Background: Patients with malignant diseases receiving chronic opioid therapy are particularly susceptible to drug–drug interactions because of extensive polypharmacy, multimodal anticancer treatment, supportive care, and comorbidities. This study aimed to determine the prevalence of potentially clinically relevant drug–drug interactions and to identify factors associated with their occurrence. Methods: This exploratory observational cross-sectional pilot study included 49 adult oncology patients receiving chronic opioid therapy. Complete medication regimens were screened using the Medscape Drug Interaction Checker and Lexicomp. Lexicomp category D and X interactions were analysed descriptively. Because category D interactions were nearly universal and category X interactions were rare, the presence of at least one Medscape “Serious—Use Alternative” interaction was used pragmatically as the binary outcome for regression modelling. Potential predictors were assessed using univariable binary logistic regression and a parsimonious adjusted model with covariates selected using a clinically informed approach. Because of quasi-complete separation, Firth’s penalized-likelihood logistic regression was used as the primary adjusted analysis. Results: Lexicomp category D interactions were identified in 48 of 49 patients (98.0%), whereas category X interactions were present in 2 patients (4.1%). Medscape serious interactions were detected in 33 patients (67.3%). In the Firth-adjusted model, female sex was associated with lower odds of a Medscape serious interaction (adjusted OR 0.12, 95% CI 0.02–0.52), while cardiovascular disease was associated with higher odds (adjusted OR 5.16, 95% CI 1.27–26.31). Stage IV disease showed a positive but statistically non-significant association, and total medication count was not independently associated with the outcome in sensitivity analysis. Because of the small pilot sample and the resulting wide confidence intervals, these findings should be interpreted as exploratory and hypothesis-generating. Conclusions: Oncology patients receiving chronic opioid therapy had a high burden of potentially clinically relevant drug–drug interactions, predominantly Lexicomp category D interactions, warranting consideration of therapy modification and individualized monitoring rather than absolute avoidance. Regular medication review, use of complementary interaction databases, and individualized clinical assessment may improve pharmacotherapy safety in this vulnerable population.

Introduction/Aim. Breast cancer (BC) represents a globally significant health issue, with incidence rates varying worldwide. Radiotherapy is crucial in treating BC, however, it can cause adverse effects, including skin reactions. The aim of this research was to evaluate the impact of two different radiotherapy fractionation regimens on the occurrence and severity of acute skin toxicity in BC patients. Methods. The prospective study involved 44 patients who underwent postoperative radiotherapy. The patients were randomly divided into two groups: one group received hypofractionated regimen (40.05 Gy in 15 fractions over three weeks), while the other group received the standard fractionated regimen (50 Gy in 25 fractions over five weeks). The patients in this study were monitored weekly for acute skin toxicity throughout the duration of radiotherapy and following the completion of treatment. Results. The patients receiving the standard fractionated regimen experienced a higher frequency and intensity of acute skin reactions, including erythema, dry desquamation, and moist desquamation. Skin reactions of grade I and II were particularly prominent in the patients receiving 50 Gy. Although the patients receiving hypofractionated radiotherapy had less severe skin reactions, mild skin changes did occur, although they were generally less prominent. Conclusion. The study points to the need for a careful selection of fractionation regimens in postoperative breast radiotherapy. Additionally, this study contributes to the understanding of the relationship between different radiotherapy modalities and the occurrence of acute skin toxicity, providing guidelines for optimizing treatment in BC patients.

Background: Post -operative atrial fibrillation (POAF) is a frequent complication after cardiac surgery. It is associated with prolonged hospital stay, increased morbidity, mortality rate and economic costs. The aim of the study was to determine the association between the values of Galectin3 and N -terminal pro -B -type natriuretic peptide (NTproBNP) with POAF after cardiac surgery. Methods: A prospective study enrolled patients aged 18-85 years old admitted due to elective coronary artery bypass graft surgery (CABG) or CABG + aortic valve replacement. The plasma Galectin-3 and NT-proBNP levels were measured one day before surgery postoperative days 1 and 7. Results: The study included a total of 103 patients. POAF was registered in 45 patients. The mean age of patients in whom POAF occurred was 68.8 years, while other patients' mean age was 65.5 years ( p =0.028). Patients with POAF did not differ from the group without POAF in the values of Galectin-3 and NT-proBNP preoperatively as well as on the first and seventh postoperative days. Changes in Galectin-3 levels on the first postoperative day had statistically significant value for predicting POAF (AUC=0.627 [0.509- 0.745], p <0.05). Decrease in Galectin-3 level concentration on the first postoperative day over 17% increases the risk of developing AF. Conclusions: Preoperative values of Galectin-3 and NT-proBNP are not associated with POAF development after cardiac surgery.

