Prevalence of extended-spectrum ß-lactamase and carbapenem-resistant Klebsiella pneumoniae in clinical samples.

OBJECTIVES: To assess the prevalence of these resistant strains in the overall isolates of Klebsiella pneumoniae (K. pneumoniae) in hospital settings. METHODS: This retrospective study was conducted from November 2020 to November 2021. The identification and antibiotic susceptibility testing were performed using standard laboratory methods according to the EUCAST standards. The detection of ESBL and carbapenemase production was performed using phenotypic methods such as E-test, combined-disk test with various inhibitors (ROSCO Diagnostica A/S), chromogenic medium for the detection of ESBL/carbapenemase-producing Enterobacteriaceae (CPE) isolates, and the VITEK 2 Compact system (BioMerieux). RESULTS: 944 isolates of K. pneumoniae were detected in various clinical specimens. Among these, ESBL-producing strains were detected in 349/944 (37%), whereas carbapenem- resistant strains in 188/944 (20%) of the isolates. The remaining isolates (407/944 [43%]) belonged to the wild type. ESBL isolates were the most common in wound swabs (138 [39.5%]), whereas CRKP isolates in screening samples (110 [58.5%]). The majority of ESBL isolates were detected in surgical departments (105 [30.1%]), whereas CRKP isolates in adult intensive care unit departments (79 [42.%]). CONCLUSION: Our results show an increasing frequency of CRKP strains. This presents a significant issue in terms of infection prevention and control in hospital settings.

Are We Scared of Clinical Trials if Not Sufficiently Informed and Educated?

Purpose: Educational interventions have already been shown to positively affect awareness of clinical trials (CTs) among medical students. We aimed to explore basic knowledge and attitudes about CTs among medical students in terms of educational interventions that should be reflected in their further involvement in performing CTs and their role in raising awareness about CTs. Methods: This cross-sectional, self-report anonymous online survey involved undergraduate medical students of the Medical Faculty University of Sarajevo enrolled in classes held within the Department of Pharmacology and Toxicology in the academic year 2015-2016. To include all accessible subjects for better representation of the whole population, consecutive sampling was applied. Results: Among 142 students who completed questionnaire, 50% of them expressed partial or full agreement with the questionnaire statement that they were satisfied with the available information on CTs. Only 38% said they would participate in a CT, 21% would not, while 41% were not sure. Positive correlations were detected for composite subscale scores of agreement with questionnaire statements conveying the student's knowledge about ethical and legal aspects of CTs and their perception about reliability/integrity and impact of CTs on medical practice. Conclusion: Students have knowledge of the basic design and ethical aspects of CTs. Positive attitudes toward the impact of CTs on medical practice were shown in students of higher years of study, where educational intervention of additional knowledge of CTs was inserted and those students expressed better knowledge of CTs. However, no significant impact was detected between knowledge and willingness to participate in CTs, irrespective of years of study, reflecting the third of students that would participate in CTs. Changes in medical curricula led to the change in students' knowledge and attitudes regarding CTs as well as their involvement in CTs.

Recanalization rate of proximal deep venous thrombosis related to therapeutic modality during six months follow-up.

Aim To evaluate the efficacy (rate of recanalization) of therapy with novel oral anticoagulants (NOAC; rivaroxaban, apixaban) compared to conventional treatment (low molecular weight heparin - LMWH and vitamin K antagonist) in the treatment of deep vein thrombosis (DVT) of the proximal segments of lower extremities. Methods The first group consisted of patients diagnosed with DVT and treated with NOAC (n = 100), while the second group consisted of patients diagnosed with DVT, who were treated by conventional treatment (low molecular weight heparin and vitamin K antagonists) (n = 100). In the first group, NOAC was included in the initial treatment. Patients in the second group were treated with LMWH for four days, and on the fifth day vitamin K antagonist was included in therapy, international ratio (INR) was titrated to therapeutic values (2.0-3.0), and then low molecular weight heparin was excluded from the therapy. Results There was a statistically significant difference in the estimated values of free lumen of the blood vessel between the examined groups after 30 days (p=0.0001), after 90 days (p=0.0001) and after 180 days (p=0.0001). After 180 days, the average free lumen values in the NOAC group were 85% (81-89%), which was significantly higher than the free lumen values in the second group, 73% (69-79%). Conclusion The use of NOAC represents more efficient treatment of DVT comparing to vitamin K antagonists.

The Significance of Interleukin-6 and Tumor Necrosis Factor-Alpha Levels in Cognitive Impairment among First-Ever Acute Ischaemic Stroke Patients.

