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BACKGROUND: New research in the field of psychological trauma has emphasized (a) the heterogeneity of psychological reactions after traumatic events and (b) the existence of distinct symptom trajectories. AIMS: In this study, existing data on post-traumatic stress disorder (PTSD) symptoms in 66 parent-child dyads were re-examined in the light of this literature in order to establish whether a similar pattern of symptom trajectories also applies to this population. STUDY DESIGN: A prospective observational cohort study. Participants' PTSD symptoms were assessed 3 and 12 months after discharge from a paediatric intensive care unit (PICU), using a short form of the Davidson Trauma Scale with parents and the Child Revised Impact of Events Scale with children aged 7-17 years. RESULTS: Results confirmed that the majority of children (58%) and parents (46%) exhibited a 'Resilient' PTSD trajectory over the year, in the sense that their scores remained in the non-clinical range at both timepoints. Children displaying a 'Resilient' trajectory were more likely to have a parent who also displayed a 'Resilient' trajectory (p = .018). However, there was also evidence of a 'Recovery' trajectory in a significant minority in this sample and over 1 in 4 children and parents exhibited a 'Chronic' or 'Delayed' symptom trajectory. CONCLUSIONS: Although average PTSD scores reduced over time in this sample and 'Resilient' trajectories were common, a significant proportion of children and parents exhibited 'Chronic' and 'Delayed' symptom trajectories. RELEVANCE TO CLINICAL PRACTICE: These results suggest that, although the majority do well, a significant number of children and family members may develop chronic or delayed symptoms of PTSD in the year following PICU discharge. The monitoring of individual family members' symptoms beyond 3 months post-discharge may help to determine those who might most benefit from further support.
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BACKGROUND: Restrictions to hospital visiting were mandated during the COVID-19 pandemic, with variability in the degree of restriction imposed. At times, paediatric intensive care units (ICU) restricted visiting to one parent/carer. Views of parents/carers and ICU staff about changes in the visiting policy are not well understood. STUDY DESIGN: This is a Service evaluation involving questionnaire survey incorporating rating scales and free-text comments. Inner-city specialist children's hospital. Parents/carers of children on ICU between December 2020-March 2021 and staff who were working on ICU during May-June 2021. Parents and staff on ICU were invited to complete a questionnaire focusing on their experience of being or working on ICU. Quantitative data were analysed descriptively and free-text comments were thematically analysed. RESULTS: Completed questionnaires were received from 81/103 (79%) parents/carers and 217/550 (39%) staff. The majority of parents (n = 60;77%) and staff (n = 191;89%) understood the need for the one-parent visiting policy but acknowledged it was a source of considerable stress. More staff than parents agreed it was appropriate other relatives/friends visiting was not permitted (Z = 3.715;p < .001). There was no association between parents' satisfaction with their child's care and views about the visiting policy. However, staff were more likely to report an impact on their ability to deliver family centred care if they disagreed with the policy. CONCLUSION: The COVID-19 visiting policy had a clear impact on parents and staff. In the event of any future threat to open-access visiting to children in hospital, the potentially damaging effect on children, parents, and staff must be considered. RELEVANCE TO CLINICAL PRACTICE: Visiting policies need to take account of parents being partners in their child's care, rather than purely visitors to the unit where their child is being cared for. Visiting for two carers should always be facilitated, including during a crisis such as a pandemic.
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COVID-19 , Pandemias , Niño , Humanos , COVID-19/epidemiología , Padres , Unidades de Cuidado Intensivo Pediátrico , Cuidados CríticosRESUMEN
Uncontrolled chemotherapy-induced nausea and vomiting can reduce patients' quality of life and may result in premature discontinuation of chemotherapy. Although nausea and vomiting are commonly grouped together, research has shown that antiemetics are clinically effective against chemotherapy-induced vomiting (CIV) but less so against chemotherapy-induced nausea (CIN). Nausea remains a problem for up to 68% of patients who are prescribed guideline-consistent antiemetics. Despite the high prevalence of CIN, relatively little is known regarding its etiology independent of CIV. This review summarizes a metagenomics approach to the study and treatment of CIN with the goal of encouraging future research. Metagenomics focuses on genetic risk factors and encompasses both human (ie, host) and gut microbial genetic variation. Little work to date has focused on metagenomics as a putative biological mechanism of CIN. Metagenomics has the potential to be a powerful tool in advancing scientific understanding of CIN by identifying new biological pathways and intervention targets. The investigation of metagenomics in the context of well-established demographic, clinical, and patient-reported risk factors may help to identify patients at risk and facilitate the prevention and management of CIN.