Tapentadol is a unique opioid analgesic due to its dual mechanism of action. Compared to other opioids with a classical mechanism of action, its analgesic potential is not far behind them, and its advantages are: a better safety profile in terms of a lower potential for drug-drug interactions and a lower potential for causing adverse events, and it is safe to use in sensitive populations. Tapentadol in the form of a immediate release formulation is an adequate drug of choice for achieving a pharmacotherapeutic analgesic response in acute pain conditions, while in the form of a extended release formulation it is an adequate pharmacotherapeutic analgesic solution for chronic pain syndromes of various etiology. Due to the specificity of the mechanism of action, tapentadol adequately relieves both pain components - nociceptive and neuropathic, and has an indication area for mixed pain syndrome as well. Based on this, the need for the use of co-analgesics is reduced, and thus the incidence of possible interactions and adverse events is reduced.

INTRODUCTION:This study aimed to compare the prevalence of potentially inappropriately prescribed drugs in hemodialysis patients and patients with chronic kidney disease who did not require renal replacement therapy, as well as to identify risk factors associated with potentially inappropriate prescribing. METHODS:The study was designed as a cross-sectional study conducted at the Department of Nephrology, Clinical Center in Nis, Serbia. The patients were divided into two groups: (1) patients on hemodialysis treatment and (2) patients with various degrees of chronic kidney disease without renal replacement therapy. The presence or absence of potentially inappropriate prescribing was determined using the 2015 AGS Beers criteria. FINDINGS:The study included a total of 218 patients aged 65 years and over. The number of patients with potentially inappropriate prescribed drugs did not differ significantly (chi-square = 0.000, p = 1.000) between patients on hemodialysis (27 of 83, i.e., 32.5%) and patients with various degrees of chronic kidney disease without renal replacement therapy (44 of 135, i.e., 32.6%). Factors associated with potentially inappropriate prescribing in hemodialysis patients were the number of drugs (hazard ratio [HR] = 1.919, 95% confidence interval [CI]: 1.325-2.780) and number of comorbidities (HR = 1.743, 95% CI: 1.109-2.740). The number of drugs (HR = 1.438, 95% CI: 1.191-1.736) was the only independent factor associated with increased risk of potentially inappropriate prescribing in patients without renal replacement therapy. DISCUSSION:Our study showed that potentially inappropriate prescribing is a relatively frequent phenomenon present in about a third of patients in both study groups. The number of prescribed drugs was the main factor associated with the increased risk of potentially inappropriate prescribing in both groups.

Objective: Tapentadol is a drug of choice for neuropathic cancer pain. DN4 questionnaire quickly determines neuropathic pain component. The aim of this study is to determine the correlation between neuropathic malignant pain component by applying tapentadol antidolorose pharmacotherapy in combination with palliative radiotherapy of osseous neuropathic metastatic changes in breast cancer patients before and after palliative radiotherapy. Methods: The first patients group comprised 30 patients with primary breast cancer and proved painful bone secondary deposits with neuropathy for which tapentadol was prescribed, and they underwent palliative radiotherapy. The second group comprised 30 patients with primary breast cancer and proved painful bone metastases with neuropathy treated only with palliative antidolorose radiotherapy. Key findings : After two-months-follow up, tapentadol group patients had lower DN4 score values (Z=2,021; p=0.043). Significantly lower number of tapentadol group patients was without neuropathic pain after a three-month-follow up (χ ²=5,711; p=0.017). Significantly greater number of tapentadol group patients had best ECOG score 0 ( χ² =7,486; p=0.023). There was statistically significant positive correlation between tapentadol dose and DN4 score in patients after a month (ρ=0,471; p=0.009) and three months after the radiotherapy completion (ρ=0,610; p<0.001). Tapentadol is an opioid analgesic efficient for neuropathy relief in these patients and DN4 questionnaire is an efficient pharmacotherapy tool.

