PURPOSE We aimed to determine the association of two of the most important functional polymorphisms of IL-8 and IL-10 with the clinical course and outcome of acute pancreatitis. METHOD Ninety-three patients with acute pancreatitis were genotyped for IL-8-251T>A and IL-10-1082G>A using PCR-RFLP. The severity of the disease was determined based on the Atlanta Classification system. RESULTS In patients treated with opioids, the odds for severe form of acute pancreatitis, its complications, and death were increased. Advanced age was associated with higher odds of organ/multiple organ failure and other systemic complications. Multivariate logistic regression analyses confirmed the observed effect of age and use of opioids, and revealed higher odds for the development of severe form of acute pancreatitis [P = 0.017, odds ratio (OR): 4.324, 95% confidence interval (CI): 1.305-14.323], its complications in general (P = 0.011, OR: 4.936, 95% CI: 1.442-16.897), pancreatic necrosis (P = 0.032, OR: 3.922, 95% CI: 1.122-13.707) and systemic inflammatory response syndrome (P = 0.037, OR: 3.838, 95% CI: 1.085-13.583) in the absence of IL-10-1082G>A variant allele. The effect of IL-8 -251T>A on acute pancreatitis severity or mortality was not detected. CONCLUSION Our study suggests the IL-10 -1082A allele as a protective factor in acute pancreatitis. Opioid analgesics treatment in acute pancreatitis is associated with severity, complications and mortality, while advanced age increases the risk of systemic complications.

Introduction: Pseudo journals, hijacked journals, fraudulent journals, fake journals, and predatory journals waste valuable research when authors publish their studies in them. Aim: This article described novel suggested features for the identification of fraudulent journals and aimed to explain this issue to help inexperienced scientists avoid publishing in predatory journals. Methods: The articles related to this topic in were retrieved from PubMed and trustable Internet sources. Results: Unfortunately, some fake journals have made their way into reputable databases, such as PubMed, PubMed Central, MEDLINE, SCOPUS, and Web of Science; thus, the serious question has been raised regarding how we should address this problematic phenomenon. We recommended 28 suggested characteristics of predatory journals for readers to take into consideration. Conclusion: Unaware of the detrimental effects associated with publishing in disreputable journals, inexperienced researchers can fall victim to them. Together, as both readers and writers, we should completely boycott predatory journals.

Introduction: The source of scientific information, methods for their evaluation, and methodology of their use are critical for serious scientific research and publishing of the scientific research results. Certain methodological principles should be inexcusably followed when designing clinical or observational research to avoid bias and presentation of results that do not reflect the truth about the phenomenon that is the object of the study. Aim: The aim of this study was to compare the methodological quality of clinical trials and observational studies published in medical journals from ex-Yugoslav countries indexed in Web of Science (WoS) and Pubmed/MEDLINE. Methods: Clinical studies published in medical journals of ex-Yugoslav countries were retrieved from the WoS and Pubmed database, and the sample for analysis was randomly chosen from the retrieved publications. The rate of the most common errors in the design of clinical/observational studies was established by a careful reading of the sampled publications and their checking against predefined criteria. Results: Number and percent of the evaluated studies that failed to meet each of the methodological criteria tested, number of the evaluated criteria not satisfied per database and number of studies that satisfied more than 4 criteria were analyzed per database. When explanatory potential of journal impact factor, number of citations, time elapsed from publication and a database where a journal is referred were tested by linear regression in regard to the number of methodological criteria satisfied per study, the linear regression model was obtained by backward deletion method and achieved R2 adjusted of 0.166 (F=13.827, df1 = 2, df2 = 127, p=0.000). The methodological quality of studies was directly related to impact factor of the journals (B = 0.976, 95% confidence interval 0.539 – 1.413, p=0.000) and inversely with the database where a journal is referred (B =–0.444, 95% confidence interval–0.824 – -0.064, p = 0.022). Each additional unit of impact factor increased number of satisfied methodological criteria for about 1, while referring a journal only in WoS decreased number of satisfied criteria for 0.45 points in comparison with journals referred in both WoS and Pubmed/MEDLINE, and for 0.9 points in comparison to journals referred only in MEDLINE. Conclusion: Methodological and scientometric quality of clinical studies published in medical journals from ex-Yugoslav region varies significantly, and the variations are higher in journals referenced only in WoS than in journals referenced in Pubmed/MEDLINE only, or in both Pubmed and Web of Science databases.

ABSTRACT Introduction The discovery of the anticonvulsant properties of valproic acid and the development of valproic acid/valproate to market authorization for specific epilepsy types and syndromes, as well as their repurposing for other indications, are illustrative examples of both the strengths and weaknesses of drug development strategies. Areas covered This review summarizes and interprets the development and repurposing history of valproic acid/valproate. The article is based on articles, including original studies and systematic reviews obtained from PubMed, Scopus, EBSCO, SCIndeks and Google Scholar databases. Expert opinion Random screening and careful observation of the experimental effects of tested substances were crucial for discovering the anticonvulsant effects of valproic acid, while rational drug design and clinical observation strategies led to repurposing valproic acid and valproate for bipolar disorder maintenance treatmentand prevention of migraine attacks. Early planning and feasibility studies of future clinical trials are essential for obtaining marketing authorization of new substances or new indications of old anticonvulsants. Significant progress has been made recently toward understanding, treatment and prevention of hepatotoxicity caused by valproic acid/valproate, making its long-term administration safer. There are ongoing efforts to repurpose valproic acid/valproate for augmentation with antipsychotic drugs for the treatment of schizophrenia.

