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1.
Nurs Crit Care ; 29(4): 745-755, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38233201

RESUMEN

BACKGROUND: Paediatric critical care (PCC) is a high-pressure working environment. Staff experience high levels of burnout, symptoms of post-traumatic stress, and moral distress. AIM: To understand challenges to workplace well-being in PCC to help inform the development of staff interventions to improve and maintain well-being. STUDY DESIGN: The Enhanced Critical Incident Technique (ECIT) was used. ECIT encompasses semi-structured interviews and thematic analysis. We identified 'critical incidents', challenges to well-being, categorized them in a meaningful way, and identified factors which helped and hindered in those moments. Fifty-three nurses and doctors from a large UK quaternary PCC unit were consented to take part. RESULTS: Themes generated are: Context of working in PCC, which examined staff's experiences of working in PCC generally and during COVID-19; Patient care and moral distress explored significant challenges to well-being faced by staff caring for increasingly complex and chronically ill patients; Teamwork and leadership demonstrated the importance of team-belonging and clear leadership; Changing workforce explored the impact of staffing shortages and the ageing workforce on well-being; and Satisfying basic human needs, which identified absences in basic requirements of food and rest. CONCLUSIONS: Staff's experiential accounts demonstrated a clear need for psychologically informed environments to enable the sharing of vulnerabilities, foster support, and maintain workplace well-being. Themes resonated with the self-determination theory and Maslow's hierarchy of needs, which outline requirements for fulfilment (self-actualization). RELEVANCE TO CLINICAL PRACTICE: Well-being interventions must be informed by psychological theory and evidence. Recommendations are flexible rostering, advanced communication training, psychologically-informed support, supervision/mentoring training, adequate accommodation and hot food. Investment is required to develop successful interventions to improve workplace well-being.


Asunto(s)
Agotamiento Profesional , COVID-19 , Cuidados Críticos , Lugar de Trabajo , Humanos , Agotamiento Profesional/psicología , Agotamiento Profesional/prevención & control , Cuidados Críticos/psicología , Reino Unido , Lugar de Trabajo/psicología , Femenino , Masculino , Investigación Cualitativa , Personal de Enfermería en Hospital/psicología , Adulto , SARS-CoV-2 , Entrevistas como Asunto , Enfermería de Cuidados Críticos , Satisfacción en el Trabajo
2.
Pediatr Crit Care Med ; 24(7): 604-613, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-36892305

RESUMEN

OBJECTIVES: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH). DESIGN: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence. SETTING: Clusters were six U.K. PICUs. PATIENTS: Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance. INTERVENTIONS: In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances. MEASUREMENTS AND MAIN RESULTS: At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03-0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd ) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between. CONCLUSIONS: NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.


Asunto(s)
Lesión Renal Aguda , Terapia de Reemplazo Renal Continuo , Hemofiltración , Diálisis Peritoneal , Humanos , Lactante , Diálisis Renal , Ultrafiltración , Estudios Transversales , Riñón
3.
JMIR Form Res ; 6(7): e33562, 2022 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-35900828

RESUMEN

BACKGROUND: Patients with end-stage kidney disease (ESKD) wait roughly 4 years for a kidney transplant. A potential way to reduce wait times is using hepatitis C virus (HCV)-viremic kidneys. OBJECTIVE: As preparation for developing a shared decision-making tool to assist patients with ESKD with the decision to accept an HCV-viremic kidney transplant, our initial goal was to assess the feasibility of using The Gambler II, a health utility assessment tool, in an ambulatory dialysis clinic setting. Our secondary goals were to collect health utilities for patients with ESKD and to explore whether the use of race-matched versus race-mismatched exemplars impacted the knowledge gained during the assessment process. METHODS: We used The Gambler II to elicit utilities for the following ESKD-related health states: hemodialysis, kidney transplant with HCV-unexposed kidney, and transplantation with HCV-viremic kidney. We created race exemplar video clips describing these health states and randomly assigned patients into the race-matched or race-mismatched video arms. We obtained utilities for these 3 health states from each patient, and we evaluated knowledge about ESKD and HCV-associated health conditions with pre- and postintervention knowledge assessments. RESULTS: A total of 63 patients with hemodialysis from 4 outpatient Dialysis Center Inc sites completed the study. Mean adjusted standard gamble utilities for hemodialysis, transplant with HCV-unexposed kidney, and transplantation with HCV-viremic kidney were 82.5, 89, and 75.5, respectively. General group knowledge assessment scores improved by 10 points (P<.05) following utility assessment process. The use of race-matched exemplars had little effect on the results of the knowledge assessment of patients. CONCLUSIONS: Using The Gambler II to collect utilities for patients with ESKD in an ambulatory dialysis clinic setting proved feasible. In addition, educational information about health states provided as part of the utility assessment process tool improved patients' knowledge and understanding about ESKD-related health states and implications of organ transplantation with HCV-viremic kidneys. A wide variation in patient health state utilities reinforces the importance of incorporating patients' preferences into decisions regarding use of HCV-viremic kidneys for transplantation.

