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The Kuiper Belt object (KBO) Arrokoth, the farthest object in the Solar System ever visited by a spacecraft, possesses a distinctive reddish surface and is characterized by pronounced spectroscopic features associated with methanol. However, the fundamental processes by which methanol ices are converted into reddish, complex organic molecules on Arrokoth's surface have remained elusive. Here, we combine laboratory simulation experiments with a spectroscopic characterization of methanol ices exposed to proxies of galactic cosmic rays (GCRs). Our findings reveal that the surface exposure of methanol ices at 40 K can replicate the color slopes of Arrokoth. Sugars and their derivatives (acids, alcohols) with up to six carbon atoms, including glucose and ribose-fundamental building block of RNA-were ubiquitously identified. In addition, polycyclic aromatic hydrocarbons (PAHs) with up to six ring units (13C22H12) were also observed. These sugars and their derivatives along with PAHs connected by unsaturated linkers represent key molecules rationalizing the reddish appearance of Arrokoth. The formation of abundant sugar-related molecules dubs Arrokoth as a sugar world and provides a plausible abiotic preparation route for a key class of biorelevant molecules on the surface of KBOs prior to their delivery to prebiotic Earth.
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BACKGROUND: Although clinicians have traditionally used the Finnegan Neonatal Abstinence Scoring Tool to assess the severity of neonatal opioid withdrawal, a newer function-based approach - the Eat, Sleep, Console care approach - is increasing in use. Whether the new approach can safely reduce the time until infants are medically ready for discharge when it is applied broadly across diverse sites is unknown. METHODS: In this cluster-randomized, controlled trial at 26 U.S. hospitals, we enrolled infants with neonatal opioid withdrawal syndrome who had been born at 36 weeks' gestation or more. At a randomly assigned time, hospitals transitioned from usual care that used the Finnegan tool to the Eat, Sleep, Console approach. During a 3-month transition period, staff members at each hospital were trained to use the new approach. The primary outcome was the time from birth until medical readiness for discharge as defined by the trial. Composite safety outcomes that were assessed during the first 3 months of postnatal age included in-hospital safety, unscheduled health care visits, and nonaccidental trauma or death. RESULTS: A total of 1305 infants were enrolled. In an intention-to-treat analysis that included 837 infants who met the trial definition for medical readiness for discharge, the number of days from birth until readiness for hospital discharge was 8.2 in the Eat, Sleep, Console group and 14.9 in the usual-care group (adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7 to 8.8), for a rate ratio of 0.55 (95% CI, 0.46 to 0.65; P<0.001). The incidence of adverse outcomes was similar in the two groups. CONCLUSIONS: As compared with usual care, use of the Eat, Sleep, Console care approach significantly decreased the number of days until infants with neonatal opioid withdrawal syndrome were medically ready for discharge, without increasing specified adverse outcomes. (Funded by the Helping End Addiction Long-term (HEAL) Initiative of the National Institutes of Health; ESC-NOW ClinicalTrials.gov number, NCT04057820.).
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Síndrome de Abstinencia Neonatal , Síndrome de Abstinencia a Sustancias , Humanos , Recién Nacido , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Narcóticos/uso terapéutico , Síndrome de Abstinencia Neonatal/terapia , Sueño , Síndrome de Abstinencia a Sustancias/diagnóstico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/terapia , Ingestión de Alimentos , Estados Unidos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Comodidad del PacienteRESUMEN
OBJECTIVES: To predict behavioral disruptions in middle childhood, we identified latent classes of prenatal substance use. STUDY DESIGN: As part of the Environmental influences on Child Health Outcomes Program, we harmonized prenatal substance use data and child behavior outcomes from 2195 women and their 6- to 11-year-old children across 10 cohorts in the US and used latent class-adjusted regression models to predict parent-rated child behavior. RESULTS: Three latent classes fit the data: low use (90.5%; n = 1986), primarily using no substances; licit use (6.6%; n = 145), mainly using nicotine with a moderate likelihood of using alcohol and marijuana; and illicit use (2.9%; n = 64), predominantly using illicit substances along with a moderate likelihood of using licit substances. Children exposed to primarily licit substances in utero had greater levels of externalizing behavior than children exposed to low or no substances (P = .001, d = .64). Children exposed to illicit substances in utero showed small but significant elevations in internalizing behavior than children exposed to low or no substances (P < .001, d = .16). CONCLUSIONS: The differences in prenatal polysubstance use may increase risk for specific childhood problem behaviors; however, child outcomes appeared comparably adverse for both licit and illicit polysubstance exposure. We highlight the need for similar multicohort, large-scale studies to examine childhood outcomes based on prenatal substance use profiles.
