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
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Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has challenged healthcare globally. An acute increase in the number of hospitalized patients has neces‑ sitated a rigorous reorganization of hospital care, thereby creating circumstances that previously have been identifed as facilitating prescribing errors (PEs), e.g. a demanding work environment, a high turnover of doctors, and prescrib‑ ing beyond expertise. Hospitalized COVID-19 patients may be at risk of PEs, potentially resulting in patient harm. We determined the prevalence, severity, and risk factors for PEs in post–COVID-19 patients, hospitalized during the frst wave of COVID-19 in the Netherlands, 3months after discharge. Methods: This prospective observational cohort study recruited patients who visited a post-COVID-19 outpatient clinic of an academic hospital in the Netherlands, 3months after COVID-19 hospitalization, between June 1 and October 1 2020. All patients with appointments were eligible for inclusion. The prevalence and severity of PEs were assessed in a multidisciplinary consensus meeting. Odds ratios (ORs) were calculated by univariate and multivariate analysis to identify independent risk factors for PEs. Results: Ninety-eight patients were included, of whom 92% had ≥1 PE and 8% experienced medication-related harm requiring an immediate change in medication therapy to prevent detoriation. Overall, 68% of all identifed PEs were made during or after the COVID-19 related hospitalization. Multivariate analyses identifed ICU admission (OR 6.08, 95% CI 2.16–17.09) and a medical history of COPD / asthma (OR 5.36, 95% CI 1.34–21.5) as independent risk fac‑ tors for PEs. Conclusions: PEs occurred frequently during the SARS-CoV-2 pandemic. Patients admitted to an ICU during COVID19 hospitalization or who had a medical history of COPD / asthma were at risk of PEs. These risk factors can be used to identify high-risk patients and to implement targeted interventions. Awareness of prescribing safely is crucial to prevent harm in this new patient population.
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Objective: To report the study protocol and baseline characteristics of a prospective cohort study to evaluate longitudinal recovery trajectories of patients recovering from COVID-19 who have visited a primary care allied health professional. Design: Report of the protocol and baseline characteristics for a prospective cohort study with a mixed-methods approach. Patients: Patients recovering from COVID-19 treated by primary care dietitians, exercise therapists, occupational therapists, physical therapists and/or speech and language therapists in the Netherlands. Methods: The prospective study will measure primary outcome domains: participation, health-related quality of life, fatigue, physical functioning, and costs, at baseline, 3, 6, 9 and 12 months. Interviews, on the patients’ experiences with allied healthcare, will be held with a subsample of patients and allied health professionals. Results: The cohort comprises 1,451 patients (57% female, mean age 49 (standard deviation 13) years). Preliminary results for the study cohort show that 974 (67%) of the participants reported mild/moderate severity symptoms during the infection period and patients reported severe restrictions in activities of daily living compared with previous research in other patient populations. Both quantitative and qualitative, will provide insight into the recovery of patients who are treated by allied health professionals. Conclusion: In conclusion, this will be the first comprehensive study to longitudinally evaluate the recovery trajectories and related costs of patients recovering from COVID-19 who are treated by allied health professionals in the Netherlands. This study will provide evidence for the optimal strategy to treat patients recovering from COVID-19 infection, including which patients benefit, and to what extent, from treatment, and which factors might impact their recovery course over time. The preliminary results of this study demonstrated the severity of restrictions and complaints at the start of therapy are substantial.
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