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1.
Artigo em Inglês | MEDLINE | ID: mdl-32403928

RESUMO

The development of highly sensitive and selective devices for rapid screening of polycyclic aromatic hydrocarbons (PAHs) in water is nowadays a crucial challenge owing to their alarming abundance in the environment and adverse health effects. Herein, inspired by the unique π-stacking interactions taking place between identical small aromatic molecules, a novel, generic, and straightforward methodology to electrochemically determine and discriminate such pollutants is described. Such a method is focused on covalently anchoring different PAHs on an indium tin oxide electrode surface by means of self-assembled monolayers. The surface-anchored PAHs act as recognition units to selectivity interact with a specific PAH target of the same nature. By tailoring the recognition platform with four different model PAH molecules (naphthalene, anthracene, pyrene, and fluoranthene) and carrying out an electronic tongue approximation, the selective discrimination and quantification of the selected PAHs in aqueous samples at ultralow concentrations were achieved impedimetrically, which were also validated using a certified reference PAH mixture.

2.
N Engl J Med ; 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32459919

RESUMO

BACKGROUND: Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). METHODS: We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. RESULTS: In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). CONCLUSIONS: In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).

3.
BMJ Glob Health ; 5(5)2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32461226

RESUMO

BACKGROUND: The best strategy for controlling morbidity due to imported strongyloidiasis in migrants is unclear. We evaluate the cost-effectiveness of six possible interventions. METHODS: We developed a stochastic Markov chain model. The target population was adult migrants from endemic countries to the European Union; the time horizon, a lifetime and the perspective, that of the health system. Average and incremental cost-effectiveness ratios (ACER and ICER) were calculated as 2016 EUR/life-year gained (LYG). Health interventions compared were: base case (no programme), primary care-based presumptive treatment (PCPresTr), primary care-based serological screening and treatment (PCSerTr), hospital-based presumptive treatment (HospPresTr), hospital-based serological screening and treatment (HospSerTr), hospital-based presumptive treatment of immunosuppressed (HospPresTrim) and hospital-based serological screening and treatment of the immunosuppressed (HospSerTrim). The willingness to pay threshold (WTP) was €32 126.95/LYG. RESULTS: The base case model yielded a loss of 2 486 708.24 life-years and cost EUR 3 238 393. Other interventions showed the following: PCPresTr: 2 488 095.47 life-years (Δ1 387.23LYG), cost: EUR 8 194 563; ACER: EUR 3573/LYG; PCSerTr: 2 488 085.8 life-years (Δ1377.57LYG), cost: EUR 207 679 077, ACER: EUR 148 407/LYG; HospPresTr: 2 488 046.17 life-years (Δ1337.92LYG), cost: EUR 14 559 575; ACER: EUR 8462/LYG; HospSerTr: 2 488 024.33 life-years (Δ1316.08LYG); cost: EUR 207 734 073; ACER: EUR 155 382/LYG; HospPresTrim: 2 488 093.93 life-years, cost: EUR 1 105 483; ACER: EUR -1539/LYG (cost savings); HospSerTrim: 2 488 073.8 life-years (Δ1365.55LYG), cost: EUR 4 274 239; ACER: EUR 759/LYG. One-way and probabilistic sensitivity analyses were undertaken; HospPresTrim remained below WTP for all parameters' ranges and iterations. CONCLUSION: Presumptively treating all immunosuppressed migrants from areas with endemic Strongyloides would generate cost savings to the health system.

4.
Microb Biotechnol ; 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32385941

RESUMO

In this paper, we reveal and characterize cross-feeding behaviour between the common gut commensal Bacteroides cellulosilyticus (Baccell) and certain bifidobacterial strains, including Bifidobacterium breve UCC2003, when grown on a medium containing Larch Wood Arabinogalactan (LW-AG). We furthermore show that cross-feeding is dependent on the release of ß-1,3-galacto-di/trisaccharides (ß-1,3-GOS), and identified that the bga gene cluster of B. breve UCC2003 allows ß-1,3-GOS metabolism. The product of bgaB is presumed to be responsible for the import of ß-1,3-GOS, while the bgaA gene product, a glycoside hydrolase family 2 member, was shown to hydrolyse both ß-1,3-galactobiose and ß-1,3-galactotriose into galactose monomers. This study advances our understanding of strain-specific syntrophic interactions between two glycan degraders in the human gut in the presence of AG-type dietary polysaccharides.

