RESUMO
OBJECTIVE: Parents experience psychologic distress during their child's admission to a PICU, but effective screening for parental mental health symptoms is not the standard of care. We aimed to test the feasibility and acceptability of a mobile phone-based mental health survey for parents/guardians of PICU patients to facilitate their support by the PICU team. DESIGN: Post hoc analysis of a single-institution pilot study conducted in 2022. Mental health surveys were delivered by text message to parents/guardians of PICU patients over 1 month, beginning 3 days after their child's PICU admission. In-person interviews 1 month after hospital discharge were used to solicit participants' opinions on the survey platform and content. SETTING: A quaternary U.S. academic medical center. PARTICIPANTS: Parents/guardians of PICU patients. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of the 53 participants who consented, 31 (58%) completed the study. Symptoms of acute stress (ASS) were the most common and most severe: 21 participants screened positive for ASS, and 20 of those that screened positive had "moderate" or "severe" symptoms. Among the 23 participants who screened positive for one mental health condition, 10 met the thresholds for all three. Scoring of the protocol's usability, acceptability, and feasibility showed a System Usability Scale equal to 82 of 100, an Acceptability of Intervention Measure score equal to 4.2 of 5, an Intervention Appropriateness Measure score equal to 4.5 of 5, and Feasibility of Intervention Measure score equal to 4.5 of 5. CONCLUSIONS AND RELEVANCE: Mobile phone-based screening for parental mental health symptoms is acceptable and may offer the advantage of privacy and flexibility.
RESUMO
Overactivation of HER2 and crosstalk of other HER family members contribute to a survival pathway of breast cancer cells exposed to trastuzumab, the therapeutic inhibitor of HER2 and thus, decrease response and promote resistance. We have explored the involvement of the intracellular cysteine protease calpain4, the common partner of isoforms calpain1 and calpain2, in the regulation of cell survival and trastuzumab-response. Increase of calpain4 expression and isoform activities were detected in breast cancer cells and HER2-positive tumors. Molecular analyses of parent and resistant cells suggested that perturbation of regulations, induced by calpain4 and of activities of HER2 and HER3, was associated with trastuzumab-resistance. The suppression of calpain4 destabilized calpain1 and calpain2, however, did not prevent the activation of HER2 and HER3 or cell proliferation in the absence of trastuzumab. To understand the significance, the survival of parent and trastuzumab-resistant cells in which calpain4 was suppressed, was assessed in the presence of trastuzumab; survival in each cell type was decreased and associated with a loss of HER2 and HER3 activity. Taken together, by contributing to the activation and the crosstalk of HER2, calpain4 promotes the survival pathway of breast cancer cells, and therefore, its suppression enhances trastuzumab-response and decreases resistance.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Calpaína/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias da Mama/genética , Calpaína/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Isoformas de Proteínas , Receptor ErbB-2/genética , Receptor ErbB-3/genética , Receptor ErbB-3/metabolismo , TrastuzumabRESUMO
BACKGROUND AND OBJECTIVE: Improved survival has shifted research focus toward understanding alternate PICU outcomes, including neurocognitive and functional changes. Bronchiolitis is a common PICU diagnosis, but its neuro-functional outcomes have not been adequately described in contemporary literature. The objective of the study is to describe the epidemiology and associated clinical characteristics of acute neuro-functional morbidity (ANFM) in critical bronchiolitis. METHODS: Patients <2 years old admitted with bronchiolitis between 2014 and 2016 were identified. Demographics, medical history, length of stay (LOS), and need for intubation were collected. Children with a history of neurologic illness or illness associated with neurologic sequelae were termed "high risk"; others were termed "low risk." ANFM was defined both at PICU and hospital discharge as the presence of swallowing difficulty, nasogastric tube feeds, hypotonia, or lethargy. Variables were compared by using χ2 and Wilcoxon rank tests. RESULTS: Among 417 children, 16.7% had ANFM, predominantly swallow difficulties (95.7%). Children with ANFM had lower weight (5.9 [4.4-8.2] vs 7.7 [5.5-9.7] kg, P = .001), longer LOS (6.6 [2.5-13.3] vs 1.9 [0.9-3.5] days, P < .001), intubation (51.4% vs 6.1%, P < .001) and high-risk status (37.1% vs 8.4%, P < .001). Among 362 low risk subjects, ANFM was identified in 44 (12%). In a multivariate logistic regression model, high-risk status, intubation, and ICU LOS were associated with ANFM. ANFM persisted to hospital discharge in 46% of cases. CONCLUSIONS: One out of 6 patients with critical bronchiolitis had documentation consistent with ANFM at PICU discharge. Risk factors included previous neurologic conditions, longer LOS, and intubation. Many were low-risk and/or did not require intubation, indicating a risk for neuro-functional morbidities despite moderate acuity.
Assuntos
Bronquiolite , Alta do Paciente , Bronquiolite/complicações , Bronquiolite/epidemiologia , Bronquiolite/terapia , Criança , Pré-Escolar , Humanos , Unidades de Terapia Intensiva Pediátrica , Morbidade , Estudos RetrospectivosRESUMO
The Early Literacy Screener (ELS) is a brief screen for emergent literacy delays in 4- and 5-year-olds. Standard developmental screens may also flag these children. What is the value of adding the ELS? Parents of children aged 4 (n = 45) and 5 (n = 26) years completed the Ages and Stages Questionnaire-3 (ASQ-3), the Survey of Well-Being in Young Children (SWYC), and the ELS. Rates of positive agreement (PA), negative agreement (NA), and overall agreement (Cohen's κ) across the various screening tools were calculated. Early literacy delays were detected in 51% of those who passed the ASQ and 38% of those who passed the SWYC. For ELS versus ASQ, κ = 0.18, PA = 0.36 (95% CI = 0.23-0.51), and NA = 0.83 (95% CI = 0.66-0.92). For ELS versus SWYC, κ = 0.42, PA = 0.61 (95% CI = 0.45-0.75), and NA = 0.82 (95% CI = 0.65-0.92). The ELS adds value by flagging early literacy delays in many children who pass either the ASQ-3 or SWYC.