Introduction/Aim. Analgesics are drugs used in the pain pharmacotherapy and are one of the most prescribed drugs in all countries. Modern pain pharmacotherapy involves the use of analgesic steps. The objective of this paper was to analyze the consumption of drugs used in the pain pharmacotherapy in the Republic of Serbia (RS), in the period from 2015 to 2018, and to compare the obtained results with the consumption of the mentioned drugs in the Kingdom of Norway (KN) and the Republic of Finland (RF) in the same time period interval. Material and methods. Data on drug consumption were taken from the website of the Agency for Medicines and Medical Devices of Serbia, the official website of the Norwegian Institute of Public Health and from the official website of the Finnish Medicines Agency. The consumption of medicines is monitored using the defined daily dose (DDD) methodology. Results. Paracetamol consumption was 13 to even 20 times lower in the RS compared to the KN and 10 to 15 times lower compared to the RF. The average consumption of diclofenac during the four observed years was about 30 DDD/1,000 inhabitants/day in the RS, about 7 in the KN and about 4 DDD/1,000 inhabitants/day in the RF. Conclusion. In the pain pharmacotherapy in the RS, the consumption of non-steroidal anti-inflammatory drugs is dominated by diclofenac, while in the KN and the RF ibuprofen and paracetamol from non-opioids.

Background: The incorporation of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has redefined therapeutic strategies for advanced ovarian cancer. This study evaluates the efficacy of bevacizumab combined with standard chemotherapy by comparing progression-free survival (PFS) and overall survival (OS) outcomes with a historical cohort of patients treated with standard chemotherapy alone. Methods: We conducted an analysis of 71 patients with advanced epithelial ovarian cancer treated at the University Clinical Center in Niš, Serbia, from April 2017 to March 2023. All patients received standard chemotherapy paired with bevacizumab and were monitored for progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier estimates. Subgroup analyses were performed based on age, ECOG performance status, presence of metastases, and pleural effusion. Additionally, a historical cohort of 30 patients treated with standard chemotherapy alone was used for comparison, and Cox regression analysis was conducted to identify factors influencing treatment outcomes. Results: The study findings indicate significant improvements in median PFS (20 months vs. 15 months) and OS (58 months vs. an undetermined upper limit) compared to the historical cohort. Subgroup analysis of the bevacizumab-treated group revealed that younger patients (<65 years) and those without metastases or pleural effusion exhibited notably better survival outcomes. The hazard ratio for PFS in patients younger than 65 was 0.65 (95% CI: 0.45-0.93), suggesting a substantial reduction in disease progression risk compared to older patients. Conclusion: Bevacizumab, when used alongside standard chemotherapy, significantly extends both PFS and OS in patients with advanced ovarian cancer. These benefits are particularly pronounced in younger patients. The results underscore the necessity of integrating bevacizumab into the treatment regimen for advanced ovarian cancer, advocating for tailored therapeutic strategies based on individual risk profiles and clinical characteristics. This study reinforces the pivotal role of bevacizumab in enhancing the current ovarian cancer treatment landscape and highlights the potential for further personalizing oncological care.

OBJECTIVE:Caudal block is a type of regional anesthesia suitable for inguinal hernia surgery in children. Our goal was to determine the effectiveness of caudal block combined with general anesthesia in providing intra- and postoperative analgesia and its effect on hemodynamic stability and drug consumption. PATIENTS AND METHODS:Prospective, randomized controlled study included 78 boys, 3-5 years, with an indication for inguinal herniorrhaphy, divided into groups G (general anesthesia, n=39) and G+C (general anesthesia + caudal block, n=39). We monitored hemodynamic parameters intraoperatively, postoperative pain, and total consumption of all medicaments in the perioperative period. The monitoring of complications and side effects of drugs was also carried out. RESULTS:Boys in group G had statistically significantly higher values of heart rate in the 5th minute (p<0.01), in the 25th minute (p<0.01), and after awakening from anesthesia (p<0.01). We obtained similar results with systolic and diastolic pressure values in the 5th minute (p<0.01), 15th minute (p<0.01), 25th minute (p<0.01), before awakening from anesthesia (p<0.01) and after awakening (p<0.01). They also had significantly statistically higher total consumption of propofol, fentanyl, and acetaminophen (p<0.01). Boys in group G+C had significantly lower postoperative pain scores: initially (p<0.01), after 2 hours (p<0.01), and after 5 hours (p<0.01). No complications occurred in this group. CONCLUSIONS:In children, the combination of general anesthesia with caudal block, compared to general anesthesia only, is more efficient in suppressing visceral pain, leading to better hemodynamic stability, and reducing the consumption of medicines in the perioperative period.