5.
mBio ; 11(3)2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398311

RESUMO

Candida auris has emerged as a multidrug-resistant pathogen of great clinical concern. Approximately 90% of clinical C. auris isolates are resistant to fluconazole, the most commonly prescribed antifungal agent, and yet it remains unknown what mechanisms underpin this fluconazole resistance. To identify novel mechanisms contributing to fluconazole resistance in C. auris, fluconazole-susceptible C. auris clinical isolate AR0387 was passaged in media supplemented with fluconazole to generate derivative strains which had acquired increased fluconazole resistance in vitro Comparative analyses of comprehensive sterol profiles, [3H]fluconazole uptake, sequencing of C. auris genes homologous to genes known to contribute to fluconazole resistance in other species of Candida, and relative expression levels of C. auris ERG11, CDR1, and MDR1 were performed. All fluconazole-evolved derivative strains were found to have acquired mutations in the zinc-cluster transcription factor-encoding gene TAC1B and to show a corresponding increase in CDR1 expression relative to the parental clinical isolate, AR0387. Mutations in TAC1B were also identified in a set of 304 globally distributed C. auris clinical isolates representing each of the four major clades. Introduction of the most common mutation found among fluconazole-resistant clinical isolates of C. auris into fluconazole-susceptible isolate AR0387 was confirmed to increase fluconazole resistance by 8-fold, and the correction of the same mutation in a fluconazole-resistant isolate, AR0390, decreased fluconazole MIC by 16-fold. Taken together, these data demonstrate that C. auris can rapidly acquire resistance to fluconazole in vitro and that mutations in TAC1B significantly contribute to clinical fluconazole resistance.IMPORTANCE Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and to be commonly resistant to antifungals. While the vast majority of clinical C. auris isolates are highly resistant to fluconazole, an essential part of the available antifungal arsenal, very little is known about the mechanisms contributing to resistance. In this work, we show that mutations in the transcription factor TAC1B significantly contribute to clinical fluconazole resistance. These studies demonstrated that mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole and that a multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant C. auris isolates from a global collection and appear specific to a subset of lineages or clades. Thus, identification of this novel genetic determinant of resistance significantly adds to the understanding of clinical antifungal resistance in C. auris.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32435829

RESUMO

COVID-19 (SARS-CoV-2 virus) pandemic was recently declared by the WHO as a global health emergency. A group of interventional radiology senior experts developed a consensus document for infection control and management of patients with COVID-19 in interventional radiology (IR) departments. This consensus statement has been brought together at short notice with the help of different protocols developed by governmental entities and scientific societies to be adapted to the current reality and needs of IR Departments. Recommendations are the specific strategies to follow in IR departments, preventive measures and regulations, step by step for donning and doffing personal protective equipment, specific IR procedures which can not be delayed, and aerosol-generating procedures in IR with COVID-19 patients. It is advisable with this document to be adapted to local workplace policies.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32366880

