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BACKGROUND: Pneumonia is the leading infectious cause of death in children under 5 years of age around the globe. In addition to preventing pneumonia, there is a critical need to provide greater access to appropriate and effective treatment. Studies in Asia have evaluated the effectiveness of 3 days of oral amoxicillin for the treatment of fast-breathing pneumonia; however, further evidence is needed to determine if 3 days of oral amoxicillin is also effective for the treatment of chest indrawing pneumonia. METHODS: This is a double-blind, randomized, non-inferiority trial with the objective to assess the effectiveness of shorter duration amoxicillin dispersible tablet (DT) treatment of chest indrawing childhood pneumonia in a malaria-endemic region of Malawi. The primary objective of this study is to determine whether 3 days of treatment with oral amoxicillin DT in HIV-uninfected Malawian children two to 59 months of age with chest indrawing pneumonia is as effective as 5 days of treatment. The study will enroll 2000 children presenting to Kamuzu Central or Bwaila District Hospitals in Lilongwe, Malawi. Each child will be randomized to either 3 days of amoxicillin DT followed by 2 days of placebo DT or 5 days of amoxicillin DT. Children in the study will be hospitalized for 48 h after enrollment and will have scheduled study visits at Days 2, 4, 6 and 14. Treatment failure by Day 6 is the primary outcome. We hypothesize that the rates of treatment failure will be similar in both arms and that 3 days of treatment will be non-inferior to 5 days of amoxicillin DT for chest indrawing pneumonia using a relative non-inferiority margin of 1.5. This trial was approved by the Western Institutional Review Board and Malawi College of Medicine Research and Ethics Committee. DISCUSSION: Given the paucity of data from Africa, African-based research is necessary to establish appropriate duration of treatment with amoxicillin DT for chest indrawing childhood pneumonia in malaria-endemic settings in the region. An expanded evidence base will contribute to future iterations of World Health Organization Integrated Management of Childhood Illness guidelines. TRIAL REGISTRATION: NCT02678195 : Pre-results. Date registered February 9, 2016.
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Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Neumonía/tratamiento farmacológico , Administración Oral , Preescolar , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Lactante , Malaui , Masculino , Efecto Placebo , Comprimidos/química , Resultado del TratamientoRESUMEN
Importance: Emergency medical services (EMS) commonly perform endotracheal intubation (ETI) or insertion of supraglottic airways, such as the laryngeal tube (LT), on patients with out-of-hospital cardiac arrest (OHCA). The optimal method for OHCA advanced airway management is unknown. Objective: To compare the effectiveness of a strategy of initial LT insertion vs initial ETI in adults with OHCA. Design, Setting, and Participants: Multicenter pragmatic cluster-crossover clinical trial involving EMS agencies from the Resuscitation Outcomes Consortium. The trial included 3004 adults with OHCA and anticipated need for advanced airway management who were enrolled from December 1, 2015, to November 4, 2017. The final date of follow-up was November 10, 2017. Interventions: Twenty-seven EMS agencies were randomized in 13 clusters to initial airway management strategy with LT (n = 1505 patients) or ETI (n = 1499 patients), with crossover to the alternate strategy at 3- to 5-month intervals. Main Outcomes and Measures: The primary outcome was 72-hour survival. Secondary outcomes included return of spontaneous circulation, survival to hospital discharge, favorable neurological status at hospital discharge (Modified Rankin Scale score ≤3), and key adverse events. Results: Among 3004 enrolled patients (median [interquartile range] age, 64 [53-76] years, 1829 [60.9%] men), 3000 were included in the primary analysis. Rates of initial airway success were 90.3% with LT and 51.6% with ETI. Seventy-two hour survival was 18.3% in the LT group vs 15.4% in the ETI group (adjusted difference, 2.9% [95% CI, 0.2%-5.6%]; P = .04). Secondary outcomes in the LT group vs ETI group were return of spontaneous circulation (27.9% vs 24.3%; adjusted difference, 3.6% [95% CI, 0.3%-6.8%]; P = .03); hospital survival (10.8% vs 8.1%; adjusted difference, 2.7% [95% CI, 0.6%-4.8%]; P = .01); and favorable neurological status at discharge (7.1% vs 5.0%; adjusted difference, 2.1% [95% CI, 0.3%-3.8%]; P = .02). There were no significant differences in oropharyngeal or hypopharyngeal injury (0.2% vs 0.3%), airway swelling (1.1% vs 1.0%), or pneumonia or pneumonitis (26.1% vs 22.3%). Conclusions and Relevance: Among adults with OHCA, a strategy of initial LT insertion was associated with significantly greater 72-hour survival compared with a strategy of initial ETI. These findings suggest that LT insertion may be considered as an initial airway management strategy in patients with OHCA, but limitations of the pragmatic design, practice setting, and ETI performance characteristics suggest that further research is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02419573.
