Background:
The best way to administer steroids for sudden sensorineural hearing loss (SSHL) is still unclear. The present study was aimed at estimating the efficacy of steroids by intratympanic, ...systemic, and combined therapy (CT) routes.
Methods:
A systematic literature search was performed from 1950 to October 2019 for randomized controlled trials comparing the use of intratympanic, systemic, and combined steroid therapy for SSHL. The outcomes of recovery rate and pure tone average (PTA) improvement were assessed by random-effects and fixed-effects meta-analysis.
Results:
A total of 20 articles identified from 7 countries were eligible for analysis. Although no significant difference in recovery rate was observed between intratympanic steroid therapy (IST) and systemic steroid therapy (SST), IST did demonstrate better hearing improvement, as evidenced by a higher PTA than SST. Compared with SST, CT comprising IST and SST had significant recovery rate improvement. Patients treated with CT had a significantly higher PTA than those treated with SST. Through subgroup analysis based on the equivalent dose of prednisone, it was shown that CT led to a significantly higher PTA than SST only in the high-dose CT versus high-dose SST groups and moderate-dose CT versus high-dose SST groups.
Conclusion:
Moderate and high dose of CT could accelerate hearing improvement in SSHL.
To evaluate the incidence of GC-DM among patients with immunoglobulin A nephropathy (IgAN) and to confirm the risk factors for the development of GC-DM.
The medical records of patients with IgAN ...newly treated with the protocol of tonsillectomy combined with steroid pulse therapy were reviewed. The primary outcome was the development of GC-DM within the hospitalization period and during one year of follow-up.
During hospitalization, 19 of the 95 patients developed GC-DM (20.0%), and the patients with GC-DM were significantly older and had a higher rate of family history of diabetes and higher HbA1c levels. The prevalence of hypertension was higher and the eGFR was numerically lower in patients with GC-DM than in those without. Older age (≥45 years) and a family history of diabetes emerged as independent risk factors for the development of GC-DM (odds ratio OR, 6.3 and 95% confidence interval CI, 1.6-27.6; OR, 4.4 and 95% CI, 1.2-16.6, respectively). No patients were newly diagnosed with GC-DM during 1-year observation period at out-patient clinic.
Among the patients with IgAN, 20% developed GC-DM during the hospitalization period, confirming the family history of diabetes is clinically necessary before starting GC therapy.
We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin’s ...lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m
2
on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m
2
on day 5, and i.v. oxaliplatin 130 mg/m
2
on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% 12/36; partial response, 38.9% 14/36). The median time to progression was 34.9 months (95% confidence interval, 23.1–46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (
p
= 0.00005 for TNF-α,
p
= 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration:
ClinicalTrials.gov
. Registered February 21, 2011,
https://clinicaltrials.gov/ct2/show/NCT01300156
Objectives
Using data of patients from the inception cohort Registro Español de Lupus Eritematoso Sistémico (RELES), we aimed to analyse the incidence of severe infection in the first two years of ...follow-up and how predictors of infection change during the course of systemic lupus erythematosus (SLE).
Material and methods
The study included 282 patients. Markers of lupus activity, prednisone doses and immunosuppressive therapy were compared between patients with and without infections in the first and second year of the disease. Drug therapy administered during the first month of follow-up has been considered as a potential predictor of infections during the first year and medications administered during the first year have been considered potential predictors of infections during the second.
Results
Nineteen patients (6.4%) had a documented episode of major infection during the first year of follow-up and 16 patients (5.67%) during the second. The following variables were associated with infections during the first year: hypocomplementaemia at diagnosis (p < 0.01), nephritis at diagnosis (p = 0.03), SLEDAI score (p < 0.01), prednisone >30 mg/day (p = 0.01), methylprednisolone pulses (p = 0.05) and mycophenolate use (p = 0.02). The independent variables in the final model were hypocomplementaemia (odds ratio (OR) 4.41, 95% confidence interval (CI) 0.96–20.20, p = 0.05) and a dose of prednisone >30 mg/day (OR 6.60, 95% CI 1.34–32.42, p = 0.02). The following variables were associated with infections during the second year: dose of prednisone > 7.5 mg/day (p = 0.05), methylprednisolone pulses (p = 0.07), duration of therapy with antimalarials (p = 0.09), therapy with mycophenolate (p = 0.01), therapy with cyclophosphamide (p = 0.05). The independent variables in the final model were a dose of prednisone >7.5 mg/day (OR 4.52, 95% CI 0.99–21, p = 0.054) and duration of therapy with antimalarials as a protective factor (OR 0.99, 95% CI 0.99–1.00, p = 0.053).
Conclusions
The low incidence of early infections in the RELES cohort is partially explained by the extended use of antimalarials and by the general avoidance of prolonged high doses of prednisone. Patients with high baseline activity are at a higher risk of infection during the first months but therapy with medium–high doses of prednisone is the main predictor of infectious events. Thus, every effort should be made to limit oral glucocorticoid use from the very beginning of the SLE course.
