scholarly journals Low versus High Dose Methylprednisolone in Adult Patients with COVID-19: Less is More

2021 ◽  
Author(s):  
Seema Joshi ◽  
Zachary Smith ◽  
Sana Soman ◽  
Saniya Jain ◽  
Atheel Yako ◽  
...  
Keyword(s):  
Low Dose ◽  
Care Center ◽  
Treatment Protocol ◽  
Optimal Dose ◽  
Supplemental Oxygen ◽  
Hospital Length Of Stay ◽  
High Dose ◽  
Less Is More ◽  
High Dose Methylprednisolone ◽  
Secondary Outcomes

Abstract Background Corticosteroids use in severe COVID-19 improves survival; however, the optimal dose is not established. We aim to evaluate clinical outcomes in patients with severe COVID-19 receiving high-dose corticosteroids (HDC) versus low-dose corticosteroids (LDC). Methods This was a quasi-experimental study conducted at a large, quaternary care center in Michigan. A corticosteroid dose change was implemented in the standardized institutional treatment protocol on 17 November 2020. All patients admitted with severe COVID-19 that received corticosteroids were included. Consecutive patients in the HDC group (1 September to 15 November 2020) were compared to the LDC group (30 November 2020 to 20 January 2021). HDC was defined as methylprednisolone 80 mg daily in two divided doses and LDC was defined as methylprednisolone 32-40 mg daily in two divided doses. The primary outcome was all-cause 28-day mortality. Secondary outcomes included progression to mechanical ventilation, hospital length of stay (LOS), discharge on supplemental oxygen, and corticosteroid-associated adverse events. Results Four-hundred and seventy patients were included; 218 (46%) and 252 (54%) in the HDC and LDC groups, respectively. No difference was observed in 28-day mortality (14.5% vs 13.5%, p=0.712). This finding remained intact when controlling for additional variables (OR 0.947, [CI 0.515-1.742], p=0.861). Median hospital LOS was 6 and 5 days in the HDC and LDC groups, respectively (p<0.001). No differences were noted in any of the other secondary outcomes. Conclusions Low-dose methylprednisolone had comparable outcomes including mortality to high-dose methylprednisolone for the treatment of severe COVID-19.

scholarly journals High-Dose Methylprednisolone Pulses for 3 Days vs. Low-Dose Dexamethasone for 10 Days in Severe, Non-Critical COVID-19: A Retrospective Propensity Score Matched Analysis

2021 ◽  
Vol 10 (19) ◽  
pp. 4465
Author(s):  
José María Mora-Luján ◽  
Manel Tuells ◽  
Abelardo Montero ◽  
Francesc Formiga ◽  
Narcís A. Homs ◽  
...  
Keyword(s):  
Propensity Score ◽  
Hospital Mortality ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Low Dose ◽  
Invasive Mechanical Ventilation ◽  
Hospital Length Of Stay ◽  
High Dose ◽  
Icu Admission ◽  
High Dose Methylprednisolone

Corticosteroids are largely recommended in patients with severe COVID-19. However, evidence to support high-dose methylprednisolone (MP) pulses is not as robust as that demonstrated for low-dose dexamethasone (DXM) in the RECOVERY trial. This is a retrospective cohort study on severe, non-critically ill patients with COVID-19, comparing 3-day MP pulses ≥ 100 mg/day vs. DXM 6 mg/day for 10 days. The primary outcome was in-hospital mortality, and the secondary outcomes were need of intensive care unit (ICU) admission or invasive mechanical ventilation (IMV). Propensity-score matching (PSM) analysis was applied. From March 2020 to April 2021, a total of 2,284 patients were admitted to our hospital due to severe, non-critically ill COVID-19, and of these, 189 (8.3%) were treated with MP, and 493 (21.6%) with DXM. The results showed that patients receiving MP showed higher in-hospital mortality (31.2% vs. 17.8%, p < 0.001), need of ICU admission (29.1% vs. 20.5%, p = 0.017), need of IMV (25.9% vs. 13.8, p < 0.001), and median hospital length of stay (14 days vs. 11 days, p < 0.001). Our results suggest that treatment with low-dose DXM for 10 days is superior to 3 days of high-dose MP pulses in preventing in-hospital mortality and need for ICU admission or IMV in severe, non-critically ill patients with COVID-19.

