This study suggests that avoidance of major polypharmacy, use of nonpharmacological measures to improve lifestyle habits and decreasing the exposure of physicians to drug promotional material may reduce the risk of PIM use in older primary care outpatients. The only modifiable protective factors for PPOs were working environment of the patients chosen GPs and more frequent ambulatory visits to specialists.

The pharmaceutical market of Serbia has undergone thorough and complete transformation from within. Serious crisis of medicine supply sustainability is currently shaking Balkan health systems due to increasing public debt worsened by global recession. More responsible reimbursement policy rooted in cost-effectiveness principle is needed in years to come.

Exactly 114 patients were analyzed, out of whom a high percent (48.25%) had distant metastases at the moment of establishing the diagnosis. Malignant neoplasms of respiratory and intrathoracic organs were leading causes of morbidity. The average costs per patient were significantly different according to the diagnosis, with the highest (13,114.10 EUR) and the lowest (4.00 EUR) ones observed in the breast cancer and melanoma, respectively. The greatest impact on total costs was observed concerning pharmaceuticals, with 42% of share (monoclonal antibodies amounted to 34% of all medicines and 14% of total costs), followed by oncology medical care (21%), radiation therapy and interventional radiology (11%), surgery (90%), imaging diagnostics (9%) and laboratory costs (8%). CONCLUSION. Cancer treatment incurs high costs, especially for end-of-life pharmaceutical expenses, ensued from medical personnel tendency to improve such patients' quality of life in spite of nearing the end of life. Reimbursement policy on monoclonal antibodies, in particular at end-stage disease, should rely on cost-effectiveness evidence as well as documented clinical efficiency.

Pharmaceutical sector of Syrian Arab Republic before the war was characterized by bold and successful development since the late 1980s. With the beginning of war in the country back in March 2011, momentum has changed significantly. Traumatism, communicable diseases related to morbidity and mortality as well as wound infections became particularly hot public health concern. This relates not only to the direct victims of military conflict but also to the displaced civilians, refugees, and ordinary citizens alike. Evolving legislative framework in Syria since 1980s tolerated dispensing of antibiotics without appropriate prescription. Such practice led to spreading of antibiotic resistance among the local bacteria frequently causing both community-acquired and nosocomial infections. Laboratory findings of resistant bacteria strains among the Syrian refugees in some European countries serve as evidence of concern spreading far beyond Middle East. Practice of self-diagnosis and self-medication with antibiotics by patients themselves and restraint to pharmacist advice is widespread. A number of recommendations is presented to stakeholders to compact antibiotic resistance after the peace is established in the country. The successful implementation of such recommendations is the way to preserve shrinking golden reserve of highly potent antibiotics as it is the last defense line against resistant bacterial strains causing severe life—threatening infections.

BACKGROUNDUlcerative colitis (UC) is a chronic disease characterized by inflammation of intestinal epithelium, primarily of the colon. An increasing prevalence of metabolic syndrome (MetS) in patients with UC has been documented recently. Still, there is no evidence that MetS alters the course of the UC.AIMTo test the influence of the MetS on the severity of UC and the local and systemic immune status.METHODSEighty nine patients with de novo histologically confirmed UC were divided in two groups, according to ATP III criteria: Group without MetS (no MetS) and group with MetS.RESULTSClinically and histologically milder disease with higher serum level of immunosuppressive cytokine interleukin-10 (IL-10) and fecal content of Galectin-3 (Gal-3) was observed in subjects with UC and MetS, compared to subjects suffering from UC only. This was accompanied with predomination of IL-10 over pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-17 (IL-17) in the sera as well as Gal-3 over TNF-α and IL-17 in feces of UC patients with MetS. Further, the patients with both conditions (UC and MetS) had higher percentage of IL-10 producing and Gal-3 expressing innate and acquired immune cells in lamina propria.CONCLUSIONLocal dominance of Gal-3 and IL-10 over pro-inflammatory mediators in patients with MetS may present a mechanism for limiting the inflammatory process and subsequent tissue damage in UC.

