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Objective: The Child Asthma Risk Assessment Tool (CARAT) identifies risk factors for asthma morbidity. We hypothesized that CARAT-identified risk factors (using a CARAT adapted for inpatient use) would be associated with future healthcare utilization and would identify areas for intervention.Methods: We reviewed CARAT data collected during pediatric asthma admissions from 2010-2015, assessing for risk factors in environmental, medical, and social domains and providing prompts for inpatient (specialist consultation or social services engagement) and post-discharge interventions (home care visit or home environmental assessment). Confirmatory factor analysis identified groups of CARAT-identified risk factors with similar effects on healthcare utilization (latent factors). Structural equation models then evaluated relationships between latent factors and future utilization.Results: There were 2731 unique patients admitted for asthma exacerbations; 1015 (37%) had complete CARAT assessments and were included in analyses. Those with incomplete CARAT assessments were more often younger and privately-insured. CARAT-identified risk factors across domains were common in children hospitalized for exacerbations. Risks in the environmental domain were most common. Inpatient asthma consults by pulmonologists or allergists and home care referrals were the most frequent interventions indicated (62%, 628/1015, and 50%, 510/1015, respectively). Two latent factors were positively associated with healthcare utilization in the year after index stay - social stressors and known/suspected allergies (both p < 0.05). Stratified analyses analyzing data just from those children with prior healthcare utilization also indicated known/suspected allergies to be positively associated with future utilization.Conclusions: Inpatient interventions to address social stressors and allergic profiles may be warranted to reduce subsequent asthma morbidity.
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Asma , Hipersensibilidade , Humanos , Criança , Asma/diagnóstico , Asma/epidemiologia , Asma/terapia , Assistência ao Convalescente , Alta do Paciente , Hospitalização , Medição de Risco , Hipersensibilidade/complicaçõesAssuntos
Oscilometria , Testes de Função Respiratória , Humanos , Pré-Escolar , Masculino , Feminino , Pulmão/fisiologiaRESUMO
One of the most widely accepted axioms of mammalian reproductive biology is that pregnancy requires the (sole) support of progesterone, acting in large measure through nuclear progesterone receptors (PRs) in uterine and cervical tissues, without which pregnancy cannot be established or maintained. However, mares lack detectable progesterone in the latter half of pregnancy. Instead of progesterone, several (mainly 5α-reduced) pregnanes are elevated and have long been speculated to provide progestational support in lieu of progesterone itself. To the authors' knowledge, evidence for the bioactivity of a second potent endogenously synthesized pregnane able to support pregnancy in the absence of progesterone has never before been reported. The 5α-reduced progesterone metabolite dihydroprogesterone (DHP) was shown in vivo to stimulate endometrial growth and progesterone-dependent gene expression in the horse at subphysiological concentrations and to maintain equine pregnancy in the absence of luteal progesterone in the third and fourth weeks postbreeding. Results of in vitro studies indicate that DHP is an equally potent and efficacious endogenous progestin in the horse but that the PR evolved with increased agonistic potency for DHP at the expense of potency toward progesterone based on comparisons with human PR responses. Sequence analysis and available literature indicate that the enzyme responsible for DHP synthesis, 5α-reductase type 1, also adapted primarily to metabolize progesterone and thereby to serve diverse roles in the physiology of pregnancy in mammals. Our confirmation that endogenously synthesized DHP is a biopotent progestin in the horse ends decades of speculation, explaining how equine pregnancies survive without measurable circulating progesterone in the last 4 to 5 mo of gestation.
