Abstract This observational clinical study was composed of two substudies: a non-comparative one (n = 166), testing only lysozyme-based compounds (LBCs), and a comparative substudy (n = 275), testing both LBCs and bicarbonate-based local compounds (BBCs) on the healing of oral mucositis during radio- or chemotherapy. The density of ulcerations has decreased significantly after the treatment with lysozyme in both substudies. The density of ulcerations in the radiotherapy group was lower in patients treated with LBCs compared to patients treated with BBCs (p < 0.001). In the chemotherapy group, reduction of ulceration density was similar with both LBCs and BBCs. The LBCs reduced pain intensity during the intake of solid food and speech more than BBCs in both patient cohorts (p < 0.05). In the radiotherapy cohort, pain intensity when consuming liquid foods was reduced more with LBCs than with BBCs (p < 0.05). No adverse events were recorded. This study demonstrates the advantages of treating oral mucositis during radiotherapy or chemo-therapy with LBCs.

Introduction: Inappropriate design of experimental studies in medicine inevitably leads to inaccurate or false results, which serve as basis for erroneous and biased conclusions. Aim The aim of our study was to investigate prevalence of implementing basic principles of experimental design (local control, replication and randomization) in preclinical experimental studies, performed either on animals in vivo, or animal/human material in vitro. Material and Methods Preclinical experimental studies were retrieved from the PubMed database, and the sample for analysis was randomly chosen from the retrieved publications. 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. 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 9% to maximum 86%. Average impact factor of the surveyed studies was high, and publication date relatively recent, suggesting generalizability of our results to highly ranked contemporary journals. Conclusion Prevalence of experimental preclinical studies that did not implement completely basic principles of research design is high, raising suspicion to validity of their results. If incorrect and biased, results of published studies may mislead authors of future studies and cause conduction of fruitless research that will waste precious resources.

Introduction: Beneficial effect of local administration of lysozyme in patients with recurrent aphthous stomatitis was demonstrated, but there are no published studies focused on treatment of chemotherapy or radiotherapy induced oral mucositis with lysozyme. Aim: The aim of this study was to compare efficacy and safety of Lysobact Complete spray (lysozyme, cetylpyridinium, and lidocaine) and compounded medication for local use in the treatment of radio- and chemo-therapy induced oral mucositis. Patients and Methods: This observational, phase IV study was designed as prospective cohort investigation, and conducted at two sites, Clinical Hospital Zenica and University Clinical Center Tuzla, Bosnia & Herzegovina, from August to November, 2018. The patients with oral mucositis after radio- or chemo-therapy were treated by either registered lysozyme-based or compounded medication (standardized and bicarbonate-based) for 21 days. Results: Both lysozyme-based (Lysobact Complete Spray) spray (lysozyme, cetylpyridinium and lidocaine) and compounded medication for local use were effective in local treatment of chemotherapy and radiotherapy-induced oral mucositis. However, lysozyme-based preparation was more effective, since signs of inflammation, number of oral ulcers and intensity of pain during eating and speaking withdrew to a greater extent than with highly variable compounded medication for local use. No adverse events were recorded in both treatment arms. Conclusions: Locally administered spray with fixed combination of lysozyme, cetylpyridinium and lidocaine (Lysobact Complete Spray) is very efficient and completely safe treatment of both radiotherapy and chemotherapy-induced oral mucositis.

OBJECTIVE Lysozyme is a natural antimicrobial and immunomodulatory enzyme, which is produced as a host response to infectious agents. The objective of this study was to compare the efficacy and safety of lysozyme-based versus benzydamine and chlorhexidinebased oral spray in patients with an acute tonsillopharyngitis associated with a common cold. PATIENTS AND METHODS A prospective twoarm pilot study (lysozyme/cetylpyridinium/lidocaine spray versus: benzydamine spray-arm 1; chlorhexidine/lidocaine spray-arm 2) was conducted in the primary health care unit. Efficacy was evaluated by the patient's self-assessment of pain, difficulty in swallowing and the throat swelling, by using the visual analog scale (VAS) at baseline and three follow-up visits. Safety was evaluated by the assessment of the frequency and severity of adverse effects. RESULTS Lysozyme-based spray reduced pain faster than benzydamine-based spray and slower than chlorhexidine-based spray. Lysozyme-based and chlorhexidinebased sprays similarly reduced difficulty in swallowing, but were faster than benzydamine-based spray. Similar effects on the reduction of throat swelling were seen in all treated groups. All tested products showed proper safety and were well tolerated, with no serious adverse events reported. CONCLUSIONS The lysozyme-based oral spray was shown to be effective and safe in the reduction of pain, difficulty in swallowing and throat swelling in patients with acute tonsillopharyngitis associated with a common cold. Lysozyme-based oral spray (containing natural compound with advantages of influencing immune system and preventing recurrences) had similar activity to benzydamine and chlorhexidine-based oral antiseptic sprays.

