Duration Of Corticosteroid Use Research Articles

Proton pump inhibitors are detrimental to overall survival of patients with glioblastoma: results from a nationwide real-world evidence database

Abstract Background Proton pump inhibitors (PPIs) are often prescribed to manage corticosteroid-induced gastrointestinal toxicity during glioblastoma (GBM) treatment, but were recently identified as strong inducers of aldehyde dehydrogenase-1A1 (ALDH1A1). ALDH1A1 is a primary metabolic enzyme impacting outcome of chemotherapy, including temozolomide. High expression of ALDH1A1 is associated with poor prognosis in multiple cancers, suggesting PPIs may have a negative impact on survival. Methods Real-world data on GBM patients was annotated from electronic medical records (EMR) according to the prospective observational study, XCELSIOR (NCT03793088). Patients with known IDH1/2 mutations were excluded. Causal effects on survival were analyzed using a multivariate, time-varying Cox Proportional Hazard (CPH) model with stratifications including MGMT methylation status, age, sex, duration of corticosteroid use, extent of resection, starting SOC, and PPI use. Results EMR data from 554 GBM patients across 225 cancer centers was collected, with 72% of patients receiving care from academic medical centers. Patients treated with PPIs (51%) had numerically lower median overall survival (mOS) and 2-year OS rates in the total population and across most strata, with the greatest difference for MGMT-methylated patients (mOS 29.2 mo vs. 40.1 mo). In a time-varying multivariate CPH analysis of the above strata, PPIs caused an adverse effect on survival (HR 1.67 [95% CI 1.15-2.44], p=0.007). Conclusions Evidence from a nationwide cancer registry has suggested PPIs have a negative impact on OS for GBM patients, particularly those with MGMT promoter methylation. This suggests PPIs should be avoided for prophylactic management of gastrointestinal toxicity in patients with GBM receiving chemoradiotherapy.

Corticosteroid use in neonatal hypotension: A survey of Canadian neonatologists

ObjectiveTo assess prescribing practices and perspectives regarding the use of corticosteroids in the management of neonatal hypotension. MethodsCross-sectional questionnaire-based electronic survey of neonatologists (n = 206) practicing at tertiary neonatal intensive care units across 30 academic centres in Canada. ResultsThe overall response rate was 33% (72/206), with a completion rate was 94%. Most (48/72, 64%) worked in a unit that covered both inborn and outborn infants, and 53% (37/70) worked in units with >100 very low birth weight infants admitted annually. Among the 72 respondents, 39% use a loading dose, of whom most (57%) use 2 mg/kg. Dosing ranges were variable, most using either 0.5 mg/kg or 1 mg/kg, q6h. Among the 56% (40/72) of neonatologists who reported measuring cortisol before initiation of hydrocortisone, cut-offs for initiation of hydrocortisone varied from <100 to <500 nmol/L, most of whom (48%) used <100 nmol/L. Of 71 respondents, 92% (65) indicated that a randomized control trial examining the use of corticosteroids in neonatal hypotension is needed, of whom 52% (37) indicated that the intervention group should receiving hydrocortisone after one vasopressor/inotrope. ConclusionsThis survey provides insight into the prescribing practices of tertiary neonatologists with regards to the use of corticosteroids in neonatal hypotension. While corticosteroids are frequently prescribed, there is variability in the indication, dosing, and duration of corticosteroid use. The findings from this survey can be used to inform further research, including a clinical trial, regarding the practice in the management of neonatal hypotension.

Patterns and Safety of Glucocorticosteroids Use Following CD19 CAR-T Cell Therapy for B-Cell Lymphoma

