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1.
N Engl J Med ; 386(12): 1121-1131, 2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35320643

RESUMO

BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).


Assuntos
Displasia Broncopulmonar/prevenção & controle , Glucocorticoides/uso terapêutico , Hidrocortisona/uso terapêutico , Recém-Nascido Prematuro , Extubação , Displasia Broncopulmonar/epidemiologia , Método Duplo-Cego , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/efeitos adversos , Lactente Extremamente Prematuro , Recém-Nascido , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Oxigenoterapia , Respiração Artificial
2.
Bioorg Chem ; 150: 107615, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38986420

RESUMO

A series of stilbene analogues, in which a phenyl ring was replaced by the pyridazin-3(2H)-one nucleus, was designed and synthesized to be explored as platelet aggregation inhibitors. The proposed stilbene-pyridazinone hybrids were successfully obtained from simple starting materials and by Wittig's reaction. Most of the target compounds displayed improved in vitro activity in comparison with the standard drug, resveratrol, highlighting as the most potent the analogues 10d and 10e, with inhibition percentages of 94.15 % at 100 µM and 100 % at 50 µM, respectively. The pharmacokinetic and toxicity (ADME/T) properties of the novel hybrids were also estimated with the SwissADME and ProTox-II web servers.


Assuntos
Desenho de Fármacos , Inibidores da Agregação Plaquetária , Agregação Plaquetária , Piridazinas , Estilbenos , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/síntese química , Piridazinas/química , Piridazinas/farmacologia , Piridazinas/síntese química , Estilbenos/química , Estilbenos/farmacologia , Estilbenos/síntese química , Relação Estrutura-Atividade , Humanos , Estrutura Molecular , Agregação Plaquetária/efeitos dos fármacos , Relação Dose-Resposta a Droga
3.
Pediatr Blood Cancer ; 70(1): e29980, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36069612

RESUMO

BACKGROUND: Screening for pulmonary hypertension (PHT) is recommended in children with sickle cell disease (SCD). However, best approaches are poorly described. We examined the utility of PHT symptoms, echocardiogram (ECHO), N-terminal-pro hormone brain natriuretic peptide (NT-proBNP), and BNP to screen for PHT in the SCD pediatric population. METHODS: Children (8-18 years old) with SCD-HbSS and HbSthal° were prospectively included and underwent PHT screening. The screening consisted of a comprehensive PHT symptoms evaluation, ECHO measurement, and NT-proBNP and BNP levels. RESULTS: A total of 73 patients were included (mean age 12 ± 5.7 years; >80% on hydroxyurea), of which 37% had a symptom consistent with PHT, including exertional dyspnea (26.5%), fatigue (17.6%), palpitation (14.7%), and chest pain (10.3%). ECHO was obtained in 53 (72.6%) patients, with only ECHO of 48 patients included in the final analysis. Elevated ECHO peak tricuspid regurgitant jet velocity (TRV) >2.5 m/s or indirect findings to suggest PHT were seen in only two of 48 (4.2%). No significant differences were seen between those with and without PHT symptoms when compared for NT-proBNP, BNP, hemoglobin, pulmonary function testing, fractional exhaled nitric oxide, asthma, oxygen saturation, and sleep apnea. CONCLUSION: PHT symptoms are not consistent with ECHO, NT-proBNP nor BNP findings in children with SCD. PHT prevalence based on TRV was low in children on hydroxyurea, therefore screening may not be warranted for this group.