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3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , 5-alfa-Di-Hidroprogesterona/metabolismo , Gravidez/metabolismo , Receptores de Progesterona/agonistas , 5-alfa-Di-Hidroprogesterona/sangue , Análise de Variância , Animais , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Feminino , Cavalos , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Progesterona/sangue , Progesterona/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Progesterona/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Especificidade da Espécie , Espectrometria de Massas em TandemRESUMO
Introduction: Asthma is characterized by preventable morbidity, cost, and inequity. We sought to build an Asthma Learning Health System (ALHS) to coordinate regional pediatric asthma improvement activities. Methods: We generated quantitative and qualitative insights pertinent to a better, more equitable care delivery system. We used electronic health record data to calculate asthma hospitalization rates for youth in our region. We completed an "environmental scan" to catalog the breadth of asthma-related efforts occurring in our children's hospital and across the region. We supplemented the scan with group-level assessments and focus groups with parents, clinicians, and community partners. We used insights from this descriptive epidemiology to inform the definition of shared aims, drivers, measures, and prototype interventions. Results: Greater Cincinnati's youth are hospitalized for asthma at a rate three times greater than the U.S. average. Black youth are hospitalized at a rate five times greater than non-Black youth. Certain neighborhoods bear the disproportionate burden of asthma morbidity. Across Cincinnati, there are many asthma-relevant activities that seek to confront this morbidity; however, efforts are largely disconnected. Qualitative insights highlighted the importance of cross-sector coordination, evidence-based acute and preventive care, healthy homes and neighborhoods, and accountability. These insights also led to a shared, regional aim: to equitably reduce asthma-related hospitalizations. Early interventions have included population-level pattern recognition, multidisciplinary asthma action huddles, and enhanced social needs screening and response. Conclusion: Learning health system methods are uniquely suited to asthma's complexity. Our nascent ALHS provides a scaffold atop which we can pursue better, more equitable regional asthma outcomes.
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BACKGROUND: Children from economically disadvantaged communities often encounter healthcare access barriers, increasing risk for poorly controlled asthma and subsequent healthcare utilization. This highlights the need to identify novel intervention strategies for these families. OBJECTIVE: To better understand the needs and treatment preferences for asthma management in children from economically disadvantaged communities and to develop a novel asthma management intervention based on an initial needs assessment and stakeholder feedback. METHODS: Semistructured interviews and focus groups were conducted with 19 children (10-17 years old) with uncontrolled asthma and their caregivers, 14 school nurses, 8 primary care physicians, and three school resource coordinators from economically disadvantaged communities. Interviews and focus groups were audio-taped and transcribed verbatim and then analyzed thematically to inform intervention development. Using stakeholder input, an intervention was developed for children with uncontrolled asthma and presented to participants for feedback to fully develop a novel intervention. RESULTS: The needs assessment resulted in five themes: (1) barriers to quality asthma care, (2) poor communication across care providers, (3) problems identifying and managing symptoms and triggers among families, (4) difficulties with adherence, and (5) stigma. A proposed video-based telehealth intervention was proposed to stakeholders who provided favorable and informative feedback for the final development of the intervention for children with uncontrolled asthma. CONCLUSIONS: Stakeholder input and feedback provided information critical to the development of a multicomponent (medical and behavioral) intervention in a school setting that uses technology to facilitate care, collaboration, and communication among key stakeholders to improve asthma management for children from economically disadvantaged neighborhoods.
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Asma , Telemedicina , Humanos , Criança , Adolescente , Avaliação das Necessidades , Asma/diagnóstico , Nebulizadores e Vaporizadores , ComunicaçãoRESUMO
Plastic bronchitis is a term used to describe group of life-threatening disorders characterized by the presence of large obstructing casts in the airways. Eosinophilic plastic bronchitis is a subtype of plastic bronchitis that occurs mainly in children and has not been well-described in the literature. Patients may have a history of asthma or atopy, but many do not. They often present with cough and wheezing, and frequently have complete collapse of one lung seen on imaging. The severity of presentation varies depending on the location of the casts, ranging from mild symptoms to severe airway obstruction and death. Bronchoscopy is often required to both diagnose and treat this condition. A variety of medical therapies have been used, although no formal studies have evaluated their efficacy. Symptoms may resolve after initial cast removal, but in some patients, cast formation recurs. Here, we report a case series of nine patients with eosinophilic plastic bronchitis and review the existing literature of this condition.