Introduction: CAR T-cell therapy is a well-established therapy for relapsed and/or refractory B cell non-Hodgkin's lymphomas (R/R B-NHL). However, CAR-T cell therapy may cause significant toxicities such as CRS and ICANS. Glucocorticosteroids play a pivotal role in managing these toxicities but can also suppress T cell function and may impede the persistence and effectiveness of CAR-T cells. The impact of glucocorticosteroids has resulted in conflicting conclusions in the literature. Objective: This single-center, retrospective, observational study aimed to compare the outcomes of patients with R/R B-NHL who received steroids to those who did not after CAR-T cell therapy. Methods: Patients' records were reviewed to identify any steroid administration within 30 days of CAR-T cell infusion. Patients receiving steroids within 7 days before CAR-T infusion were excluded to focus on CAR-T impact without confounding baseline steroid use. Information on the type of steroids, indication, timing and duration was collected. Steroids were expressed as dexamethasone equivalent. Steroids-associated variables were analyzed as both continuous and categorical variables, using median as the threshold. Cox regression models and Kaplan-Meier analysis was employed for PFS and OS estimation using steroids as a time-dependent covariate and a 30-day landmark analysis, with events as disease progression or death for PFS and death only for OS. Results: 292 patients with R/R B-NHL received commercial CAR-T cell therapy (48% axi-cel, 24% tisa-cel, 22% liso-cel, and 6% Brexu-cel), primarily for large B cell cell lymphoma (85%), mantle cell (11%) or follicular (4%) lymphoma. Only 49 of the 292 patients (17%) received steroids between the day of infusion (day 0) to 30 days after. The median cumulative dexamethasone-equivalent dose at 30 days was 60 mg (range: 1-1982), the median day from CAR-T cells infusion to steroids initiation was 7 days (range 0-26) and the median duration of corticosteroid use was 3 days (range, 1-27). Patients receiving steroids had a significantly higher number of lines of prior therapies (p=0.036), more stage 3-4 disease (p=0.027), and elevated pre-lymphodepletion LDH levels(p=0.004). However, there were no other significant differences, including CD19 CAR-T product type, between the groups. The rates of grade 2 or higher CRS and ICANS were documented in 42% and 18%, respectively. ICANS (47%), CRS (14%), or both (21%) were the leading indications for steroid administration. Other indications for administration of steroids were progression of disease (n=4), adrenal insufficency (n=3), graft vs host disease (n=1), and premedication with intravenous immune globulin (n=1). With a median follow-up of 20 months, median PFS and OS were 6.8 months (95% CI 6-11) and 27 months (95% CI 18-not reached), respectively. The use, duration, and cumulative dose of steroids, whether analyzed as continuous or categorial variables in univariable Cox regression models, were not associated with PFS and OS in a 30 landmark analysis ( Figure). The analysis of the adminstration of steroids as a time-dependent covariate did not show significant differences for either PFS or OS. Importantly, patients exposed to steroids were also not at increased risk for bloodstream infections (p=0.68). Conclusion: In this largest analysis to date on the impact of steroids on CAR-T outcomes, steroid exposure following CAR-T cell infusion was not associated with a greater likelihood of CAR-T cell therapy failure. Our results deviate from previous observations that associate using steroids with shorter PFS and OS (Starti et al, Blood 2021, Terao et al, JTCT 2023). The discrepancy is likely due to our study's exclusion of steroid use prior to CAR-T and statistical analysis. Overall, our findings suggest that steroid administration for CAR-T cell therapy toxicity management is safe and does not appear to have a negative impact on efficacy.

A215 EVALUATING THE COMPARABILITY OF CARE FOR PERSONS ADMITTED TO TORONTO AREA HOSPITALS WITH ACUTE SEVERE ULCERATIVE COLITIS

Abstract Background Approximately 20% of patients with ulcerative colitis will experience an acute severe exacerbation requiring hospitalization. Acute severe ulcerative colitis (ASUC) is a medical emergency associated with significant morbidity and a mortality rate of 1%. Timely initiation of treatment and assessment of clinical response is critical in the management of ASUC. With an aim to reduce treatment variability and improve outcomes, multiple gastrointestinal societies have published guidelines highlighting recommendations for optimal care in ASUC. It remains unclear how closely these guidelines are implemented in clinical practice. Measuring adherence to these recommended processes of care may act as a surrogate measure for quality of care and a way to indirectly evaluate outcomes in the management of patients with ASUC. Studies have shown that even amongst experienced providers practice pattern variability exists. Identifying significant variations in the management of patients with ASUC will highlight where improvement in guideline dissemination and greater adherence is required. Purpose We sought to evaluate how quality of care indicators varied across 7 hospital sites for patients admitted ASUC in the Greater Toronto Area. Method Using GEMINI, a research collaborative that collects and analyses data from inpatient admissions at 7 Toronto area hospitals, we identified patients admitted to hospital with ASUC from June 2016-December 2019. Hospital sites were further categorized into 3 hospital types; 1 IBD specialty centre (ISC), 3 other academic centres (AC) and 3 community centres (CC). Process measures assessed included proportion tested for C-reactive protein at baseline and following treatment initiation, duration of corticosteroid use, timing and initiation of biologic agents, rates of venous thromboembolism prophylaxis and opioid use. Outcome measures included hospital length of stay, rates of colectomy and mortality. Result(s) 765 hospitalizations were included in the study; 320 occurring at ISC, 308 at AC and 137 at CC. Corticosteroid use on admission were highest at the ISC at 78% compared to 64% at AC and 63% at CC (p &amp;lt;0.001). Among those who received steroids on admission, 47% of patients remained on intravenous corticosteroids for at least 5 days in the ISC compared to 39% in AC and 75% in CC (p&amp;lt; 0.001). Initiation of biologic rescue therapy was highest at the ISC occurring in 37% of hospitalizations compared to 22% in AC and 23% in CC (p&amp;lt;0.001). In addition, VTE prophylaxis rates were highest at the ISC at 83% followed by 60% in AC and 45% in CC (p&amp;lt;0.001). Rates of colectomy were highest at ISC (12% of hospitalizations vs. 7% in AC). Conclusion(s) Greater adherence to indicators of quality of care were seen at the ISC compared to ACs and CCs, although patient outcomes assessed were not clearly different between sites. Further strategies are required to improve adherence to markers of quality care for patients admitted with ASUC. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Long-term Observation in Patients with Duchenne Muscular Dystrophy with Early Introduction of a Standing Program Using Knee-ankle-foot Orthoses.

