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.

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.

Demarcated Opacities as Predictors of Progression of the Molar Incisor Hypomineralisation: a Pilot Study.

OBJECTIVES: Demarcated opacities (DO) on teeth affected by Molar Incisor Hypomineralisation (MIH) were observed to investigate if parameters of DO existence and the number of teeth affected could be used to predict the progression of disease. MATERIAL AND METHODS: In 2009, the MIH prevalence was 11.5% (n=51) among 446 subjects in Sarajevo, aged from 6 to 9 years. In subjects with MIH who gave consent for further participation (n=25), the teeth with DO were observed after a 12-month period. RESULTS: our sample included 29 permanent incisors and 14 first permanent molars with DO. The number of teeth with light opacities was significantly higher than the number of teeth with dark opacities. Opacities were more numerous on surfaces which were not exposed to masticatory pressure. The size of tooth surface affected by DO occurrence ranged from 1.33% to 56.56%. The number of affected teeth ranged from two to six. A strong positive correlation between MIH progression and dark colored opacities located on the occlusal/incisal surface of teeth was noted. Larger part of tooth surface was affected by hypomineralisation in the case of dark-colored opacities. The DO presence on incisors was more likely to be located on vestibular surfaces and on the first permanent molars on their occlusal surfaces. CONCLUSIONS: The color of DO occurrence was the best predictor for MIH progression both independently and in combination with the number of affected teeth. Location of DO occurrence was a good independent predictor for MIH progression. It is important to collect information about color and location of DO presence.

Use of chest CT scan scoring system for diagnostic and therapeutic decision making in pleural effusion.

Aim To investigate the usage of chest computed tomography (CT) scan score for improvement in diagnostic and treatment efficacy of repetitive pleural effusion. Methods CT scan scoring system was used as a part of diagnostic procedures in patients with repetitive pleural effusion. Patients with at least two pleurocentesis were included in the study. Chest and abdominal ultrasound, chest x-ray, bronchoscopy, biochemical, microbiological and cytological analysis of pleural fluid specimen were performed for all patients. Results In a two-year period (during 2017-2018) 79 patients were analysed, 27 (34.17%) female and 52 (65.82%) male patients. Malignant pleural diseases were confirmed in 32 cases (40.5%), nonmalignant pleural effusions in 38 (48.1 %) cases, and nine (11.4%) patients rested without exact cause of pleural effusion after two pleurocenteses. Binary regression model showed odds ratio of 1.314; CI 95% 1.119-1.543) (p=0.00088). Confirmed malignancies with pleural effusion were in high correlation with the number of points in CT scan score. Conclusion CT scan scoring system was helpful for diagnostic and treatment decision making in patients with repetitive pleural effusion.

Review of Standard Laboratory Blood Parameters in Patients with Schizophrenia and Bipolar Disorder.

INTRODUCTION: Symptomatic and etiopathologic heterogeneity of schizophrenia (SCH) and bipolar disorder (BD) can be adequately addressed using a dimensional approach to psychopathology, as well as interpreting physiological properties and markers as predictors of disease onset and relapse. Risk factors, genetic and environmental, are likely to modify the neurobiological processes characteristic of certain physiological processes that manifest to a greater degree of overlapping symptoms. One of the most common laboratory tests in psychiatric patients is a standard laboratory blood test. It gives us an insight into the general somatic condition of the patient. It assesses the ability to transport oxygen to tissues and carbon dioxide back to the lungs via erythrocytes (RBC) and hemoglobin (HGB) as their most important constituents, and is also an indicator of iron status and blood oxygenation. AIM: Schizophrenia (SCH) and bipolar disorder (BD) are psychiatric disorders whose complex etiology and pathogenesis are still far from known. A correlation between red blood cell abnormalities and these diseases has been recognized in some studies. One of the most common laboratory tests in psychiatric patients is a standard laboratory blood test. However, so far there is a small number of published papers that relate to the relationship between laboratory parameters of blood and the aim of this paper is to reveal more light in this subject. METHODS: The research was done as an observational prospective clinical study that has evaluated different physiological and pathological parameters in patients with BD and SCH over a two-year period. A total of 159 patients with schizophrenia, 61 patients diagnosed with bipolar disorder and 82 healthy subjects participated in this study. RESULTS: At baseline, BD compared to SCH patients had higher mean lymphocyte count (2,6±0,7 vs. 2,0±0,6x109; p=0,006) and haemoglobin concentration (146,8±12,2 vs. 140,2±14,7 g/L; p=0,03), and significantly lower red cell distribution width (13,6±2,2 vs. 14,7±1,8%; p=0,008). In both BD and SCH patients there was a significant number of patients with low red blood cells count and low haemoglobin concentration, and high MCH and MCHC at baseline and at 3 and 6 months of follow up. CONCLUSIONS: The finding that SCH as well as BD differed from controls with respect to red blood cells, hemoglobin, lymphocytes, and average platelet count was consistent with previous findings and could be understood as a qualitative measure in the evaluation of this sample. The fact that no association with other parameters was found, as well as an association with the diagnosis, does not exclude that these associations can be found in larger samples.