4.
J Pediatr Intensive Care ; 11(2): 124-129, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35734206

RESUMEN

We describe the critical care course of children with a novel hyperinflammatory syndrome associated with coronavirus disease 2019 (COVID-19) pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with focus on trajectory before and after immunomodulation. Overall, 10 patients who met the U.K. Royal College of Pediatrics and Child Health case definition during a 2-month study period were analyzed. All tested positive for SARS-CoV-2 IgG antibody. Although only 20% were ventilated, 100% required inotropic or vasopressor support. All children had significantly raised inflammatory markers with a median C-reactive protein of 248 (175-263) mg/L, ferritin of 1,561 (726-2,255) µg/L, and troponin-I of 723 (351-2,235) ng/L. Six patients had moderately impaired myocardial function and two had severe impairment. None needed extracorporeal membrane oxygenation. Despite severe illness only a brief period of critical care support of 3 to 5 days was required. Eight received at least one dose of intravenous immunoglobulin. Six received high-dose steroids. Clinical improvement including cardiovascular stability and reduction in inflammatory markers may have occurred with and without immunomodulation.

5.
BMJ Open ; 12(4): e056742, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35365529

RESUMEN

AIMS AND OBJECTIVES: To explore what wellbeing means to medical and nursing staff working in a large paediatric intensive care (PIC). DESIGN: Exploratory qualitative design using an appreciative inquiry framework. SETTING: PIC unit; primary, secondary and tertiary. PARTICIPANTS: 46 nurses and doctors working on PIC. INTERVENTIONS: A set of images were used together with open-ended questions to prompt staff to discuss what wellbeing means to them. Interviews were audiorecorded and transcribed. Data were analysed thematically. RESULTS: Images depicting nature, children and groups of adults were selected most. Meanings of wellbeing for PIC staff can be understood through three themes: (1) Being nurtured and supported at work, (2) Importance of nature and (3) Social support independent of work. The first theme considered the importance of being listened to at work as well as staff highlighting the value of being in control at work. Within the second theme, being active in nature and outdoors as well as the importance of being in the present moment was illustrated. Within the final theme, staff expressed the value of having support independent of work and highlighted the importance of spending time with family. CONCLUSIONS: This study provides a unique insight into how individuals working in PIC experience wellbeing and what wellbeing means to them. Understanding how healthcare professionals in PIC settings experience wellbeing and what wellbeing means to them will enable researchers to develop interventions designed to enhance staff wellbeing based on lived experience.


Asunto(s)
Personal de Enfermería , Médicos , Adulto , Niño , Cuidados Críticos , Personal de Salud , Humanos , Investigación Cualitativa
6.
JAMA Netw Open ; 4(12): e2138464, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34902035