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Trastornos de la Conducta Infantil , Efectos Tardíos de la Exposición Prenatal , Problema de Conducta , Trastornos Relacionados con Sustancias , Embarazo , Humanos , Niño , Femenino , Análisis de Clases Latentes , Trastornos Relacionados con Sustancias/epidemiología , Conducta Infantil , Trastornos de la Conducta Infantil/epidemiología , Trastornos de la Conducta Infantil/etiología , Efectos Tardíos de la Exposición Prenatal/epidemiologíaRESUMEN
OBJECTIVES: (1) To evaluate the direct (un-mediated) and indirect (mediated) relationship between antenatal exposure to opioid agonist medication as treatment for opioid use disorder (MOUD) and the severity of neonatal opioid withdrawal syndrome (NOWS), and (2) to understand the degree to which mediating factors influence the direct relationship between MOUD exposure and NOWS severity. METHODS: This cross-sectional study includes data abstracted from the medical records of 1294 opioid-exposed infants (859 MOUD exposed and 435 non-MOUD exposed) born at or admitted to one of 30 US hospitals from July 1, 2016, to June 30, 2017. Regression models and mediation analyses were used to evaluate the relationship between MOUD exposure and NOWS severity (i.e., infant pharmacologic treatment and length of newborn hospital stay (LOS)) to identify potential mediators of this relationship in analyses adjusted for confounding factors. RESULTS: A direct (un-mediated) association was found between antenatal exposure to MOUD and both pharmacologic treatment for NOWS (aOR 2.34; 95%CI 1.74, 3.14) and an increase in LOS (1.73 days; 95%CI 0.49, 2.98). Delivery of adequate prenatal care and a reduction in polysubstance exposure were mediators of the relationship between MOUD and NOWS severity and as thus, were indirectly associated with a decrease in both pharmacologic treatment for NOWS and LOS. CONCLUSIONS FOR PRACTICE: MOUD exposure is directly associated with NOWS severity. Prenatal care and polysubstance exposure are potential mediators in this relationship. These mediating factors may be targeted to reduce the severity of NOWS while maintaining the important benefits of MOUD during pregnancy.
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Síndrome de Abstinencia Neonatal , Trastornos Relacionados con Opioides , Lactante , Recién Nacido , Humanos , Embarazo , Femenino , Analgésicos Opioides/efectos adversos , Estudios Transversales , Trastornos Relacionados con Opioides/complicaciones , Trastornos Relacionados con Opioides/tratamiento farmacológico , Síndrome de Abstinencia Neonatal/tratamiento farmacológico , PartoRESUMEN
OBJECTIVE: The coronavirus disease (COVID-19) pandemic has amplified preexisting racism and xenophobia. In this study, we investigated (a) whether perceived personal and group discrimination make distinct contributions to Chinese Canadians' negative affect and concern that the heightened discrimination they experienced during the pandemic will continue after the pandemic; (b) whether Canadian and Chinese identities and social support moderate the effect of discrimination on this concern; and (c) whether race-based rejection sensitivity (RS) explains why each type of discrimination predicts negative affect and expectation of future discrimination. METHOD: A sample of Chinese Canadian adults across Canadian provinces (N = 516; Mage = 42.74, 53.3% females) completed a questionnaire assessing personal and group discrimination, Chinese and Canadian identity, a short form of race-based RS, negative affect, and expectation of future discrimination. RESULTS: Personal and group discrimination were intercorrelated and positively associated with negative emotion and expectation of future discrimination. Chinese Canadians who identified more strongly as Chinese experienced a less adverse impact related to group discrimination. However, those who identified more (vs. less) strongly as Canadians were more likely to be impacted by personal discrimination. Finally, path analysis revealed that both personal and group discrimination were positively associated with RS, which in turn predicted an expectation that long-lasting racism would continue after the pandemic. CONCLUSION: Group and personal discrimination play different roles in Chinese Canadians' experiences during and expectations after the pandemic. Maintaining Chinese identity can be beneficial to Chinese Canadians, particularly in mitigating the negative effect of group discrimination during the pandemic. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Racismo , Identificación Social , Adulto , Femenino , Humanos , Masculino , Pueblo Asiatico , Canadá , Pueblos del Este de Asia , Racismo/psicologíaRESUMEN
BACKGROUND: Studies have shown that data collection by medical record abstraction (MRA) is a significant source of error in clinical research studies relying on secondary use data. Yet, the quality of data collected using MRA is seldom assessed. We employed a novel, theory-based framework for data quality assurance and quality control of MRA. The objective of this work is to determine the potential impact of formalized MRA training and continuous quality control (QC) processes on data quality over time. METHODS: We conducted a retrospective analysis of QC data collected during a cross-sectional medical record review of mother-infant dyads with Neonatal Opioid Withdrawal Syndrome. A confidence interval approach was used to calculate crude (Wald's method) and adjusted (generalized estimating equation) error rates over time. We calculated error rates using the number of errors divided by total fields ("all-field" error rate) and populated fields ("populated-field" error rate) as the denominators, to provide both an optimistic and a conservative measurement, respectively. RESULTS: On average, the ACT NOW CE Study maintained an error rate between 1% (optimistic) and 3% (conservative). Additionally, we observed a decrease of 0.51 percentage points with each additional QC Event conducted. CONCLUSIONS: Formalized MRA training and continuous QC resulted in lower error rates than have been found in previous literature and a decrease in error rates over time. This study newly demonstrates the importance of continuous process controls for MRA within the context of a multi-site clinical research study.
