Background/Objectives: Diabetes mellitus is a growing global health concern, driving the exploration of new therapies like cannabidiol (CBD), which shows potential in improving insulin sensitivity and glycemic control, though its effects on glucose metabolism remain unclear. This study evaluates CBD’s dose-dependent effects on glycemia, insulin, and hepatic carbohydrate metabolism in diabetic rats. Methods: The Oral Glucose Tolerance Test (OGTT) was performed in healthy rats to compare intragastric vs. intraperitoneal CBD (0.5, 5, 50 mg/kg). Diabetic rats were treated with intragastric CBD (25, 50, 100 mg/kg) or metformin (70 mg/kg) for 8 days. Blood glucose, insulin, lipid profiles, and key carbohydrate-metabolizing enzymes were analyzed. Results: In the OGTT, intragastric CBD reduced glycemic AUC, with 50 mg/kg showing the strongest effect, while intraperitoneal CBD had no impact. In diabetic rats, metformin and 25 mg/kg CBD lowered blood glucose, but only CBD increased insulin. The 50 mg/kg dose caused the greatest glucose reduction and moderate insulin rise, while 100 mg/kg had no effect. At 25 mg/kg, CBD inhibited glucose-6-phosphatase and increased glucose-6-phosphate. The 50 mg/kg dose further suppressed gluconeogenic enzymes, reduced glycogen phosphorylase and liver glucose, and enhanced glucose-6-phosphate, showing the strongest metabolic effects. The 100 mg/kg dose increased hexokinase but had weaker metabolic effects. Metformin improved glucose utilization and glycogen storage. CBD at 25 and 50 mg/kg reduced triacylglycerols and increased HDL, while 100 mg/kg had no effect. Conclusions: This study provides strong evidence of CBD’s antidiabetic potential, especially at 50 mg/kg, particularly through its modulation of glucose metabolism and tendency to regulate insulin levels.

Antipsychotic drugs are widely used in the treatment of schizophrenia and psychotic disorder. The lack of antipsychotic response and treatment-induced side-effects, such as neuroleptic syndrome, polydipsia, metabolic syndrome, weight gain, extrapyramidal symptoms, tardive dyskinesia or prolactin increase, are the two main reasons for non-compliance and increased morbidity in schizophrenic patients. During the past decades intensive research has been done in order to determine the influence of genetic variations on antipsychotics dosage, treatment efficacy and safety. The present work reviews the molecular basis of treatment response of schizophrenia. It highlights the most important findings about the impact of functional polymorphisms in genes coding the CYP450 metabolizing enzymes, ABCB1 transporter gene, dopaminergic and serotonergic drug targets (DRD2, DRD3, DRD4, 5-HT1, 5HT-2A, 5HT-2C, 5HT6) as well as genes responsible for metabolism of neurotransmitters and G signalling pathways (5-HTTLPR, BDNF, COMT, RGS4) and points their role as potential biomarkers in everyday clinical practice. Pharmacogenetic testing has predictive power in the selection of antipsychotic drugs and doses tailored according to the patient’s genetic profile. In this perception pharmacogenetics could help in the improvement of treatment response by using different medicinal approaches that would avoid potential adverse effects, reduce stabilization time and will advance the prognosis of schizophrenic patients.

Introduction: Identifying early predictive factors of how rheumatoid arthritis (RA) patients respond to rituximab (RTX) treatment is crucial for both individual treatment outcome and the improvement of clinical practice overall. This study aimed to identify early predictive factors available in standard clinical practice for predicting RTX treatment outcomes in RA patients.Material and methods: Data on seventy patients diagnosed with RA treated with RTX (two 1,000 mg doses 2 weeks apart or two 500 mg doses 2 weeks apart) were retrospectively collected. Baseline information collected at the initiation of RTX treatment included patient characteristics such as age, sex, disease duration, disease activity, Health Assessment Questionnaire score, erythrocyte sedimentation rate, C-reactive protein, and serological status regarding rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Clinical responses were analyzed 6 months after RTX initiation using the European Alliance of Associations for Rheumatology criteria. Potential predictors associated with positive RTX response at 6 months were identified using a multivariate ordinal logistic regression model.Results: The analysis showed that persistently active RA disease, Disease Activity Score in 28 Joints (DAS28) values at the treatment onset and after 3 months, along with erythrocyte sedimentation rate at treatment initiation, were negatively correlated with the response to RTX therapy (p < 0.05). All these correlations were statistically significant at the 99% confidence interval. The correlation and logistic regression analyses indicate that there are no significant association between rheumatoid factor and anti-cyclic citrullinated peptide antibodies concerning therapy response, despite a higher number of rituximab responders in the seropositive groups. Additionally, the study emphasizes the prognostic significance of the DAS28 value at treatment initiation in predicting therapy response at 6 months.Conclusions: The optimal model for predicting RTX response at 6 months involves the interaction of all clinical factors examined in this study, as revealed by the analysis of multiple variables.

