Background: Acute nasopharyngitis is often treated with hypertonic saline that can be combined with additional compounds, such as lysozyme. The aim of this study was to compare efficacy and safety of hypertonic saline solution with or without lysozyme in the treatment of acute nasopharyngitis. Methods: Non-interventional, prospective, multicentre, observational, parallel study was conducted on adult subjects with symptoms of acute nasopharyngitis. Subjects were divided into hypertonic saline or lysozyme group (receiving slightly hypertonic nasal spray with addition of lysozyme). Time until the patency of both nasal passages was measured after the first application of therapy. The congestion severity was assessed by using a visual analogue scale before the therapy application, after 30 minutes, and after seven days. Adverse reactions were monitored and evaluated.   Results: The total number of included subjects was 252 (60 in the hypertonic saline group and 192 in the lysozyme group). In both groups, a significantly better assessment of the severity of the nasal passages’ obstruction was recorded after 30 minutes and seven days from therapy start (for all compared time intervals p<0.001). The lysozyme group had a significantly lower nasal congestion score compared to hypertonic saline 30 minutes after therapy (p<0.001) and seven days from the therapy start (p=0.001). In the hypertonic saline group, a significantly shorter time was observed to establish the patency of the nasal passages after the first therapy application (p<0.001). All adverse events were mild. Conclusions: Addition of lysozyme to slightly hypertonic nasal spray brings added value in the pharmacotherapy of acute nasopharyngitis.

Introduction: Benign prostatic hyperplasia (BHP) is one of the most common, progressive diseases in elderly men. It is very important to diagnose this disease in its early stages. The international prostate symptom score (IPSS) is a very helpful tool to be used for this purpose. Aims: The main goal of this study was to analyze the signs and symptoms of benign prostatic hyperplasia and its impact on a patient's quality of life. Patients and Methods: This descriptive randomized study included 112 male examinees aged 50-70 years. We used IPSS as a survey tool. Results: The average age of the examinees was 61.02 (± 6,18). 56.3% of examinees had mild symptoms, 31.3% had moderate symptoms and 12.5% of our examinees had severe lower urinary tract symptoms. Nocturia was the most common symptom. Irritative symptoms were present in 76.8% of examinees compared to obstructive symptoms which occurred in 8.9%, and 14.3% had both types of symptoms. Hypertension was the most common comorbidity (in 50.9% of cases). The majority of examinees answered that they would be satisfied with their quality of life if their symptoms do not change in the future. Conclusions: Assessment of symptoms and signs of benign prostatic hyperplasia using IPSS in clinical practice has proven to be useful in the timely approach of clinical physicians.

Background: Acute nasopharyngitis is a common condition usually accompanied by nasal congestion. The aim of this study was to compare efficacy and safety of the spray containing xylometazoline and lysozyme with spray containing only xylometazoline in the treatment of acute nasopharyngitis.Methods: Prospective, comparative, post-marketing study was performed on subjects with acute nasopharyngitisdivided into xylometazoline+lysozyme or xylometazoline nasal spray groups. Data collection was performed at the baseline before and 30 minutes after the therapy application and seven days after baseline.Main findings: Out of 173 included subjects, 59 were in the xylometazoline+lysozyme and 114 in the xylometazoline group. In both groups nasal patency was significantly improved 30 minutes after the therapy application (p<0.001). In the xylometazoline+lysozyme group all subjects had nasal decongestion within 20 minutes and this was significantly shorter (p=0.037) compared to xylometazoline group where 16 subjects (14%) needed 20 to 120 minutes for nasal decongestion. All adverse events were mild and there was no significant difference in the number of adverse events between the groups.Principal conclusions: Nasal sprays containing xylometazoline with or without lysozyme were effective and safe in the treatment of acute nasopharyngitis. Nasal spray containing xylometazoline with lysozyme showed a faster effect with significantly shorter time to nose decongestion. All recorded adverse events were mild and there was no difference between the groups in the number of recorded adverse events. Key words: nasopharyngitis, nasal obstruction, lysozyme, xylometazoline,nasal sprays