RESUMO

In Ghana, more than 77% of the population depends on biomass fuels for cooking. Previous studies show that solid fuel use (SFU) has adverse effects on pregnancy and child health outcomes. Yet, no previous study considered potential effects on early child development indicators (ECDI), nor how SFU effects may vary by gender, and rural and urban areas. We investigated the associations of SFU with ECDI measures, and whether these associations exhibited sex and urban/rural differences. We used the 2011-2012 Ghana's Multiple Indicator Cluster Surveys-UNICEF (N = 3326 children; 3-4 years). We derived a binary ECDI measure reflecting whether the child is developmentally on track or not from a caregiver-report of ten yes/no/do not know questions designed specifically to assess four domains of early child development: learning-cognition, literacy-numeracy, socio-emotional, and physical. We used multilevel Poisson regressions adjusting for neighborhood, household, mother, and child's characteristics to estimate covariate-adjusted prevalence ratios (PRs) of the associations between SFU and ECDI and its four dimensions. We run stratified analyses and used z-score tests of differences to evaluate effect modification by sex and urbanicity. Overall, 85% of children were exposed to SFU and 28% of children were not developmentally on track. After adjustment for confounders, children exposed to SFU were more likely to be not developmentally on track in comparison with nonexposed children (PR = 1.16; 95% confidence interval, [95% CI]: 1.10,1.22). These associations were stronger in girls (PR = 1.36; 95% CI: 1.03,1.79) in comparison with boys (PR = 0.87; 95% CI: 0.73,1.04). No difference in associations was observed between urban and rural children. Overall, these associations were mainly driven by the literacy-numeracy dimension. In this study, we show that SFU was associated with developmental delays in Ghanaian girls. Policy efforts which tackle SFU should be mindful of gender disparities in susceptibility to indoor pollution.

10.
Am J Ophthalmol ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32278771

RESUMO

PURPOSE: To assess efficacy of intravitreal ranibizumab injections and targeted pan-retinal photocoagulation (TRP) for radiation retinopathy-related macular edema. DESIGN: Phase IIb, prospective, randomized clinical trial. SETTING: multi-center PATIENTS: 40 eyes in 40 treatment-naïve patients with radiation-induced macular edema and a resulting decrease in visual acuity ranging between 20/25 and 20/400 (Snellen-equivalent). INTERVENTION: Patients either received intravitreal 0.5mg ranibizumab monthly, monthly ranibizumab with TRP, or 3 monthly ranibizumab (loading doses) followed by as-needed (PRN) injections and TRP. After Week 52, all subjects entered a treat-and-extend protocol for ranibizumab. MAIN OUTCOME MEASURES: Mean ETDRS BCVA change from baseline. RESULTS: Mean patient age was 57 years (range, 22-80), ETDRS BCVA was 56.7 letters (20/74 Snellen-equivalent), and central macular thickness (CMT) was 423 um (range, 183-826). Thirty-seven patients completed the Month-12 visit (92.5%), at which time the change in mean BCVA was +4.0 letters, -1.9 letters and +0.9 letters in the monthly, monthly plus laser, and PRN plus laser cohorts, respectively. There was a significant difference in mean BCVA at 1 year among all three cohorts (p<0.001), as well as between cohorts in pairwise comparisons, with the most significant gains in the monthly group. 82.5% of the patients retained visual acuity of 20/200 or better, and 20.0% improved 10 or more ETDRS letters. CONCLUSIONS: Ranibizumab may improve vision and anatomy in patients with radiation retinopathy-related macular edema and prevent vision loss through 48 weeks of therapy. Monthly injections were more effective than as-needed approach, and the addition of TRP yielded no therapeutic benefits.

11.
Rev. esp. enferm. dig ; 112(4): 269-272, abr. 2020. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-187505

RESUMO

INTRODUCCIÓN: la lesión de Dieulafoy en intestino delgado es una causa infrecuente de hemorragia digestiva que recidiva frecuentemente tras su tratamiento endoscópico. MATERIAL Y MÉTODOS: se presenta un estudio observacional, descriptivo, retrospectivo y unicéntrico de 15 pacientes con hemorragia de intestino delgado, diagnosticados de lesión de Dieulafoy con cápsula endoscópica o enteroscopia doble balón, en los que se realizó tratamiento endoscópico combinado. Resultados y conclusiones: durante una mediana de seguimiento de 33,5 meses (rango 2-145), recidivaron tres de los 12 casos que se pudieron seguir (25 %) y todos ocurrieron precozmente en las primeras 48 horas tras la terapéutica. Se retrataron con éxito dos de ellos con una nueva enteroscopia


No disponible


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Intestino Delgado/irrigação sanguínea , Intestino Delgado/cirurgia , Hemorragia Gastrointestinal/cirurgia , Recidiva , Estudos Retrospectivos , Enteroscopia de Duplo Balão , Endoscopia por Cápsula , Seguimentos
12.
J Epidemiol Community Health ; 74(6): 502-509, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32238476