scholarly journals Racial/ethnic Disparities on Inflammation and Response to Methylprednisolone in Severe Covid-19 Pneumonia

2021 ◽  
Author(s):  
Ronaldo C. Go ◽  
Themba Nyirenda ◽  
Maryam Bojarian ◽  
Davood Karimi Hosseini ◽  
Kevin Kim ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Asian Indians ◽  
Low Dose ◽  
Ethnic Disparities ◽  
Prolonged Survival ◽  
High Dose ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
High Dose Methylprednisolone ◽  
Racial Ethnic

Abstract BACKGROUNDRacial/Ethnic minorities are at higher risk for Severe COVID-19. This may be related to social determinants that lead to chronic inflammatory states. The aims of the study were to determine if there are racial/ethnic differences between the inflammatory markers of survivors and non-survivors and if there was a dose dependent association of methylprednisolone to in hospital survival. METHODSThis was a secondary analysis of a retrospective cohort. Patients were older than 18 years of age and admitted for severe COVID-19 Pneumonia Between March to June 2020 in 13 Hospitals in New Jersey, United States. Comparison of inflammatory markers used Kruskal-Wallis followed by pairwise comparison using two-sided Wilcoxon rank sum test. A Youden Index Method was used to determine the cut-off between low dose and high dose methylprednisolone. For each racial/ethnic group, cox regression was used to determine the association to survival between no methylprednisolone and methylprednisolone (high dose versus low dose). RESULTSPropensity matched sample (n=759) between no methylprednisolone (n=380) and methylprednisolone (n=379) had 338 Whites, 102 Blacks, 61 Asian/Indians, and 251 Non-Black Non-White Hispanics. Interleukin-6, C-reactive protein, ferritin, and d-dimer values were higher in non-survivors compared to survivors except in Asian/Indian survivors who had higher ferritin values compared to non-survivors (median: 1,265 vs 418 ug/L, P=0.0211). Black and Hispanic survivors had persistently elevated C-reactive protein, (10.2 mg/mL) and (13.70 mg/mL) respectively. Low dose methylprednisolone was associated with prolonged 60 days in hospital survival over no methylprednisolone in Whites (P<0.0001), Asian/Indians (P=0.0180), and Hispanics (P=0.0004). Regardless of dose, methylprednisolone was not associated with prolonged survival in Blacks. High dose methylprednisolone was associated with worse survival in Hispanics. (P=0.0181). CONCLUSIONRacial/Ethnic disparities with inflammatory markers in survivors and non-survivors preclude the use of one marker as predictor of survival. Low dose methylprednisolone is associated with prolonged survival in Asian/Indians, Hispanics, and Whites. Methylprednisolone, regardless of dose, was not associated with prolonged survival in Blacks.

scholarly journals Dose-Response Effects of Strawberries on Atherogenic Lipoproteins: A Randomized Controlled Crossover Trial

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 75-75
Author(s):  
Ann Skulas-Ray ◽  
Chesney Richter ◽  
Trent Gaugler ◽  
Stacey Meily ◽  
Kristina Petersen ◽  
...  
Keyword(s):  
Low Dose ◽  
Optimal Dose ◽  
Serum Lipoprotein ◽  
High Dose ◽  
Funding Sources ◽  
Supplementation Period ◽  
Freeze Dried ◽  
Middle Aged Adults ◽  
Post Hoc ◽  
Main Effects

