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.

Effects of additive corticosteroid therapy on 90-day survival in patients with community-onset pneumonia.

INTRODUCTION: Systemic corticosteroid therapy is occasionally used as an additive therapy, especially for patients with severe pneumonia. However, its recommendation for use in patients with pneumonia varies worldwide, and its efficacy is unclear. METHODS: Adult Japanese patients hospitalized with community-onset pneumonia between January and December 2012 were analyzed using the Diagnostic Procedure Combination database. The patients were classified into mild-to-moderate and severe groups using the A-DROP (age, dehydration, respiration, orientation, and blood pressure) system. The 90-day survival rate was evaluated between the presence or absence of corticosteroid treatment using the Kaplan-Meier method in the overall, mild-to-moderate and severe groups, respectively. The patients' clinical characteristics were adjusted between the two groups using the inverse probability of treatment weighting method. RESULTS: Among 123,811, 110,534 patients were classified as mild-to-moderate grade (corticosteroid group: 8,465, non-corticosteroid group: 102,069) and 13,277 patients were classified as severe grade (corticosteroid group: 1,338, non-corticosteroid group: 11,939). The 90-day survival rate was higher in the non-corticosteroid group than in the corticosteroid group in patients with pneumonia of overall grade (weighted hazard ratio [HR]: 1.36; P < 0.001) and those with mild-to-moderate grade (weighted HR: 1.46; P < 0.001). However, there were no significant differences in the outcomes between the two groups in those with severe grade (weighted HR: 1.08; P = 0.38). CONCLUSIONS: Additive systemic corticosteroid therapy may be related to poor 90-day prognosis in patients with mild-to-moderate grade community-onset pneumonia, although it may not be positively associated with its prognosis in those with severe grade.

The occurrence timeline of steroid-induced ocular hypertension and cataract in children with systemic autoimmune diseases.

PURPOSE: Steroid-induced ocular hypertension (SIOH) and cataract can result in visual loss. This study evaluated the timetable of SIOH and steroid-induced posterior subcapsular cataract (SI-PSC) occurrences in children with systemic autoimmune diseases (SAD) undergoing long-term systemic corticosteroid treatment. METHODS: Thirty-seven children with SAD treated with long-term oral corticosteroids were enrolled in this study. Intraocular pressure (IOP), SI-PSC occurrences, visual field and peripapillary retinal nerve fibre layer (pRNFL) thicknesses were recorded every 3 months for at least 6 months. RESULTS: Of the 37 children, with average age 11.0 ± 2.9 years, 22 patients (59.5%) had SIOH, 2 progressed as glaucoma at the 18-month and 3-year follow-up, respectively, and 12 (32.4%) patients had SI-PSC. Among patients with SIOH, 45.5% (10/22) of them had SI-PSC occurrence, and among patients with normal IOP, 13.3% (2/15) of them had SI-PSC. Seventeen patients participated in a longitudinal study with a follow-up period of at least 18 months. The incidence of SIOH started at 1 month 52.9% (9/17) and gradually increased to 70.6% (12/17) at 6 months, then decreased to 35.3% (6/17). SI-PSC onset started at 6 months (17.6%, 3/17), and its occurrence increased to 35.3% (6/17) at 12 months and reached to 41.2% (7/17) at 18 months. The pRNFL was thicker in the children with SIOH than the healthy controls (p = 0.01). CONCLUSION: SIOH and SI-PSC are common coexistent complications in children with long-term corticosteroids treatment, and the occurrence time is during the first month and 6 months, respectively. Patients with SIOH have a higher probability of cataract.

Which LABA/LAMA should be chosen in COPD patients in real life?

