavirus disease (COVID-19) pandemic, one of the most dramatic was the immediate closure of in-person schooling in March/April 2020 when parents were faced with much greater responsibility in supporting their children's learning. Despite this, few studies have examined parents' own perspectives of this experience. The aims of this preliminary study were to (a) identify challenges, benefits, and useful strategies related to remote learning and (b) examine differences in findings across two countries, between parents of youth with and without attention-deficit/hyperactivity disorder (ADHD), and between parents of children and adolescents. To address these aims, parent responses to open-ended questions on the Home Adjustment to COVID-19 Scale (HACS; Becker, Breaux, et al., 2020) were examined across three studies conducted in the United States and Australia (N = 606, children: 68.5% male, ages 6-17 years). The challenges most frequently expressed by parents included the child's difficulty staying on task (23.8% of parents), lack of motivation (18.3%), remote learning factors (17.8%), and lack of social interaction (14.4%). The most frequently expressed strategy related to using routines and schedules (58.2%) and the biggest benefit was more family time (20.3%). Findings were largely consistent across countries, ADHD status, and age, with a few notable group differences. Given that the most common challenges involved child- (e.g., difficulties with staying on task and motivation), parent- (e.g., balancing remote learning with work responsibilities), and school- (e.g., remote instruction difficulties) related factors, there is a need for improved support across these systems going forward. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , COVID-19 , Adolescente , Criança , Feminino , Humanos , Masculino , Pandemias , Pais , SARS-CoV-2 , Estados UnidosRESUMO
Pediatric irritability can be highly impairing and is implicated in adverse outcomes. The phasic component, characterized by temper outbursts, is a frequent impetus to seek treatment. This study tested whether a previously described anger-distress model of tantrums applies to an outpatient sample of school-age children with clinically impairing temper outbursts (TO; 5.0-9.9 years; N = 86), and examined the clinical relevance of resulting factors through associations with measures of psychopathology, and differences between children with TO and two groups without: children with ADHD (n = 60) and healthy controls (n = 45). Factor analyses established a three-factor model: High Anger, Low Anger, Distress. These factors had unique associations with measures of irritability, externalizing problems, and internalizing problems in the TO group. Additionally, an interaction between groups and outburst factors emerged. Results provide evidence for the presence and clinical utility of the anger-distress model in children's outbursts and suggest avenues for future pediatric irritability research.
Assuntos
Ira , Humor Irritável , Agressão , Criança , Pré-Escolar , HumanosRESUMO
Initial research has indicated that college students have experienced numerous stressors as a result of the pandemic. The current investigation enrolled the largest and most diverse sample of college students to date (N = 4714) from universities in New York (NY) and New Jersey (NJ), the epicenter of the North American pandemic in Spring 2020. We described the impact on the psychological, academic, and financial health of college students who were initially most affected and examined racial/ethnic group differences. Results indicated that students' mental health was severely affected and that students of color were disproportionately affected by academic, financial, and COVID-related stressors. Worry about COVID-19 infection, stressful living conditions, lower grades, and loneliness emerged as correlates of deteriorating mental health. COVID-19's mental health impact on college students is alarming and highlights the need for public health interventions at the university level.
RESUMO
Reducing the cost of care while enhancing its quality and experience are essential components to success in value-based care. Because emergency department (ED) and hospital settings represent high-cost environments, the authors sought to reduce their unnecessary use by deploying a novel care delivery service that offers mobile, on-demand care for high-acuity conditions in patient homes. This study is a retrospective quality improvement evaluation of the initial year of the mobile acute care model in a health system with a substantial penetration of value-based care. Although all patients were eligible for mobile services as clinically indicated, those in accountable care organizations were prioritized by the care management teams. A variety of operational, clinical, and financial metrics were assessed to determine the program's performance and value. There were 3436 patient encounters during the study period, a utilization rate of 71% that trended upward throughout the year. Of these visits, 44% involved patients in value-based payment models; 80% of these represented patients in Medicare risk agreements. Throughout the year, progressively improving operational and clinical performance were observed, as were consistently high patient satisfaction scores. An estimated 63.8% of total mobile visits resulted in ED avoidance; 21.6% were emergency medical transport avoidant; 14.1% led to avoided hospital observation or inpatient stays. Patients were highly satisfied with the service. In-home mobile care for high-acuity illness can prevent unnecessary ED and hospital use for some patients and is associated with high patient satisfaction. Acute mobile care is a useful component of a value-based care strategy.