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The link between cholesterol homeostasis and cleavage of the amyloid precursor protein (APP), and how this relationship relates to Alzheimer's disease (AD) pathogenesis, is still unknown. Cellular cholesterol levels are regulated through crosstalk between the plasma membrane (PM), where most cellular cholesterol resides, and the endoplasmic reticulum (ER), where the protein machinery that regulates cholesterol levels resides. The intracellular transport of cholesterol from the PM to the ER is believed to be activated by a lipid-sensing peptide(s) in the ER that can cluster PM-derived cholesterol into transient detergent-resistant membrane domains (DRMs) within the ER, also called the ER regulatory pool of cholesterol. When formed, these cholesterol-rich domains in the ER maintain cellular homeostasis by inducing cholesterol esterification as a mechanism of detoxification while attenuating its de novo synthesis. In this manuscript, we propose that the 99-aa C-terminal fragment of APP (C99), when delivered to the ER for cleavage by γ-secretase, acts as a lipid-sensing peptide that forms regulatory DRMs in the ER, called mitochondria-associated ER membranes (MAM). Our data in cellular AD models indicates that increased levels of uncleaved C99 in the ER, an early phenotype of the disease, upregulates the formation of these transient DRMs by inducing the internalization of extracellular cholesterol and its trafficking from the PM to the ER. These results suggest a novel role for C99 as a mediator of cholesterol disturbances in AD, potentially explaining early hallmarks of the disease.
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Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Membrana Celular/metabolismo , Colesterol/metabolismo , Retículo Endoplásmico/metabolismo , Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/genética , Animales , Línea Celular , Colesterol/biosíntesis , Retículo Endoplásmico/genética , Fibroblastos/metabolismo , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Humanos , Células Madre Pluripotentes Inducidas , Metabolismo de los Lípidos , Lipidómica , Ratones , Mitocondrias/metabolismo , Presenilina-1/genética , Presenilina-1/metabolismo , Presenilina-2/genética , Presenilina-2/metabolismo , Dominios Proteicos , ARN Interferente Pequeño , Esfingomielina Fosfodiesterasa/metabolismoRESUMEN
OBJECTIVE: To compare the characteristics and healthcare use of children with medical complexity who receive paid certified nursing assistant (CNA) care by a family member (family CNA) and by a traditional nonfamily member (nonfamily CNA). STUDY DESIGN: This was retrospective cohort study of children who received CNA care through Colorado's Medicaid paid family caregiving program between 2017 and 2019 by a home healthcare agency. We compared patient characteristics between the family CNA and nonfamily CNA groups. A multivariable Poisson regression model was used to compare hospitalization rates (days in the hospital per year), adjusting for patient age patient sex, nursing care, and complex chronic condition. RESULTS: Of 861 patients, 79% (n = 680) received family CNA care and 21% (n = 181) received nonfamily CNA care. Patient demographics and hospitalization did not differ between the groups, although patients who had family CNAs were less likely to receive additional nursing-level care (42% vs 60%, P < .01). Family and nonfamily CNA caregivers had similar characteristics, except that family CNA caregivers had substantially better 3-year retention (82% vs 9%, P < .01) despite lower average hourly pay ($14.60 vs $17.60 per hour, P < .01). Hospitalizations were rare (<10% of patients). In the adjusted model, patients who received family CNA care experienced 1 more hospitalized day per year, compared with patients who received nonfamily CNA care (P < .001). CONCLUSIONS: Paid family caregivers provided CAN-level care to children with medical complexity with a greater employee retention compared with nonfamily CNA caregivers, with marginally different hospitalization rates using a family-centered approach. This model may help address workforce shortages while also providing income to family caregivers.
