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Advances in Therapy Oct 2022To compare the mortality of hospitalized patients with COVID-19 between those that required supplemental oxygen and received dexamethasone with a comparable set of...
INTRODUCTION
To compare the mortality of hospitalized patients with COVID-19 between those that required supplemental oxygen and received dexamethasone with a comparable set of patients who did not receive dexamethasone.
METHODS
We utilized the Premier Health Database to identify hospitalized adult patients with COVID-19 from July 1, 2020-January 31, 2021. Index date was when patients first initiated oxygen therapy. The primary endpoint was in-hospital mortality for patients receiving dexamethasone versus those not receiving dexamethasone 1-day pre- to 1-day post-index period. Secondary endpoints included 28-day mortality, time to in-hospital mortality, progression to invasive mechanical ventilation or death, time to discharge, and proportion discharged alive by day 28. Twenty-three models using weighting, matching, stratification, and regression were deployed through the concept of frequentist model average (FMA) to estimate the effect of dexamethasone on all-cause mortality up to the 28-day hospitalization period.
RESULTS
A total of 1,208,881 patients with COVID-19 were screened; as an inpatient 255,216 used oxygen, and 251,536 were included in the analysis. In the dexamethasone group, odds of in-hospital mortality were higher than those of the comparator (FMA: odds ratio [OR] 1.15, 95% CI 1.08, 1.22). Using a best fit model, OR for in-hospital mortality was non-significant for the dexamethasone group compared with the comparator (OR 1.02, 95% CI 0.92, 1.14). Dexamethasone treatment was associated with poorer outcomes versus the comparator group across the majority of secondary endpoints, except for number of days in hospital, which was lower in the dexamethasone group versus the comparator group (mean difference - 2.14, 95% CI - 2.43, - 1.47).
CONCLUSIONS
Hospitalized adult patients with COVID-19 who required supplemental oxygen and received dexamethasone did not have a survival benefit versus similar patients not receiving dexamethasone. The dexamethasone group was not associated with favorable responses for outcomes such as progression to death or mechanical ventilation and time to in-hospital death.
Topics: Adult; Dexamethasone; Hospital Mortality; Humans; Inpatients; Oxygen; SARS-CoV-2; United States; COVID-19 Drug Treatment
PubMed: 35962234
DOI: 10.1007/s12325-022-02267-2 -
The European Respiratory Journal Jul 2022Dexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely...
BACKGROUND
Dexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS.
METHODS
We included patients admitted to US Veterans Affairs hospitals between 7 June 2020 and 31 May 2021 within 14 days after a positive test for severe acute respiratory syndrome coronavirus 2. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weighting (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality.
RESULTS
Of 19 973 total patients (95% men, median age 71 years, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514 out of 9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472 out of 5954 (75%) patients on low-flow nasal cannula (NC) only received dexamethasone and 857 (14%) died. In IPTW stratified models, patients on no oxygen who received dexamethasone experienced 76% increased risk for 90-day mortality (hazard ratio (HR) 1.76, 95% CI 1.47-2.12); there was no association with mortality among patients on NC only (HR 1.08, 95% CI 0.86-1.36).
CONCLUSIONS
In patients hospitalised with COVID-19, early initiation of dexamethasone was common and was associated with no mortality benefit among those on no oxygen or NC only in the first 48 h; instead, we found evidence of potential harm. These real-world findings do not support the use of early dexamethasone in hospitalised COVID-19 patients without IRS.
Topics: Aged; Dexamethasone; Female; Hospitalization; Humans; Male; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34824060
DOI: 10.1183/13993003.02532-2021 -
Respiratory Research Jun 2022Dexamethasone improves clinical outcomes in COVID-19 patients requiring supplementary oxygen. We investigated possible mechanisms of action by comparing sixteen plasma...
Dexamethasone improves clinical outcomes in COVID-19 patients requiring supplementary oxygen. We investigated possible mechanisms of action by comparing sixteen plasma host response biomarkers in general ward patients before and after implementation of dexamethasone as standard of care. 48 patients without and 126 patients with dexamethasone treatment were sampled within 48 h of admission. Endothelial cell and coagulation activation biomarkers were comparable. Dexamethasone treatment was associated with lower plasma interleukin (IL)-6 and IL-1 receptor antagonist levels, whilst other inflammation parameters were not affected. These data argue against modification of vascular-procoagulant responses as an early mechanism of action of dexamethasone in COVID-19.
Topics: Biomarkers; Dexamethasone; Humans; Patients' Rooms; COVID-19 Drug Treatment
PubMed: 35659223
DOI: 10.1186/s12931-022-02060-3 -
The American Journal of Sports Medicine Apr 2022Corticosteroid treatments such as dexamethasone are commonly used to treat tendinopathy but with mixed outcomes. Although this treatment can cause tendon rupture, it can...