BACKGROUND: Acute ischemic stroke (AIS) frequently results in the development of cognitive impairment, which quite often persists. The pathophysiological mechanisms involved in the development of cognitive impairment are only partially elucidated. The aim of this study was to evaluate the correlation between interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) serum levels with cognitive impairment in AIS patients. SUBJECTS AND METHODS: This hospital-based case-control study was performed during December 2014 - May 2018. A total number of 130 randomly selected patients were prospectively recruited from the Department of Neurology, Clinical Center University of Sarajevo. The study examined 100 first-ever AIS patients, while 30 comprised the non-stroke control group of patients with discogenic lumbosacral radiculopathy. All participants were evaluated using the Mini-Mental State Examination, the Montreal Cognitive Assessment, the Frontal Assessment Battery, and the Addenbrooke's Cognitive Examination-Revised. Cognitive testing and laboratory analyses were performed within the first three days of admission in all patients while AIS patients were reassessed on the 15thday of hospitalization. RESULTS: Female stroke patients with cognitive impairment had significantly higher baseline levels of IL-6 (p<0.017), and TNF-α (p<0.017) than those without cognitive impairment. In the control measurement, a significant difference in IL-6 levels (p=0.037) in male and TNF-α levels (p=0.042) in female stroke patients with cognitive impairment was observed. CONCLUSIONS: These findings indicate that pro-inflammatory cytokines are probably implicated in the pathogenesis of cognitive decline in AIS patients.

Effects of topically applied diclofenac and ketoprofen on prostaglandin E2 and Stat3 sera levels and body temperature in two different acute inflammation models in rats.

INTRODUCTION: Cytokines exert biological function through signal transducer and activator of transcription factors. Prostaglandins have function as promotors, where play a key role in generation of the inflammatory response and as ones that solve inflammatory process.Non-steroidal anti-inflammatory drugs, inhibit prostaglandin synthesis but the existence of additional mechanisms is present. Thus, we aimed to explore effects of topically applied NSAIDs on the levels of PGE2 and Stat3 in the setting of two in vivo induced acute inflammation models. METHODS: Male Wistar rats were randomized into five equal groups: 4 treated and a control group. Diclofenac or ketoprofen patches were applied in two different doses, i.e. equivalent to human therapeutic dose, and three times higher dose. Three hours later either model of inflammation (with 20% yeast, or with 1% carrageenan) was induced.Blood samples were taken 3 hours after and concentration levels of PGE 2 and Stat3 were determined using ELISA. Body temperature was measured at 0. 1st, 3rd and 5th hour after inflammation induction and presented in Celsius degrees. Shapiro-Wilk, Leven's, Welch's One-Way ANOVA, Kruskal-Wallis test and adjustment by Bonferroni correction were applied. RESULTS: In both inflammation models, no differences in the mean values of PGE 2 between control, low and high dose groups treated by either diclofenac or ketoprofen were found. In yeast inflammation, the mean value of Stat3 was significantly higher in both dose ketoprofen groups compared to control group. After ketoprofen application, no significant differences in body temperature between groups at hour 0 and 5 in either model of inflammation induced, while at 1st hour after carrageenan inflammation, significant differences were found with significantly higher values in low dose ketoprofen group compared to control group. In yeast application, significant differences in body temperature were found at hour 3 after inducing inflammation and post hoc pairwise comparison test revealed significant higher values in low dose ketoprofen group compared to control. CONCLUSION: Elevated Stat3 values post ketoprofen application in yeast model of induced inflammation were detected. Further investigation of cytokine microenvironment as well as the mechanisms of ketoprofen influence on inflammation are needed.

Analysis of Serum Inflammatory Markers in Cognitive Impairment among Acute Ischaemic Stroke Patients.

