Objective Serum parameters of calcium homeostasis were measured based on previously published evidence linking osteoporotic fractures and/or bone/mineral loss with antipsychotics. Methods Prospective, four-week, time-series trial was conducted and study population consisted of patients of both genders, aged 35-85 years, admitted within the routine practice, with acute psychotic symptoms, to whom an antipsychotic drug was either introduced or substituted. Serial measurements of serum calcium, phosphorous, magnesium, 25(OH)D, parathyroid hormone, calcitonin, osteocalcin and C-telopeptide were made from patient venous blood samples. Results Calcium serum concentrations significantly decreased from baseline to the fourth week (2.42±0.12 vs. 2.33±0.16 mmol/L, p=0.022, n=25). The mean of all calcemia changes from the baseline was -2.6±5.7% (-24.1 to 7.7) with more decreases than increases (78 vs. 49, p=0.010) and more patents having negative sum of calcemia changes from baseline (n=28) than positive ones (n=10) (p=0.004). There were simultaneous falls of calcium and magnesium from baseline (63/15 vs. 23/26, p<0.001; OR=4.75, 95% CI 2.14-10.51), phosphorous (45/33 vs. 9/40, p<0.001; 6.06, 2.59-14.20) and 25(OH)D concentrations (57/21 vs. 13/35, p<0.001; 7.31, 3.25-16.42), respectively. Calcemia positively correlated with magnesemia, phosphatemia and 25(OH)D values. Parathyroid hormone and C-telopeptide showed only subtle oscillations of their absolute concentrations or changes from baseline; calcitonin and osteocalcin did not change. Adjustment of final calcemia trend (depletion/accumulation) for relevant risk factors, generally, did not change the results. Conclusion In patients with psychotic disorders and several risks for bone metabolism disturbances antipsychotic treatment was associated with the decrease of calcemia and changes in levels of the associated ions.

Background: Clinical development of antiepileptic drugs is demanding due to complex character of the disorder and to diversity of its forms and etiologies. Objective: The aim of this review was to suggest improvements in regulatory procedures for clinical development of antiepileptic drugs. Methods: The following databases of scientific articles were searched: MEDLINE, SCOPUS and SCINDEKS. In total 558 publications were retrieved. The types of articles selected were reviews, reports on clinical trials and letters to the Editor. Results: There are several changes of regulatory documents necessary for improving process of clinical development of antiepileptic drugs: preference of parallel groups design for add-on trials should be explicit; the non-inferiority design for monotherapy clinical trials should be acceptable; restrictive formulations when trials of antiepileptic drugs in children are in question should be avoided; requirements in regard to the efficacy measures should be harmonized among the regulatory bodies; proactive attitude towards discovery of adverse events; and precise requirements for clinical trials specifically designed to prove anti-epileptogenic effects should be made clear. Conclusion: Current regulatory documents are incomplete in many aspects; an international effort to improve and harmonize guidelines for clinical development of antiepileptic drugs is necessary for improvement of this process.

Aim : To gather and review data describing the epidemiology of schizophrenia and clinical guidelines for schizophrenia therapy in seven Central and Eastern European countries, with a focus on negative symptoms. Methods : A literature search was conducted which included publications from 1995 to 2012 that were indexed in key databases. Results : Reports of mean annual incidence of schizophrenia varied greatly, from 0.04 to 0.58 per 1,000 population. Lifetime prevalence varied from 0.4% to 1.4%. One study reported that at least one negative symptom was present in 57.6% of patients with schizophrenia and in 50–90% of individuals experiencing their first episode of schizophrenia. Primary negative symptoms were observed in 10–30% of patients. Mortality in patients with schizophrenia was greater than in the general population, with a standardized mortality ratio of 2.58–4.30. Reasons for higher risk of mortality in the schizophrenia population included increased suicide risk, effect of schizophrenia on lifestyle and environment, and presence of comorbidities. Clinical guidelines overall supported the use of second-generation antipsychotics in managing negative symptoms of schizophrenia, although improved therapeutic approaches are needed. Conclusion : Schizophrenia is one of the most common mental illnesses and poses a considerable burden on patients and healthcare resources alike. Negative symptoms are present in many patients and there is an unmet need to improve treatment offerings for negative symptoms beyond the use of second-generation antipsychotics and overall patient outcomes.

