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1.
Biometrics ; 80(1)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38465989

RESUMO

Computing the agreement between 2 continuous sequences is of great interest in statistics when comparing 2 instruments or one instrument with a gold standard. The probability of agreement quantifies the similarity between 2 variables of interest, and it is useful for determining what constitutes a practically important difference. In this article, we introduce a generalization of the PA for the treatment of spatial variables. Our proposal makes the PA dependent on the spatial lag. We establish the conditions for which the PA decays as a function of the distance lag for isotropic stationary and nonstationary spatial processes. Estimation is addressed through a first-order approximation that guarantees the asymptotic normality of the sample version of the PA. The sensitivity of the PA with respect to the covariance parameters is studied for finite sample size. The new method is described and illustrated with real data involving autumnal changes in the green chromatic coordinate (Gcc), an index of "greenness" that captures the phenological stage of tree leaves, is associated with carbon flux from ecosystems, and is estimated from repeated images of forest canopies.


Assuntos
Ecossistema , Florestas , Probabilidade , Tamanho da Amostra
2.
Eur Respir J ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331459

RESUMO

BACKGROUND: Long COVID impacts ∼10% of people diagnosed with COVID-19, yet the pathophysiology driving ongoing symptoms is poorly understood. We hypothesised that 129Xe magnetic resonance imaging (MRI) could identify unique pulmonary phenotypic subgroups of long COVID, therefore we evaluated ventilation and gas exchange measurements with cluster analysis to generate imaging-based phenotypes. METHODS: COVID-negative controls and participants who previously tested positive for COVID-19 underwent 129XeMRI ∼14-months post-acute infection across three centres. Long COVID was defined as persistent dyspnea, chest tightness, cough, fatigue, nausea and/or loss of taste/smell at MRI; participants reporting no symptoms were considered fully-recovered. 129XeMRI ventilation defect percent (VDP) and membrane (Mem)/Gas, red blood cell (RBC)/Mem and RBC/Gas ratios were used in k-means clustering for long COVID, and measurements were compared using ANOVA with post-hoc Bonferroni correction. RESULTS: We evaluated 135 participants across three centres: 28 COVID-negative (40±16yrs), 34 fully-recovered (42±14yrs) and 73 long COVID (49±13yrs). RBC/Mem (p=0.03) and FEV1 (p=0.04) were different between long- and COVID-negative; FEV1 and all other pulmonary function tests (PFTs) were within normal ranges. Four unique long COVID clusters were identified compared with recovered and COVID-negative. Cluster1 was the youngest with normal MRI and mild gas-trapping; Cluster2 was the oldest, characterised by reduced RBC/Mem but normal PFTs; Cluster3 had mildly increased Mem/Gas with normal PFTs; and Cluster4 had markedly increased Mem/Gas with concomitant reduction in RBC/Mem and restrictive PFT pattern. CONCLUSION: We identified four 129XeMRI long COVID phenotypes with distinct characteristics. 129XeMRI can dissect pathophysiologic heterogeneity of long COVID to enable personalised patient care.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38318929

RESUMO

The extreme low humidity and temperatures in Antarctica make it one of the harsher areas for life on our planet. In a global change context, environmental barriers that prevented the arrival of alien species in Antarctica are weakening. Deception Island, one of the four active volcanoes of Antarctica, is especially vulnerable to the impacts of alien species. Geothermal areas (GA) in this Island offer unique microclimatic conditions that could differentially affect native and alien soil arthropods. Here we explore the desiccation tolerance of a native (Cryptopygus antarcticus) and an alien (Proisotoma minuta) springtail (Collembola) species to these extreme environmental conditions. GA and non-geothermal areas (NGA) were selected to evaluate intra- and interspecific variation in desiccation tolerance. Populations of P. minuta from GA had greater desiccation tolerance than populations from NGA. However, desiccation tolerance of C. antarcticus did not differ between GA and NGA. This native species had greater desiccation tolerance than the alien P. minuta, but also greater body size. Our findings show that the alien P. minuta responds differently to environmental conditions than the native C. antarcticus. Furthermore, body size may influence desiccation tolerance in these two springtail species.