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Antieméticos , Antineoplásicos , Neoplasias , Antieméticos/uso terapéutico , Antineoplásicos/uso terapéutico , Humanos , Metagenómica , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Náusea/prevención & control , Neoplasias/inducido químicamente , Neoplasias/tratamiento farmacológico , Calidad de Vida , Vómitos/inducido químicamenteRESUMEN
OBJECTIVE: To investigate the efficacy and safety of sildenafil added to inhaled nitric oxide (iNO) for newborn infants with persistent pulmonary hypertension of newborn (PPHN) or hypoxic respiratory failure (HRF) at risk of PPHN. STUDY DESIGN: Part A of a multinational, randomized, double-blind, placebo-controlled trial. Infants ≤96 hours' old, >34 weeks of gestation, receiving iNO (10-20 ppm on ≥50% FiO2) for PPHN or HRF at risk of PPHN, and oxygen index >15 to <60, were randomized (1:1) to intravenous (IV) sildenafil (loading: 0.1 mg/kg, over 30 minutes; maintenance: 0.03 mg/kg/h) or placebo, for up to 14 days. Coprimary end points were treatment failure rate (day 14/discharge) and time on iNO without treatment failure. Secondary end points included time on ventilation and oxygenation measures. RESULTS: Of 87 infants screened, 29 were randomized to IV sildenafil and 30 to placebo; 13 discontinued treatment (sildenafil, n = 6; placebo: n = 7), including 3 deaths (sildenafil: n = 2; placebo: n = 1). Treatment failure rates did not differ with sildenafil (27.6%) vs placebo (20.0%; P = .4935). Mean time on iNO was not different with sildenafil (4.1 days) vs placebo (4.1 days; P = .9850). No differences were noted in secondary end points. Most common adverse events (AEs) with sildenafil (≥10% infants) were hypotension (n = 8/29), hypokalemia (n = 7/29), anemia, drug withdrawal syndrome (n = 4/29, each), and bradycardia (n = 3/29). One serious AE (hypotension) was considered treatment-related. CONCLUSIONS: IV sildenafil added to iNO was not superior to placebo in infants with PPHN or HRF at risk of PPHN. A review of AEs did not identify any pattern of events indicative of a safety concern with IV sildenafil. Infants will have developmental follow-up (Part B). TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT01720524.
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Síndrome de Circulación Fetal Persistente/tratamiento farmacológico , Citrato de Sildenafil/uso terapéutico , Vasodilatadores/uso terapéutico , Administración por Inhalación , Método Doble Ciego , Factores Relajantes Endotelio-Dependientes/administración & dosificación , Femenino , Humanos , Recién Nacido , Infusiones Intravenosas , Masculino , Óxido Nítrico/administración & dosificaciónRESUMEN
Fecal specimen collection in the clinical setting is often unfeasible for large population studies, especially because cancer patients on immunotherapy often experience constipation. A method for constructing and using an at-home stool collection kit designed for epidemiological studies in cancer patients is presented. Participation and compliance rates of the collection kit among late-stage cancer patients from an ongoing, longitudinal study are also discussed. The kit includes three different media on which samples are introduced. Using one stool sample, patients collect specimens by smearing stool onto a fecal occult blood test (FOBT) card, containing three slides for collection. Additional specimens from the same stool sample are added to one tube containing 8 mL of RNAlater preservative and one tube containing 8 mL of 95% ethanol. Stool specimens are stored at room temperature and returned to researchers within 3 days of collection. The purpose of this kit is to yield stool specimens on a variety of media that can be preserved for extended periods of time at room temperature and are compatible with multi-omics approaches for specimen analysis. According to leading microbiome researchers and published literature, each collection method is considered optimal for use in large epidemiological studies. Moreover, the kit is comprised of various components that make stool collection easy, so as not to burden the patient and hence maximize overall compliance. Use of this kit in a study of late-stage lung cancer patients had a participation rate of 83% and baseline compliance rate of 58%.