BACKGROUND: Given COPD heterogeneity, we do not know if some LABA/LAMAs are more suitable for some COPD phenotypes. This real-life database study aimed to evaluate retrospectively the 4 LABA/LAMA effectiveness and highlight possible specificities that could better guide us in choosing the right LABA/LAMA to be used. METHODS: We searched for subjects (1,779) adherent to umeclidinium/vilanterol (UM/VI), indacaterol/glycopyrronium (IND/GLY), aclidinium/formoterol (ACLI/FOR) and tiotropium/olodaterol (TIO/OLO) treatments in our prescribing/dispensing database. Prescriptions for systemic corticosteroids (SC), antibiotics and salbutamol during one year of LABA/LAMA treatment were analyzed. RESULTS: A better adherence was found in individuals taking IND/GLY (10.42 ± 1.86 packages/year) compared with UM/VI (10.09 ± 1.9; p = 0.008), ACLI/FOR (9.8 ± 1.8; p = 0.001) and TIO/OLO (10.1 ± 2.1; p = 0.047). The number of patients that were prescribed at least one package of SC/year and their package numbers/year were similar in males/females, across age groups and in "non-frequent exacerbators" with the 4 LABA/LAMAs. More SC were taken by frequent exacerbators, whereas fewer SC/antibiotic packages were prescribed to subjects aged >80 years with all treatments. In patients treated with ACLI/FOR or TIO/OLO, lower risks to having antibiotic prescriptions were observed when UM/VI (0.698[0.516-0.945] and 0.696[0.491-0.985; p = 0.020 and p = 0.041) and IND/GLY (0.597[0.445-0.802] and 0.595[0.423-0.836]; p = 0.001 and p = 0.003) were considered as landmarks. Lower risks for salbutamol prescriptions were detected with UM/VI (0.678[0.480-0.958]; p = 0.027) and TIO/OLO (0.585[0.365-0.937]; p = 0.026) when ACLI/FOR was used as a reference. CONCLUSION: According to our retrospective database study, each LABA/LAMA could have a specific efficacy profile in COPD that might be considered for personalized therapy. However, head-to-head targeted trials aimed to assess the impact of different LABA/LAMAs on COPD are needed to confirm/disprove such results.

Are Systemic Corticosteroids Causing Psoriasis Flare-Ups? Questionnaire for Danish Dermatologists, Gastroenterologists and Rheumatologists.

BACKGROUND: Psoriasis flare-ups and the change of morphology from nonpustular to pustular psoriasis following tapering and withdrawal of systemic corticosteroids have been reported. Despite these risks, systemic corticosteroids are still widely prescribed for patients with psoriasis, but the knowledge about psoriasis flare-ups and whether the physicians take precautions during these treatments is limited. METHODS: We conducted a questionnaire study among all dermatologists, gastroenterologists and rheumatologists in Denmark who work at a hospital or in a private practice to investigate the use, opinion and experience with oral, intramuscular and intra-articular corticosteroids in the treatment of patients with psoriasis. RESULTS: We received answers from a total of 248 physicians. Compared with oral and intramuscular corticosteroids, intra-articular corticosteroids were the most reported treatment in patients with psoriasis and only used by the rheumatologists. It was mainly the dermatologists and rheumatologists who had observed psoriasis flare-ups following treatment with oral, intramuscular and intra-articular corticosteroids. Half of the dermatologists (50%) and a fourth of the rheumatologists (29%) had observed at least one psoriasis flare-up following treatment with oral corticosteroids. About 10% of both the dermatologists and the rheumatologists had observed at least one psoriasis flare-up following treatment with intramuscular and/or intra-articular corticosteroids. Overall, 44% of the respondents took precautions, when they treated a patient with psoriasis with oral, intramuscular and intra-articular corticosteroids. CONCLUSION: The results from the questionnaire indicate that systemic corticosteroids for patients with psoriasis can cause flare-ups and should be used with care.

Advantage of inhaled corticosteroids as additional therapy to systemic corticosteroids for pediatric acute asthma exacerbations: a cost-effectiveness analysis.