Context: Rivaroxaban is an oral direct factor Xa inhibitor reducing the risk of systemic embolism and stroke in patients with nonvalvular atrial fibrillation. Aims: The primary objective was to evaluate the effectiveness of rivaroxaban therapy in reducing the risk of systemic embolism and stroke in patients with nonvalvular atrial fibrillation, whereas secondary objectives were to monitor therapy safety and the patients' adherence to treatment. Settings and Design: The prospective, postmarketing clinical trial was conducted on patients with nonvalvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, and diabetes mellitus, who suffered a stroke or a transient ischemic attack. Subjects and Methods: At the baseline visit, the CHA2DS2 score was determined, and therapy was introduced. At three control visits (1, 3, and 6 months after baseline), systemic embolism, stroke, bruises, or bleeding occurrences were recorded. Furthemore, adverse events were monitored, and the Morisky score (MMAS-8) for treatment compliance was determined. Results were compared to previous studies. Results: The study included 471 patients. The incidence rate in events per 100 patient-years (95% confidence interval) was 2.6 (0.1–5.1) for systemic embolism and 4.3 (1.6–7.0) for stroke. The most common form of bleeding during rivaroxaban therapy was epistaxis. Adverse events were reported in 12 (2.7%) patients. Therapy adherence was in the range of medium adherence for the entire study period, with the average score decreasing significantly from the 1st to 6th months (P < 0.001). Conclusions: Rivaroxaban showed good efficacy and safety in reducing the risk of systemic embolism and stroke in patients with nonvalvular atrial fibrillation including patients with comorbidities.

Background: Acute gastroenteritis remains an extremely common problem among the general population. In Western countries, an average person will probably face one or two episodes of gastrointestinal infections every year. Objective: The aim of this study was to compare the efficacy of nifuroxazide and probiotic preparation containing lactic acid bacteria in the treatment of acute diarrheal syndrome. Methods: The study was prospective, comparative study. Patients who suffered from acute infective diarrhoea for ≤72 hours and had ≥3 unformed stools per day, with no administration of antibiotics during 10 days before enrolment were divided into two groups: nifuroxazide group and the lactic acid probiotic group. All patients received therapies four times a day for three days. Data was collected at the baseline visit (before the initiation of the treatment) and two follow-up examinations on the third and seventh day from the treatment start. Results: The study included 61 patients, 36 in nifuroxazide group and 25 in probiotic group. Nifuroxazide group compared to probiotic group showed faster improvement of patients’ condition with lower number of stools three and seven days after therapy start (p=0.001 and p<0.001 respectively) and faster stool consistency normalization. On the seventh day from therapy start medium mushy stool consistency was observed in the majority of patients in nifuroxazide group (n=31, 86%) and only in small number of patients in probiotic group (n=5, 20%). Patients were feeling better and there was a trend of reporting better therapy efficacy in nifuroxazide group. Subjective assessment of therapy tolerability was also better in nifuroxazide group. Compliance to therapy and recommended dietary regime was similar between groups and there were no significant differences between groups regarding age, gender, elevated body temperature, abdominal pain, cramps, nausea and vomiting. Conclusion: Although probiotics are sometimes used in the treatment of acute diarrheal syndrome, nifuroxazide has better efficacy and greater patients’ satisfaction. Nifuroxazide can be recommended as the first choice empirical treatment in adult patients with the acute diarrheal syndrome.

