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PURPOSE: To examine which workplace factors contribute to health care leader well-being in rural settings. METHODS: Working with two rurally focused organizations, we administered a Rural Leader Burnout survey to executive leaders. The survey contained 25 questions; 24 were closed-item multiple choice and 1 open-ended question. The survey was based on the Mini Z 10 item burnout survey with 5 additional items for leaders. Logistic regression and qualitative content analysis determined factors associated with job satisfaction, burnout, and intent to leave (ITL). FINDINGS: There were 288 respondents (response rate 22%). Of 272 with complete data, 61.4% were women and 51.8% had worked > 10 years. About 81% reported job satisfaction, 40.2% were burned out, and 49.8% intended to leave their administrative roles within 2 years. Factors statistically associated with satisfaction were work control (OR = 3.0), values alignment with leadership (OR = 2.1), and trust in organization (OR = 2.0). Work control (OR = 0.3), trust in organization (OR = 0.4), and stress (OR = 4.1) were associated with burnout. Trust in organization (OR = 0.5), feeling valued (OR = 0.6), and stress (OR = 1.8) associated with ITL. Qualitative data revealed three themes relevant to rural leaders: (1) industry challenges, (2) daily operational issues, and (3) difficult relationships. CONCLUSIONS: These exploratory analyses demonstrate practical ways to improve work conditions to mitigate burnout and turnover in rural leaders. Promoting thriving in leaders would be an important step in maintaining the rural health care workforce.
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OBJECTIVES: To provide up-to-date complication rates for vasectomy in the UK using 15 years of data collected by the Association of Surgeons in Primary Care (ASPC). PATIENTS AND METHODS: Data were collected between 2007 and March 2022. A patient questionnaire was completed on the day of surgery and at 4 months postoperatively. Rates of early and late failure, infection, hospital admission or re-admission, haematoma and post-vasectomy pain syndrome (PVPS) were recorded. There were no specific exclusion criteria. Complication rates were compared to those published by major urological organisations. Descriptive statistics were utilised, without formal statistical analysis. RESULTS: Over the 15-year study period, data from 105 393 vasectomies were collected, performed by >150 surgeons. In 2022, 94.4% of surgeons used one test to prove sterility. In all, 65% of patients used a postal sperm test after vasectomy to confirm sterility. Early failure rates were available for 69 500 patients. Early failure occurred in 648 patients (0.93%). Of 99 124 patients, late failure occurred in 41 (0.04%). Of 102 549 vasectomies, postoperative infection was reported in 1250 patients (1.22%), haematoma in 1599 patients (1.56%), and PVPS was reported in 139 patients (0.14%). CONCLUSIONS: Vasectomy remains a safe and reliable contraceptive method. The rates of complication were generally lower than those published by major urological organisations. This large, prospective audit provides accurate, contemporaneous complication rates that can form the basis for pre-vasectomy counselling.
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Age-related declines in episodic memory do not affect all types of mnemonic information equally: when to-be-remembered information is in line with one's prior knowledge, or schema-congruent, older adults often show no impairments. There are two major accounts of this effect: One proposes that schemas compensate for memory failures in aging, and the other proposes that schemas instead actively impair older adults' otherwise intact memory for incongruent information. However, the evidence thus far is inconclusive, likely due to methodological constraints in teasing apart these complex underlying dynamics. We developed a paradigm that separately examines the contributions of underlying memory and schema knowledge to a final memory decision, allowing these dynamics to be examined directly. In the present study, healthy older and younger adults first searched for target objects in congruent or incongruent locations within scenes. In a subsequent test, participants indicated where in each scene the target had been located previously, and provided confidence-based recognition memory judgments that indexed underlying memory, in terms of recollection and familiarity, for the background scenes. We found that age-related increases in schema effects on target location spatial recall were predicted and statistically mediated by age-related increases in underlying memory failures, specifically within recollection. We also found that, relative to younger adults, older adults had poorer spatial memory precision within recollected scenes but slightly better precision within familiar scenes-and age increases in schema bias were primarily exhibited within recollected scenes. Interestingly, however, there were also slight age-related increases in schema effects that could not be explained by memory deficits alone, outlining a role for active schema influences as well. Together, these findings support the account that age-related schema effects on memory are compensatory in that they are driven primarily by underlying memory failures, and further suggest that age-related deficits in memory precision may also drive schema effects.
