A Prospective Observational Study Analyzing the Diagnostic Value of Hepcidin-25 for Anemia in Patients with Inflammatory Bowel Diseases.

Iron deficiency (IDA) and chronic disease (ACD) anemia are complications of inflammatory bowel diseases (IBDs). Therapeutic modalities in remission and active IBD depend on the type of anemia. This study evaluated the link between hepcidin-25, proinflammatory cytokines, and platelet activation markers as biomarkers of anemia and inflammation in active IBD and remission. This prospective observational study included 62 patients with IBD (49 with ulcerative colitis and 13 with Crohn's) and anemia. Patients were divided into Group I (no or minimal endoscopic signs of disease activity and IDA), Group II (moderate and major endoscopic signs of disease activity and mild ACD), and Control group (10 patients with IBD in remission, without anemia). We assessed the difference among groups in the levels of CRP, hemoglobin (Hgb), serum iron, ferritin, hepcidin-25, interleukins, TNF-α, IFN-γ, soluble CD40 ligand, and sP-selectin. Hepcidin-25 levels were significantly higher in Group II versus Group I (11.93 vs. 4.48 ng/mL, p < 0.001). Ferritin and CRP values showed similar patterns in IBD patients: significantly higher levels were observed in Group II (47.5 ng/mL and 13.68 mg/L) than in Group I (11.0 ng/mL and 3.39 mg/L) (p < 0.001). In Group II, hepcidin-25 was positively correlated with ferritin (ρ = 0.725, p < 0.001) and CRP (ρ = 0.502, p = 0.003). Ferritin was an independent variable influencing hepcidin-25 concentration in IBD patients, regardless of disease activity and severity of anemia. IBD hepcidin-25 best correlates with ferritin, and both parameters reflected inflammation extent and IBD activity.

The significance of biomarkers of inflammation in predicting the activity of Lupus nephritis.

Background: Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE). There are increased studies examining the role of different markers that would facilitate diagnosis, LN activity monitoring, relapse occurrence, and the right time to introduce maintenance therapy. We aimed to examine the importance of determining the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immuneinflammatory index (SII) and systemic inflammatory response index (SIRI) in LN, comparing their significance with other standard parameters of active disease. Methods: The clinical examination included 66 patients (34 with active and 32 with LN in remission) and 23 healthy controls. The investigated parameters were CRP, CBC, creatinine, albumin, GFR, C3, C4, ANA, anti-ds DNA Ab, in urine: sediment analysis, SLEDAI/r, proteinuria 24h and Up/cre. We determined the derived markers: NLR, PLR, SIRI, and SII and their correlation with other parameters of active disease.

Vaccine Effectiveness against SARS-CoV-2 Infection during the Circulation of Alpha, Delta, or Omicron Variants: A Retrospective Cohort Study in a Tertiary Hospital in Serbia.

The COVID-19 pandemic prompted rapid vaccine development and deployment worldwide. Despite widespread vaccination efforts, understanding the effectiveness of vaccines in hospitalized patients remains a critical concern. This retrospective cohort study, conducted at a tertiary healthcare centre in Serbia, tracked patients hospitalized during different waves of COVID-19 variants-Alpha, Delta, and Omicron. Data collection included demographics, comorbidities, symptoms, and vaccination status. Among 3593 patients, those with prior exposure to COVID-19 cases or hospital treatment showed higher positivity rates. Symptom prevalence varied across waves, with coughs persisting. Patients without chronic diseases were more frequent among those testing negative. Vaccine effectiveness varied, with Sinopharm demonstrating a 45.6% effectiveness initially and Pfizer-BioNTech showing an effectiveness of up to 74.8% within 0-84 days after the second dose. Mixed-dose strategies, notably Sinopharm as a primary dose followed by a Pfizer-BioNTech booster, suggested increased protection. Despite substantial vaccination availability, a significant portion of hospitalized patients remained unvaccinated. This study underscores the dynamic nature of vaccine effectiveness and advocates for booster strategies to address evolving challenges in combating COVID-19, particularly in hospitalized patients.

