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BACKGROUND: Closed-loop oxygen control systems automatically adjust the fraction of inspired oxygen (FiO2) to maintain oxygen saturation (SpO2) within a predetermined target range. Their performance with low and high-flow oxygen therapies, but not with non-invasive ventilation, has been established. We compared the effect of automated oxygen on achieving and maintaining a target SpO2 range with nasal high flow (NHF), bilevel positive airway pressure (bilevel) and continuous positive airway pressure (CPAP), in stable hypoxaemic patients with chronic cardiorespiratory disease. METHODS: In this open-label, three-way cross-over trial, participants with resting hypoxaemia (n=12) received each of NHF, bilevel and CPAP treatments, in random order, with automated oxygen titrated for 10 min, followed by 36 min of standardised manual oxygen adjustments. The primary outcome was the time taken to reach target SpO2 range (92%-96%). Secondary outcomes included time spent within target range and physiological responses to automated and manual oxygen adjustments. RESULTS: Two participants were randomised to each of six possible treatment orders. During automated oxygen control (n=12), the mean (±SD) time to reach target range was 114.8 (±87.9), 56.6 (±47.7) and 67.3 (±61) seconds for NHF, bilevel and CPAP, respectively, mean difference 58.3 (95% CI 25.0 to 91.5; p=0.002) and 47.5 (95% CI 14.3 to 80.7; p=0.007) seconds for bilevel and CPAP versus NHF, respectively. Proportions of time spent within target range were 68.5% (±16.3), 65.6% (±28.7) and 74.7% (±22.6) for NHF, bilevel and CPAP, respectively.Manually increasing, then decreasing, the FiO2 resulted in similar increases and then decreases in SpO2 and transcutaneous carbon dioxide (PtCO2) with NHF, bilevel and CPAP. CONCLUSION: The target SpO2 range was achieved more quickly when automated oxygen control was initiated with bilevel and CPAP compared with NHF while time spent within the range across the three therapies was similar. Manually changing the FiO2 had similar effects on SpO2 and PtCO2 across each of the three therapies. TRIAL REGISTRATION NUMBER: ACTRN12622000433707.
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Presión de las Vías Aéreas Positiva Contínua , Estudios Cruzados , Hipoxia , Ventilación no Invasiva , Terapia por Inhalación de Oxígeno , Saturación de Oxígeno , Humanos , Masculino , Femenino , Terapia por Inhalación de Oxígeno/métodos , Hipoxia/terapia , Hipoxia/etiología , Persona de Mediana Edad , Ventilación no Invasiva/métodos , Anciano , Presión de las Vías Aéreas Positiva Contínua/métodos , Oxígeno/administración & dosificación , Enfermedades Cardiovasculares/terapia , AdultoRESUMEN
BACKGROUND: Eczema is a chronic, relapsing skin condition commonly managed by emollients and topical corticosteroids. Prevalence of use and demand for effective botanical therapies for eczema is high worldwide, however, clinical evidence of benefit is limited for many currently available botanical treatment options. Robustly-designed and adequately powered randomised controlled trials (RCTs) are essential to determine evidence of clinical benefit. This protocol describes an RCT that aims to investigate whether a manuka oil based emollient cream, containing 2% ECMT-154, is a safe and effective topical treatment for moderate to severe eczema. METHODS: This multicentre, single-blind, parallel-group, randomised controlled trial aims to recruit 118 participants from community pharmacies in Aotearoa New Zealand. Participants will be randomised 1:1 to receive topical cream with 2% ECMT-154 or vehicle control, and will apply assigned treatment twice daily to affected areas for six weeks. The primary outcome is improvement in subjective symptoms, assessed by change in POEM score. Secondary outcomes include change in objective symptoms assessed by SCORAD (part B), PO-SCORAD, DLQI, and treatment acceptability assessed by TSQM II and NRS. DISCUSSION: Recruitment through community pharmacies commenced in January 2022 and follow up will be completed by mid-2023. This study aims to collect acceptability and efficacy data of manuka oil based ECMT-154 for the treatment of eczema. If efficacy is demonstrated, this topical may provide an option for a novel emollient treatment. The community-based design of the trial is anticipated to provide a generalisable result. ETHICS AND DISSEMINATION: Ethics approval was obtained from Central Health and Disability Ethics Committee (reference: 2021 EXP 11490). Findings of the study will be disseminated to study participants, published in peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001096842. Registered on August 18, 2021 ( https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382412&isReview=true ). PROTOCOL VERSION: 2.1 (Dated 18/05/2022).
