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Journal of Infection in Developing... Jul 2023The aim of this study was to demonstrate the purpose of adding antiviral (remdesivir) to the existing steroidal (dexamethasone) therapy in treating coronavirus disease... (Observational Study)
Observational Study
INTRODUCTION
The aim of this study was to demonstrate the purpose of adding antiviral (remdesivir) to the existing steroidal (dexamethasone) therapy in treating coronavirus disease 2019 (COVID-19).
METHODOLOGY
A retrospective observational case cohort study was carried out to compare the effect of dexamethasone alone and in combination with remdesivir in treating moderate and severe COVID-19 disease. The patients were divided into 2 groups: Group 1 included patients treated with dexamethasone alone, and Group 2 included patients treated with dexamethasone and remdesivir. Levels of inflammatory markers (C-reactive protein, D- dimer and lactate dehydrogenase), World Health Organization (WHO) ordinal scale scoring, symptomatic improvement in terms of fever, cough, shortness of breath, 6-minutes' walk test and SpO2 levels on day of admission (D0), 3 days and 5 days after admission (D3 and D5), and 10 days overall outcome (determined as death, or discharge with or without Long Term Oxygenation Therapy) were collected and analyzed.
RESULTS
Addition of remdesivir to dexamethasone in treating COVID 19 did not have any additional benefits. No additional role of remdesivir is seen in combating the disease except in case of 10 days outcome. However, the better 10-day outcome associated with the use of remdesivir was thought to be due to the patients who were on mechanical ventilation in the dexamethasone treated group at the time of inclusion.
CONCLUSIONS
Since a similar trend was seen in both groups, our study concluded no additional role of remdesivir in combating COVID-19.
Topics: Humans; COVID-19; SARS-CoV-2; Retrospective Studies; Cohort Studies; COVID-19 Drug Treatment; Antiviral Agents; Dexamethasone
PubMed: 37515802
DOI: 10.3855/jidc.17971 -
Journal of Cellular and Molecular... Dec 2023Steroid-induced femoral head necrosis (SIFHN) is a serious clinical complication that is caused by prolonged or excessive use of glucocorticoids (GCs). Osteoblast...
Steroid-induced femoral head necrosis (SIFHN) is a serious clinical complication that is caused by prolonged or excessive use of glucocorticoids (GCs). Osteoblast apoptosis and osteogenic differentiation dysfunction caused by GC-induced oxidative stress and mitochondrial impairment are strongly implicated in SIFHN. Apocynin (APO) is a kind of acetophenone extracted from an herb. In recent years, APO has received much attention for its antiapoptotic and antioxidant properties. This study aimed to investigate whether APO could protect against SIFHN and explore the mechanism. In our study, low-dose APO had no toxic effects on osteoblasts and restored dexamethasone (Dex)-treated osteoblasts by improving survival, inhibiting OS and restoring mitochondrial dysfunction. Mechanistically, APO alleviated Dex-induced osteoblast injury by activating the Nrf2 pathway, and the use of ML385 to block Nrf2 significantly eliminated the protective effect of APO. In addition, APO could reduce the formation of empty lacunae, restore bone mass and promote the expression of Nrf2 in SIFHN rats. In conclusion, APO protects osteoblasts from Dex-induced oxidative stress and mitochondrial dysfunction through activation of the Nrf2 pathway and may be a beneficial drug for the treatment of SIFHN.
Topics: Rats; Animals; Dexamethasone; NF-E2-Related Factor 2; Osteogenesis; Glucocorticoids; Oxidative Stress; Acetophenones; Apoptosis; Osteoblasts; Mitochondrial Diseases
PubMed: 37749949
DOI: 10.1111/jcmm.17974 -
Journal of Medical Virology Jul 2022Dexamethasone has demonstrated efficacy in reducing mortality in COVID-19. However, its practical use is badly defined. We aimed to investigate factors associated with...