Assuntos
Anemia Falciforme , Hipertensão Pulmonar , Criança , Humanos , Adolescente , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/epidemiologia , Hidroxiureia/uso terapêutico , Anemia Falciforme/epidemiologia , Fragmentos de Peptídeos , Testes de Função Respiratória , Prevalência
4.
J Pediatr Gastroenterol Nutr ; 76(1): 59-65, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36574003

RESUMO

OBJECTIVES: Eosinophilic esophagitis (EoE) is a chronic disease which requires endoscopy with biopsies for diagnosis and monitoring. We aimed to identify a panel of non-invasive markers that could help identify patients with active EoE. METHODS: In this prospective cohort study, we enrolled 128 children aged 5-18 years old, scheduled for endoscopy for suspected esophageal or peptic disease. On the day of the endoscopy, fractionated exhaled nitric oxide (FeNO) was measured; and blood was collected for peripheral absolute eosinophil count (AEC), plasma amino acids, and plasma polyamine analysis. Patients were grouped into controls (n = 91), EoE in remission (n = 16), or active EoE (n = 21), based on esophageal eosinophilia and history of EoE. RESULTS: AEC was not statistically significant different among the groups compared ( P = 0.056). Plasma amino acids: citrulline (CIT), ß-alanine (ß-ALA), and cysteine (CYS) were higher in active EoE compared to controls ( P < 0.05). The polyamine spermine was lower in active EoE versus controls ( P < 0.05). Receiver operator characteristic (ROC) curve to assess the predictive capability of a combined score made of FeNO, ß-ALA, CYS, and spermine had an area under curve (AUC) of 0.90 (95% CI: 0.80-0.96) in differentiating active EoE from controls and 0.87 (95% CI: 0.74-1.00) when differentiating active EoE from EoE in remission. CONCLUSION: A panel comprising FeNO, 2 plasma amino acids (ß-ALA, CYS) and the polyamine spermine can be used as a non-invasive tool to differentiate active EoE patients from controls.


Assuntos
Esofagite Eosinofílica , Criança , Humanos , Pré-Escolar , Adolescente , Esofagite Eosinofílica/patologia , Teste da Fração de Óxido Nítrico Exalado , Estudos Prospectivos , Espermina , Biomarcadores , Aminoácidos , Eosinófilos/metabolismo
5.
J Asthma ; 60(9): 1787-1792, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36867136

RESUMO

BACKGROUND: Asthma in preschool children is poorly defined, proving to be a challenge for early detection. The Breathmobile Case Identification Survey (BCIS) has been shown to be a feasible screening tool in older SCD children and could be effective in younger children. We attempted to validate the BCIS as an asthma screening tool in preschool children with SCD. METHODS: This is a prospective, single-center study of 50 children aged 2-5 years with SCD. BCIS was administered to all patients and a pulmonologist blinded to the results evaluated patients for asthma. Demographic, clinical, and laboratory data were obtained to assess risk factors for asthma and acute chest syndrome in this population. RESULTS: Asthma prevalence (n = 3/50; 6%) was lower than atopic dermatitis (20%) and allergic rhinitis (32%). Sensitivity (100%), specificity (85%), positive predictive value (30%), and negative predictive value (100%) of the BCIS were high. Clinical demographics, atopic dermatitis, allergic rhinitis, asthma, viral respiratory infection, hematology parameters, sickle hemoglobin subtype, tobacco smoke exposure, and hydroxyurea were not different between patients with or without history of ACS, although eosinophil was significantly lower in the ACS group (p = 0.0093). All those with asthma had ACS, known viral respiratory infection resulting in hospitalization (3 RSV and 1 influenza), and HbSS (homozygous Hemoglobin SS) subtype. CONCLUSION: The BCIS is an effective asthma screening tool in preschool children with SCD. Asthma prevalence in young children with SCD is low. Previously known ACS risk factors were not seen, possibly from the beneficial effects of early life initiation of hydroxyurea.


Assuntos
Anemia Falciforme , Asma , Dermatite Atópica , Rinite Alérgica , Humanos , Pré-Escolar , Idoso , Asma/diagnóstico , Asma/epidemiologia , Asma/etiologia , Hidroxiureia , Estudos Prospectivos , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Rinite Alérgica/complicações
6.
BMC Pulm Med ; 23(1): 156, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37143026