This study investigated the outcomes of the early introduction of a standing program for patients with Duchenne muscular dystrophy (DMD). This was a retrospective observational study of 41 outpatients with DMD aged 15-20 years. We introduced the standing program using knee-ankle-foot orthoses (KAFO) to slow the progression of scoliosis when ankle dorsiflexion became less than 0° in the ambulatory period. Thirty-two patients with DMD were offered the standing program with KAFO; 12 continued the program until the age of 15 years (complete group) and 20 discontinued the program before the age of 15 years (incomplete group). The non-standing program group included 9 patients. The standing program with KAFO was significantly associated with the Cobb angle at the age of 15 years after adjustment for the duration of corticosteroid use and DMD mutation type (P=0.0004). At the age of 15 years, significant correlations were found between the ankle dorsiflexion range of motion (ROM) and non-ambulatory period (P=0.0010), non-ambulatory period and Cobb angle (P<0.0001), Cobb angle and percent predicted forced vital capacity (P=0.0004), and ankle dorsiflexion ROM and Cobb angle (P=0.0066). In the complete group, the age at ambulation loss (log-rank P=0.0015), scoliosis progression (log-rank P=0.0032), and pulmonary dysfunction (log-rank P=0.0006) were significantly higher than in the non-standing program group. The early introduction of a standing program for DMD patients may prolong the ambulation period and slow the progression of scoliosis and pulmonary dysfunction.

The Effects of Immunomodulation with Corticosteroids to Manage an AAV Capsid Immune response in the Phase I/II Study of SPK-8011

Background: Hemophilia A (HA) is an inherited blood disorder caused by deficiency or dysfunction of coagulation factor VIII (FVIII). SPK-8011 is an adeno-associated viral (AAV) vector gene therapy targeting hepatocyte expression of FVIII, aiming to provide durable FVIII expression and long-term bleed prevention. A Phase I/II trial of SPK-8011 (NCT03003533/NCT03432520) has demonstrated multiyear sustained FVIII expression and notably reduced bleeding in people with HA, with no major safety concerns. There are challenges around preventing and managing cellular immune responses to transduced hepatocytes. Here, we present the outcomes of participants who received corticosteroids following vector administration to prevent and/or treat a presumed AAV capsid immune response. Methods: In this open-label, multicenter, non-randomized, dose-escalation trial, people with HA were infused with SPK-8011 at one of four doses ranging from 5×1011 to 2×1012 vg/kg (full methods published in George et al. New Engl J Med 2021). Participants had baseline FVIII activity of ≤2% of normal levels and were negative for neutralizing antibodies to SPK200. Participants were monitored for 52 weeks after vector administration and enrolled in a 4-year long-term follow-up trial. Corticosteroids were used reactively at the investigators’ discretion upon a presumed capsid immune response, i.e., decrease in FVIII expression, increase in alanine aminotransferase (ALT) level, and/or positive peripheral blood mononuclear cells using interferon-γ enzyme-linked immunospot (ELISpot) to SPK200 peptides. Following loss of FVIII expression in two participants, a prophylactic regimen was explored. Assessments included duration of corticosteroid use and associated adverse events (AEs). Results: Twenty-three males with HA were dosed with SPK-8011 and 17 received corticosteroids (12 reactively, 5 prophylactically); five did not have evidence of a capsid immune response, and one remains in the window of a capsid immune response in the follow-up period (data cut-off: 30 Jun 2022). The median (range) time to initiation of reactive corticosteroids was 9.3 (4.3-12.1) weeks post vector infusion in the 12 participants, with a median (range) duration of treatment of 8.5 (2-18) weeks. Two of these 12 participants completely lost FVIII expression following a presumed capsid immune response (one initiated emicizumab; one resumed FVIII prophylaxis); FVIII expression was maintained in the remaining 10 participants. Corticosteroids were administered prophylactically (2-4 weeks post vector) in five participants, with transgene expression maintained in all five. In four of these five participants, length of exposure was prolonged (31-49 weeks), with attempted corticosteroid tapering resulting in decreased FVIII expression, increased ALT and/or positive ELISpot assays outside the typical window of capsid immune responses. Four participants had AEs related to corticosteroid therapy (Table), with weight gain (8.7%; n=2) and insomnia (8.7%; n=2) being the most common. The occurrence of AEs attributed to corticosteroids increased with duration of use, particularly in those with exposure of >30 weeks. Prophylactic corticosteroids did not consistently prevent a presumed capsid immune response in these five participants and four experienced prolonged courses of corticosteroids necessitating steroid-sparing agents (Figure). All five participants who received prophylactic corticosteroids and four participants who received reactive corticosteroids experienced a recurrence of one or more laboratory trigger(s) potentially linked to a presumed capsid immune response during their corticosteroid taper. Subsequent increased corticosteroid use did not consistently resolve these laboratory changes. Conclusions: Overcoming the challenge of capsid immune responses to achieve long-term stable and predictable FVIII expression remains a goal of AAV gene transfer for HA. Reactive oral corticosteroids were well tolerated but did not prevent loss of FVIII expression in all participants. Early prophylactic corticosteroids did not consistently prevent presumed capsid immune responses and resulted in prolonged immunomodulatory courses with associated AEs. Data so far have permitted refinement of laboratory triggers and investigation is ongoing to identify an alternative, safe and optimal immunomodulatory regimen. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Corticosteroids reduce vascular ultrasound sensitivity in fast- track pathways (FTP): results from Coventry Multi-Disciplinary FTP for cranial Giant Cell Arteritis