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Heces/microbiología , Microbiota , Neoplasias/microbiología , Manejo de Especímenes/métodos , Humanos , Manejo de Especímenes/instrumentaciónRESUMEN
OBJECTIVES: Adults report high levels of fatigue after intensive care, but little is known about pediatric survivors. This study aimed to explore rates of self-reported fatigue in children after critical illness. DESIGN: Prospective cohort study. SETTING: Tertiary children's hospital. PATIENTS: Ninety-seven children aged 7-17 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children completed the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale 3 months after discharge from PICU. Comparisons with normative data (n = 209) showed that PICU survivors reported similar mean (SD) total fatigue scores to their healthy peers (79.6 [16.3] vs 81.8 [12.5]; p = 0.239), but greater cognitive fatigue (77.4 [21.9] vs 82.4 [16.4]; p = 0.048). Also children who had sustained a traumatic brain injury reported "less" sleep/rest fatigue (84.6 [15.0] vs 76.8 [16.3]; p = 0.006). Baseline indices of severity of illness were not associated with fatigue. CONCLUSIONS: The Pediatric Quality of Life Inventory Multidimensional Fatigue Scale appears to be a promising tool for use in outcomes research with PICU survivors. These results highlight the need to bear in mind the heterogeneity of PICU patients and the multidimensional nature of fatigue symptoms.
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Fatiga/epidemiología , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Calidad de Vida , Adolescente , Niño , Cognición , Femenino , Humanos , Masculino , Estudios Prospectivos , Psicometría , Autoinforme , Índice de Severidad de la Enfermedad , SueñoRESUMEN
BACKGROUND: In our recent study, most non-small-lung cancer (NSCLC) tumor specimens harbored viral DNA but it was absent in non-neoplastic lung. However, their targets and roles in the tumor cells remain poorly understood. We analyzed gene expression microarrays to identify genes and pathways differentially altered between virus-infected and uninfected NSCLC tumors. METHODS: Gene expression microarrays of 30 primary and 9 metastatic NSCLC patients were preprocessed through a series of quality control analyses. Linear Models for Microarray Analysis and Gene Set Enrichment Analysis were used to assess differential expression. RESULTS: Various genes and gene sets had significantly altered expressions between virus-infected and uninfected NSCLC tumors. Notably, 22 genes on the viral carcinogenesis pathway were significantly overexpressed in virus-infected primary tumors, along with three oncogenic gene sets. A total of 12 genes, as well as seven oncogenic and 133 immunologic gene sets, were differentially altered in squamous cell carcinomas, depending on the virus. In adenocarcinoma, 14 differentially expressed genes (DEGs) were identified, but no oncogenic and immunogenic gene sets were significantly altered. In bronchioloalveolar carcinoma, several genes were highly overexpressed in virus-infected specimens, but not statistically significant. Only five of 69 DEGs (7.2%) from metastatic tumor analysis overlapped with 1527 DEGs from the primary tumor analysis, indicating differences in host cellular targets and the viral impact between primary and metastatic NSCLC. CONCLUSIONS: The differentially expressed genes and gene sets were distinctive among infected viral types, histological subtypes, and metastatic disease status of NSCLC. These results support the hypothesis that tumor viruses play a role in NSCLC by regulating host genes in tumor cells during NSCLC differentiation and progression.
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Adenocarcinoma/virología , Carcinoma de Pulmón de Células no Pequeñas/virología , Carcinoma de Células Escamosas/virología , Proteínas de Neoplasias/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Interacciones Huésped-Patógeno/genética , Humanos , Masculino , Análisis por Micromatrices , Metástasis de la Neoplasia , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
In this exploratory case-control study, we investigated basal cortisol regulation in 5-16-year-old children, 3-6 months following PICU (paediatric intensive care) admission. This was nested within a study of child psychological and cognitive function; 47 children were assessed alongside 56 healthy controls. Saliva samples were collected three times per day (immediately after waking, waking +30 min, and waking +12 h) over two consecutive weekdays. In addition, data on posttraumatic stress symptoms were ascertained from 33 PICU admitted children using the Impact of Events Scale-8 (IES-8). Primary analysis revealed no significant differences in basal cortisol concentrations between PICU discharged children and healthy controls (p > 0.05). Secondary analysis in the PICU group identified a significant positive association between posttraumatic stress symptoms and evening (waking +12 h) cortisol concentrations (p = 0.004). However, when subject to multivariate analysis, evening cortisol was a modest independent predictor of IES-8 scores, relative to the presence of septic illness and poor pre-morbid health. We conclude that paediatric critical illness does not appear to result in marked perturbations to basal cortisol at 3-6 month following discharge. There was evidence of a link between evening cortisol and symptoms of PTSD, but this was not a robust effect and requires further elucidation.