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Cuidadores , Medicaid , Estados Unidos , Humanos , Niño , Colorado , Estudios Retrospectivos , Necesidades y Demandas de Servicios de SaludRESUMEN
Traumatic brain injury (TBI) can lead to neurodegenerative diseases such as Alzheimer's disease (AD) through mechanisms that remain incompletely characterized. Similar to AD, TBI models present with cellular metabolic alterations and modulated cleavage of amyloid precursor protein (APP). Specifically, AD and TBI tissues display increases in amyloid-ß as well as its precursor, the APP C-terminal fragment of 99 a.a. (C99). Our recent data in cell models of AD indicate that C99, due to its affinity for cholesterol, induces the formation of transient lipid raft domains in the ER known as mitochondria-associated endoplasmic reticulum (ER) membranes ("MAM" domains). The formation of these domains recruits and activates specific lipid metabolic enzymes that regulate cellular cholesterol trafficking and sphingolipid turnover. Increased C99 levels in AD cell models promote MAM formation and significantly modulate cellular lipid homeostasis. Here, these phenotypes were recapitulated in the controlled cortical impact (CCI) model of TBI in adult mice. Specifically, the injured cortex and hippocampus displayed significant increases in C99 and MAM activity, as measured by phospholipid synthesis, sphingomyelinase activity and cholesterol turnover. In addition, our cell type-specific lipidomics analyses revealed significant changes in microglial lipid composition that are consistent with the observed alterations in MAM-resident enzymes. Altogether, we propose that alterations in the regulation of MAM and relevant lipid metabolic pathways could contribute to the epidemiological connection between TBI and AD.
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Enfermedad de Alzheimer , Lesiones Traumáticas del Encéfalo , Ratones , Animales , Enfermedad de Alzheimer/metabolismo , Mitocondrias/metabolismo , Regulación hacia Arriba , Retículo Endoplásmico/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , LípidosRESUMEN
AIM: Procedures, such as immunisation and venepuncture, can be distressing for paediatric patients, especially those with needle phobia and neurodevelopmental disorders. Procedural sedation helps provide access to equitable health care in this population. The aim of this study was to evaluate the pilot outpatient procedural sedation clinics at the Women's and Children's Hospital and the impact on patient care and outcomes. METHODS: A prospective review was undertaken between July 2021 and May 2022 on all patients who attended the procedural sedation clinics at the Women's and Children's Hospital. These clinics were the COVID Specialist Immunisation Sedation Clinic (SISC) and Paediatric Sedation Clinic (PSC). RESULTS: There were 182 visits in a total of 110 children with a 92% primary procedure success rate. Sixty-three per cent of patients had neurodevelopmental disorders with autism spectrum disorder being most common. There was a significant reduction in anxiety scores pre- and post-sedation and a reduction in anxiety scores if patients were to return without the use of sedation. CONCLUSIONS: Outpatient procedural sedation is beneficial for a specific cohort of the paediatric population. This can also have a significant positive impact on patient care and potentially, long-term outcomes.
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Trastorno del Espectro Autista , COVID-19 , Niño , Humanos , Femenino , Australia del Sur , Estudios Prospectivos , Hospitales Pediátricos , Pacientes Ambulatorios , Sedación Consciente/métodosRESUMEN
OBJECTIVES: To evaluate the effect of hepatic metastatic lesion size on inter-reader reproducibility of CT-based 2D radiomics imaging features. METHODS: Computerized tomography (CT) scans of 59 liver metastases from 34 patients with colorectal cancer were evaluated. Image segmentation was performed manually by three readers blinded to each other's results. For each radiomics feature, we created two datasets by sorting measurements according to size, i.e., (i) from the smallest to the largest lesion and (ii) from the largest to the smallest lesion. The Lin concordance correlation coefficient (CCC) was employed to analyze the reproducibility of radiomics features. In particular, the CCC was computed as a function of a number of elements in the dataset, by gradually adding lesions from each sorted dataset. To evaluate the effect of lesion size, we analyzed the difference between these two functions thus assessing the contribution of small and large lesions into the reproducibility of radiomics features. RESULTS: Inter-reader reproducibility of CT-based 2D radiomics features assessed using Lin's CCC demonstrates tumor-size dependence. For example, the Lin CCC for GLCM contrast equals 0.88 (95% C.I. 0.84 to 0.92, p < 0.003) and could change by an additional + / - 0.06 depending on the presence of large or small lesions. CONCLUSIONS: Groups of "large" and "small" lesions show different inter-reader reproducibility. The inter-reader reproducibility from the mixed group consisting of "large" and "small" lesions depends on the lesion-size distribution and can vary widely. This finding could partially explain variability in reproducibility of radiomics features in the literature. KEY POINTS: ⢠Groups of "large" and "small" lesions show different inter-reader reproducibility. ⢠The inter-reader reproducibility from the mixed group consisting of "large" and "small" lesions depends on the lesion-size distribution.