Assessment and Prediction of Adherence to Methotrexate Using Three Self-Report Questionnaires in Patients with Rheumatoid Arthritis.

Introduction: Methotrexate (MTX) reduces rheumatoid arthritis activity and ameliorates the long-term functional status in these patients. To achieve this aim, patients need to take their medication regularly. Nevertheless, non-adherence to MTX still remains a considerable issue in the management of rheumatoid arthritis. Objective: This study aimed to estimate the adherence to methotrexate in patients with rheumatoid arthritis and to identify specific non-adherence risk factors. Methods: A cross-sectional study included 111 patients (mean age 56.2 ± 10.6 years, 78.4% female, and mean disease duration 6 years (3-13)). Three adherence self-assessment questionnaires were used: the Compliance-Questionnaire-Rheumatology (CQR19), the Medication Adherence Reports Scale (MARS-5), and the Visual Analogue Scale (VAS). We also collected demographic data, disease and treatment characteristics, and anxiety/depression estimation results (Hospital Anxiety and Depression Scale, HADS). Results: Adherence was identified in 48.6% of patients (COR19), 70.3% of patients (MARS-5), and 82.9% of patients (VAS questionnaire). All three questionnaires displayed a significant positive mutual correlation: CQR19 with MARS-5 and VAS (r = 0.364, r = 0.329, respectively, p < 0.001 for both) and between the VAS and MARS-5 scores (r = 0.496, p < 0.001). A significant positive prediction was shown for urban residence (0.347 (0.134-0.901), p = 0.030) using the MARS-5, female sex (0.264 (0.095-0.730), p = 0.010) according to the CQR19, and for a dose of methotrexate (0.881 (0.783-0.992), p = 0.036) using the VAS, while negative predictions were shown for comorbidity number (3.062 (1.057-8.874), p = 0.039) and depression (1.142 (1.010-1.293), p = 0.035) using the MARS-5 and for older age (1.041 (1.003-1.081), p = 0.034) according to the CQR19. The use of steroids was a significant positive predictor in all three questionnaires and remained an independent predictor for methotrexate adherence in the multivariate logistic regression. Conclusions: We showed non-adherence to methotrexate in a significant number of patients using all three questionnaires. Concomitant steroid therapy emerged as an independent positive predictor for adherence.

Analysis and Forecast of Indicators Related to Medical Workers and Medical Technology in Selected Countries of Eastern Europe and Balkan.

Health indicators measure certain health characteristics in a specific population or country and can help navigate the health systems. As the global population is rising, the demand for an increase in the number of health workers is simultaneously rising. The aim of this study was to compare and predict the indicators related to the number of medical workers and medical technologies in selected countries in Eastern Europe and Balkan in the studied period. The article analyzed the reported data of selected health indicators extracted from the European Health for All database. The indicators of interest were the number of physicians, pharmacists, general practitioners and dentists per 100,000 people. To observe the changes in these indicators through the available years, we used linear trends, regression analysis and forecasting to the year 2025. The regression analysis shows that the majority of the observed countries will experience an increase in the number of general practitioners, pharmacists, health workers/professionals and dentists, as well as in the number of computerized tomography scanners and the number of magnetic resonance units, predicted to occur by 2025. Following trends of medical indicators can help the government and health sector to focus and navigate the best investments for each country according to the level of their development.