Objectives This study aims to assess the feasibility of the Coventry ultidisciplinary fast-track cranial giant cell arteritis (FTGCA) pathway, which was set up in 2013 in collaboration with vascular physiology and ophthalmology to enable prompt multidisciplinary assessment, including ultrasound (US). This study also looks at the impact of prior corticosteroid (CS) use on the performance of US in real life. Method Data were collected retrospectively for patients who attended the Coventry FTGCA pathway between 1 January 2014 and 31 December 2017. Patients were identified from US lists and clinical details were obtained from electronic medical records. Results In total, 620 eligible patients were included in this study. US had a sensitivity of 50%, which improved to nearly 56% in CS-naïve patients. The median duration of CS use prior to US was 2 days, and sensitivity was around 46% in this group. The specificity of US was > 96%, and CS use was avoided completely in 345 patients (56%). CSs natively impacted on the utility of US, with US more likely to be false negative. Conclusions This novel multidisciplinary pathway demonstrates excellent feasibility and minimizes the use of CSs in patients without giant cell arteritis. US was performed promptly, was cost effective- and had reassuring real-life sensitivity and specificity in this cohort, with excellent patient feedback. CS-naïve patients showed higher sensitivity for US despite the short duration of CS use.

Prevalence and Risk Factors for Adrenal Insufficiency in Patients with Multiple Myeloma Receiving Long-Term Chemotherapy including Corticosteroids: A Retrospective Cohort Study.

Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18 μg/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid (odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.98–0.99; P = 0.020) and megestrol acetate use (OR = 2.63, 95% CI 1.48–4.67; P = 0.001) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI (OR = 2.54, 95% CI 1.41–4.60; P = 0.002). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.

394. Descriptive Evaluation of Epidemiology and Microbiology of Patients with COVID-19 Pre/post Implementation of Corticosteroids as Standard of Care

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic continues to present a significant global public health concern. As of June 2021, nearly 174 million cases of SARS-CoV-2 infection worldwide have been reported to the World Health Organization. Rigorous data on the efficacy of corticosteroids have now established its role as standard of care (SOC). Less recognition has been given to corticosteroid therapy and its association with risk of infection especially in those who are critically ill and prone to nosocomial pathogens.MethodsThis is a retrospective study of mechanically ventilated patients with COVID - 19 from March 2020 to September 2020 at a single center. The primary endpoint for this study was description of microbiology and epidemiology of secondary infections and co -infections, defined as any infection following treatment for COVID - 19. Secondary endpoints included the duration of corticosteroid use, length of hospital stay, ICU length of stay, and mortality.ResultsOf the 104 patients, 73% had co-infections or secondary infections. Pre-SOC patients were more likely to receive >10 days of corticosteroids (71% vs 30%). Co-infections were present in 12% of patients (13% in pre-SOC vs 11% in post-SOC), secondary infections occurred in 61% of patients (74% in pre-SOC vs 53% in post-SOC). The most common causative organism of co-infections and secondary infections were Staphylococcus aureus in the pre-SOC group and Escherichia coli and Pseudomonas aeruginosa in the post-SOC group. The mean hospital length of stay was 43 days pre-SOC vs 33 days post-SOC with a mean ICU length of stay of 33 vs 29 days, respectively. Mortality rate was similar between the two groups (55% vs 58%).ConclusionDifferences in epidemiology and microbiology was seen pre and post implementation of dexamethasone in June, 2020. Higher rates of co-infections were seen with this prolonged use of corticosteroids pre-SOC but it is unclear whether patients developed more co-infections as result of extended corticosteroid use, a longer hospital stay, or other factors. Further studies are needed to assess the optimal duration of corticosteroid use in this patient population with consideration to weigh benefit vs risk.Disclosures All Authors: No reported disclosures