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Neoplasias de la Mama , Neoplasias Hepáticas , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos X/métodosRESUMEN
The radiation dose sheet generated by the CT scanner is a form that displays important information about an examination. It functions as a road map for the examination, detailing what CT examinations were performed and what parameters were used to perform them. One essential element of the radiation dose sheet, the volume CT dose index (CTDIvol), is a commonly used radiation dose index that is displayed on most CT scanners. The CTDIvol is used for quality control and is helpful for comparing the radiation output among different protocols and different scanners. The dose-length product (DLP) is a radiation dose index that builds on the CTDIvol by incorporation of the scan length. The DLP is combined with a conversion coefficient and used to determine the effective dose from the CT examination. Determining the effective dose is a way to estimate the whole-body radiation dose, even if the CT examination is confined to a smaller part of the body. In addition to these values, other data about the study from the CT scanner manufacturer, including the tube voltage and tube current-time product, usually are displayed on CT scanners. These values are major determinants of the image quality and radiation dose. The radiation dose sheet is a useful tool for radiologists, technologists, and physicists, allowing them to comprehend the technical details of a CT examination. The authors describe the components of the radiation dose sheet, the relationships of these components with one another, and the contributions of these components to the radiation dose. ©RSNA, 2022.
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Tomografía Computarizada por Rayos X , Humanos , Dosis de Radiación , Tomografía Computarizada por Rayos X/métodosRESUMEN
AIM: To identify the highest-priority clinical research areas related to children with neurological impairment and medical complexity among clinicians and caregivers. METHOD: A modified, three-stage Delphi study using online surveys and guided by a steering committee was completed. In round 1, clinicians and family caregivers suggested clinical topics and related questions that require research to support this subgroup of children. After refinement of the suggestions by the steering committee, participants contributed to 1 (family caregivers) or 2 (clinicians) subsequent rounds to develop a prioritized list. RESULTS: A diverse international expert panel consisting of 49 clinicians and 12 family caregivers provided 601 responses. Responses were distilled into 26 clinical topics comprising 126 related questions. The top clinical topics prioritized for research were irritability and pain, child mental health, disorders of tone, polypharmacy, sleep, aspiration, behavior, dysautonomia, and feeding intolerance. The clinician expert panel also prioritized 10 specific research questions. INTERPRETATION: Study findings support a research agenda for children with neurological impairment and medical complexity focused on addressing clinical questions, prioritized by an international group of clinicians and caregivers.
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Investigación Biomédica , Consenso , Países Desarrollados , Enfermedades del Sistema Nervioso , Cuidadores , Niño , Comorbilidad , Técnica Delphi , Familia , Humanos , Enfermeras Practicantes , Médicos , Participación de los InteresadosRESUMEN
In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by ß-secretase to generate a 99-aa C-terminal fragment (C99) that is then cleaved by γ-secretase to generate the ß-amyloid (Aß) found in senile plaques. In previous reports, we and others have shown that γ-secretase activity is enriched in mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) and that ER-mitochondrial connectivity and MAM function are upregulated in AD We now show that C99, in addition to its localization in endosomes, can also be found in MAM, where it is normally processed rapidly by γ-secretase. In cell models of AD, however, the concentration of unprocessed C99 increases in MAM regions, resulting in elevated sphingolipid turnover and an altered lipid composition of both MAM and mitochondrial membranes. In turn, this change in mitochondrial membrane composition interferes with the proper assembly and activity of mitochondrial respiratory supercomplexes, thereby likely contributing to the bioenergetic defects characteristic of AD.