RESUMEN

Importance: Persons experiencing homelessness (PEH) are at higher risk for SARS-CoV-2 infection and severe illness due to COVID-19 because of a limited ability to physically distance and a higher burden of underlying health conditions. Objective: To describe and assess a hotel-based protective housing intervention to reduce incidence of SARS-CoV-2 infection among PEH in Chicago, Illinois, with increased risk of severe illness due to COVID-19. Design, Setting, and Participants: This retrospective cohort study analyzed PEH who were provided protective housing in individual hotel rooms in downtown Chicago during the COVID-19 pandemic from April 2 through September 3, 2020. Participants were PEH at increased risk for severe COVID-19, defined as (1) aged at least 60 years regardless of health conditions, (2) aged at least 55 years with any underlying health condition posing increased risk, or (3) aged less than 55 years with any underlying health condition posing substantially increased risk (eg, HIV/AIDS). Exposures: Participants were housed in individual hotel rooms to reduce the risk of SARS-CoV-2 infection; on-site health care workers provided daily symptom monitoring, regular SARS-CoV-2 testing, and care for chronic health conditions. Additional on-site services included treatment of mental health and substance use disorders and social services. Main Outcomes and Measures: The main outcome measured was SARS-CoV-2 incidence, with SARS-Cov2 infection defined as a positive upper respiratory specimen using any polymerase chain reaction diagnostic assay authorized for emergency use by the Food and Drug Administration. Secondary outcomes were blood pressure control, glycemic control as measured by hemoglobin A1c, and housing placements at departure. Results: Of 259 participants from 16 homeless shelters in Chicago, 104 (40.2%) were aged at least 65 years, 190 (73.4%) were male, 185 (71.4%) were non-Hispanic Black, and 49 (18.9%) were non-Hispanic White. There was an observed reduction in SARS-CoV-2 incidence during the study period among the protective housing cohort (54.7 per 1000 people [95% CI, 22.4-87.1 per 1000 people]) compared with citywide rates for PEH residing in shelters (137.1 per 1000 people [95% CI, 125.1-149.1 per 1000 people]; P = .001). There was also an adjusted change in systolic blood pressure at a rate of -5.7 mm Hg (95% CI, -9.3 to -2.1 mm Hg) and hemoglobin A1c at a rate of -1.4% (95% CI, -2.4% to -0.4%) compared with baseline. More than half of participants (51% [n = 132]) departed from the intervention to housing of some kind (eg, supportive housing). Conclusions and Relevance: This cohort study found that protective housing was associated with a reduction in SARS-CoV-2 infection among high-risk PEH during the first wave of the COVID-19 pandemic in Chicago. These findings suggest that with appropriate wraparound supports (ie, multisector services to address complex needs), such housing interventions may reduce the risk of SARS-CoV-2 infection, improve noncommunicable disease control, and provide a pathway to permanent housing.


Asunto(s)
COVID-19 , Atención a la Salud/métodos , Vivienda , Personas con Mala Vivienda , Enfermedades no Transmisibles , Evaluación de Programas y Proyectos de Salud , Adulto , Anciano , Presión Sanguínea , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/virología , Prueba de COVID-19 , Chicago , Enfermedad Crónica , Femenino , Hemoglobina Glucada/metabolismo , Disparidades en el Estado de Salud , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Enfermedades no Transmisibles/epidemiología , Enfermedades no Transmisibles/terapia , Estudios Retrospectivos , SARS-CoV-2 , Problemas Sociales
7.
MDM Policy Pract ; 6(2): 23814683211056537, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34734119

RESUMEN

Introduction. While use of (hepatitis C virus) HCV-viremic kidneys may result in net benefit for the average end-stage kidney disease (ESKD) patient awaiting transplantation, patients may have different values for ESKD-related health states. Thus, the best decision for any individual may be different depending on the balance of these factors. Our objective was to explore the feasibility of sampling health utilities from hemodialysis patients in order to perform patient-specific decision analyses considering various transplantation strategies. Study Design. We assessed utilities on a convenience sample of hemodialysis patients for health states including hemodialysis, and transplantation with either an HCV-uninfected kidney or an HCV-viremic kidney. We performed patient-specific decision analyses using each patient's age, race, gender, dialysis vintage, and utilities. We used a Markov state transition model considering strategies of continuing hemodialysis, transplantation with an HCV-unexposed kidney, and transplantation with an HCV-viremic kidney and HCV treatment. We interviewed 63 ESKD patients from four dialysis centers (Dialysis Clinic Inc., DCI) in the Cincinnati metropolitan area. Results. Utilities for ESKD-related health states varied widely from patient to patient. Mean values were highest for -transplantation with an HCV-uninfected kidney (0.89, SD: 0.18), and were 0.825 (SD: 0.231) and 0.755 (SD: 0.282), respectively, for hemodialysis and transplantation with an HCV-viremic kidney. Patient-specific decision analyses indicated 37 (59%) of the 63 ESKD patients in the cohort would have a net gain in quality-adjusted life years from transplantation of an HCV-viremic kidney, while 26 would have a net loss. Conclusions. It is feasible to gather dialysis patients' health state utilities and perform personalized decision analyses. This approach could be used in the future to guide shared decision-making discussions about transplantation strategies for ESKD patients.

