Administration Of Systemic Corticosteroids Research Articles

36 The long-term consequences of short-course systemic corticosteroid therapy for childhood acute asthma exacerbations

Abstract Background Paediatric emergency department (ED) asthma guidelines recommend the administration of short-course systemic corticosteroids (SCS) for moderate to severe asthma exacerbations. The potential adverse implications of frequent, short-course SCS in children are poorly characterized. Objectives To determine the risk of adverse outcomes in children with asthma who receive multiple short-courses of SCS for asthma exacerbation management. Design/Methods In this population-based, retrospective cohort study, we identified children aged 1-16 years with an ED asthma presentation/hospitalization between October 1, 2017, and February 28, 2020. We divided participants into an SCS-exposed and unexposed cohort. A minimum washout period of 3 years was applied to exclude any SCS use before the index date. During a 24-month follow-up period, we captured cumulative short-courses of SCS for acute asthma management and the primary outcome, development of steroid-associated complications. We excluded participants with steroid-treated comorbidities, non-asthma-related SCS exposure and development of adverse outcome(s) before the index visit. We compared baseline characteristics between cohorts using descriptive statistics. A Prentice-Williams-Peterson model was used to determine the risk of adverse outcomes amongst children receiving SCS for asthma management with results expressed as adjusted hazard ratios (HR) and 95% Wald confidence intervals (CI). Results We identified 1468 participants with an asthma ED visit who received ≥1 SCS course for acute management and 541 participants who did not receive SCS during our study window, after applying inclusion/exclusion criteria. Baseline demographics were balanced between cohorts aside from age at index, which was significantly younger (4.31 ± 3.71 vs 7.64 ± 4.21 p<0.001) in the SCS-exposed cohort. Overall, the risk of developing a recurrent SCS-associated adverse outcome was not increased in the SCS-exposed cohort (HR = 0.95, 95% CI: 0.74-1.23, p=0.7). However, when the number of SCS courses was considered, a significant risk of recurrent SCS-associated outcomes emerged, especially for those receiving 4+ SCS courses (HR = 2.30, 95% CI: 0.92-5.80). This potential dose-response effect was negated when patients who were likely on medium to high dose maintenance inhaled corticosteroids, were removed in a sensitivity analysis (HR = 1.38, 95% CI: 0.35-5.39). Conclusion At a tertiary care Canadian paediatric hospital, children and adolescents receiving short-course SCS for asthma exacerbation management overall do not demonstrate an increased risk of developing complications after two years follow-up. However, complication risk may be increased among those receiving 4+ cumulative SCS courses.

Biologics for eosinophilic otitis media: a retrospective case study in a multidisciplinary center.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is refractory to conventional treatments and is strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The diagnostic criteria for EOM were established by IINO in 2011. With the recognition of type 2 inflammatory diseases, the gold standard of treatment is the systemic and topical administration of corticosteroids. Recently, several retrospective studies have demonstrated the efficacy of biologic treatments in EOM. We aimed to share our experience regarding the response of EOM after the use of biologics. This is a retrospective observational analysis including patients with refractory EOM treated with different biologics (benralizumab, omalizumab, mepolizumab, dupilumab) for concomitant severe asthma, urticaria and/or severe uncontrolled CRSwNP from 2011 to 2023. Treatment effectiveness in terms of EOM severity was measured using medical Global Evaluation of Treatment Effectiveness (GETE). We illustrated 4 clinical cases of uncontrolled comorbid EOM and demonstrated the complexity of multidisciplinary medical pathway with good response to biologics. We also observed that response to EOM and CRSwNP does not always follow that of asthma. The results of our small sample were consistent with those found in the literature and showed control of EOM with biologics. We need a larger multicentric sample and methodology to confirm these results and to compare the efficacy of different biologics.

Clinical characteristics, treatment, and outcomes of nivolumab induced immune thrombocytopenia.