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Obstrução das Vias Respiratórias , Asma , Bronquite , Criança , Humanos , Bronquite/diagnóstico , Bronquite/diagnóstico por imagem , Asma/diagnóstico , Pulmão , Obstrução das Vias Respiratórias/diagnóstico , BroncoscopiaRESUMO
RATIONALE: Identifying neonatal and post-discharge exposures among extremely low gestational age newborns (ELGANs) that drive increased pulmonary morbidity and abnormal lung function at 1 year of age proves challenging. OBJECTIVE: The NIH-sponsored Prematurity and Respiratory Outcomes Program (PROP), evaluated infant pulmonary function tests (iPFTs) at 1 year corrected age to determine which demographic and clinical factors are associated with abnormal lung function. METHODS: iPFTs were performed on a PROP subcohort of 135 participants following Institutional Review Board (IRB)-approved written consent. Demographic data, Neonatal Intensive Care Unit (NICU) clinical care, and post-NICU exposures were analyzed for association with iPFTs. MAIN RESULTS: A significant decrease in forced expiratory volume at 0.5 s (FEV0.5 ) and/or forced expiratory flows at 75% of forced vital capacity (FEF75 ), were associated with male sex and African American race. Clinical factors including longer duration of ventilatory support, exposure to systemic steroids, and weight less than the 10th percentile at 36 weeks postmenstrual age were also associated with airflow obstruction, whereas supplemental oxygen requirement and bronchopulmonary dysplasia were not. Additionally, the need for respiratory medications, technology, or hospitalizations during the first year, ascertained by a quarterly survey, were the only post-NICU factors associated with decreased FEV0.5 and FEF75 . Only 7% of infants had reversible airflow obstruction. CONCLUSIONS: Neonatal demographic factors, respiratory support in the NICU, and a history of greater post-NICU medical utilization for respiratory disease had the strongest association with lower lung function at 1 year in ELGANs.
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Assistência ao Convalescente , Displasia Broncopulmonar , Displasia Broncopulmonar/complicações , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Alta do Paciente , Testes de Função RespiratóriaRESUMO
OBJECTIVES: To determine the usefulness of urinary bromotyrosine, a noninvasive marker of eosinophil-catalyzed protein oxidation, in tracking with indexes of asthma control and in predicting future asthma exacerbations in children. STUDY DESIGN: Children with asthma were recruited consecutively at the time of clinic visit. Urine was obtained, along with spirometry, exhaled nitric oxide, and Asthma Control Questionnaire data. Follow-up phone calls were made 6 weeks after enrollment. RESULTS: Fifty-seven participants were enrolled. Urinary bromotyrosine levels tracked significantly with indexes of asthma control as assessed by Asthma Control Questionnaire scores at baseline (R = 0.38, P = .004) and follow-up (R = 0.39, P = .008). Participants with high baseline levels of bromotyrosine were 18.1-fold (95% CI 2.1-153.1, P = .0004) more likely to have inadequately controlled asthma and 4.0-fold more likely (95% CI 1.1-14.7, P = .03) to have an asthma exacerbation (unexpected emergency department visit; doctor's appointment or phone call; oral or parenteral corticosteroid burst; acute asthma-related respiratory symptoms) over the ensuing 6 weeks. Exhaled nitric oxide levels did not track with Asthma Control Questionnaire data; and immunoglobulin E, eosinophil count, spirometry, and exhaled nitric oxide levels failed to predict asthma exacerbations. CONCLUSIONS: Urinary bromotyrosine tracks with asthma control and predicts the risk of future asthma exacerbations in children.
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Asma/urina , Biomarcadores/urina , Tirosina/análogos & derivados , Adolescente , Asma/fisiopatologia , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Feminino , Seguimentos , Fluxo Expiratório Forçado , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Recidiva , Espirometria , Fatores de Tempo , Tirosina/urina , Adulto JovemRESUMO
Healthcare disparities exist in pediatric asthma in the United States. Children from minority, low-income families in inner-city areas encounter barriers to healthcare, leading to greater rates of poorly controlled asthma and healthcare utilization. Finding an effective way to deliver high-quality healthcare to this underserved population to improve outcomes, reduce morbidity and mortality, and reduce healthcare utilization is of the utmost importance. The purpose of this study was to assess the feasibility and efficacy of a novel school-based care delivery model that incorporates video-based telehealth (VBT) medical and self-management visits with electronic inhaler monitoring to improve asthma outcomes. Over a 6-month period, children from inner-city, low-income schools with uncontrolled asthma completed seven scheduled medical visits with an asthma specialist and five self-management visits with an adherence psychologist at school using VBT. Composite Asthma Severity Index (CASI) scores and electronic inhaler monitor data were recorded and analyzed. A total of 21 patients were enrolled in the study. Study subjects with higher baseline severity (CASI ≥ 4 at visit 1) demonstrated a greater reduction in their score than those with lower baseline severity (CASI < 4 at visit 1). The CASI domains showed improvement in daytime symptoms, nighttime symptoms, and exacerbations. Adherence results demonstrated a significant improvement in adherence from baseline to postintervention. Study retention was 100%. This study demonstrates that a multicomponent medical and behavioral interventional program delivered by VBT to a school-based setting is feasible and can significantly improve asthma outcomes and care in a challenging population.