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Envelhecimento , Memória Episódica , Rememoração Mental , Reconhecimento Psicológico , Humanos , Idoso , Feminino , Masculino , Adulto Jovem , Reconhecimento Psicológico/fisiologia , Rememoração Mental/fisiologia , Adulto , Envelhecimento/fisiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , AdolescenteRESUMO
BACKGROUND: Trials evaluating implantable hemodynamic monitors to manage patients with heart failure (HF) have shown reductions in HF hospitalizations but not mortality. Prior meta-analyses assessing mortality have been limited in construct because of an absence of patient-level data, short-term follow-up duration, and evaluation across the combined spectrum of ejection fractions. OBJECTIVES: The purpose of this meta-analysis was to determine whether management with implantable hemodynamic monitors reduces mortality in patients with heart failure and reduced ejection fraction (HFrEF) and to confirm the effect of hemodynamic-monitoring guided management on HF hospitalization reduction reported in previous studies. METHODS: The patient-level pooled meta-analysis used 3 randomized studies (GUIDE-HF [Hemodynamic-Guided Management of Heart Failure], CHAMPION [CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients], and LAPTOP-HF [Left Atrial Pressure Monitoring to Optimize Heart Failure Therapy]) of implantable hemodynamic monitors (2 measuring pulmonary artery pressures and 1 measuring left atrial pressure) to assess the effect on all-cause mortality and HF hospitalizations. RESULTS: A total of 1,350 patients with HFrEF were included. Hemodynamic-monitoring guided management significantly reduced overall mortality with an HR of 0.75 (95% CI: 0.57-0.99); P = 0.043. HF hospitalizations were significantly reduced with an HR of 0.64 (95% CI: 0.55-0.76); P < 0.0001. CONCLUSIONS: Management of patients with HFrEF using an implantable hemodynamic monitor significantly reduces both mortality and HF hospitalizations. The reduction in HF hospitalizations is seen early in the first year of monitoring and mortality benefits occur after the first year.
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Insuficiência Cardíaca , Monitorização Hemodinâmica , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Próteses e Implantes , Hemodinâmica , Diuréticos , HospitalizaçãoRESUMO
Reversal or mitigation against an age-related decline in NAD+ has likely benefits, and this premise has driven academic and commercial endeavour to develop dietary supplements that achieve this outcome. We used a systems-based approach to improve on current supplements by targeting multiple points in the NAD+ salvage pathway. In a double-blind, randomised, crossover trial, the supplement - Nuchido TIME+® (NT) - increased NAD+ concentration in whole blood. This was associated with an increase in SIRT1 and an increase in nicotinamide phosphoribosyltransferase (NAMPT) in peripheral blood mononucleocytes, lower concentrations of pro-inflammatory cytokines in plasma, including a reduction in interleukin 2 (IL2), a reduction in glycated serum protein and a shift in the glycosylation profile of immunoglobulin G (IgG) toward a younger biological age, all of which are likely to promote a healthier ageing trajectory.