Oko 40 na svakih 100,000 stanovika u svim starosnim grupama svake godine prokrvari iz ulkusa želuca ili duodenuma. Smrtnost ovih pacijenta je i dalje visoka, između 8 i 10%, bez obzira na stalan napredak u modalitetima lecenja. Kod pacijenata koji krvare iz ulkusa treba sto pre uraditi endoskopiju i sprovesti direktnu lokalnu hemostazu mehanickim, hemijskim ili termickim metodama. Dok pacijent ceka na endoskopiju treba poceti sa intravenskom primenom visokih doza blokatora protonske pumpe, koja se nastavlja do isteka 72 sata od njenog uvođenja. Primena eritromicina oko sat vremena pre endoskopije povecava vidljivost unutrasnjosti želuca i olaksava endoskopsku terapiju. Intravensku primenu blokatora protonske pumpe treba nastaviti oralnim preparatima istih lekova tokom 7 nedelja, i ukoliko je pacijent pozitivan na Helicobacter pylori, sprovesti eradikacionu terapiju. Za uspesno izlecenje i prevenciju ponovnog krvarenja neophodni su optimalni izbor, raspored primene i doziranje lekova koji prate endoskopsku dijagnostiku i terapiju.

Background: To investigate the impact of schizophrenia on quality of life (QoL) of patients and caregivers in seven CEE countries, by conducting a literature search. Methods: Search was performed in publicly available databases to identify publications from 1995 to 2012 related to schizophrenia and QoL. Publications included those describing health-related QoL data of negative symptoms in patients with schizophrenia. Results: Out of an initial search of 2882 abstracts, 1587 were excluded based on duplication or preliminary screening of titles, and a further 1550 publications were excluded based on screening of the abstracts (1510) or full-texts (40). Thus, 37 primary publications related to QoL of patients with schizophrenia and caregivers were identified. Due to differences observed in the identified studies, it was not possible to make direct comparisons nor to pool data for analysis. However, it was consistently reported that schizophrenia greatly affected the QoL of patients and had a significant negative impact on the QoL of caregivers, such that their QoL was considered similar to the patients themselves. In addition, patients with schizophrenia experienced significant stigmatization and discrimination. In general, the presence of negative symptoms was not well-documented in the literature and available antipsychotics had limited impact on the treatment of negative symptoms. Conclusion: Schizophrenia significantly reduces QoL of patients and their caregivers. Further research is needed to better understand the drivers of impaired QoL caused by schizophrenia, in particular the negative symptoms of schizophrenia, and how best the burden of illness and associated stigmatization and discrimination may be reduced.

Abstract Acute pancreatitis represents an acute nonbacterial inflammation of the pancreas caused by a premature and ectopic activation of pancreatic digestive enzymes. Two of the most important genes in pancreatic autodigestion, PRSS1 and SPINK1, were implicated in the earliest discoveries of the genetic background of pancreatitis. However, the distribution of their variations displays interethnic variability, which could significantly affect the magnitude of their proposed effects on this disease worldwide. The aim of the present study was to investigate the distribution of the most important functional variations of PRSS1 (86A>T and 365G>A) and SPINK1 (101A>G), and their influence on the clinical course of acute pancreatitis in Serbian patients. The study enrolled 81 subjects, the severity of disease course was determined using the Atlanta Classification system, and the genotyping was conducted using a PCR-RFLP method. PRSS1 86A>T and 365G>A SNPs were not observed in the study population, while SPINK1 101A>G was present with the frequency of 0.62% (95% CI: 0.00, 3.83%). Due to extremely low frequencies or absences of examined variations, the proposed effect of these SNPs on the severity of acute pancreatitis could not be confirmed. The results do not support routine genotyping of either PRSS1 or SPINK1 in Serbs.