5.
Head Neck ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38344932

RESUMO

INTRODUCTION: Clinical trials on tyrosine kinase inhibitors (TKI) treatment have shown an improvement in overall and progression-free survival in patients with advanced differentiated thyroid cancer. However, it is necessary to evaluate these studies to assess methodological biases and inconsistencies that may impact the effects. OBJECTIVE: To map and assess the methodological quality of randomized clinical trials (RCTs) regarding randomization, allocation concealment, blinding, and selective reporting bias. METHODS: RCTs assessing the efficacy and safety of TKI for the treatment of advanced differentiated thyroid cancer were included. The search was performed in the MEDLINE database. The included RCTs were assessed for the adequacy of the methodological steps, as recommended by the Cochrane Risk of Bias tool. RESULTS: Nine studies were analyzed, of which 77.7% were classified as low risk of bias regarding selective reporting and 33.3% as high risk of reporting bias. The mean time between protocol registration and study publication was approximately 5.11 years. Moreover, 66.7% were classified as low risk of bias for randomization and allocation concealment, and 33.3% did not specify the randomization process and allocation concealment in a way that would allow the identification of occurrences of bias. Concerning blinding of participants and outcome assessors, 77.8% of the RCTs reported adequate blinding and were classified as having a low risk of bias, 11.1% had a high risk of bias, and 11.1% had insufficient information and were classified as having unclear risk of bias. Regarding the blinding of the outcome assessors, 33.3% did the blinding correctly, 11.1% did not blind, and 55.6% did not provide enough information. CONCLUSION: Overall, the assessed RCTs were predominantly at low risk of bias. The critical evaluation of these studies is essential to have confidence in the treatment estimated effect that will support clinical decision-making and provide information to preclude future clinical study flaws.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38237675

RESUMO

BACKGROUND: Early life respiratory syncytial virus (RSV) bronchiolitis is a significant risk factor for childhood asthma. In vitro and in vivo studies suggested that decreasing levels of airway matrix metalloproteinase (MMP)-9 during RSV bronchiolitis may be associated with clinical benefits. OBJECTIVE: To investigate whether azithromycin therapy during severe RSV bronchiolitis reduces upper airway MMP-9 levels, whether upper airway MMP-9 levels correlate with upper airway interleukin IL-8 levels, and whether MMP-9 level reduction is associated with reduced post-RSV recurrent wheeze (RW). METHODS: A total of 200 otherwise healthy 1- to 18-month-old infants hospitalized with RSV bronchiolitis were randomized into a double-blind, placebo-controlled trial of oral azithromycin (10 mg/kg daily for 7 days followed by 5 mg/kg daily for 7 days) or placebo. Infants were followed for 2 to 4 years for the outcome of RW (3 or more wheezing episodes). Nasal lavage samples for MMP-9 levels were obtained at baseline, day 14 (end of the study treatment), and after 6 months. RESULTS: Upper airway MMP-9 levels were highly correlated with IL-8 levels at all 3 time points: randomization, day 14, and 6 months (r = 0.80; P < .0001 for all time points). MMP-9 levels were similar between treatment groups at randomization, were lower on day 14 among children treated with azithromycin (P = .0085), but no longer different after 6 months. MMP-9 levels at baseline and change from baseline to day 14 were not associated with the development of RW (P = .49, .39, respectively). CONCLUSION: Azithromycin therapy in children hospitalized with RSV bronchiolitis had a short-term anti-inflammatory effect in reducing upper airway MMP-9 levels. However, the reduction in MMP-9 levels did not relate to subsequent RW post-RSV. TRIAL REGISTRATION: This study is a secondary analysis of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis-II clinical trial registered at Clinicaltrials.gov (NCT02911935).