Outpatient management of oral anticoagulation therapy in patients with nonvalvular atrial fibrillation.

Due to heightened risk for thromboembolic complications, nonvalvular atrial fibrillation (NVAF) presents an absolute indication for long-term oral anticoagulation therapy. This was an observational, analytical, randomised, one-year clinical study, conducted in the Blood Transfusion Institute Sarajevo, Bosnia & Herzegovina. The aim of this study was to present the oral anticoagulation treatment in terms of International normalised ratio (INR) monitoring and warfarin/acenocoumarol dose titration in 117 patients with NVAF. INR values, the doses of warfarin and acenocoumarol, as well as the tendency and adequacy of their changes were monitored. Percentages of the therapeutic INR values were 51,77% and 53,62%, subtherapeutic 42,84% and 35,86%, and supratherapeutic 5,39% and 10,53% for the warfarin and acenocoumarol treatment, respectively. The average total weekly doses (TWD) which most frequently achieved the therapeutic INR values were 27,89+/-12,34 mg and 20,44+/-9,94 mg, for warfarin and acenocoumarol, respectively. The dose changes with the INR values 1,7 or lower/3,3 or higher were omitted in 13,46% and 15,63%, and with the INR values 1,8-3,2 were noted in 8,62% and 13,48% of all the check-up visits in the warfarin and acenocoumarol group, respectively. The annual dose changes were noted in 24,65% and 31,41%, and the daily dose changes in 74,43% and 73,36% of all the check-up visits of warfarin and acenocoumarol group, respectively. We can conclude that the management of the oral anticoagulation treatment in our country is in accordance with the relevant recommendations, but with the present tendency toward underdosing and unnecessary frequent dose changing.

Role of inhaled corticosteroids in the exacerbation rate of moderate chronic obstructive pulmonary disease.

Aim To analyse frequency of chronic obstructive pulmonary disease (COPD) exacerbation in patients on therapy with inhaled corticosteroids (ICS) and relevant factors that influence the rate of COPD exacerbations in a subgroup of moderate illness, like FEV1, comorbidities and other concomitant therapy. Methods The study included patients with moderate COPD with at least 10 pack-years history of smoking and accompanying cardiovascular comorbidity. Demographic data, frequency of exacerbations and information about proscribed treatments - ICS alone or in combination with long acting beta agonist (LABA), were collected from medical records for the previous 12 months from the index date. Results Data were collected for 210 patients (170 males) with the mean age 65.63±8.66 years, 72 of which were treated with a fixed combination of long acting beta blocker (LABA) and ICS. Significantly more frequent exacerbations were detected in patients using ICS p<0.0001) and having higher Modified British Medical Research Council (mMRC) score p=0.004). No statistically significant difference was registered related to ratio of FEV1 /FVC (p=0.121) or a number of cardiovascular comorbidities per patient (p=0.969). CONCLUSIONS: Our results present a small contribution to the current scientific discussion about the use of ICS in COPD treatment. Further prospective studies are needed to confirm the impact of ICS on the frequency of COPD exacerbations.