BACKGROUND
Corticosteroid treatments such as dexamethasone are commonly used to treat tendinopathy but with mixed outcomes. Although this treatment can cause tendon rupture, it can also stimulate the tendon to heal. However, the mechanisms behind corticosteroid treatment during tendon healing are yet to be understood.
PURPOSE
To comprehend when and how dexamethasone treatment can ameliorate injured tendons by using a rat model of Achilles tendon healing.
STUDY DESIGN
Controlled laboratory study.
METHODS
An overall 320 rats were used for a sequence of 6 experiments. We investigated whether the drug effect was time-, dose-, and load-dependent. Additionally, morphological data and drug administration routes were examined. Healing tendons were tested mechanically or used for histological examination 12 days after transection. Blood was collected for flow cytometry analysis in 1 experiment.
RESULTS
We found that the circadian rhythm and drug injection timing influenced the treatment outcome. Dexamethasone treatment at the right time point (days 7-11) and dose (0.1 mg/kg) significantly improved the material properties of the healing tendon, while the adverse effects were reduced. Local dexamethasone treatment did not lead to increased peak stress, but it triggered systemic granulocytosis and lymphopenia. Mechanical loading (full or moderate) is essential for the positive effects of dexamethasone, as complete unloading leads to the absence of improvements.
CONCLUSION
We conclude that dexamethasone treatment to improve Achilles tendon healing is dose- and time-dependent, and positive effects are perceived even in a partly unloaded condition.
CLINICAL RELEVANCE
These findings are promising from a clinical perspective, as the positive effect of this drug was seen even when given at lower doses and in a moderate loading condition, which better mimics the load level in patients with tendon ruptures.
Topics: Achilles Tendon; Animals; Biomechanical Phenomena; Dexamethasone; Disease Models, Animal; Humans; Rats; Tendon Injuries; Wound Healing
PubMed: 35234541
DOI: 10.1177/03635465221077101 -
International Journal of Molecular... Sep 2022Functional recovery following traumatic brain injury (TBI) is limited due to progressive neuronal damage resulting from secondary injury-associated neuroinflammation....
Functional recovery following traumatic brain injury (TBI) is limited due to progressive neuronal damage resulting from secondary injury-associated neuroinflammation. Steroidal anti-inflammatory drugs, such as dexamethasone (DX), can reduce neuroinflammation by activated microglia and infiltrated macrophages. In our previous work, we developed hydrolytically degradable poly(ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) hydrogels with dexamethasone (DX)-conjugated hyaluronic acid (HA-DXM) and demonstrated that dexamethasone-loaded hydrogels (PEG-bis-AA/HA-DXM) can reduce neuroinflammation, apoptosis, and lesion volume and improve neuronal cell survival and motor function recovery at seven days post-injury (DPI) in a rat mild-TBI model. In this study, we investigate the effects of the local application of PEG-bis-AA/HA-DXM hydrogels on motor function recovery at 7 DPI and cognitive functional recovery as well as secondary injury at 14 DPI in a rat mild-CCI TBI model. We observed that PEG-bis-AA/HA-DXM-treated animals exhibit significantly improved motor functions by the rotarod test and cognitive functions by the Morris water maze test compared to untreated TBI animals. We also observed that PEG-bis-AA/HA-DXM hydrogels reduce the inflammatory response, apoptosis, and lesion volume compared to untreated animals at 14 DPI. Therefore, PEG-bis-AA/HA-DXM hydrogels can be promising a therapeutic intervention for TBI treatment.
Topics: Animals; Anti-Inflammatory Agents; Biocompatible Materials; Brain Concussion; Brain Injuries, Traumatic; Cognition; Dexamethasone; Disease Models, Animal; Ethylenes; Hyaluronic Acid; Hydrogels; Polyethylene Glycols; Rats
PubMed: 36232454
DOI: 10.3390/ijms231911153 -
Diagnostic evaluation of insulin and glucose dynamics in light-breed horses receiving dexamethasone.The Canadian Veterinary Journal = La... Jun 2022Insulin dysregulation is a hallmark of equine metabolic syndrome (EMS) and increases the risk for development of laminitis. Accurate diagnosis of insulin dysregulation...
OBJECTIVE
Insulin dysregulation is a hallmark of equine metabolic syndrome (EMS) and increases the risk for development of laminitis. Accurate diagnosis of insulin dysregulation is crucial for implementation of preventative strategies in this population. The objective was to assess the effects of dexamethasone administration on insulin and glucose dynamics in light-breed horses and assess the agreement of various diagnostic tests for insulin dysregulation [basal [insulin] (BI), oral sugar test (OST), and combined glucose-insulin test (CGIT)].
ANIMAL
Fourteen adult light-breed horses.