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Exactitud de los Datos , Registros Médicos , Recolección de Datos , Humanos , Recién Nacido , Proyectos de Investigación , Estudios RetrospectivosRESUMEN
NASA's New Horizons mission unveiled a diverse landscape of Pluto's surface with massive regions being neutral in color, while others like Cthulhu Macula range from golden-yellow to reddish comprising up to half of Pluto's carbon budget. Here, we demonstrate in laboratory experiments merged with electronic structure calculations that the photolysis of solid acetylene - the most abundant precipitate on Pluto's surface - by low energy ultraviolet photons efficiently synthesizes benzene and polycyclic aromatic hydrocarbons via excited state photochemistry thus providing critical molecular building blocks for the colored surface material. Since low energy photons deliver doses to Pluto's surface exceeding those from cosmic rays by six orders of magnitude, these processes may significantly contribute to the coloration of Pluto's surface and of hydrocarbon-covered surfaces of Solar System bodies such as Triton in general. This discovery critically enhances our perception of the distribution of aromatic molecules and carbon throughout our Solar System.
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Early in the COVID-19 pandemic, Canadians faced much ambiguity in the public health messages around face mask use. As public health messaging plays a pivotal role in the provision of directives during a health crisis, this study examines Canadians' opinions on the early messaging they received regarding personal protection, especially around mask use, with the goal of identifying potential improvements to strengthen future health messaging. Nine online focus group interviews with 47 Canadians were conducted. These natural conversations focused on personal protective equipment (PPE) choices, mask-relevant public health information sources, and advice to Canadian authorities to improve public health messaging on mask use. Responses were imported into NVivo for thematic analysis. Four meta-themes of relevance were identified. Despite demonstrating trust in scientific evidence and public health authorities, the inconsistencies in public health messaging fostered confusion, and induced mistrust toward health professionals. Further, several information deficits were identified pertaining to the scientific efficacy, safe use, and disposal of masks. Rooted in loyalty to healthcare workers, these Canadians eschewed using medical grade masks during PPE shortages to ensure a sufficient supply for medical workers. The findings stress that consistency in public health messages should be prioritized, with necessary changes clearly justified and explained. More information should reach the public on the scientific benefits and proper use of masks. Public health recommendations should be evidence-based, simple, transparent, and realistic in the current circumstances to guide Canadians to make more informed personal protection choices in the rapidly evolving pandemic.
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COVID-19/prevención & control , Comunicación en Salud , Máscaras , Pandemias/prevención & control , COVID-19/epidemiología , Canadá , Humanos , Percepción , Salud Pública , SARS-CoV-2 , ConfianzaRESUMEN
BACKGROUND: The preferred timing of umbilical-cord clamping in preterm infants is unclear. METHODS: We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births. RESULTS: Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed-clamping group and 9.0% in the immediate-clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities. CONCLUSIONS: Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088 .).
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Parto Obstétrico/métodos , Enfermedades del Prematuro/epidemiología , Recien Nacido Prematuro , Mortalidad Perinatal , Cordón Umbilical , Puntaje de Apgar , Constricción , Femenino , Hematócrito , Humanos , Incidencia , Recién Nacido/sangre , Masculino , Circulación Placentaria , Embarazo , Factores de TiempoRESUMEN
BACKGROUND: The prevalence of substance use, both prescribed and non-prescribed, is increasing in many areas of the world. Substance use by women of childbearing age contributes to increasing rates of neonatal abstinence syndrome (NAS). Neonatal opioid withdrawal syndrome (NOWS) is a newer term describing the subset of NAS related to opioid exposure. Non-pharmacological care is the first-line treatment for substance withdrawal in newborns. Despite the widespread use of non-pharmacological care to mitigate symptoms of NAS, there is not an established definition of, and standard for, non-pharmacological care practices in this population. Evaluation of safety and efficacy of non-pharmacological practices could provide clear guidance for clinical practice. OBJECTIVES: To evaluate the safety and efficacy of non-pharmacological treatment of infants at risk for, or having symptoms consistent with, opioid withdrawal on the length of hospitalization and use of pharmacological treatment for symptom management. Comparison 1: in infants at risk for, or having early symptoms consistent with, opioid withdrawal, does non-pharmacological treatment reduce the length of hospitalization