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DNA- based vaccines have demonstrated the potential as a safe and effective modality. PlaCCine, a DNA-based vaccine approach described subsequently relies on a synthetic DNA delivery system and is independent of virus or device. The synthetic functionalized polymer combined with DNA demonstrated stability over 12 months at 4C and for one month at 25C. Transfection efficiency compared to naked DNA increased by 5-15-fold in murine skeletal muscle. Studies of DNA vaccines expressing spike proteins from variants D614G (pVAC15), Delta (pVAC16), or a D614G + Delta combination (pVAC17) were conducted. Mice immunized intramuscular injection (IM) with pVAC15, pVAC16 or pVAC17 formulated with functionalized polymer and adjuvant resulted in induction of spike-specific humoral and cellular responses. Antibody responses were observed after one immunization. And endpoint IgG titers increased to greater than 1x 105 two weeks after the second injection. Neutralizing antibodies as determined by a pseudovirus competition assay were observed following vaccination with pVAC15, pVAC16 or pVAC17. Spike specific T cell immune responses were also observed following vaccination and flow cytometry analysis demonstrated the cellular immune responses included both CD4 and CD8 spike specific T cells. The immune responses in vaccinated mice were maintained for up to 14 months after vaccination. In an immunization and challenge study of K18 hACE2 transgenic mice pVAC15, pVAC16 and pVAC17 induced immune responses lead to decreased lung viral loads by greater than 90 % along with improved clinical score. These findings suggest that PlaCCine DNA vaccines are effective and stable and further development against emerging SARS-CoV-2 variants is warranted.
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COVID-19 , Vacinas de DNA , Camundongos , Animais , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Camundongos Transgênicos , Anticorpos Neutralizantes , DNA , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus/genética , Imunogenicidade da VacinaRESUMO
We investigated how sensitive visual processing is to spatiotemporal disruptions in ongoing visual events. Prior work has demonstrated that participants often miss spatiotemporal disruptions in videos presented in the form of scene edits or disruptions during saccades. Here, we asked whether this phenomenon generalizes to spatiotemporal disruptions that are not tied to saccades. In two flicker paradigm experiments, participants were instructed to identify spatiotemporal disruptions created when videos either jumped forward or backward in time. Participants often missed the jumps, and forward jumps were reported less frequently compared with backward jumps, demonstrating that a flicker paradigm produces effects similar to a saccade contingent disruption paradigm. These results suggest that difficulty detecting spatiotemporal disruptions is a general phenomenon that extends beyond trans-saccadic events.
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Movimentos Sacádicos , Percepção Visual , HumanosRESUMO
As infants view visual scenes every day, they must shift their eye gaze and visual attention from location to location, sampling information to process and learn. Like adults, infants' gaze when viewing natural scenes (i.e., photographs of everyday scenes) is influenced by the physical features of the scene image and a general bias to look more centrally in a scene. However, it is unknown how infants' gaze while viewing such scenes is influenced by the semantic content of the scenes. Here, we tested the relative influence of local meaning, controlling for physical salience and center bias, on the eye gaze of 4- to 12-month-old infants (N = 92) as they viewed natural scenes. Overall, infants were more likely to fixate scene regions rated as higher in meaning, indicating that, like adults, the semantic content, or local meaning, of scenes influences where they look. More importantly, the effect of meaning on infant attention increased with age, providing the first evidence for an age-related increase in the impact of local meaning on infants' eye movements while viewing natural scenes.
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Fixação Ocular , Percepção Visual , Adulto , Lactente , Humanos , Movimentos Oculares , Aprendizagem , SemânticaRESUMO
IMPORTANCE: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. OBJECTIVE: To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. DESIGN, SETTING, and PARTICIPANTS: This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. Intervention: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. MAIN OUTCOMES AND MEASURES: The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. RESULTS: Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. CONCLUSIONS AND RELEVANCE: In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.
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Insuficiência Cardíaca , Coração Auxiliar , Acidente Vascular Cerebral , Tromboembolia , Masculino , Humanos , Feminino , Aspirina/efeitos adversos , Coração Auxiliar/efeitos adversos , Fibrinolíticos/efeitos adversos , Método Duplo-Cego , Insuficiência Cardíaca/fisiopatologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia/etiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controleRESUMO
Humans rapidly process and understand real-world scenes with ease. Our stored semantic knowledge gained from experience is thought to be central to this ability by organizing perceptual information into meaningful units to efficiently guide our attention in scenes. However, the role stored semantic representations play in scene guidance remains difficult to study and poorly understood. Here, we apply a state-of-the-art multimodal transformer trained on billions of image-text pairs to help advance our understanding of the role semantic representations play in scene understanding. We demonstrate across multiple studies that this transformer-based approach can be used to automatically estimate local scene meaning in indoor and outdoor scenes, predict where people look in these scenes, detect changes in local semantic content, and provide a human-interpretable account of why one scene region is more meaningful than another. Taken together, these findings highlight how multimodal transformers can advance our understanding of the role scene semantics play in scene understanding by serving as a representational framework that bridges vision and language.