Outcomes of immune checkpoint inhibitor-mediated colitis: Multicenter cohort study.

2643 Background: Immune checkpoint inhibitor (ICI)-mediated colitis (IMC) is a common and serious adverse event. Although small series have described the clinical presentation of IMC, large multicenter series that integrate clinical, endoscopic, and histologic findings are lacking. Methods: We retrospectively assessed patients who received ICI and had endoscopically confirmed IMC from 2010 to 2019. IMC was graded based on the CTCAE version 5.0 criteria. Multivariate logistic regression analyses were conducted to assess factors associated with recurrence of IMC symptoms and long duration of corticosteroids use (&gt; 70 days). Results: 675 patients were included. 387 patients were males (57%). Median age was 63 years. Melanoma was the most common cancer type (327; 48%). Most (365; 54%) patients received CTLA-4 inhibitor ICI, as monotherapy or in combination with PD-(L)1. Median time from ICI therapy to IMC was 62 days. IMC was grade 2 in 335 (50%) patients, Grade 3 in 181 (27%), and grade 4 in 16 (3%). 155 (23%) patients had mucosal ulceration on endoscopy, 91 of them had severe features (deep, large, or multiple ulcers); 336 (50%) patients had non-ulcerative inflammation. The rest had normal endoscopic findings with histologic inflammation. Most patients were admitted to the hospital for management of IMC (405; 60%) and 16 (3%) needed ICU-level of care. Treatment included corticosteroids in 577 (85%) patients (median duration 52 days), TNF inhibitor in 245 (36%), and vedolizumab in 90 (13%). 202 (32%) patients had recurrent IMC after resolution of symptoms. On multivariate logistic regression, factors associated with IMC recurrence and long (&gt; 70 days) duration of corticosteroid therapy were grade of IMC ( p = 0.049), treatment with infliximab or vedolizumab ( p = 0.044), presence of mucosal ulceration ( p = 0.034 ), or features of active histologic inflammation ( p = 0.076). Of note, patients with mucosal ulceration received infliximab or vedolizumab more frequently ( p &lt; 0.001). For patients with grade 2 IMC, mucosal inflammation on endoscopy and delay in performing endoscopy with time from IMC onset to endoscopy more than a month were associated with IMC recurrence and longer duration of corticosteroid use ( p = 0.029 and p &lt; 0.001, respectively). 16 (3%) patients had colonic perforation, 7 of them underwent surgical resection. No IMC-related death occurred. Conclusions: IMC is a clinically significant adverse event that can lead to premature termination of ICI therapy with high rates of hospital admission. Rarely, it results in colonic perforation requiring surgical intervention and ICU admission. Our data suggest that there is a utility of endoscopic and histologic evaluation in the prediction of worse outcomes from IMC. This finding is particularly important for grade 2 IMC as current guidelines do not recommend endoscopic evaluation for this group.

Short-Term Versus Long-Term Systemic Corticosteroid Use in the Acute Exacerbation of Chronic Obstructive Pulmonary Disease Patients.

BackgroundThe administration of systemic corticosteroids in chronic obstructive pulmonary disease (COPD) exacerbation is the first line of management. The duration of this administration, however, is not well established in clinical practice. The objective of this study is to compare the clinical outcomes between short-term and long-term corticosteroid use in the acute exacerbation of COPD patients.MethodsA single-centre, retrospective cohort study was conducted. From 2014 to 2018, all patients over 40 years old with COPD who were admitted to the hospital with a case of COPD exacerbation and received systemic corticosteroids at presentation were included. The subjects were divided into two groups according to the duration of systemic corticosteroid therapy. The primary outcome was hospital re-admission within 180 days. The secondary outcomes were 30 days mortality and length of hospitalisation. The two groups were compared using an independent sample t-test, a Chi-square test, and a Mann-Whitney U test, according to the data type.ResultsEighty patients met the inclusion criteria. A total of 52 (65%) patients completed long-term therapy, while 28 (35%) patients were on short-term treatment. A total of 15 (28.8%) patients reached the primary endpoint in the long-term treatment group versus 19 (67.9%) in the short-term treatment group (P = 0.001). The 30-day mortality was 4 (7.7%) and 0 (0%), respectively, and the median length of hospitalisation was 6.5 and 7.5 days in the long-term group and short-term group, respectively (P = 0.32, P = 0.88).ConclusionLong-term corticosteroid use in the management of acute COPD exacerbation was significantly associated with fewer 180 days re-admission. The duration of corticosteroid use remains controversial, and further studies are recommended to assess the relationship between patient profile and adherence to therapy post-discharge with re-exacerbation.