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Eccema , Farmacias , Humanos , Emolientes/uso terapéutico , Nueva Zelanda , Índice de Severidad de la Enfermedad , Australia , Eccema/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Aim: This study investigated an optimal extracellular matrix (ECM) biomarker panel for measurement in acute myocardial infarction (AMI). Materials & methods: Blood samples were collected from 12 healthy volunteers, and from 23 patients during hospital admission (day 1-3) and 6 months following AMI. Protein assays measured: FGFb, MMP-2, -3, -8, -9, osteopontin, periostin, PINP, TGF-ß1, TIMP-1, -4 and VEGF. Results: When compared with healthy levels, seven ECM biomarkers were significantly altered in AMI patients, and six of these biomarkers displayed stable expression during hospital admission. Clinical characteristics and baseline cardiac function were not well correlated with ECM biomarkers. Conclusion: We suggest, MMP-2, MMP-3, MMP-8, MMP-9, periostin, PINP and TIMP-1 may be useful ECM biomarkers for future studies in AMI patients.
Plain language summary The cardiac extracellular matrix (ECM) maintains the structural integrity of the heart, and can be measured in human circulation using ECM biomarkers. Understanding the levels of variation and temporal dynamics that exist in ECM biomarkers following a heart attack is important for establishing an optimal biomarker panel that may be useful in heart research. A single blood sample was collected from 12 healthy volunteers. Multiple bloods samples were collected from 23 heart attack patients during hospital admission (day 13) and 6 months post heart attack. About 12 ECM biomarkers were measured from these blood samples. When compared with healthy levels, seven ECM biomarkers were significantly altered in heart attack patients, and six of these biomarkers displayed stable expression during hospital admission. Variability existed within biomarker levels and this was not well described by traditional heart attack risk factors, such as age or heart attack size. Thus, the source of biomarker variability remains unknown in this study. Overall, we suggest these seven ECM biomarkers may be of interest for future studies in the setting of heart attack research.
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Matriz Extracelular , Infarto del Miocardio , Biomarcadores , Matriz Extracelular/metabolismo , Humanos , Infarto del Miocardio/metabolismoRESUMEN
INTRODUCTION: In addition to their role in facilitating leukocyte-mediated inflammation, platelets can dampen leukocyte pro-inflammatory responses in some contexts. Consequently, platelets are increasingly appreciated as regulators of inflammation. Together, platelets and neutrophils play a role in inflammation through Toll-like receptor (TLR) expression, although we do not fully understand how platelets shape neutrophil responses to TLR stimulation. Here, we aimed to determine the extent to which platelets can modulate neutrophil function in response to in vitro stimulation with TLR4, TLR2/1, and TLR2/6 agonists. METHODS: Neutrophils from 10 healthy individuals were cultured alone or with autologous platelets. Neutrophils ± platelets were left unstimulated or were stimulated with 1 or 100 ng/mL lipopolysaccharide (LPS; a TLR4 agonist), Pam3CSK4 (a TLR2/1 agonist) and fibroblast-stimulating lipopeptide (FSL)-1 (a TLR2/6 agonist). Neutrophil activation and phagocytic activity were assessed by flow cytometry, and elastase and interleukin-8 secretion were assessed by ELISA. RESULTS: The addition of platelets attenuated neutrophil CD66b and CD11b expression in response to various doses of Pam3CSK4 and FSL-1. Furthermore, platelet co-culture was associated with higher CD62L expression (indicating reduced CD62L shedding) in response to these TLR agonists. Platelets also reduced elastase secretion in unstimulated cultures and in response to low-dose TLR stimulation. Conversely, platelet co-culture increased neutrophil phagocytosis in unstimulated cultures and in response to low-dose Pam3CSK4 and FSL-1. Platelets also increased IL-8 secretion in response to low-dose LPS. CONCLUSION: Platelets are complex immunomodulators that can attenuate some, and simultaneously augment other, neutrophil functions. This modulation can occur both in the absence and presence of TLR stimulation.