What is Known and Objective Many investigators agree that appropriate rational utilization of therapeutic drug monitoring (TDM) with Bayesian feedback dosage adjustment facilitates epilepsy treatment with carbamazepines and/or valproates by increasing the seizure control and safety, as well as by reducing treatment costs. In previous works we have developed and used in clinical practice population pharmacokinetic (PK) models of different dosage forms for valproate (VPA) and post – induction carbamazepine (CBZ) behaviour as well as for combined therapy with CBZ plus another “old” antiepileptic drug (AED). An important step of external validation is to evaluate how well a procedure of Bayesian individualizing AED dosage regimens based on a proposed population PK model and sparse TDM data “works”, and how helpful it is in real practical clinical settings. The aim of this study was to evaluate the predictability of individualized dosage regimens for monotherapy with CBZ in the post-induction period or with VPA, as well as for CBZ and VPA given as combination therapy based on TDM data of epileptic patients and the earlier developed population models. Methods Four groups of TDM data were analyzed using the USC*PACK software for PK/PD analysis: 556 predictions for adult epileptic patients on CBZ monotherapy, 662 predictions for VPA monotherapy, 402 predictions of CBZ serum levels and 430 predictions of VPA serum levels for adult epileptic patients on CBZ+VPA combination therapy. Statistical characteristics of the prediction errors and weighted prediction errors were used to estimate bias and precision of predictions. Intraindividual and interoccasional variability of predictions were also estimated. Results and Discussion This study demonstrated that in most cases of CBZ and VPA monotherapy and combination therapy, predictions of future AED concentrations based on the earlier developed population PK models, TDM data and patient-specific maximum aposteriori probability (MAP) Bayesian posterior parameter values provided clinically acceptable estimates. Statistical analysis of the residuals demonstrated that the distributions of residuals and weighted residuals were close to a Normal distribution (Kolmogorov – Smirnov test, p>0.05) and their mean values did not differ statistically significantly from zero (no statistically significant bias, p>0.05) for all groups of predictions. The observed decreased quality of predictions of VPA concentrations during VPA+CBZ combination therapy, especially when CBZ dosages were changed, might well be explained by their PK interactions. For all groups, in linear regression analysis, the observed trend of decreasing of the prediction quality over various future prediction time horizons was considered statistically significant (p<0.05). Prediction of serum levels further into the future was less precise than those closer to the present for a 1.5 to 3.5-year observation period. No bias in predictions was associated with the time horizons. What is New and Conclusion Our validation res...

<p>This study assessed the features of the course of acute coronary syndrome in patients with diabetic neuropathy. Additionally, the role of antihyperglycaemic therapy as a cardio protection factor in this syndrome was determined by analysing the available literature data and clinical guidelines. Various antihyperglycaemic drug groups demonstrate possible molecular mechanisms of protection against ischemic cardiomyocytes. Cardiovascular disease treatment for patients with type 2 diabetes mellitus is rapidly developing. However, many aspects, including the exact mechanisms of the cardio protective action of antihyperglycaemic drugs, the presence of an additional positive effect of antihyperglycaemic drugs for patients with other diseases (e.g. kidney disease and chronic heart failure), and possible primary prevention of cardiovascular events in patients with type 2 diabetes, remain unclear.</p><p>Received 11 September 2020. Revised 16 January 2021. Accepted 10 February 2021.</p><p><strong>Funding: </strong>The study did not have sponsorship.</p><p><strong>Conflict of interest: </strong>Authors declare no conflict of interest.</p>

Aim. To study the influence of hypoglycemic therapy on hospital and long-term prognosis in patients with acute coronary syndrome (ACS) and diabetes type 2.Methods. The study included 63 patients with ACS and type 2 diabetes. All patients had a clinical examination, assessment of mortality risk and myocardial infarction on GRACE scale (Global Registry of Acute Coronary Events) and TIMI (Thrombolisis In Myocardial Infarction) in-hospital and six months after hospitalization.Results. Metformin is associated with a lower estimated risk of in-hospital mortality and within 6 months after discharge in patients with acute coronary syndrome on the background of type 2 diabetes and with less risk of adverse cardiovascular events within 14 days of their occurrence in patients with unstable angina pectoris on the background of diabetes. High daily doses of metformin have also been associated with a decrease in the estimated risk of in-hospital mortality and within 6 months after discharge in patients with ACS associated with diabetes. The inverse association between the daily dosage of metformin and the presence of angina pectoris in patients with ACS and diabetes type 2 indicates a protective effect of metformin high daily dosages in relation to the risk of complications within six months after the discharge from hospital.Conclusion. One of the important aspects of ACS treatment, along with effective therapy, is the impact on concomitant risk factors, including blood glucose control. The main groups of hypoglycemic drugs have currently been identified; their effect on cardiovascular events, long-term effects and long-term prognosis are being investigated.