Dexamethasone has demonstrated efficacy in reducing mortality in COVID-19. However, its practical use is badly defined. We aimed to investigate factors associated with dexamethasone efficacy in real life. Our retrospective study was conducted in two university hospitals between September and November 2020 and included all the consecutive hospitalized patients with a laboratory-confirmed SARS-CoV-2 infection assessed by RT-PCR, treated with intravenous dexamethasone (6 mg/day). Among 111 patients, 10.6% necessitated a transfer into the intensive care unit (ICU) and the 28-day mortality rate was 17.1%. The 28-day mortality rate was significantly lower in patients who demonstrated improvement at 48 h (hazard ratio [HR]: 0.17, 95% confidence interval [CI]: 0.04-0.78, p = 0.02) and 96 h (HR: 0.07, 95% CI: 0.02-0.31, p = 0.0005) after dexamethasone initiation. Apart from well-known risk factors (age, hypertension, active cancer, severe lesions on chest computed tomography [CT] scan), we found that a high viral load in nasopharyngeal swab (Cycle threshold <30) at dexamethasone initiation was associated with higher 28-day mortality (66.6% vs. 36.7%, p = 0.03). Patients who did not receive antibiotics at dexamethasone initiation had a higher rate of transfer into the ICU (55.6% vs. 23.5%, p = 0.045) with a trend towards higher mortality in case of severe or critical lesions on CT scan (75.0% vs. 25.0%, p = 0.053). Patients who did not improve within 2-4 days after steroid initiation have a bad prognosis and should receive additional anti-inflammatory drugs. Our data suggest better efficacy of dexamethasone in patients with a low or negative viral load, receiving broad-spectrum antibiotics.
Topics: Anti-Bacterial Agents; Cohort Studies; Dexamethasone; Humans; Retrospective Studies; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35277862
DOI: 10.1002/jmv.27712 -
Medicine Sep 2022This meta-analysis aimed to evaluate the efficacy and safety of dexamethasone in the treatment of acute respiratory distress syndrome (ARDS). (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to evaluate the efficacy and safety of dexamethasone in the treatment of acute respiratory distress syndrome (ARDS).
METHODS
A systematic search of electronic databases was carried out from inception to May 1, 2022, including PUBMED, EMBASE, Cochrane Library, Wangfang, VIP, and CNKI. Other searches were also checked for dissertations/theses and the reference lists of the included studies. Two team members examined all citations and selected eligible articles. Randomized controlled trials (RCTs) reporting the efficacy and safety of dexamethasone for the treatment of ARDS were included, and the quality of eligible RCTs was assessed using the Cochrane Risk of Bias Tool. If necessary, we conducted data synthesis and meta-analysis. The primary outcome was all-cause mortality. Secondary outcomes were mechanical ventilation duration (day), ventilator-free status at 28 days; intensive care unit (ICU) free (day), ICU mortality, hospital mortality, sequential organ failure assessment (SOFA) as mean and range, SOFA as No. of patients, peak airway pressure (cmH2O), arterial oxygen pressure (mm Hg), days with PaO2 > 10kPa, PaO2, and the occurrence rate of adverse events.
RESULTS
Four studies involving 702 patients were included in this analysis. This study showed that dexamethasone could significantly reduce all-cause mortality (odds ratio (OR) = 0.62, 95% confidence interval (CI) [0.44, 0.88], I2 = 30%, P < .001), and decrease ventilator-free status at 28 days (MD = 3.65, 95% CI [1.49, 5.80], I2 = 51%, P < .001). No significant differences in occurrence rates of adverse events were found between dexamethasone and routine or standard care.
CONCLUSIONS
Evidence from the meta-analysis suggests that dexamethasone is an effective and relatively safe treatment for all-cause mortality and ventilator-free status at 28 days in patients with ARDS. Owning to the small number of eligible RCTs, the conclusions of present study are warranted in the future study.
Topics: Dexamethasone; Humans; Intensive Care Units; Oxygen; Respiration, Artificial; Respiratory Distress Syndrome
PubMed: 36181003
DOI: 10.1097/MD.0000000000030195 -
Medicina Clinica Dec 2022The most effective way to control severity and mortality rate of the novel coronavirus disease (COVID-19) is through sensitive diagnostic approaches and an appropriate...
BACKGROUND AND AIM
The most effective way to control severity and mortality rate of the novel coronavirus disease (COVID-19) is through sensitive diagnostic approaches and an appropriate treatment protocol. We aimed to identify the effect of adding corticosteroid and Tocilizumab to a standard treatment protocol in treating COVID-19 patients with chronic disease through hematological and lab biomarkers.