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BACKGROUND: In patients with symptomatic heart failure (HF) and previous heart failure hospitalization (HFH), hemodynamic-guided HF management using a wireless pulmonary artery pressure (PAP) sensor reduces HFH, but it is unclear whether these benefits extend to patients who have not been recently hospitalized but remain at risk because of elevated natriuretic peptides (NPs). OBJECTIVES: This study assessed the efficacy and safety of hemodynamic-guided HF management in patients with elevated NPs but no recent HFH. METHODS: In the GUIDE-HF (Hemodynamic-Guided Management of Heart Failure) trial, 1,000 patients with New York Heart Association (NYHA) functional class II to IV HF and either previous HFH or elevated NP levels were randomly assigned to hemodynamic-guided HF management or usual care. The authors evaluated the primary study composite of all-cause mortality and total HF events at 12 months according to treatment assignment and enrollment stratum (HFH vs elevated NPs) by using Cox proportional hazards models. RESULTS: Of 999 evaluable patients, 557 were enrolled on the basis of a previous HFH and 442 on the basis of elevated NPs alone. Those patients enrolled by NP criteria were older and more commonly White persons with lower body mass index, lower NYHA class, less diabetes, more atrial fibrillation, and lower baseline PAP. Event rates were lower among those patients in the NP group for both the full follow-up (40.9 per 100 patient-years vs 82.0 per 100 patient-years) and the pre-COVID-19 analysis (43.6 per 100 patient-years vs 88.0 per 100 patient-years). The effects of hemodynamic monitoring were consistent across enrollment strata for the primary endpoint over the full study duration (interaction P = 0.71) and the pre-COVID-19 analysis (interaction P = 0.58). CONCLUSIONS: Consistent effects of hemodynamic-guided HF management across enrollment strata in GUIDE-HF support consideration of hemodynamic monitoring in the expanded group of patients with chronic HF and elevated NPs without recent HFH. (Hemodynamic-Guided Management of Heart Failure [GUIDE-HF]; NCT03387813).
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COVID-19 , Insuficiência Cardíaca , Humanos , Hospitalização , Peptídeos Natriuréticos , HemodinâmicaRESUMO
Carboxylic acids participate in many metabolic pathways including tricarboxylic acid (TCA) cycle. Therefore, there have been ongoing attempts to develop sensitive liquid chromatography-mass spectrometry methods over the last decades. Derivatization of the carboxylic acids with 3-nitrophenylhydrazine presents a well-established methodology, and yet the derivatized species of polycarboxylic acids and their fragmentation in collision-induced dissociation have not been fully studied before. In our study, we elucidated how annotation of most abundant 3-nitrophenylhydrazine derivatives and optimization of their fragmentation in multiple reaction monitoring can boost the sensitivity, especially for polycarboxylic acids. Finally, the optimized liquid chromatography-tandem mass spectrometry method allowed for low detection limits ranging from 10 pM for 2-oxoglutaric acid to 800 pM for pyruvic acid. All TCA carboxylates were quantified in 20 µL of human plasma and the targeted method was validated in the same matrix. The same methodology with a modified gradient elution was also applied to untargeted screening of fatty acids by using high-resolution mass spectrometry enabling identification of 29 medium- to long-chain fatty acids in human plasma. The TCA carboxylates were also quantified in 105 of C2C12 mouse myuotube cells grown under different treatments to proof applicability of the methodology to biological studies in a wider sense. However, unfortunately all the TCA carboxylates were also found in the derivatized blanks in substantial amounts, which prevents from using the methodology for quantification of the carboxylates in less than 105 cells.