Metformin use associated with protective effects for ocular complications in patients with type 2 diabetes - observational study.

OBJECTIVE: The aim was to study the association of the use of an oral antihyperglycemic agent metformin with the presence of ocular complications in patients with type 2 diabetes (T2D). METHODS: Medical records were reviewed for 234 patients with diagnosed T2D. 81.2% (n=190) patients were using metformin and 18.8% (n=44) using other oral antihyperglycemic agents. Plasma glucose concentration, glycated haemoglobin, and the presence of ocular complications in patients treated with metformin were compared to those in patients treated with other oral antihyperglycemic agents. RESULTS: Ocular complications occurred in 65 patients (27.8%). Patients treated with metformin had fewer ocular complications compared to patients treated with other oral antihyperglycemic agents (χ2=19.985; p<0.0001). After adjustment for gender, age, duration of T2D, serum concentration of cholesterol, smoking, body mass index and presence of other diseases, treatment with metformin decreased the odds of both glaucoma (OR=0.14, 95% CI: 0.03-0.57, p=0.006) and diabetic retinopathy (OR=0.33, 95% CI: 0.14-0.82, p=0.017) compared with other oral antihyperglycemic agents. CONCLUSION: Our results suggest that metformin may have a protective effect on ocular complications, especially glaucoma, in patients with T2D. The effects of metformin either regarding prevention of ocular complications or ocular complications already developed in patients with T2D, should be further investigated.

Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis.

Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of the clinical condition in patients with multiple Sclerosis (MS). The goal of the present research was to evaluate met-enkephalin in vitro effects on the number and type of chromosome aberrations in the peripheral blood lymphocytes of patients with MS. Our research detected disappearance of ring chromosomes and chromosome fragmentations in the cultures of the peripheral blood lymphocytes treated with met-enkephalin (1.2 µg/mL). However, this research did not detect any significant effects of met-enkephalin on the reduction of structural chromosome aberrations and disappearance of dicentric chromosomes. Chromosomes with the greatest percent of inclusion in chromosome aberrations were noted as: chromosome 1, chromosome 2 and chromosome 9. Additionally, we confirmed chromosome 14 as the most frequently included in translocations. Furthermore, met-enkephalin effects on the increase of the numerical aberrations in both concentrations applied were detected. Those findings should be interpreted cautiously and more research in this field should be conducted.

Better stability of acenocoumarol compared to warfarin treatment in one-year observational, clinical study in patients with nonvalvular atrial fibrillation.

AIM: To evaluate differences in the treatment quality between often used oral anticoagulants, warfarin and acenocoumarol in patients with nonvalvular atrial fibrillation (NVAF). METHODS: This was an observational, comparative, one-year clinical study, conducted in the Blood Transfusion Institute of Sarajevo, Bosnia & Herzegovina. All patients who were using warfarin/ acenocoumarol and monitored were eligible. Patients who met inclusion criteria (the age of 40-80, diagnosed NVAF, CHADS index score > or = 2, the planned long-term treatment) were includes in two parallel groups of 60 patients, composed according to the warfarin/acenocoumarol treatment as well as the gender and age. Routinely measured International normalised ratio (INR) values were the basic parameter for individual quality and stability assessment. RESULTS: All average, monthly INR values were in therapeutic range (2.0-3.0) in both therapeutic groups. There were no significant differences either in the number of therapeutic INR values per patient (50.53 +/- 23.72% vs. 51.74 +/- 26.68%, P = 0.795) or in individual quality of treatment: > 50% therapeutic INR values (60.0% vs. 64.9%, P = 0.721) and > 75% therapeutic INR values (18.3% vs. 22.8%, P = 0.714) in the warfarin and acenocoumarol group, respectively. Significantly better stability was determined for acenocoumarol as compared with warfarin treatment in terms of a longer period of the total observed time during which therapeutic INR values were stable (37.6% vs. 35.7%, P = 0.0002). CONCLUSION: Both drugs have shown similar quality of individual anticoagulation control, but acenocoumarol have shown significantly better anticoagulation stability with therapeutic INR values covering significantly longer time of treatment.