Objective. The objective of this non-interventional post-marketing clinical trial was to analyze the antihypertensive effect and safety of a fixed combination of perindopril and indapamide in the treatment of unregulated essential hypertension. Patients and Methods. The prospective clinical trial included patients aged 20 to 75 years with essential hypertension and blood pressure values ≥140/90 mmHg at baseline. On the basis of the investigator’s decision, patients received 2 mg perindopril + 0.625 mg indapamide (group 2+0.625) or 4 mg perindopril + 1.25 mg indapamide (group 4+1.25). Results. The study included 1173 patients (426 patients in group 2+0.625 and 747 patients in group 4+1.25) at 27 investigational centers in Bosnia and Herzegovina. Mean blood pressure values at baseline and visits after nine months were significantly higher in the 4+1.25 group compared to the 2+0.625 group. There was a significant drop in systolic and diastolic blood pressure in both groups. The target values of systolic and diastolic blood pressure, according to the European Society of Cardiology (2018), were reached after nine months of therapy by more than 80% of patients in the 2+0.625 group, and this number was significantly higher compared to the 4+1.25 group where more than 60% of patients reached target values. Newly diagnosed patients had a better response to therapy. The percentage of patients receiving additional antihypertensive therapy decreased by the end of the study. Age, gender and the existence of diabetes mellitus were identified as negative predictors of target blood pressure achievement. The therapy showed a good safety profile. Conclusion. A fixed combination of perindopril and indapamide was effective and safe in the treatment of unregulated essential hypertension.

Objective. This study aimed to evaluate the efficacy and safety of lysozyme-based oral antiseptic in the therapy of non-infectious sore throat in teachers. Materials and Methods. A non-interventional, prospective, pilot study was conducted with two examinations. The first was performed as part of a general medical examination. If a non-infectious sore throat was confirmed by clinical checkup and all other inclusion and non-exclusion criteria confirmed, patients were offered to be enrolled in the study. After signing the informed consent form, patients were advised to use lysozyme-based lozenges, six times a day, for a period of five days. A telephone call follow-up examination was performed within 24 hours from the therapy completion. Results. This was a pilot study involving 25 adult patients of both genders. Lysozyme-based lozenges showed positive effects in relieving the symptoms of non-infectious sore throat in teachers. At the same time, the lozenges showed excellent tolerability, and no side effects were reported during the study. 92% of patients confirmed they would take the same medicine again due to the same problem. Conclusion. The results of this “proof-of-concept” study indicated that lysozyme-based antiseptic could be effective and safe in the treatment of non-infectious sore throat in teachers and should be further evaluated as treatment option in this condition.

Background: For many years, pharmacy and medicine were inseparable sciences, so everything that was done in the field of medicine, that is, treatment, can be related to pharmacy. The history of pharmacy therefore also includes the history of medicine, at least until the 13th century, when pharmacy was officially separated from medicine. Objective: The aim of this study was: to describe the books and monographs that are available on the Internet, which deal with the study of the history of Pharmacy; and to show pharmaceutical history museums around the world and their unique collections of pharmaceutical artifacts. Methods: During the preparation of this paper, a descriptive method of analysis from the available literature was used. The analysis of available literature included professional books, monographs, articles and other literature available on online browsers. Results and Discussion: Today there are a large number of societies, academies, associations and foundations dealing with the history of pharmacy. Also, a lot of books, monographs and scientific papers published in on-line databases. The goal of each organization is the research of historical facts in the field of pharmacy and medicine that will be shared with professionals, but also persons who are not from the profession (doctors, librarians, archaeologists, archivists). A large number of museums have been opened for the history of pharmacy, and almost every developed country has such a museum. Such museums represent a national treasure, because they preserve the valuables of pharmacy from the territory of the country, as well as the world.