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Ciclo do Ácido Cítrico , Espectrometria de Massas em Tandem , Humanos , Camundongos , Animais , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Ácidos Graxos , Ácidos Carboxílicos/químicaRESUMO
While object meaning has been demonstrated to guide attention during active scene viewing and object salience guides attention during passive viewing, it is unknown whether object meaning predicts attention in passive viewing tasks and whether attention during passive viewing is more strongly related to meaning or salience. To answer this question, we used a mixed modeling approach where we computed the average meaning and physical salience of objects in scenes while statistically controlling for the roles of object size and eccentricity. Using eye-movement data from aesthetic judgment and memorization tasks, we then tested whether fixations are more likely to land on high-meaning objects than low-meaning objects while controlling for object salience, size, and eccentricity. The results demonstrated that fixations are more likely to be directed to high meaning objects than low meaning objects regardless of these other factors. Further analyses revealed that fixation durations were positively associated with object meaning irrespective of the other object properties. Overall, these findings provide the first evidence that objects are, in part, selected by meaning for attentional selection during passive scene viewing.
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Fixação Ocular , Percepção Visual , Humanos , Estimulação Luminosa/métodos , Movimentos Oculares , JulgamentoRESUMO
Prior research on film viewing has demonstrated that participants frequently fail to notice spatiotemporal disruptions, such as scene edits in the movies. Whether such insensitivity to spatiotemporal disruptions extends beyond scene edits in film viewing is not well understood. Across three experiments, we created spatiotemporal disruptions by presenting participants with minute long movie clips, and occasionally jumping the movie clips ahead or backward in time. Participants were instructed to press a button when they noticed any disruptions while watching the clips. The results from experiments 1 and 2 indicate that participants failed to notice the disruptions in continuity about 10% to 30% of the time depending on the magnitude of the jump. In addition, detection rates were lower by approximately 10% when the videos jumped ahead in time compared to the backward jumps across all jump magnitudes, suggesting a role of knowledge about the future affects jump detection. An additional analysis used optic flow similarity during these disruptions. Our findings suggest that insensitivity to spatiotemporal disruptions during film viewing is influenced by knowledge about future states.
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Filmes Cinematográficos , Fluxo Óptico , HumanosRESUMO
As we age, we accumulate a wealth of information about the surrounding world. Evidence from visual search suggests that older adults retain intact knowledge for where objects tend to occur in everyday environments (semantic information) that allows them to successfully locate objects in scenes, but may overrely on semantic guidance. We investigated age differences in the allocation of attention to semantically informative and visually salient information in a task in which the eye movements of younger (N = 30, aged 18-24) and older (N = 30, aged 66-82) adults were tracked as they described real-world scenes. We measured the semantic information in scenes based on "meaning map" ratings from a norming sample of young and older adults, and image salience as graph-based visual saliency. Logistic mixed-effects modeling was used to determine whether, controlling for center bias, fixated scene locations differed in semantic informativeness and visual salience from locations that were not fixated, and whether these effects differed for young and older adults. Semantic informativeness predicted fixated locations well overall, as did image salience, although unique variance in the model was better explained by semantic informativeness than image salience. Older adults were less likely to fixate informative locations in scenes than young adults were, though the locations older adults' fixated were independently predicted well by informativeness. These results suggest young and older adults both use semantic information to guide attention in scenes and that older adults do not overrely on semantic information across the board. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Envelhecimento Saudável , Percepção Visual , Humanos , Idoso , Envelhecimento , Movimentos Oculares , Semântica , Fixação OcularRESUMO
Models of visual search in scenes include image salience as a source of attentional guidance. However, because scene meaning is correlated with image salience, it could be that the salience predictor in these models is driven by meaning. To test this proposal, we generated meaning maps that represented the spatial distribution of semantic informativeness in scenes, and salience maps which represented the spatial distribution of conspicuous image features and tested their influence on fixation densities from two object search tasks in real-world scenes. The results showed that meaning accounted for significantly greater variance in fixation densities than image salience, both overall and in early attention across both studies. Here, meaning explained 58% and 63% of the theoretical ceiling of variance in attention across both studies, respectively. Furthermore, both studies demonstrated that fast initial saccades were not more likely to be directed to higher salience regions than slower initial saccades, and initial saccades of all latencies were directed to regions containing higher meaning than salience. Together, these results demonstrated that even though meaning was task-neutral, the visual system still selected meaningful over salient scene regions for attention during search.