RESUMO

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an underrecognized genetic disorder associated mainly with pulmonary emphysema and Chronic Obstructive Pulmonary Disease (COPD). All individuals with COPD regardless of age or ethnicity should be tested for AATD, but in Colombia its prevalence in unknown. MAIN OBJECTIVE: To determine the prevalence of the genetic mutations, present in AATD in adult patients with COPD in Colombia, using a genotyping test on cells from the oral mucosa. METHODS: This was a multicentre, observational, cross-sectional study which included adult patients attending seven COPD care centres in Colombia. Demographic data, medical history, including history of exposure to smoking and biomass smoke, most recent spirometry, pharmacological and non-pharmacological treatment received, serum AAT levels, and mutations detected by the genotyping test were recorded for all the recruited patients. For the comparison of variables between the groups with and without mutation, we used the X2 test for the qualitative variables and the Student's t-test or Mann-Whitney U test according to their distribution. MAIN FINDINGS: We collected a sample of 1,107 patients, the median age was 73.8 years (87.6-79.9). Mutations were documented in 144 patients (13.01%), the majority had the M/S mutation (78.50%), followed by M/Z (9.72%). One patient had a ZZ mutation and two patients had null alleles. In total, 23 patients had mutations associated with serum AAT deficiency (levels below 60 mg/dl). CONCLUSIONS: Genetic mutations were documented in 13.01% of patients with COPD in Colombia and 2.07% were AATD-related, showing that there is a significant number of underdiagnosed patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Deficiência de alfa 1-Antitripsina , Idoso , Humanos , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/complicações , Deficiência de alfa 1-Antitripsina/epidemiologia , Deficiência de alfa 1-Antitripsina/genética , Colômbia/epidemiologia , Estudos Transversais , Mutação , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Idoso de 80 Anos ou mais
7.
Int J Mol Sci ; 24(3)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36768259

RESUMO

The radial spoke head protein 4 homolog A (RSPH4A) gene is one of more than 50 genes that cause Primary ciliary dyskinesia (PCD), a rare genetic ciliopathy. Genetic mutations in the RSPH4A gene alter an important protein structure involved in ciliary pathogenesis. Radial spoke proteins, such as RSPH4A, have been conserved across multiple species. In humans, ciliary function deficiency caused by RSPH4A pathogenic variants results in a clinical phenotype characterized by recurrent oto-sino-pulmonary infections. More than 30 pathogenic RSPH4A genetic variants have been associated with PCD. In Puerto Rican Hispanics, a founder mutation (RSPH4A (c.921+3_921+6delAAGT (intronic)) has been described. The spectrum of the RSPH4A PCD phenotype does not include laterality defects, which results in a challenging diagnosis. PCD diagnostic tools can combine transmission electron microscopy (TEM), nasal nitric oxide (nNO), High-Speed Video microscopy Analysis (HSVA), and immunofluorescence. The purpose of this review article is to provide a comprehensive overview of current knowledge about the RSPH4A gene in PCD, ranging from basic science to human clinical phenotype.


Assuntos
Síndrome de Kartagener , Humanos , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/genética , Cílios/metabolismo , Proteínas/metabolismo , Mutação , Axonema/metabolismo , Proteínas do Citoesqueleto/metabolismo
8.
J Pediatr Hematol Oncol ; 44(7): 354-357, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35383664

RESUMO

BACKGROUND: Screening for obstructive sleep apnea (OSA) is recommended by current guidelines in children with sickle cell anemia (SCA), but no specific approach is described. The Pediatric Sleep Questionnaire (PSQ) is a validated detection tool for OSA in children. We assessed the utility of PSQ to screen for OSA in children with concomitant SCA and snoring. MATERIALS AND METHODS: A prospective study, in children 4 to 18 years old with SCA. Subjects were assessed for snoring and PSQ administered at the same visit. All children with snoring were then referred for polysomnography. RESULTS: A total of 106 subjects were screened. Habitual snoring prevalence was 51/106 (48.1%). In the snoring group, OSA was detected in 83.9% (apnea-hypopnea index [AHI] ≥1.0/h) and 22.6% (AHI ≥5.0/h), respectively. Sensitivity and specificity of PSQ in children with snoring was 46.2% and 20.0% (AHI ≥1.0/h), and 57.1% and 50.0% (AHI ≥5.0/h), respectively. Physician assessment for snoring had a high sensitivity of 70.3% but low specificity of 58.4% (AHI ≥1.0/h), and 87.5% and 41.5% (AHI ≥5.0/h), respectively. CONCLUSION: PSQ is a poor screening tool for detection of OSA in those children with SCA who snore. Physician assessment for snoring could however be an initial approach before polysomnography.