The Inappropriate design of experimental studies in medicine inevitably leads to inaccurate results and biased conclusions. The aim of our study was to compare prevalence of implementing basic principles of experimental design in preclinical experimental studies published in international journals with low and high impact factor. The samples for analysis ware randomly chosen among publications retrieved from PubMed and Web of Science (WoS). Implementation rate of basic experimental research principles (local control, randomization and replication) was established by careful reading of the sampled publications and their checking against predefined criteria. The difference in number of satisfied criteria among the groups was not significant, however, number of citations was significantly higher in the group of studies published in high-impact factor journals (30.5 ± 38.5 vs 2.6 ± 4.1, p=0.000). The studies published in low-IF journals less frequently used pseudo replication (30% vs 56%, p=0.000) and more often randomized their units of observation (40% vs 5%, p=0.000). Prevalence of experimental preclinical studies that did not implement completely basic principles of research design was high in both low- and high-impact factor journals. Although much more cited, studies published in high-impact factor journals bore the same risk of incorrectness, bias, and consequent misleading of future researchers.

Introduction: Certain methodological principles should be inexcusably followed when designing clinical or observational research to avoid bias and presentation of results that do not reflect the truth about the phenomenon that is the object of the study. Aim: The aim of this study was to compare the methodological quality of clinical trials and observational studies published in medical journals from ex-Yugoslav countries indexed in Pubmed/MEDLINE. Methods: Clinical studies published in medical journals of ex-Yugoslav countries were retrieved from the Pubmed/MEDLINE database, and the sample for analysis was randomly chosen from the retrieved publications. The rate of the most common errors in the design of clinical/observational studies was established by a careful reading of the sampled publications and their checking against predefined criteria. Results: The studies published in two countries that are now member states of the European Union (Slovenia and Croatia) have significantly higher citation rates, impact factor, and methodological quality scores than studies from other ex-Yugoslav countries. While publications from Croatia show clear improvement trend throughout the last two decades, which is visible also in the last 10 years in Slovenia and Bosnia and Herzegovina, quality of clinical research published in journals from Serbia was stagnating in the same period. Conclusions: There are significant differences in methodological quality and scientometric characteristics of clinical research published in medical journals of ex-Yugoslav countries that could be mitigated by more intensive training of clinical researchers in statistics and research design, as well as by more rigorous editorial practices.

ABSTRACT Objectives: To examine a relationship between protein C (PC) and antithrombin III (AT III) activities with ejection fraction of left ventricle (EFLV), in the early phase of acute ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), and to investigate whether PC and AT III are associated with major adverse cardiovascular events (MACE) within 6 months following from pPCI. Patients and methods: The research had a prospective character and included 357 patients who had, following the diagnosis of the STEMI, undergone pPCI at the Clinic of Cardiology and Emergency Internal Medicine, Military Medical Academy, Belgrade, Serbia, from January 2010 until April 2019. Results: The EFLV positively correlated with PC values (rho = 0.229). There was a statistically significant increase in the PC values between patients with MACE compared with those without MACE at 6 months’ follow-up evaluation (p < 0.0001). Also, significant difference in PC values between patients who died in hospital and those who were alive at 6 months’ follow-up (p < 0.01) was observed. PC values were different across different EFLV groups (p < 0.001), increasing from the 1st to the 4th EFLV quartiles: the median and the interquartile values for the 1st, 2nd, 3rd and 4th quartiles were 1.0400IU/l ± 0.15, 1.1400IU/l ± 0.15, 1.1350IU/l ± 0.16 and 1.2200IU/l ± 0.14, respectively. Conclusion: Increased PC activity in the early phase of STEMI is associated with higher EFLV 5 days after the pPCI as well as with MACE at 6 months after the pPCI.

ABSTRACT Introduction: Zonisamide is a benzisoxazole with 3-methanesulfonamide side chain, chemically unrelated with other anticonvulsants, and approved as mono-therapy of newly diagnosed focal epilepsy with or without secondary generalization in adults or adjunctive therapy in the treatment of partial seizures, with or without secondary generalization, in adults, adolescents, and children aged 6 years and above. Areas covered: Pharmacokinetics, clinical efficacy, and the adverse effects of zonisamide are discussed in the article. The discussion is based on data from published preclinical studies, clinical trials, observational studies, systematic reviews, and approved summary of product characteristics. Expert opinion: Zonisamide is an anticonvulsant with multiple mechanisms of action on neuronal tissue, which achieves seizure freedom in more than 80% of patients with newly-onset focal epilepsy and in 6.2 to 18.1% of patients with focal onset seizures inadequately controlled by first-line anticonvulsants. Within the recommended dose range, it follows linear kinetic of elimination; it is metabolized in the liver by two cytochrome isoforms, so pharmacokinetic interactions are rare and with little clinical significance. Up to 10% of patients taking zonisamide will have problems with weight loss and more than 10% with irritability, confusion or depression, and long-lasting therapy may cause renal calculi in 1.2% of patients.