PROCEDURE
Prospective, experimental study to assess insulin and glucose dynamics by performing basal insulin, OST, and CGIT before (baseline) and post-dexamethasone administration (0.08 mg/kg, PO, q24h) for 7 d. Insulin and glucose dynamics were assessed by the BI, OST, CGIT, and insulin sensitivity proxy measurements (RISQI, QUICKI, FGIR, HOMA-IR, IG) at the baseline and post-dexamethasone time points.
RESULTS
The OST area under the insulin and glucose curves were increased following dexamethasone treatment ( < 0.001 and < 0.01, respectively). Basal insulin, OST [insulin] at 60 min and CGIT [insulin] at 45 min were increased at the post-dexamethasone time point ( < 0.001, < 0.001, and < 0.01). Similarly, time spent in the positive glucose phase during the CGIT was longer at the post-dexamethasone time point ( < 0.001). The proxy measurements for insulin sensitivity (RISQI, QUICKI, FGIR) were decreased ( < 0.01) and the proxy measurements for insulin resistance (HOMA-IR) and β-cell function (IG) were increased after dexamethasone administration ( < 0.01). More horses were classified with following dexamethasone administration, based on the diagnostic criteria for basal insulin ( = 0.03), OST ( = 0.01), and CGIT ( < 0.01). coefficients, measuring agreement between basal insulin, OST, and CGIT, showed none to moderate agreement at the baseline time point.
CONCLUSION
Dexamethasone administration at 0.08 mg/kg, PO, q24h for 7 d worsened insulin dysregulation in adult light-breed horses based on findings of a basal insulin, OST, CGIT, and insulin sensitivity proxy measurements. There was none to moderate agreement between the basal insulin, OST, CGIT for the diagnosis of insulin dysregulation.
CLINICAL RELEVANCE
Horses administered dexamethasone at a dose of 0.08 mg/kg, PO, q24h for 7 d should be considered insulin dysregulation and appropriate preventative strategies should be implemented. The variability of diagnostic performance of common tests for insulin dysregulation (basal insulin, OST, CGIT) may affect clinical decisions; therefore, performing multiple tests, including proxy measurements, may improve diagnostic accuracy of insulin dysregulation.
Topics: Animals; Blood Glucose; Dexamethasone; Glucose; Glucose Tolerance Test; Horse Diseases; Horses; Insulin; Insulin Resistance; Prospective Studies
PubMed: 35656529
DOI: No ID Found -
PloS One 2022Liver sinusoidal endothelial cells (LSECs) are specialized fenestrated scavenger endothelial cells involved in the elimination of modified plasma proteins and tissue...
INTRODUCTION
Liver sinusoidal endothelial cells (LSECs) are specialized fenestrated scavenger endothelial cells involved in the elimination of modified plasma proteins and tissue turnover waste macromolecules from blood. LSECs also participate in liver immune responses. A challenge when studying LSEC biology is the rapid loss of the in vivo phenotype in culture. In this study, we have examined biological processes and pathways affected during early-stage primary culture of rat LSECs and checked for cell responses to the pro-inflammatory cytokine interleukin (IL)-1β and the anti-inflammatory drug dexamethasone.
METHODS
LSECs from male Sprague Dawley rats were cultured on type I collagen in 5% oxygen atmosphere in DMEM with serum-free supplements for 2 and 24 h. Quantitative proteomics using tandem mass tag technology was used to examine proteins in cells and supernatants. Validation was done with qPCR, ELISA, multiplex immunoassay, and caspase 3/7 assay. Cell ultrastructure was examined by scanning electron microscopy, and scavenger function by quantitative endocytosis assays.
RESULTS
LSECs cultured for 24 h showed a characteristic pro-inflammatory phenotype both in the presence and absence of IL-1β, with upregulation of cellular responses to cytokines and interferon-γ, cell-cell adhesion, and glycolysis, increased expression of fatty acid binding proteins (FABP4, FABP5), and downregulation of several membrane receptors (STAB1, STAB2, LYVE1, CLEC4G) and proteins in pyruvate metabolism, citric acid cycle, fatty acid elongation, amino acid metabolism, and oxidation-reduction processes. Dexamethasone inhibited apoptosis and improved LSEC viability in culture, repressed inflammatory and immune regulatory pathways and secretion of IL-1β and IL-6, and further upregulated FABP4 and FABP5 compared to time-matched controls. The LSEC porosity and endocytic activity were reduced at 24 h both with and without dexamethasone but the dexamethasone-treated cells showed a less stressed phenotype.
CONCLUSION
Rat LSECs become activated towards a pro-inflammatory phenotype during early culture. Dexamethasone represses LSEC activation, inhibits apoptosis, and improves cell viability.