MATERIALS AND METHODS
This study was performed retrospectively on 68 COVID-19 patients with chronic disease who were treated by different therapeutic protocols. The patients were categorized into four groups: control group represented the patients' lab results at admission before treatment protocols were applied; group 1 included patients treated with anticoagulants, Hydroxychloroquine, and antibiotics; group 2 comprised patients treated with Dexamethasone; and group 3 included patients treated with Dexamethasone and Tocilizumab.
RESULTS
The WBC and neutrophil counts were increased significantly in group 3 upon the treatment when they were compared with patients in group 1 (p=0.004 and p=0.001, respectively). The comparison of C-reactive Protein (CRP) level at admission was higher in group 3 than in group 1 with p=0.030. After 10 days of treatment, CRP level was decreased in all groups, but in group 3 it was statistically significant (p=0.002).
CONCLUSION
The study paves the way into the effectiveness of combining Dexamethasone with Tocilizumab in treatment COVID-19 patients with chronic diseases.
Topics: Humans; Retrospective Studies; COVID-19; Treatment Outcome; Dexamethasone; Chronic Disease
PubMed: 35659421
DOI: 10.1016/j.medcli.2022.02.013 -
Clinical Lymphoma, Myeloma & Leukemia Sep 2021Daratumumab plus bortezomib/dexamethasone (D-Vd) significantly improved outcomes versus Vd in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3... (Randomized Controlled Trial)
Randomized Controlled Trial
Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Chinese Patients with Relapsed or Refractory Multiple Myeloma: Phase 3 LEPUS (MMY3009) Study.
BACKGROUND
Daratumumab plus bortezomib/dexamethasone (D-Vd) significantly improved outcomes versus Vd in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 CASTOR study. We report the results of a prespecified interim analysis of the phase 3 LEPUS study of D-Vd versus Vd in Chinese patients with RRMM.
PATIENTS AND METHODS
Chinese patients with ≥ 1 prior line of therapy were randomized 2:1 to receive 8 cycles (21 days/cycle) of bortezomib (1.3 mg/m subcutaneously) and dexamethasone (20 mg orally/intravenously) ± daratumumab (16 mg/kg intravenously). The primary endpoint was progression-free survival (PFS).
RESULTS
A total of 211 patients were randomized (D-Vd, 141; Vd, 70). After an 8.2-month median follow-up, D-Vd significantly prolonged PFS versus Vd (median, not reached vs. 6.3 months; hazard ratio, 0.28; 95% confidence interval, 0.17-0.47; P < .00001) and significantly improved the rates of overall response (83% vs. 65%; P = .00527), ≥ very good partial response (65% vs. 33%; P = .00002), ≥ complete response (33% vs. 11%; P = .00079), and minimal residual disease negativity (10 sensitivity; 22% vs. 3%; P = .0002). The PFS benefit of D-Vd versus Vd was maintained across prespecified subgroups, including patients with prior bortezomib treatment and with high-risk cytogenetics. Thrombocytopenia (D-Vd, 51%; Vd, 37%), lymphopenia (44%; 29%), and lung infection (30%; 22%) were the 3 most common grade 3/4 treatment-emergent adverse events. Although patients in both treatment groups experienced higher rates of grade 3/4 lymphopenia and infections versus patients in CASTOR, the safety profile was generally consistent with that of CASTOR.
CONCLUSION
These data support the use of D-Vd in Chinese patients with RRMM.
Topics: Adult; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; China; Dexamethasone; Female; Humans; Male; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local
PubMed: 34108127
DOI: 10.1016/j.clml.2021.04.012 -
BMC Medical Research Methodology Aug 2022The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is aimed at addressing the urgent need to find effective treatments for patients hospitalised with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is aimed at addressing the urgent need to find effective treatments for patients hospitalised with suspected or confirmed COVID-19. The trial has had many successes, including discovering that dexamethasone is effective at reducing COVID-19 mortality, the first treatment to reach this milestone in a randomised controlled trial. Despite this, it continues to use standard or 'fixed' randomisation to allocate patients to treatments. We assessed the impact of implementing response adaptive randomisation within RECOVERY using an array of performance measures, to learn if it could be beneficial going forward. This design feature has recently been implemented within the REMAP-CAP platform trial.