Background: Alternative The topic of this article is the development of pharmacy in the Middle Ages. Objective: The aim of this paper is to bring readers closer to the development and importance of pharmacy and health activities in general of this century. Methods: This is sistematic review of the published papers about historical facts about development pharmacy in Bosnia and Herzegovina in the past. Results and Discusion: There are few documents that speak and testify about health and hygiene data and opportunities in Bosnia and Herzegovina from the Middle Ages and the time of the independent Bosnian state, because very little was written and mostly knowledge was transmitted by narrative. Bosnia, as an independent state, was first mentioned in the Charter of Kulin Ban in the 12th century. The Charter was sent to the Republic of Dubrovnik and provided safe passage for merchants through Bosnia and tax exemption. The Republic of Dubrovnik also had many influences on the development of all social conditions, including medicine and pharmacy. Doctors and pharmacists were able to come to Bosnia unhindered and engage in treatment and the sale of medicines, without having to fear whether they would pay taxes to the state or be robbed. Conclusion: Until Bosnia came under Ottoman influence, treatment in Bosnia was rather primitive, the number of pharmacies and health facilities was minimal, and hygienic conditions were rather poor. Folk medicine and spells were mainly practiced, which were passed down from generation to generation, by narrative tradition. Only with the arrival of the Ottomans, hospitals and pharmacies began to open, and the health care system was better regulated.

Background: Mobile pharmacies are special organizational units or infrastructures that serve to supply medicines to remote communities or are stationed on ships or as such exist during war conflicts on the battlefields to provide first aid to the wounded and to provide the necessary medicines. The establishment of mobile pharmacies is regulated by the law of each state and only preparations approved by law can be found in it. There are also regulations for the good storage and warehousing of these drugs. Objective: The aim of this article was to provide an overview of the available literature on the topic “Mobile pharmacies through history”, which shows the development and progress in the structure and function of mobile pharmacies throughout history. Methods: This is an descriptive study based on the searched available literature from the on-line databases regarding to present a historical overview of mobile pharmacies during the most significant war events in Europe and the USA. Results and Discussion: Mobile pharmacies were first mentioned in Egypt and the Roman Empire, but it was not until 1500 that military and ship’s doctors began using them, and wealthy nobles had their own boxes of medicines, which they carried on long voyages. Mobile pharmacies became more and more popular, so in the 18th century, practical manuals on the use of the contents of the box began to be published. The importance of a mobile pharmacy was shown in the wars, where people, before their appearance, died due to the impossibility of providing first aid on the battlefield. The advanced medicine and pharmacy that developed on land, greatly affected the health care at the sea. The constant incidence of infectious diseases, poverty and inadequate nutrition, insecurity of navigation and long voyages are the main reasons why sailors often fell ill and were exposed to injuries at work. A situation like that required that the problem of health protection on ships gets solved in accordance with the then principles of medicine and pharmacy. Conclusion: Authors demonstrated the importance of mobile pharmacies in treating and providing medical protection on boat trips. Regarding the ship’s pharmacies, pharmacists have the role of supplying ships with medicines, conducting training for captains and ship staff, advising shipping companies and captains on equipping ship pharmacies and advising on the preparation of national regulations and national ship pharmacy supply policy.