Topics: Animals; Dexamethasone; Endothelial Cells; Liver; Male; Proteome; Rats; Rats, Sprague-Dawley; Secretome
PubMed: 36054185
DOI: 10.1371/journal.pone.0273843 -
Pain Research & Management 2022Postendodontic pain is one of the problems of root canal therapy. This clinical study aimed to evaluate the effect of infiltration injection of dexamethasone and... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the Efficacy of Dexamethasone and Methylprednisolone in Infiltration Injection for Postendodontic Pain in Patients with Necrotic Pulp: A Randomized Controlled Clinical Trial.
PURPOSE
Postendodontic pain is one of the problems of root canal therapy. This clinical study aimed to evaluate the effect of infiltration injection of dexamethasone and methylprednisolone on postendodontic pain in patients with necrotic pulp.
METHODS
A total of 80 volunteers with necrotic pulp teeth were included and assigned to two groups ( = 40). After the administration of local anesthesia and before root canal therapy, in group 1, an infiltration injection of 1 ml of dexamethasone was done and in group 2, an infiltration injection of 1 ml of methylprednisolone was done in the buccal vestibule of each tooth. Patients' pain was reported using a visual analogue scale at pretreatment and 6, 12, 24, and 48 hours after treatment.
RESULTS
There was no significant difference between the two groups receiving dexamethasone and methylprednisolone at pretreatment and 6, 12, 24, and 48 hours after endodontic treatment.
CONCLUSIONS
Infiltration injection of dexamethasone and methylprednisolone had a significant effect in reducing pain after the endodontic treatment in necrotic pulp teeth, but between 6 and 12 hours, methylprednisolone had significantly more effect on pain relief than dexamethasone. Overall, the use of any of these drugs to reduce postendodontic pain is recommended.
Topics: Dexamethasone; Double-Blind Method; Humans; Methylprednisolone; Pain, Postoperative; Root Canal Therapy
PubMed: 35251416
DOI: 10.1155/2022/4163120 -
Drug Delivery Dec 2022Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug administered via intratympanic injection for the treatment of acute hearing loss, but its...
Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug administered via intratympanic injection for the treatment of acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of administering dexamethasone nanosuspensions via intratympanic injection because hydrophobic drugs might be more effective in penetrating the inner ear. Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanoparticles in the three nanosuspensions were between approximately 250 and 350 nm in size. To compare the efficiency of Dex-SP and dexamethasone nanosuspension in delivering dexamethasone to the inner ear, the concentrations of dexamethasone in perilymph and cochlear tissues were compared by liquid chromatography-mass spectrometry. The dexamethasone nanosuspensions resulted in significantly higher drug concentrations in perilymph and cochlear tissues than Dex-SP at 6 h; interestingly, animals treated with nanosuspensions showed a 26-fold higher dexamethasone concentrations in their cochlear tissues than animals treated with Dex-SP. In addition, dexamethasone nanosuspension caused better glucocorticoid receptor phosphorylation than Dex-SP both and , and in the ototoxic animal model, the nanosuspension showed a significantly better hearing-protective effect against ototoxic drugs than Dex-SP. In the safety evaluation, the nanosuspension showed no toxicity at concentrations up to 20 mg/mL. In conclusion, a nanosuspension of dexamethasone was able to deliver dexamethasone to the cochlea very safely and efficiently and showed potential as a formula for intratympanic injection.
Topics: Animals; Anti-Inflammatory Agents; Cell Line; Chemistry, Pharmaceutical; Dexamethasone; Drug Carriers; Drug Liberation; Hearing Loss; Injection, Intratympanic; Male; Mice; Mice, Inbred BALB C; Nanoparticle Drug Delivery System; Particle Size; Solubility; Surface Properties; Suspensions
PubMed: 34967280
DOI: 10.1080/10717544.2021.2021320 -
Aging Clinical and Experimental Research Apr 2021This statement addresses the need to provide clinically relevant and practical guidance for long-term care staff working in care homes and other stakeholders engaged in... (Review)
Review
Dexamethasone and oxygen therapy in care home residents with diabetes: a management guide and algorithm for treatment: a rapid response action statement from the European Diabetes Working Party for Older People (EDWPOP) and European Geriatric Medicine Society (EuGMS).
This statement addresses the need to provide clinically relevant and practical guidance for long-term care staff working in care homes and other stakeholders engaged in the care of residents who require consideration for dexamethasone and oxygen therapy. It had been provided following a series of consensus discussions between the EDWPOP and the EuGMS in January and February 2021. Its main aim is to minimise morbidity and mortality from serious acute illnesses including COVID-19 requiring these treatments within the long-term care sector.
Topics: Aged; Aged, 80 and over; Algorithms; Dexamethasone; Diabetes Mellitus; Humans; Oxygen; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33856663
DOI: 10.1007/s40520-021-01822-1