Immune thrombocytopenia (ITP) represents an uncommon hematological side effect associated with nivolumab, and its distinct clinical attributes remain poorly defined. This research aimed to explore the clinical manifestations and outcomes of ITP induced by nivolumab. Reports on nivolumab induced ITP up to April 30, 2024, were collected for retrospective analysis. The study involved 34 patients with a median age of 67 years (range 32, 82). The onset of ITP varied from 10 to 100 days post initial dosage, with a median onset at 70 days. The majority of patients exhibited no symptoms, with only 23.5% experiencing clinically significant bleeding and 11.8% facing non-clinically significant bleeding. The median platelet count was 12 × 109/L (range 0, 115), with 67.6% of patients having platelet levels below 25 × 109/L. Bone marrow biopsy revealed mainly elevated megakaryocytes. Platelet-associated IgG levels were elevated with a median of 210 ng/107 cells (range 73, 1130). Subsequent interventions, which included cessation of nivolumab, administration of systemic corticosteroids, intravenous immunoglobulin therapy, a thrombopoietin receptor agonist, platelet transfusion, and rituximab treatment, resulted in 82.4% of subjects achieving normalized platelet counts, whereas 5.9% passed away due to ITP. ITP is a rare life-threatening immune-related adverse event and necessitates close monitoring. Systemic steroids are the primary treatment for ITP, while intravenous immunoglobulin, thrombopoietin receptor agonist and rituximab are other options.

1-year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort study.

In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge. Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions-Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI -0.026-0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change -0.12±0.22 versus -0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups. Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed.

Nanotechnology-Mediated Immunomodulation Strategy for Inflammation Resolution.

Inflammation serves as a common characteristic across a wide range of diseases and plays a vital role in maintaining homeostasis. Inflammation can lead to tissue damage and the onset of inflammatory diseases. Although significant progress is made in anti-inflammation in recent years, the current clinical approaches mainly rely on the systemic administration of corticosteroids and antibiotics, which only provide short-term relief. Recently, immunomodulatory approaches have emerged as promising strategies for facilitating the resolution of inflammation. Especially, the advanced nanosystems with unique biocompatibility and multifunctionality have provided an ideal platform for immunomodulation. In this review, the pathophysiology of inflammation and current therapeutic strategies are summarized. It is mainly focused on the nanomedicines that modulate the inflammatory signaling pathways, inflammatory cells, oxidative stress, and inflammation targeting. Finally, the challenges and opportunities of nanomaterials in addressing inflammation are also discussed. The nanotechnology-mediated immunomodulation will open a new treatment strategy for inflammation therapy.

Successful Tezepelumab Response and the Usefulness of Serum TARC Level as a Biomarker in a Severe Type 2 Bronchial Asthma Patient After Dupilumab, Mepolizumab, and Benralizumab Failure

Background: Treatment for severe type 2 bronchial asthma (BA) has advanced rapidly with the development of biologics. However, research on the responders and biomarkers for each biologic remains limited. Case Presentation: A 64-year-old female non-smoker with eosinophilic chronic rhinosinusitis and severe type 2 BA was administered dupilumab due to worsening nasal obstruction and olfactory impairment. Following this, the patient experienced secondary eosinophilia and worsening asthma control, necessitating frequent administration of systemic corticosteroids. Additionally, widespread maculopapular exanthema developed. Consequently, the treatment was switched to mepolizumab, which reduced blood eosinophil count; however, asthma control did not improve, and the maculopapular exanthema worsened, prompting another change to benralizumab. Due to persistent inadequate asthma control, the treatment was subsequently switched to tezepelumab, which resolved the maculopapular exanthema and decreased asthma exacerbations. Additionally, improvements in forced expiratory volume in one second and the asthma control test score were observed, along with a reduction in the serum thymus and activation-regulated chemokine (TARC) level. Conclusions: In some patients with severe type 2 BA who experience secondary eosinophilia and worsening asthma control after dupilumab administration, tezepelumab can be effective, and serum TARC levels could serve as a biomarker.