Assuntos
Anemia Falciforme , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Adolescente , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Criança , Pré-Escolar , Humanos , Estudos Prospectivos , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/etiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Ronco/diagnóstico , Ronco/epidemiologia , Ronco/etiologia
9.
J Asthma ; 58(5): 596-603, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-31994954

RESUMO

Objective: To assess whether an asthma intervention program reduces treatment days outside the home among children with severe asthma receiving comprehensive care (CC) in our center.Methods: Between October 21, 2014 and September 28, 2016, children with severe asthma were randomized to receive CC alone (n = 29) or CC plus the asthma intervention program (n = 34) which involved collaboration with pharmacists and school nurses, motivational interviewing, and tracking the one-second forced expiratory volume at home. All patients were followed through March 31, 2017. Frequentist and Bayesian intent-to-treat analyses were performed.Results: The asthma intervention program doubled the telephone calls between the staff and families (753 vs 356 per 100 child years for the intervention group vs. control group; Rate Ratio [RR], 2.11 [95% confidence interval, 1.29-3.45]). Yet, we found no evidence that it reduced the composite number of days of healthcare outside home which includes: clinic visits, ED visits, and hospital admissions (1179 vs 958 per 100 child-years in the intervention group vs. control group; [RR], 1.23 [95% CI, 0.82-1.84]) or secondary outcomes which are individual components (clinic visits, ED visits, hospitalizations, PICU admissions and school absences; RR 1.15 - 2.30; p > 0.05). Bayesian analysis indicated a 67% probability that the intervention program increases total treatment days outside the home and only a 14% probability of a true decrease of >20% as originally hypothesized.Conclusion: A multi-component intervention program provided to children with severe asthma failed to reduce and may have increased days of healthcare outside home and school absenteeism.


Assuntos
Asma/terapia , Adesão à Medicação , Absenteísmo , Adolescente , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Asma/fisiopatologia , Criança , Pré-Escolar , Comunicação , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Volume Expiratório Forçado , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Motivação , Equipe de Assistência ao Paciente , Avaliação de Programas e Projetos de Saúde , Melhoria de Qualidade , Testes de Função Respiratória
10.
J Asthma ; 58(6): 782-790, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32160791

RESUMO

Background: Asthma is a chronic airway disorder with variable/recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an inflammation. The expert panel report of the National Heart Lung and Blood Institute recommends asthma screening in sickle cell disease (SCD); however, specific approach is not mentioned. We hypothesize that the breathmobile case identification survey (BCIS) is a valid asthma screening tool in children with SCD.Methods: This prospective, single-center study enrolled 129 SCD patients aged 5 to 18 years from March 2016 to March 2018. All patients completed BCIS, spirometry, and fractional exhaled nitric oxide (FeNO). A single pulmonologist blinded to the BCIS results evaluated patients for asthma.Results: Asthma prevalence was 41%. Male gender (60.4%; p = 0.041), allergic rhinitis (86.8%; p < 0.01), hydroxyurea usage (73.6%; p < 0.01), and family history of asthma (34%; p < 0.01) were higher but not self-reported parental asthma history, eczema, and tobacco smoke exposure in the asthma group compared to the nonasthma group. FEV1 (p = 0.003), FVC (p = 0.02), FEV1/FVC (p = 0.053), and FEF25-75% (p = 0.02) were lower in asthma. FeNO levels were comparable in both groups. The sensitivity, specificity, positive predictive value, and negative predictive value of the abbreviated BCIS were 67.3%, 90.8%, 83.3%, and 80.2% for asthma; and 82.1%, 90.8%, 76.7%, and 93.2% for persistent asthma, respectively. Persistent asthma patients had a trend of higher hydroxyurea use (82.8% vs. 58.3%; p = 0.049) and tobacco smoke exposure (55.2% vs. 29.2%; p = 0.057) compared to intermittent asthma.Conclusion: We have validated the BCIS to screen for asthma in SCD. Spirometry but not FeNO may support an asthma diagnosis.