Objectives: The aim of the study was to test the efficiency, compliance of patients and tolerance to the lisinopril and hydrochlorothiazide treatment. Methods: We conducted an observational, nonintervention multicentric study in 19 centers in Bosnia and Herzegovina. The study included 147 patients of both sexes diagnosed with essential hypertension who were already ordinated by antihypertensive therapy. The patients were monitored for 12 weeks, i.e. one initial and four control examinations. Results: The fixed combination of lisinopril and hydrochlorothiazide lowered the values of systolic and diastolic blood pressure for an average of 31/15 mmHg in patients aged 30 to 59 and for an average of 30/10 mmHg in patients over 60 years. The aimed blood pressure values were achieved in 82.31% of patients. The patients’ compliance was evaluated as very good for 87.07% of patients, good for 10.88% of patients and unsatisfactory for 2.04% of patients. Conclusion: Fixed combination of lisinopril and hydrochlorothiazide is efficient and well tolerable with very good compliance of patients. Keywords: Lisinopril, hydrochlorothiazide, fixed combination, efficiency, compliance

Aim To examine the efficiency of paroxetine treatment of anxiety disorders in adult patients over the period of 12 months and the improvement of symptoms of anxiety disorder during this period, as well as to examine the tolerability of the administered treatment and patient compliance during the study. Methods This observational, multicenter, cohort, clinical study included 171 patients with diagnosed anxiety disorder who were administrated paroxetine film-coated tablets 20 mg and followed up during the next 12 months. Patients were observed at 6 points, baseline and five additional assessments. The Beck Anxiety Inventory was used to determine the baseline severity of anxiety and Patients Health Questionnaire module GAD-7 was used to determine the severity of anxious symptoms and to follow up patients during the additional observations. Tolerability and patient compliance were followed throughout the study. Results Statistically significant decline in severity of anxiety disorder over the observation period (p=0.001) was found. At the beginning of the study, 64 (45.7%) patients had severe anxiety symptoms, 43 (30.7%) moderate, 25 (17.9%) mild and eight (5.7%) had none to minimal symptoms. At the end of the study, there were no more patients with severe anxiety, while four (3.4%) had moderate symptoms. On the other hand, 26 (22.2%) had mild symptoms and 87 (74.4%) had none to minimal symptoms of anxiety disorder. Conclusion The results of this study provide further evidence for paroxetine's efficacy and tolerability in the treatment of anxiety disorders with good patient compliance.

Objectives: The aim of this study was to investigate the effects of carvedilol treatment through improvement of New York Heart Association (NYHA) class, ejection fraction (EF) and blood pressure (BP) values in patients with chronic heart failure (CHF). Methods: This multicenter, observational, non-interventional was conducted in 25 medical centers in Bosnia and Herzegovina, from April 2015 until December 2015 (nine months). It included 167 patients of both genders, older than 50 years, who were diagnosed with CHF according to the NYHA classification and had EF <50%. The patients were administered carvedilol tablets and were followed during six visits: baseline and five follow-ups, over the period of 24 weeks. Results: At the beginning of the study, CHF NYHA class I was present in 5 (3.0%) patients, NYHA class II in 76 (45.5%) and NYHA class III in 66 (39.5%) patients. After 24 weeks, CHF NYHA class I was present in 43 (25.7%) patients, NYHA class II in 75 (44.9%) and NYHA class III in 21 (12.6%) patients. There is a statistically significant change of NYHA class before and after 24 weeks of treatment with carvedilol (rho=0.272; p=0.002). At the baseline observation, mean value of EF was 43.06±9.6%. after 24 weeks of treatment, the mean value of EF increased to 48.15±10.51% (p=0.0001). Average increase of EF after the treatment was 5%, or ranging from 1.5-7.5%. Systolic and diastolic blood pressure significantly decreased from baseline to final observation (-15.4 mmHg and -9.18 mmHg; p=0.0001). Conclusion: Carvedilol is effective in improvement of NYHA class and ejection fraction as well as in reduction of high blood pressure in patients with congestive heart failure. Keywords: chronic heart failure, NYHA classification, carvedilol, treatment efficacy