8.
Clin Exp Allergy ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253462

RESUMO

INTRODUCTION: Previous bronchoalveolar lavage fluid (BALF) proteomic analysis has evaluated limited numbers of subjects for only a few proteins of interest, which may differ between asthma and normal controls. Our objective was to examine a more comprehensive inflammatory biomarker panel in quantitative proteomic analysis for a large asthma cohort to identify molecular phenotypes distinguishing severe from nonsevere asthma. METHODS: Bronchoalveolar lavage fluid from 48 severe and 77 nonsevere adult asthma subjects were assessed for 75 inflammatory proteins, normalized to BALF total protein concentration. Validation of BALF differences was sought through equivalent protein analysis of autologous sputum. Subjects' data, stratified by asthma severity, were analysed by standard statistical tests, principal component analysis and 5 machine learning algorithms. RESULTS: The severe group had lower lung function and greater health care utilization. Significantly increased BALF proteins for severe asthma compared to nonsevere asthma were fibroblast growth factor 2 (FGF2), TGFα, IL1Ra, IL2, IL4, CCL8, CCL13 and CXCL7 and significantly decreased were platelet-derived growth factor a-a dimer (PDGFaa), vascular endothelial growth factor (VEGF), interleukin 5 (IL5), CCL17, CCL22, CXCL9 and CXCL10. Four protein differences were replicated in sputum. FGF2, PDGFaa and CXCL7 were independently identified by 5 machine learning algorithms as the most important variables for discriminating severe and nonsevere asthma. Increased and decreased proteins identified for the severe cluster showed significant protein-protein interactions for chemokine and cytokine signalling, growth factor activity, and eosinophil and neutrophil chemotaxis differing between subjects with severe and nonsevere asthma. CONCLUSION: These inflammatory protein results confirm altered airway remodelling and cytokine/chemokine activity recruiting leukocytes into the airways of severe compared to nonsevere asthma as important processes even in stable status.

9.
Respir Med ; 224: 107535, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38272376

RESUMO

BACKGROUND: TRAVERSE (NCT02134028), a phase 3 open-label extension study, assessed dupilumab safety and efficacy in patients with asthma aged ≥12 years who completed a previous dupilumab asthma study. This analysis evaluated changes in multiple lung function parameters in patients with moderate-to-severe asthma with elevated type 2 biomarkers (baseline eosinophils ≥150 cells·µL-1 or fractional exhaled nitric oxide ≥25 ppb) who completed QUEST (parent study) and 2 years of dupilumab treatment in TRAVERSE. METHODS: Endpoints analyzed included: pre-bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow (FEF25-75 %), and pre- and post-bronchodilator FEV1/FVC at parent study baseline (PSBL) at Weeks 0, 2, 48, and 96 in TRAVERSE, as well as pre- and post-bronchodilator FEV1 slopes in QUEST and TRAVERSE. Statistical analyses were descriptive. RESULTS: Dupilumab improved pre-bronchodilator FEV1, FVC, and FEF25-75 % in QUEST; these improvements were sustained in TRAVERSE. In QUEST patients who received placebo, dupilumab initiation in TRAVERSE resulted in rapid lung function improvements. Mean (standard deviation) changes from PSBL at TRAVERSE Weeks 48 and 96 in pre-bronchodilator FEV1 were 0.52 (0.59) and 0.45 (0.49) L in the dupilumab/dupilumab group and 0.47 (0.42) and 0.44 L (0.45) in the placebo/dupilumab group, respectively. Similar trends were observed for FVC and FEF25-75 %. Dupilumab also improved FEV1 slopes in QUEST and TRAVERSE. CONCLUSION: Dupilumab demonstrated sustained improvements across multiple spirometric lung function measurements for up to 3 years; patients who received placebo in QUEST experienced rapid lung function improvement upon initiation of dupilumab in TRAVERSE.


Assuntos
Asma , Broncodilatadores , Humanos , Broncodilatadores/uso terapêutico , Asma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Pulmão , Método Duplo-Cego
10.
Ann Am Thorac Soc ; 21(1): 38-46, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37796618