Assuntos
Anemia Falciforme/epidemiologia , Asma/diagnóstico , Asma/epidemiologia , Programas de Rastreamento/métodos , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Hidroxiureia/administração & dosagem , Masculino , Programas de Rastreamento/normas , Anamnese , Prevalência , Estudos Prospectivos , Testes de Função Respiratória , Rinite Alérgica/epidemiologia , Índice de Gravidade de Doença , Fatores Sexuais , Inquéritos e Questionários/normas , Poluição por Fumaça de Tabaco/estatística & dados numéricos
11.
Ann Hematol ; 99(4): 877-884, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32062742

RESUMO

Autologous stem cell transplant (ASCT) is a widely used and safe procedure to treat mostly hematologic diseases. These patients are at risk of infectious complications, which represents a major cause of morbidity and it is the second cause of mortality. This retrospective 12-year analysis of the incidence, type, and severity of infections in 266 consecutive unselected ASCT patients at our institution provides novel information addressing this issue. We included 266 ASCT procedures. Patients included in the 2006-2013 period are referred to as group 1 (ciprofloxacin prophylaxis and ceftazidime-amikacin as empirical antibiotics), and those in the 2013-2017 period are group 2 (levofloxacin prophylaxis and meropenem as empirical antibiotics). The incidence of febrile neutropenia was 72% in group 1 and 86.2% in group 2 (p = 0.004). The majority of infectious episodes were associated with fever of unknown origin: 55% in group 1 and 59% in group 2. Febrile of unknown origin episodes were 82.6% in group 1 and 80% in group 2. Significant differences between both groups were found in age, hypogammaglobulinemia, and advanced disease at ASCT. No differences were found between groups regarding the most common agent documented in positive blood cultures (Gram+ were 66.6% in group 1 and 69% in group 2 (p = 0.68)). Mortality within 100 days of transplant was low, 1.87%. Regardless of the prophylactic regimen used, most patients experience febrile episodes in the ASCT setting, fever of unknown origin is the most common infection complication, and Gram+ agents are prevalent in both groups. Mortality rates were low. According to our results, ASCT is a safe procedure and there is no clear benefit in favor of levofloxacin versus ciprofloxacin prophylaxis. Both anti-infectious approaches are acceptable, yielding similar outcomes.


Assuntos
Antibioticoprofilaxia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bacteriemia/prevenção & controle , Neutropenia Febril/prevenção & controle , Adolescente , Adulto , Idoso , Amicacina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bacteriemia/etiologia , Ceftazidima/uso terapêutico , Ciprofloxacina/uso terapêutico , Neutropenia Febril/induzido quimicamente , Feminino , Febre de Causa Desconhecida/prevenção & controle , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/terapia , Humanos , Incidência , Levofloxacino/uso terapêutico , Masculino , Meropeném/uso terapêutico , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/métodos , Estudos Retrospectivos , Transplante Autólogo , Uruguai , Adulto Jovem
12.
Pulm Pharmacol Ther ; 61: 101898, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31978547