BACKGROUND: Previous studies have indicated that changes in the expression of certain inflammatory biomarkers are associated with cognitive impairment (CI), but only a limited number of studies were conducted in patients with acute ischemic stroke (AIS). The present study aimed to evaluate the potential association between serum levels of several inflammatory markers and cognitive impairment in AIS patients. These markers included interleukin 6 (IL-6), C-reactive protein (CRP), plasma fibrinogen, erythrocyte sedimentation rate (ESR), and white blood cell (WBC) count. SUBJECTS AND METHODS: All participants were prospectively recruited from the Department of Neurology, Clinical Center University of Sarajevo. A total of 100 patients with first-ever AIS were included in stroke group and 30 in the non-stroke control group. Each patient underwent a comprehensive cognitive assessment and laboratory tests (IL-6, CRP, fibrinogen, ESR and WBC) within the first three days of admission. Cognitive status was assessed using cognitive instruments: the Mini-Mental State Examination, the Montreal Cognitive Assessment, the Frontal Assessment Battery, and the Addenbrooke's Cognitive Examination-Revised. RESULTS: Female stroke patients with CI had higher levels of IL-6 compared to those without CI and controls (p<0.017). AIS patients with CI had significantly higher plasma fibrinogen (p<0.001) and CRP levels (p<0.001) than controls, whereas there was no significant difference in comparison with cognitively intact patients. There were no statistical differences in ESR or WBC count between groups. CONCLUSIONS: Of the inflammatory markers, only IL-6 levels were associated with CI in AIS patients. Measuring circulating IL-6 could be used as a screening test to identify all such patients.

Depressive Symptoms Among Sarajevo University Students: Prevalence and Socio-Demographic Correlations.

OBJECTIVES: The aim of this research was to detect the presence of depressive symptoms among the student population at a Faculty of Medicine, as well to determine the correlation between the socio-demographic characteristics and students' lifestyle and depressive symptoms. SUBJECTS AND METHODS: Of 800 students enrolled and asked to participate, 412 responded to the survey. The study included students from all 6 years of studies. The degree of depressive symptoms was measured by a 21-item revised form of the Beck Depression Inventory (BDI). We built bivariate logistic regression models to study whether age, gender, housing accommodation, year of medical training, and school success status (Grade Point Average - GPA) were associated with depressive symptoms. The results are reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: The study revealed that almost one third of students reported BDI >16 (30.1%). The present study did not find any association between BDI scores and study year or age difference, but we found that there was an association between housing accommodation and depressive symptoms. Students who lived with their parents had lower BDI scores than those who lived in a dormitory. The results of this study showed there is a negative correlation between physical activity and depressive symptoms in students, as well as that there is a positive correlation between depressive symptoms and substance abuse. CONCLUSION: Overall, our study confirms that the factors associated with an increase in medical students' depressive symptoms are housing accommodation, a lack of physical activity and substance abuse. Regarding failing a year of study at the medical school, as well as gender and age differences, we did not find any significant difference between students with higher compared to those with lower depressive symptoms.

Minimally invasive treatment of pancreatic pseudocysts.

A pancreatic pseudocyst (PPC) is typically a complication of acute and chronic pancreatitis, trauma or pancreatic duct obstruction. The diagnosis of PPC can be made if an acute fluid collection persists for 4 to 6 wk and is enveloped by a distinct wall. Most PPCs regress spontaneously and require no treatment, whereas some may persist and progress until complications occur. The decision whether to treat a patient who has a PPC, as well as when and with what treatment modalities, is a difficult one. PPCs can be treated with a variety of methods: percutaneous catheter drainage (PCD), endoscopic transpapillary or transmural drainage, laparoscopic surgery, or open pseudocystoenterostomy. The recent trend in the management of symptomatic PPC has moved toward less invasive approaches such as endoscopic- and image-guided PCD. The endoscopic approach is suitable because most PPCs lie adjacent to the stomach. The major advantage of the endoscopic approach is that it creates a permanent pseudocysto-gastric track with no spillage of pancreatic enzymes. However, given the drainage problems, the monitoring, catheter manipulation and the analysis of cystic content are very difficult or impossible to perform endoscopically, unlike in the PCD approach. Several conditions must be met to achieve the complete obliteration of the cyst cavity. Pancreatic duct anatomy is an important factor in the prognosis of the treatment outcome, and the recovery of disrupted pancreatic ducts is the main prognostic factor for successful treatment of PPC, regardless of the treatment method used. In this article, we review and evaluate the minimally invasive approaches in the management of PPCs.

The Incidence of Antihypertensive Drug-induced Side Effects in Patients with Diabetes Mellitus Type 2 and Hypertension.