RESUMO

Rationale: Pulmonary function testing (PFT) is performed to aid patient selection before surgical resection for non-small cell lung cancer (NSCLC). The interpretation of PFT data relies on normative equations, which vary by race, but the relative strength of association of lung function using race-specific or race-neutral normative equations with postoperative pulmonary complications is unknown. Objectives: To compare the strength of association of lung function, using race-neutral or race-specific equations, with surgical complications after lobectomy for NSCLC. Methods: We studied 3,311 patients who underwent lobectomy for NSCLC and underwent preoperative PFT from 2001 to 2021. We used Global Lung Function Initiative equations to generate race-specific and race-neutral normative equations to calculate percentage predicted forced expiratory volume in 1 second (FEV1%). The primary outcome of interest was the occurrence of postoperative pulmonary complications within 30 days of surgery. We used unadjusted and race-adjusted logistic regression models and least absolute shrinkage and selection operator analyses adjusted for relevant comorbidities to measure the association of race-specific and race-neutral FEV1% with pulmonary complications. Results: Thirty-one percent of patients who underwent surgery experienced pulmonary complications. Higher FEV1, whether measured with race-neutral (odds ratio [OR], 0.98 per 1% change in FEV1% [95% confidence interval (CI), 0.98-0.99]; P < 0.001) or race-specific (OR, 0.98 per 1% change in FEV1% [95% CI, 0.98-0.98]; P < 0.001) normative equations, was associated with fewer postoperative pulmonary complications. The area under the receiver operator curve for pulmonary complications was similar for race-adjusted race-neutral (0.60) and race-specific (0.60) models. Using least absolute shrinkage and selection operator regression, higher FEV1% was similarly associated with a lower rate of pulmonary complications in race-neutral (OR, 0.99 per 1% [95% CI, 0.98-0.99]) and race-specific (OR, 0.99 per 1%; 95% CI, 0.98-0.99) models. The marginal effect of race on pulmonary complications was attenuated in all race-specific models compared with all race-neutral models. Conclusions: The choice of race-specific or race-neutral normative PFT equations does not meaningfully affect the association of lung function with pulmonary complications after lobectomy for NSCLC, but the use of race-neutral equations unmasks additional effects of self-identified race on pulmonary complications.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/complicações , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/complicações , Estudos Retrospectivos , Pneumonectomia/efeitos adversos , Pulmão/cirurgia , Volume Expiratório Forçado , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia
11.
JCI Insight ; 9(3)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38127464

RESUMO

BACKGROUNDInformation about the size, airway location, and longitudinal behavior of mucus plugs in asthma is needed to understand their role in mechanisms of airflow obstruction and to rationally design muco-active treatments.METHODSCT lung scans from 57 patients with asthma were analyzed to quantify mucus plug size and airway location, and paired CT scans obtained 3 years apart were analyzed to determine plug behavior over time. Radiologist annotations of mucus plugs were incorporated in an image-processing pipeline to generate size and location information that was related to measures of airflow.RESULTSThe length distribution of 778 annotated mucus plugs was multimodal, and a 12 mm length defined short ("stubby", ≤12 mm) and long ("stringy", >12 mm) plug phenotypes. High mucus plug burden was disproportionately attributable to stringy mucus plugs. Mucus plugs localized predominantly to airway generations 6-9, and 47% of plugs in baseline scans persisted in the same airway for 3 years and fluctuated in length and volume. Mucus plugs in larger proximal generations had greater effects on spirometry measures than plugs in smaller distal generations, and a model of airflow that estimates the increased airway resistance attributable to plugs predicted a greater effect for proximal generations and more numerous mucus plugs.CONCLUSIONPersistent mucus plugs in proximal airway generations occur in asthma and demonstrate a stochastic process of formation and resolution over time. Proximal airway mucus plugs are consequential for airflow and are in locations amenable to treatment by inhaled muco-active drugs or bronchoscopy.TRIAL REGISTRATIONClinicaltrials.gov; NCT01718197, NCT01606826, NCT01750411, NCT01761058, NCT01761630, NCT01716494, and NCT01760915.FUNDINGAstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi-Genzyme-Regeneron, and TEVA provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative.


Assuntos
Asma , Humanos , Broncoscopia , Pulmão/diagnóstico por imagem , Muco , Tomografia Computadorizada por Raios X
12.
Rev. bras. educ. méd ; 48(1): e019, 2024. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1535552