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Manejo de la Vía Aérea/métodos , Intubación Intratraqueal/métodos , Laringe , Paro Cardíaco Extrahospitalario/terapia , Anciano , Manejo de la Vía Aérea/instrumentación , Reanimación Cardiopulmonar , Estudios Cruzados , Femenino , Humanos , Intubación Intratraqueal/instrumentación , Masculino , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/mortalidad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: Several studies have shown a bimodal curve in the distribution of glucose in populations with a high prevalence of type 2 diabetes, but bimodality has not been reported among whites of Northern European ancestry. It is not clear whether this difference reflects the lower prevalence of diabetes, obscuring a second mode, or implies a more fundamental difference between whites and nonwhites. We investigate this issue by studying glucose distributions in older white patients. RESEARCH DESIGN AND METHODS: A study of diabetes was conducted among older community-dwelling white residents of a suburban Southern California community between 1984 and 1987. Two-hour plasma glucose data were collected from 2,326 older white men and women aged 23-92. To investigate bimodality of glucose distributions, we fit unimodal and bimodal normal models to 2-h plasma glucose concentrations transformed by the Box-Cox family of transformations. RESULTS: We found that the bimodal normal mixture model fit the data significantly better than the unimodal skewed distribution model for both sexes and all age-groups except those > or =80 years. The cut points separating the two modes were generally within the 11.1- to 13.6-mmol/l range. CONCLUSIONS: The bimodality of glucose distributions among whites, combined with previous findings, indicates that this phenomenon may be universal. A smaller second mode in our study compared with other studies suggests that whites have diabetes susceptibility but may require more obesity to demonstrate it. With increasing obesity in the U.S., the predicted epidemic of diabetes may affect all ethnic groups including whites.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Distribución Normal , Prevalencia , Población BlancaAsunto(s)
Amoxicilina , Neumonía , Antibacterianos , Niño , Preescolar , Método Doble Ciego , Humanos , Lactante , Organización Mundial de la SaludRESUMEN
OBJECTIVE: Characterize intra-individual HIV-1 subtype B pol evolution in antiretroviral naive individuals. DESIGN: Longitudinal cohort study of individuals enrolled during primary infection. METHODS: Eligible individuals were antiretroviral naïve participants enrolled in the cohort from December 1997-December 2005 and having at least two blood samples available with the first one collected within a year of their estimated date of infection. Population-based pol sequences were generated from collected blood samples and analyzed for genetic divergence over time in respect to dual infection status, HLA, CD4 count and viral load. RESULTS: 93 participants were observed for a median of 1.8 years (Mean = 2.2 years, SD =1.9 years). All participants classified as mono-infected had less than 0.7% divergence between any two of their pol sequences using the Tamura-Nei model (TN93), while individuals with dual infection had up to 7.0% divergence. The global substitution rates (substitutions/nucleotide/year) for mono and dually infected individuals were significantly different (p<0.001); however, substitution rates were not associated with HLA haplotype, CD4 or viral load. CONCLUSIONS: Even after a maximum of almost 9 years of follow-up, all mono-infected participants had less than 1% divergence between baseline and longitudinal sequences, while participants with dual infection had 10 times greater divergence. These data support the use of HIV-1 pol sequence data to evaluate transmission events, networks and HIV-1 dual infection.