and use of pharmacological treatment? Comparison 2: in infants receiving pharmacological treatment for symptoms consistent with opioid withdrawal, does concurrent non-pharmacological treatment reduce duration of pharmacological treatment, maximum and cumulative doses of opioid medication, and length of hospitalization? SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 10); Ovid MEDLINE; and CINAHL on 11 October 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs), quasi-RCTs, and cluster trials. SELECTION CRITERIA: We included trials comparing single or bundled non-pharmacological interventions to no non-pharmacological treatment or different single or bundled non-pharmacological interventions. We assessed non-pharmacological interventions independently and in combination based on sufficient similarity in population, intervention, and comparison groups studied. We categorized non-pharmacological interventions as: modifying environmental stimulation, feeding practices, and support of the mother-infant dyad. We presented non-randomized studies identified in the search process narratively. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Primary outcomes in infants at risk for, or having early symptoms consistent with, opioid withdrawal included length of hospitalization and pharmacological treatment with one or more doses of opioid or sedative medication. Primary outcomes in infants receiving opioid treatment for symptoms consistent with opioid withdrawal included length of hospitalization, length of pharmacological treatment with opioid or sedative medication, and maximum and cumulative doses of opioid medication. MAIN RESULTS: We identified six RCTs (353 infants) in which infants at risk for, or having symptoms consistent with, opioid withdrawal participated between 1975 and 2018. We identified no RCTs in which infants receiving opioid treatment for symptoms consistent with opioid withdrawal participated. The certainty of evidence for all outcomes was very low to low. We also identified and excluded 34 non-randomized studies published between 2005 and 2018, including 29 in which infants at risk for, or having symptoms consistent with, opioid withdrawal participated and five in which infants receiving opioid treatment for symptoms consistent with opioid withdrawal participated. We identified seven preregistered interventional clinical trials that may qualify for inclusion at review update when complete. Of the six RCTs, four studies assessed modifying environmental stimulation in the form of a mechanical rocking bed, prone positioning, non-oscillating waterbed, or a low-stimulation nursery; one study assessed feeding practices (comparing 24 kcal/oz to 20 kcal/oz formula); and one study assessed support of the maternal-infant dyad (tailored breastfeeding support). There was no evidence of a difference in length of hospitalization in the one study that assessed modifying environmental stimulation (mean difference [MD) -1 day, 95% confidence interval [CI) -2.82 to 0.82; 30 infants; very low-certainty evidence) and the one study of support of the maternal-infant dyad (MD -8.9 days, 95% CI -19.84 to 2.04; 14 infants; very low-certainty evidence). No studies of feeding practices evaluated the length of hospitalization. There was no evidence of a difference in use of pharmacological treatment in three studies of modifying environmental stimulation (typical risk ratio [RR) 1.00, 95% CI 0.86 to 1.16; 92 infants; low-certainty evidence), one study of feeding practices (RR 0.92, 95% CI 0.63 to 1.33; 49 infants; very low-certainty evidence), and one study of support of the maternal-infant dyad (RR 0.50, 95% CI 0.13 to 1.90; 14 infants; very low-certainty evidence). Reported secondary outcomes included neonatal intensive care unit (NICU) admission, days to regain birth weight, and weight nadir. One study of support of the maternal-infant dyad reported NICU admission (RR 0.50, 95% CI 0.13 to 1.90; 14 infants; very low-certainty evidence). One study of feeding practices reported days to regain birth weight (MD 1.10 days, 95% CI 2.76 to 0.56; 46 infants; very low-certainty evidence). One study that assessed modifying environmental stimulation reported weight nadir (MD -0.28, 95% CI -1.15 to 0.59; 194 infants; very low-certainty evidence) and one study of feeding practices reported weight nadir (MD -0.8, 95% CI -2.24 to 0.64; 46 infants; very low-certainty evidence). AUTHORS' CONCLUSIONS: We are uncertain whether non-pharmacological care for opioid withdrawal in newborns affects important clinical outcomes including length of hospitalization and use of pharmacological treatment based on the six included studies. The outcomes identified for this review were of very low- to low-certainty evidence. Combined analysis was limited by heterogeneity in study design and intervention definitions as well as the number of studies. Many prespecified outcomes were not reported. Although caregivers are encouraged by experts to optimize non-pharmacological care for opioid withdrawal in newborns prior to initiating pharmacological care, we do not have sufficient evidence to inform specific clinical practices. Larger well-designed studies are needed to determine the effect of non-pharmacological care for opioid withdrawal in newborns.
