Ubiquinone, Ezetimibe/Simvastatin and Rosuvastatin Effects on Mitochondrial Function in Diabetic Polyneuropathy

Diabetic polyneuropathy (DPN) pathophysiologic findings include loss of multifocal and focal nerve fibers secondary to axonal degeneration and segmental demyelization due to oxidative stress and mitochondrial dysfunction induced by chronic hyperglycaemia

Pharmacological Opportunities for Prevention of Preeclampsia

Preeclampsia (PE) is a disorder that occurs during pregnancy, it has an estimated worldwide prevalence of 5–8%, being one of the leading causes of maternal and perinatal morbidity and mortality. Currently, different diagnostic criteria exist, however, due to its complexity; the clinical presentation that makes up this syndrome could make its presence unclear. The pathophysiology of PE has been recently postulated and divided into three processes: inadequate uterine remodeling, placental dysfunction and maternal endothelial dysfunction. Despite the advances in the treatment of PE, the outcome of the medical interventions has failed to decrease the morbidity and mortality of this disease. The main reason might be the multifactorial origin of pathogenic processes that lead to the development of PE. That is why treatment is focused on the prevention of PE in patients that might present the risk before developing it late in pregnancy. The knowledge of the pathophysiological factors that trigger the processes that culminate in the presentation of PE, is key for prevention of this disease. However, the origin of these processes is poorly understood. It may be attributed to the ethical considerations that come with the study of these population of patients compared with the study of non-pregnant women

Clinical Trials in Pregnant Women with Preeclampsia

Preeclampsia (PE) is the leading cause of preterm birth by medical indication when associated with premature detachment of placenta normoinserta, and Intrauterine growth restriction (IUGR) is associated with high perinatal morbidity and mortality and long-term sequelae. The main problem of PE is threefold: the diagnostic difficulty, the complicated interrelationship of the pathophysiological processes, and the vulnerability of the maternal-fetal binomial to the therapeutic interventions. The approach for management with PE is preventing its late occurrence in pregnancy. The key to preventing PE is knowledge of the factors that trigger the pathophysiological processes that culminate in the presentation of PE. Understanding the developmental characteristics of the placenta in pregnancy at high risk for PE is essential for understanding the pathophysiology and developing strategies for prevention. When deciding that the population of study is a group of pregnant women, the first ethical criteria that need to be reviewed are those aimed at the protection of the fetus. There are no specific guidelines on how to assess fetal well-being during pregnancy routinely in the clinic, and this deficiency is shifted to clinical research with pregnant women

Very Low-Calorie Diets in Type 2 Diabetes Mellitus: Effects on Inflammation, Clinical and Metabolic Parameters

Type 2 diabetes mellitus (DM) is a chronic and multifactorial disease strongly linked to a low-grade inflammatory process. Thus far, type 2 DM is generally regarded as an incurable disease by common therapies. However, very low-calorie diet (VLCD) regimens have demonstrated beneficial and rapid effects on glucose metabolism in subjects with type 2 DM. These beneficial effects include improvement of diabetes complications, insulin sensitivity and reduction in glycaemia, glycated hemoglobin (HbA1C), and triglyceride levels. VLCD regimens commonly comprise no more than 800 kcal/day and are therefore associated with rapid weight loss in overweight and obese individuals. This group of diets positively affects local/systemic inflammation and oxidative stress (OS) by modulating inflammatory cytokines, adipokines and endogenous antioxidant levels. The investigation of VLCDs in the field of type 2 DM treatment is progressively augmenting due to the multiple benefits in cardiometabolic health of overweight/obese subjects with type 2 DM. Here, we gather and review the evidence regarding the role of inflammation and OS in individuals with type 2 DM under VLCD regimens

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor 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. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Colombian consensus recommendations for diagnosis, management and treatment of the infection by SARS-COV-2/ COVID-19 in health care facilities - Recommendations from expert´s group based and informed on evidence

La Asociación Colombiana de Infectología (ACIN) y el Instituto de Evaluación de Nuevas Tecnologías de la Salud (IETS) conformó un grupo de trabajo para desarrollar recomendaciones informadas y basadas en evidencia, por consenso de expertos para la atención, diagnóstico y manejo de casos de Covid 19. Estas guías son dirigidas al personal de salud y buscar dar recomendaciones en los ámbitos de la atención en salud de los casos de Covid-19, en el contexto nacional de Colombia

Real-World Evidence Evaluation on the Lipid Profile, Therapeutic Goals, and Safety of the Fixed-Dose Combination of Rosuvastatin/Ezetimibe (Trezete®) in Dyslipidemia Patients

Introduction. Cardiovascular diseases are the leading cause of death worldwide. The combination of statins and cholesterol-absorption inhibitors promotes the decrease in risk factors, such as high concentrations of LDL (low-density lipoproteins). The aim of the study was to evaluate changes in the lipid profile and the effect on therapeutic goals, as well as the safety of dyslipidemia patients treated with Rosuvastatin/Ezetimibe (Trezete®). Materials and Methods. A real-world evidence study was conducted with retrospective data collection through a review of clinical records from dyslipidemia patients treated with Trezete® in routine medical practice. Clinical records included results of biochemical markers before treatment and at least one follow up between weeks 8 and 16. Results. The study included 103 patients’ clinical records (55.4% men) with a mean age of 56.0 ± 13.0 years. More than 57% of the patients had mixed dyslipidemia and a median disease progression of 3.1 (IQR, 1.5; 9.1) years. Regarding LDL concentrations, 72.8% of the patients achieved therapeutic goals according to cardiovascular risk (CVR), which was statistically significant. Similarly, 94.1% achieved goals for total cholesterol (<200 mg/dL) and 56.0% for triglycerides (<150 mg/dL), a p value <0.001. No cardiovascular events were observed. Conclusion. Trezete® shows an important clinical impact on CVR-related target markers during the treatment of dyslipidemia patients. It is relevant to mention that a significant percentage of patients achieved therapeutic goals during the first months of treatment. Fixed-dose combination therapy has shown to be as safe as monotherapy treatment. ClinicalTrials.gov Identifier: NCT04862962