Background:In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19.Objective:Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19.Methods:This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand.Results:As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024.Conclusions:This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment.Trial Registration:ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359International Registered Report Identifier (IRRID):DERR1-10.2196/48183
MULTIFILE
BACKGROUND: Since the benefit-harm balance of adding inhaled corticosteroids to long-acting β2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) for patients with chronic obstructive pulmonary disease is unclear, we evaluated this addition for a range of patient profiles. METHODS: Analyses considered the effects of low-to-moderate doses of inhaled corticosteroids, LABA, and LAMA compared with LABA and LAMA alone, outcome incidences, and preference weights assigned to averted moderate-to-severe exacerbations (benefit) and severe pneumonia, candidiasis, and dysphonia (harm). Using exponential models, we estimated the preference weight-adjusted 2-year net clinical benefit (ie, benefits outweighing harms) indices. Exacerbation risk thresholds for triggering inhaled corticosteroids, LABA, and LAMA were established when the probability of a 2-year net clinical benefit reached 60%. We estimated the proportion of patients benefiting from added inhaled corticosteroids using an externally validated prediction model for acute exacerbations in primary care. FINDINGS: Adding low-to-moderate dose inhaled corticosteroids to LABA and LAMA provided a net clinical benefit in patients with a 2-year baseline exacerbation risk of 54-83%. Low-dose inhaled corticosteroids showed a net clinical benefit if the baseline risk was 40-91%, but not at higher doses. The benefit was modified by blood eosinophil count (BEC) and age. Although no net benefit was associated with a BEC of less than 150 cells per μL, patients with a BEC of 150 cells per μL or more had a net benefit from low-dose inhaled corticosteroids with a 2-year exacerbation risk of 32-95% in those aged 40-79 years and 41-93% in those older than 80 years. A moderate dose of inhaled corticosteroids showed a net benefit in patients younger than 80 years with a BEC of 150 cells per μL or more at 52-86% 2-year exacerbation risk. Depending on the subgroups, the proportion of patients with a net benefit from added inhaled corticosteroids ranged from 0 to 68%. INTERPRETATION: The net clinical benefit of adding different inhaled corticosteroid doses to LABA and LAMA varies greatly with exacerbation risk, BEC, and age. Personalised treatment decisions based on these factors and predicted exacerbation risks might reduce overtreatment and undertreatment with inhaled corticosteroids.None.
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Aim and method: To examine in obese people the potential effectiveness of a six-week, two times weekly aquajogging program on body composition, fitness, health-related quality of life and exercise beliefs. Fifteen otherwise healthy obese persons participated in a pilot study. Results: Total fat mass and waist circumference decreased 1.4 kg (p = .03) and 3.1 cm (p = .005) respectively. The distance in the Six-Minute Walk Test increased 41 meters (p = .001). Three scales of the Impact of Weight on Quality of Life-Lite questionnaire improved: physical function (p = .008), self-esteem (p = .004), and public distress (p = .04). Increased perceived exercise benefits (p = .02) and decreased embarrassment (p = .03) were observed. Conclusions: Aquajogging was associated with reduced body fat and waist circumference, and improved aerobic fitness and quality of life. These findings suggest the usefulness of conducting a randomized controlled trial with long-term outcome assessments.
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