Phenytoin-induced toxic epidermal necrolysis (TEN). Combined treatment with steroids and human intravenous immunoglobulin: Case report

Background. Toxic epidermal necrolysis (TEN) is a severe systemic disease that affects the skin and mucosa, with a mortality rate above 30%. Pharmaceutical drugs are the main causal agents of this reaction, with most cases being largely associated with phenytoin. There is no generally accepted treatment for TEN. The administration of systemic corticosteroids combined with human intravenous immunoglobulin (IVIG) may be a possible adjuvant therapy. Case presentation. A 72-year-old patient who received phenytoin for four weeks as a prophylactic treatment after undergoing surgery to drain a chronic subdural hematoma developed TEN-compatible symptoms, which prompted treatment with methylprednisolone (1 g/day for 3 days) combined with IVIG (0.5 gr/kg/day for 5 days), with favorable response. Conclusion. Our patient’s response to the combination of corticosteroids and IVIG was favorable. However, due to the nature of this report, the function this combination of drugs has must be further researched.

Disseminated Intravascular Coagulation during a Course of Miliary Tuberculosis with Acute Respiratory Distress Syndrome

Abstract Miliary tuberculosis (TB) can occasionally lead to acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). In this case report, we present the case of an 18-year-old male who was diagnosed with miliary TB based on miliary shadows on X-ray and computed tomography of the chest, as well as positivity for mycobacterium TB in endotracheal aspirate by cartridge-based nucleic acid amplification. The patient’s hospital stay was complicated by ARDS and DIC, which was successfully managed with ventilatory support, administration of antitubercular treatment, systemic corticosteroids, and blood products.

Risk Factors for Acute Asthma Exacerbations in Adults With Mild Asthma

Although individuals with mild asthma account for 30% to 40% of acute asthma exacerbations (AAEs), relatively little attention has been paid to risk factors for AAEs in this population. To identify risk factors associated with AAEs in patients with mild asthma. This was a retrospective cohort study. We used administrative data from a large managed care organization to identify 199,010 adults aged 18 to 85 years who met study criteria for mild asthma between 2013 and 2018. An asthma-coded qualifying visit (index visit) was identified for each patient. We then used information at the index visit or from the year before the index visit to measure potential risk factors for AAEs in the subsequent year. An AAE was defined as either an asthma-coded hospitalization or emergency department visit, or an asthma-related systemic corticosteroid administration (intramuscular or intravenous) or oral corticosteroid dispensing. Poisson regression models with robust SEs were used to estimate the adjusted risk ratios for future AAEs. In the study cohort, mean age was 44 years and 64% were female; 6.5% had AAEs within 1 year after the index visit. In multivariate models, age, sex, race, ethnicity, smoking status, body mass index, prior acute asthma care, and a variety of comorbidities and other clinical characteristics were significant predictors for future AAE risk. Population-based disease management strategies for asthma should be expanded to include people with mild asthma in addition to those with moderate to severe disease.

The association of prehospital systemic corticosteroids with emergency department and in-hospital outcomes for patients with asthma exacerbations.

Timely administration of systemic corticosteroids is a cornerstone of asthma exacerbation treatment, yet little is known regarding potential benefits of prehospital administration by emergency medical services (EMS) clinicians. We examined factors associated with prehospital corticosteroid administration with hospitalization and hospital length of stay (LOS). We performed a retrospective study of EMS encounters for patients 2-50 years of age with suspected asthma exacerbation from a national data set. We evaluated factors associated with systemic corticosteroid administration using generalized estimating equations. We performed propensity matching based on service level, age, encounter duration, vital signs, and treatments to evaluate the association of prehospital corticosteroid administration with hospitalization and LOS using weighted logistic regression. We evaluated the association of prehospital corticosteroid administration with admission using Bayesian models. Of 15,834 encounters, 4731 (29.9%) received prehospital systemic corticosteroids. Administration of corticosteroids was associated with older age; sex; urbanicity; advanced life support provider; vital sign instability; increasing doses of albuterol; and provision of ipratropium bromide, magnesium, epinephrine, and supplementary oxygen. Within the matched sample, prehospital corticosteroids were not associated with hospitalization (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.73-1.01) or LOS (multiplier 0.76, 95% CI 0.56-1.05). Administration of corticosteroids was associated with lower odds of admission and shorter LOS in longer EMS encounters (>34 min), lower admission odds in patients with documented wheezing, and shorter LOS among patients treated with albuterol. In a Bayesian model with noninformative priors, the OR for admission among encounters given corticosteroids was 0.86 (95% credible interval 0.77-0.96). Prehospital systemic corticosteroid administration was not associated with hospitalization or LOS in the overall cohort of asthma patients treated by EMS, though they had a lower probability of admission within Bayesian models. Improved outcomes were noted among subgroups of longer EMS encounters, documented wheezing, and receipt of albuterol.