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Albuterol/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Adesão à Medicação , Serviços de Saúde Escolar , Telemedicina , Adolescente , Criança , Feminino , Humanos , Masculino , Ohio , Áreas de Pobreza , AutogestãoRESUMO
Objective measures of lung function are important in the diagnosis and management of asthma. Spirometry, the pulmonary function test most widely used in asthma, requires respiratory maneuvers that may be difficult for preschoolers. Impulse oscillometry (IOS) is a noninvasive method of measuring lung function during tidal breathing; hence, IOS is an ideal test for use in preschool asthma. Fractional exhaled nitric oxide (FeNO) levels correspond to eosinophilic inflammation and predict responsiveness to corticosteroids. Basic concepts of IOS, methodology, and interpretation, including available normative values, and recent findings regarding FeNO are reviewed in this article.
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Asma/diagnóstico , Testes Respiratórios/métodos , Eosinófilos/imunologia , Inflamação/imunologia , Oscilometria/métodos , Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Biomarcadores Farmacológicos , Pré-Escolar , Expiração , Humanos , Óxido Nítrico/metabolismoAssuntos
Síndrome de Down/epidemiologia , Pneumopatias/epidemiologia , Transtornos Respiratórios/epidemiologia , Distribuição por Idade , Asma/diagnóstico , Asma/epidemiologia , Criança , Pré-Escolar , Comorbidade , Síndrome de Down/diagnóstico , Feminino , Humanos , Incidência , Lactente , Pneumopatias/diagnóstico , Masculino , Prognóstico , Transtornos Respiratórios/diagnóstico , Medição de Risco , Distribuição por Sexo , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Visitas de PreceptoriaRESUMO
RATIONALE: Risk factors for severe asthma exacerbations in children requiring admission to the intensive care unit (ICU) may occur in variety of medical, environmental, economic, and socioeconomic domains. OBJECTIVES: We sought to characterize medical and sociodemographic risk factors among children who required admission to the intensive care unit for asthma. METHODS: Data were obtained from the Greater Cincinnati Asthma Risk Study, a population-based, prospective, observational cohort of children admitted for treatment of acute asthma or bronchodilator-responsive wheezing. Data collected on 774 children included race, socioeconomic status, allergen sensitization, environmental exposures, psychosocial strain, and financial hardship. Analyses compared children admitted to the ICU to those admitted to a medical inpatient unit. MEASUREMENTS AND MAIN RESULTS: One hundred sixty-one (20.9%) children required admission to intensive care. There was no difference in sex, race, insurance status, caregiver educational level, income, financial strain, psychological distress, or marital status between the ICU and non-ICU cohorts. Risk for medication nonadherence assessed by parent report was not different between groups. Although previous hospital admission or emergency department visit history did not differ between the groups, prior ICU admission was more common among those admitted to the ICU at the index admission (27 vs. 16%, P = 0.002). Children requiring intensive care admission were more likely to be sensitized to multiple aeroallergens. Exposure to cigarette smoke (measured as salivary cotinine), although a risk factor for hospital admission, was negatively associated with risk of ICU admission. CONCLUSIONS: Social and economic risk factors typically predictive of increased asthma morbidity, including exposure to tobacco smoke, were not associated with ICU admission among a population of children admitted to the hospital for treatment of acute asthma. Intrinsic disease factors, including allergic sensitization, may be more important predictors of ICU admission.