Abstract The aim of this study was to perform screening for anxiety disorders among children with asthma and to reveal factors associated with general anxiety disorder and its specific forms. This was a cross-sectional study conducted among out-patients with asthma during routine visits to pediatricians. They were screened for anxiety disorders using SCARED self-reported questionnaire. Additional data were collected using specially designed questionnaire as well as the patient files. Statistical analysis was performed by the SPPS software using descriptive statistics and logistic regression. Study population consisted mostly of schoolchildren (n=58), 8-12 years old, and adolescents (13-17 years) (n=13). Approximately 33.8% respondents were positive for general anxiety disorder. The most common were separation anxiety and social anxiety, recorded among 49.3% and 32.4% of patients, respectively. Generalized anxiety and panic/somatic disorder were recorded in the same percentage of patients (21.3%), while avoiding school was the least frequent (14.08%). Influence of numerous factors was tested, but only the following showed significant effects: peak expiratory flow test was associated with general anxiety disorder, patient’s age and gender with PD, and living place, asthma control according to GINA and age on GAD. Parent’s smoking was associated with SAD, age and patient’s weight status with SPH, and GINA asthma control with SA. These findings suggest that anxiety disorders are common among children and adolescents with asthma. Various factors can be associated with general anxiety disorder and its specific forms, but some of them being preventable as avoiding smoking in the family.

Introduction: Results of preclinical and clinical studies in medicine could be trusted only if their design and statistical analysis were appropriate. Aim: The aim of our study was to investigate whether preclinical and clinical studies published in medical journals of Bosnia and Herzegovina satisfy basic requirements for appropriate design and statistical interpretation of data. Methods: Preclinical and clinical studies published in medical journals of Bosnia and Herzegovina were retrieved from the PubMed database, and the sample for analysis was randomly chosen from the retrieved publications. Implementation rate of basic principles of experimental design (local control, randomization and replication) and rate of the most common errors in design of clinical/observational studies was established by careful reading of the sampled publications and their checking against predefined criteria. Results: Our study showed that only a minority of experimental preclinical studies had basic principles of design completely implemented (7%), while implementation rate of single aspects of appropriate experimental design varied from as low as 12% to as high as 77%. Only one of the clinical/observational studies had none of the errors searched for (2%), and specific errors rates varied from 10% to 89%. Average impact factor of the surveyed studies was around one, and average publication date recent, less than 5 years ago. Conclusion: Prevalence of preclinical studies that did not follow completely basic principles of research design, and that of clinical/observational studies with errors are high, raising suspicion to validity of their results. If incorrect and not protected against bias, results of published studies may adversely influence future research.

Increased antibiotic utilization in hospital is linked to higher total treatment costs, together with increased length of stay, surgery and emergency admission. The aim of our retrospective cohort study was to investigate predictors of antibiotic utilization per single patient from an intensive care unit (ICU) of a tertiary care, university hospital in Serbia. Average utilization of antibiotics per patient was 23.9 ± 20.4 defined daily doses (DDDs). Diagnosis of systemic infection increased antibiotics utilization per patient for 10.0 DDDs, positive blood culture for 5.4 DDDs, isolation of Pseudomonas spp. for 19.5 DDDs, isolation of Acinetobacter spp. for 6.3 DDDs and injury for 7.3 DDDs per patient. Each new day of hospitalization and each additional drug prescribed increased utilization for further 0.3 DDDs and 1.2 DDDs, respectively. Appropriate and limited use of antibiotics in ICU is of key importance for preserving their effectiveness and decrease of bacterial resistance.

ABSTRACT Introduction: Seizures, which could not be controlled by drug therapy, have profound negative influence on the quality of life of the affected person. If with clear locus of origin and accompanied by loss of consciousness, drug-resistant epilepsy could be treated by surgery. Areas covered: The aim of this article was to review current status of epilepsy surgery through description of the most important operative methods and narrative comparison of their benefits and harms. In total 1154 articles were retrieved from MEDLINE, SCOPUS, EBSCO, and SCINDEKS databases, and 78 included in the review. The review included systematic reviews, meta-analyses, clinical trials, observational studies on humans, case series, and case reports. Expert opinion: Sophisticated diagnostic methods nowadays offer much more precise localization of epileptogenic focus and detailed planning of a surgical procedure which will make minimal damage of neural pathways and structures essential for movements, speech, cognition, and emotions. Advent of perioperative care, and improved diagnostics and surgical techniques resulted with significant drop in rates of postoperative complications, long-term neurological deficit, and mortality in the last decade, while seizure freedom rate and quality of life increased.