scholarly journals Comparison of Low-Versus High-Dose Steroids in the Clinical Outcome of Hospitalized COVID-19 Patients

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1510
Author(s):  
Zubia Jamil ◽  
Fahad N. Almajhdi ◽  
Samreen Khalid ◽  
Muhammad Asghar ◽  
Jamal Ahmed ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Low Dose ◽  
High Dose ◽  
High Dependency Unit ◽  
Invasive Ventilation ◽  
Hospital Survival ◽  
Elapsed Time ◽  
High Dose Dexamethasone ◽  
Kaplan Meier ◽  
High Dependency

(1) Objectives: Patients with COVID-19 infection have been given various formulations and dosages of steroids over the last year and a half. This study aims to compare the effects of different formulations and doses of steroids on the 30 day in-hospital clinical outcome of patients with severe COVID-19 infection. (2) Material and Methods: An analysis of a retrospective cohort was carried out on patients with severe COVID-19 infection in a high-dependency unit (HDU) between February and July 2021. In total, 557 patients were included in this study. Patients who did not receive steroids (124) were excluded. Patients were divided into three groups based on dosages of steroids (Dexamethasone = 6 mg/day, Dexamethasone > 6 mg/day, and Methylprednisolone = 500 mg/day), given for 10 days. First, clinical outcome was evaluated on the 10th day of steroid administration in relation to mode of oxygen delivery. Then, Kaplan–Meier analysis was employed to determine 30 day in-hospital survival in relation to the use of steroid. (3) Results: Three groups were statistically equal according to biochemical characteristics. After 10 days of Methylprednisolone = 500 mg/day vs. Dexamethasone = 6 mg/day, 10.9% vs. 6.2% of patients required invasive ventilation (p = 0.01). The 30 day in-hospital mortality was lowest, 3%, in individuals receiving Dexamethasone = 6 mg/day, compared to 3.9% in individuals receiving Dexamethasone > 6 mg/day and 9.9% in individuals receiving Methylprednisolone = 500 mg/day, respectively. The median elapsed time was longer than 28 days between admission and outcome for Dexamethasone = 6 mg/day, compared to 18 days for Dexamethasone > 6 mg/day and 17 days for Methylprednisolone = 500 mg/day (p = < 0.0001). Dexamethasone = 6 mg/day was found to be a positive predictor of clinical outcome in COVID-19 patients on regression analysis. (4) Conclusions: Low-dose Dexamethasone (6 mg/day) is more effective than high-dose Dexamethasone and Methylprednisolone in improving the survival outcome of severe COVID-19 cases.

scholarly journals Dexamethasone prevents virus-induced hyperresponsiveness via multiple mechanisms

2003 ◽  
Vol 285 (2) ◽  
pp. L451-L455 ◽  
Author(s):  
Liliana Moreno ◽  
David B. Jacoby ◽  
Allison D. Fryer
Keyword(s):  
Virus Infection ◽  
Airway Hyperresponsiveness ◽  
Low Dose ◽  
Acetylcholine Release ◽  
Parainfluenza Virus ◽  
High Dose ◽  
Muscarinic Agonist ◽  
Receptor Function ◽  
Parasympathetic Nerves ◽  
High Dose Dexamethasone

In the lungs, neuronal M2 muscarinic receptors inhibit acetylcholine release from the parasympathetic nerves. Parainfluenza virus infection causes loss of M2 receptor function, which increases acetylcholine release and vagally mediated bronchoconstriction. Because glucocorticoids are known to inhibit airway hyperresponsiveness, we tested whether dexamethasone (6.5 or 65 μg/kg ip) prevents virus-induced hyperresponsiveness and M2 receptor dysfunction in guinea pigs. In controls, pilocarpine, a muscarinic agonist, inhibited vagally induced bronchoconstriction, demonstrating functional M2 receptors. However, in virus-infected animals, pilocarpine failed to inhibit vagally induced bronchoconstriction, demonstrating M2 receptor dysfunction. Frequency-dependent bronchoconstriction was greater in virus-infected animals than in controls, indicating airway hyperresponsiveness. Low-dose dexamethasone (6.5 μg/kg ip) treatment prevented virus-induced airway hyperresponsiveness, ameliorated M2 receptor dysfunction, and decreased viral content in the lungs without inhibiting virus induced inflammation. High-dose dexamethasone (65 μg/kg ip) prevented virus-induced hyperresponsiveness, completely reversed M2 receptor dysfunction, decreased viral titers, and decreased virus-induced inflammation. This high-dose dexamethasone also increased M2 receptor function in uninfected animals. In conclusion, dexamethasone prevented virus-induced hyperresponsiveness and M2 receptor dysfunction via multiple mechanisms.