Abstract Objectives Previous research indicates that consumption of strawberries may provide benefits for reduction of atherogenic lipoproteins but has not identified an optimal dose. Our objective was to evaluate effects of 2 doses of strawberry powder, approximately equivalent to 1 and 3 servings of strawberries per day, on serum lipoprotein concentrations. Methods Middle-aged adults (n = 40, age 49 ± 1 year) with elevated LDL-C (140 ± 4 mg/dL) and elevated BMI (29.4 ± 0.4 kg/m2) consumed 0 g/d (control), 13 g/d (low-dose), and 40 g/d (high-dose) of freeze-dried strawberry powder in a randomized crossover design (4-week supplementation periods separated by a 2 week compliance break). Fasting blood samples were obtained on two separate days (and averaged) at study-entry baseline and following each supplementation period. Results There were significant main effects of treatment (P ≤ 0.05) for calculated LDL-C, nonHDL-C, and total cholesterol (TC). In post hoc tests, the low-dose resulted in 5% lower LDL-C vs. the high-dose (P = 0.01), 4% lower nonHDL-C vs. control (P = 0.04), and 3% lower TC for the low-dose vs. control and high-dose (P ≤ 0.04). Compared to baseline, low-dose strawberry supplementation also significantly reduced direct LDL-C (−6.8 mg/dL, P = 0.02), but there was not a main effect of treatment. Conclusions Our results suggest that low-dose supplementation with freeze dried strawberry powder, roughly equivalent to one serving of strawberries per day, was superior to high-dose supplementation for improving atherogenic lipoproteins in overweight adults. Funding Sources California Strawberry Commission.

scholarly journals High Dose and Low Dose Oxytocin Regimen as Determinants of Successful Induction: A multicenter comparative study

2019 ◽  
Author(s):  
MELESE GEZAHEGN TESEMMA ◽  
Demisew Amenu Sori ◽  
Desta Hiko Gemeda
Keyword(s):  
Low Dose ◽  
Optimal Dose ◽  
Cross Sectional Study ◽  
Induction Of Labor ◽  
P Value ◽  
High Dose ◽  
Bishop Score ◽  
Delivery Time ◽  
Cross Sectional ◽  
Successful Induction

Abstract Background Induction of labor by Oxytocin is a routine obstetric procedure. However, little is known regarding the optimal dose of oxytocin so as to bring successful induction. This study is aimed at comparing the effect of high dose versus low dose oxytocin regimen on success of induction.Methods Hospital based comparative cross-sectional study was conducted in four selected hospitals in Ethiopia from October 1, 2017 to May 30, 2018. A total of 216 pregnant women who undergo induction of labor at gestational age of 37 weeks and above were included. Data was entered into Epi-data version 3.1 and then exported to SPSS version 20 for cleaning and analysis. Chi-square test and logistic regression were done to look for determinants of successful induction. The result is presented using 95% confidence interval of crude and adjusted odds ratios. P-value < 0.05 was used to declare statistical significance.Result Mean “Induction to delivery time” was 5.9 hours and 6.3 hours for participants who received high dose Oxytocin and low dose Oxytocin respectively. Higher successful induction (72.2% versus 61.1%) and lower Cesarean Section rate (27.8% vs. 38.9) was observed among participants who received low dose Oxytocin compared to high dose. Favourable bishop score [AOR 4.0 95% CI 1.9, 8.5], elective induction [AOR 0.2 95% CI 0.1, 0.4], performing artificial rupture of membrane [AOR 10.1 95% CI 3.2, 32.2], neonatal birth weight of < 4Kg [AOR 4.3, 95% CI 1.6, 11.6] and being parous [AOR 2.1 95% CI 1.1, 4.0] were significantly associated with success of induction. Conclusions : In this study, oxytocin regimen didn’t show significant association with success of induction. But, high dose oxytocin regimen is significantly associated with slightly shorter induction to delivery time. Favourable bishop score, emergency induction, performing artificial rupture of membrane and delivery to non-macrosomic neonate are positive determinants of successful induction. Thus, we recommend ripening cervix when condition allows, estimating fetal weight and performing artificial rupture of membrane. We also recommend researchers to conduct more strong research that controls confounders to see the real effect of different oxytocin regimen on induction success.