METHODS
Trial data was simulated to closely match the data for patients allocated to standard care, dexamethasone, hydroxychloroquine, or lopinavir-ritonavir in the RECOVERY trial from March-June 2020, representing four out of five arms tested throughout this period. Trials were simulated in both a two-arm trial setting using standard care and dexamethasone, and a four-arm trial setting utilising all above treatments. Two forms of fixed randomisation and two forms of response-adaptive randomisation were tested. In the two-arm setting, response-adaptive randomisation was implemented across both trial arms, whereas in the four-arm setting it was implemented in the three non-standard care arms only. In the two-arm trial, randomisation strategies were performed at the whole trial level as well as within three pre-specified patient subgroups defined by patients' respiratory support level.
RESULTS
All response-adaptive randomisation strategies led to more patients being given dexamethasone and a lower mortality rate in the trial. Subgroup specific response-adaptive randomisation reduced mortality rates even further. In the two-arm trial, response-adaptive randomisation reduced statistical power compared to FR, with subgroup level adaptive randomisation exhibiting the largest power reduction. In the four-arm trial, response-adaptive randomisation increased statistical power in the dexamethasone arm but reduced statistical power in the lopinavir arm. Response-adaptive randomisation did not induce any meaningful bias in treatment effect estimates nor did it cause any inflation in the type 1 error rate.
CONCLUSIONS
Using response-adaptive randomisation within RECOVERY could have increased the number of patients receiving the optimal COVID-19 treatment during the trial, while reducing the number of patients needed to attain the same study power as the original study. This would likely have reduced patient deaths during the trial and lead to dexamethasone being declared effective sooner. Deciding how to balance the needs of patients within a trial and future patients who have yet to fall ill is an important ethical question for the trials community to address. Response-adaptive randomisation deserves to be considered as a design feature in future trials of COVID-19 and other diseases.
Topics: Dexamethasone; Humans; Lopinavir; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 35933340
DOI: 10.1186/s12874-022-01691-w -
Computational Intelligence and... 2022The study focuses on the potential function of dexamethasone on ropivacaine in sciatic nerve blocks. Nine Sprague-Dawley (SD) rats were randomly divided into three...
The study focuses on the potential function of dexamethasone on ropivacaine in sciatic nerve blocks. Nine Sprague-Dawley (SD) rats were randomly divided into three groups: normal group (NG), control group (CG), and experimental group (EG), with three rats in each group. The CG was injected with diluted ropivacaine (0.5% concentration); the EG was injected with a diluted ropivacaine+dexamethasone mixture, and the NG was injected with an equal amount of saline. The sciatic nerve in the thigh was collected for sequencing two days after injection in each group. Differential analysis was performed for NG-vs-CG, NG-vs-EG, and CG-vs-EG based on the sequencing dataset. The modular genes associated with ropivacaine and ropivacaine+ dexamethasone were screened by weighted coexpression network analysis (WGCNA), differentially expressed modules among them were enriched for analysis, and protein-protein interaction (PPI) networks were constructed to observe high and low expression among key genes in immune cells. Twenty-two and three differential genes associated with ropivacaine (green-yellow module) and ropivacaine+dexamethasone (palevioletred3 module) were acquired, respectively, which played important roles in biological processes such as erythrocyte homeostasis, erythroid differentiation, and hemoglobin metabolic processes. PPI revealed that AHSP, ALAS2, EPB42, HBB, and SLC4A1 were interacting and the expression of these five genes was upregulated in the CG compared with the NG, while the expression of them was downregulated in the EG compared with the CG. The immunological analysis also showed significant differences in the expression of various immune cells in the 3 groups. AHSP, ALAS2, EPB42, HBB, and SLC4A1 are genes associated with hemoglobin, and dexamethasone combined with ropivacaine may prolong anesthesia by affecting local vasoconstriction to some extent.
Topics: Amides; Anesthetics, Local; Animals; Computational Biology; Dexamethasone; Nerve Block; Rats; Rats, Sprague-Dawley; Ropivacaine
PubMed: 35990127
DOI: 10.1155/2022/5869103 -
International Journal of Molecular... Jun 2023Glioblastoma (GB) is an aggressive cancer with a high probability of recurrence, despite active chemoradiotherapy with temozolomide (TMZ) and dexamethasone (DXM). These...