BACKGROUND:In the present study, two structurally similar alkaloids from trees of Cinchona genus, chloroquine and cinchonine, were examined for their vasorelaxant effects in a model of phenylephrine-induced smooth muscle contractions. METHODS:Potential mechanisms of action associated with endothelial vasorelaxant compounds, voltage-gated Ca2+ channels (LTCCs), and inositol triphosphate receptors were examined in isolated rat aortic rings. Also, an in silico approach was used to predict the activity of the two test compounds. RESULTS:Experimental results revealed that both chloroquine and cinchonine significantly decrease phenylephrine-induced smooth muscle contractions, although to a different extent. Evaluated mechanisms of action indicate that endothelium is not involved in the vasorelaxant action of the two tested alkaloids. On the other hand, voltage-gated Ca2+ channels were found to be the dominant way of action associated with the vasorelaxant action of chloroquine and cinchonine. Finally, IP3R is found to have only a small impact on the observed activity of the tested compounds. CONCLUSION:Molecular docking studies predicted that chloroquine possesses a significant activity toward a suitable model of LTCCs, while cinchonine does not. The results of the present study point to the fact that great caution should be paid while administering chloroquine to vulnerable patients, especially those with cardiovascular disorders (Tab. 3, Fig. 3, Ref. 28).

OBJECTIVE:Laryngoscopy and endotracheal intubation (EI) often provoke a marked sympathetic response, which leads to tachycardia and hypertension. The aim of this study was to investigate the effect of different doses of remifentanil on the cardiovascular response to laryngoscopy and EI.PATIENTS AND METHODS:100 patients were included in this randomized study. The participants were divided into four groups of 25 patients each. The patients in the control group did not receive remifentanil. The patients from other three groups received remifentanil prior to induction of anesthesia at doses of 0.5 µg/kg, 1 µg/kg, and 1.5 µg/kg. Hemodynamic parameters were measured before and after administration of remifentanil, after induction of anesthesia and one minute after EI.RESULTS:After administration of remifentanil and induction of anesthesia, a decrease in arterial pressure and heart rate occurred in most patients. After EI, an increase in arterial pressure and heart rate was observed in most patients. The largest increase was recorded in the group of patients who did not receive remifentanil. The best hemodynamic response was observed in patients who received 1 and 1.5 µg/kg of remifentanil.CONCLUSIONS:Remifentanil at the doses of 1-1.5 µg/kg is absolutely safe for co-induction of anesthesia with thiopental. Such dosing regimen provides optimal conditions for reducing hemodynamic response to laryngoscopy and EI.

OBJECTIVE:The aim of this study was to establish the effects of prolonged formulation of tapentadol in combination with palliative radiotherapy on bone metastatic changes in oncology patients with primary breast cancer and proven bone metastases. PATIENTS AND METHODS:The research was conducted as a prospective study at the Clinic for Oncology, University Clinical Center Nis, Nis, Serbia, during a three-month interval of monitoring the patients. The first group comprised 30 patients with mentioned malignancy for which tapentadol was prescribed, and they underwent palliative radiotherapy for bone metastatic changes. The second group comprised 30 patients with the same disease treated only with pain relief radiotherapy to metastatic changes. All the patients were interviewed using the Pain Detect questionnaire. RESULTS:Significantly more patients from the first group had severe pain in comparison to patients from the control group (χ2=16.596; p<0.001) at the second measurement and also at the third measurement (χ2=15.357; p<0.001). At the third measurement, pain with a neuropathic component was significantly more present in patients from the control group (χ2=8.541; p=0.014). There was a significant pain reduction in both groups - Tapentadol group (χ2=59.513; p<0.001) and control group (χ2=60.000; p<0.001) - and also a significant reduction of neuropathic pain component: Tapentadol group (χ2=56.267; p<0.001) and control group (χ2=60,000; p<0.001). There was a statistically significant positive correlation between tapentadol dose and pain intensity according to the numerical pain scale at all three measurements. CONCLUSIONS:Tapentadol prolonged-release formulation is an effective pharmacotherapy solution, along with palliative radiotherapy, for pain relief in patients with skeletal metastatic breast cancer. Palliative radiotherapy in these patients does not provide adequate neuropathic pain component relief.

