Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID-19 pneumonia: An open-label randomised trial.

BACKGROUND: The efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID-19 has shown mixed outcomes in controlled trials and observational studies. We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID-19. METHODS: A randomised, open-label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days. RESULTS: Of the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, -8.8 to 9.1%]; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non-invasive respiratory or high-flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, -18.9% [95% CI, -31.8 to - 5.6%]; p = 0.007). CONCLUSIONS: Among severe but not critical patients with COVID-19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation.

Relationship between the FRAX index and physical and cognitive functioning in older people.

OBJECTIVE: To assess the relationship between the FRAX index and the Barthel index/MiniMental State Examination in older people. PATIENTS AND METHODS: Observational descriptive study. Demographic data, comorbidity, dependency and cognitive state, and risk of osteoporotic fracture were collected. RESULTS: A total of 375 patients were included (60% female) Patients with a low-risk FRAX for hip fractures had a higher Mini-mental (25, 95% CI = 24-27 vs. 22, 95% = 21 to 23, p = .0001), a higher Barthel index (88, 95% CI = 84-93 vs 72, 69 to 76, p = .0001) without differences in the Charlson index. Bivariate analysis showed an inverse association between FRAX and scales but logistic regression showed only female sex (OR 4.4, 95% CI = 2.6-7.6) and the non-dependent Barthel index (OR = 0.104, 95% CI = 0.014-0.792) remained significant and. Barthel index/Mini-mental constructed a significant model capable of predicting a risk of hip fracture of >3% measured by the FRAX index, with an area under the curve of 0.76 (95% CI = 0.7-0.81). CONCLUSIONS: The FRAX index is related to other markers of geriatric assessment and the association between these variables can predict a risk of hip fracture of >3% measured by the FRAX index. Key messages Geriatric assessment indexes may be as important as the FRAX index, which is based on clinical risk factors, in predicting the fracture risk in older patient.

Relationship among angiotensin-converting enzyme polymorphism, cardiovascular risk, and osteoporotic fractures.

OBJECTIVE: Angiotensin-converting enzyme (ACE) has been related to cardiovascular physiology and bone remodeling. Our aim was to assess the relationship among ACE polymorphisms, cardiovascular risk, and osteoporotic fractures. MATERIAL AND METHODS: We prospectively enrolled 71 patients with hypertension from 2001 to 2014. Sociodemographic and medical data were collected. Comorbidity was evaluated with Charlson index. Densitometric studies on lumbar spine were performed. ACE polymorphism was analyzed by polymerase chain reaction. Data were analyzed using SPSS 15.0 (p value <0.05). RESULTS: Homozygous deletion (DD) genotype was described in 32.4% of patients, homozygous insertion (II) in 19.7%, and heterozygous insertion/deletion (ID) in 47.9%. On stratifying data by ACE polymorphism, we observed that DD carriers demonstrated neither greater cardiovascular risk factors (30.4% vs. 33.3%, p=0.4) and higher comorbidity (34.8% vs. 22.9%, p=0.3) nor higher osteoporotic fracture incidence (17.4% vs. 16.8%, p=0.9). In women, no significant differences were observed between DD homozygous individuals and ID+II subjects. CONCLUSION: It is unclear whether DD genotype is an independent risk factor for cardiovascular disease. In contrast to our expectations, we found no relationship among the DD genotype, cardiovascular risk, and osteoporotic fracture incidence.

Vitamin d levels and lipid response to atorvastatin.

Adequate vitamin D levels are necessary for good vascular health. 1,25-dihydroxycholecalciferol activates CYP3A4, an enzyme of the cytochrome P450 system, which metabolizes atorvastatin to its main metabolites. The objective of this study was to evaluate the response of cholesterol and triglycerides to atorvastatin according to vitamin D levels. Sixty-three patients with acute myocardial infarction treated with low and high doses of atorvastatin were included. Levels of total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol were measured at baseline and at 12 months of follow-up. Baseline levels of 25-hydroxyvitamin D (25-OHD) were classified as deficient (<30 nmol/L), insufficient (30-50 nmol/L), and normal (>50 nmol/L). In patients with 25-OHD <30 nmol/L, there were no significant changes in levels of total cholesterol (173 +/- 47 mg/dL versus 164 +/- 51 mg/dL), triglycerides (151 +/- 49 mg/dL versus 177 +/- 94 mg/dL), and LDL cholesterol (111 +/- 48 mg/dL versus 92 45 +/- mg/dL); whereas patients with insufficient (30-50 nmol/L) and normal vitamin D (>50 nmol/L) had a good response to atorvastatin. We suggest that vitamin D concentrations >30 nmol/L may be required for atorvastatin to reduce lipid levels in patients with acute myocardial infarction.