Objective: Although the efficacy of systemic corticosteroids (SCs) in acute asthma exacerbations is well established, the fact that many children still require admission to hospital and that SCs have a slow onset of action are cause of concern. For this reason, the use of inhaled corticosteroids (ICS) as a therapy added to SCs has been explored, with no clarity about its cost-effectiveness. The aim of the present study was to evaluate the cost-effectiveness of ICS in addition to SCs (ICS + SCs) compared to standard therapy with SCs for treating pediatric asthma exacerbations.Methods: A decision-analysis model was developed to estimate the cost-effectiveness of SCs compared to ICS + SCs for treating pediatric patients with acute asthma exacerbations. Effectiveness parameters were obtained from a systematic review of the literature. Cost data obtained from hospital bills and from the national manual of drug prices. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome of the model was avoidance of hospital admission.Results: For the base-case analysis, the model showed that compared to SCs, therapy with ICS + SCs was associated with lower total costs (US$88.76 vs.US$97.71 average cost per patient) and a lower probability of hospital admission (0.9060 vs. 0.9000), thus showing dominance.Conclusions: This study shows that compared with standard therapy with SCs, ICS + SCs for treating pediatric patients with acute asthma exacerbations is the preferred strategy because it was associated with a lower probability of hospital admission, at lower total treatment costs.

Correlation between decreased choroidal blood flow velocity and the pathogenesis of acute zonal occult outer retinopathy.

BACKGROUND: To evaluate changes of choroidal circulation quantitatively using laser speckle flowgraphy in patients with acute zonal occult outer retinopathy. DESIGN: Retrospective observational case series. PARTICIPANTS: Sixteen eyes of 11 acute zonal occult outer retinopathy patients: seven non-treated eyes with good visual acuity and nine systemic corticosteroid-treated eyes with progressive visual acuity loss. Six eyes with thyroid-associated ophthalmopathy receiving systemic corticosteroid therapy served as controls. METHODS: The mean blur rate, an index of quantitative relative blood flow velocity, in the affected area was measured by laser speckle flowgraphy. The changes of mean blur rate, best-corrected visual acuity and the average threshold at the affected area on Humphrey perimetry during 24-week follow up were analysed. MAIN OUTCOME MEASURES: Mean blur rate, best-corrected visual acuity, and the average threshold. RESULTS: In non-treated eyes, the average mean blur rate significantly increased at 24 weeks, with a significant increase of the average threshold. In corticosteroid-treated eyes, the mean blur rates at 1, 4, 12 and 24 weeks were significantly higher than the pretreatment value, with significant improvement of best-corrected visual acuity and the average threshold. The increase in mean blur rate at 4 weeks in corticosteroid-treated acute zonal occult outer retinopathy eyes was significantly higher than that in corticosteroid-treated control eyes. CONCLUSIONS: In eyes with acute zonal occult outer retinopathy, the mean blur rate at the affected area significantly increases along with improvement of visual functions. These results suggest that impaired choroidal circulation is involved in the pathogenesis of acute zonal occult outer retinopathy.

Real-world association between systemic corticosteroid exposure and complications in US patients with severe asthma.