Cytokine release syndrome (CRS) or cytokine storm is thought to be the cause of inflammatory lung damage, worsening pneumonia and death in patients with COVID-19. Steroids (Methylprednislone or ...Dexamethasone) and Tocilizumab (TCZ), an interleukin-6 receptor antagonist, are approved for treatment of CRS in India. The aim of this study was to evaluate the efficacy and safety of combination therapy of TCZ and steroid in COVID-19 associated CRS.This retrospective cohort study was conducted at Noble hospital and Research Centre (NHRC), Pune, India between April 2 and November 2, 2020. All patients administered TCZ and steroids during this period were included. The primary endpoint was incidence of all cause mortality. Secondary outcomes studied were need for mechanical ventilation and incidence of systemic and infectious complications. Baseline and time dependent risk factors significantly associated with death were identified by Relative risk estimation.Out of 2831 admitted patients, 515 (24.3% females) were administered TCZ and steroids. There were 135 deaths (26.2%), while 380 patients (73.8%) had clinical improvement. Mechanical ventilation was required in 242 (47%) patients. Of these, 44.2% (107/242) recovered and were weaned off the ventilator. Thirty seven percent patients were managed in wards and did not need intensive care unit (ICU) admission. Infectious complications like hospital acquired pneumonia, blood stream bacterial and fungal infections were observed in 2.13%, 2.13% and 0.06% patients respectively. Age ≥ 60 years (P = .014), presence of co-morbidities like hypertension (P = .011), IL-6 ≥ 100 pg/ml (P = .002), D-dimer ≥ 1000 ng/ml (P < .0001), CT severity index ≥ 18 (P < .0001) and systemic complications like lung fibrosis (P = .019), cardiac arrhythmia (P < .0001), hypotension (P < .0001) and encephalopathy (P < .0001) were associated with increased risk of death.Combination therapy of TCZ and steroids is likely to be safe and effective in management of COVID-19 associated cytokine release syndrome. Efficacy of this anti-inflammatory combination therapy needs to be validated in randomized controlled trials.
In contrast to dexamethasone, the clinical efficacy of methylprednisolone (MP) remains controversial, and a systems biology study on its mechanism is lacking. In this study, a total of 38 severe ...COVID-19 patients were included. The demographics, clinical characteristics, and severity biomarkers including C-reactive protein (CRP), d-dimer, albumin, and Krebs von den Lungen 6 of patients receiving MP (n=26, 40 mg or 80 mg daily for 3-5 days) and supportive therapy (n=12) were compared. Longitudinal measurements of 92 cytokines in MP group from admission to over six months after discharge were performed by multiplex Proximity Extension Assay. The results showed that demographics, baseline clinical characteristics were similar in MP and non-MP groups. No death occurred and the hospital stays between the two groups were similar. Kinetics studies showed that MP was not better than supportive therapy at improving the four severity biomarkers. Cytokines in MP group were characterized by five clusters according to their baseline levels and responses to MP. The immunological feature of severe COVID-19 could be defined by the "core signature" cytokines in cluster 2: MCP-3, IL-6, IFN-γ, and CXCL10, which strongly correlated with each other and CRP, and are involved in cytokine release storm. The "core signature" cytokines were significantly upregulated at baseline and remained markedly elevated after MP treatment. Our work showed a short course of MP therapy could not rapidly improve the immune disorders among severe COVID-19 patients or clinical outcomes, also confirmed "core signature" cytokines, as severity biomarkers similar to CRP, could be applied to evaluate clinical treatment effect.
Methylprednisolone (MP) is usually used to reduce inflammation reaction and tissue damage, which may have a beneficial treatment effect on coronavirus disease 2019 (COVID‐19). However, we present the ...case of a child who manifests significant bradycardia with the use of just low dose MP on the premise of the long‐term use of arbidol. Arbidol can affect the activity of CYP3A4, which is also a key metabolic enzyme of MP by competitive inhibition, and which is easy to aggravate the side effects of MP. Therefore, more attention should be paid to bradycardia occurrence in the patient with COVID‐19 when MP is considered in COVID‐19.
Highlights
The joint use of low dose MP and arbidol can also induce bradycardia in COVID‐19.
The mechanism of the MP‐induced bradycardia need to be demonstrated in more detail.
Background:
Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation.
Objective:
To ...validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers.
Methods:
CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA).
Results:
In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL.
Conclusion:
These findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.
Acute asthma is a common cause of presentations to acute care centres, such as the emergency department (ED), and while the majority of patients can be discharged, relapse requiring additional ...medical care is common. Systemic corticosteroids are a major part in the treatment of moderate to severe acute asthma; however, there is no clear evidence regarding the most effective route of administration for improving outcomes in patients discharged from acute care.
To examine the effectiveness and safety of a single dose of intramuscular (IM) corticosteroids provided prior to discharge compared to a short course of oral corticosteroids in the treatment of acute asthma patients discharged from an ED or equivalent acute care setting.