RESUMO

INTRODUCTION: Long-acting bronchodilators are the therapy with the best evidence for treating stable chronic obstructive pulmonary disease (COPD). Long-acting combinations of ß2 agonists and anticholinergics (LABA-LAMA) are recommended in advanced stages when monotherapy has not generated the desired effects. Pulmonary Rehabilitation (PR) is an effective non-pharmacological strategy. The aim of this study was to compare the results obtained in patients with COPD who received monotherapy versus dual bronchodilator therapy in terms of functional aerobic capacity, symptoms and quality of life. MATERIALS AND METHODS: Prospective non randomized intervention study; the patients were divided into two groups: in one group patients were treated with LAMA (Tiotropium Bromide, 5 µg every 24 h) and in the other group patients were treated with LABA + LAMA (Indacaterol/Glycopyrronium, 110/50 µg once a day). After receiving the concept of pulmonology, patients were intervened with 8 weeks of PR. The study was approved by the committee of the Clinica Neumológica del Pacifico in Cali and the Institución Universitaria Escuela Nacional del Deporte, Colombia. To determine the differences, t pair test for intragroup, and t-test was performed for intergroup analysis. For all tests, a p-value <0.05 was considered as statistically significant. RESULTS: 53 patients participated in this study, of which 20 were assigned to the LAMA group and 33 to the LAMA + LABA group. Patients in both groups presented changes in the distance of the 6MWT, in the VO2e, dyspnea and in all the SGRQ domains. Regarding the comparison between groups, there were found no differences in the variables at the beginning of the PR and significant differences (p < 0.05) at the end of the 8 week-period in favor of the LABA + LAMA group, in symptoms with the mMRC scale, functional aerobic capacity with the 6 min walking test and in health related quality of life specifically in the symptoms domain, where the dual therapy group obtained better results. CONCLUSION: The addition of LABA to the treatment with LAMA showed better response results compared with the monotherapy in patients with COPD who attended PR.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/administração & dosagem , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Glicopirrolato/uso terapêutico , Humanos , Indanos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Estudos Prospectivos , Quinolonas/uso terapêutico , Brometo de Tiotrópio/uso terapêutico
13.
BMC Pediatr ; 20(1): 194, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375736

RESUMO

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by respiratory system abnormalities, including alveolar hypoventilation and autonomic nervous system dysregulation. CCHS is associated with compromised brain development and neurocognitive functioning. Studies that evaluate cognitive skills in CCHS are limited, and no study has considered cognitive abilities in conjunction with psychosocial and adaptive functioning. Moreover, the roles of pertinent medical variables such as genetic characteristics are also important to consider in the context of neurocognitive functioning. METHODS: Seven participants with CCHS ranging in age from 1 to 20 years underwent neuropsychological evaluations in a clinic setting. RESULTS: Neurocognitive testing indicated borderline impaired neurocognitive skills, on average, as well as relative weaknesses in working memory. Important strengths, including good coping skills and relatively strong social skills, may serve as protective factors in this population. CONCLUSION: CCHS was associated with poor neurocognitive outcomes, especially with some polyalanine repeat expansion mutations (PARMS) genotype. These findings have important implications for individuals with CCHS as well as medical providers for this population.


Assuntos
Hipoventilação , Apneia do Sono Tipo Central , Adolescente , Adulto , Criança , Pré-Escolar , Proteínas de Homeodomínio/genética , Humanos , Hipoventilação/congênito , Hipoventilação/genética , Lactente , Mutação , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/genética , Fatores de Transcrição/genética , Adulto Jovem
14.
J Pediatr ; 206: 232-239.e3, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30522751

RESUMO

OBJECTIVE: To assess the sustainability of the benefits relative to usual care of a medical home providing comprehensive care for high-risk children with medical complexity (≥2 hospitalizations or ≥1 pediatric intensive care unit [PICU] admission in the year before enrollment) after we made comprehensive care our standard practice and expanded the program. STUDY DESIGN: We conducted pre-post comparisons of the rate of children with serious illness (death, PICU admission, or >7-day hospitalization) and health-system costs observed after program expansion (March 2014-June 2015) to those during the clinical trial (March 2011-August 2013) for each of the trial's treatment groups (usual care, n = 96, and comprehensive care, n = 105; primary analyses), and among all children given comprehensive care (nPost-trial = 233, including trial usual care children who transitioned to comprehensive care post-trial and newly enrolled medically complex children, and nTrial = 105; secondary analyses). We also analyzed the findings for the trial patients as a 2-phase stepped-wedge study. RESULTS: In intent-to-treat analyses, rates of children with serious illness and costs were reduced or unchanged post-trial vs trial for the trial's usual care group (rate ratio [RR], 0.36; 95% CI, 0.20-0.64; cost ratio [CR], 0.68; 95% CI, 0.28-1.68), the trial's comprehensive care group (RR, 0.74; 95% CI, 0.39-1.41; CR, 0.67; 95% CI, 0.51-0.89), and among all children given comprehensive care (RR, 0.97; 95% CI, 0.61-1.52; CR, 0.75; 95% CI, 0.61-0.93). Conservative stepped-wedge analyses identified overall benefits with comprehensive care across both study periods (RR, 0.46; 95% CI, 0.30-0.72; CR, 0.64; 95% CI, 0.43-0.99). CONCLUSIONS: Major benefits of comprehensive care did not diminish with post-trial program expansion.