OBJECTIVE: To determine types and frequency of side effects of antihypertensive drugs in patients with diabetes mellitus (DM) type 2 and hypertension. SUBJECTS AND METHODS: We performed a prospective study of 79 patients with DM type 2 and hypertension, randomly selected by systematic sampling, who were followed over a period of six months. Patients were assessed at baseline and once a month measuring following parameters: types of used antihypertensive drugs and frequency of side effects, the values (mmHg) of systolic (SBP) and diastolic blood pressure (DBP). RESULTS: Out of 79 patients, 48/79 (60.8%) were males and 31/79 (39.2%) were females. The median age in males was 53 years (IQR=48 to 55 years), in females was 53 years (IQR=49 to 56 years). There was no statistically significant difference in median age between males and females (P=0.368). There is a statistically significant difference in the values of SBP [χ2(5)=312.296, P<0.001] and DBP [χ2(5)=216.051, P<0.001] over a period of six months follow-up. The drug side effects were noted in 9/79 (11.4%) patients between 1-2 months, in 6/79 (7.6%) between 2-3 months, in 1/79 (1,3%) between 3-4 months. The most common side effect was cough (11/79 or 13.9%) associated with the combination of ACE inhibitor and thiazide diuretics. In 5/79 (6.3%) patients there were reports of: flushing, palpitations, headache, dizziness and leg edema associated with Ca blockers. CONCLUSION: The most common side effect of antihypertensive treatment was cough (13.9%) associated with the combination of ACE inhibitor and thiazide diuretic.

Polypharmacy in the treatment of schizophrenic patients in three University Centers in the Federation of Bosnia and Herzegovina (F/BH).

BACKGROUND: Polypharmacy in psychiatry is becoming the rule rather than the exception. Using more drugs at same time usually occurs where single drugs are considered insufficiently effective. SUBJECTS AND METHODS: The sample consisted of 216 patients: 85 from Sarajevo, and 44 and 87 respectively from Mostar and Tuzla. All schizophrenic patients who were hospitalised in three University Centers of F/BiH (Sarajevo, Tuzla, Mostar) on a particular day are included in the study. This included patients of both sexes (131 (60.65%) males and 85 females (39.35%)), 20-60 ages, who were on antipsychotic treatment with an established diagnosis of schizophrenia by the treating psychiatrist. The research was performed in the year 2004. The census of patients was conducted simultaneously in all three Centers, using a questionnaire in which all routine prescribed antipsychotics were registered, as the common method of the administration, and the doses as well saving as data for other medications that were simultaneously prescribed to the patients that day. RESULTS: Within the total sample the most frequently applied classical antipsychotics were haloperidol, promazine and from the group of new antipsychotics clozapine. The most frequently used other medications were biperidine and diazepam. The administration of all medication was followed through recording of individual doses, daily doses and frequency of administration. There are statistically significant differences regarding the frequency of biperidine use between the centers (p=0.008). CONCLUSION: In three University Clinical Centers of the Federation of Bosnia and Herzegovina (Sarajevo, Tuzla and Mostar), the applied rule is that more drugs in the treatment of schizophrenic psychosis and doing polypharmacy is the inevitable approach to treatment. The concept behind the polypharmacy is based on the fact that antipsychotic drugs do not cover all the symptoms of schizophrenic psychosis, and that additional medications may correct iatrogenic side effects caused by antipsychotic drugs. It is expected that the new atypical antipsychotics will treat much broader symptoms of psychosis and will not cause extrapyramidal side effects, as do the typical antipsychotics.

Antipsychotics and the quality of life of schizophrenic patients.

Patients' attitudes and values, their concept of illness and health as well as their previous experiences with medication may significantly affect the subjective response to antipsychotics. Quality of Life (QOL) has holistic concept that includes consideration of economic development, social vitality and environmental health. For most of the researches, QOL has an umbrella concept, which covers all aspects of life and includes physical and mental health, family relations, friendship, employment, leisure activities, medical treatment and quality of care, psychological and social benefit. In the domain of mental health, increasing the quality of treatment can be demonstrated through improvements of QOL of those using the mental health services. When measuring QOL in patients taking antipsychotics, it is important to acknowledge that a variety of factors may influence the QOL outcomes: these include side effects and daily dosage of the antipsychotic, depressive and negative symptoms, duration of treatment, and subjective tolerability.

Cannabis and psychiatric disorders.

There are connection between use of cannabis and many psychiatric disturbances in adolescents, especially "cannabis psychosis", depression, panic attacks and suicide. Negative effects could occur either as a result of a specific pharmacological effect of cannabis, or as the result of stressful experiences during the intoxication of cannabis in young people. Potentially is very dangerous high frequency suicidal ideation among cannabis users.

Psychiatrists between personal freedom to prefer antipsychotic in treatment of schizophrenic patients and algorithms and guidelines.