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Tiempo de Internación , Narcóticos/efectos adversos , Síndrome de Abstinencia Neonatal/terapia , Lechos , Lactancia Materna , Planificación Ambiental , Humanos , Hipnóticos y Sedantes/uso terapéutico , Equipo Infantil , Recién Nacido , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Síndrome de Abstinencia Neonatal/tratamiento farmacológico , Casas Cuna , Tratamiento de Sustitución de Opiáceos/métodos , Posicionamiento del Paciente/métodos , Posición Prona , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Fabry disease is an X-linked disorder resulted from deficiency of α-galactosidase A (GLA) activity. In Taiwan, a total of 792,247 newborns were screened from 2008 to 2014 in two newborn screening centers, and 13 variants of uncertain significance (VOUS) in the GLA gene were identified. To determine whether these variants were pathogenic or not, functional, biochemical, clinical and pedigree analyses were performed. In vitro functional assay was established through site-directed mutagenesis, and four in silico tools were used to predict pathogenesis. The enzyme activity of dried blood spots and plasma metabolite lyso-Gb3 level from subjects with the variants were measured. Additionally, clinical manifestations were evaluated extensively from the subjects and their relatives. Our results revealed that p.G104V, p.I232T, p.D322H, and p.G360C all exhibited relatively low residual enzyme activities and elevated plasma lyso-Gb3 level. These data strongly suggest that these Fabry mutations may cause classical or later-onset phenotypes. In contrast, neither significantly clinical symptoms nor elevated lyso-Gb3 level was found in cases with p.P60S, p.A108T, p.S304T, p.R356Q, and p.P362T variants, which may be non-pathogenic or milder forms of Fabry variants. More data need to be included for the patients with p.N53D, p.P210S, p.M296L, and p.K391T variants. The established system provides us more information to classify these GLA variants.
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Biomarcadores/sangre , Pruebas con Sangre Seca , Enfermedad de Fabry/diagnóstico , Mutación , alfa-Galactosidasa/sangre , alfa-Galactosidasa/genética , Bioensayo , Recolección de Muestras de Sangre , Enfermedad de Fabry/epidemiología , Enfermedad de Fabry/genética , Enfermedad de Fabry/metabolismo , Femenino , Humanos , Recién Nacido , Masculino , Tamizaje Neonatal , Taiwán/epidemiologíaRESUMEN
BACKGROUND: Seizures are common following perinatal asphyxia and may exacerbate secondary neuronal injury. Barbiturate therapy has been used for infants with perinatal asphyxia in order to prevent seizures. However, barbiturate therapy may adversely affect neurodevelopment leading to concern regarding aggressive use in neonates. OBJECTIVES: To determine the effect of administering prophylactic barbiturate therapy on death or neurodevelopmental disability in term and late preterm infants following perinatal asphyxia. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 11), MEDLINE via PubMed (1966 to 30 November 2015), EMBASE (1980 to 30 November 2015), and CINAHL (1982 to 30 November 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCT) and quasi-RCTs. SELECTION CRITERIA: We included all RCTs or quasi-RCTs of prophylactic barbiturate therapy in term and late preterm infants without clinical or electroencephalographic evidence of seizures compared to controls following perinatal asphyxia. DATA COLLECTION AND ANALYSIS: Three review authors independently selected, assessed the quality of, and extracted data from the included studies. We assessed methodologic quality and validity of studies without consideration of the results. The review authors independently extracted data and performed meta-analyses using risk ratios (RR) and risk differences (RD) for dichotomous data and mean difference for continuous data with 95% confidence intervals (CI). For significant results, we calculated the number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH). MAIN RESULTS: In this updated review, we identified nine RCTs of any barbiturate therapy in term and late preterm infants aged less than three days old with perinatal asphyxia without evidence of seizures. Eight of these studies compared prophylactic barbiturate therapy to conventional treatment (enrolling 439 infants) and one study compared barbiturate therapy to treatment with phenytoin (enrolling 17 infants). Prophylactic barbiturate therapy versus conventional treatment: one small trial reported a decreased risk of death or severe neurodevelopmental disability for barbiturate therapy (phenobarbital) versus conventional treatment (RR 0.33, 95% CI 0.14 to 0.78; RD -0.55, 95% CI -0.84 to -0.25; NNTB 2, 95% CI 1 to 4; 1 study, 31 infants) (very low quality evidence).Eight trials comparing prophylactic barbiturate therapy with conventional treatment following perinatal asphyxia demonstrated no significant impact on the risk of death (typical RR 0.88, 95% CI 0.55 to 1.42; typical RD -0.02, 95% CI -0.08 to 0.05; 8 trials, 429 infants) (low quality evidence) and the one small trial noted above reported a significant decrease in the risk of severe neurodevelopmental disability (RR 0.24, 95% CI 0.06 to 0.92; RD -0.43, 95% CI -0.73 to -0.13; NNTB 2, 95% CI 1 to 8; 1 study, 31 infants) (very low quality evidence).A meta-analysis of the six trials reporting on seizures in the neonatal period demonstrated a statistically significant reduction in seizures in the prophylactic barbiturate group versus conventional treatment (typical RR 0.62, 95% CI 0.48 to 0.81; typical RD -0.18, 95% CI -0.27 to -0.09; NNTB 5, 95% CI 4 to 11; 6 studies, 319 infants) (low quality evidence). There were similar results in subgroup analyses based on type of barbiturate and Sarnat score. Prophylactic barbiturate therapy versus other prophylactic anticonvulsant therapy: one study reported on prophylactic barbiturate versus prophylactic phenytoin. There was no significant difference in seizure activity in the neonatal period between the two study groups (RR 0.89, 95% CI 0.07 to 12.00; 1 trial, 17 infants). AUTHORS' CONCLUSIONS: We found only low or very low quality evidence addressing the use of prophylactic barbiturates in infants with perinatal asphyxia. Although the administration of prophylactic barbiturate therapy to infants following perinatal asphyxia did reduce the risk of seizures, there was no reduction seen in mortality and there were few data addressing long-term outcomes. The administration of prophylactic barbiturate therapy for late preterm and term infants in the immediate period following perinatal asphyxia cannot be recommended for routine clinical practice. If used at all, barbiturates should be reserved for the treatment of seizures. The results of the current review support the use of prophylactic barbiturate therapy as a promising area of research. Future studies should be of sufficient size and duration to detect clinically important reductions in mortality and severe neurodevelopmental disability and should be conducted in the context of the current standard of care, including the use of therapeutic hypothermia.