BACKGROUND/AIM Femoropopliteal bypass is a revascularization technique of lower extremities with excellent outcome. The great saphenous vein is the best graft material, but if it is not adequate or has been removed, synthetic grafts are an useful alternative. Graft occlusion is the most significant complication with the most serious consequences. The aim of this study was to analyse predictive factors for the synthetic femoropopliteal bypass occlusions. METHODS This retrospective case-control study included all patients who underwent synthetic femoropopliteal bypass due to peripheral arterial occlusive disease at the Vascular Surgery Center, Clinical Center of Kragujevac, Serbia, from 2007 to 2013. The cases group were the patients with femoropopliteal graft occlusion (n = 44), with the control group consisted of the patients without such an outcome (n = 88). RESULTS Significant effects to occlusion were: concomitant cardiovascular disease (adjustedOR 27.05; 95% CI 4.74; 154.35), a type of femoropopliteal bypass (adjustedOR 16.50; 95% CI 4.05; 67.24), previous vascular intervention (adjustedOR 4.67; 95% CI 1.20; 18.14), clinical stage of the disease (adjustedOR 3.73; 95% CI 1.94; 7.18), administration of postoperative oral anticoagulant therapy (adjustedOR 0.05; 95% CI 0.01; 0.23) and the use of angiotensin converting enzyme inhibitors (adjustedOR 0.14; 95% CI 0.03; 0.70). A significant synergism was shown for the following combinations of the observed risk factors: type of femoropopliteal bypass and cardiovascular disease, type of femoropopliteal bypass and previous vascular intervention, previous vascular intervention and cardiovascular disease, previous vascular intervention and beta blockers, cardiovascular disease and diabetes, type of femoropopliteal bypass and antiaggregant therapy, clinical stage of disease and cardiovascular disease, previous vascular intervention and antiaggregant therapy. CONCLUSION Concomitant cardiovascular disease, below-knee femoropopliteal bypass, advanced stage of vascular disease and non-use of anticoagulant therapy and angiotensin-converting enzyme inhibitors are the significant predictors of graft occlusion after synthetic femoropopliteal bypass. Their synergistic effect determines the importance of diabetes, use of beta blockers and platelet antiaggregant therapy.

Abstract Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08), indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26), higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47) and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79) of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed.

Abstract Acute necrotizing pancreatitis (ANP) is a severe form of acute pancreatitis that is associated with high morbidity and mortality. Thus, an adequate initial treatment of patients who present with acute pancreatitis (AP) based on correct interpretation of early detected laboratory and clinical abnormalities may have a significant positive impact on the disease course. The aim of the study was to determine patient- and initial treatment-related risk factors for the development of acute necrotizing pancreatitis. For the purpose of this study a case-control design was chosen, including adult patients treated for AP in the surgical Intensive Care Unit (sICU) of Clinical Center of Kragujevac, from January 2006 to January 2011. The cases (n=63) were patients who developed ANP, while the controls (n=63) were patients with AP without the presence of pancreatic necrosis. The controls were randomly selected from a study sample after matching with the cases by age and sex. Significant association with the development of ANP was found for the presence of comorbidity (adjusted OR 6.614 95%CI 1.185-36.963), and the use of somatostatin (adjusted OR 7.460, 95%CI 1.162-47.833) and furosemide (adjusted OR 2710.57, 95%CI 1.996-56.035) started immediately upon admission to the sICU. This study suggests that comorbidities, particularly the presence of serious cardio-vascular disease, can increase the risk for development of acute necrotizing pancreatitis. The probability for the development of ANP could be reduced by the avoidance of the initial use of loop diuretics and somatostatin.