Introduction: Quality of life in patients with acute pharyngitis or tonsillitis is significantly lower than in healthy persons, and it should be taken into account when efficacy of new therapeutic options is investigated. Objective: The aim of this study was to develop and validate a reliable instrument that can measure quality of life in adult outpatients with sore throat caused by acute pharyngitis or acute tonsillitis. Method: The study was of a cross-sectional type, and assessed reliability and validity of newly developed questionnaire for measurement of quality of life in adult outpatients with sore throat (STQoL) caused by acute pharyngitis or acute tonsillitis. It was conducted on a sample of 282 patients, with mean age 39.0 ± 14.8 years, male/female ratio 104/178 (36.9%/63.1%). Results: Final version of the STQoL scale with 21 items showed excellent reliability, with Cronbach’s alpha 0.949. It was temporally stable, and both divergent and convergent validity tests had good results. Factorial analysis revealed three domains, Social/psychic aspects, Physical aspects and Environmental aspects of sore throat related quality of life. Conclusions: The STQoL scale is reliable and valid specific instrument for measuring sore throat related quality of life, which is an important treatment outcome in patients with acute pharyngitis or tonsillitis.

Aim To investigate the effects of carbocisteine treatment in the reduction of frequency of productive cough episodes, preventing disease progression and improving the quality of life as well as the tolerability of the administered treatment and patient compliance during the study. Methods This observational, non-interventional, multicenter, cohort study included 501 patients with chronic obstructive pulmonary disease (COPD) who were administrated carbocisteine capsules 375 mg and followed up during the next 15 days. The patients were observed at 3 points, baseline and two additional assessments. General clinical condition of patients, along with the spirometry testing at all three points were examined. Thr quality of life was assessed on the 1st and 3rd observation with Leicester Cough Questionnaire. Tolerability and patient compliance were measured throughout the study. Results There was a significant change of forced expiratory volume in 1 second (FEV1) status between the second and third observation (p=0.002). Examination of general symptoms showed a statistically significant reduction in cough by 74.9%, in sputum production by 48.5%, in dyspnea by 29% and in fatigue by 50%. After the administration of carbocisteine the median value of overall quality of life was 3.79 (3.63 - 3.89). Conclusion 375mg carbocisteine capsules were found to be effective and well-tolerated in the treatment of COPD, with a small percentage of reported mild adverse reactions and with a significant improvement of quality of life.

Objectives : The primary objective of the study was to examine the effectiveness of azithromycin in the treatment of acute tonsillitis, pharyngitis, tonsillopharyngitis in adults (reduction or withdrawal of clinical symptoms), and the secondary objective of the study was to examine the tolerability of the administered treatment and patient compliance during the study. Methods : This multi-centric, non-interventional study included 297 subjects with acute tonsillitis, pharyngitis or tonsillopharyngitis. Patients were administered film-coated tablets - azithromycin 500 mg (Azomex®) and followed-up 4 to 5 days. The patients were observed at 2 time points; baseline and one additional assessment. At both time points, we examined physical findings, general condition of the patient to establish severity of the disease. We also measured the tolerability and patient compliance. In the test lists of subjects, the physician, assessed the effectiveness of azithromycin according to the Likert’s scale. Results : A total of 297 patients were included in the study. The median of symptom improvement was 3 (2.0-4.0) days, with 60 (28.1%) patients who had improvement after 2 days of administration, 135 patients (45.8%) after 3 days of administration, while the 77 patients (26.1%) experienced symptoms improvement within the period of 4 to 6 days after the start of treatment. The treatment outcome was successful in 260 (89.0%) patients, while in 32 (11.0%) the treatment outcome was unsuccessful, which was a significant difference in the successfulness of treatment with azithromycin ( X 2 =159.0; p<0.001). Tolerability of azithromycin was reported to be very good by 235 patients (80.8%), good by 32 (11.0%) and unsatisfactory reported by 8 (2.7%) patients. Conclusion : The effectiveness and tolerability of the drug azithromycin (Azomex ® ) film-tablets in the treatment of acute tonsillitis, pharyngitis, tonsillopharyngitis, was found to be good with a small percentage of reported mild side effects. Keywords : azithromycin, upper respiratory tract infection, tonsillitis, pharyngitis, drug effectiveness