8.
Arch Dis Child ; 106(3): 215-218, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32788204

RESUMEN

The national implementation groups of early warning systems in the UK and Ireland have identified a need to understand implementation, adoption and maintenance of these complex interventions. The literature on how to implement, scale, spread and sustain these systems is sparse. We describe a successful adoption and maintenance over 10 years of a paediatric early warning system as a sociotechnical intervention using the Nonadoption, Abandonment, Challenges to the Scale-Up, Spread, and Sustainability Framework for Health and Care Technologies. The requirement for iterative processes within environment, culture, policy, human action and the wider system context may explain the possible reasons for improved outcomes in small-scale implementation and meta-analyses that are not reported in multicentre randomised control trials of early warning systems.


Asunto(s)
Tecnología Biomédica/instrumentación , Evento Inexplicable, Breve y Resuelto/prevención & control , Implementación de Plan de Salud/métodos , Calidad de la Atención de Salud/organización & administración , Actitud del Personal de Salud , Tecnología Biomédica/métodos , Evento Inexplicable, Breve y Resuelto/diagnóstico , Niño , Consenso , Puntuación de Alerta Temprana , Indicadores de Salud , Humanos , Irlanda/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Reino Unido/epidemiología
9.
Sci Adv ; 6(47)2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33208373

RESUMEN

Lupus nephritis (LN) is an autoimmune disease with substantial morbidity/mortality and limited efficacy of available therapies. Memory T (Tm) lymphocytes infiltrate LN kidneys, contributing to organ damage. Analysis of LN, diabetic nephropathy, and healthy donor kidney biopsies revealed high infiltration of active CD8+ Tm cells expressing high voltage-dependent Kv1.3 potassium channels-key T cell function regulators-in LN. Nanoparticles that selectively down-regulate Kv1.3 in Tm cells (Kv1.3-NPs) reduced CD40L and interferon-γ (IFNγ) in Tm cells from LN patients in vitro. Kv1.3-NPs were tested in humanized LN mice obtained by engrafting peripheral blood mononuclear cells (PBMCs) from LN patients into immune-deficient mice. LN mice exhibited features of the disease: increased IFNγ and CD3+CD8+ T cell renal infiltration, and reduced survival versus healthy donor PBMC engrafted mice. Kv1.3-NP treatment of patient PBMCs before engraftment decreased CD40L/IFNγ and prolonged survival of LN mice. These data show the potential benefits of targeting Kv1.3 in LN.


Asunto(s)
Canal de Potasio Kv1.3 , Lupus Eritematoso Sistémico , Nefritis Lúpica , Linfocitos T , Animales , Ligando de CD40 , Técnicas de Silenciamiento del Gen , Humanos , Interferón gamma , Riñón/patología , Canal de Potasio Kv1.3/genética , Leucocitos Mononucleares/patología , Nefritis Lúpica/etiología , Nefritis Lúpica/patología , Ratones , Nanopartículas
10.
Sci Rep ; 10(1): 11366, 2020 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-32647214