Diagnosing and Treating IgAN: Steroids, Budesonide, or Maybe Both?

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, is characterized by a mesangial IgA deposit and a variety of histological lesions, as described by the Oxford classification system. Despite the well-described "four-hit hypothesis", there are still plenty of less or undescribed mechanisms that participate in the disease pathogenesis, such as B-cell priming, which seems to be initiated by different antigens in the intestinal microbiota. Diagnosis of the disease is currently based on kidney biopsy findings, as the sensitivity and specificity of the many serum and urinary biomarkers described so far do not seem to have diagnostic accuracy. Therapeutic strategies consist of the initial step of non-immune medication, aiming to reduce both the intraglomerular pressure and proteinuria to below 0.5 g/day, followed by systemic corticosteroid administration in patients who remain at high risk for progressive chronic kidney disease despite the maximum non-immune treatment. The 6-month systemic corticosteroid treatment reduces proteinuria levels; however, the increased possibility of adverse events and increased relapse rate after treatment raises the need for a new therapeutic approach. Targeted-release budesonide is a therapeutic modality that aims to inhibit disease pathogenetic pathways at early stages; it has minor systemic absorption and proven beneficial effects on renal function and proteinuria. In the present systemic review, the benefits and adverse events of steroids and budesonide are described, and the possibility of combined treatment is questioned in selected cases with active histologic lesions.

Outcomes of postnatal systemic corticosteroids administration in ventilated preterm newborns: a systematic review of randomized controlled trials.

Prolonged mechanical ventilation, commonly used to assist preterm newborns, increases the risk of developing bronchopulmonary dysplasia (BPD). In recent decades, studies have demonstrated that systemic corticosteroids play a significant role in the prevention and management of BPD. In this systematic review of randomized controlled trials (RCTs), we evaluated the association between the administration of systemic corticosteroids in preterm infants and its long-term outcomes, such as neurodevelopment, growth, extubation rate, and related adverse effects. We conducted an electronic search in Medline, Scopus, and PubMed using the following terms: "premature infants" and "corticosteroids." We considered all RCTs published up to June 2023 as eligible. We included all studies involving preterm newborns treated with systemic corticosteroids and excluded studies on inhaled corticosteroids. A total of 39 RCTs were evaluated. The influence of steroids administered systemically during the neonatal period on long-term neurological outcomes remains unknown, with no influence observed for long-term growth. The postnatal administration of systemic corticosteroids has been found to reduce the timing of extubation and improve respiratory outcomes. Dexamethasone appears to be more effective than hydrocortisone, despite causing a higher rate of systemic hypertension and hyperglycemia. However, in the majority of RCTs analyzed, there were no differences in the adverse effects related to postnatal corticosteroid administration. Dexamethasone administered during the neonatal period appears to be more effective than hydrocortisone in terms of respiratory outcomes; however, caution should be taken when administering dexamethasone. Data derived from current evidence, including meta-analyses, are inconclusive on the long-term effects of the administration of systemic steroids in preterm infants or the possibility of neurodevelopmental consequences.

Managing Pediatric Asthma Exacerbations: The Role of Timely Systemic Corticosteroid Administration in Emergency Care Settings-A Multicentric Retrospective Study.

Asthma is the most prevalent chronic respiratory condition in children. An asthma exacerbation (AE) is a frequent reason for emergency department (ED) visits. An important step in the management of a moderate to severe AE is the administration of systemic corticosteroids (SCS) within 1 h after ED presentation. This study aimed to determine the timing of SCS administration and correlate this with the length of stay and oxygen therapy duration and to explore factors predicting timely administration. This study used a retrospective multicenter observational design based on electronic medical records review. Children aged < 18 years, presenting to the ED with a moderate to severe AE were included. 205 patients were included. Only 28 patients received SCS within 60 min after ED arrival. The median time to SCS administration was 169 min (Q1 92-Q3 380). A correlation was found between timing and oxygen treatment duration (r = 0.363, p < 0.001) and length of stay (r = 0.368, p < 0.001). No patient characteristics predicted timely SCS administration. Three in four children who presented with a moderate to severe AE at the ED did not receive SCS within the first hour. A prolonged timing of SCS administration correlated with a prolonged length of stay and extended need for oxygen support.

