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
ObjectiveThis study investigates the feasibility of delivering inspiratory muscle training as part of the physical therapy treatment for patients with post-COVID dyspnoea.DesignMixed-methods pilot study.Subjects/patientsPatients with complaints of dyspnoea after COVID-19 infection and their physical therapists.MethodsThe Amsterdam University of Applied Sciences and the Amsterdam University Medical Centers conducted this study. Participants performed daily inspiratory muscle training at home for 6 weeks, consisting of 30 repetitions against a pre-set resistance. The primary outcome was feasibility assessed as acceptability, safety, adherence and patient- and professional experience obtained through diaries and semi-structured interviews. The secondary outcome was maximal inspiratory pressure.ResultsSixteen patients participated. Nine patients and 2 physical therapists partook in semi-structured interviews. Two patients dropped out before initiating the training. Adherence was 73.7%, and no adverse events occurred. Protocol deviations occurred in 29.7% of the sessions. Maximal inspiratory pressure changed from 84.7% of predicted at baseline to 111.3% at follow-up. Qualitative analysis identified barriers to training: ‘Getting acquainted with the training material’ and ‘Finding the right schedule’. Facilitators were: ‘Support from physical therapists’ and ‘Experiencing improvements’.ConclusionDelivering inspiratory muscle training to patients with post-COVID dyspnoea seems feasible. Patients valued the simplicity of the intervention and reported perceived improvements. However, the intervention should be carefully supervised, and training parameters adjusted to individual needs and capacity.
DOCUMENT
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.
MULTIFILE
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.
DOCUMENT
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 mixedmethods 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.
DOCUMENT
Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6–12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.
DOCUMENT
Introduction: Awake proning may result in lower intubation and mortality rates in COVID-19 patients with hypoxemia refractory to simple oxygen therapy. Aims. To summarize available evidence for benefit and develop a set of pragmaticrecommendations for awake proning in COVID-19 patients.Methods. An international group of 43 healthcare professionals searched MEDLINE for articles on awake proning, and formulated recommendations for its use.Results. The professionals reached consensus regarding indications and contraindications, feasibility and safety; they recommended applying awake proning if SpO2/FiO2 < 315, or SpO2 < 93% under supplementary oxygen, and if patient is able to follow instructions. Severe hypoxemia (SpO2/FiO2 < 140) and hemodynamic instability are absolute contraindications in the ward, but relative contraindications in the ICU. Morbid obesity was also seen as a relative contraindication, depending on assistance needed to help turn the patient. Pregnancy was not seen as a contraindication, but extra monitoring in the last trimester was seen as mandatory, and extra pillows for stabilization and prevention of aortocaval compression are necessary. Five steps may improve safety: i. adequate patient information; ii. help in positioning; iii. ensuring oxygen supply and placing of tubing free at sight; iv. optimized position to prevent harm; and v. monitor oxygen saturation and respiratory rate. Dissensus remained regarding duration, and number of sessions per day, and use of sedation during prone positioning.Conclusion. Awake proning is an attractive, simple and safe way to improve oxygenation in hypoxemic COVID–19 patients. Studies remain needed to see if it effects intubation and mortality rates.