Epidemiological Predictors of Positive SARS-CoV-2 Polymerase Chain Reaction Test in Three Cohorts: Hospitalized Patients, Healthcare Workers, and Military Population, Serbia, 2020.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resulting coronavirus disease 2019 (COVID-19) has caused a fast-moving pandemic. Diagnostic testing, aimed to identify patients infected with SARS-CoV-2, plays a key role in controlling the COVID-19 pandemic in different populations. (2) Methods: This retrospective cohort study aimed to investigate predictors associated with positive polymerase chain reaction (PCR) SARS-CoV-2 test results in hospitalized patients, healthcare workers (HCWs), and military personnel (MP) during 2020, before the widespread availability of COVID-19 vaccines. Persons with a positive test result were compared with persons with a negative test result in three cohorts during the study period. (3) Results: A total of 6912 respondents were tested, and 1334 (19.3%) of them had positive PCR SARS-CoV-2 test results. Contact with a known COVID-19 case within 14 days (p < 0.001; OR: 1.48; 95% CI: 1.25-1.76), fever (p < 0.001; OR: 3.66; 95% CI: 3.04-4.41), cough (p < 0.001; OR: 1.91; 95% CI: 1.59-2.30), headache (p = 0.028; OR: 1.24; 95% CI: 1.02-1.50), and myalgia/arthralgia (p < 0.001; OR: 1.99; 95% CI: 1.65-2.42) were independently associated with positive PCR SARS-CoV-2 test results in the cohort of MP. Furthermore, fever (p < 0.001; OR: 2.75; 95% CI: 1.83-4.13), cough (p < 0.001; OR: 2.04; 95% CI: 1.32-3.13), headache (p = 0.008; OR: 1.76; 95% CI: 1.15-2.68), and myalgia/arthralgia (p = 0.039; OR: 1.58; 95% CI: 1.02-2.45) were independently associated with positive PCR SARS-CoV-2 test results in the cohort of HCWs. Moreover, independent predictors of positive PCR SARS-CoV-2 test results in hospitalized patients were contact with a known COVID-19 case within 14 days (p < 0.001; OR: 2.56; 95% CI: 1.71-3.83), fever (p < 0.001; OR: 1.89; 95% CI: 1.38-2.59), pneumonia (p = 0.041; OR: 1.45; 95% CI: 1.01-2.09), and neurological diseases (p = 0.009; OR: 0.375; 95% CI: 0.18-0.78). (4) Conclusions: According to data gathered from cohorts of hospitalized patients, HCWs, and MP, before the widespread availability of COVID-19 vaccines in Serbia, we can conclude that predictors of positive PCR SARS-CoV-2 test results in MP and HCWs were similar. Accurate estimates of COVID-19 in different population groups are important for health authorities.

Evolution of acute "black hole" lesions in patients with relapsing-remitting multiple sclerosis.

OBJECTIVE: Gadolinium-enhanced T1-weighted lesions are a well-established marker of areas with acute inflammatory activity. A majority of these gadolinium-enhanced T1 lesions are isointense relative to the surrounding white matter, but 20-40% of such active lesions will evolve during one year into areas of low signal ("black hole"). This study sought to characterize evolution of "black hole" lesions in patients with relapsing-remitting multiple sclerosis (MS) using the magnetic resonance imaging (MRI), which measures active lesions via the count of new or enlarged T2 and gadolinium-enhanced T1-weighted lesions. MATERIALS AND METHODS: This was a prospective, observational case-series study which utilized pre- and post-gadolinium contrast T1-weighted and Proton density MRI scans. Twenty-nine patients (8 males and 21 females) with average age of 38.86 ± 6.58 years and disease duration of 5.75 ± 7.00 years were used to analyze 196 acute demyelinating plaques detected on MRI images during the 24-month follow-up of post-gadolinium signal intensity enhancement of MS plaques. RESULTS: Significant difference in black hole development was found between the shapes of acute and chronic "black holes". Ring-shaped and patchy plaques were 4.09 (1.87-8.91) times more likely and 1.49 (0.71-3.12) times less likely to develop an acute "black holes" than homogeneous plaques, respectively. Acute plaques with higher lesion-to-CSF SI ratio and larger surface area showed a greater tendency to develop into acute and chronic "black holes". CONCLUSIONS: The value of lesion-to-CSF SI ratio and surface area were found as the predictors of the "black hole" formation.

An assessment of burden of hospital-acquired pneumonia among abdominal surgical patients in tertiary university hospital in Serbia: A matched nested case-control study.