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Asma/epidemiologia , Unidades de Terapia Intensiva , Admissão do Paciente/estatística & dados numéricos , Determinantes Sociais da Saúde , Doença Aguda , Adolescente , Alérgenos/efeitos adversos , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Classe Social , Estados UnidosRESUMO
RATIONALE: Chorioamnionitis is an important cause of preterm birth, but its impact on postnatal outcomes is understudied. OBJECTIVES: To evaluate whether fetal exposure to inflammation is associated with adverse pulmonary outcomes at 6 to 12 months' chronological age in infants born moderate to late preterm. METHODS: Infants born between 32 and 36 weeks' gestational age were prospectively recruited (N = 184). Chorioamnionitis was diagnosed by placenta and umbilical cord histology. Select cytokines were measured in samples of cord blood. Validated pulmonary questionnaires were administered (n = 184), and infant pulmonary function testing was performed (n = 69) between 6 and 12 months' chronological age by the raised volume rapid thoracoabdominal compression technique. MEASUREMENTS AND MAIN RESULTS: A total of 25% of participants had chorioamnionitis. Although infant pulmonary function testing variables were lower in infants born preterm compared with historical normative data for term infants, there were no differences between infants with chorioamnionitis (n = 20) and those without (n = 49). Boys and black infants had lower infant pulmonary function testing measurements than girls and white infants, respectively. Chorioamnionitis exposure was associated independently with wheeze (odds ratio [OR], 2.08) and respiratory-related physician visits (OR, 3.18) in the first year of life. Infants exposed to severe chorioamnionitis had increased levels of cord blood IL-6 and greater pulmonary morbidity at age 6 to 12 months than those exposed to mild chorioamnionitis. Elevated IL-6 was associated with significantly more respiratory problems (OR, 3.23). CONCLUSIONS: In infants born moderate or late preterm, elevated cord blood IL-6 and exposure to histologically identified chorioamnionitis was associated with respiratory morbidity during infancy without significant changes in infant pulmonary function testing measurements. Black compared with white and boy compared with girl infants had lower infant pulmonary function testing measurements and worse pulmonary outcomes.
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Corioamnionite/fisiopatologia , Recém-Nascido Prematuro , Interleucina-6/sangue , Pulmão/fisiopatologia , Adulto , População Negra/estatística & dados numéricos , Feminino , Sangue Fetal/metabolismo , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Análise Multivariada , Ohio , Gravidez , Estudos Prospectivos , Testes de Função Respiratória , Sons Respiratórios/etiologia , Fatores Sexuais , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
A new equine abortigenic disease, mare reproductive loss syndrome (MRLS), was recognized and significantly impacted the Ohio Valley in the springs of 2001 and 2002. MRLS caused approximately 330 million US dollars in losses in 2001. An epidemiological investigation of MRLS associated occurrence of the disease with exposure to eastern tent caterpillars (M. americanum). This work investigates the epidemiological association between M. americanum and MRLS to determine if this association was correlative or causative. A pilot study and simulated exposure to M. americanum and their excreta on pasture grasses. The pilot study advanced exposure of pregnant mares to M. americanum materials and 18 of the 29 mares in the study aborted with symptoms of MRLS before other cases were reported in the region. In, three of seven mares exposed to M. americanum aborted, while mares in control (n=6) and M. americanum frass (n=7) treatments had no losses. In, mares were fed frozen insect larvae in feed buckets mixed with oats. Abortions occurred in three of five mares receiving frozen M. americanum, while mares that were fed autoclaved M. americanum (n=5) or frozen gypsy moth larvae (n=4) had no abortions due to MRLS. In, M. americanum larvae were dissected and fractionated. Statistically significant numbers of abortions occurred only in the positive control group and in association with the M. americanum exoskeleton. All abortions induced by exposure to M. americanum exhibited changes in echogenicity of fetal fluids and bacteriological findings post abortion that were consistent with MRLS. These studies support the hypothesis that ingestion of M. americanum larvae induces the MRLS-type equine abortions, and provide experimental evidence that this lepidopteran larva can cause an abortigenic disease in a vertebrate host.