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Anticonvulsivantes/uso terapéutico , Asfixia Neonatal/tratamiento farmacológico , Barbitúricos/uso terapéutico , Convulsiones/prevención & control , Asfixia Neonatal/complicaciones , Asfixia Neonatal/mortalidad , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Trastornos del Neurodesarrollo/etiología , Trastornos del Neurodesarrollo/prevención & control , Fenobarbital/uso terapéutico , Fenitoína/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Convulsiones/mortalidad , Tiopental/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the impact and feasibility of community pharmacist-directed influenza screening and to evaluate the proportion of influenza-positive cases that resulted in the initiation of antiviral therapy by pharmacists. METHODS: Patients aged 5 and older with symptoms suggestive of influenza were recruited at 2 Shoppers Drug Mart locations in Toronto, Ontario, from December 12, 2014, to February 4, 2015. Nasal swabs were collected by pharmacists and screened using the BD Veritor system for Rapid Detection of Flu A+B. Positive tests for influenza were reported to patients' physicians and recommendations for antiviral therapy were made when indicated. Supportive care recommendations and telephone follow-up within 48 hours of assessment were provided to all patients. RESULTS: A total of 59 patients participated in the influenza screening program. Sixty-one percent of patients were at high risk for influenza-related complications, while 15% had more than one risk factor. Thirty-four percent of patients screened positive for influenza, of which 100% were influenza A. Of the patients who screened positive, a prescription for oseltamivir was obtained in 40% of cases. The majority of prescriptions were provided directly to the pharmacy (63%), while the balance was provided after the patients underwent medical examination at the request of their physicians (37%). The pharmacy team offered supportive care to all patients for symptom management. Over-the-counter pharmacotherapy was provided to 85% of patients. CONCLUSION: These results highlight the readiness of community pharmacists to participate in the management of patients with influenza and their ability to implement screening into pharmacy workflow. Community pharmacy-based influenza screening may facilitate prompt access to pharmacologic treatment for patients with influenza, as well as decrease burden on the health care system by redirecting influenza-negative patients from physicians' offices and hospitals. Timely physician communication remains a barrier to access to treatment, suggesting a potential key role for advanced pharmacist prescribing. Can Pharm J (Ott) 2016;149:83-89.
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Importance: Infants with neonatal opioid withdrawal syndrome (NOWS) cared for with the Eat, Sleep, Console (ESC) care approach receive less pharmacologic treatment and have shorter hospital stays compared to usual care with the Finnegan Neonatal Abstinence Scoring Tool, but the effects of these approaches on feeding and weight are unknown. Objective: To evaluate feeding practices and weight trajectories in infants cared for with ESC vs usual care. Design, Setting, and Participants: ESC-NOW is a cluster randomized trial of infants with NOWS born at 36 weeks' gestation or later at 26 US hospitals from September 2020 to March 2022. Each site transitioned from usual care to ESC (the study intervention) at a randomized time. Feeding was per site practice and not specified by the intervention. Feeding and weight outcomes were assessed at hospital discharge. Intervention: ESC vs usual care. Main Outcomes and Measures: Outcomes include prospectively identified secondary end points related to feeding and weight. z Scores were used for growth to account for corrected gestational age at the time of measurement. All analyses were intention to treat and adjusted for study design. Maternal/infant characteristics were included in adjusted models. Results: The analyses included 1305 infants (702 in usual care and 603 in ESC; mean [SD] gestational age, 38.6 [1.3] weeks; 655 [50.2%] male and 650 [49.8%] female). Baseline demographic characteristics were similar between groups. The proportion of breastfed infants was higher in the ESC group (52.7% vs 41.7%; absolute difference, 11%; 95% CI, 1.0-20.9). A higher proportion of infants cared for with ESC received exclusive breast milk (15.1% vs 6.7%; absolute difference, 8.4%; 95% CI, 0.9-5.8) or any breast milk (38.8% vs 27.4%; absolute difference, 11.4%; 95% CI, 0.2-23.1) and were directly breastfeeding at discharge (35.2% vs 19.5%; absolute difference, 15.7%; 95% CI, 4.1-27.3). There was no difference in proportion of infants with weight loss greater than 10% or maximum percentage weight loss, although infants cared for with ESC had a lower weight z score on day of life 3 (-1.08 vs -1.01; absolute difference, 0.07; 95% CI, 0.02-0.12). When pharmacologic treatment was added into the model, no breastfeeding outcomes were statistically significant. Conclusions and Relevance: In this study, infants cared for with ESC were more likely to initiate and continue breastfeeding and had no difference in percentage weight loss. The improvement in breastfeeding with ESC may be driven by reduction in pharmacologic treatment and provision of effective nonpharmacologic care. Trial Registration: ClinicalTrials.gov Identifier: NCT04057820.