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Hidrocortisona/metabolismo , Unidades de Cuidado Intensivo Pediátrico , Saliva/metabolismo , Trastornos por Estrés Postraumático/diagnóstico , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Ritmo Circadiano/fisiología , Enfermedad Crítica/psicología , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Hidrocortisona/análisis , Londres , Masculino , Análisis Multivariante , Escalas de Valoración Psiquiátrica , Saliva/química , Trastornos por Estrés Postraumático/metabolismo , Trastornos por Estrés Postraumático/psicología , Factores de TiempoRESUMEN
OBJECTIVE: To evaluate the efficacy, safety, and pharmacokinetics of the endothelin receptor antagonist bosentan as adjunctive therapy for neonates with persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: This was a phase 3, multicenter, randomized, placebo-controlled exploratory trial (FUTURE-4). Eligible patients were >34 weeks gestation, <7 days old, receiving inhaled nitric oxide (iNO) treatment (≥4 hours), and had persistent respiratory failure (oxygenation index [OI] ≥12). After 2:1 randomization, bosentan 2 mg/kg or placebo was given by nasogastric tube twice daily for ≥48 hours and up to 1 day after iNO weaning. RESULTS: Twenty-one neonates received a study drug (13 bosentan, 8 placebo). Compared with the placebo group, the group treated with bosentan had a higher median baseline OI and greater need for vasoactive agents. One treatment failure (need for extracorporeal membrane oxygenation) occurred in the group treated with bosentan. The time to weaning from iNO or mechanical ventilation was not different between the groups. Bosentan was well tolerated and did not adversely affect systemic blood pressure or hepatic transaminase levels. Anemia and edema were more frequent in patients receiving bosentan. Blood concentrations of bosentan were low and variable on day 1, and achieved steady state on day 5. CONCLUSION: Adjunctive bosentan was well tolerated, but did not improve oxygenation or other outcomes in our patients with PPHN. This effect may be related to delayed absorption of bosentan on treatment initiation in critically ill neonates or to more severe illness of the neonates who received bosentan. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01389856.
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Antagonistas de los Receptores de Endotelina/uso terapéutico , Síndrome de Circulación Fetal Persistente/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Bosentán , Método Doble Ciego , Antagonistas de los Receptores de Endotelina/efectos adversos , Femenino , Humanos , Recién Nacido , Masculino , Óxido Nítrico/administración & dosificación , Respiración Artificial , Sulfonamidas/efectos adversos , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
OBJECTIVE: To study 12-month persistence of neuropsychological deficits in PICU survivors. DESIGN: Prospective follow-up study. SETTING: Two PICUs. PARTICIPANTS: Children 5-16 years old with neuropsychological deficits 3-6 months following PICU care for meningoencephalitis, sepsis, and other critical illnesses (excluding other primary neurological disorders). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Neuropsychological function was assessed using the Cambridge Neuropsychological Test Automated Battery, the Children's Memory Scale, and the Wechsler Abbreviated Scale of Intelligence or Wide Range Intelligence Test. Forty-seven of 88 PICU admitted children (53%) were identified as neuropsychologically impaired 3-6 months after discharge; of these, 23 provided 12-month follow-up data. In spite of significant improvements in measures of memory, there was little change in intelligence quotient and visual attention over the study period, and children's educational progress remained below expectation. CONCLUSIONS: We found persistently reduced neuropsychological function following PICU admission in the critical illnesses under study.
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Enfermedad Crítica , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Sobrevivientes , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Inteligencia , Masculino , Memoria , Pruebas Neuropsicológicas , Estudios ProspectivosRESUMEN
OBJECTIVE: To assess mental and physical well-being in school-aged children following admission to pediatric intensive care and to examine risk factors for worse outcome. DESIGN: A prospective cohort study. SETTING: Two PICUs. SUBJECTS: A consecutive sample of 88 patients 5-16 years old (median age, 10.00 yr; interquartile range, 6.00-13.00 yr) admitted to PICU from 2007 to 2010 with septic illness, meningoencephalitis, or other critical illnesses were assessed a median of 5 months following discharge and outcomes compared with 100 healthy controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Parents completed questionnaires documenting child mental and physical well-being, including the Strengths and Difficulties Questionnaires, Chalder Fatigue Scale, and Child Sleep Habits Questionnaire. Children over 8 years completed the Impact of Event Scale -8. The children admitted to PICU scored worse on all measures in comparison with the healthy controls, with 20% scoring at risk for psychiatric disorder, 34% with high levels of post-traumatic stress symptoms, 38% at risk for fatigue disorder, and 80% scoring at risk for sleep disturbance. In the PICU group, multivariable regression analyses identified septic illness as an independent predictor of post-traumatic stress symptoms and family status, past child health problems, and PICU length of stay as predictors of reduced general mental well-being. CONCLUSIONS: Our findings indicate that a significant minority of school-aged children admitted to PICU are at risk for reduced mental and physical well-being in the short term. Symptoms of poor mental well-being were linked to both vulnerability factors and critical illness factors.