High response rate to low-dose rituximab plus high-dose dexamethasone as frontline therapy in adult patients with primary immune thrombocytopenia

2013 ◽  
Vol 90 (6) ◽  
pp. 494-500 ◽  
Author(s):  
David Gómez-Almaguer ◽  
Luz Tarín-Arzaga ◽  
Brizio Moreno-Jaime ◽  
José Carlos Jaime-Pérez ◽  
Adrián Alejandro Ceballos-López ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Low Dose ◽  
Response Rate ◽  
High Response Rate ◽  
High Response ◽  
Adult Patients ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Primary Immune Thrombocytopenia ◽  
Frontline Therapy

Phase II Trial of Bevacizumab Combined with Low Dose Dexamethasone and Lenalidomide (BEV/REV/DEX) for Relapsed or Refractory Myeloma (MM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1173-1173 ◽  
Author(s):  
Martha Raschko ◽  
Stephanie Markovina ◽  
Shigeki Miyamoto ◽  
Walter Longo ◽  
Eliot Williams ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Low Dose ◽  
Plasma Cells ◽  
Response Rate ◽  
Myeloma Cell ◽  
Median Number ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Grade 3

Abstract The interaction between malignant plasma cells and non malignant bone marrow microenvironment has been recognized as both an important feature of MM propagation and a therapeutic target. One critical interaction appears to involve angiogenesis as evidenced by increased blood vessel density in areas of myeloma cell proliferation. The potent anti MM compound lenalidomide may work partly through down regulation of VEGF expression by bone marrow stromal cells. We hypothesized that the addition of the VEGF-A receptor inhibitor, bevacizumab, in combination with low dose weekly dexamethasone, would provide more complete blockade of VEGF activation and translate to increased activity in MM patients with relapsed or refractory disease. ELIGIBILTY: relapsed or refractory MM patients (pts), failing >1 therapy, with no previous exposure to lenalidomide, measurable M protein in serum and/or urine, no current history of unstable cardiovascular disease or uncontrolled thrombosis, no therapy for ≥28 days, and no contraindication to aspirin. METHODS: Each 4 week cycle consisted of lenalidomide 25 mg PO d1–21, bevacizumab 10 mg/kg IV over 2 hours every two weeks, and dexamethasone 40 mg PO q week. All pts received aspirin 325 mg PO daily. Prior to therapy pts underwent bone marrow biopsy and aspirate. MM and stromal cells were isolated for analysis of STAT 3 activation to assess the treatment’s effect on stromal/MM cell interactions. Clinical responses were assessed using IBMTR criteria. RESULTS: 17 pts have been enrolled, ages 53––89, with median number of previous regimens 3 (range 1–6). Two pts were taken off study during the first cycle, one due to GI perforation occurring d 6 of therapy, and one pt due to rapidly progressive disease during first week of therapy. Ten pts have completed ≥ 4 cycles and can be evaluated for response. Seven of 10 pts achieved a PR after a median of two cycles and have maintained that response. One pt progressed after completing one cycle, one pt progressed after 5 cycles, and one pt had stable disease after 6 cycles. Expected grade 3 toxicities included DVT in 2 patients (both of whom were on aspirin but received erythropoiesis stimulating agents) and 2 pts developed shortness of breath attributed to bevacizumab, with resolved after discontinuation of the drug; one patient developed atrial fibrillation which spontaneously converted. No patient developed hypertension or proteinuria. Most required a dose reduction of lenalidomide due to fatigue. Analysis of STAT3 DNA-binding in MM cells alone or in co-culture with MM-BMSCs revealed variable low levels of constitutive STAT3 activity and enhanced activity in co-culture. No additional effect of bevacizumab + revlimid on constitutive STAT3 activity was observed. CONCLUSIONS: the combination of lenalidomide, bevacizumab and low dose dexamethasone has activity in relapsed and refractory myeloma. The initial 70% response rate compares favorably with the 58% response rate reported by Stadtmauer et al (Blood 108:3552) in previously treated MM pts receiving lenalidomide and high dose dexamethasone. Toxicities of this regimen are predictable but manageable. The use of ESAs may contribute to the development of DVT and the protocol has been modified to preclude their use.