RESUMEN

To assist in the early warning of deterioration in hospitalised children we studied the feasibility of collecting continuous wireless physiological data using Lifetouch (ECG-derived heart and respiratory rate) and WristOx2 (pulse-oximetry and derived pulse rate) sensors. We compared our bedside paediatric early warning (PEW) score and a machine learning automated approach: a Real-time Adaptive Predictive Indicator of Deterioration (RAPID) to identify children experiencing significant clinical deterioration. 982 patients contributed 7,073,486 min during 1,263 monitoring sessions. The proportion of intended monitoring time was 93% for Lifetouch and 55% for WristOx2. Valid clinical data was 63% of intended monitoring time for Lifetouch and 50% WristOx2. 29 patients experienced 36 clinically significant deteriorations. The RAPID Index detected significant deterioration more frequently (77% to 97%) and earlier than the PEW score ≥ 9/26. High sensitivity and negative predictive value for the RAPID Index was associated with low specificity and low positive predictive value. We conclude that it is feasible to collect clinically valid physiological data wirelessly for 50% of intended monitoring time. The RAPID Index identified more deterioration, before the PEW score, but has a low specificity. By using the RAPID Index with a PEW system some life-threatening events may be averted.


Asunto(s)
Deterioro Clínico , Monitoreo Fisiológico/métodos , Tecnología Inalámbrica , Niño , Preescolar , Electrocardiografía/instrumentación , Electrocardiografía/métodos , Estudios de Factibilidad , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Estudios Longitudinales , Masculino , Monitoreo Fisiológico/instrumentación , Oximetría/instrumentación , Oximetría/métodos , Admisión del Paciente/estadística & datos numéricos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Frecuencia Respiratoria/fisiología , Sensibilidad y Especificidad , Factores de Tiempo
11.
Pediatr Crit Care Med ; 21(6): 543-549, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32343109

RESUMEN

OBJECTIVES: To describe implementation and early evaluation of using quantitative electroencephalography for electrographic seizure detection by PICU clinician staff. DESIGN: Prospective observational study of electrographic seizure detection by PICU clinicians in patients monitored with quantitative electroencephalography. Quantitative electroencephalography program implementation included a continuous education and training package. Continuous quantitative electroencephalography monitoring consisted of two-channel amplitude-integrated electroencephalography, color density spectral array, and raw-electroencephalography. SETTING: PICU. PATIENTS: Children less than 18 years old admitted to the PICU during the 14-month study period and deemed at risk of electrographic seizure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Real time electrographic seizure detection by a PICU team was analyzed for diagnostic accuracy and promptness, against electrographic seizure identification by a trained neurophysiologist, retrospectively reading the same quantitative electroencephalography and blinded to patient details. One-hundred one of 1,510 consecutive admissions (6.7%) during the study period underwent quantitative electroencephalography monitoring. Status epilepticus (35%) and suspected hypoxic-ischemic injury (32%) were the most common indications for quantitative electroencephalography. Electrographic seizure was diagnosed by the neurophysiologist in 12% (n = 12) of the cohort. PICU clinicians correctly diagnosed all 12 patients (100% sensitivity and negative predictive value). An additional eleven patients had a false-positive diagnosis of electrographic seizure (false-positive rate = 52% [31-73%]) leading to a specificity of 88% (79-94%). Median time to detect seizures was 25 minutes (5-218 min). Delayed recognition of electrographic seizure (> 1 hr from onset) occurred in five patients (5/12, 42%). CONCLUSIONS: Early evaluation of quantitative electroencephalography program to detect electrographic seizure by PICU clinicians suggested good sensitivity for electrographic seizure detection. However, the high false-positive rate is a challenge. Ongoing work is needed to reduce the false positive diagnoses and avoid electrographic seizure detection delays. A comprehensive training program and regular refresher updates for clinical staff are key components of the program.