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Aborto Animal/etiologia , Ração Animal/efeitos adversos , Morte Fetal/etiologia , Contaminação de Alimentos , Cavalos/fisiologia , Mariposas/patogenicidade , Animais , Estrogênios/sangue , Feminino , Larva/patogenicidade , Ohio , Projetos Piloto , Gravidez , Resultado da Gravidez/veterinária , Prenhez/sangue , Progesterona/sangueRESUMO
An epidemiological association among black cherry trees (Prunus serotina), eastern tent caterpillars (Malacosoma americana), and the spring 2001 episode of mare reproductive loss syndrome in central Kentucky focused attention on the potential role of environmental cyanogens in the causes of this syndrome. To evaluate the role of cyanide (CN (-)) in this syndrome, a simple, rapid, and highly sensitive method for determination of low parts per billion concentrations of CN (-) in equine blood and other biological fluids was developed. The analytical method is an adaptation of methods commonly in use and involves the evolution and trapping of gaseous hydrogen cyanide followed by spectrophotometric determination by autoanalyzer. The limit of quantitation of this method is 2 ng/mL in equine blood, and the standard curve shows a linear relationship between CN (-) concentration and absorbance (r >. 99). The method throughput is high, up to 100 samples per day. Normal blood CN (-) concentrations in horses at pasture in Kentucky in October 2001 ranged from 3-18 ng/mL, whereas hay-fed horses showed blood CN (-) levels of 2-7 ng/mL in January 2002. Blood samples from a small number of cattle at pasture showed broadly similar blood CN (-) concentrations. Intravenous administration of sodium cyanide and oral administration of mandelonitrile and amygdalin yielded readily detectable increases in blood CN (-) concentrations. This method is sufficiently sensitive and specific to allow the determination of normal blood CN (-) levels in horses, as well as the seasonal and pasture-dependent variations. The method should also be suitable for investigation of the toxicokinetics and disposition of subacutely toxic doses of CN (-) and its precursor cyanogens in the horse as well as in other species.
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The epidemiological association between black cherry trees and mare reproductive loss syndrome has focused attention on cyanide and environmental cyanogens. This article describes the toxicokinetics of cyanide in horses and the relationships between blood cyanide concentrations and potentially adverse responses to cyanide. To identify safe and humane blood concentration limits for cyanide experiments, mares were infused with increasing doses (1-12 mg/min) of sodium cyanide for 1 h. Infusion at 12 mg/min produced clinical signs of cyanide toxicity at 38 min; these signs included increased heart rate, weakness, lack of coordination, loss of muscle tone, and respiratory and behavioral distress. Peak blood cyanide concentrations were about 2500 ng/mL; the clinical and biochemical signs of distress reversed when infusion stopped. Four horses were infused with 1 mg/min of sodium cyanide for 1 h to evaluate the distribution and elimination kinetics of cyanide. Blood cyanide concentrations peaked at 1160 ng/mL and then declined rapidly, suggesting a two-compartment, open model. The distribution (alpha) phase half-life was 0.74 h, the terminal (beta phase) half-life was 16.16 h. The mean residence time was 12.4 h, the steady-state volume of distribution was 2.21 L/kg, and the mean systemic clearance was 0.182 L/h/kg. Partitioning studies showed that blood cyanide was about 98.5% associated with the red cell fraction. No clinical signs of cyanide intoxication or distress were observed during these infusion experiments. Mandelonitrile was next administered orally at 3 mg/kg to four horses. Cyanide was rapidly available from the orally administered mandelonitrile and the C max blood concentration of 1857 ng/mL was observed at 3 min after dosing; thereafter, blood cyanide again declined rapidly, reaching 100 ng/mL by 4 h postadministration. The mean oral bioavailability of cyanide from mandelonitrile was 57% +/- 6.5 (SEM), and its apparent terminal half-life was 13 h +/- 3 (SEM). No clinical signs of cyanide intoxication or distress were observed during these experiments. These data show that during acute exposure to higher doses of cyanide (~600 mg/horse; 2500 ng/mL of cyanide in blood), redistribution of cyanide rapidly terminated the acute toxic responses. Similarly, mandelonitrile rapidly delivered its cyanide content, and acute cyanide intoxications following mandelonitrile administration can also be terminated by redistribution. Rapid termination of cyanide intoxication by redistribution is consistent with and explains many of the clinical and biochemical characteristics of acute, high-dose cyanide toxicity. On the other hand, at lower concentrations (<100 ng/mL in blood), metabolic transformation of cyanide is likely the dominant mechanism of termination of action. This process is slow, with terminal half-lives ranging from 12-16 hours. The large volume of distribution and the long terminal-phase-elimination half-life of cyanide suggest different mechanisms for toxicities and termination of toxicities associated with low-level exposure to cyanide. If environmental exposure to cyanide is a factor in the cause of MRLS, then it is likely in the more subtle effects of low concentrations of cyanide on specific metabolic processes that the associations will be found.