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Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Retículo Endoplásmico/metabolismo , Membranas Intracelulares/metabolismo , Mitocondrias/metabolismo , Enfermedad de Alzheimer/patología , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Línea Celular , Respiración de la Célula , Retículo Endoplásmico/ultraestructura , Humanos , Membranas Intracelulares/ultraestructura , Ratones , Mitocondrias/ultraestructura , Mutación/genética , Consumo de Oxígeno , Presenilinas/genética , Transporte de Proteínas , Esfingolípidos/metabolismo , Regulación hacia ArribaRESUMEN
Background There are characteristic findings of coronavirus disease 2019 (COVID-19) on chest images. An artificial intelligence (AI) algorithm to detect COVID-19 on chest radiographs might be useful for triage or infection control within a hospital setting, but prior reports have been limited by small data sets, poor data quality, or both. Purpose To present DeepCOVID-XR, a deep learning AI algorithm to detect COVID-19 on chest radiographs, that was trained and tested on a large clinical data set. Materials and Methods DeepCOVID-XR is an ensemble of convolutional neural networks developed to detect COVID-19 on frontal chest radiographs, with reverse-transcription polymerase chain reaction test results as the reference standard. The algorithm was trained and validated on 14 788 images (4253 positive for COVID-19) from sites across the Northwestern Memorial Health Care System from February 2020 to April 2020 and was then tested on 2214 images (1192 positive for COVID-19) from a single hold-out institution. Performance of the algorithm was compared with interpretations from five experienced thoracic radiologists on 300 random test images using the McNemar test for sensitivity and specificity and the DeLong test for the area under the receiver operating characteristic curve (AUC). Results A total of 5853 patients (mean age, 58 years ± 19 [standard deviation]; 3101 women) were evaluated across data sets. For the entire test set, accuracy of DeepCOVID-XR was 83%, with an AUC of 0.90. For 300 random test images (134 positive for COVID-19), accuracy of DeepCOVID-XR was 82%, compared with that of individual radiologists (range, 76%-81%) and the consensus of all five radiologists (81%). DeepCOVID-XR had a significantly higher sensitivity (71%) than one radiologist (60%, P < .001) and significantly higher specificity (92%) than two radiologists (75%, P < .001; 84%, P = .009). AUC of DeepCOVID-XR was 0.88 compared with the consensus AUC of 0.85 (P = .13 for comparison). With consensus interpretation as the reference standard, the AUC of DeepCOVID-XR was 0.95 (95% CI: 0.92, 0.98). Conclusion DeepCOVID-XR, an artificial intelligence algorithm, detected coronavirus disease 2019 on chest radiographs with a performance similar to that of experienced thoracic radiologists in consensus. © RSNA, 2020 Supplemental material is available for this article. See also the editorial by van Ginneken in this issue.
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Inteligencia Artificial , COVID-19/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Radiografía Torácica/métodos , Algoritmos , Conjuntos de Datos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Sensibilidad y Especificidad , Estados UnidosRESUMEN
AIM: Kawasaki disease (KD) is one of the most common causes of acquired cardiac disease in children in high-income countries. The incidence of coronary artery disease (CAD), despite treatment with intravenous immunoglobulin, ranges from 5 to 20%. Determining risk factors for CAD may assist with management and reduce long-term complications. METHODS: Retrospective data were collected for all patients presenting to the Women's and Children's Hospital with a discharge diagnosis of KD over a 10.5-year period, from 2007 to 2018. RESULTS: A total of 141 patients were included in the review; 101 patients fulfilled complete criteria for KD; 25 incomplete criteria and 15 did not meet criteria but were treated for KD. CAD was present in 27.7% of all patients, ranging from ectasia to giant aneurysms based on Z-scores and echocardiogram descriptions. Medium to large aneurysms accounted for 8.5% of all patients with suspected KD. Patients with CAD were more likely to: fulfil incomplete criteria (odds ratio (OR) 4.3, 95% confidence interval (CI) 1.7-10.8, P = 0.0027), be less than 12 months of age (OR 11.38, 95% CI 2.94-44.11, P = 0.0001), have CRP > 100 (OR 2.8, 95% CI 1.31-6.02, P = 0.0068) and have a delay in treatment (average day of illness prior to treatment 8.89 vs. 6.78 (OR 1.19, 95% CI 1.05-1.35, P = 0.0055)). Patients with a Kobayashi score ≥4 had a higher rate of re-treatment with intravenous immunoglobulin (OR 3.16, 95% CI 1.27-7.83, P = 0.013). CONCLUSION: Our data are consistent with previously reported risk factors, and high rates of CAD despite standard treatment.
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Síndrome Mucocutáneo Linfonodular , Niño , Femenino , Hospitales Pediátricos , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Lactante , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/epidemiología , Estudios Retrospectivos , Australia del SurRESUMEN
OBJECTIVE: We assessed the association between (1) severity of vessel wall calcification, (2) number of patent vessels at the ankle and (3) arterial spectral waveform features, as assessed on a focused ankle Duplex ultrasound (DUS), and healing at 12-months in a cohort of patients who had their diabetic foot ulcers conservatively managed. RESEARCH DESIGN AND METHODS: Scans performed on 50 limbs in 48 patients were included for analysis. Patient health records were prospectively reviewed for 12-months to assess for the outcome of ulcer healing. RESULTS: We identified that the number of waveform components, peak systolic velocity, systolic rise time and long forward flow as well as the number of vessels patent at the ankle on DUS, may be useful independent predictors of healing, as noted by the trend towards statistical significance. CONCLUSION: Arterial spectral waveform features may be useful in predicting the chance of diabetic foot ulcer healing.
