Efficacy and Safety of Tinzaparin in Prophylactic, Intermediate and Therapeutic Doses in Non-Critically Ill Patients Hospitalized with COVID-19: The PROTHROMCOVID Randomized Controlled Trial.

Hospitalized patients with COVID-19 are at increased risk of thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. The aim was to evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. PROTHROMCOVID is a randomized, unblinded, controlled, multicenter trial enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) groups. All tinzaparin doses were administered once daily during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days. Of the 311 subjects randomized, 300 were included in the prespecified interim analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]). The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (p = 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences. Due to these results and the futility analysis, the trial was stopped. In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to affect the risk of thrombotic event, non-invasive ventilation, or mechanical ventilation or death. Trial RegistrationClinicalTrials.gov Identifier (NCT04730856). Edura-CT registration number: 2020-004279-42.

Relationship between thyroid dysfunction and body weight: a not so evident paradigm.

PURPOSE: Hypothyroidism has traditionally been associated with obesity, whereas hyperthyroidism has been linked to being underweight. However, very few studies have assessed these associations. The aim of this work is to evaluate the association between thyroid dysfunction and body mass index (BMI) at baseline and after normalization of the hormone levels. PATIENTS AND METHODS: A retrospective, observational study of a cohort of otherwise healthy patients that were referred for evaluation of thyroid dysfunction to the Endocrine Department of Pontevedra University Complex Hospital, Spain was conducted. We collected data of BMI and thyroid hormone levels before treatment and after normalization of thyroid function within a follow-up period of 12 months. RESULTS: A total of 330 patients were initially selected for the study. In order to exclude variables that for any reason could influence on BMI, 235 were excluded for further studies. Another 61 patients were also excluded because incomplete data on their medical records, failure to achieve euthyroidism, or lost to follow-up. Therefore, the eligible final study group consisted of 34 patients (17 with hypothyroidism and 17 with hyperthyroidism). No differences were observed in mean baseline BMI between hypo and hyperthyroid patients (27.07±3.22 vs 26.39±4.44, p=0.609). Overweight or obesity was observed in 76.5% and 58.8% of hypothyroid and hyperthyroid patients, respectively (p=0.23). After normalization of thyroid function, the weight of hypothyroid patients decreased from 70.93±10.06 kg to 68.68±10.14 (p=0.000), while the weight of hyperthyroid patients increased from 65.45±11.64 kg to 68.37±12.80 (p=0.000). Their mean BMI was 26.22±3.36 and 27.57±4.98 (p=0.361) for hypo- and hyperthyroid patients, respectively. 58.8% and 64.7% patients remained in the overweight/obesity range in each group (p=0.72). CONCLUSION: Untreated thyroid dysfunction is not associated with BMI. Normalization of thyroid levels significantly changed the weight of patients, but remaining most patients within overweight ranges.

Liraglutide in a real-world setting: Joint modeling of metabolic response, prediction of efficacy, and cardiovascular risk.

INTRODUCTION AND OBJECTIVES: The worldwide prevalence of type 2 diabetes mellitus increases in parallel to that of obesity. Liraglutide (LRG), a glucagon-like peptide-1 receptor agonist, can reduce body weight. This study assessed the metabolic efficacy of LRG in real-world clinical practice. METHODS: An observational, retrospective cohort study including patients treated with LRG for at least one year (187 patients). Anthropometric and metabolic variables, a composite endpoint, factors predicting response to LRG, and cardiovascular risk over time were assessed. A linear mixed-effects model with a bivariate structure was constructed to investigate the time-dependent relationship between weight and HbA1c values. RESULTS: HbA1c levels and weight significantly decreased in the first 12 weeks, and the decrease persisted at 12 and 24 months in all subgroups studied. Mean weight and HbA1c decreases after 24 months were 8.5kg and 1.7% respectively. HbA1c values <7% were achieved by 42% of patients at 12 months and by 40% at 24 months. Treatment with LRG allowed for reduction in insulin dose. No serious adverse events were noted. Cardiovascular risk decreased from high to moderate-low. CONCLUSIONS: Under standard clinical practice conditions, LRG achieved a better metabolic response than seen in clinical trials. Efficacy at 12 weeks of treatment is a good predictor of response. LRG allows for delaying or reducing insulin dose by improving both weight and glucose control. Cardiovascular risk improved.