The coronavirus disease 19 (COVID-19) pandemic has caused millions of deaths, and new treatments are urgently needed. Factors associated with a worse COVID-19 prognosis include old age (> 65 years), ...ethnicity, male sex, obesity, and people with comorbidities. Furthermore, vitamin D deficiency was reported as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. According to a recent clinical case series, vitamin D deficiency is a modifiable risk factor, which has the prospect of reducing hospital stay, intensive care, and fatal outcomes. Vitamin D has potent immunomodulatory properties, and its supplementation might improve important outcomes in critically ill and vitamin D-deficient COVID-19 patients. Despite the evidence that supports an association between vitamin D deficiency and COVID-19 severity, there is uncertainty about the direct link. Therefore, the aim of the trial is to assess if high-dose vitamin D supplementation has a therapeutic effect in vitamin D-deficient patients with COVID-19.
As the trial design, a randomized, placebo-controlled, double-blind, multi-center approach was chosen to compare a high single dose of vitamin D (140,000 IU) followed by treatment as usual (TAU) (VitD + TAU) with treatment as usual only (placebo + TAU) in patients with COVID-19 and vitamin D deficiency.
Vitamin D substitution in patients with COVID-19 and vitamin D deficiency should be investigated for efficacy and safety. The study aim is to test the hypothesis that patients with vitamin D deficiency suffering from COVID-19 treated under standardized conditions in hospital will recover faster when additionally treated with high-dose vitamin D supplementation. Latest studies suggest that vitamin D supplementation in patients with COVID-19 is highly recommended to positively influence the course of the disease. With this randomized controlled trial, a contribution to new treatment guidelines shall be made.
ClinicalTrials.gov NCT04525820 and SNCTP 2020-01401.
Abstract
Background
Despite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in ...early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS.
Methods
This multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 μg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization.
Discussion
Treatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19.
Trial registration
ClinicalTrials.gov,
NCT04536350
. Registered 02 September 2020.
Despite advances in therapy, community-acquired pneumonia (CAP) is still associated with significant morbidity and mortality. Several studies conducted in different countries have reported suboptimal ...adherence to the guidelines. However, there are currently no available data on adherence to CAP guidelines specifically in Switzerland.
The aim of this study was to audit the quality of diagnosis and therapy of CAP at a Swiss general hospital.
A retrospective, observational, single-center cohort study was conducted, including patients older than 18 years diagnosed with CAP and admitted to a medical ward throughout 2019 without prior antibiotic therapy prescribed by their general practitioner (GP). The baseline characteristics of the patients were analyzed, and the diagnostic workup and treatment were compared to the Swiss guidelines for CAP.
A total of 254 patients diagnosed with CAP were included in this study (median age 78 years, 51.6% males). Atypical pneumonia was diagnosed in 4% of patients, while an organism was identified in 33% of cases, with Streptococcus pneumoniae being the most frequently detected pathogen (57%). A chest image was taken in almost all patients. Documentation of respiratory rate was missing in 23% of cases. Procalcitonin was measured in 23.2% of cases. Pneumococcal and legionella urinary antigen testing was performed on approximately 90% of all patients and blood cultures were drawn in approximately 80% of patients. In 39% of cases, arterial blood gas analysis was performed. Guideline adherence for the administration of empiric antibiotics was documented/recorded in 75% of cases. Twelve different antibiotic regimens were administered, and they were mostly amoxicillin/clavulanate with or without macrolides, as suggested by the guidelines. In particular, the use of ceftriaxone was higher (19.7%) compared to the Swiss guidelines. The average length of antibiotic therapy was longer (8.2 days) compared to the guidelines (5-7 days). Oral steroid therapy was administered to 29.1% of patients, including to 75% of those diagnosed with COPD.
Overall, guideline adherence was moderately low, especially with regards to the assessment of respiratory rate, performance of arterial blood gas analysis, and sputum collection. Regarding antibiotic therapy, the use of ceftriaxone and the length of antibiotic therapy should be reduced. Further research is needed to identify the reasons for guideline non-adherence, and to find effective measures for the improvement of guideline adherence.
Background: Induction of labour (IOL) is a way to stimulate the onset of labour using mechanical and pharmacological methods. IOL is one of the most frequently performed obstetric procedures ...worldwide. We aimed to determine compliance with guidelines and to investigate factors associated with the success of labour. Methods: In this retrospective, observational study, we analysed all induced deliveries in a Swiss hospital between January 2020 and December 2022. Results: Out of 1705 deliveries, 349 women underwent IOL, and 278 were included in this study, with an average age of 32 years (range 19–44 years). Most of the women were induced for missed deadlines (20.1%), the premature rupture of membranes (16.5%), and gestational diabetes mellitus (9.3%), and there was a good adherence to the guideline, especially with the indication and IOL monitoring (100%). However, an improvement needs to be made in measuring and documenting the Bishop score (41%). The success of labour was associated with multiparity (81.8% vs. 62.4% p = 0.001) and maternal non-obesity (73.4 vs. 54.1% p = 0.026). Conclusions: An improvement is needed in the measurement and documentation of the Bishop score. Further research is needed to confirm the found associations between parity, obesity, and the success of IOL.
Vitamin D and its role in the coronavirus-19 disease (COVID-19) pandemic has been controversially discussed, with inconclusive evidence about vitamin D3 (cholecalciferol) supplementation in COVID-19 ...patients. Vitamin D metabolites play an important role in the initiation of the immune response and can be an easily modifiable risk factor in 25-hydroxyvitamin D
(25(OH)D
)-deficient patients. This is a multicenter, randomized, placebo-controlled double-blind trial to compare the effect of a single high dose of vitamin D
followed by treatment as usual (TAU) of daily vitamin D
daily until discharge versus placebo plus TAU in hospitalized patients with COVID-19 and 25(OH)D
-deficiency on length hospital stay. We included 40 patients per group and did not observe a significant difference in the median length of hospital stay (6 days in both groups,
= 0.920). We adjusted the length of stay for COVID-19 risk factors (β = 0.44; 95% CI: -2.17-2.22), and center (β = 0.74; 95% CI: -1.25-2.73). The subgroup analysis in patients with severe 25(OH)D
-deficiency (<25 nmol/L) showed a non-significant reduction in the median length of hospital stay in the intervention group (5.5 vs. 9 days,
= 0.299). The competing risk model with death did not reveal significant differences between the group in the length of stay (HR = 0.96, 95% CI 0.62-1.48,
= 0.850). Serum 25(OH)D
level increased significantly in the intervention group (mean change in nmol/L; intervention: +26.35 vs. control: -2.73,
< 0.001). The intervention with 140,000 IU vitamin D
+ TAU did not significantly shorten the length of hospital stay but was effective and safe for the elevation of serum 25(OH)D
levels.
The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe ...asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care.
In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021.
1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%).
Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.
An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. ...Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.
In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11-18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately.
In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13-0.25), maintenance OCS use (OR 0.75, 95% CI 0.61-0.92) and dose (mean -3.93 mg·day
, 95% CI -5.24-2.62 mg·day
) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.
By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
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