Efficacy and safety of low-dose corticosteroids for acute respiratory distress syndrome: A systematic review and meta-analysis.

There are conflicting results regarding whether corticosteroids have better efficacy than placebo in acute respiratory distress syndrome (ARDS) patients. Therefore, we aim to further evaluate the efficacy and safety of corticosteroids in adult ARDS patients. The databases, including Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, were searched from their inception to May 2, 2020. Randomized controlled trials (RCTs) and observational cohort studies were selected to assess the use of corticosteroids in adult ARDS patients. The quality of the results was judged by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The inverse-variance method with random or fixed effects modeling was used to compute pooled odds ratio (OR), standardized mean difference (SMD), and their 95% confidence interval (CI). Eight eligible RCTs and six cohort studies were included. The use of corticosteroids was associated with reduced mortality (OR 0.57, 95% CI 0.43-0.76, I2=35.1%, P=0.148) in ARDS patients, and the result was confirmed in the included cohort studies (OR 0.51, 95% CI 0.27-0.95, I2=66.7%, P=0.010). The subgroup analysis stratified by the initiation time and duration of corticosteroid use showed that early ARDS and prolonged corticosteroid use had significant survival benefits in the RCTs. The low-dose corticosteroid use was also associated with significantly more ventilator-free days and a reduced rate of new infections in ARDS patients. The low-dose corticosteroid therapy may be safe and reduce mortality, especially in patients with prolonged treatment and early ARDS.

Treatment patterns in adults with immune thrombocytopenia before, during and after use of thrombopoietin receptor agonists: a longitudinal prescription database study from Germany

ABSTRACT Objective To assess real-world treatment patterns in patients with immune thrombocytopenia (ITP) who received thrombopoietin receptor agonists (TPO-RAs) in Germany. Methods This was a longitudinal, retrospective study using anonymized patient-level data (IQVIA healthcare prescription database, covering 82% of German statutory prescriptions). Eligible patients (aged ≥18 years) had received ≥1 TPO-RA prescription (romiplostim/eltrombopag) from July 2016 to June 2019 (treatment duration ≥30 days). ITP medication use was assessed for 18 months prior to, during and for ≥6 months after TPO-RA treatment. Results A total of 3553 patients (median age 64 years) were included. Median persistence on TPO-RAs was 12 months (range 1–34). In the periods before, during and after TPO-RA treatment, oral corticosteroids were the most commonly used therapy (64.4%, 43.4% and 36.1% of patients, respectively); median cumulative doses across each period were 2521.9, 2000.0 and 2277.8 mg. The median total duration of corticosteroid use before, during and after TPO-RA therapy was 15, 18 and 32 weeks, respectively. The total median cumulative corticosteroid dose was 6799.7 mg. Conclusion We identified a potential overuse of corticosteroids in patients with ITP in Germany. Earlier use of TPO-RA therapy after a short course of corticosteroids could avoid side effects associated with long-term use.

PREVALENCE OF FRICTION INJURY AND ASSOCIATED FACTORS IN ELDERLY IN INTENSIVE THERAPY

ABSTRACT Objective: to analyze the prevalence of friction injuries and associated factors in the elderly admitted to the Intensive Care Unit. Method: a cross-sectional analytical study, developed in an Intensive Care Unit of a Teaching hospital, with a sample of 101 elderly. Data collection was conducted from November 2017 to May 2018, through interviews, consulting medical records and physical examination. For analysis, descriptive and inferential statistics were performed. Strength of associations between variables measured by odds ratio and 95% confidence intervals. Statistical significance level was set at 5% for all analyzes. Results: the sample studied had a mean age of 71.39 years, mostly male, married and without schooling, with more than one comorbidity, dependent, with dry and scaly skin and bruising on the extremities. The prevalence of friction injury was 28.7%, with an average of 1.93 injuries per elderly. There was a statistically significant association between the occurrence of friction injury with age, comorbidities, dry and scaly skin. Conclusion: the prevalence of friction injury was high and associated with age, comorbidities, dry and scaly skin, and mean duration of corticosteroid use.