BACKGROUND: Systemic corticosteroid (SCS) use remains widespread among patients with severe asthma, despite associated complications. OBJECTIVE: Evaluate the association between cumulative SCS exposure and SCS-related complications in severe asthma. METHODS: This retrospective, longitudinal study used claims data from the Optum Clinformatics Data Mart database (GSK ID: 214469). Eligible patients (≥ 12 years old) had an asthma diagnosis and were divided into two cohorts: SCS use and non/burst-SCS use. Patients in the SCS use cohort had a claim for a daily prednisone-equivalent dose ≥ 5 mg SCS following ≥ 6 months of continuous SCS use; those in the non/burst-SCS cohort had no evidence of continuous SCS use and had a non-SCS controller/rescue medication initiation claim. For each cohort, the date of the qualifying claim was the index date. SCS users were further stratified by SCS use during each quarter of follow-up: low (≤ 6 mg/day), medium (> 6-12 mg/day), high (> 12 mg/day), and continuous high (≥ 20 mg/day for 90 days). SCS-related complications were evaluated in the quarter following SCS exposure. The adjusted odds ratios (OR) of experiencing SCS-related complications during follow-up in each of the SCS use groups versus the non/burst SCS cohort were calculated using generalized estimating equations models. RESULTS: SCS and non/burst-SCS use cohorts included 7473 and 89,281 patients (mean follow-up: 24.6 and 24.2 months), respectively. Compared with the non/burst-SCS use cohort, medium, high, and continuous high SCS use was associated with greater odds of any SCS-related complication (adjusted OR [95% confidence interval]: 1.30 [1.21, 1.39], 1.49 [1.35, 1.64] and 1.63 [1.40, 1.89], respectively) including increased acute gastrointestinal, cardiovascular, and immune system-related complications, and chronic cardiovascular, metabolic/endocrine, central nervous system, bone-/muscle-related, ophthalmologic, and hematologic/oncologic complications. Low-dose SCS use was also associated with significantly increased odds of acute gastrointestinal and immune system-related complications, and chronic bone-/muscle-related and hematologic/oncologic complications versus the non/burst-SCS use cohort. CONCLUSION: SCS use, even at low doses, is associated with increased risk of SCS-related complications among patients with severe asthma.

Radioclinical Profile of Eosinophilic Lung: A Case Series.

In this study, we present findings from an analysis of 17 patients diagnosed with eosinophilic lung disease, with a majority (64.70%) being male. The average age of the patients was 54 ± 13.22 years. A history of uncontrolled asthma was noted in nine cases. The clinical picture was characterized by persistent dyspnea and cough. Blood hypereosinophilia was present in all cases, with a median of 1770 cells/ul. Two patients had a pulmonary eosinophilia greater than 25%. Radiological findings were consistent with diffuse bilateral ground-glass opacities or areas of consolidation in the majority of cases. The main etiologies identified were chronic eosinophilic pneumonia (12 cases), followed by eosinophilic granulomatosis with polyangiitis (3 cases), idiopathic hypereosinophilic syndrome (1 case) and drug-induced hypereosinophilia (1 case). All patients were treated with systemic corticosteroids, with the addition of immunosuppressive therapy necessary in three cases. Notably, five relapses were recorded after corticosteroid therapy was stopped.

Suprachoroidal CLS-TA with and without Systemic Corticosteroid and/or Steroid-Sparing Therapy: A Post-Hoc Analysis of the Phase 3 PEACHTREE Clinical Trial.

PURPOSE: To study the efficacy and safety of suprachoroidal CLS-TA (proprietary suspension of triamcinolone acetonide) in uveitic macular edema (UME) with and without concurrent systemic corticosteroid or steroid-sparing therapy (ST). METHODS: Post hoc analysis of the PEACHTREE phase 3 randomized trial. RESULTS: Among UME patients receiving no ST, at week 24, mean BCVA change was +15.6 letters in 68 CLS-TA patients versus +4.9 letters in 49 sham-control patients (p < .001), while mean CST change was -169.8 µm versus -10.3 µm, respectively (p < .001). Among patients receiving ST, at week 24, mean BCVA change was +9.4 letters in 28 CLS-TA patients versus -3.2 letters in 15 sham-control patients (p = .019), while mean CST change was -108.3 µm versus -43.5 µm, respectively (p = .190). No SAEs related to treatment were reported. CONCLUSIONS: A clinically meaningful benefit of CLS-TA was noted in UME patients, regardless of concurrent ST usage.Abbreviation and AcronymsCST = central subfield thickness; BCVA = best corrected visual acuity; ME = macular edemaI; IVT = intravitreal; AE = adverse event; FA = fluocinolone acetonide; SD-OCT = spectral-domain optical coherence tomography; NIU = noninfectious uveitis; SAE = serious adverse event; TEAE = treatment emergent adverse event; ITT = intent to treat; CI = confidence interval.

Non-Dexamethasone Corticosteroid Therapy's Effect on COVID-19 Prognosis in Cancer Patients: A Retrospective Study.