High- versus low-dose leucovorin in 5-fluorouracil-based oxaliplatin- or irinotecan-containing regimen in metastatic colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15054-e15054
Author(s):  
E. Song ◽  
N. Lee ◽  
J. Kwak ◽  
H. Yhim ◽  
K. Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Large Scale ◽  
Low Dose ◽  
Palliative Chemotherapy ◽  
Optimal Dose ◽  
Phase Iii ◽  
High Dose ◽  
Significant Difference ◽  
Gastrointestinal Side Effects

e15054 Background: Although leucovorin (LV) is widely used as a modulator of 5-fluorouracil (5-FU) for the chemotherapy of advanced colorectal cancer, the optimal dose has not yet been established. Low-dose LV appears to be as active as high-dose LV in the several studies. So, we tried to compare the efficacy of high-versus low-dose LV in the commonly used palliative chemotherapy regimen. Methods: Between May 2003 and May 2008, 40 patients with metastatic colorectal cancer were randomly treated with high-LV (200mg/m2/i.v.) or low-LV (20mg/m2/i.v.) in 5-FU based oxaliplatin (FOLFOX-4) or irinotecan (FOLFIRI) containing regimen. The primary endpoint of the study was the comparison of response rates and the secondary endpoint was the assessment of survival and tolerability. Results: The response rate was 40% in low-LV group with 2 CR and 6 PR, and 35% in high-LV group with 2 CR and 5 PR, without any significant difference (P = 0.89). The median overall survival was 24.3 months in low-LV group and 25.2 months in high-LV group, with no difference between treatments. Toxicity mainly consisted of gastrointestinal side effects, which were rare and similar in the two groups. Conclusions: In this randomized phase II study, the low and high doses of LV appeared to be equivalent in palliative chemotherapy of metastatic colorectal cancer although large-scale phase III study are necessary. No significant financial relationships to disclose.

Experimental osteonecrosis induced by a combination of low-dose lipopolysaccharide and high-dose methylprednisolone in rabbits

2008 ◽  
Vol 75 (5) ◽  
pp. 573-578 ◽  
Author(s):  
Xinghuo Wu ◽  
Shuhua Yang ◽  
Deyu Duan ◽  
Yukun Zhang ◽  
Jing Wang
Keyword(s):  
Low Dose ◽  
High Dose ◽  
High Dose Methylprednisolone

Preterm newborn lamb renal and cardiovascular responses after fetal or maternal antenatal betamethasone

1997 ◽  
Vol 272 (6) ◽  
pp. R1972-R1979 ◽  
Author(s):  
L. M. Berry ◽  
D. H. Polk ◽  
M. Ikegami ◽  
A. H. Jobe ◽  
J. F. Padbury ◽  
...  
Keyword(s):  
Low Dose ◽  
Cardiovascular Responses ◽  
Optimal Dose ◽  
Sodium Reabsorption ◽  
High Dose ◽  
Preterm Newborn ◽  
Short Term ◽  
To Receive ◽  
Renal Sodium Reabsorption ◽  
Dose Dependent

The optimal dose, route of administration, and treatment-to-delivery interval necessary to induce beneficial extrapulmonary effects of glucocorticoids are not known. Pregnant ewes (127 days gestation) were randomized to receive maternal or fetal intramuscular injections of betamethasone (0.2 or 0.5 mg/kg body wt) or saline 24 h before cesarean delivery of their lambs. Three hours after delivery, low-dose maternal vs. control lamb mean arterial pressure [64 +/- 4 vs. 47 +/- 2 (SE) mmHg], glomerular filtration rate (1.7 +/- 0.2 vs. 0.7 +/- 0.1 ml.min-1.kg-1), and total renal sodium reabsorption (219 +/- 31 vs. 85 +/- 12 mueq.min-1.kg-1) were increased. Comparable increases were observed in the high-dose maternal and fetal groups without effects in the low-dose fetal group. This study provides the first quantitative data demonstrating that even short-term (24-h) antenatal betamethasone exposure alters preterm newborn cardiovascular and renal functions. These responses are route and dose dependent and are comparable to glucocorticoid-induced maturational effects after longer-term antenatal exposure.

scholarly journals Safety and immunogenicity of a new inactivated polio vaccine made from Sabin strains: a randomized, double-blind, active-controlled, phase 2/3 seamless study