Assuntos
Assistência Integral à Saúde , Cuidados Críticos , Estado Terminal , Custos de Cuidados de Saúde , Assistência Centrada no Paciente , Avaliação de Programas e Projetos de Saúde , Criança , Feminino , Hospitalização , Humanos , Masculino
15.
J Pediatr ; 214: 113-120.e1, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31540760

RESUMO

OBJECTIVES: To evaluate factors associated with admission from emergency department (ED) encounters for children with medical complexity (CMC) and to quantify the hospital admission rate as well as variation in adjusted hospital admission rates across EDs. STUDY DESIGN: Retrospective study of 271 806 visits to 37 EDs in freestanding children's hospitals from January 1, 2014, to June 30, 2017, for patients of all ages with a complex chronic condition. Associations between patient demographic, clinical, and health services characteristics and the likelihood of hospital admission were identified using generalized linear models, which were then used to calculate adjusted hospital admission rates. RESULTS: Hospital admission occurred with 25.7% of ED visits. Characteristics with the greatest aOR of hospitalization were ≥3 compared with 0 prior hospitalizations in 365 days (4.7; 95% CI, 4.5-4.9), ED arrival overnight compared with during workday 3.2 (95% CI, 3.1-3.3)], and ≥6 vs 0-1 chronic conditions (1.6; 95% CI, 1.5-1.6). Adjusted hospital admission rates varied significantly (P < .001) across EDs (21.1% [10th percentile]) and 30.0% [90th percentile]). Significant variation remained when excluding low-intensity ED visits, excluding hospitalizations requiring surgery and/or intensive care, or restricting the cohort to overnight ED arrival and to children with ≥3 prior hospitalizations. CONCLUSIONS: CMC are frequently admitted from the ED. Substantial variation in CMC hospital admission rates across EDs exists after case-mix adjustment.


Assuntos
Doença Crônica/terapia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Multimorbidade , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
16.
Molecules ; 24(1)2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30609677

RESUMO

The high sensitivity of chiroptical responses to conformational changes and supramolecular interactions has prompted an increasing interest in the development of chiroptical applications. However, prediction of and understanding the chiroptical responses of the necessary large systems may not be affordable for calculations at high levels of theory. In order to facilitate the development of chiroptical applications, methodologies capable of evaluating the chiroptical responses of large systems are necessary. The exciton chirality method has been extensively used for the interaction between two independent chromophores through the Davydov model. For systems presenting C2 or D2 symmetry, one can get the same results by applying the selection rules. In the present article, the analysis of the selection rules for systems with symmetries Cn and Dn with n = 3 and 4 is used to uncover the origin of their chiroptical responses. We foresee that the use of the Chiroptical Symmetry Analysis (CSA) for systems presenting the symmetries explored herein, as well as for systems presenting higher symmetries will serve as a useful tool for the development of chiroptical applications.