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Diabetes Mellitus , Pie Diabético , Arterias , Estudios de Cohortes , Humanos , Ultrasonografía Doppler Dúplex , Cicatrización de HeridasRESUMEN
The discovery of contact sites was a breakthrough in cell biology. We have learned that an organelle cannot function in isolation, and that many cellular functions depend on communication between two or more organelles. One such contact site results from the close apposition of the endoplasmic reticulum (ER) and mitochondria, known as mitochondria-associated ER membranes (MAMs). These intracellular lipid rafts serve as hubs for the regulation of cellular lipid and calcium homeostasis, and a growing body of evidence indicates that MAM domains modulate cellular function in both health and disease. Indeed, MAM dysfunction has been described as a key event in Alzheimer disease (AD) pathogenesis. Our most recent work shows that, by means of its affinity for cholesterol, APP-C99 accumulates in MAM domains of the ER and induces the uptake of extracellular cholesterol as well as its trafficking from the plasma membrane to the ER. As a result, MAM functionality becomes chronically upregulated while undergoing continual turnover. The goal of this review is to discuss the consequences of C99 elevation in AD, specifically the upregulation of cholesterol trafficking and MAM activity, which abrogate cellular lipid homeostasis and disrupt the lipid composition of cellular membranes. Overall, we present a novel framework for AD pathogenesis that can be linked to the many complex alterations that occur during disease progression, and that may open a door to new therapeutic strategies.
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Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Colesterol/metabolismo , Retículo Endoplásmico/metabolismo , Mitocondrias/metabolismo , Fragmentos de Péptidos/metabolismo , Enfermedad de Alzheimer/patología , Animales , Transporte Biológico/fisiología , Retículo Endoplásmico/patología , Humanos , Mitocondrias/patologíaRESUMEN
Pulmonary mucormycosis (PM) is an uncommon fungal infection most often seen in immunocompromised patients. The fungus grows on decaying food, soil, and animal excrement. Patients usually become infected by inhalation of spores. The most common risk factors include diabetes mellitus, hematologic malignancy, and solid organ or stem cell transplant. PM can have a nonspecific appearance at imaging. For example, early imaging may show peribronchial ground-glass opacity. Later, the disease progresses to consolidation, nodules, or masses. Because patients are usually immunocompromised, the differential diagnosis often includes invasive pulmonary aspergillosis (IPA). Various radiologic findings suggestive of PM have been identified to help differentiate it from IPA. For example, the reverse halo sign is more closely associated with PM than with IPA. The reverse halo sign is an area of ground-glass opacity surrounded by a rim of consolidation. In addition, the presence of pleural effusions and more than 10 nodules is more suggestive of PM than it is of IPA. PM can progress rapidly in neutropenic patients. Identification of the hyphae in tissue by using endobronchial or percutaneous sampling can allow differentiation from IPA and help confirm the diagnosis of mucormycosis. Because of the high mortality rate associated with PM, early identification of the disease is critical for an improved likelihood of survival. A multimodality treatment approach with antifungal agents and surgical débridement has been shown to improve outcomes. The authors review the risk factors for PM, describe its imaging appearance and disease process, and describe the treatment of the disease. ©RSNA, 2020.