Asunto(s)
Convulsiones , Estado Epiléptico , Adolescente , Niño , Electroencefalografía , Humanos , Unidades de Cuidado Intensivo Pediátrico , Estudios Retrospectivos , Convulsiones/diagnóstico
12.
Clin Cancer Res ; 25(24): 7594-7608, 2019 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-31540977

RESUMEN

PURPOSE: Glioblastoma (GBM) is a fatal primary malignant brain tumor. GBM stem cells (GSC) contribute to resistance to the DNA-damaging chemotherapy, temozolomide. The epidermal growth factor receptor (EGFR) displays genomic alterations enabling DNA repair mechanisms in half of GBMs. We aimed to investigate EGFR/DNA combi-targeting in GBM. EXPERIMENTAL DESIGN: ZR2002 is a "combi-molecule" designed to inflict DNA damage through its chlorethyl moiety and induce irreversible EGFR tyrosine kinase inhibition. We assessed its in vitro efficacy in temozolomide-resistant patient-derived GSCs, mesenchymal temozolomide-sensitive and resistant in vivo-derived GSC sublines, and U87/EGFR isogenic cell lines stably expressing EGFR/wild-type or variant III (EGFRvIII). We evaluated its antitumor activity in mice harboring orthotopic EGFRvIII or mesenchymal TMZ-resistant GSC tumors. RESULTS: ZR2002 induced submicromolar antiproliferative effects and inhibited neurosphere formation of all GSCs with marginal effects on normal human astrocytes. ZR2002 inhibited EGF-induced autophosphorylation of EGFR, downstream Erk1/2 phosphorylation, increased DNA strand breaks, and induced activation of wild-type p53; the latter was required for its cytotoxicity through p53-dependent mechanism. ZR2002 induced similar effects on U87/EGFR cell lines and its oral administration significantly increased survival in an orthotopic EGFRvIII mouse model. ZR2002 improved survival of mice harboring intracranial mesenchymal temozolomide-resistant GSC line, decreased EGFR, Erk1/2, and AKT phosphorylation and was detected in tumor brain tissue by MALDI imaging mass spectrometry. CONCLUSIONS: These findings provide the molecular basis of binary EGFR/DNA targeting and uncover the oral bioavailability, blood-brain barrier permeability, and antitumor activity of ZR2002 supporting potential evaluation of this first-in-class drug in recurrent GBM.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Daño del ADN/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Glioblastoma/tratamiento farmacológico , Quinazolinas/farmacología , Temozolomida/farmacología , Animales , Antineoplásicos Alquilantes/farmacología , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/fisiología , Neoplasias Encefálicas/mortalidad , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Receptores ErbB/antagonistas & inhibidores , Femenino , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , Ratones , Ratones Desnudos , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Nat Commun ; 10(1): 2891, 2019 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-31253791

RESUMEN

Our ability to manage acute myeloid leukemia (AML) is limited by our incomplete understanding of the epigenetic disruption central to leukemogenesis, including improper histone methylation. Here we examine 16 histone H3 genes in 434 primary AML samples and identify Q69H, A26P, R2Q, R8H and K27M/I mutations (1.6%), with higher incidence in secondary AML (9%). These mutations occur in pre-leukemic hematopoietic stem cells (HSCs) and exist in the major leukemic clones in patients. They increase the frequency of functional HSCs, alter differentiation, and amplify leukemic aggressiveness. These effects are dependent on the specific mutation. H3K27 mutation increases the expression of genes involved in erythrocyte and myeloid differentiation with altered H3K27 tri-methylation and K27 acetylation. The functional impact of histone mutations is independent of RUNX1 mutation, although they at times co-occur. This study establishes that H3 mutations are drivers of human pre-cancerous stem cell expansion and important early events in leukemogenesis.


Asunto(s)
Epigenómica , Regulación Leucémica de la Expresión Génica/fisiología , Histonas/metabolismo , Leucemia Mieloide Aguda/metabolismo , Animales , Animales Modificados Genéticamente , Antineoplásicos/farmacología , Secuencia de Bases , Células de la Médula Ósea , Diferenciación Celular , Transformación Celular Neoplásica , ADN/genética , Drosophila melanogaster/genética , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Hematopoyesis/fisiología , Células Madre Hematopoyéticas/metabolismo , Humanos , Ratones , Mutación , Neoplasias Experimentales
14.
J Clin Monit Comput ; 33(4): 713-724, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30264218