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Estado de Salud , Hospitalización/estadística & datos numéricos , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Salud Mental , Trastornos por Estrés Postraumático/epidemiología , Adolescente , Niño , Preescolar , Familia/psicología , Femenino , Humanos , Tiempo de Internación , Masculino , Trastornos Mentales/epidemiología , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Sueño , Factores SocioeconómicosRESUMEN
OBJECTIVE: To assess short-term neuropsychological function and academic performance in school children following admission to intensive care and to explore the role of critical neurologic and systemic infection. DESIGN: A prospective observational case-control study. SETTING: Two PICUs. SUBJECTS: A consecutive sample of 88 children aged 5-16 years (median age=10.00, interquartile range=6.00-13.00) who were admitted to intensive care between 2007 and 2010 with meningoencephalitis, septic illness, or other critical illnesses. They were assessed 3 to 6 months following discharge, and their performance was compared with that of 100 healthy controls. Patients were without prior neurologic or neurodevelopmental disorder. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data encompassing demographic and critical illness details were obtained, and children were assessed using tests of intellectual function, memory, and attention. Questionnaires addressing academic performance were returned by teachers. After adjusting for covariates, the children admitted to PICUs significantly underperformed on neuropsychological measures in comparison to healthy controls (p<0.02). Teachers deemed more children admitted to PICUs than controls as performing educationally worse and having problems with school work (ps=0.001), as well as performing below average on aspects of executive function and attention (ps<0.04). Analysis of the effect of illness type on outcome revealed that aspects of neuropsychological function, such as memory function, and teacher-rated academic performance were most reduced in children with meningoencephalitis and septic illness. In the PICU group, multivariable linear regression revealed that worse performance on a composite score of neuropsychologic impairment was more prevalent when children were younger, from a lower social class, and had experienced seizures during their admission (ps<0.02). CONCLUSIONS: Admission to intensive care is followed by deficits in neuropsychologic performance and educational difficulties, with more severe difficulties noted following meningoencephalitis and septic illness. These results highlight the importance of future studies on cognition and educational outcome incorporating type of illness as a moderating factor.
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Trastornos del Conocimiento/epidemiología , Enfermedad Crítica/epidemiología , Discapacidades para el Aprendizaje/epidemiología , Meningoencefalitis/epidemiología , Sepsis/epidemiología , Adolescente , Desarrollo del Adolescente , Estudios de Casos y Controles , Causalidad , Niño , Desarrollo Infantil , Preescolar , Comorbilidad , Escolaridad , Femenino , Estudios de Seguimiento , Humanos , Unidades de Cuidado Intensivo Pediátrico , Masculino , Examen Neurológico , Pruebas Neuropsicológicas , Estudios Prospectivos , Ajuste Social , Reino UnidoRESUMEN
OBJECTIVES: A number of studies have reported on parental/clinician reports of children's quality of life after intensive care treatment. The aim of this study was to establish children's own views of their outcome. [corrected]. DESIGN: Prospective cohort study. [corrected]. SETTING: Twenty-one bed PICU in a tertiary Children's Hospital. PATIENTS: Ninety-seven children aged over 7 yr, with no preexisting learning difficulties, consecutively admitted to PICU over an 18 month period INTERVENTIONS: Patients completed the Pediatric Quality of Life Inventory and a post-traumatic stress screener, at 3 months and again at 1 year (n = 72) after discharge from PICU. MEASUREMENTS AND MAIN RESULTS: At 3 months post-discharge, the mean total Pediatric Quality of Life Inventory score reported by the PICU group was lower than that reported in the literature for a non-clinical community sample (PICU mean = 79.1 vs community mean = 83.9, p = 0.003), but by 1 year, they were comparable (82.2, p = 0.388). The mean physical functioning subscale score remained lower (PICU mean=81.6 vs. community mean=88.5, p = 0.01), but improved significantly from 73.4 at 3 months (p = 0.001).Sub-group analyses revealed that the elective group reported higher emotional functioning than the community sample (91.0, p=0.005 at 3 months and 88.2, p = 0.038 at 1 year vs community mean=78.5), and made significant gains in social functioning between timepoints (79.1 to 91.4, p = 0.015).Finally, although total PedsQL scores at 1 year were not associated with measures of severity of illness during admission, they were significantly negatively associated with concurrent post-traumatic stress symptom scores (r = -0.40, p = 0.001). CONCLUSIONS: The self-report version of the Pediatric Quality of Life Inventory proved to be a feasible and sensitive tool for assessing health related quality of life in this group of PICU survivors.