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Asthma is the most common chronic disorder of childhood and continues to be a leading cause of pediatric hospital admission. The National Asthma Education and Prevention Program (NAEPP) recommends that spirometry be obtained for asthma patients upon hospital admission, after bronchodilation during the acute phase of asthma symptoms, and at least one additional time before discharge from the hospital. The objectives of this study were to describe the use of spirometry in children hospitalized with asthma and to determine association of pulmonary function with future exacerbations. A retrospective cohort study design was utilized involving review of medical records of children ≥5 years old admitted with asthma to Cincinnati Children's Hospital Medical Center from September 1, 2009 to March 31, 2011. Hospitalization or emergency department (ED) visits were identified by the ICD-9-CM codes of having either a primary diagnosis of asthma (493) or a respiratory illness (460-496) plus a secondary diagnosis of asthma. Asthma re-exacerbation was defined as either having an ED visit or hospitalization for asthma that occurred within 3 months after the index hospitalization. All spirometries were performed in a pediatric pulmonary function laboratory. Among 1,037 admissions included in this study, 89 (8.6%) had spirometry that was recommended by a consulting asthma specialist and usually performed on the day of discharge. Spirometries for forty-five of these patients (54.9%) met all acceptability and repeatability criteria of the American Thoracic Society. Patients who performed acceptable spirometry were significantly older (12.4 ± 3.8 vs. 10.7 ± 3.0 years; P = 0.041). The average forced expiratory volume in the first second (FEV1 ) was 84.4 ± 19.7% predicted; forced vital capacity (FVC) was 98.1 ± 16.0% predicted; FEV1 /FVC was 74.6 ± 9.6%; forced expiratory flow at 25-75% (FEF25-75 ) was 61.2 ± 30.1% predicted. Ten patients (22%) who performed spirometry developed a re-exacerbation. Patients with versus without re-exacerbation had significantly lower FEV1 /FVC (P = 0.027) and FEF25-75 (P = 0.031). Nevertheless, separate logistic regression models found that FEV1 /FVC and FEF25-75 were not associated with re-exacerbation when adjusted for age and length-of-stay. We found that few children admitted with asthma had spirometry as recommended in the NAEPP guidelines unless recommended by specialists and both lower lung function (FEV1 /FVC and FEF25-75 ) and history of more frequent and more recent prior health-care utilization for asthma were associated with repeat asthma exacerbation. However, the value of performing spirometry on asthmatic children prior to hospital discharge remains unclear and will require prospective study.
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Asma/diagnóstico , Fidelidade a Diretrizes/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Pulmão/fisiopatologia , Guias de Prática Clínica como Assunto , Adolescente , Fatores Etários , Asma/fisiopatologia , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Tempo de Internação , Modelos Logísticos , Masculino , Fluxo Máximo Médio Expiratório , Estudos Retrospectivos , Espirometria/estatística & dados numéricos , Capacidade VitalRESUMO
The main purpose of the research was to determine if three weekly samplings would produce consistent results for low strongyle egg shedders, generally associated with older horses. Strongyle egg counts per gram of feces (EPG) were done for 661 Thoroughbred mares on 14 farms in 2012-2013 once a week for three consecutive weeks. None of the mares had been treated with ivermectin or moxidectin for more than 90 days and with fenbendazole, oxibendazole, or pyrantel pamoate for more than 60 days. Strongyle EPG count data indicated that 38.3% of the mares were positive at first and second sampling, and 37.8%--at third sampling. There were 5.6-63.3% of horses positive per farm. Correlations between EPG count data in all three weeks are quite high (Rs = 0.84, p<0.001). Level of horse infection was found to be dependent on horse age, type of farm and individual characters of horse. This study documented that strongyle egg counts (EPGs) from individual horses did not differ significantly between weeks. Thus, a single strongyle EPG count can be interpreted as indicative of the level of egg shedding for a given horse. These data support the current trend of not deworming all adult horses on a farm, so that high shedders can be identified and treated. This saves horse owners money and reduces development of potential drug resistance of parasites because of less frequent usage of antiparasitic compounds. Information from this study helps to conclude recommendations for parasite control in horses globally.