RESUMO

BACKGROUND: It is estimated that more than 270 000 people die yearly in alcohol-related crashes globally. To tackle this burden, government interventions, such as laws which restrict blood alcohol concentration (BAC) levels and increase penalties for drunk drivers, have been implemented. The introduction of private-sector measures, such as ridesharing, is regarded as alternatives to reduce drunk driving and related sequelae. However, it is unclear whether state and private efforts complement each other to reduce this public health challenge. METHODS: We conducted interrupted time-series analyses using weekly alcohol-related traffic fatalities and injuries per 1 000 000 population in three urban conglomerates (Santiago, Valparaíso and Concepción) in Chile for the period 2010-2017. We selected cities in which two state interventions-the 'zero tolerance law' (ZTL), which decreased BAC, and the 'Emilia law' (EL), which increased penalties for drunk drivers-were implemented to decrease alcohol-related crashes, and where Uber ridesharing was launched. RESULTS: In Santiago, the ZTL was associated with a 29.1% decrease (95% CI 1.2 to 70.2), the EL with a 41.0% decrease (95% CI 5.5 to 93.2) and Uber with a non-significant 28.0% decrease (95% CI -6.4 to 78.5) in the level of weekly alcohol-related traffic fatalities and injuries per 1 000 000 population series. In Concepción, the EL was associated with a 28.9% reduction (95% CI 4.3 to 62.7) in the level of the same outcome. In Valparaíso, the ZTL had a -0.01 decrease (95% CI -0.02 to -0.00) in the trend of weekly alcohol-related crashes per 1 000 000 population series. CONCLUSION: In Chile, concomitant decreases of alcohol-related crashes were observed after two state interventions were implemented but not with the introduction of Uber. Relationships between public policy interventions, ridesharing and motor vehicle alcohol-related crashes differ between cities and over time, which might reflect differences in specific local characteristics.

13.
J Sci Food Agric ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32323323

RESUMO

BACKGROUND: Nowadays, it is of great interest to develop stable and sustainable formulations that act as nanocarriers of active ingredients. In this work, the droplet size distribution, rheology and physical stability of nanoemulsions with improved properties containing rosemary essential oil and biopolymers as a function of the concentration of these polysaccharides were investigated. RESULTS: Mean diameters below 150 nm were achieved, indicating nanostructures were obtained. Regardless of gum type, a gel-like structure and a shear thinning behaviour was achieved. In addition, an increase of G', G″ and viscosity and a decrease of J0 , J1 , J2 , λ1 and λ2 with increasing gum concentration were observed, due to the formation of a three-dimensional network in the aqueous phase. Slight differences between nanoemulsions containing welan or xanthan were found. Creaming, depletion flocculation and gel aggregation were the main destabilization processes at low, intermediate and high gum concentration, respectively. A 0.4 wt% gum nanoemulsion exhibited the best physical stability. CONCLUSION: These stable and sustainable nanoemulsions with improved rheological properties contribute to the development of biodegradable and non-toxic food or agrochemical products. © 2020 Society of Chemical Industry.

16.
mBio ; 11(2)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345637

RESUMO

Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris IMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.

17.
Epidemiology ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32243276

RESUMO

BACKGROUND: In April 2016 Chile enacted the Law 20.900, which restricted electoral publicity on public roads. It established two important regulations: first, candidates were allowed, 30 days before any election, to publicize their campaigns in specific street locations. Second, roadside publicity must follow strict size standards to avoid visual contamination. This paper examines the impact of this regulation in reducing road traffic crashes. METHODS: We obtained number of traffic injuries and fatalities per population from public records. A time-series difference-in-difference study, using generalized linear models with an interaction between time-period and intervention, compared a municipal election period before the introduction of Law 20,900 (2012) to the first municipal election affected by the law (2016). We adjusted for precipitation and temperature, and applied models to three cities: Santiago, Gran-Valparaíso, and Concepción. We assessed the overall impact of the intervention using random effects meta-analyses. RESULTS: The law was associated with a decrease of 0.01 (95% Confidence Interval [CI]: -0.02; -0.00) in Santiago, a decrease of 0.01 (95% CI: -0.03; -0.00) in Valparaíso and an increase of 0.09 (95% CI: 0.06; 0.13) in Concepción, in all daily injuries and fatalities per 100,000 population. After 40 days of its implementation, the intervention was associated with a mild absolute reduction of 34 (95% Reduction Interval: -270; 67) traffic injuries and fatalities. CONCLUSIONS: This study estimates that regulation of public road publicity had an overall mild effect on reducing traffic injuries and fatalities in three large cities in Chile.