The Cochrane Airways Group conducted searches of the Cochrane Airways Group Register of Trials, most recently on 14 March 2018. In addition in April 2017 we completed an extensive search of nine electronic databases including Medline, Embase, EBM ALL, Global Health, International Pharmaceutical Abstracts, CINAHL, SCOPUS, Proquest Dissertations and Theses Global, and LILACS. Furthermore, we searched the grey literature to identify any additional studies.
We included randomized controlled trials or controlled clinical trials if they compared the effectiveness of intramuscular (IM) versus oral corticosteroids to treat paediatric or adult patients presenting with acute asthma to an ED or equivalent acute care setting. Two independent reviewers assessed study eligibility and study quality. We resolved disagreements via a third party and assessed risk of bias using the Cochrane 'Risk of bias' tool. We assessed the quality of the evidence using GRADE.
For dichotomous outcomes, we calculated individual and pooled statistics as risk ratios (RRs) with 95% confidence intervals (CIs) using a random-effects model. We reported continuous outcomes using mean difference (MD) or standardised mean difference (SMD) with 95% CIs using a random-effects model. We reported heterogeneity using I² and Cochran Q statistics. We used standard procedures recommended by Cochrane.
Nine studies involving 804 participants (IM = 402 participants; oral = 402 participants) met our review inclusion criteria. Four studies enrolled children (n = 245 participants), while five studies enrolled adults (n = 559 participants). All of the studies recruited participants presenting to an ED, except one study which recruited participants attending a primary care clinic. All of the paediatric studies compared intramuscular (IM) dexamethasone to oral prednisone/prednisolone. In the adult studies, the IM corticosteroid provided ranged from methylprednisolone, betamethasone, dexamethasone, or triamcinolone, while the regimen of oral corticosteroids provided consisted of prednisone, methylprednisolone, or dexamethasone. Only five studies were placebo controlled. For the purposes of this review, we did not take corticosteroid dose equivalency into account in the analysis. The most common co-intervention provided to participants during the acute care visit included short-acting beta₂-agonists (SABA), methylxanthines, and ipratropium bromide. In some instances, some studies reported providing some participants with supplemental oral or IV corticosteroids during their stay in the ED. Co-interventions provided to participants at discharge consisted primarily of SABA, methylxanthine, long-acting beta₂-agonists (LABA), and ipratropium bromide. The risk of bias of the included studies ranged from unclear to high across various domains. The primary outcome of interest was relapse to additional care defined as an unscheduled visit to a health practitioner for worsening asthma symptoms, or requiring subsequent treatment with corticosteroids which may have occurred at any time point after discharge from the ED.We found intramuscular and oral corticosteroids to be similarly effective in reducing the risk for relapse (RR 0.94, 95% CI 0.72 to 1.24; 9 studies, 804 participants; I² = 0%; low-quality evidence). We found no subgroup differences in relapse rates between paediatric and adult participants (P = 0.71), relapse occurring within or after 10 days post-discharge (P = 0.22), or participants with mild/moderate or severe exacerbations (P = 0.35). While we found no statistical difference between participants receiving IM versus oral corticosteroids regarding the risk for adverse events (RR 0.83, 95% CI 0.64 to 1.07; 5 studies, 404 participants; I² = 0%; moderate-quality evidence), an estimated 50 fewer patients per 1000 receiving IM corticosteroids reported experiencing adverse events (95% from 106 fewer to 21 more). We found inconsistent reporting of specific adverse events across the studies. There were no differences in the frequency of specific adverse events including nausea and vomiting, pain, swelling, redness, insomnia, or personality changes. We did not seek additional adverse events data.Participants receiving IM corticosteroids or oral corticosteroids both reported decreases in peak expiratory flow (MD -7.78 L/min, 95% CI -38.83 L/min to 23.28 L/min; 4 studies, 272 participants; I² = 33%; moderate-quality evidence), similar symptom persistence (RR 0.41, 95% CI 0.14 to 1.20; 3 studies, 80 participants; I² = 44%; low-quality evidence), and 24-hour beta-agonist use (RR 0.54, 95% CI 0.21 to 1.37; 2 studies, 48 participants; I² = 0%; low-quality evidence).
There is insufficient evidence to identify whether IM corticosteroids are more effective in reducing relapse compared to oral corticosteroids among children or adults discharged from an ED or equivalent acute care setting for acute asthma. While we found no statistical differences, patients receiving IM corticosteroids reported fewer adverse events. Additional studies comparing the effectiveness of IM versus oral corticosteroids could provide further evidence clarity. Furthermore, there is a need for studies comparing different IM corticosteroids (e.g. IM dexamethasone versus IM methylprednisone) and different oral corticosteroids (e.g. oral dexamethasone versus oral prednisone), with consideration for dosing and pharmacokinetic properties, to better identify the optimal IM or oral corticosteroid regimens to improve patient outcomes. Other factors, such as patient preference and potential issues with adherence, may dictate practitioner prescribing.
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