Purpose: This study aimed to assess the cost-effectiveness of medical nutritional support in a cancer care program in North Macedonia, comparing specialized oral nutritional supplements (ONS) with the standard of care (SOC) in managing disease-related malnutrition (DRM) in patients with or at risk of tumor cachexia syndrome. Methods: A previously published decision tree model was employed to evaluate the economic impact of supportive treatment in cancer patients eligible for ONS. Monthly transition probabilities between health states, length of hospital stay for each treatment strategy, and utility parameters were derived from the literature. For base-case analysis, the cancer care program duration was set at 30 days. The analysis was conducted from the perspective of a national health insurance fund, utilizing a 13-year time horizon with monthly cycles. Only direct supportive care costs, estimated from publicly available data, were considered. Quality-adjusted life-years (QALYs) gained per patient and associated costs were calculated, with outcomes and costs discounted at 3.0% annually. One-way and probabilistic sensitivity analyses were performed to assess results robustness. Results: In the base case analysis, ONS was the dominant treatment strategy, with total costs per patient of € 2605.01 for ONS versus € 3759.23 for SOC, indicating a significant cost reduction. Reduced hospitalization expenses outweighed the higher acquisition costs of ONS. Additionally, ONS provided greater health benefits, achieving 8.21 QALY vs 7.91QALY in the SOC group. The resulting Incremental Cost-Effectiveness Ratio (ICER) was negative, reinforcing ONS as the dominant strategy. Sensitivity analyses confirmed that the cost-effectiveness was primarily driven by cancer program duration, with cost-saving benefits up to 132 days. Conclusion: Our findings demonstrate that specialized ONS is a cost-effective treatment option within a cancer care program compared with SOC. While this study focuses on North Macedonia, the results are applicable to countries with similar economic and healthcare structures, reinforcing ONS as a valuable intervention across comparable healthcare systems. Plain Language Summary: Approximately 50% of patients with advanced cancer present with cachexia syndrome, a severe form of disease-related malnutrition (DRM). Medical nutrition is a specialized category of nutrition that addresses specific dietary needs and deficiencies. Early nutritional interventions with specialized oral nutritional supplements (ONSs) have demonstrated the ability to alleviate the negative effects of cancer and its treatments on nutritional status. Assessing the economic impact of specialized ONSs is essential for managing chronic diseases such as cancer, which creates considerable financial challenges. Evidence of economic implications is limited and differs across healthcare settings, intervention types, and patient demographics. This study aimed to provide decision-makers in the Republic of North Macedonia with supportive evidence on the relative and incremental cost-effectiveness of ONS in managing patients with cancer who are malnourished or at risk of severe DRM. Our findings indicate that the cost-effectiveness of early ONS intervention is primarily driven by the duration of the cancer care program, with cost-saving benefits observed within the 30-day base-case scenario and up to 132 days in sensitivity analysis. Beyond this period, ONS remained cost-effective within the willingness-to-pay threshold. This supports reimbursement decisions for addressing malnutrition in this vulnerable patient group, helping to maximize health benefits within constrained budgets.

Aims: The present observational cohort study evaluated the association between the AKR1D1*36 (rs1872930) allele and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in clopidogrel treated patients. Methods: We screened 198 consecutive cardiovascular patients on clopidogrel therapy admitted in October to November 2010 with cardiovascular or cerebrovascular symptoms; of these 118 met the study protocol entry criteria; the median age of the cohort was 62.5 years (IQR 57–66 years), and 55% were females. Results: The median follow up time was 38.5 (IQR 24–48) months; Kaplan-Meier/Log-rank analysis showed that patients carrying the AKR1D1*36 allelic variant have a shorter event-free-survival compared to wild type patients, hazard ratio = 2.193 (95% CI, 1.091 to 4.406); p = 0.0155. Multivariable Cox regression analysis confirmed the AKR1D1*36 allele as an independent risk factor (HR = 2.36; 95% CI, 1.34 to 4.18) and identified 3 other risk factors for MACCE; previous percutaneous interventions (PCI), HR = 2.78; (95% CI, 1.34 to 5.78), and a history of myocardial infarction, HR = 2.62; (95% CI, 1.48 to 4.64) at baseline and the previously reported CYP2C19*2 polymorphism (HR = 2.33; 95% CI, 1.33 to 4.06). Conclusion: The AKR1D1*36 (rs1872930) variant is independently associated with a higher risk for MACCE and shorter event-free survival time.

The relative contribution of CYP2C9 allelic variants to the pharmacokinetics (PK) of ibuprofen (IBP) enantiomers has been studied extensively, but the potential clinical benefit of pharmacogenetically guided IBP treatment is not evident yet. The role of AKR1D1*36C>T (rs 1872930) allelic variant in interindividual variability of CYP450 mediated drug metabolism was recently elucidated. A total of 27 healthy male subjects, volunteers in IBP single-dose two-way cross-over bioequivalence studies were genotyped for CYP2C9*2, CYP2C9*3 and AKR1D1*36 polymorphisms. The correlation between CYP2C9 and AKR1D1 genetic profile and the PK parameters for S -(+) and R -(−)-IBP was evaluated. Remarkable changes in the PK values pointing to reduced CYP2C9 enzyme activity were detected only in the CYP2C9*2 allelic variant carriers. Statistically significant association between the AKR1D1*36 allele and the increased IBP metabolism (low AUC _0-t and _0–∞ , high Cl _tot and short t _max values for both enantiomers) was observed in subjects carrying the CYP2C9 *1/*3 or CYP2C9*1/*1 genotype. The clinical value of concomitant CYP2C9 and AKR1D1 genotyping has to be further verified.

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.

Clopidogrel, is a standard treatment in the prevention of major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD). Clopidogrel response is highly variable, mainly due to the presence of polymorphisms in the genes involved in drug metabolism. The aim of this study was to evaluate the association between the presence of the ABCB1 C3435T and CYP2C19* 2 polymorphism and the clinical outcome in patients with CAD treated with clopidogrel. A total of 96 patients with CAD were included in the study. Genomic DNA from peripheral blood was extracted from all patients with standard phenol/chloroform protocol. The genotyping was performed by Real-Time PCR using TagMan assays. The frequency of the reduced-function allele, in both genes, was higher in patients with negative outcome (36.36% vs 21.15%). A negative clinical outcome and an increased risk for MACE was observed in patients with concomitant inheritance of the CYP2C19 *1/*2 and ABCB1 CT genotype vs patients with other genotypes (22.73% vs 9.62%; OR 3.455; 95% CI= [0.936–12.743], p=0.05722. A trend towards higher risk of MACE was also noted in carriers of the CYP2C19*1/*1 and ABCB1 CC/CT genotype. Our results support the data on the association of the CYP2C19 *2 alone, or in combination with the ABCB1 C polymorphism with the increased risk of MACE. The results also indicate that the presence of ABCB1 C343T polymorphism might be potentially considered as independent predictor of MACE in patients on clopidogrel. However, these results are preliminary and should be confirmed on a larger number of patients.