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Cuidados Críticos , Calidad de Vida , Adolescente , Niño , Cuidados Críticos/psicología , Femenino , Humanos , Unidades de Cuidado Intensivo Pediátrico , Masculino , Estudios Prospectivos , Calidad de Vida/psicología , Recuperación de la Función , Índice de Severidad de la Enfermedad , Participación Social , Estadísticas no Paramétricas , Trastornos por Estrés Postraumático/etiología , Estrés Psicológico/complicaciones , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
INTRODUCTION: High-grade pneumonitis is a severe and potentially life-threatening adverse event associated with concurrent chemoradiation (cCRT) in patients with non-small cell lung cancer (NSCLC). The aim of this study was to summarize and quantify the incidence of severe (grade 3-5) cCRT-induced pneumonitis in unresectable stage III NSCLC patients. METHODS: A systematic literature review and meta-analysis were performed in accordance with PRISMA guidelines. Published literature was searched for randomized controlled trials (RCTs), observational studies, and non-randomized trials from 2014 to April 2020. The primary outcome of interest was incidence of grade 3-5 pneumonitis. RESULTS: Included were 17 studies for the review and 11 for the meta-analysis (1,788 participants); all studies examined radiation-related pneumonitis (RP). The pooled incidence of cCRT-induced grade 3-5 RP in unresectable stage III NSCLC patients was estimated to be 3.62% [95% confidence interval (CI): 1.65-6.21] in RCTs, 5.98% [95% CI: 2.26-12.91] in observational studies, and 7.85% [95% CI: 4.08-13.10] in observational studies using platinum-based doublet chemotherapies. CONCLUSION: These results suggest the incidence of severe and fatal RP in patients with unresectable stage III NSCLC treated with cCRT ranges from 3.62% to 7.85%, with incidence varying by study design and chemotherapy regimen. Estimates of RP incidence were higher in the real-world setting compared to RCTs. These results can be used to contextualize the baseline risk of cCRT-induced pneumonitis in unresectable stage III NSCLC to better understand the adverse event of pneumonitis associated with novel immunotherapy treatments indicated for concomitant use with this modality.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neumonía , Neumonitis por Radiación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Neumonitis por Radiación/diagnóstico , Neumonitis por Radiación/epidemiología , Neumonitis por Radiación/etiología , Neumonía/etiología , Neumonía/inducido químicamenteRESUMEN
BACKGROUND: Recent studies show that human gut microbial composition can determine whether a patient is a responder or non-responder to immunotherapy but have not identified a common microbial signal shared by responding patients. The functional relationship between immunity, intestinal microbiota, and NSCLC response to immune checkpoint inhibitor/inhibition (ICI) in an American cohort remains unexplored. METHODS: RNAlater-preserved fecal samples were collected from 65 pre-treatment (baseline) and post-treatment stage III/IV NSCLC patients undergoing ICI therapy, categorized as responders or non-responders according to RECIST criteria. Pooled and individual responder and non-responder microbiota were transplanted into a gnotobiotic mouse model of lung cancer and treated with ICIs. 16S rDNA and RNA sequencing was performed on patient fecal samples, 16S rDNA sequencing on mouse fecal samples, and flow cytometric analysis on mouse tumor tissue. RESULTS: Responder patients have both a different microbial community structure than non-responders (P = 0.004) and a different bacterial transcriptome (PC2 = 0.03) at baseline. Taxa significantly enriched in responders include amplicon sequence variants (ASVs) belonging to the genera Ruminococcus, Akkermansia, and Faecalibacterium. Pooled and individual responder microbiota transplantation into gnotobiotic mice decreased tumor growth compared to non-responder colonized mice following ICI (P = 0.023, P = 0.019, P = 0.008, respectively). Responder tumors showed an increased anti-tumor cellular phenotype following ICI treatment. Responder mice are enriched with ASVs belonging to the genera Bacteroides, Blautia, Akkermansia, and Faecalibacterium. Overlapping taxa mapping between human and mouse cohorts correlated with tumor size and weight revealed a network highlighting responder-associated ASVs belonging to the genera Colidextribacter, Frisingicoccus, Marvinbryantia, and Blautia which have not yet been reported. CONCLUSIONS: The role of isolate-specific function and bacterial gene expression in gut microbial-driven responsiveness to ICI has been underappreciated. This work supports further investigation using isolate-driven models to characterize the mechanisms underlying this phenomenon.