Background: In the population of abdominal surgical patients hospital-acquired pneumonia (HAP) significantly increases morbidity and mortality. Patients and methods: Through regular hospital surveillance of patients who received abdominal operations, we identified postoperative HAP from 2007 to 2019. In an initial nested case-control study, every surgical patient with HAP was compared with three control patients without HAP. Control patients were matched to the cases by age, gender, the American Society of Anesthesiologists score, and type of surgical operation. Also, the patients with HAP, who died were compared with those who survived. Results: Multivariate logistic regression analysis (MLRA) revealed that other postoperative infections, length of intensive care unit stay, use of H2RA, use of PPI/ H2RA, multiple transfusion, and use of vancomycin in surgical prophylaxis were independent RFs for occurrence of HAP. Also, MLRA identified that age, lenght of hospital stay, use of mechanical ventilation and ceftriaxone in HAP therapy were indepedenttly associated with poor outcome of HAP. All Acinetobacter baumannii isolates were resistant to aminoglycoside antimicrobial agents and showed carbapenem resistance. The most frequently used antibiotics in patients with HAP and without HAP were vancomycin and metronidazole, respectively. Conclusion: Our study provided an insight into the burden of HAP in abdominal surgical patients, and highlighted several priority areas and targets for quality improvement.

Association between Antibiotic Use and Hospital-Onset Clostridioides difficile Infection in University Tertiary Hospital in Serbia, 2011-2021: An Ecological Analysis.

This ecological study is the largest to date examining the association between rates of antibiotic use (AU) and hospital-onset (HO) Clostridioides difficile infection (CDI) in a tertiary university hospital in Serbia. There was no clear trend in the incidence of HO-CDI over time. Total utilization of antibacterials for systemic use increased from 38.57 DDD/100 bed-days (BD) in 2011 to 56.39 DDD/100 BD in 2021. The most commonly used antibiotics were third-generation cephalosporins, especially ceftriaxone, with maximum consumption in 2021 (19.14 DDD/100 BD). The share of the Access group in the total utilization of antibiotics ranged from 29.95% to 42.96% during the observed period. The utilization of the Reserve group of antibiotics indicated a statistically significant increasing trend (p = 0.034). A statistically significant difference in the consumption of medium-risk antibiotics from 2011 to 2021 was shown for penicillins and a combination of sulfamethoxazole and trimethoprim. The consumption of cefotaxime showed a statistically significant negative association with the rate of HO-CDI (r = -0.647; p = 0.031). Ampicillin and the combination of amoxicilline with clavulanic acid have shown a negative statistically significant correlation with the ID of HO-CDI (r = -0.773 and r = -0.821, respectively). Moreover, there was a statistically significant negative correlation between consumption of "medium-risk antibiotics" and the rate of HO-CDI (r = -0.677). The next challenging step for the hospital multidisciplinary team for antimicrobials is to modify the antibiotic list according to the Access, Watch, and Reserve classification, in such a way that at least 60% of the AU should be from the Access group, according to the World Health Organization recommendation.

Influence of Gender, Body Mass Index, and Age on the Pharmacokinetics of Itraconazole in Healthy Subjects: Non-Compartmental Versus Compartmental Analysis.

Itraconazole is a triazole antifungal agent with highly variable pharmacokinetics, with not yet fully identified factors as the source of this variability. Our study aimed to examine the influence of body mass index, gender, and age on the first dose pharmacokinetics of itraconazole in healthy subjects, using pharmacokinetic modeling, non-compartmental versus compartmental ones. A total of 114 itraconazole and hydroxy-itraconazole sets of plasma concentrations of healthy subjects of both genders, determined using a validated liquid chromatographic method with mass spectrometric detection (LC-MS), were obtained for pharmacokinetic analyses performed by the computer program Kinetica 5®. Genetic polymorphism in CYP3A4, CYP3A5, CYP1A1, CYP2C9, and CYP2C19 was analyzed using PCR-based methods. Multiple linear regression analysis indicated that gender had a significant effect on AUC as the most important pharmacokinetics endpoint, whereas body mass index and age did not show such an influence. Therefore, further analysis considered gender and indicated that both geometric mean values of itraconazole and hydroxy-itraconazole plasma concentrations in men were prominently higher than those in women. A significant reduction of the geometric mean values of Cmax and AUC and increment of Vd in females compared with males were obtained. Analyzed genotypes and gender differences in drug pharmacokinetics could not be related. Non-compartmental and one-compartmental models complemented each other, whereas the application of the two-compartmental model showed a significant correlation with the analysis of one compartment. They indicated a significant influence of gender on itraconazole pharmacokinetics after administration of the single oral dose of the drug, given under fed conditions. Women were less exposed to itraconazole and hydroxy-itraconazole than men due to poorer absorption of itraconazole, its more intense pre-systemic metabolism, and higher distribution of both drug and its metabolite.