18.
Fungal Genet Biol ; 140: 103395, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32325168

RESUMO

Paracoccidioidomycosis (PCM) is a life-threatening systemic mycosis widely reported in the Gran Chaco ecosystem. The disease is caused by different species from the genus Paracoccidioides, which are all endemic to South and Central America. Here, we sequenced and analyzed 31 isolates of Paracoccidioides across South America, with particular focus on isolates from Argentina and Paraguay. The de novo sequenced isolates were compared with publicly available genomes. Phylogenetics and population genomics revealed that PCM in Argentina and Paraguay is caused by three distinct Paracoccidioides genotypes, P. brasiliensis (S1a and S1b) and P. restrepiensis (PS3). P. brasiliensis S1a isolates from Argentina are frequently associated with chronic forms of the disease. Our results suggest the existence of extensive molecular polymorphism among Paracoccidioides species, and provide a framework to begin to dissect the connection between genotypic differences in the pathogen and the clinical outcomes of the disease.

19.
Nanoscale ; 12(17): 9884-9889, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32347277

RESUMO

A carbohydrate-based nanohybrid of superparamagnetic nanoparticles embedded in unilamellar bilayer vesicles of amphiphilic ß-cyclodextrins (magnetic cyclodextrin vesicles, mCDVs) has been engineered as a novel magnetic biorecognition probe for electrosensing. As a proof-of-concept, the synergistic properties of these mCDVs on a magneto nanocomposite carbon-paste electrode (mNC-CPE) have been used for the picomolar determination of thyroxine (T4) as a model analyte (taking advantage of the host-guest chemistry of ß-cyclodextrin and T4), resulting in the most sensitive electrochemical T4 system reported in the literature. Accordingly, a first demonstration of mCDVs as alternative water-soluble magnetic nanobiocarriers has been devised foreseeing their successful use as alternative electrochemical biosensing platforms for the supramolecular trace determination of alternative targets.

20.
Hosp Pediatr ; 10(4): 318-324, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32179570

RESUMO

BACKGROUND AND OBJECTIVES: To determine the effect of discharge criteria on discharge readiness and length of stay (LOS). Discharge inefficiency is a common barrier to hospital flow, affecting admissions, discharges, cost, patient satisfaction, and quality of care. Our center identified increasing discharge efficiency as a method to improve flow and better meet the needs of our patients. METHODS: A multidisciplinary team was assembled to examine discharge efficiency and flow. Discharge criteria were created for the 3 most common diagnoses on the hospital medicine service then expanded to 10 diagnoses 4 months into the project. Discharge workflow was evaluated through swim lane mapping, and barriers were evaluated through fishbone diagrams and a key driver diagram. Progress was assessed every 2 weeks through statistical process control charts. Additional interventions included provider education, daily review of criteria, and autotext added to daily notes. Our primary aim was to increase the percentage of patients discharged within 3 hours of meeting discharge criteria from 44% to 75% within 12 months of project implementation. RESULTS: Discharge within 3 hours as well as 2 hours of meeting criteria improved significantly, from 44% to 87% and from 33% to 78%, respectively. LOS for the 10 diagnoses decreased from 2.89 to 1.47 days, with greatest gains seen for patients with asthma, pneumonia, and bronchiolitis without a change in the 30-day readmission rate. CONCLUSIONS: Discharge criteria for common diagnoses may be an effective way to decrease variability and improve LOS for hospitalized children.

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