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Carcinoma de Pulmón de Células no Pequeñas , Microbioma Gastrointestinal , Neoplasias Pulmonares , Animales , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/tratamiento farmacológico , Ratones , Receptor de Muerte Celular Programada 1 , Estados UnidosRESUMEN
OBJECTIVES: Because patients' preoperative nutritional status influences the outcomes, we have used a preoperative nutrition program for surgical patients for a 2-year period and compared the results with those from a cohort treated in the previous 2 years. METHODS: We retrospectively reviewed curative thoracic neoplasm resections from July 15, 2016, to July 15, 2018, in patients who had received a preoperative nutritional-enhanced recovery after surgery (N-ERAS) protocol. The protocol consisted of 5 days of an oral immunonutrition drink 3 times daily, daily receipt of probiotics, and a carbohydrate-loading drink the night before surgery. The historical control cohort (standard group) included those patients who had undergone surgery by the same surgeon during the previous 24 months. We excluded patients who had undergone esophageal, diagnostic, benign, emergency, or palliative procedures. Nonparametric and parametric statistical tests were used to analyze the data. RESULTS: The data from 462 patients were analyzed: 229 N-ERAS patients and 233 standard patients. No significant demographic or caseload differences were found between the 2 groups. The major significant outcome differences included fewer postoperative complications (30 [13.1%] in the N-ERAS group vs 60 [25.8%] in the standard group; P < .001) and shorter hospital stays (3.8 ± 1.9 days for the N-ERAS group vs 4.4 ± 2.6 days for the standard group; P = .001). Use of the N-ERAS protocol resulted in a 16% reduction ($2198; P < .001) in the mean direct hospital costs/patient. Consequently, for the N-ERAS cohort, the hospital was likely saved $503,342 during the 2-year period for the 229 patients just by using the N-ERAS protocol. CONCLUSIONS: Thoracic surgeons should consider using the nontoxic, patient-compliant N-ERAS protocol for their patients, with an expectation of improved clinical results at lower hospital costs-an important consideration when exploring methods to decrease costs because hospitals are increasingly being paid by a negotiated prospective bundled payment reimbursement model.
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Recuperación Mejorada Después de la Cirugía , Estado Nutricional , Apoyo Nutricional , Cuidados Preoperatorios , Neoplasias Torácicas/cirugía , Procedimientos Quirúrgicos Torácicos , Anciano , Bebidas , Ahorro de Costo , Análisis Costo-Beneficio , Carbohidratos de la Dieta/administración & dosificación , Femenino , Alimentos Formulados , Estado Funcional , Costos de Hospital , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Apoyo Nutricional/efectos adversos , Apoyo Nutricional/economía , Valor Nutritivo , Cuidados Preoperatorios/efectos adversos , Cuidados Preoperatorios/economía , Probióticos/administración & dosificación , Recuperación de la Función , Estudios Retrospectivos , Neoplasias Torácicas/economía , Procedimientos Quirúrgicos Torácicos/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The objective of this study was to examine whether cytomegalovirus (CMV), herpes simplex virus type-1 (HSV-1), and C-reactive protein (CRP) are associated with functional impairment in older Latinos. METHODS: A cross-sectional analysis of a cohort study was conducted with a community-dwelling elderly population. The sample was a subset (N = 1559/1789) of participants in the Sacramento Area Latino Study on Aging (SALSA) ages 60-101 with available serum samples and functional impairment measures. Baseline serum samples were assayed for levels of immunoglobulin G antibodies to CMV and HSV-1 and for levels of CRP. Several measures were used to assess functional impairment, including activities of daily living (ADL), instrumental activities of daily living (IADL), and walking pace. RESULTS: CMV and CRP showed statistically significant graded associations with ADL functional impairment, even after controlling for age and gender. The relationship between CMV and ADL was slightly attenuated, and the confidence interval contained the null value when adjusted for total number of health conditions, body mass index, and household income. Only high levels of CRP were significantly related to ADL and IADL impairment even after adjusting for all other covariates. CONCLUSION: Inflammation is clearly linked to physical functioning among aging Latinos. This study also suggests a role for CMV infection in relation to ADL impairment. Further research examining the influence of infection, immune response, and inflammation on longitudinal trajectories of physical functioning is warranted.