A System to Determine Risk of Osteoporosis in Patients With Autoimmune Hepatitis

Osteoporosis is a feared complication of autoimmune hepatitis (AIH), but bone disease has not been well studied in these patients. We aimed to identify specific risk factors for osteoporosis in patients with AIH and to develop a scoring system that could be used to identify patients with increased risk of osteoporosis. We performed a retrospective cross-sectional study of 211 patients (mean age, 56.8 years; 79.1% women) in Germany with a diagnosis of AIH from 2012 through 2017 and an indication for assessment of bone mineral status. The patients underwent bone mineral density measurements by dual energy X-ray absorptiometry. A subgroup of 99 patients underwent a second measurement. We used logistic regression to identify patient and clinical factors associated with the presence of osteoporosis. We developed a weighted sum score for estimating risk of osteoporosis and tested it in development (n= 141) and validation (n= 70) sets of patients. According to dual energy X-ray absorptiometry measurements, 15.6% of patients had osteoporosis 42.9% were in the range for osteopenia. The prevalence of osteoporosis in patients 50 years or older was 19.2%. Univariate and logistic regression analyses showed that age older than 54 years, duration of glucocorticoid use >90 months, body mass index <23 kg/m2 and transient elastography values >8 kPA increased risk of osteoporosis 13.8-fold, 6.2-fold, 5.9-fold, and 3.0-fold, respectively. Based on these factors, we developed an index that identified patients at low-, moderate-, and high-risk of osteoporosis with an area under the curve of 0.811. Of the patients with a second osteodensitometry measurement, the rate of bone loss progression ranged from 2.7% after 1 year to 8.4% after 7 years (mean bone loss, 1.2% per year). Almost 20% of patients with AIH older than 50 years have osteoporosis. Older age, duration of corticosteroid use, low body mass index, and liver fibrosis are independent risk factors for bone loss.

Corticosteroids for pediatric septic shock patients

Background Septic shock remains a major cause of mortality and admission to the pediatric intensive care unit (PICU) in children. Management includes adequate fluid resuscitation, followed by catecholamine infusion, if needed. Corticosteroid therapy is advised for catecholamine-refractory shock, although this practice is controversial, as it was not beneficial in other studies.&#x0D; Objective To assess corticosteroid use in pediatric septic shock patients in Cipto Mangunkusumo Hospital.&#x0D; Methods This cross-sectional study included all patients aged 1 month-18 years with a diagnosis of septic shock during the study period of January 2014 to July 2018 admitted in PICU Dr. Cipto Mangunkuskumo Hospital, Jakarta. Data obtained from medical records were, age, sex, immunology status, port d’entrée of sepsis, inotropic and vasopressor usage, mechanical ventilation, corticosteroid type, hospital length of stay (LOS), and mortality outcome.&#x0D; Results Of 217 children with septic shock, 12 patients (5.5%) received corticosteroid therapy. The most common corticosteroid given was hydrocortisone (80%), with a 2 mg/kg BW loading dose, followed by a continuous infusion dose of 2-50 mg/kg BW/day. Almost all patients (11/12) received corticosteroid therapy until they died. Median duration of corticosteroid use was 2 (range 1-7) days, median number of inotropes and vasopressors used was 3 (range 2-4) agents, median LOS was 3 (range 1-9) days, and mortality rate was 100%.&#x0D; Conclusion A small proportion of pediatric septic shock patients received corticosteroid therapy. Their mortality rate was 100%. Further clinical study is needed to evaluate the benefit of corticosteroid therapy in pediatric septic shock patients.

Age distribution and seasonality in acute eosinophilic pneumonia: analysis using a national inpatient database

BackgroundAcute eosinophilic pneumonia (AEP) is a rare inflammatory lung disease. Previous studies have shown that most patients with AEP are aged 20 to 40 years, whereas several case studies have included older patients with AEP. These studies also suggested that AEP is more prevalent in summer, but they were limited due to their small sample sizes. We therefore investigated the age distribution and seasonality among patients with AEP using a national inpatient database.MethodsUsing the Japanese Diagnosis Procedure Combination database, we identified patients with a recorded diagnosis of AEP from 1 July 2010 to 31 March 2015. We examined patient characteristics and clinical practices including age, sex, seasonal variation, length of stay, use of corticosteroids, use of mechanical ventilation, and in-hospital mortality.ResultsDuring the 57-month study period, we identified 213 inpatients with AEP. The age distribution of AEP peaked twice: at 15 to 24 years and 65 to 79 years. The proportion of patients with AEP was highest in summer for those aged < 40 years, whereas it was distributed evenly throughout the year for those aged ≥ 40 years. The interval from hospital admission to corticosteroid administration and the duration of corticosteroid use were significantly longer in the older than younger age group.ConclusionsThe age distribution of patients with AEP was bimodal, and seasonality was undetected in older patients. Older patients may be more likely to have delayed and prolonged treatment.