Algorithms and guidelines in treatment of schizophrenia behind which is the consensus of experts, institutions and associations are more and more in use among psychiatrists. However, the final conclusion about them will be possible only after their use in everyday practice with full freedom of psychiatrists to make changes according their personal judgment about risk and benefit of treatment.

Comorbidity in psychiatry: its impact on psychopharmacological treatment.

The existence of two or more diagnoses (psychiatric, or a combination with somatic) in one person leads to a dilemma when choosing psychopharmacs for the treatment of the patient. There are no acceptable and comprehensive guidelines or algorithms for the treatment of innumerable possible combinations of psychiatric and somatic disorders. A strategy for treatment of such conditions is needed.

Models of treatment with antipsychotics of the schizophrenic patients.

The aim of this study were to determine which antipsychotic are currently in use, to establish which doses are administrated to patients, to find out is there a practice of proscribing simultaneously more then one antipsychotic drug, to determine whether antipsychotic are proscribed in divided doses, to establish whether there is, besides antipsychotics, treatment with other medicaments (co-administration), especially with antiparkinsonics. The research (study) is epidemiological-clinical prospective, descriptive and analytical and it was conducted at University hospitals in Sarajevo, Tuzla and Mostar. Criteria for inclusion, non-inclusion and exclusion from the study were precisely defined as a mean for formation of sample. Based on this hypothesis were established, zero and alterative. According to zero hypothesis in the treatment of schizophrenia at University hospitals in FBiH new antipsychotic drugs are in use, small doses are proscribed (up to 20 mg), not more then one antipsychotic drug is used simultaneously, antipsychotics are administrated once a day and alongside with antipsychotics other medicaments are not co-administrated, especially antiparkinsons. The results of our study are showing that majority of patients are treated with classical antipsychotics. Minority of patients is treated with atypical neuroleptics like olanzapine, which is proscribed only in Sarajevo. Use of risperidone and ziprasidone is registered also only in Sarajevo, but only small number of patients is treated with these drugs. Most frequent antipsychotics were promazine and haloperidol. The range between minimal and maximal daily dose of promazine was from 50 to 450 mg/daily, and for haloperidol from 1 to 75 mg/daily. Above-mentioned drugs were administrated in an average from two to three times a day. Alongside with antipsychotics, other drugs were used. Most frequent was the use of biperidine in oral and parenteral formulation, as well as nitrazepam and diazepam. The importance of this study is following: data are useful for the current mental health care reform in FBiH, results will point out place and position of FBiH in contemporary world trends in the treatment of schizophrenia, they will contribute to rational use of antipsychotic therapy, they will point out possible ways in reduction of side effects, often dangerous adverse effects of antipsychotics, and they will give contribution to faster rehabilitation of schizophrenics with the reduction of financial means for the treatment of patients with schizophrenia.

Sertraline and alprazolam in the treatment of panic desorder.

A compared, 12 week, placebo controlled study, with fixed dose, outpatient study of patients diagnosed with panic disorder with and without agoraphobia according to ICD-10, was conducted to evaluate the efficacy and safety of sertraline and alprazolam. The study included 40 patients, divided in two groups. We evaluated number of ICD-10-defined panic attacks, agoraphobia and anticipatory anxiety. All patients were aged 18 year and older and were randomized to either sertraline or alprazolam. Sertraline applied in fixed doses of 20 mg/day and alprazolam in doses 1-1,5 mg/day significantly reduced the frequency of panic attacks in panic disorder patients, reduced symptoms of agoraphobia and anticipatory anxiety.

Frequency and characteristics of side effects associated with antidepressant drugs.

Depression is among the most common of chronic health problems. WHO report predicts that depression will be the leading cause of disability in the industrial world by the year 2020. To be successful, treatment for the patients suffering from depression must be continued until complete recovery, but most patients do not stay on their antidepressant medication long enough. One of the most frequent reasons for break down is appearance of unpleasant side effects. In this study we followed up dynamics of the characteristic side effects of antidepressant therapy, with the major goal to assess their frequency and characteristics. The sample was all female patients taking antidepressant drugs in the Department of Psychiatry of Clinical Centre of University in Sarajevo. The treatment with antidepressants was efficient in most of the patients. A major advantage of SSRI over TCA was less pronounced side effects. The most intensive side effects of TCA (amitriptyline) were dry mouth, tremor and tachycardia while the most frequent side effects included blurred vision, tachycardia, dry mouth, tremor and sedation. Side effects of SSRI (fluoxetine/fluvoxamine) were mild, and the most frequent were nausea, tachycardia, swelling, dry mouth.