Glioblastoma (GB) is an aggressive cancer with a high probability of recurrence, despite active chemoradiotherapy with temozolomide (TMZ) and dexamethasone (DXM). These systemic drugs affect the glycosylated components of brain tissue involved in GB development; however, their effects on heparan sulfate (HS) remain unknown. Here, we used an animal model of GB relapse in which SCID mice first received TMZ and/or DXM (simulating postoperative treatment) with a subsequent inoculation of U87 human GB cells. Control, peritumor and U87 xenograft tissues were investigated for HS content, HS biosynthetic system and glucocorticoid receptor (GR, ). In normal and peritumor brain tissues, TMZ/DXM administration decreased HS content (5-6-fold) but did not affect HS biosynthetic system or GR expression. However, the xenograft GB tumors grown in the pre-treated animals demonstrated a number of molecular changes, despite the fact that they were not directly exposed to TMZ/DXM. The tumors from DXM pre-treated animals possessed decreased HS content (1.5-2-fold), the inhibition of HS biosynthetic system mainly due to the -3-3.5-fold down-regulation of N-deacetylase/N-sulfotransferases ( and ) and sulfatase 2 () expression and a tendency toward a decreased expression of the GRalpha but not the GRbeta isoform. The GRalpha expression levels in tumors from DXM or TMZ pre-treated mice were positively correlated with the expression of a number of HS biosynthesis-involved genes (, , , , ), unlike tumors that have grown in intact SCID mice. The obtained data show that DXM affects HS content in mouse brain tissues, and GB xenografts grown in DXM pre-treated animals demonstrate attenuated HS biosynthesis and decreased HS content.
Topics: Humans; Mice; Animals; Glioblastoma; Mice, SCID; Neoplasm Recurrence, Local; Heparitin Sulfate; Temozolomide; Dexamethasone; Sulfotransferases
PubMed: 37373391
DOI: 10.3390/ijms241210243 -
Journal of Pharmacokinetics and... Jun 2021Population pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed for extensive data for differing dosage forms and routes for dexamethasone (DEX) and... (Observational Study)
Observational Study
Population pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed for extensive data for differing dosage forms and routes for dexamethasone (DEX) and betamethasone (BET) in 48 healthy nonpregnant Indian women in a partial and complex cross-over design. Single doses of 6 mg dexamethasone phosphate (DEX-P), betamethasone phosphate (BET-P), or 1:1 mixture of betamethasone phosphate and acetate (BET-PA) were administered orally (PO) or intramuscularly (IM) where each woman enrolled in a two-period cross-over study. Plasma concentrations collected over 96 h were described with a two-compartment model with differing PO and IM first-order absorption inputs. Overall, BET exhibited slower clearance, similar volume of distribution, faster absorption, and longer persistence than DEX with BET acetate producing extremely slow absorption but full bioavailability of BET. Six biomarkers were assessed over a 24-h baseline period with four showing circadian rhythms with complex baselines. These baselines and the strong responses seen after drug dosing were fitted with various indirect response models using the Laplace estimation methods in NONMEM 7.4. Both the PK and six biomarker responses were well-described with modest variability likely due to the homogeneous ages, weights, and ethnicities of the women. The drugs either inhibited or stimulated the influx processes with some models requiring joint inclusion of drug effects on circadian cortisol suppression. The biomarkers and order of sensitivity (lowest IC/SC to highest) were: cortisol, T-helper cells, basophils, glucose, neutrophils, and T-cytotoxic cells. DEX sensitivities were generally greater than BET with corresponding mean ratios for these biomarkers of 2.86, 1.27, 1.72, 1.27, 2.69, and 1.06. Overall, the longer PK (e.g. half-life) of BET, but lesser PD activity (e.g. higher IC), produces single-dose response profiles that appear quite similar, except for the extended effects from BET-PA. This comprehensive population modeling effort provides the first detailed comparison of the PK profiles and six biomarker responses of five commonly used dosage forms of DEX and BET in healthy women.
Topics: Administration, Oral; Adult; Betamethasone; Biomarkers; Chronopharmacokinetics; Circadian Rhythm; Cross-Over Studies; Dexamethasone; Dose-Response Relationship, Drug; Female; Half-Life; Healthy Volunteers; Humans; India; Inhibitory Concentration 50; Injections, Intramuscular; Models, Biological; Young Adult
PubMed: 33954911
DOI: 10.1007/s10928-021-09755-y