Evaluation of Published Preclinical Experimental Studies in Medicine: Methodology Issues.

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.

Efficacy and Safety of Lysozyme, Cetylpyridinium and Lidocaine Fixed Combination for Treatment of Chemotherapy- and Radiotherapy-Induced Oral Mucositis: a Pilot Study.

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.

Efficacy and safety of local lysozyme treatment in patients with oral mucositis after chemotherapy and radiotherapy.

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.

Comparative Study of the Efficacy of the Lysozyme, Benzydamine and Chlorhexidine Oral Spray in the Treatment of Acute Tonsillopharyngitis - Results of a Pilot Study.

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.

Observational multicenter study of efficacy of paroxetine filmcoated tablet in the treatment of anxiety disorder.

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.

An Instrument for Rating Quality of Life Related to Sore Throat in Patients Suffering from Acute Pharyngitis or Tonsillitis.

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.

Efficacy of carbocisteine in the treatment of chronic obstructive pulmonary disease and impact on the quality of life.

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.