Preterm Birth and in Utero Exposure to Corticosteroids Are Associated With Increased Infection Risk in Children of Mothers With IBD.

Corticosteroids, thiopurines, and biologics may come into play during pregnancy in women with inflammatory bowel disease and potentially impact the developing fetal immune system. We aimed to assess the risk of serious infections in children stratified by in utero exposure to biologics and immunomodulators or concomitant treatment with corticosteroids. All singleton IBD pregnancies between 2008 and 2022 at a tertiary IBD center in Denmark were included. Maternal and offspring demographics, maternal disease activity, antenatal medical treatment, and infant infections resulting in hospital admission were recorded after review of medical records. In 602 live births (99.0%), we registered exposure to antenatal treatment as follows: biological monotherapy (n = 61, 10.2%), thiopurines (n = 110, 17.9%), biologics and concomitant thiopurines (n = 63, 10.3%), and controls (ie, no treatment with biological and/or thiopurines; n = 369, 60.6%). Preterm delivery (<37 gestational weeks) and systemic steroid administration during the third trimester were associated with an increased risk of serious infection in the offspring immediately after birth (relative risk = 17.5; 95% confidence interval, 7.8-39.8; P < .001, and relative risk = 4.8; 95% confidence interval, 1.5-12.7; P = 0.003, respectively).Intra-uterine exposure to biologics or combination treatment were not associated with a statistically significant higher risk of serious infections compared with controls; however, combination treatment showed an inclination towards an increased risk across analyses. Preterm birth and systemic corticosteroid administration late in pregnancy are significant risk factors for serious infections in the offspring of IBD mothers.

Pregnancy outcomes in women with rheumatoid arthritis: an 11-year French nationwide study

BackgroundRheumatoid arthritis (RA) can affect women of childbearing age. The management of patients with RA during pregnancy has evolved over the past decades, especially with the availability of new therapeutic...

Prognostic factors of virus-associated pneumonia other than COVID-19 in adults

ObjectiveTo determine prognostic factors of virus-associated pneumonia other than coronavirus disease 2019. MethodsWe retrospectively studied patients suffering from virus-associated community-acquired pneumonia, and who were admitted to Saitama Cardiovascular and Respiratory Center from 2002 to 2020. Prognostic factors were analyzed by univariable and multivariable regression analysis of patient demographics, laboratory data, chest imaging, severity on admission, and initial treatment. PatientsHIV-positive patients, those with non-resected lung cancer or receiving chemotherapy, and those with COVID-19 were excluded. Included were 363 patients diagnosed by nucleic acid amplification method, paired sera, and rapid diagnostic tests. ResultsA CURB-65 score of ≥3 was significant by univariable analysis for 60-day mortality but was nonsignificant by multivariable analysis. The poor prognostic factors that were significant by multivariable analysis (p < 0.05) included immunosuppressive state due to systemic corticosteroid or immunosuppressant administration, acute kidney injury on admission, and corticosteroid administration initiated within 5 days or 5 days to 2 weeks from onset. ConclusionA CURB-65 score of ≥3, which is considered to indicate severe pneumonia, was of limited value for predicting mortality of virus-associated pneumonia. We showed patients’ underlying diseases and complications to be independent factors of poor prognosis for 60-day mortality. Timing of the initiation of corticosteroid administration remains to be elucidated.

Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature

BackgroundNon-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs.Case presentationA 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone.ConclusionsSuppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

Evaluation of the implementation of evidence-based pediatric asthma exacerbation treatments in a regional consortium of emergency medical Services Agencies

Objective Asthma exacerbations are a frequent reason for pediatric emergency medical services (EMS) encounters. The objective of this study was to examine the implementation of evidence-based treatments for pediatric asthma in a regional consortium of EMS agencies. Methods This retrospective study applied the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) implementation framework to data from an EMS agency consortium in the Cincinnati, Ohio region. The study analyzed one year before an oral systemic corticosteroid (OCS) option was added to the agencies’ protocol, and five years after the protocol change. We constructed logistic regression models for the primary outcome of Reach, defined as the proportion of pediatric asthma patients who received a systemic corticosteroid. We modeled Maintenance (Reach measured monthly over time) using time series models. Results A total of 713 patients were included, 133 pre- and 580 post-protocol change. In terms of Reach, 3% (n = 4) of eligible patients received a systemic corticosteroid pre-OCS versus 20% (n = 116) post-OCS. Multivariable modeling of Reach revealed the study period, EMS transport time, months since implementation of OCS, and number of bronchodilators administered by EMS as significant covariates for the administration of a systemic corticosteroid. For Maintenance, it took approximately two years to reach maximal administration of systemic corticosteroids. Conclusions Indicators of asthma severity and time since the protocol change were significantly associated with EMS administration of systemic corticosteroids to pediatric asthma patients. The two-year time for maximal Reach suggests further work is required to understand how to best implement evidence-based pediatric asthma treatments in EMS.

Favorable outcome without corticosteroids during post-artesunate delayed hemolysis with positive direct antiglobulin test in severe imported Plasmodium falciparum malaria, France

Objectives: Positive direct antiglobulin tests (DATs) have been reported in cases of post-artesunate delayed hemolysis (PADH), but the causal role of auto-immune hemolysis remains unclear. We aimed to analyze a cohort of patients with PADH and DAT during severe malaria.Methods: We describe PADH and DAT results in a 7-year multi-center retrospective cohort of patients receiving artesunate for severe imported malaria.Results: Of 337 patients treated with artesunate, 46 (13.6%) had at least one DAT result within 30 days of treatment initiation, and 25/46 (54.3%) had at least one positive DAT. Among 40 patients with available data, 17 (42.5%) experienced PADH. Patient characteristics were similar for patients with a positive or negative DAT, and DAT positivity was not associated with PADH occurrence (P = 0.36). Among patients, 5/13 (38.5%) with a positive DAT after day 7 experienced PADH, compared to 10/13 (76.9%) of those with a negative DAT after day 7 (P = 0.11). Overall, 41% of patients required blood transfusions, and outcome was favorable without corticosteroids, even in cases of PADH.Conclusions: DAT does not appear to be a marker of PADH, but rather an indirect marker of an immune-mediated mechanism. DAT positivity should not lead to the administration of systemic corticosteroids during PADH.

Distinct temporal trajectories and risk factors for Post-acute sequelae of SARS-CoV-2 infection.

The understanding of Post-acute sequelae of SARS-CoV-2 infection (PASC) can be improved by longitudinal assessment of symptoms encompassing the acute illness period. To gain insight into the various disease trajectories of PASC, we assessed symptom evolution and clinical factors associated with the development of PASC over 3 months, starting with the acute illness period. We conducted a prospective cohort study to identify parameters associated with PASC. We performed cluster and case control analyses of clinical data, including symptomatology collected over 3 months following infection. We identified three phenotypic clusters associated with PASC that could be characterized as remittent, persistent, or incident based on the 3-month change in symptom number compared to study entry: remittent (median; min, max: -4; -17, 3), persistent (-2; -14, 7), or incident (4.5; -5, 17) (p = 0.041 remittent vs. persistent, p < 0.001 remittent vs. incident, p < 0.001 persistent vs. incident). Despite younger age and lower hospitalization rates, the incident phenotype had a greater number of symptoms (15; 8, 24) and a higher proportion of participants with PASC (63.2%) than the persistent (6; 2, 9 and 52.2%) or remittent clusters (1; 0, 6 and 18.7%). Systemic corticosteroid administration during acute infection was also associated with PASC at 3 months [OR (95% CI): 2.23 (1.14, 4.36)]. An incident disease phenotype characterized by symptoms that were absent during acute illness and the observed association with high dose steroids during acute illness have potential critical implications for preventing PASC.