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Actividades Cotidianas , Proteína C-Reactiva/análisis , Infecciones por Citomegalovirus/fisiopatología , Herpes Simple/fisiopatología , Herpesvirus Humano 1 , Hispánicos o Latinos , Caminata/fisiología , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Renta , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Survivors of critical illness in childhood commonly display subsequent psychiatric symptoms including emotional and behavioural difficulties, and manifestations of post-traumatic stress disorder (PTSD). Anomalies in inflammatory profiles are an established finding in these childhood psychiatric conditions. OBJECTIVE: This exploratory study aimed to investigate whether abnormal peripheral blood inflammatory markers measured during paediatric intensive care unit (PICU) admission were associated with psychiatric symptoms after discharge. METHODS: We performed a prospective observational cohort study on 71 children with septic illness, meningoencephalitis and other critical disorders admitted to two PICUs between 2007 and 2010. 3-6 months following discharge, subjects were assessed for global psychiatric risk (ie, presence of emotional and behavioural difficulties on the parental Strengths and Difficulties Questionnaire (SDQ)), and for PTSD risk using the child-rated Impact of Events Scale (IES-8). Inflammatory and related biological markers were transcribed from PICU admission notes (white cell count, lymphocytes, neutrophils, C reactive protein (CRP), platelets, fibrinogen and lactate). FINDINGS: Global psychiatric risk at follow-up was associated with abnormal lymphocyte count during admission (χ2=6.757, p=0.014, n=48). In children with sepsis, partial correlation analyses controlling for age and gender highlighted associations between (i) SDQ scores and low lymphocyte count (r=-0.712; p=0.009, n=14), and (ii) IES-8 score and high CRP levels (r=0.823; p=0.006, n=11). These associations remained after correction for multiple comparisons. CONCLUSION: These results support the hypothesis that acute inflammation may play a role in determining the development of psychopathology following PICU admission. CLINICAL IMPLICATIONS: If the findings are replicated, they may help to better highlight which children are at risk of post-PICU psychopathology and appropriately target follow-up.
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Enfermedad Crítica/terapia , Hospitalización , Inflamación/sangre , Unidades de Cuidado Intensivo Pediátrico , Trastornos Mentales/diagnóstico , Adolescente , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Trastornos Mentales/etiología , Riesgo , SobrevivientesRESUMEN
AIM: To examine the association between corticosteroid use in paediatric intensive care units (PICU) and subsequent symptoms of post-traumatic stress disorder (PTSD). METHODS: The subjects were children aged 8-16 years admitted to PICU with sepsis, meningoencephalitis (ME) and other disorders. Illness information was extracted from case notes; 3-6 months post discharge children completed a PTSD symptom questionnaire (eight-item Impact of Events Scale (IES-8)) assessing intrusion and avoidance symptoms. Saliva samples were also collected for cortisol profile analysis. RESULTS: 53 children completed the IES-8 questionnaires. 33 provided saliva samples. 19 (36%) received corticosteroids. In children with sepsis (n=15), corticosteroid use was associated with significantly lower PTSD intrusion symptom scores. There was a trend towards an association between corticosteroid use and lower evening cortisol levels. There was a comparable but weaker trend in children with ME. DISCUSSION: Corticosteroid use may be associated with fewer PTSD symptoms and lower evening cortisol levels following PICU admission in children with sepsis.
Asunto(s)
Cuidados Críticos/psicología , Glucocorticoides/uso terapéutico , Unidades de Cuidado Intensivo Pediátrico , Trastornos por Estrés Postraumático/etiología , Adolescente , Niño , Cuidados Críticos/métodos , Femenino , Estudios de Seguimiento , Humanos , Hidrocortisona/metabolismo , Tiempo de Internación/estadística & datos numéricos , Londres , Masculino , Meningoencefalitis/metabolismo , Meningoencefalitis/terapia , Saliva/metabolismo , Sepsis/metabolismo , Sepsis/terapia , Trastornos por Estrés Postraumático/metabolismo , Trastornos por Estrés Postraumático/prevención & controlRESUMEN
Immune deficiency can be part of CHARGE syndrome but often receives only limited attention. We present two patients with CHARGE syndrome confirmed CHD7 mutations who had severe T-cell deficiency, and review 15 CHARGE patients from the literature with immunological problems. Most of them had severe T-cell deficiency, although the spectrum also included mild T-cell deficiency and isolated humoral immune deficiency. We conclude that immunodeficiency can form an important symptom in CHARGE syndrome although the frequency and exact nature are still insufficiently known. We propose to evaluate immune functions in all CHARGE syndrome patients, to estimate the frequency and nature of the accompanying immunodeficiency, and to obtain better data regarding prognosis and management.