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Enfermedades Pulmonares Fúngicas/diagnóstico por imagen , Mucormicosis/diagnóstico por imagen , Terapia Combinada , Diagnóstico Diferencial , Humanos , Huésped Inmunocomprometido , Enfermedades Pulmonares Fúngicas/inmunología , Enfermedades Pulmonares Fúngicas/patología , Enfermedades Pulmonares Fúngicas/terapia , Mucormicosis/inmunología , Mucormicosis/patología , Mucormicosis/terapia , Factores de RiesgoRESUMEN
OBJECTIVE: To compare health care use and spending in children using vs not using respiratory medical equipment and supplies (RMES). STUDY DESIGN: Cohort study of 20 352 children age 1-18 years continuously enrolled in Medicaid in 2013 from 12 states in the Truven Medicaid MarketScan Database; 7060 children using RMES were propensity score matched with 13 292 without RMES. Home RMES use was identified with Healthcare Common Procedure Coding System and International Classification of Diseases codes. RMES use was regressed on annual per-member-per-year Medicaid payments, adjusting for demographic and clinical characteristics, including underlying respiratory and other complex chronic conditions. RESULTS: Of children requiring RMES, 47% used oxygen, 28% suction, 22% noninvasive positive-pressure ventilation, 17% tracheostomy, 8% ventilator, 5% mechanical in-exsufflator, and 4% high-frequency chest wall oscillator. Most children (93%) using RMES had a chronic condition; 26% had ≥6. The median per-member-per-year payments in matched children with vs without RMES were $24 359 vs $13 949 (P < .001). In adjusted analyses, payment increased significantly (P < .001 for all) with mechanical in-exsufflator (+$2657), tracheostomy (+$6447), suction (+$7341), chest wall oscillator (+$8925), and ventilator (+$20 530). Those increased payments were greater than the increase associated with a coded respiratory chronic condition (+$2709). Hospital and home health care were responsible for the greatest differences in payment (+$3799 and +$3320, respectively) between children with and without RMES. CONCLUSION: The use of RMES is associated with high health care spending, especially with hospital and home health care. Population health initiatives in children may benefit from consideration of RMES in comprehensive risk assessment for health care spending.
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Servicios de Salud del Niño/provisión & distribución , Enfermedad Crónica/terapia , Recursos en Salud/provisión & distribución , Ventilación no Invasiva/instrumentación , Aceptación de la Atención de Salud/estadística & datos numéricos , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Terapia Respiratoria/instrumentación , Estudios Retrospectivos , Estados UnidosRESUMEN
OBJECTIVE: Tissue macrophages induce and perpetuate proinflammatory responses, thereby promoting metabolic and cardiovascular disease. Lipoprotein lipase (LpL), the rate-limiting enzyme in blood triglyceride catabolism, is expressed by macrophages in atherosclerotic plaques. We questioned whether LpL, which is also expressed in the bone marrow (BM), affects circulating white blood cells and BM proliferation and modulates macrophage retention within the artery. APPROACH AND RESULTS: We characterized blood and tissue leukocytes and inflammatory molecules in transgenic LpL knockout mice rescued from lethal hypertriglyceridemia within 18 hours of life by muscle-specific LpL expression (MCKL0 mice). LpL-deficient mice had ≈40% reduction in blood white blood cell, neutrophils, and total and inflammatory monocytes (Ly6C/Ghi). LpL deficiency also significantly decreased expression of BM macrophage-associated markers (F4/80 and TNF-α [tumor necrosis factor α]), master transcription factors (PU.1 and C/EBPα), and colony-stimulating factors (CSFs) and their receptors, which are required for monocyte and monocyte precursor proliferation and differentiation. As a result, differentiation of macrophages from BM-derived monocyte progenitors and monocytes was decreased in MCKL0 mice. Furthermore, although LpL deficiency was associated with reduced BM uptake and accumulation of triglyceride-rich particles and macrophage CSF-macrophage CSF receptor binding, triglyceride lipolysis products (eg, linoleic acid) stimulated expression of macrophage CSF and macrophage CSF receptor in BM-derived macrophage precursor cells. Arterial macrophage numbers decreased after heparin-mediated LpL cell dissociation and by genetic knockout of arterial LpL. Reconstitution of LpL-expressing BM replenished aortic macrophage density. CONCLUSIONS: LpL regulates peripheral leukocyte levels and affects BM monocyte progenitor differentiation and aortic macrophage accumulation.