Prevalence of traditional cardiovascular risk factors for coronary artery disease and elevated fibrinogen among active military personnel in Republic of Serbia: A cross-sectional study.

Background: It is well known that less than 1% of the population achieves ideal cardiovascular health, and 65% of patients do not have their conventional risk biomarkers under control. Military service has its own particularities that may contribute to cardiovascular risk. Methods: To define the preventive strategy goals, we analysed the prevalence of traditional cardiovascular risk factors for coronary artery disease and elevated fibrinogen among active military personnel in the Republic of Serbia. Results: The cross-sectional study included 738 individuals older than 20 years, mostly between 31 and 40 years old. The mean value of SBP for the whole group was 122.39± 9.42 mmHg, and for the DBP, it was 79.94±6.56 mmHg. Among active military personnel, 72.7% (533) had prehypertension, and 13.8% (101) was hypertensive. Both body mass and BMI index among the observed age subgroups were found to increase with the age of the patients and cholesterol values. HDL cholesterol values also differed statistically significantly between age subgroups, with the proportion of individuals with HDL less than 1.5 mmol/L in all subgroups being about 85%, the only in the 41-50 age group was lower, 76.4%. LDL cholesterol and the proportion of individuals who had LDL 3.5 increases with the age of patients, and an identical trend was recorded with triglycerides. With ageing, fibrinogen levels increased. Conclusions: Those findings considering cardio and cerebrovascular risk factors would help create a new approach for primary prevention for these categories of individuals.

Dynamic monitoring of carcinoembryonic antigen, CA19-9 and inflammation-based indices in patients with advanced colorectal cancer undergoing chemotherapy.

BACKGROUND: The roles of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) in monitoring the patient response to chemotherapy for metastatic colorectal cancer (mCRC) are not clearly defined, and inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII), have been sparsely investigated for this purpose. AIM: To aim of this study was to evaluate the relationship between the kinetics of CEA, CA19-9, NLR, LMR, PLR and SII in serum and patient response to chemotherapy estimated by computed tomography (CT) in patients with unresectable mCRC. METHODS: Patients with mCRC treated with a 1st-line and 2nd-line chemotherapy underwent at least 3 whole-body spiral CT scans during response monitoring according to the Response Evaluation Criteria in Solid Tumour 1.1 (RECIST 1.1), and simultaneous determination of CEA, CA19-9, neutrophil, lymphocyte, platelet and monocyte levels was performed. The kinetics of changes in the tumour markers and inflammatory indices were calculated as the percentage change from baseline or nadir, while receiver operating characteristic curves were drawn to select the thresholds to define patients with progressive or responsive disease with the highest sensitivity (Se) and specificity (Sp). The correlation of tumour marker kinetics with inflammatory index changes and RECIST response was determined by univariate and multivariate logistic regression analysis and the clinical utility index (CUI). RESULTS: A total of 102 patients with mCRC treated with chemotherapy were included. Progressive disease (PD), defined as a CEA increase of 25.52%, resulted in an Se of 80.3%, an Sp of 84%, a good CUI negative [CUI (Ve-)] value of 0.75 and a good fraction correct (FC) value of 81.2; at a CEA cut-off of -60.85% with an Se of 100% and an Sp of 35.7% for PD, CT could be avoided in 25.49% of patients. The 21.49% CA19-9 cut-off for PD had an Se of 66.5%, an Sp of 87.4%, an acceptable CUI (Ve-) value of 0.65 and an acceptable FC value of 75. An NLR increase of 11.5% for PD had an Se of 67% and an Sp of 66%; a PLR increase of 5.9% had an Se of 53% and an Sp of 69%; an SII increase above -6.04% had an Se of 72% and an Sp of 63%; and all had acceptable CUI (Ve-) values at 0.55. In the univariate logistic regression analysis, CEA (P < 0.001), CA19-9 (P < 0.05), NLR (P < 0.05), PLR (P < 0.05) and SII (P < 0.05) were important predictors of tumour progression, but in the multivariate logistic regression analysis, CEA was the only independent predictor of PD (P < 0.05). CONCLUSION: CEA is a useful marker for monitoring the chemotherapy response of patients with unresectable mCRC and could replace a quarter of CT examinations. CA19-9 has poorer diagnostic characteristics than CEA but could be useful in some clinical circumstances, particularly when CEA is not increased. Dynamic changes in the inflammatory indices NLR, PLR and SII could be promising for further investigation as markers of the chemotherapy response.