Effect of insulin on dexamethasone-induced ultrastructural changes in skeletal and cardiac muscle

Biologia ◽  
2012 ◽  
Vol 67 (3) ◽  
Author(s):  
Jian Qin ◽  
Rong Du ◽  
Yaqun Yang ◽  
Hongqiang Zhang ◽  
Ying Zhou
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Cardiac Muscle ◽  
Muscle Atrophy ◽  
Low Dose ◽  
The Body ◽  
Muscle Size ◽  
Ultrastructural Changes ◽  
High Dose ◽  
High Dose Dexamethasone

AbstractGlucocorticoids help animals respond to stressors but excessive glucocorticoids cause muscle atrophy, while insulin can promote anabolism and growth. In order to compare the glucocorticoids-induced ultrastructural changes between skeletal muscle and cardiac muscle, and investigate the preventive effects of insulin on the changes, eighteen male chicks with similar initial weight were randomly divided into three groups. The two test groups were respectively treated with high-dose dexamethasone alone or together with low-dose insulin by intraperitoneal injection, and the control group was treated with an equal volume of saline solution. The experiment lasted for ten days, and then the body weight, muscle size and ultrastructure in skeletal and cardiac muscles of twelve chicks were qualitatively or quantitatively analyzed. The results showed that high-dose dexamethasone induced obvious skeletal and cardiac muscle atrophy. The differences of ultrastructural changes between skeletal muscle and cardiac muscle (such as for the former or the latter, the intermyofibrillar-and-interfilamentary spaces reducing or enlarging, the mitochondria swelling seriously or enlarging lightly, the myofibril filaments compacting or loosing) suggested that dexamethasone induced skeletal and cardiac muscle atrophy by different mechanisms. Low-dose insulin did not affect the dexamethasone-induced decreases of body weight and skeletal muscle size, but alleviated lightly the dexamethasone-induced ultrastructural changes in skeletal muscle. Different from skeletal muscle, low-dose insulin almost resisted the dexamethasone-induced ultrastructural changes in cardiac muscle.

Long-Term Effect of High-Dose Dexamethasone with or without Low-Dose Dexamethasone Maintenance in Untreated Immune Thrombocytopenia

2014 ◽  
Vol 133 (1) ◽  
pp. 124-128 ◽  
Author(s):  
Banhe Din ◽  
Xingwen Wang ◽  
Yuye Shi ◽  
Yufeng Li
Keyword(s):  
Immune Thrombocytopenia ◽  
Low Dose ◽  
Overall Response Rate ◽  
Control Group ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Group 4 ◽  
Long Term Effect ◽  
Group 2

Background: To tackle the problems associated with high-dose dexamethasone (HD-DXM) in patients with immune thrombocytopenia (ITP). Aim: To compare the efficacy of HD-DXM with or without low-dose dexamethasone maintenance in untreated ITP patients. Results: Dexamethasone (40 mg/day) was given in 4-day pulses every 14 days for 3 cycles in 61 patients with ITP. Among them, 30 cases were given dexamethasone (0.035 mg/kg per day) for maintenance between pulsed HD-DXM and after 3 HD-DXM courses (HD-DXM-M group) and another 31 cases did not receive dexamethasone maintenance (HD-DXM-nM group). The control group comprised the patients who received prednisone (prednisone group). The following results were obtained: (1) at the end of the 3rd cycle, the overall response rate (ORR) was higher in the HD-DXM group than in the prednisone group; (2) the ORR of the HD-DXM group peaked after the 3rd cycle; (3) the ORR after each course was higher in the HD-DXM-M group than in the HD-DXM-nM group; (4) in the 12th month after HD-DXM discontinuation, the relapse rate of the HD-DXM-M group was lower than that of the other groups (prednisone and HD-DXM-nM). Conclusion: Treatment with 3 cycles of HD-DXM pulses with low-dose dexamethasone maintenance is an effective method for untreated ITP.