BACKGROUND: Anti-inflammatory corticosteroids are used in cancer treatment and COVID-19 infections. Data on the impact of non-dexamethasone corticosteroids on COVID-19 infection severity in cancer patients are minimal. This study investigates if corticosteroid treatment affects the disease severity in adult cancer patients. METHODS: A total of 116 COVID-19-infected cancer patients on hydrocortisone (H) or prednisone (P) were compared to 343 untreated patients. The study included patients who received corticosteroids before (B), after (A), or both before and after (B and A) COVID-19 infections. Ventilation support, hospitalization and mortality were investigated. RESULTS: Our data showed that a significantly greater number of patients taking H or P required ventilation support and hospitalization and that mortality rates were higher than the control group. Patients who received H or P after COVID-19 infection had a significantly worse prognosis than the other sub-groups and the control group. CONCLUSION: Corticosteroids impacted cancer patients' COVID-19 prognosis. Despite the limited sample size, H- and P-treated patients' corticosteroids performed worse than the control, especially if treatments were received after COVID-19 infection. Hence, when a cancer patient already on H or P treatment is diagnosed with COVID-19, we recommend switching to a steroid treatment as suggested by international guidelines.

Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis.

PURPOSE: To investigate the real-world dose of systemic corticosteroids in the treatment of non-infectious uveitis (NIU) in Japan. STUDY DESIGN: A retrospective, observational study. METHODS: Patients newly registered at the Japan Medical Data Center health insurance claims database with a diagnosis of NIU who received systemic corticosteroids were identified, and their systemic corticosteroid dose (prednisolone equivalent) was assessed over 12 months of treatment (data extraction period: January 2008 to May 2017). RESULTS: The mean cumulative systemic corticosteroid dose in 12 months in 1641 new patients with NIU who received systemic corticosteroids was 593.7 mg. The mean systemic corticosteroid dose was highest at month 1 (10.7, 218.1, 16.7, and 23.0 mg/day in Behçet's disease [BD]-associated NIU [n = 19], Vogt-Koyanagi-Harada [VKH] disease-associated NIU [n = 49], sarcoidosis-associated NIU [n = 27], and "undifferentiated NIU" [NIU without specific primary disease information, n = 1545], respectively) and decreased over time. Systemic corticosteroids were prescribed at month 12 to 68.4%, 22.4%, 44.4%, and 5.6% of patients with BD-associated NIU, VKH disease-associated NIU, sarcoidosis-associated NIU, and undifferentiated NIU, respectively (mean dose, 6.0-14.3 mg/day). Multivariate regression analysis identified female sex, middle age (30 to < 40 years), VKH disease, and immunosuppressive agent use as background factors associated with higher systemic corticosteroid dose. CONCLUSIONS: The systemic corticosteroid dose was highest at month 1 and decreased over time in all disease categories. This database research revealed that some patients with NIU continued being prescribed systemic corticosteroids for at least 1 year.

Uncontrolled severe T2 asthma: Which biological to choose? A biomarker-based approach.

In recent years, advances in knowledge of molecular mechanisms involved in asthma have changed uncontrolled severe asthma (USA) treatment, with the appearance of biological treatment. USA is a heterogeneous entity with different endotypes and phenotypes. Nowadays, the biological drugs approved with asthma indication are omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. Tezepelumab is approved by the Food and Drug Administration (FDA) in the United States and, recently, by the European Medicines Agency (EMA). All these biological drugs have shown their efficacy in clinical trials, especially in reducing exacerbations, improving asthma control, quality of life, pulmonary function, and withdrawing systemic corticosteroids or at least reducing their daily dose, with some differences between them. Except for mepolizumab and reslizumab, biological drugs have different targets and thus different therapeutic indications should be expected; however, in some patients, more than one drug could be indicated, making the election more difficult. Because there are no direct comparisons between biological drugs, some biomarkers are used to choose between them, but they are not unbeatable. In this article, an algorithm to choose the first biological drug in a specific patient is proposed based on different study results and patient' characteristics.