Assuntos
Modelos Teóricos , Algoritmos , Dicroísmo Circular
17.
Inorg Chem ; 56(4): 2124-2134, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-28134513

RESUMO

In order to better understand the epoxide-formation step of the Sharpless epoxidation process, a set of 263 oxygen-transfer reactions reflecting the complexity of the Sharpless epoxidation process were studied using density functional theory (DFT) and Bader's quantum theory of atoms in molecules (QTAIM). The diversity within these reactions reflects the different ligands in the coordination sphere of vanadium and also different substrates (alkene and an allylic alcohol both free and in the form of an alcoxo ligand). The transition states for 76 of these reactions were also characterized using DFT and QTAIM, allowing for an estimation of the impact of the different ligands and substrates on the activation barriers. A smaller subset of the latter was further subjected to an ab initio molecular dynamics (AIMD) simulation coupled to QTAIM analysis. The results show that the type of active catalyst plays an important role in the thermodinamic outcome of these reactions, with vanadium(V) tert-butylhydroperoxide adducts being responsible for the most exoenergetic reactions. On the other hand, the different ligands tested play only a limited role in modulating the thermodynamics and kinetics of these reactions. Moreover, no evidence was found to support a thermodynamic or kinetic preference for the epoxidation of an allylic alcohol over that of an unfunctionalized alkene. However, the results suggest that the reaction path is strongly influenced by the orientation of the substrate upon approximation to the active catalyst, confirming the well-known regioselectivity of the Sharpless epoxidation process.

18.
Chemphyschem ; 17(17): 2666-71, 2016 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-27197944

RESUMO

Despite the fact that transferability and chemistry go hand in hand, transferability studies in electronically excited states (EESs) are normally omitted, although these states are becoming extremely important in modern processes and applications. In this work, it is shown that this kind of studies can be used to understand how substituent effects can be modified in EESs. Thus, for example, the analysis of the carbonyl oxygen transferability in different HCO-R molecules allowed us to find that the nO→πCO* excitation can be used to break the π conjugation associated to the resonance substituent effect. Moreover, as a direct consequence, the oxygen transferability is enhanced in the first electronically excited state.

19.
Inorg Chem ; 55(7): 3653-62, 2016 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-26974465

RESUMO

The possibility of linkage isomerism in a number of vanadium(IV) and vanadium(V) complexes with acetate was surveyed using Density Functional Theory (DFT) and Bader's Quantum Theory of Atoms in Molecules (QTAIM). The results show that vanadium-acetate linkages may be classified as bidentate symmetrical, bidentate asymmetrical, or monodentate, the latter being observed in about 40% of the cases. These latter ones correspond to situations where the two oxygen atoms of the acetate moiety are not equivalent. They are associated with an energy penalty of about 263 kJ·mol(-1), as determined by the distribution of the scaled kinetic energy of the atomic basins forming the acetate ligand. In the presence of bidentate symmetrical vanadium-acetate linkages, the inner valence-shell charge concentrations on the vanadium atom deviate from the traditional VSEPR-derived arrangement, with an energy penalty of about 780 kJ·mol(-1). A compromise situation is partially accomplished in the case of bidentate asymmetrical linkages, which allow a Gillespiean-like arrangement of the inner valence-shell charge concentrations. In this case, one of these local charge concentrations lies close to a V-OAcO bond, which slightly disrupts the equivalence between the two oxygen atoms in the acetate ligand.

20.
Phys Chem Chem Phys ; 17(11): 7424-34, 2015 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-25703955

RESUMO

A method based on a real space partitioning to measure the importance of Lewis structures is proposed in this work. A matrix containing diverse QTAIM atomic and diatomic properties endowed with significance within a Lewis structure framework is expanded in terms of what we call Lewis-structure matrices. Each of these matrices flawlessly describes an individual resonance structure and its associated linear expansion coefficient (Q-ALE coefficient) indicates the importance or convenience of the given Lewis structure. These coefficients were inspected looking at their evolution in a series of usual chemical issues. Among all the results, we find of interest that σ resonance structures in systems with π electrons are more important than normally expected, which justifies why the qualitative predictions arising from the application of the resonance model and the quantitative results based on QTAIM properties are sometimes discrepant. Likewise, we observe that the variation of the dielectric constant of the medium affects the π resonance to a greater extent than it does the σ one. Other interesting results in this manuscript are connected to homolytic dissociation of diatomic molecules, periodic trends in hydrogen compounds, and polarization of aromatic systems as a consequence of their interaction with electric fields and with diverse ions.

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