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Genes Virales/genética , Genes pol/genética , Infecciones por VIH/genética , VIH-1/genética , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Recuento de Linfocito CD4/métodos , Estudios de Cohortes , Evolución Molecular , Femenino , Variación Genética/genética , Infecciones por VIH/tratamiento farmacológico , Antígenos HLA/genética , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Carga Viral/métodos , Adulto JovenRESUMEN
The goal of this work was to study white matter (WM) integrity in children with cystinosis, a rare lysosomal storage disorder resulting in cystine accumulation in peripheral and central nervous system tissue. Based on previous reports of cystine crystal formation in myelin precursors as well as evidence for specific cognitive deficits in visuospatial functioning, diffusion tensor imaging (DTI) was applied to 24 children with cystinosis (age 3-7 years) and to 24 typically developing age-matched controls. Scalar diffusion indices, fractional anisotropy (FA) and mean diffusivity (MD), were examined in manually defined regions of interest within the parietal and inferior temporal lobes. Diffusion indices were correlated with performance on measures of visuospatial cognition and with white blood cell cystine levels. Bilaterally decreased FA and increased MD were evident in the inferior and superior parietal lobules in children with cystinosis, with comparable FA and MD to controls in inferior temporal WM, and implicate a dissociation of the dorsal and ventral visual pathways. In older cystinosis children (age>5), diminutions in visuospatial performance were associated with reduced FA in the right inferior parietal lobule. In addition, increased MD was found in the presence of high cystine levels in all children with cystinosis. This study provides new information that the average diffusion properties in children with cystinosis deviate from typically developing children. Findings suggest the presence of early microstructural WM changes in addition to a secondary effect of cystine accumulation. These alterations may impact the development of efficient fiber networks important for visuospatial cognition.
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Cistinosis/patología , Fibras Nerviosas Mielínicas/patología , Lóbulo Parietal/crecimiento & desarrollo , Lóbulo Parietal/patología , Lóbulo Temporal/crecimiento & desarrollo , Lóbulo Temporal/patología , Anisotropía , Niño , Desarrollo Infantil , Preescolar , Cognición , Cistina/metabolismo , Cistinosis/metabolismo , Imagen de Difusión Tensora , Femenino , Humanos , Leucocitos/metabolismo , Masculino , Vías Nerviosas/crecimiento & desarrollo , Vías Nerviosas/patología , Pruebas Neuropsicológicas , Percepción Espacial , Percepción VisualRESUMEN
The Risk Amplification and Abatement Model (RAAM), demonstrates that negative contact with socializing agents amplify risk, while positive contact abates risk for homeless adolescents. To test this model, the likelihood of exiting homelessness and returning to familial housing at 2 years and stably exiting over time are examined with longitudinal data collected from 183 newly homeless adolescents followed over 2 years in Los Angeles, CA. In support of RAAM, unadjusted odds of exiting at 2 years and stably exiting over2 years revealed that engagement with pro-social peers, maternal social support, and continued school attendance all promoted exiting behaviors. Simultaneously, exposure to family violence and reliance on shelter services discouraged stably exiting behaviors. Implications for family-based interventions are proposed.