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Semântica , Percepção Visual , Humanos , Movimentos Sacádicos , Fixação OcularRESUMO
BACKGROUND: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK). METHODS: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum. RESULTS: Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda. CONCLUSIONS: This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally.
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Asma , Humanos , Estudos Transversais , Asma/epidemiologia , Asma/tratamento farmacológico , Fenótipo , Brasil/epidemiologia , Nova Zelândia/epidemiologiaRESUMO
RATIONALE: Early-life exposures may influence lung function at different stages of the life course. However, the relative importance of characteristics at different stages of infancy and childhood are unclear. OBJECTIVES: To examine the associations and relative importance of early-life events on lung function at age 24â years. METHODS: We followed 7545 children from the Avon Longitudinal Study of Parents and Children from birth to 24â years. Using previous knowledge, we classified an extensive list of putative risk factors for low lung function, covering sociodemographic, environmental, lifestyle and physiological characteristics, according to timing of exposure: 1) demographic, maternal and child; 2) perinatal; 3) postnatal; 4) early childhood; and 5) adolescence characteristics. Lung function measurements (forced vital capacity (FVC), forced expiratory volume in 1â s (FEV1), FEV1/FVC and forced expiratory flow at 25-75% of FVC) were standardised for sex, age and height. The proportion of the remaining variance explained by each characteristic was calculated. The association and relative importance (RI) of each characteristic for each lung function measure was estimated using linear regression, adjusted for other characteristics in the same and previous categories. RESULTS: Lower maternal perinatal body mass index (BMI), lower birthweight, lower lean mass and higher fat mass in childhood had the largest RI (0.5-7.7%) for decreased FVC. Having no siblings, lower birthweight, lower lean mass and higher fat mass were associated with decreased FEV1 (RI 0.5-4.6%). Higher lean mass and childhood asthma were associated with decreased FEV1/FVC (RI 0.6-0.8%). CONCLUSIONS: Maternal perinatal BMI, birthweight, childhood lean and fat mass and early-onset asthma are the factors in infancy and childhood that have the greatest influence on early-adult lung function.
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Asma , Pulmão , Criança , Feminino , Adulto , Gravidez , Adolescente , Humanos , Pré-Escolar , Adulto Jovem , Estudos Longitudinais , Peso ao Nascer , Capacidade Vital/fisiologia , Volume Expiratório Forçado , Comportamentos Relacionados com a SaúdeRESUMO
BACKGROUND: Therapy guided by pulmonary artery (PA) pressure monitoring reduces PA pressures and heart failure hospitalizations (HFH) during the first year, but the durability of efficacy and safety through 2 years is not known. METHODS AND RESULTS: The CardioMEMS Post-Approval Study investigated whether benefit and safety were generalized and sustained. Enrollment at 104 centers in the United States included 1200 patients with NYHA Class III symptoms on recommended HF therapies with prior HFH. Therapy was adjusted toward PA diastolic pressure 8-20 mmHg. Intervention frequency and PA pressure reduction were most intense during first 90 days, with sustained reduction of PA diastolic pressure from baseline 24.7 mmHg to 21.0 at 1 year and 20.8 at 2 years for all patients. Patients completing two year follow-up (nâ¯=â¯710) showed similar 2-year reduction (23.9 to 20.8 mmHg), with reduction in PA mean pressure (33.7 to 29.4 mmHg) in patients with reduced left ventricular ejection. The HFH rate was 1.25 events/patient/year prior to sensor implant, 0.54 at 1 year, and 0.37 at 2 years, with 59% of patients free of HFH during follow-up. CONCLUSIONS: Reduction in PA pressures and hospitalizations were early and sustained during 2 years of PA pressure-guided management, with no signal of safety concerns regarding the implanted sensor.