The Effect of Maintenance Treatment with Erdosteine on Exacerbation Treatment and Health Status in Patients with COPD: A Post-Hoc Analysis of the RESTORE Dataset.

Purpose: To explore the effect of erdosteine on COPD exacerbations, health-related quality of life (HRQoL), and subjectively assessed COPD severity. Patients and methods: This post-hoc analysis of the RESTORE study included participants with COPD and spirometrically moderate (GOLD 2; post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted; n = 254), or severe airflow limitation (GOLD 3; post-bronchodilator FEV1 30‒49% predicted; n = 191) who received erdosteine 300 mg twice daily or placebo added to usual maintenance therapy for 12 months. Antibiotic and oral corticosteroid use was determined together with patient-reported HRQoL (St George's Respiratory Questionnaire, SGRQ). Patient and physician subjective COPD severity scores (scale 0‒4) were rated at baseline, 6 and 12 months. Data were analyzed using descriptive statistics for exacerbation severity, COPD severity, and treatment group. Comparisons between treatment groups used Student's t-tests or ANCOVA as appropriate. Results: Among GOLD 2 patients, 43 of 126 erdosteine-treated patients exacerbated (7 moderate-to-severe exacerbations), compared to 62 of 128 placebo-treated patients (14 moderate-to-severe exacerbations). Among those with moderate-to-severe exacerbations, erdosteine-treated patients had a shorter mean duration of corticosteroid treatment (11.4 days vs 13.3 days for placebo, P = 0.043), and fewer patients required antibiotic treatment with/without oral corticosteroids (71.4% vs 85.8% for placebo, P < 0.001). Erdosteine-treated GOLD 2 patients who exacerbated showed significant improvements from baseline in SGRQ total scores and subjective disease severity scores (patient- and physician-rated), compared with placebo-treated patients regardless of exacerbation severity. Among GOLD 3 patients, there were no significant differences between treatment groups on any of these measures. Conclusion: Adding erdosteine to the usual maintenance therapy of COPD patients with moderate airflow limitation reduced the number of exacerbations, the duration of treatment with corticosteroids and the episodes requiring treatment with antibiotics. Additionally, treatment with erdosteine improved HRQoL and patient-reported disease severity.

Tocilizumab and Systemic Corticosteroids in the Management of Patients with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: To date, there is no effective treatment for the new coronavirus disease (COVID-19). We aimed to systematically review the literature on the association between the combination of tocilizumab (TCZ) and systemic corticosteroid therapy (SCT) on outcomes of COVID-19 patients. METHODS: We searched MEDLINE, Cochrane Central, and preprints, for studies in which health outcomes were compared between adults with severe COVID-19 who received TCZ and SCT and those who received standard of care without TCZ. Record screening, data extraction, and risk of bias assessment were performed in duplicate. Random effect models were used when pooling crude numbers and adjusted effect estimates of study outcomes. RESULTS: Our search identified seventeen studies. The pooled crude mortality rate was lower in the combination arm (relative risk, RR=0.62, 95% confidence interval [CI]=0.42 - 0.91; I2=60%). The adjusted mortality rates were also lower in the combination arm (RR=0.58, 95% CI=0.42 - 0.81; I2=71%). The rate of superinfections did not differ between the two interventions. CONCLUSIONS: The findings of this study show that combination of TCZ and SCT compared to SOC has lower mortality rates. There is an urgent need for well-designed randomized trials to assess the safety and efficacy of this combination in subjects with severe COVID-19.

Impact of the corticosteroid indication and administration route on overall survival and the tumor response after immune checkpoint inhibitor initiation.