Objective: The increased level of interleukin (IL)-33 is considered as a predictor of severe coronavirus disease 2019 (COVID-19) infection, but its role at different stages of the disease is still unclear. Our goal was to analyze the correlation of IL-33 and other innate immunity cytokines with disease severity.Methods: In this study, 220 patients with COVID-19 were included and divided into two groups, mild/moderate and severe/critical. The value of the cytokines, clinical, biochemical, radiographic data was collected and their correlation with disease severity was analyzed.Results: Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (p < 0.05) in these two groups between clinical features (dyspnea, dry cough, fatigue, and auscultatory findings); laboratory [(neutrophil count, lymphocyte count, monocyte count, hemoglobin, plasma glucose, urea, creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), albumin (ALB), lactate dehydrogenase (LDH), creatinine kinase (CK), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), Fe, and Ferritin)], arterial blood gases (oxygen saturation-Sa02, partial pressure of oxygen -p02), and chest X-rays (CXR) lung findings (p = 0.000). We found a significantly higher serum concentration (p < 0.05) of TNF-α, IL-1β, IL-6, IL-12, IL-23, and IL-33 in patients with COVID-19 with severe disease. In the milder stage of COVID-19, a positive correlation was detected between IL-33 and IL-1β, IL-12 and IL-23, while a stronger positive correlation between the serum values of IL-33 and TNF-α, IL-1β, IL-6, and IL-12 and IL-23 was detected in patients with COVID-19 with severe disease. A weak negative correlation (p < 0.05) between pO2 and serum IL-1β, IL-12, and IL-33 and between SaO2 and serum IL-33 was noted. The positive relation (p < 0.05) between the serum values of IL-33 and IL-12, IL-33 and IL-6, and IL-6 and IL-12 is proven.Conclusion: In a more progressive stage of COVID-19, increased IL-33 facilitates lung inflammation by inducing the production of various innate proinflammatory cytokines (IL-1β, IL-6, TNF-α, IL-12, and IL-23) in several target cells leading to the most severe forms of the disease. IL-33 correlates with clinical parameters of COVID-19 and might represent a promising marker as well as a therapeutic target in COVID-19.

Hepatitis C virus infection (HCV), one of the greatest causes of liver disease, is a frequent complication in patients with end-stage renal disease (ESRD) on dialysis. ESRD is defined as decreased glomerular filtration and also accompanied by impaired function of the immune system. Galectin-3 is a β-galactoside-binding lectin, involved in various biological processes including pathogenesis of chronic renal disease. The aim of our study was to estimate disease severity in ESRD HCV+ patients and analyze the serum concentrations of IL-1β, IL-4, IL-23, and IL-6; anti-HCV antibodies; and galectin-3. Also, we attempted to determine potential correlation between galectin-3 level and parameters of disease severity ALT and AST. Our results showed decreased levels of ALT and AST (p = 0.00), demonstrating less liver destruction in ESRD HCV+ patients in comparison to HCV+ patients. Increased levels of IL-6 (p = 0.03) implicate a hepatoprotective role of IL-6 in these patients. Also, level of galectin-3 (p = 0.00) in the serum of ESRD HCV+ patients was higher than that of HCV+ patients. This alteration was accompanied with negative correlation between galectin-3 and AST and ALT, respectively (p = 0.029; p = 0.033). The presence of increased systemic levels of IL-6 and Gal-3 in ESRD HCV+ patients may be an attempt to counteract or limit ongoing proinflammatory processes and to downregulate chronic inflammation, suggesting the new aspects of HCV infection in ESRD patients.

Dysregulation of the type 17 immune pathway has already been considered in schizophrenia and we previously measured decreased sera values of interleukin (IL)-17 in early stages. We further explored the possible correlation of IL-17 systemic levels with proinflammatory cytokines and cognitive scores and additionally analyzed the percentage of IL-17 producing lymphocytes in peripheral blood of patients with stable schizophrenia. We included 27 patients diagnosed with schizophrenia (F20), after a three-month stable depot antipsychotic therapy (risperidone or paliperidone) and 18 healthy control subjects. Positive and Negative Syndrome Scale of Schizophrenia and the Montreal-Cognitive Assessment (MoCA) were conducted. Sera concentrations of IL-17, IL-6, tumor necrosis factor alpha (TNF-α) and soluble ST2 receptor (sST2) were measured. Flow cytometry and Natural Killer (NK) and T cell analyses were done in 10 patients and 10 healthy controls. Moderate positive correlation was established between IL-17 and TNF-α (r = 0.640; p = 0.001), IL-17 and IL-6 (r = 0.514; p = 0.006), IL-17 and sST2 (r = 0.394; p = 0.042). Furthermore, a positive correlation between the serum levels of IL-17 and MoCA scores was observed, especially with visuospatial and executive functioning, as well as language functioning and delayed recall (p < 0.05). Significantly higher percentage of IL-17 producing CD56+ NK cells was measured in peripheral blood of patients with schizophrenia in remission vs. healthy individuals (p = 0.001). The percentage of CD4+ T cells and CD4+ T cells that produce IL-17 was significantly increased in patients (p = 0.001). This study revealed the involvement of innate type 17 immune response in the progression of inflammation and this could be related to cognitive functioning in stable schizophrenia.