MULTIFILE
IntroductionIt is unknown how awake prone positioning was practiced in patients with COVID–19 in the second wave of the national outbreak in the Netherlands.ObjectivesWe studied the practice of awake prone positioning in COVID–19 patients admitted to the ICU because of acute hypoxemic respiratory failure, and determined associations with demographics and outcomes.MethodsInvestigator–initiated, national, multicenter study in 16 hospitals in the Netherlands. Patients that received awake prone positioning were compared to patients that did not receive this intervention. The primary endpoint was a composite of various aspects of awake prone positioning practice. The secondary endpoint was ‘treatment failure’, a composite of intubation for invasive ventilation and death before day 28. We used propensity matching to control for observed confounding factors.ResultsIn 546 non–intubated patients, awake prone positioning was used in 88 (16.1%) patients, within median 1 [0 to 2] days after ICU admission, for median 1.0 [0.8–1.4] days and median 12.0 [8.4–14.5] hours per day. High–flow oxygen therapy was the most often used oxygen interface at start of awake prone positioning. Patients in the awake prone positioning group less often had a history of cardiovascular disease. In unmatched analysis, treatment failure occurred more often in patients that received awake prone positioning (HR, 1.80 [1.41–2.31]; P<0.001); in matched analysis, differences remained present, but did no longer reach statistical significance (HR, 1.17 [0.87-1.59]; P=0.30). ConclusionsIn this national cohort of COVID–19 patients in the second wave of the national outbreak, awake prone positioning was used in one in six patients. Awake prone positioning started early, but was often discontinued because of need for intubation. Patients that received awake prone positioning had higher risk for treatment failure.
MULTIFILE
BACKGROUND: There is uncertainty about how much positive end-expiratory pressure (PEEP) should be used in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19).OBJECTIVE: To investigate whether a higher PEEP strategy is superior to a lower PEEP strategy regarding the number of ventilator-free days (VFDs).DESIGN: Multicentre observational study conducted from 1 March to 1 June 2020.SETTING AND PATIENTS: Twenty-two ICUs in The Netherlands and 933 invasively ventilated COVID-19 ARDS patients.INTERVENTIONS: Patients were categorised retrospectively as having received invasive ventilation with higher (n=259) or lower PEEP (n=674), based on the high and low PEEP/FIO2 tables of the ARDS Network, and using ventilator settings and parameters in the first hour of invasive ventilation, and every 8 h thereafter at fixed time points during the first four calendar days. We also used propensity score matching to control for observed confounding factors that might influence outcomes.MAIN OUTCOMES AND MEASURES: The primary outcome was the number of VFDs. Secondary outcomes included distant organ failures including acute kidney injury (AKI) and use of renal replacement therapy (RRT), and mortality.RESULTS: In the unmatched cohort, the higher PEEP strategy had no association with the median [IQR] number of VFDs (2.0 [0.0 to 15.0] vs. 0.0 [0.0 to 16.0] days). The median (95% confidence interval) difference was 0.21 (-3.34 to 3.78) days, P = 0.905. In the matched cohort, the higher PEEP group had an association with a lower median number of VFDs (0.0 [0.0 to 14.0] vs. 6.0 [0.0 to 17.0] days) a median difference of -4.65 (-8.92 to -0.39) days, P = 0.032. The higher PEEP strategy had associations with higher incidence of AKI (in the matched cohort) and more use of RRT (in the unmatched and matched cohorts). The higher PEEP strategy had no association with mortality.CONCLUSION: In COVID-19 ARDS, use of higher PEEP may be associated with a lower number of VFDs, and may increase the incidence of AKI and need for RRT.TRIAL REGISTRATION: Practice of VENTilation in COVID-19 is registered at ClinicalTrials.gov, NCT04346342.
DOCUMENT
The NANOSPRESSO project is a pioneering response to the complex challenge of treating orphan diseases, which, despite affecting millions of people globally, have only scant therapeutic options. This initiative represents a paradigm shift by decentralizing the production of personalized nucleic acid nanomedicines. Integrating advanced microfluidic technology with lipid nanoparticle engineering platforms—validated by their efficacy in COVID-19 messenger (m)RNA vaccines— the NANOSPRESSO model enables hospital pharmacists to seamlessly assemble tailored therapeutic cartridges for gene/RNA therapy administration at the patient’s bedside. This innovative model subverts the traditional constraints of high-cost, intricate manufacturing and the instability of nucleic acid-based treatments, offering a streamlined. localized, flexible, and patient-centric alternative. Inspired by the traditional art of compounding in pharmacy, NANOSPRESSO strives to democratize access to innovative treatments for rare diseases, challenging the conventional, monolithic medical approach.
MULTIFILE