RESUMEN

A cardiac arrest is a life-threatening event, often fatal. Whilst clinicians classify some of the cardiac arrests as potentially predictable, the majority are difficult to identify even in a post-incident analysis. Changes in some patients' physiology when analysed in detail can however be predictive of acute deterioration leading to cardiac or respiratory arrests. This paper seeks to exploit the causally-related changing patterns in signals such as heart rate, respiration rate, systolic blood pressure and peripheral cutaneous oxygen saturation to evaluate the predictability of cardiac arrests in critically ill paediatric patients in intensive care. In this paper we report the results of a framework constituting feature space embedding and time series forecasting methods to build an automated prediction system. The results were compared with clinical assessment of predictability. A sensitivity of 71% and specificity of 69% was obtained when the maximum value of Anomaly Index (12) in the 50 min (starting one hour and ending 10 min) before the arrest was considered for the case patients and a random 50 min of data was considered for the control set patients. A positive predictive value of 11% and negative predictive value of 98% was obtained with a prevalence of 5% by our method of prediction. While clinicians predicted 4 out of the 69 cardiac arrests (6%), the prediction system predicted 63 (91%) cardiac arrests. Prospective validation of the automated system remains.


Asunto(s)
Cuidados Críticos/métodos , Paro Cardíaco/diagnóstico , Unidades de Cuidado Intensivo Pediátrico , Aprendizaje Automático , Monitoreo Fisiológico/instrumentación , Presión Sanguínea , Niño , Preescolar , Enfermedad Crítica , Frecuencia Cardíaca , Humanos , Lactante , Recién Nacido , Monitoreo Fisiológico/métodos , Oxígeno/metabolismo , Reproducibilidad de los Resultados , Frecuencia Respiratoria , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador , Programas Informáticos , Sístole
15.
J Clin Monit Comput ; 32(3): 559-569, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28752472

RESUMEN

Most existing, expert monitoring systems do not provide the real time continuous analysis of the monitored physiological data that is necessary to detect transient or combined vital sign indicators nor do they provide long term storage of the data for retrospective analyses. In this paper we examine the feasibility of implementing a long term data storage system which has the ability to incorporate real-time data analytics, the system design, report the main technical issues encountered, the solutions implemented and the statistics of the data recorded. McLaren Electronic Systems expertise used to continually monitor and analyse the data from F1 racing cars in real time was utilised to implement a similar real-time data recording platform system adapted with real time analytics to suit the requirements of the intensive care environment. We encountered many technical (hardware and software) implementation challenges. However there were many advantages of the system once it was operational. They include: (1) The ability to store the data for long periods of time enabling access to historical physiological data. (2) The ability to alter the time axis to contract or expand periods of interest. (3) The ability to store and review ECG morphology retrospectively. (4) Detailed post event (cardiac/respiratory arrest or other clinically significant deteriorations in patients) data can be reviewed clinically as opposed to trend data providing valuable clinical insight. Informed mortality and morbidity reviews can be conducted. (5) Storage of waveform data capture to use for algorithm development for adaptive early warning systems. Recording data from bed-side monitors in intensive care/wards is feasible. It is possible to set up real time data recording and long term storage systems. These systems in future can be improved with additional patient specific metrics which predict the status of a patient thus paving the way for real time predictive monitoring.


Asunto(s)
Unidades de Cuidado Intensivo Pediátrico , Monitoreo Fisiológico/instrumentación , Pediatría/métodos , Adolescente , Algoritmos , Niño , Preescolar , Sistemas de Computación , Computadores , Cuidados Críticos , Electrocardiografía , Humanos , Lactante , Recién Nacido , Tiempo de Internación , Estudios Retrospectivos , Medición de Riesgo , Programas Informáticos
16.
J Public Health Manag Pract ; 23(5): 439-446, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28181967