RESUMO

Resumo Introdução: A matriz curricular do curso de Medicina pode variar de acordo com o projeto pedagógico de curso (PPC) de cada instituição de ensino superior (IES). Nem sempre a visão da coordenação e do corpo docente do curso de Medicina está alinhada às opiniões dos alunos. Assim, a utilização de uma metodologia para identificar a visão do corpo discente seria fundamental. O design thinking (DT) é um processo que propõe a busca, de forma empática, colaborativa e criativa, de soluções para problemas complexos. Objetivo: Este estudo apresenta o DT como uma metodologia para identificar como os alunos do internato acreditam que deva ser a matriz curricular do primeiro ao quarto ano de um curso de Medicina no estado de São Paulo, e, para tanto, coletaram-se sugestões e pontos que exigiram a reavaliação na matriz original. Método: Realizou-se uma avaliação qualitativa com base no modelo do DT. Os alunos foram divididos em três grupos de cinco alunos, e cada grupo dedicou-se a discutir livremente sobre suas ideias acerca da matriz curricular. Posteriormente, apresentou-se um painel para cada grupo com a separação dos semestres correspondentes - do primeiro ao quarto ano - com post-it representando a matriz curricular vigente do curso de Medicina, e cada grupo teve uma hora para remontar a matriz curricular da maneira que julgasse mais adequado. Resultado: Após a fase de discussão, cada grupo montou sua matriz curricular, e propuseram-se algumas mudanças do ano em que a disciplina era ministrada e a inclusão de algumas matérias. A maioria das sugestões foi julgada procedente e incorporada na matriz curricular. Conclusão: A metodologia do DT contribuiu para a identificação de várias demandas acerca da matriz curricular de uma forma ordenada, empática e colaborativa, levando em consideração a opinião do estudante, sendo, portanto, uma estratégia de planejamento capaz de evidenciar fragilidades e fortalezas do currículo que talvez não fossem percebidas por outras estratégias.


Abstract Introduction: The medical school curricular structure may vary according to the educational planning of each higher education institution (HEI). The viewpoint of the coordination and the medical school faculty is not always aligned with the students' opinions. Thus, using a methodology to identify the students' point of view would be essential. Design thinking (DT) is a process that proposes a search, in an empathetic, collaborative, and creative way, for solutions to complex problems. Objectives: To present DT as a methodology to identify how clinical internship students believe the curricular structure from the 1st to the 4th year of a São Paulo state medical school should be, by collecting suggestions and points that require a re-evaluation process of the current curricular structure. Methods: This is a qualitative assessment, which will use the DT model. Students were divided into three groups of five, and each group was committed to having a free discussion on its ideas concerning the curricular structure. Then, a panel was presented to each group, dividing the semesters from the 1st to the 4th year with post-it notes representing the current curricular structure of the medical school, and each group had one hour to reassemble the curricular structure as they deemed appropriate. Results: After the discussion stage, each group assembled its curricular structure. Some changes concerning the year in which the discipline was provided were proposed, and the inclusion of others. Most of the suggestions were considered valid and were incorporated into the curriculum. Conclusions: The DT methodology contributed to the identification of several demands regarding the curricular structure in an orderly, empathetic, and collaborative way, taking into account the students' opinions. It is, therefore, a planning strategy able to evidence weaknesses and strengths of the curriculum that might not have been noticed by the use of other strategies.

13.
BMC Med Ethics ; 24(1): 109, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066498

RESUMO

BACKGROUND: Doctors are increasingly faced with end-of-life decisions. Little is known about how medical students approach euthanasia. The objective of this study was to evaluate, among medical students and residents, the view on euthanasia and its variants; correlate such a view with empathy and religiosity/spiritualism; and with the stages of medical training in Brazil. METHODS: This is an exploratory cross-sectional study using an online questionnaire to be filled out on a voluntary basis among medical students and residents, consisting of: socio-demographic data, an empathy questionnaire and questions with elaborate clinical cases that typify situations of the variants of euthanasia. RESULTS: From 1550 invitations, 273 volunteer participants responded (17.6%). The percentages of strong agreement/agreement on the concepts were: passive euthanasia (72.9%); active euthanasia (22.3%), orthothanasia (90.1%), dysthanasia (18.7%), assisted suicide (33%) and sedation (82.8%). Passive euthanasia, active euthanasia, dysthanasia and assisted suicide showed greater refusal with increasing length of medical training. Religious belief and degree of empathy did not significantly influence the opinion about the concepts. Strong agreement/agreement were: passive euthanasia (72.9%); active euthanasia (22.3%), orthothanasia (90.1%), dysthanasia (18.7%), assisted suicide (33%) and sedation (82.8%). CONCLUSIONS: Passive euthanasia, active euthanasia, dysthanasia and assisted suicide showed greater refusal with increasing length of medical training. The external validation of our findings relies on the distinct legal, cultural, and religious frameworks found across various countries.