Sore throat is a common reason for seeking medical help [1]. It can have infectious and non-infectious etiology [2]. The term “sore throat” is usually associated with an infectious agent (bacteria, viruses, and less commonly fungi) [1,3,4]. The terms “throat discomfort“, “throat irritation“, or “functional dysphonia due to the occupational diseases“ (which represents voice disorder) are often used in the same sense as non-infectious sore throat [2,3]. It is identified by the exclusion of infectious etiology symptoms accompanied with persistent sore throat symptoms (tingling and scratching sensation in the throat, hoarseness or muffled voice, foreign body sensation in the throat, coughing, and difficulty in swallowing accompanied by pain) [2,5]. Various factors can lead to non-infectious sore throat. The most important are: environmental (exposure to smog and irritants), individual risk factors (smoking, alcohol and excessive caffeine consumption, incorrect technique of using voice, and snoring), existence of other diseases (allergies, hormonal disorders, gastroesophageal refluxes, and anxiety disorders), and the use of some medications [2,6]. Epidemiological studies for non-infectious sore throat are rare. In a study performed on 1326 adults in the USA, it was found that 6.6% of respondents had current voice disorders while lifetime prevalence was 29.9% [6]. Professions more susceptible to non-infectious sore throat have high demands on vocal performance (for example, teachers, singers, sports coaches, receptionists, television and radio presenters, lawyers, touristic tour guides, and politicians) [2,3,7]. In modern societies, about one-third of the working population belongs to occupations in which the voice is the primary tool [8]. Teaching is a high-risk occupation for developing voice disorders. In a study performed on 2531 adults in the USA, teachers had higher prevalence of lifetime voice disorders (57.7%) as compared to other professions (28.8%) [5]. Voice problems may lead to a lower quality of teaching and a serious personal and emotional burden. This can have detrimental effects on the career of teachers, with negative consequences on pupils and employers [9]. Despite the adverse impact of non-infectious sore throat on professional performance and reduced quality of life, only a small number of teachers is seeking professional medical help [10]. This can be due to a low level of awareness on this topic. Although exact mechanisms of non-infectious sore throat development vary with etiology, inflammation can be found in the majority of cases [2], with elevated pro-inflammatory cytokines such as interleukin (IL)-6, IL-β, and tumor necrosis factor-α (TNF-α) [2,11,12]. There has been little systematic assessment of treatments for non-infectious sore throat. The field lacks objective outcomes, with most studies relying on subjective (self-reported) endpoints [2]. Although there is no unique doctrine in the treatment, anti-inflammatory medicines and antiseptics are usually used. Inflammation is the pathophysiological mechanism of both infectious and non-infectious sore throat, so similar anti-inflammatory therapies have beneficial effects in both etiologies [2]. Few studies showed positive effects of non-steroidal anti-inflammatory medicines, paracetamol, and steroids [13]. Various herbal formulations and antiseptic lozenges, sprays, and mouthwashes (with or without the addition of an anesthetic or analgesic) are most commonly used [2,12]. Lysozyme is natural enzybiotic with properties that could be beneficial in the treatment of non-infectious sore throat. Different types of lysozymes can be found in nature. They have similar structures and share the ability to hydrolyze bacterial cell wall peptidoglycan [14]. Lysozyme is a significant part of the immune system. In humans, it can be found in body secretions, mucosal surfaces, liver, blood, and immune cells [14]. Human milk is rich in lysozyme, which plays an important role in our immunity from the first days of life [15]. The pharmaceutical industry is mainly using hen egg white lysozyme in products for treatment of certain infectious and inflammatory diseases [16]. Besides its direct antibacterial activity, lysozyme has immunomodulatory and anti-inflammatory effects. Immunomodulatory effects have been demonstrated in cancer patients after chemotherapy, where it improved the recovery of CD4+/CD8+ lymphocyte ratio [17]. One of the proposed mechanisms is through the release of immunomodulatory Lysozyme in the treatment of non-infectious sore throat

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.

Aim To develop and validate a screening questionnaire for migraine without aura with sufficient diagnostic accuracy to be used in primary care settings. Methods The study was designed as cross-sectional, multicentric, diagnostic accuracy trial of new questionnaire for screening patients who visit general practitioners, with an aim to reveal migraine without aura. The instrument was constructed for the purpose of this study, and validated on the sample of 429 primary care outpatients. The gold standard of diagnosing migraine without aura was clinical estimate by a neurologist based on the International Classification of Headache Disorders 3rd edition (ICHD-III) criteria. Diagnostic accuracy of the instrument was tested through construction of the Receiver Operator Curve. Results The Balkan Migraine Screening Questionnaire (BMSQ) instrument showed good diagnostic accuracy (sensitivity 83.4% and specificity 79.9%) for migraine without aura, with significant screening yield among previously undiagnosed patients of 75.9%. The study also confirmed a high percentage of patients with hidden migraine without aura (MWA) (52.9%) revealed by the BMSQ and the ICHD-III criteria that would otherwise remain undiagnosed. Conclusion The BMSQ is a valid and reliable clinical instrument for revealing migraine without aura, which could be easily selfadministered by patients. It has high screening yield, discovering majority of patients with previously undiagnosed migraine without aura, whose definite diagnosis should later on be confirmed by the attending physicians using the ICHD-III criteria.