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Aorta/enzimología , Enfermedades de la Aorta/enzimología , Aterosclerosis/enzimología , Hiperlipoproteinemia Tipo I/enzimología , Lipoproteína Lipasa/deficiencia , Macrófagos/enzimología , Monocitos/enzimología , Células Progenitoras Mieloides/enzimología , Mielopoyesis , Animales , Aorta/patología , Enfermedades de la Aorta/sangre , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/patología , Aterosclerosis/sangre , Aterosclerosis/genética , Aterosclerosis/patología , Proliferación Celular , Citocinas/metabolismo , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Hiperlipoproteinemia Tipo I/sangre , Hiperlipoproteinemia Tipo I/genética , Hiperlipoproteinemia Tipo I/patología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Lipoproteína Lipasa/genética , Macrófagos/patología , Ratones Noqueados , Monocitos/patología , Células Progenitoras Mieloides/patología , Transducción de Señal , Triglicéridos/metabolismoRESUMEN
PURPOSE: To assess the feasibility of implementing fully automated computer-aided diagnosis (CAD) for detection of pulmonary nodules on CT pulmonary angiography (CTPA) studies in emergency setting. MATERIALS AND METHODS: CTPA of 48 emergency patients was retrospectively reviewed. Fully automated CAD nodule detection was performed at the scanner and results were automatically submitted to PACS. A third-year radiology resident (RAD1) and a cardiothoracic radiologist with 6 years' experience (RAD2) reviewed the scans independently to detect pulmonary nodules in two different sessions 8 weeks apart: session 1, CAD was reviewed first and then all images were reviewed; session 2, CAD was reviewed last after all images were reviewed. Time spent by RAD to evaluate image sets was measured for each case. Fisher's exact test and t test were used. RESULTS: There were 17 male and 31 female patients with mean ± SD age of 48.7 ± 16.4 years. Using CAD at the beginning was associated with lower average reading time for both readers. However, difference in reading time did not reach statistical significance for RAD1 (RAD1 94.6 s vs. 102.7 s, P > 0.05; RAD2 61.1 s vs. 76.5 s, P < 0.05). Using CAD at the end significantly increased rate of RAD1 and RAD2 nodule detection by 34% (2.52 vs. 2.12 nodule/scan, P < 0.05) and 27% (2.23 vs. 1.81 nodule/scan, P < 0.05), respectively. CONCLUSION: Routine utilization of CAD in emergency setting is feasible and can improve detection rate of pulmonary nodules significantly. Different methods of incorporating CAD in detecting pulmonary nodules can improve both the rate of detection and interpretation speed.
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Angiografía por Tomografía Computarizada , Servicio de Urgencia en Hospital , Neoplasias Pulmonares/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Nódulo Pulmonar Solitario/diagnóstico por imagen , Flujo de Trabajo , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Objectives One goal of Healthy People 2020 is to reduce the number of children and young adults living in nursing homes. However, little is known about the prevalence of nursing home use among children and young adults on a state-by-state basis. The objective of this study was to determine the prevalence of nursing home use among children and young adults in each state from 2005 to 2012. The study also looked for prevalence trends between 2005 and 2012. Methods The Centers for Medicare and Medicaid Services Minimum Data Set and US Census data were used to calculate the prevalence of nursing home residents among children and young adults aged 0-30 in each US state in 2012 and assess trends in each state from 2005 to 2012. Results In 2012, the prevalence of nursing home residents among children and young adults aged 0-30 varied across states, ranging from 14 in 100,000 (New Jersey) to 0.8 in 100,000 (Alaska). Testing for trends from 2005 to 2012 also revealed significant trends (p < 0.05), with Florida trending upward with borderline statistical significance (p = 0.05) and six states trending downward. Conclusion There is wide variation in the prevalence of nursing home residents among children and young adults aged 0-30 across states. There is also variation in the nursing home prevalence trends across states. Observed variations may represent potential opportunities for some states to reduce their population of children and young adults in nursing homes.
Asunto(s)
Política de Salud , Casas de Salud/estadística & datos numéricos , Características de la Residencia , Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Masculino , Prevalencia , Estudios Retrospectivos , Estados Unidos , Adulto JovenRESUMEN
The hypothesis of this study was that those refugee children with Helicobacter pylori are thinner than their non-infected counterparts. This cross-sectional study investigated the height and weight of newly arrived refugee children up to age 19 years, who were screened for H. pylori using a stool antigen test at the Migrant Health Service in Adelaide between August 2010 and October 2013. Of 460 children, 21% were infected with H. pylori. After adjusting for vitamin B12 and iron levels, ethnicity, age and sex, the odds of being thin in the 10- to 19-year-old age group was 4.28-fold higher (95% CI 1.48-12.4) if they were H. pylori positive compared with those who were H. pylori negative. The difference between the two groups is statistically significant (P=0.01). Screening and treatment for H. pylori in the general population in developed countries is not recommended unless there are symptoms such as dyspepsia or risk of peptic ulcer, duodenal ulcer or gastric cancer. Given the findings of this study, a recommendation could be made that newly arrived refugee children who are thin should be tested for H. pylori. Thinness in children may influence their cognitive ability, school performance, physical endurance and hence their ability to successfully settle into their new country.