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BACKGROUND: To develop less costly methods to virologically monitor patients receiving antiretroviral therapy, we evaluated methods that use pooled blood samples and quantitative information available from viral load assays to monitor a cohort of patients on first-line antiretroviral therapy for virologic failure. METHODS: We evaluated 150 blood samples collected after 6 months of therapy from participants enrolled in a San Diego primary infection program between January 1998 and January 2007. Samples were screened for virologic failure with individual viral load testing, 10 x 10 matrix pools and minipools of five samples. For the pooled platforms (matrix and minipools), we used a search and retest algorithm based on the quantitative viral load data to resolve samples that remained ambiguous for virologic failure. Viral load thresholds were more than 500 and more than 1500 copies/ml for the matrix and more than 250 and more than 500 copies/ml for the minipool. Efficiency, accuracy and result turnaround times were evaluated. RESULTS: Twenty-three percent of cohort samples were detectable at more than 50 HIV RNA copies/ml. At an algorithm threshold of more than 500 HIV RNA copies/ml, both minipool and matrix methods used less than half the number of viral load assays to screen the cohort, compared with testing samples individually. Both pooling platforms had negative predictive values of 100% for viral loads of more than 500 HIV RNA copies/ml and at least 94% for viral loads of more than 250 HIV RNA copies/ml. CONCLUSION: In this cohort, both pooling methods improved the efficiency of virologic monitoring over individual testing with a minimal decrease in accuracy. These methods may allow for the induction and sustainability of the virologic monitoring of patients receiving antiretroviral therapy in resource-limited settings.
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Antirretrovirales/uso terapéutico , Infecciones por VIH/virología , VIH-1 , ARN Viral/sangre , Carga Viral , Adulto , Anciano , Farmacorresistencia Viral/efectos de los fármacos , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/economía , Humanos , Masculino , Persona de Mediana Edad , Técnicas de Amplificación de Ácido Nucleico/economía , Técnicas de Amplificación de Ácido Nucleico/métodos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Current public health efforts often use molecular technologies to identify and contain communicable disease networks, but not for HIV. Here, we investigate how molecular epidemiology can be used to identify highly related HIV networks within a population and how voluntary contact tracing of sexual partners can be used to selectively target these networks. METHODS: We evaluated the use of HIV-1 pol sequences obtained from participants of a community-recruited cohort (n = 268) and a primary infection research cohort (n = 369) to define highly related transmission clusters and the use of contact tracing to link other individuals (n = 36) within these clusters. The presence of transmitted drug resistance was interpreted from the pol sequences (Calibrated Population Resistance v3.0). RESULTS: Phylogenetic clustering was conservatively defined when the genetic distance between any two pol sequences was less than 1%, which identified 34 distinct transmission clusters within the combined community-recruited and primary infection research cohorts containing 160 individuals. Although sequences from the epidemiologically linked partners represented approximately 5% of the total sequences, they clustered with 60% of the sequences that clustered from the combined cohorts (odds ratio 21.7; P < or = 0.01). Major resistance to at least one class of antiretroviral medication was found in 19% of clustering sequences. CONCLUSION: Phylogenetic methods can be used to identify individuals who are within highly related transmission groups, and contact tracing of epidemiologically linked partners of recently infected individuals can be used to link into previously defined transmission groups. These methods could be used to implement selectively targeted prevention interventions.
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Trazado de Contacto/métodos , Infecciones por VIH/transmisión , VIH-1/genética , Adulto , California/epidemiología , Farmacorresistencia Viral , Métodos Epidemiológicos , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/efectos de los fármacos , VIH-1/aislamiento & purificación , Humanos , Masculino , Modelos Organizacionales , Filogenia , Parejas Sexuales , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
The present study used a chimeric stimuli task to assess the magnitude of the left-hemispace bias in children with congenital unilateral brain damage (n = 46) as compared to typically developing matched controls (n = 46). As would be expected, controls exhibited a significant left-hemispace bias. In the presence of left hemisphere (LH) damage, the left-hemispace preference was found to be present, but attenuated, whereas right hemisphere (RH) damage resulted in a less lateralized process. Examination of lesion severity revealed that large lesions in the RH were associated with a reversal of the typical left-hemispace bias, while small lesions resulted in a left bias approximating that of controls. In contrast, the left-hemispace preference in children with LH damage was similar across lesion size. We conclude that damage to either hemisphere early in brain development may alter hemispheric preference for processing of nonverbal stimuli, and that at least in the case of RH damage, alteration of the normal perceptual asymmetry may depend on the interaction between lesion side and severity.