Assuntos
Eutanásia , Estudantes de Medicina , Suicídio Assistido , Humanos , Estudos Transversais , Morte
14.
Artigo em Inglês | MEDLINE | ID: mdl-38097180

RESUMO

BACKGROUND: A multicenter clinical trial in patients with mild persistent asthma indicated that response to inhaled corticosteroids (ICS) is limited to those with sputum eosinophilia. However, testing for sputum eosinophilia is impractical in most clinical settings. OBJECTIVE: We examined associations between sputum eosinophilia and type 2 inflammatory biomarkers in untreated mild persistent asthma. METHODS: Induced sputum, blood eosinophil count (BEC), fractional exhaled nitric oxide (FeNO), and serum periostin were obtained twice during the 6-week run-in period in a clinical trial that enrolled patients 12 years and older with symptomatic, mild persistent asthma without controller therapy. The optimal threshold for each biomarker was based on achieving 80% or greater sensitivity. Performance of biomarkers (area under the receiver operating characteristics curve [AUC], range 0.0-1.0) in predicting sputum eosinophilia 2% or greater was determined; AUCs of 0.8 to 0.9 and more than 0.9 define excellent and outstanding discrimination, respectively. RESULTS: Of 564 participants, 27% were sputum eosinophilic, 83% were atopic, 70% had BEC of 200/uL or higher or FeNO of 25 ppb or greater; 64% of participants without sputum eosinophilia had elevated BEC or FeNO. The AUCs for BEC, FeNO, and both together in predicting sputum eosinophilia were all below the threshold for excellent discrimination (AUC 0.75, 0.78, and 0.79, respectively). Periostin (in adults) had poor discrimination (AUC 0.59; P = .02). CONCLUSIONS: In untreated mild persistent asthma, there is substantial discordance between sputum eosinophilia, BEC, and FeNO. Until prospective trials test the ability of alternative biomarkers to predict ICS response, BEC or FeNO phenotyping may be an option to consider ICS through a shared decision-making process with consideration of other clinical features.

15.
Chest ; 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38123124

RESUMO

BACKGROUND: Bronchial thermoplasty (BT) is a treatment for patients with poorly controlled, severe asthma. However, predictors of treatment response to BT are defined poorly. RESEARCH QUESTION: Do baseline radiographic and clinical characteristics exist that predict response to BT? STUDY DESIGN AND METHODS: We conducted a longitudinal prospective cohort study of participants with severe asthma receiving BT across eight academic medical centers. Participants received three separate BT treatments and were monitored at 3-month intervals for 1 year after BT. Similar to prior studies, a positive response to BT was defined as either improvement in Asthma Control Test results of ≥ 3 or Asthma Quality of Life Questionnaire of ≥ 0.5. Regression analyses were used to evaluate the association between pretreatment clinical and quantitative CT scan measures with subsequent BT response. RESULTS: From 2006 through 2017, 88 participants received BT, with 70 participants (79.5%) identified as responders by Asthma Control Test or Asthma Quality of Life Questionnaire criteria. Responders were less likely to undergo an asthma-related ICU admission in the prior year (3% vs 25%; P = .01). On baseline quantitative CT imaging, BT responders showed less air trapping percentage (OR, 0.90; 95% CI, 0.82-0.99; P = .03), a greater Jacobian determinant (OR, 1.49; 95% CI, 1.05-2.11), greater SD of the Jacobian determinant (OR, 1.84; 95% CI, 1.04-3.26), and greater anisotropic deformation index (OR, 3.06; 95% CI, 1.06-8.86). INTERPRETATION: To our knowledge, this is the largest study to evaluate baseline quantitative CT imaging and clinical characteristics associated with BT response. Our results show that preservation of normal lung expansion, indicated by less air trapping, a greater magnitude of isotropic expansion, and greater within-lung spatial variation on quantitative CT imaging, were predictors of future BT response. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01185275; URL: www. CLINICALTRIALS: gov.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38113166