BACKGROUND: Based on their indications, systemic corticosteroids appear to negatively affect clinical outcomes in immune checkpoint inhibitor (ICI)-treated patients. There are few data on the influence of topical and inhaled corticosteroids on the ICIs' effectiveness. METHODS: In a single-center study, we retrospectively investigated the impact of systemic corticosteroids according to their indication [an immune-related adverse event (irAE) or another indication] on overall survival (OS) and the tumor response in all consecutive patients after initiation of ipilimumab, nivolumab or pembrolizumab over a 9-year period. The impacts of topical and inhaled corticosteroids were also examined. RESULTS: Three hundred and seventy-two patients were included. The mean ± standard deviation age was 64.0 ± 12.1 years. The most frequently prescribed ICI was nivolumab (in 58.3% of the patients) and the most frequent indications were lung cancer (44.6%) and melanoma (29.6%). Systemic corticosteroid use for an irAE did not have a negative impact on OS [adjusted hazard ratio (HR) [95% confidence interval (CI)] 1.04 (0.56-1.95), p = 0.902] or the best overall tumor response [adjusted odds ratio (OR) (95% CI) 1.69 (0.52-6.56), p = 0.413], while systemic corticosteroid use for another indication was associated with shorter OS [adjusted HR (95% CI) 1.34 (1.05-2.03), p = 0.046] and a poor best overall tumor response [adjusted OR (95% CI) 2.04 (1.07-5.80), p = 0.039] with a cumulative dose cut-off of 3215 mg prednisolone equivalent (specificity 71.4%; sensitivity 65.3%) and a time cut-off of 132 days (specificity 71.4%; sensitivity 89.8%). The use of topical corticosteroids was associated with a longer OS; this was probably due to dermatological irAEs. Inhaled corticosteroid use did not influence OS. CONCLUSION: Systemic corticosteroid use for an irAE does not impact OS or the tumor response, whereas use for other indications (themselves often associated with a worse prognosis) does. Topical and inhaled steroids do not have a negative impact on OS.

Influence of corticosteroid therapy on viral reactivation in drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms.

Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction characteristically associated with sequential reactivation of herpesviruses, such as human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Since systemic corticosteroids are thought to result in viral reactivation due to their immunosuppressive effects, we clarified the influence of systemic corticosteroid therapy on viral reactivation in DIHS/DRESS. Viral DNA in peripheral whole blood and serum sIL-2R level were measured during the disease course in twenty DIHS/DRESS patients. Six of seven patients treated without corticosteroids experienced HHV-6 viremia associated with elevated serum sIL-2R levels. In contrast, high-dose corticosteroids started within 1 week after onset tended to inhibit the occurrence of HHV-6 reactivation with remarkable suppression of serum sIL-2R level. Low-dose corticosteroids or late-start high-dose corticosteroids did not suppress occurrence of HHV-6 viremia and the increase of sIL-2R levels. HHV-6 load in the blood was clearly correlated with the serum sIL-2R level. On the other hand, increased CMV load were found in patients treated with corticosteroids regardless of the start time. The frequency of detection of EBV DNA in peripheral blood was similarly observed in all groups. In conclusion, high-dose corticosteroids started within 1 week tended to suppress HHV-6 reactivation through suppression of T cell activation. However, CMV proliferation was promoted by corticosteroids regardless of the start time. These observations suggested that careful consideration should be given to the dose and timing of administration of systemic corticosteroids in the treatment of DIHS/DRESS.

Combination treatment of short-course systemic corticosteroid and favipiravir in a successfully treated case of critically ill COVID-19 pneumonia with COPD.

Use of systemic corticosteroids for the treatment for coronavirus disease 2019 (COVID-19) among chronic obstructive pulmonary disease (COPD) patients is not well described. A 58-year-old man with fever and progressive dyspnea was admitted to the Showa University Hospital, and showed severe respiratory failure which needed mechanical ventilation. His chest computed tomography scanning showed emphysema and bilateral ground-glass opacity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. He received 30 mg prednisolone for five days with antiviral drug of favipiravir, and was successfully extubated on day five. A SARS-CoV-2 polymerase chain reaction (PCR) test became negative on day 15. He was discharged on day 21. Serum IgM and IgG antibodies against SARS-CoV-2 converted to positive on day 7 and they kept positive on day 54 for both IgM and IgG. Combination treatment of short-course systemic corticosteroid and favipiravir might improve the prognosis for critically ill COVID-19 pneumonia with COPD without negative influence on viral clearance or antibody production.