Outcomes for core decompression with multiple drilling of the osteonecrosis of the femoral head in patients with solid organ transplantation.

This study aims to investigate the clinical and radiological outcomes of core decompression surgery performed with multiple drilling in solid organ transplantation patients with osteonecrosis of femoral head (ONFH) and evaluate the effectiveness of this procedure in regard to duration of corticosteroid use and stage of osteonecrosis. A total of 22 solid organ transplantation (kidney, liver or heart) patients (14 males, 8 females; mean age 43.3 years; range, 23 to 67 years) who were scheduled to undergo core decompression surgery with multiple drilling for ONFH were evaluated. Patients' Harris hip scores (HHSs) and radiographic data including Association Research Circulation Osseous (ARCO) staging and Kerboul grading were retrospectively reviewed at pre- and postoperative controls. Patients were followed-up for mean 34.3 months (range, 12 to 76 months). Two patients (9.09%) were performed total hip arthroplasty. These two patients' Kerboul grade was 3. There was no statistically significant relationship between preoperation and postoperative final control in terms of ARCO staging. There was no statistically significant difference between pre- and postoperative HHSs. Although multiple drilling is a safe and minimally invasive surgery, its effect is limited, particularly in solid organ transplantation patients with ONFH due to long-term corticosteroid use. Therefore, solid organ transplantation patients should be closely monitored in terms of ONFH development.

Duration of corticosteroid use and long‐term outcomes after adult heart transplantation: A contemporary analysis of the International Society for Heart and Lung Transplantation Registry

Long-term corticosteroid (CS) maintenance remains an effective option for immunosuppression following heart transplantation. We used the International Society for Heart and Lung Transplantation Registry to examine characteristics and long-term survival among heart transplant recipients with different duration of CS therapy. Primary adult heart recipients transplanted between 2000 and 2008 who survived at least 5years were categorized into three groups according to CS use: early withdrawal (≤2years) (EARLY D/C), late withdrawal (between 2 and 5years) (LATE D/C), or long-term use (>5years) (LONG-TERM). Recipient and donor characteristics, post-transplant morbidities, and mortality were compared among groups. Kaplan-Meier was used to estimate survival up to 10years post-transplant. The study cohort included 8161 recipients (2043 in EARLY D/C; 2031 in LATE D/C; and 4087 in LONG-TERM). LONG-TERM use of CS decreased over time, from 60% in 2000 to 43% in 2008, while EARLY D/C increased from 19% to 33%, respectively. Survival at 10years after transplant was lower among the LONG-TERM group (73% vs EARLY D/C 82% vs LATE D/C 80%; P<0.0001). In this large multinational cohort, the practice of long-term CS maintenance was associated with lower long-term survival compared with shorter CS use.

Prevalence and predictors of asymptomatic vertebral fractures in inflammatory myositis

To assess the frequency and risk factors of asymptomatic vertebral fractures in inflammatory myositis. Dorsal and lumbar spine lateral radiographs were taken for adults with inflammatory myositis and scored using Genant's semi-quantitative technique. Demographic data, weight, height, postmenopausal status, duration of corticosteroid use, drug intake, co-morbidities and past history of fractures were recorded. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry (DEXA). Myositis Damage Index (MDI) was also assessed. All results are expressed in median and interquartile range. One hundred patients (82 female) with myositis of median age 35.5 (28.5-46) years and disease duration 3.0 (1.81-8.0) years were studied. Thirty-five patients had adult dermatomyositis (DM), 26 polymyositis, 31 connective tissue disease-associated myositis and eight had juvenile onset myositis. Seventeen were postmenopausal women. Forty-six patients had asymptomatic vertebral fractures and 19 had more than one fracture. Half the fractures occurred in those with disease duration of <5years. Of the 69 fractures, 47 (68.1%), 16 (23.2%) and 6 (8.7%) were mild, moderate and severe, respectively. The 11th and 12th thoracic vertebrae were together the most commonly (30.4%) affected. Of the 70 who underwent BMD assessment, 62.7% were osteopenic and 26.9% were osteoporotic. T scores of DEXA scan at the lower third of the radius correlated negatively with fracture number (r=-0.27 (-0.50 to -0.005), P=0.04). Gender, age, disease duration, years of corticosteroid intake, body mass index, years post-menopause and MDI had no correlation with number of fractures. Patients with inflammatory myositis have high prevalence of asymptomatic vertebral fractures.