Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

Background Hyperglycaemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19. Methods This is a retrospective multi-centre study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: <140 mg/dL, 140–180 mg/dL and >180 mg/dL. The primary endpoint was all-cause in-hospital mortality. Results Of the 11,312 patients, only 2128 (18.9%) had diabetes and 2289 (20.4%) died during hospitalization. The in-hospital mortality rates were 15.7% (<140 mg/dL), 33.7% (140–180 mg) and 41.1% (>180 mg/dL), p <.001. The cumulative probability of mortality was significantly higher in patients with hyperglycaemia compared to patients with normoglycaemia (log rank, p <.001), independently of pre-existing diabetes. Hyperglycaemia (after adjusting for age, diabetes, hypertension and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dL: HR 1.50; 95% confidence interval (CI): 1.31–1.73) (BG 140–180 mg/dL; HR 1.48; 95%CI: 1.29–1.70). Hyperglycaemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality. Conclusions Admission hyperglycaemia is a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless of prior history of diabetes. KEY MESSAGE Admission hyperglycaemia is a stronger and independent risk factor for mortality in COVID-19. Screening for hyperglycaemia, in patients without diabetes, and early treatment of hyperglycaemia should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycaemia should not be overlooked in all patients regardless prior history of diabetes.

Context. Calcifediol has been proposed as a potential treatment for COVID-19 patients. Objective: To compare the administration or not of oral calcifediol on mortality risk of patients hospitalized because of COVID-19. Design: Retrospective, multicenter, open, non-randomized cohort study. Settings: Hospitalized care. Patients: Patients with laboratory-confirmed COVID-19 between 5 February and 5 May 2020 in five hospitals in the South of Spain. Intervention: Patients received calcifediol (25-hydroxyvitamin D3) treatment (0.266 mg/capsule, 2 capsules on entry and then one capsule on day 3, 7, 14, 21, and 28) or not. Main Outcome Measure: In-hospital mortality during the first 30 days after admission. Results: A total of 537 patients were hospitalized with COVID-19 (317 males (59%), median age, 70 years), and 79 (14.7%) received calcifediol treatment. Overall, in-hospital mortality during the first 30 days was 17.5%. The OR of death for patients receiving calcifediol (mortality rate of 5%) was 0.22 (95% CI, 0.08 to 0.61) compared to patients not receiving such treatment (mortality rate of 20%; p < 0.01). Patients who received calcifediol after admission were more likely than those not receiving treatment to have comorbidity and a lower rate of CURB-65 score for pneumonia severity ≥ 3 (one point for each of confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, systolic blood pressure < 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg, and age ≥ 65 years), acute respiratory distress syndrome (moderate or severe), c-reactive protein, chronic kidney disease, and blood urea nitrogen. In a multivariable logistic regression model, adjusting for confounders, there were significant differences in mortality for patients receiving calcifediol compared with patients not receiving it (OR = 0.16 (95% CI 0.03 to 0.80). Conclusion: Among patients hospitalized with COVID-19, treatment with calcifediol, compared with those not receiving calcifediol, was significantly associated with lower in-hospital mortality during the first 30 days. The observational design and sample size may limit the interpretation of these findings.

Older age and cardiovascular comorbidities are well-known risk factors for all-cause mortality in COVID-19 patients. Hypertension (HT) and age are the two principal determinants of arterial stiffness (AS). This study aimed to estimate AS in COVID-19 patients requiring hospitalization and analyze its association with all-cause in-hospital mortality. This observational, retrospective, multicenter cohort-study analyzed 12,170 patients admitted to 150 Spanish centers included in the SEMI-COVID-19 Network. We compared AS, defined as pulse pressure {greater than or equal to} 60 mmHg, and clinical characteristics between survivors and nonsurvivors. Mean age was 67.5 {plus minus} 16.1 years and 42.5% were women. Overall, 2,606 (21.4%) subjects died. Admission systolic blood pressure (SBP) < 120 and {greater than or equal to} 140 mmHg was a predictor of higher all-cause mortality (23.5% and 22.8%, respectively, p < .001), compared to BP =120-140 mmHg (18.6%). The 4,379 patients with AS (36.0%) were older and had higher systolic and lower diastolic BP. Multivariate analysis showed that AS and SBP < 120 mmHg significantly and independently predicted all-cause in-hospital mortality (ORadj: 1.27, p=.0001; ORadj: 1.48, p=.0001, respectively) after adjusting for sex (males, ORadj: 1.6, p=.0001), age tertiles (second and third tertiles, ORadj: 2.0 and 4.7, p=.0001), Charlson Comorbidity Index (second and third tertiles, ORadj: 4.8 and 8.6, p=.0001), heart failure, and previous and in-hospital antihypertensive treatment. Our data show that AS and admission SBP < 120 mmHg had independent prognostic value for all-cause mortality in COVID-19 patients requiring hospitalization.