Purpose: A rational use of statins has a major and increasing importance in public health and allocation of financial resources by the health insurance funds (HIFs). The aim of this study was to evaluate the market share and utilization trends of statins in the Republic of Macedonia (R. Macedonia) from 2013 to 2016. Materials and methods: A retrospective analysis and data comparison for the utilization of HMG-CoA inhibitors (C10AA) in R. Macedonia from 2013 to 2016 were conducted. The data obtained from HIF, IMS Health, pharmaceutical industry and marketing authorization holders (MAHs) were evaluated through defined daily doses per 1000 insurers per day (DDD/TID). Results: Cardiovascular drugs are the most commonly prescribed and utilized drugs in R. Macedonia. The HIF cost for cardiovascular disease (CVD) increased to €2,243,777.00 in the period from 2013 to 2016. Since 2012, the reimbursement shows that atorvastatin accounts for the highest expenditure reaching €2,162,958.00 while rosuvastatin reached €1,645,860.00 in 2016. The increased consumption of statins is confirmed from the records obtained from IMS Health databases in the evaluated period in R. Macedonia suggesting increased expenditures with total growth of 35.65% reaching €4,421,280.24 in 2016. Evident growth of statin consumption is confirmed from the data obtained from the pharmaceutical industry and MAH. The statin use increased from 42.347 DDD/TID in 2013 to 71.697 DDD/TID in 2016, although it is lower in comparison to other European Union (EU) countries (1.1–2.5-fold). Conclusion: The rapid increase in the consumption of statins can be attributed mostly to an increase in the consumption volume. It is inevitable to widen the price reduction concept with initiatives that may control statin consumption amounts with measures such as educational programs for rational drug utilization and targeting eligible population.

Introduction: Antimicrobial resistance (AMR) is a pressing global health issue exacerbated by the overuse of antibiotics during the COVID-19 pandemic. Despite WHO guidelines against antibiotics for mild-to-moderate COVID-19 cases without bacterial co-infection, significant misuse has been reported globally. This study aimed to evaluate antibiotic consumption during the COVID-19 pandemic at a hospital in North Macedonia and to analyze adherence to WHO guidelines, with a focus on antimicrobial stewardship, using the ATC and WHO AWaRe classification systems. Objective: To analyze antibiotic utilization trends from January 2020 to December 2021 and assess adherence to WHO guidelines, focusing on the potential impact on AMR. Method: This retrospective observational study measured antibiotic consumption in defined daily doses (DDD) per 100 occupied bed-days (DDD/100 OBD) using ATC and WHO AWaRe classifications. Data were obtained only from ICU inpatients treated at the Clinical Hospital in Shtip, North Macedonia. Trends in annual consumption were analyzed, including rate-of-change calculations for individual antibiotics between 2020 and 2021. Result: Total antibiotic consumption decreased from 2902.6 DDD/100 OBD in 2020 to 2286.5 DDD/100 OBD in 2021. A third-generation cephalosporin, ceftriaxone, was the most consumed antibiotic, accounting for 57.62% of total consumption in 2020 and 48.55% in 2021. Tetracycline use slightly increased from 13.88% in 2020 to 15.83% in 2021. Fluoroquinolone use decreased significantly from 15.22% in 2020 to 6.5% in 2021. Carbapenem consumption rose sharply from 1.7% in 2020 to 14.37% in 2021, while azithromycin use declined threefold. Antibiotics in the Access group accounted for less than 20% of total usage, while those in the Watch group predominated. result: Total antibiotic consumption decreased from 2902.6 DDD/100 OBD in 2020 to 2286.5 DDD/100 OBD in 2021. Third-generation cephalosporin ceftriaxone was the most consumed antibiotic, representing 57.62% of total consumption in 2020 and 48.55% in 2021. Tetracycline use slightly increased from 13.88% in 2020 to 15.83% in 2021. Fluoroquinolone use decreased significantly from 15.22% in 2020 to 6.5% in 2021. Carbapenem consumption rose sharply from 1.7% in 2020 to 14.37% in 2021, while azithromycin use declined threefold. Antibiotics in the Access group accounted for less than 20% of total usage, while those in the Watch group predominated. Discussion: The study highlights a continued reliance on broad-spectrum antibiotics during the pandemic, diverging from WHO recommendations emphasizing Access to antibiotics. These trends suggest inadequate implementation of antimicrobial stewardship practices and raise concerns about their long-term impact on AMR. Limitations include the retrospective, single-center design, which may limit the generalizability of the findings. Conclusion: The findings underscore the high dependency on Watch category antibiotics and a limited focus on Access antibiotics, contrary to WHO recommendations. This highlights the urgent need for robust antimicrobial stewardship programs to control inappropriate antibiotic use and combat AMR.