Impact of Right Heart Failure on Clinical Outcome of Left Ventricular Assist Devices (LVAD) Implantation: Single Center Experience.

The aim of this study was to examine the incidence and significance of right heart failure (RHF) in the early and late phase of left ventricular assist device (LVAD) implantation with the identification of predictive factors for the development of RHF. This was a prospective observational analytical cohort study. The study included 92 patients who underwent LVAD implantation and for whom all necessary clinical data from the follow-up period were available, as well as unambiguous conclusions by the heart team regarding pathologies, adverse events, and complications. Of the total number of patients, 43.5% died. The median overall survival of patients after LVAD implantation was 22 months. In the entire study population, survival rates were 88.04% at one month, 80.43% at six months, 70.65% at one year, and 61.96% at two years. Preoperative RHF was present in 24 patients, 12 of whom died and 12 survived LVAD implantation. Only two survivors developed early RHF (ERHF) and two late RHF (LRHF). The most significant predictors of ERHF development are brain natriuretic peptide (BNP), pre-surgery RHF, FAC < 20%, prior renal insufficiency, and total duration of ICU stay (HR: 1.002, 0.901, 0.858, 23.554, and 1.005, respectively). RHF following LVAD implantation is an unwanted complication with a negative impact on treatment outcome. The increased risk of fatal outcome in patients with ERHF and LRHF after LVAD implantation results in a need to identify patients at risk of RHF, in order to administer the available preventive and therapeutic methods.

IMPLEMENTATION OF THE NATIONWIDE ELECTRONIC HEALTH RECORD SYSTEM IN SERBIA: CHALLENGES, LESSONS LEARNED, AND EARLY OUTCOMES.

Objectives: Many countries around the world have recognized the need for using an electronic health record (EHR) system. However, there is limited literature that could serve as a guide during a lengthy and challenging process of planning, development, and implementation of the e-Health system. Since the EHR system was recently introduced in Serbia, the purpose of this communication is to describe our experience and lessons learned along the way. Methods: The key personnel involved in the implementation of the EHR system in Serbia that began in 2015 conducted in 2019 a retrospective narrative review of the process and early outcomes. Results: An incremental approach in the planning, development, and implementation of the nationwide EHR system was taken. The process was split into phases with the gradual introduction of different regions of the country. The gradual shift from the existing to a new workflow for the prospective users was also implemented. The significant milestones were the achievement of quick legislative changes, the hiring of a professional team of experts in the field, the provision of timely and appropriate information and training to prospective users, the close collaboration between the implementation team and the Ministry of Health and mutual understanding of the aims and expectations, and the flexibility in accepting the evolving nature of the process, goals, and the system model. Conclusions: A successful implementation of the nationwide EHR system is feasible providing careful planning, the assembly of a multi-disciplinary team, the use of a stepwise approach, the early and continued involvement of the intended users, and the willingness to make adjustments along the way. The end-result sets the stage for the reform of the health care system itself.