Background Most patients with COVID-19 receive antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased complications, including antibacterial resistance. We aim to analyze risk factors for inappropriate antibiotic prescription in these patients and describe possible complications arising from their use. Methods The SEMI-COVID-19 Registry is a multicenter, retrospective patient cohort. Patients with antibiotic were divided into two groups according to appropriate or inappropriate prescription, depending on whether the patient fulfill any criteria for its use. Comparison was made by means of multilevel logistic regression analysis. Possible complications of antibiotic use were also identified. Results Out of 13,932 patients, 3047 (21.6%) were prescribed no antibiotics, 6116 (43.9%) were appropriately prescribed antibiotics, and 4769 (34.2%) were inappropriately prescribed antibiotics. The following were independent factors of inappropriate prescription: February-March 2020 admission (OR 1.54, 95%CI 1.18–2.00), age (OR 0.98, 95%CI 0.97–0.99), absence of comorbidity (OR 1.43, 95%CI 1.05–1.94), dry cough (OR 2.51, 95%CI 1.94–3.26), fever (OR 1.33, 95%CI 1.13–1.56), dyspnea (OR 1.31, 95%CI 1.04–1.69), flu-like symptoms (OR 2.70, 95%CI 1.75–4.17), and elevated C-reactive protein levels (OR 1.01 for each mg/L increase, 95% CI 1.00–1.01). Adverse drug reactions were more frequent in patients who received ANTIBIOTIC (4.9% vs 2.7%, p < .001). Conclusion The inappropriate use of antibiotics was very frequent in COVID-19 patients and entailed an increased risk of adverse reactions. It is crucial to define criteria for their use in these patients. Knowledge of the factors associated with inappropriate prescribing can be helpful.

OBJECTIVECell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling.RESEARCH DESIGN AND METHODSThe expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-α or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects.RESULTSSAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In obese subjects, CASP3/7 activation and BCL2 downregulation correlated with the IRS-1/2–expression levels. Expression levels of caspases, BCL2, p21, p53, IRS-1/2, GLUT4, protein tyrosine phosphatase 1B, and leukocyte antigen-related phosphatase in TNF-α– or IL-6–treated explants from lean subjects were comparable with those found in adipose tissue samples from morbidly obese subjects. These insulin component expression levels were reverted with CASP3/7 inhibition in these TNF-α– or IL-6–treated explants.CONCLUSIONSBody fat mass increase is associated with CASP3/7 and BCL2 expression in adipose tissue. Moreover, this proapoptotic state correlated with insulin signaling, suggesting its potential contribution to the development of insulin resistance.

Background. Spain has been one of the countries most affected by the COVID-19 pandemic. Objective. To create a registry of patients with COVID-19 hospitalized in Spain in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. Methods. A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. Results. Up to April 30th 2020, 6,424 patients from 109 hospitals were included. Their median age was 69.1 years (range: 18-102 years) and 56.9% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.2%, 39.7%, and 18.7%, respectively. The most frequent symptoms were fever (86.2%) and cough (76.5%). High values of ferritin (72.4%), lactate dehydrogenase (70.2%), and D-dimer (61.5%), as well as lymphopenia (52.6%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.7%) and lopinavir/ritonavir (62.4%). 31.5% developed respiratory distress. Overall mortality rate was 21.1%, with a marked increase with age (50-59 years: 4.2%, 60-69 years: 9.1%, 70-79 years: 21.4%, 80-89 years: 42.5%, ≥ 90 years: 51.1%). Conclusions. The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.

Objective The hypertriglyceridemic waist (HTGW) phenotype is characterized by abdominal obesity and high levels of triglycerides. In a cross‐sectional assessment of PREDIMED‐Plus trial participants at baseline, HTGW phenotype prevalence was evaluated, associated risk factors were analyzed, and the lifestyle of individuals with metabolic syndrome and HTGW was examined. Methods A total of 6,874 individuals aged 55 to 75 with BMI ≥ 27 and < 40 kg/m2 were included and classified by presence (HTGW+) or absence (HTGW−) of HTGW (waist circumference: men ≥ 102 cm, women ≥ 88 cm; fasting plasma triglycerides ≥ 150 mg/dL). Analytical parameters and lifestyle (energy intake and expenditure) were analyzed. Results A total of 38.2% of the sample met HTGW+ criteria. HTGW+ individuals tended to be younger, have a greater degree of obesity, be sedentary, and be tobacco users. They had higher peripheral glucose, total cholesterol, and low‐density lipoprotein cholesterol levels; had lower high‐density lipoprotein cholesterol levels; and had increased prevalence of type 2 diabetes mellitus. Mediterranean diet (MedDiet) adherence and physical activity were greater in HTGW− patients. Age, BMI, tobacco use, total energy expenditure, hypertension, type 2 diabetes mellitus, and MedDiet adherence were associated with HTGW+. Conclusions HTGW is a highly prevalent phenotype in this population associated with younger age, higher BMI, tobacco use, and decreased MedDiet adherence. HTGW− individuals were more physically active with greater total physical activity, and fewer had hypertension.