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Importance: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown. Objective: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool. Design, Setting, and Participants: This post hoc subgroup analysis involved infants pharmacologically treated in ESC-NOW, a stepped-wedge cluster randomized clinical trial conducted at 26 US hospitals. Hospitals maintained pretrial practices for pharmacologic treatment, including opioid type, scheduled opioid dosing, and use of adjuvant medications. Infants were born at 36 weeks' gestation or later, had evidence of antenatal opioid exposure, and received opioid treatment for NOWS between September 2020 and March 2022. Data were analyzed from November 2022 to January 2024. Exposure: Opioid treatment for NOWS and the ESC care approach. Main Outcomes and Measures: For each outcome (total opioid exposure, peak opioid dose, time from birth to initiation of first opioid dose, length of opioid treatment, and LOS), we used generalized linear mixed models to adjust for the stepped-wedge design and maternal and infant characteristics. Results: In the ESC-NOW trial, 463 of 1305 infants were pharmacologically treated (143/603 [23.7%] in the ESC care approach group and 320/702 [45.6%] in the usual care group). Mean total opioid exposure was lower in the ESC care approach group with an absolute difference of 4.1 morphine milligram equivalents per kilogram (MME/kg) (95% CI, 1.3-7.0) when compared with usual care (4.8 MME/kg vs 8.9 MME/kg, respectively; P = .001). Mean time from birth to initiation of pharmacologic treatment was 22.4 hours (95% CI, 7.1-37.7) longer with the ESC care approach vs usual care (75.4 vs 53.0 hours, respectively; P = .002). No significant difference in mean peak opioid dose was observed between groups (ESC care approach, 0.147 MME/kg, vs usual care, 0.126 MME/kg). The mean length of treatment was 6.3 days shorter (95% CI, 3.0-9.6) in the ESC care approach group vs usual care group (11.8 vs 18.1 days, respectively; P < .001), and mean LOS was 6.2 days shorter (95% CI, 3.0-9.4) with the ESC care approach than with usual care (16.7 vs 22.9 days, respectively; P < .001). Conclusion and Relevance: When compared with usual care, the ESC care approach was associated with less opioid exposure and shorter LOS for infants pharmacologically treated for NOWS. The ESC care approach was not associated with a higher peak opioid dose, although pharmacologic treatment was typically initiated later. Trial Registration: ClinicalTrials.gov Identifier: NCT04057820.
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Analgésicos Opioides , Síndrome de Abstinencia Neonatal , Humanos , Síndrome de Abstinencia Neonatal/tratamiento farmacológico , Femenino , Recién Nacido , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Masculino , Tiempo de Internación/estadística & datos numéricos , Sueño/efectos de los fármacosRESUMEN
Kuiper Belt objects exhibit a wider color range than any other solar system population. The origin of this color diversity is unknown, but likely the result of the prolonged irradiation of organic materials by galactic cosmic rays (GCRs). Here, we combine ultrahigh-vacuum irradiation experiments with comprehensive spectroscopic analyses to examine the color evolution during GCR processing methane and acetylene under Kuiper Belt conditions. This study replicates the colors of a population of Kuiper Belt objects such as Makemake, Orcus, and Salacia. Aromatic structural units carrying up to three rings as in phenanthrene (C14H10), phenalene (C9H10), and acenaphthylene (C12H8), of which some carry structural motives of DNA and RNA connected via unsaturated linkers, were found to play a key role in producing the reddish colors. These studies demonstrate the level of molecular complexity synthesized of GCR processing hydrocarbon and hint at the role played by irradiated ice in the early production of biological precursor molecules.