Utilization of Mycophenolic Acid, Azathioprine, Tacrolimus, Cyclosporin, Sirolimus, and Everolimus: Multinational Study.

Background: Organ transplantations are difficult, complicated and very expensive interventions. In order to preserve the transplanted organs, it is necessary to provide medical care to the patients in terms of immunosuppression. According to the guidelines, the first-line therapy choices for achieving immunosuppression after transplantation are tacrolimus, cyclosporine, mycophenolic acid, azathioprine, sirolimus, everolimus" and corticosteroids. The aim of our study was to examine the utilization of this drugs in Montenegro and to compare the results with the ones from Finland, Croatia, and Serbia. Methods: In our investigation we used Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology. Prices per DDD of drugs are presented in euros (€). Results: In all observed countries, there is a positive trend in the consumption of all 6 drugs during the analyzed period. The prices per DDD of these drugs generally show a negative trend. Tacrolimus and mycophenolic acid in Montenegro recorded the largest reduction in the price per DDD. Price per one DDD of tacrolimus decreased from €13.28 in 2009 to €5.11 in 2019, thus by about 260%, and as regards mycophenolic acid, the price per one DDD decreased from €9.59 in 2009 to € 3.36 in 2019, thus by almost 300%. Conclusion: Despite the reduction in the price per DDD, drugs that are used as immunosuppressants are showing increasing costs from year to year. Since these drugs are expensive, they participate in a significant percentage in the budget for medicines in each country.

Cost Analysis of Health Examination Screening Program for Ischemic Heart Disease in Active-Duty Military Personnel in the Middle-Income Country.

Cardiovascular diseases, including ischemic heart disease, are the most common causes of morbidity and death in the world, including Serbia, as a middle-income European country. The aim of the study was to determine the costs of preventive examinations for ischemic heart disease in active-duty military personnel, as well as to assess whether this was justified from the point of view of the limited health resources allocated for the treatment of the Republic of Serbia population. This is a retrospective cost-preventive study which included 738 male active-duty military personnel, aged from 23 to 58. The costs of primary prevention of ischemic heart disease in this population were investigated. Out of 738 subjects examined, arterial hypertension was detected in 101 subjects (in 74 of them, arterial hypertension was registered for the first time, while 27 subjects were already subjected to pharmacotherapy for arterial hypertension). Average costs of all services during the periodic-health-examination screening program were €76.96 per subject. However, average costs of all services during the periodic-health-examination screening program for patients with newfound arterial hypertension and poorly regulated arterial hypertension were €767.54 per patient and €2,103.63 per patient, respectively. Since periodic-health-examination screening program in military personnel enabled not only discovery of patient with newfound arterial hypertension but also regular monitoring of those who are already on antihypertensive therapy, significant savings of €690.58 per patient and €2,026.67 per patient can be achieved, respectively. As financial resources for providing health care in Serbia, as a middle-income country, are limited, further efforts should be put on screening programs for ischemic heart disease due to possible significant savings.

An overview of antiviral strategies for coronavirus 2 (SARS-CoV-2) infection with special reference to antimalarial drugs chloroquine and hydroxychloroquine.

At present, neither specific antiviral drugs, nor vaccine is recommended for coronavirus disease 2019 (COVID-19) treatment. In this review we discuss the drugs suggested as therapy for COVID-19 infection, with a focus on chloroquine and hydroxychloroquine. The list of drugs used for COVID-19 treatment includes a combination of lopinavir and ritonavir, remdesivir, favipiravir, alpha-interferon, ribavirin, atazanavir, umifenovir, and tocilizumab. As their efficacy and safety are under investigation, none of the regulatory agencies approved them for the treatment of COVID-19 infection. Although chloroquine and hydroxychloroquine possess antiviral and immunomodulatory effects, in practice benefit of their use for COVID-19 treatment is controversial. Several studies investigating hydroxychloroquine were stopped and the French national medicines regulator suspended its use in clinical trials because of safety concerns. The results from the double-blind, randomised clinical trials, including large number of participants, will add better insight into the role of these two drugs as already available and affordable, antimalarial therapy. The ethical issue on emergency use of chloroquine and hydroxychloroquine in the settings of COVID-19 should be carefully managed, with adherence to the "monitored emergency use of unregistered and experimental interventions" (MEURI) framework or be ethically approved as a trial, as stated by the WHO. Potential shortage of chloroquine/hydroxychloroquine on the market can be overbridged with regular prescriptions by medical doctors and national drug agency should ensure sufficient quantities of these drugs for standard indications.