RESUMO

BACKGROUND: Density thresholds in computed tomography (CT) lung scans quantify air trapping (AT) at the whole lung level but are not informative for AT in specific bronchopulmonary segments. OBJECTIVES: To apply a segment-based measure of AT in asthma to investigate the clinical determinants of AT in asthma. METHODS: In each of 19 bronchopulmonary segments in CT lung scans from 199 asthma patients, AT was categorized as present if lung attenuation was < -856 Hounsfield units at expiration in ≥ 15% of lung area. The resulting AT segment score (0-19) was related to patient outcomes. RESULTS: AT varied at the lung segment level and tended to persist at the patient and lung segment level over 3 years. Patients with widespread AT (>10 segments) had more severe asthma (p<0.05). The mean (± SD) AT segment score in patients with a BMI > 30 was lower than in patients with a BMI < 30 (3.5 ± 4.6 vs. 5.5 ± 6.3, p=0.008), and the frequency of AT in lower lobe segments in obese patients was less than in upper and middle lobe segments (35 vs. 46%, p=0.001). The AT segment score in patients with sputum eosinophil % > 2 was higher than in patients without sputum eosinophilia (7.0 ± 6.1 vs. 3.3 ± 4.9, p<0.0001). Lung segments with AT more frequently had airway mucus plugging than lung segments without AT (48 vs. 18%, p≤0.0001). CONCLUSIONS: In patients with asthma, air trapping is more severe in those with airway eosinophilia and mucus plugging whereas those who are obese have less severe trapping because their lower lobe segments are spared.

18.
medRxiv ; 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38106101

RESUMO

Rationale: Although airway oxidative stress and inflammation are central to asthma pathogenesis, there is limited knowledge of the relationship of asthma risk, severity, or exacerbations to mitochondrial dysfunction, which is pivotal to oxidant generation and inflammation. Objectives: We investigated whether mitochondrial DNA copy number (mtDNA-CN) as a measure of mitochondrial function is associated with asthma diagnosis, severity, oxidative stress, and exacerbations. Methods: We measured mtDNA-CN in blood in two cohorts. In the UK Biobank (UKB), we compared mtDNA-CN in mild and moderate-severe asthmatics to non-asthmatics. In the Severe Asthma Research Program (SARP), we evaluated mtDNA-CN in relation to asthma severity, biomarkers of oxidative stress and inflammation, and exacerbations. Measures and Main Results: In UK Biobank, asthmatics (n = 29,768) have lower mtDNA-CN compared to non-asthmatics (n = 239,158) (beta, -0.026 [95% CI, -0.038 to -0.014], P = 2.46×10-5). While lower mtDNA-CN is associated with asthma, mtDNA-CN did not differ by asthma severity in either UKB or SARP. Biomarkers of inflammation show that asthmatics have higher white blood cells (WBC), neutrophils, eosinophils, fraction exhaled nitric oxide (FENO), and lower superoxide dismutase (SOD) than non-asthmatics, confirming greater oxidative stress in asthma. In one year follow-up in SARP, higher mtDNA-CN is associated with reduced risk of three or more exacerbations in the subsequent year (OR 0.352 [95% CI, 0.164 to 0.753], P = 0.007). Conclusions: Asthma is characterized by mitochondrial dysfunction. Higher mtDNA-CN identifies an exacerbation-resistant asthma phenotype, suggesting mitochondrial function is important in exacerbation risk.

19.
Phys Rev Lett ; 131(22): 226801, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101376

RESUMO

We provide a model capable of accounting for the multiferroicity in certain materials. The model's base is on free electrons and spin moments coupled within nonrelativistic quantum mechanics. The synergistic interplay between the magnetic and electric degrees of freedom that turns into the multiferroic phenomena occurs at a profound quantum mechanical level, conjured by Berry's phases and the quantum theory of polarization. Our results highlight the geometrical nature of the multiferroic order parameter that naturally leads to magnetoelectric domain walls, with promising technological potential.

20.
JAMA ; 330(24): 2354-2363, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-37976072

RESUMO

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Design, Setting, and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Interventions: Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607). Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28. Results: Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.


Assuntos
COVID-19 , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Fluvoxamina/uso terapêutico , SARS-CoV-2 , Pacientes Ambulatoriais , Vacinas contra COVID-19 , Resultado do Tratamento , Tratamento Farmacológico da COVID-19 , Método Duplo-Cego
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