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Background: Medical record abstraction (MRA) is a commonly used method for data collection in clinical research, but is prone to error, and the influence of quality control (QC) measures is seldom and inconsistently assessed during the course of a study. We employed a novel, standardized MRA-QC framework as part of an ongoing observational study in an effort to control MRA error rates. In order to assess the effectiveness of our framework, we compared our error rates against traditional MRA studies that had not reported using formalized MRA-QC methods. Thus, the objective of this study was to compare the MRA error rates derived from the literature with the error rates found in a study using MRA as the sole method of data collection that employed an MRA-QC framework. Methods: Using a moderator meta-analysis employed with Q-test, the MRA error rates from the meta-analysis of the literature were compared with the error rate from a recent study that implemented formalized MRA training and continuous QC processes. Results: The MRA process for data acquisition in clinical research was associated with both high and highly variable error rates (70 - 2,784 errors per 10,000 fields). Error rates for the study using our MRA-QC framework were between 1.04% (optimistic, all-field rate) and 2.57% (conservative, populated-field rate) (or 104 - 257 errors per 10,000 fields), 4.00 - 5.53 percentage points less than the observed rate from the literature (p<0.0001). Conclusions: Review of the literature indicated that the accuracy associated with MRA varied widely across studies. However, our results demonstrate that, with appropriate training and continuous QC, MRA error rates can be significantly controlled during the course of a clinical research study.
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Background: In clinical research, prevention of systematic and random errors of data collected is paramount to ensuring reproducibility of trial results and the safety and efficacy of the resulting interventions. Over the last 40 years, empirical assessments of data accuracy in clinical research have been reported in the literature. Although there have been reports of data error and discrepancy rates in clinical studies, there has been little systematic synthesis of these results. Further, although notable exceptions exist, little evidence exists regarding the relative accuracy of different data processing methods. We aim to address this gap by evaluating error rates for 4 data processing methods. Methods: A systematic review of the literature identified through PubMed was performed to identify studies that evaluated the quality of data obtained through data processing methods typically used in clinical trials: medical record abstraction (MRA), optical scanning, single-data entry, and double-data entry. Quantitative information on data accuracy was abstracted from the manuscripts and pooled. Meta-analysis of single proportions based on the Freeman-Tukey transformation method and the generalized linear mixed model approach were used to derive an overall estimate of error rates across data processing methods used in each study for comparison. Results: A total of 93 papers (published from 1978 to 2008) meeting our inclusion criteria were categorized according to their data processing methods. The accuracy associated with data processing methods varied widely, with error rates ranging from 2 errors per 10,000 fields to 2,784 errors per 10,000 fields. MRA was associated with both high and highly variable error rates, having a pooled error rate of 6.57% (95% CI: 5.51, 7.72). In comparison, the pooled error rates for optical scanning, single-data entry, and double-data entry methods were 0.74% (0.21, 1.60), 0.29% (0.24, 0.35) and 0.14% (0.08, 0.20), respectively. Conclusions: Data processing and cleaning methods may explain a significant amount of the variability in data accuracy. MRA error rates, for example, were high enough to impact decisions made using the data and could necessitate increases in sample sizes to preserve statistical power. Thus, the choice of data processing methods can likely impact process capability and, ultimately, the validity of trial results.
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Early in the COVID-19 pandemic, journalists and scholars noted differences between Asians and North Americans in their support for public mask use. These differences were primarily assumed to be due d to variations in ethnocultural norms and practices. To better ascertain people's motives for wearing masks and potential cultural differences in these rationales, this comparative, mixed-methods research examines Chinese and non-East Asian Canadians' mask use attitudes utilizing online group interviews (Study 1) and a nation-wide survey (Study 2) Study 1, conducted in the early stages of the pandemic, captured an ambivalent, yet evolving attitude toward public mask use among the non-East Asian Canadians, which differed from their Chinese counterparts who more uniformly perceived mask use favorably. Study 2, conducted 2 months later, suggests that both groups primarily wore masks for disease protection- and prevention-related reasons. However, age and education appeared to influence the mask wearing frequency of the non-East Asian Canadians, for whom public mask use was less prevalent and normative. The attitudinal differences in public mask use call for targeted strategies to support mask wearing for different ethnocultural groups, which may be achieved partially through enhancing interethnic understanding on the diversified use of and opinions about masks. The findings suggest that favorable social norms, along with evidence-based information campaigns involving personal appeals may encourage greater mask use by the non-East Asian population.
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Pluto, Titan, and Triton make up a unique class of solar system bodies, with icy surfaces and chemically reducing atmospheres rich in organic photochemistry and haze formation. Hazes play important roles in these atmospheres, with physical and chemical processes highly dependent on particle sizes, but the haze size distribution in reducing atmospheres is currently poorly understood. Here we report observational evidence that Pluto's haze particles are bimodally distributed, which successfully reproduces the full phase scattering observations from New Horizons. Combined with previous simulations of Titan's haze, this result suggests that haze particles in reducing atmospheres undergo rapid shape change near pressure levels ~0.5 Pa and favors a photochemical rather than a dynamical origin for the formation of Titan's detached haze. It also demonstrates that both oxidizing and reducing atmospheres can produce multi-modal hazes, and encourages reanalysis of observations of hazes on Titan and Triton.