scholarly journals Eltrombopag, Low-Dose Rituximab, and High-Dose Dexamethasone Combination for Patients with Newly Diagnosed Immune Thrombocytopenia: A Pilot "Total Therapy" Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1369-1369
Author(s):  
David Gomez-Almaguer ◽  
Olga Cantu-Rodriguez ◽  
Cesar Homero Gutierrez-Aguirre ◽  
Jose Carlos Jaime-Perez ◽  
Luz C. Tarin-Arzaga ◽  
...  
Keyword(s):  
Partial Response ◽  
Board Of Directors ◽  
Low Dose ◽  
Complete Response ◽  
High Dose ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
High Dose Dexamethasone ◽  
Frontline Therapy

Abstract Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder that results from platelet destruction and production suppression. Frontline-therapy includes corticosteroids, intravenous immune globulin or anti-D immunoglobulin. Single-agent treatments have not been successful in inducing prolonged remission, as relapse will occur in approximately 50% of patients. Low-dose rituximab (100 mg) has been used for the treatment of ITP, showing an activity almost similar to the 375 mg/m2 standard dose. We and others have reported sustained response rates ranging from 58% to 76% using rituximab plus dexamethasone as a frontline therapy. Eltrombopag is a thrombopoietin nonpeptide mimetic that has been shown to raise platelet count in chronic ITP, and we have previously reported eltrombopag/dexamethasone as a feasible frontline therapy for ITP reaching 100% response rates.The lack of sustained response in many adult patients with newly diagnosed acute ITP has stimulated the search for a treatment that modifies the natural course of the disease. Objetive: We aim to evaluate efficacy, safety, and response duration of low-dose weekly rituximab (100 mg weekly, four doses) plus high-dose dexamethasone (40 mg PO, days 1-4) in combination with eltrombopag (50 mg, days 1-28) as frontline therapy in newly diagnosed primary ITP in an ambulatory setting. Methods: This is an ongoing open-label, single-arm study performed in patients with newly diagnosed ITP from the Hospital Universitario Dr. Jose Eleuterio Gonzalez in Monterrey, Mexico (Clinical trials.gov NCT02834286). Eligible patients are 16 years or older, with bleeding manifestations and/or a platelet count ²30×109/L, without previous treatment. Patients are excluded if they had active infection, pregnancy, or a malignant disease. A complete blood count is performed at baseline, on days 3, 5, 7 and then weekly for 28 days, monthly until month 6, and every 3 months thereafter. Partial and complete responses are defined as an increase in platelet counts ³30×109/L and ³100×109/L, respectively. Results: Ten consecutive patients have been enrolled from March 2015 until July 2016. Median age was 37 years (16-61). Six patients were women (60%) and four were men (40%). Median platelet account at diagnosis was 7 « 109/L (range 1.2-28). Median follow-up has been 7 months (range 1-13). All patients achieved at least a partial response (PR) at a median of 4 days (range 3-14). Complete response (CR) was achieved in 9 patients in a median of 7 days (7-22); all of them were still in CR at the end of treatment (Day 28). One patient lost response at 28 days and received a second high-dexamethasone course maintaining CR. No significant adverse effects have occurred during treatment, only 1 patient reported mild myalgia. No relapses have been documented until now.Currently, 8 patients remain in CR and 2 in PR. Conclusion:This is the first trial evaluating the response of low-dose rituximab in combination with eltrombopag and high-dose dexamethasone in newly diagnosed patients with ITP.Low-dose rituximab in combination with eltrombopag and high dose dexamethasone is a feasible frontline therapy for ITP. This drug combination showed high response rates achieved very rapidly, with a low incidence of side effectsand might represent an attractive option in patients with ITP and substantial bleeding. Table Characteristics and follow-up of patients M: Male, F: Female, CR: Complete Response, PR: Partial Response Table. Characteristics and follow-up of patients. / M: Male, F: Female, CR: Complete Response, PR: Partial Response Disclosures Gomez-Almaguer: Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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