Five-Year Outcomes in Bariatric Surgery Patients.

Background and objectives: Obesity presents as a multifactorial, pandemic disease that arises as a consequence of unequal energy intake and energy consumption. Obesity adversely affects the quality of life, leading not only to disability, but also to various other disorders. Bariatric surgery is the most effective method for achieving significant and sustained weight loss in individuals with extreme obesity. The aim of this study was to examine how well surgically induced weight loss is maintained after five years of follow-up and its effects on cardiovascular risk factors and outcome. Materials and Methods: This is a retrospective cross-sectional study of 66 patients with morbid obesity, with body mass index (BMI) ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 and obesity-related health conditions, aged 20 to 61 years, mostly women (77.3%) who underwent laparoscopic Roux-en-Y gastric bypass surgery. Results: Average follow-up was 6.42 years (95% CI 6.30-6.54 years) after surgery, with survival rate of 97% in operated individuals. There was a statistically significant reduction of weight and body mass index 6 months and 5 years after surgery in comparison to the initial values (p < 0.001). Of 62 patients who presented weight loss at the end of the follow-up period, 38 were able to maintain the amount of weight loss that was attained 6 months after surgery, while 24 patients regained weight compared to their postoperative weight at 6 months. Two patients reported no weight loss after treatment. Significant weight reduction was associated with better control of diabetes and increased self-reported physical activity at 6 months and 5 years after surgery, as well as with a reduction of the use of anti-diabetic and anti-hypertensive medications. Conclusions: Our research demonstrates a positive long-term impact of bariatric surgery on patients' health conditions, significant and sustained weight loss, and decrease in BMI, which were associated with a reduction of co-morbidities and risk factors for cardiovascular diseases.

Predictors of (in)efficiencies of Healthcare Expenditure Among the Leading Asian Economies - Comparison of OECD and Non-OECD Nations.

PURPOSE: The goal of this study was to assess the effectiveness of healthcare spending among the leading Asian economies. METHODS: We have selected a total of nine Asian nations, based on the strength of their economic output and long-term real GDP growth rates. The OECD members included Japan and the Republic of Korea, while the seven non-OECD nations were China, India, Indonesia, Malaysia, Pakistan, the Philippines, and Thailand. Healthcare systems efficiency was analyzed over the period 1996-2017. To assess the effectiveness of healthcare expenditure of each group of countries, the two-way fixed effects model (country- and year effects) was used. RESULTS: Quality of governance and current health expenditure determine healthcare system performance. Population density and urbanization are positively associated with a healthy life expectancy in the non-OECD Asian countries. In this group, unsafe water drinking has a statistically negative effect on healthy life expectancy. Interestingly, only per capita consumption of carbohydrates is significantly linked with healthy life expectancy. In these non-OECD Asian countries, unsafe water drinking and per capita carbon dioxide emissions increase infant mortality. There is a strong negative association between GDP per capita and infant mortality in both sub-samples, although its impact is far larger in the OECD group. In Japan and South Korea, unemployment is negatively associated with infant mortality. CONCLUSION: Japan outperforms other countries from the sample in major healthcare performance indicators, while South Korea is ranked second. The only exception is per capita carbon dioxide emissions, which have maximal values in the Republic of Korea and Japan. Non-OECD nations' outcomes were led by China, as the largest economy. This group was characterized with substantial improvement in efficiency of health spending since the middle of the 1990s. Yet, progress was noted with remarkable heterogeneity within the group.