2020 ◽  
Author(s):  
Maria Rosario Capeding ◽  
Grace Devota Gomez-Go ◽  
Peninnah Oberdorfer ◽  
Charissa Borja-Tabora ◽  
Lulu Bravo ◽  
...  
Keyword(s):  
Low Dose ◽  
Seroconversion Rate ◽  
Optimal Dose ◽  
Stage I ◽  
Stage Ii ◽  
High Dose ◽  
Phase 2 ◽  
Double Blind ◽  
Inactivated Polio Vaccine ◽  
Polio Vaccine

Abstract Background A new inactivated polio vaccine made from Sabin strains (sIPV) was developed as part of the global polio eradication initiative. Methods This randomized, double-blind, active-controlled, phase 2/3 seamless study was conducted in two stages. Healthy infants aged 6 weeks were randomly assigned to receive three doses of one of four study vaccines at 6, 10, and 14 weeks of age (336 received low-, middle-, or high-dose sIPV, or conventional IPV [cIPV] in Stage I, and 1086 received lot A, B, or C of the selected sIPV dose, or cIPV in Stage II). The primary outcome was the seroconversion rate 4 weeks after the third vaccination. Results In Stage I, low-dose sIPV was selected as the optimal dose. In Stage II, consistency among the three manufacturing lots of sIPV was demonstrated. The seroconversion rates for Sabin and wild strains of the 3 serotypes after the three-dose primary series were 95.8% to 99.2% in the lot-combined sIPV group and 94.8% to 100% in the cIPV group, proving the non-inferiority of sIPV compared to cIPV. No notable safety risks associated with sIPV were observed. Conclusions Low-dose sIPV administered as a three-dose vaccination was safe and immunogenic compared to cIPV.

scholarly journals Effects of Oxygen Supplementation on Injectable and Inhalant Anesthesia in C57BL/6 Mice

2021 ◽  
Author(s):  
Caroline E Blevins ◽  
Natalie A Celeste ◽  
James O Marx
Keyword(s):  
Low Dose ◽  
Supplemental Oxygen ◽  
High Dose ◽  
Oxygen Supplementation ◽  
Pilot Studies ◽  
Long Duration ◽  
Oxygen Oxygen ◽  
Physiologic Parameters ◽  
High Doses ◽  
Medium Dose

Oxygen supplementation is rarely considered when anesthetizing laboratory mice, despite reports that mice become profoundlyhypoxic under anesthesia. Little is known about the effects of hypoxia on anesthetic performance. This article focuses on the effects of oxygen supplementation on physiologic parameters and depth of anesthesia in male and female C57BL/6 mice. Anesthesia was performed via common injectable anesthetic protocols and with isoflurane. Mice anesthetized with injectable anesthesia received one of 3 drug protocols. Low-dose ketamine/xylazine (100/8 mg/kg) was chosen to provide immobilization of mice, suitable for imaging procedures. Medium-dose ketamine/xylazine/acepromazine (100/10/1 mg/kg) was chosen as a dose that has been recommended for surgical procedures. High-dose ketamine/xylazine/acepromazine (150/12/3 mg/kg) was chosen after pilot studies to provide a long duration of a deep plane of anesthesia. We also tested the effects of oxygen supplementation on the minimum alveolar concentration (MAC) of isoflurane in mice. Mice breathed supplemental 100% oxygen, room air, or medical air with 21% oxygen. Anesthetized mice that did not receive supplemental oxygen all became hypoxic, while hypoxia was prevented in mice that received oxygen. Oxygen supplementation did not affect the MAC of isoflurane. At the high injectable dose, all mice not receiving oxygen supplementation died while all mice receiving oxygen supplementation survived. At low and medium doses, supplemental oxygen reduced the duration of the surgical plane of anesthesia (low dose with oxygen: 22 ± 14 min; low dose without supplementation: 29 ± 18 min; medium dose with oxygen: 43 ± 18 min; medium dose without supplementation: 61 ± 27 min). These results suggest that mice anesthetized with injectable and inhalant anesthesia without supplemental oxygen are routinely hypoxic. This hypoxia prolongs the duration of anesthesia with injectable drug protocols and affects survival at high doses of injectable anesthetics. Because of variable responses to injectable anesthetics in mice, oxygen supplementation is recommended for all anesthetized mice.

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