Background and Objectives: Catalase and glutathione peroxidase (GPx) are important antioxidant enzymes that break down hydrogen peroxide (H2O2) in order to control its intracellular concentration, thus enabling its physiological role and preventing toxic effects. A lack or disruption of their function leads to the accumulation of hydrogen peroxide and the occurrence of oxidative stress. Accumulating studies have shown that the activities of key antioxidant enzymes are impaired in patients with schizophrenia. Since the published results are contradictory, and our previous studies found significantly higher erythrocyte superoxide dismutase (SOD) activity in patients with schizophrenia, the aim of this study was to determine the activity of enzymes that degrade hydrogen peroxide in the same group of patients, as well as to examine their dependence on clinical symptoms, therapy, and parameters associated with this disease. Materials and Methods: Catalase and GPx activities were determined in the erythrocytes of 68 inpatients with schizophrenia and 59 age- and gender-matched healthy controls. The clinical assessment of patients was performed by using the Positive and Negative Syndrome Scale (PANSS). The catalase activity was measured by the kinetic spectrophotometric method, while the GPx activity was determined by the commercially available Ransel test. Results: Erythrocyte catalase and GPx activities were significantly lower (p < 0.001 and p < 0.01, respectively) in subjects with schizophrenia than they were in healthy individuals. Lower catalase activity does not depend on heredity, disease onset, the number of episodes, or disease duration, while GPx activity showed significant changes in patients who had more than one episode and in those who had been suffering from the disease for over a year. Significantly lower catalase activity was noted in the PANSS(+/−) group in comparison with the PANSS(+) and PANSS(−) groups. The lowest catalase activity was found in subjects who were simultaneously treated with first- and second-generation antipsychotics; this was significantly lower than it was in those who received only one class of antipsychotics. Conclusion: These results indicate the presence of oxidative stress in the first years of clinically manifested schizophrenia and its dependence on the number of psychotic episodes, illness duration, predominant symptomatology, and antipsychotic medication.

Background and Objectives: Women with cervical cancer may experience depression or anxiety, influencing their quality of life and even their adherence to cancer treatments. This study aimed to explore and measure the levels of anxiety and depression in patients suffering from cervical cancer and to identify the possible predictors among known risk factors such as age, cancer stage, smoking status, number of partners, use of contraceptives, and annual gynecological visits. Materials and Methods: In total, 59 patients with cervical cancer were included. A consecutive sampling method was used to select participants in this research. Depression and anxiety were assessed using the Zung Anxiety Scale (SAS) and Zung Depression Scale (SDS). The subjects were divided into three groups, according to the stage of cancer. Results: Scores of depression and anxiety were increased in all recruited cervical cancer patients. A significant correlation was found between disease stage and the scores of depression (p = 0.002) and anxiety (p = 0.016). More severe depressive symptoms correlated to a more advanced stage of the disease. A multiple linear regression showed that disease stage and annual visits to the gynecologist are the risk factors associated with higher depression scores. Conclusions: Patients diagnosed with cervical cancer are a vulnerable group for the development of the psychiatric disorders and they require screening programs, which could potentially detect candidates for co-psychiatric and/or psychotherapeutic treatment. They demand particular attention because anxiety and depression are associated with the significant burden of the underlying disease and unfavorable survival rates.

Obstructive sleep apnea (OSA) is highly prevalent in general population and has a bidirectional association with cerebrovascular insult (CVI), one of the leading causes of global morbidity and mortality.Untreated severe OSA doubles the risk for CVI.OSA may be associated with an increase of all-cause mortality and it may impair neurological outcome in CVI patients.Pathophysiological basis of the association and the possibilities of prevention and improvements of outcomes require further evaluation.Continuous positive airway pressure (CPAP) therapy during sleep is associated with a reduced risk of CVI in OSA patients, but the results are inconsistent.Treatment of post CVI OSA patients with CPAP therapy is recommended as part of the elimination of several risk factors involved in pathogenesis of CVI.

Salivary gland tumors are neoplasms characterized by a high level of pleomorphism and histological overlap. One tumor may contain several cell types; therefore, it is necessary to include immunohistochemical staining, as well as morphometric analysis of tumor cells as prerequisites for an appropriate diagnosis. Our research included 120 tumors, such as pleomorphic adenoma, Warthin tumor, basal cell adenoma, myoepithelioma, adenoid cystic carcinoma, mucoepidermoid carcinoma, salivary duct carcinoma, polymorphous low-grade carcinoma and myoepithelial carcinoma. The aim of the study was to differentiate benign and malignant tumors based on the characteristics of nuclei. The expression of Ki67 and the morphometric nuclear parameters ? area, perimeter, Feret diameter, integrated optical density, circularity, and roundness, were analyzed. It was observed that the Ki67 proliferative index was statistically significantly higher in malignant tumors (P<0.001). Adenoid cystic carcinoma exhibited the highest value, whereas the lowest value was exhibited in basal cell adenoma. Morphometric analysis showed statistically significantly increased values of integrated optical density (P<0.001) and nuclear size parameters (P<0.05) in malignant tumors. The determination of the Ki67 proliferative index and morphometric analysis of the integrated optical density and area can differentiate benign from malignant tumors with high precision. The presented values suggest the obtained results as cut-off values.