RESUMEN

OBJECTIVE: The Centers for Disease Control and Prevention (CDC) created the Public Health Associate Program (PHAP) to establish a continuous source of public health professionals who can deliver frontline services at the federal, state, tribal, local, and territorial levels. The article describes preliminary evaluation findings for PHAP. DESIGN: The evaluation's primary purposes are to assess the quality and effectiveness of PHAP, determine its value and impact, and provide information to continuously improve the program. Because the evaluation is both formative and summative and focuses on aggregate outputs and outcomes of PHAP, the methodology is complex and builds over time as different cohorts cycle into and out of the program. Results presented are outcomes of various Web-based surveys and reporting systems. PARTICIPANTS: Four PHAP cohorts, consisting of 579 individuals, participated in 1 or more of the evaluation activities described in this article. RESULTS: The majority of participants report satisfaction with their PHAP experiences, and 74% of recent graduates indicate they are continuing their careers or education in public health immediately after program completion. Seventy-eight percent of recent PHAP graduates who accept a job in public health are employed by the federal government. One year post-PHAP, 74% of alumni report that PHAP has been influential in their careers. CONCLUSION: CDC's investment in PHAP has increased the capacity and capabilities of the public health workforce. Results presented are early indicators of program quality, effectiveness, and impact. Today's public health workers are asked to do more with less, in the face of a dynamic array of complex public health challenges. PHAP offers public health agencies assistance in tackling these losses and challenges.

17.
J Public Health Manag Pract ; 23(5): 434-438, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28181968

RESUMEN

The "learn by doing" approach to training is common in the public health field and is a core component of service-learning programs. Trainee satisfaction, learning, and application of learning have been studied. What is less understood is the perspective of the agencies that host trainees. This study aimed to identify whether and how the Centers for Disease Control and Prevention's Public Health Associate Program (PHAP) adds value to the agencies that host trainees during 2-year field assignments. An exploratory, qualitative study design consisting of 9 semistructured telephone interviews with PHAP host agency supervisors was used. Results suggested that PHAP increased host agencies' capacity by assigning capable trainees to host agencies. Trainees made quality contributions that led to agency- and/or community-wide improvements and positively affected the agencies' culture. Further evaluation of the host perspective is necessary; as coupled with the trainee's perspective, it will provide a more holistic understanding of program value.

20.
Resuscitation ; 92: 19-25, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25906941

RESUMEN

BACKGROUND: It is unknown whether targeted temperature management (TTM) improves survival after pediatric out-of-hospital cardiac arrest (OHCA). The aim of this study was to assess the evolution, safety and efficacy of TTM (32-34 °C) compared to standard temperature management (STM) (<38 °C). METHODS: Retrospective, single center cohort study. Patients aged >one day up to 16 years, admitted to a UK Paediatric Intensive Care Unit (PICU) after OHCA (January 2004-December 2010). Primary outcome was survival to hospital discharge; efficacy and safety outcomes included: application of TTM, physiological, hematological and biochemical side effects. RESULTS: Seventy-three patients were included. Thirty-eight patients (52%) received TTM (32-34 °C). Prior to ILCOR guidance adoption in January 2007, TTM was used infrequently (4/25; 16%). Following adoption, TTM (32-34 °C) use increased significantly (34/48; 71% Chi(2); p < 0.0001). TTM (32-34 °C) and STM (<38 °C) groups were similar at baseline. TTM (32-34 °C) was associated with bradycardia and hypotension compared to STM (<38 °C). TTM (32-34 °C) reduced episodes of hyperthermia (>38 °C) in the 1st 24h; however, excessive hypothermia (<32 °C) and hyperthermia (>38 °C) occurred in both groups up to 72 h, and all patients (n = 11) experiencing temperature <32 °C died. The study was underpowered to determine a difference in hospital survival (34% (TTM (32-34 °C)) versus 23% (STM (<38 °C)); p = 0.284). However, the TTM (32-34 °C) group had a significantly longer PICU length of stay. CONCLUSIONS: TTM (32-34 °C) was feasible but associated with bradycardia, hypotension, and increased length of stay in PICU. Temperature <32 °C had a universally grave prognosis. Larger studies are required to assess effect on survival.


Asunto(s)
Reanimación Cardiopulmonar/métodos , Hipertermia Inducida/métodos , Hipotermia Inducida/métodos , Paro Cardíaco Extrahospitalario/terapia , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Paro Cardíaco Extrahospitalario/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Temperatura , Resultado del Tratamiento , Reino Unido/epidemiología
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