Investigating the Hypothesis of Stress System Dysregulation as a Risk Factor for Central Serous Chorioretinopathy: A Literature Mini-Review.

Background: This mini-review addressed the question "what do we know about the association between the dysregulation of stress systems (HPA axis and SAM) and the onset and prognosis of CSC in adult populations?" Methods: The literature mini-review was conducted through electronic searches using the PubMed, Web of Science, and Scopus databases. All published human and animal studies with both observational and experimental designs from 1966 to October 2018 were included. Results: Our search identified 229 reports, of which 32 articles were ultimately identified to be reviewed in this paper. Among these key articles, twenty-three were related to exogenous and/or endogenous high glucocorticoids as risk factors for CSC, seven were related to Type-A behavior and chronic psychological distress as risk factors for idiopathic CSC, and two were related to stress-induced animal models of CSC. Nineteen out of twenty-three studies in the first group reported a consistent association between high circulating corticosteroids and the onset and prognosis of CSC. Six out of seven studies in the second group reported a consistent association between stress-induced allostatic (over)load and the appearance of more- or less-severe CSC disorders, assuming that elevated circulating steroids may constitute a kind of risk factor for the eye through dysregulation of the HPA axis. All the selected studies reported HPA axis dysregulation as a possible common factor to explain the association between high circulating corticosteroids and CSC. In contrast, the involvement of the SAM system is only indirectly taken into consideration through the PA and HR measures and/or plasma and 24-h urinary catecholamine levels. Therefore, information regarding the involvement of SAM system dysregulation in the onset and prognosis of CSC is lacking. This observation is particularly relevant in view of the fact that animal models of CSC in monkeys are primarily induced by adrenergic hypertonia and that the course of experimental CSC is not further exacerbated by the administration of corticosteroids.

Nebulized Corticosteroids in the Treatment of COPD Exacerbations: Systematic Review, Meta-Analysis, and Clinical Perspective.

BACKGROUND: COPD guidelines report that systemic corticosteroids are preferred over inhaled corticosteroids in the treatment of exacerbations, but the inhaled route is considered to be an option. OBJECTIVES: To conduct a systematic review and meta-analysis regarding the efficacy and safety of inhaled corticosteroids for COPD exacerbations. The second objective was to provide pharmacologic and clinical perspectives of inhaled corticosteroids for COPD exacerbations. METHODS: The primary outcome was a change in FEV1 baseline versus the last measured value. Secondary outcomes were a change in (PaO2 ) and (PaCO2 ) baselines versus the last measured values; FEV1, PaO2 , and PaCO2 at 24 or 72 h; and hyperglycemia. RESULTS: Each of the 9 studies included in the meta-analysis was conducted in subjects who were hospitalized and not critically ill. Our meta-analysis indicated that high-dose nebulized budesonide 4-8 mg/d was noninferior to systemic corticosteroids on the change in FEV1 between baseline and the last measured value (mean difference of 0.05, 95% CI -0.01 to 0.12, P = .13) and PaCO2 (mean difference of -1.14, 95% CI -2.56 to 0.27, P = .11) but of inferior efficacy for PaO2 changes (mean difference of -1.46, 95% -2.75 to -0.16, P = .03). Hyperglycemia was less frequent with high-dose nebulized budesonide (risk ratio, 0.13; 95% CI 0.03-0.46; P = .002). CONCLUSIONS: Based on our meta-analysis with a change in FEV1 as the primary end point, high-dose nebulized budesonide was an acceptable alternative to systemic corticosteroids in hospitalized subjects with COPD exacerbations who were not critically ill. Additional well-designed prospective studies are needed in both the acute care and ambulatory settings. We provide perspective on how this evidence might be applied in clinical practice.