Introduction: Oganophosphorus compounds (OP) bind to acetylcholinesterase (AChE) and inactivate it. In the synaptic cleft, undestroyed and accumulated acetylcholine produce the acute cholinergic effects. The aim of this study was to determine the frequency, speed of onset and intensity of certain signs of paraoxon poisoning depending on dose and outcome of poisoning. Methods: The study was conducted in adult Wistar rats. The median lethal dose (LD50) of paraoxon as well as protective ratio (PR) of atropine (10 mg/kg intramuscularly) was determined. Clinical signs of poisoning were observed: fasciculations, tremor, seizures, ataxia, piloerection, lacrimation, exophthalmos, bizzare/stereotypic behaviour and dyspnoea. The time from paraoxon injection to the first appearance of the sign of poisoning was recorded as well as the intensity of poisoning with evaluation at 10 time intervals throughout the 4 h observational period. Results: The LD50 of paraoxon was 0.33 mg/kg (subcutaneously) and PR of atropine was 2.73. Dose-dependent, piloerection occurred more often (p = 0.009) and at higher intensity (p = 0.016) at higher doses. Fasciculations, tremor, seizures and ataxia occurred significantly earlier at higher doses of paraoxon (p = 0.015, 0.002, 0.021 and 0.016, respectively), as well as the intensity of seizure, tremor and fasciculation. Piloerection (p = 0.002) and seizures occurred more frequently (p = 0.009) in non-survivors. Fasciculations, tremor, seizures and ataxia occurred significantly earlier and at higher intensity in non-survivors (p < 0.001, for all parameters), as well as dyspnoea (p = 0.009 and p = 0.048). In atropine-protected rats, nicotinic effects persevered, so they were the prognostic parameter of the severity of the poisoning. Conclusion: Seizures and fasciculations followed by tremor were strong prognostic parameters of the probability of lethal outcome of paraoxon poisoning. Also, the mentioned poisoning signs were with their intensity and speed of occurrence in a clear positive correlation with the administered dose of paraoxon. Even at high doses of paraoxon, atropine blocked the muscarinic (but not nicotinic) effects and somewhat mitigated the CNS toxic effects.

This editorial presents the analysis of volumes 50 (2019) and 51 (2020) of Scripta Medica. Original articles made 53 % of 80 articles published in these two volumes. Article rejection rate was 38 %. Mean duration of period until reaching the first decision on an article was 20 days, while mean time until reaching the final decision was 31 days. Mean time needed for accepting the revised manuscript was 3 days, reflecting a significant decrease from 5 days in 2019 to 2 days in 2020. Mean time needed for reaching a decision to reject an article was 7 days. Coverage of the journal included both basic and clinical research and a considerable space was devoted to articles on COVID-19. Further efforts will be made in order to reach a more international recognition of the journal.

In Issues 1 and 2 the scientific biomedical journal Scripta Medica devoted a total of six articles to the aetiological, epidemiological and clinial aspects of serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease caused by this virus coronavirus disease 2019 (COVID-19). The present Issue 2 also contains an obituary on the occasion of demise of Professor Folke Sjöqvist, one of the founding fathers of clinical pharmacology as a discipline and several other articles from the fields of quality assurance in healthcare, experimental and clinical medicine.

Background: The purpose of this study was to assess the antiviral efficacy and safety of the direct-acting antivirals (DAAs) in therapy of chronic hepatitis C virus (HCV) infection. Methods: This real-life multi-centric study was performed at the Clinic for Infectious Diseases, University Clinical Centre of the Republic of Srpska, Banja Luka and it included a total of 89 patients. All patients received the adequate doses of ombitasvir (OBV)/ paritaprevir (PTV)/ritonavir (RTV) + dasabuvir (DSV) plus ribavirin (RBV). RBV was given to all patients except to those with HCV sub-genotype 1b. DSV was not administered to patients infected with HCV genotype 4. For the majority of patients the treatment duration was 12 weeks. For ten patients with liver cirrhosis the duration of treatment was 24 weeks. Viraemia was assessed at three points in time: at baseline, 12 or 24 weeks after the beginning of treatment (end of treatment response ETR), and 12 weeks after the end of treatment (sustained viral response SVR). Results: Complete ETR after 12 weeks of treatment was achieved in 79 patients, while in 10 high-risk patients it was achieved after 24 weeks of treatment. Full SVR was recorded in 88 patients 12 weeks after the end of treatment. This therapy was well tolerated and mild adverse effects were recorded in only 10 patients. Conclusion: Treatment of patients with chronic HCV infection with OBV/PTV/ RTV+ DSV + RBV resulted in excellent antiviral activity and mild adverse events.

Background/Aim. Drug utilisation monitoring could identify drug-related problems and hence improve the awareness of irrational drug use. The objective of this study was to analyse the drug utilisation patterns in a rehabilitation hospital over the period 2011?2016. Methods. The Anatomic Therapeutic Chemical classification/Defined Daily Dose (ATC/DDD) methodology was used to monitor the drug utilisation expressed as a number of DDD per 100 patient-days (HPD). The values of DDDs were obtained from the World Health Organisation (WHO) Collaborating Centre for Drug Statistics Methodology. Utilisation trends were analysed by means of the Compound Aggregate Growth Rate (CAGR), which is defined as an average annual change rate of some value during the period of interest. Results. The number of patient-days increased during the six years period; the CAGR being1.8% annually. At the same time, the total number of dispensed DDDs as well as the number of DDD/HPD decreased with the CAGR of -2.0% and -3.7% respectively. The average drug cost per patient-day varied from BAM 1.38 in 2013 to 0.95 in 2016; the CAGR being -1.8%. The most utilised drugs belonged to the ATC groups C, A, B, M and N and they contributed to an average of 77% of all drugs used each year. On the top of the list of most utilised drugs were: hydroxocobalamin, thioctic acid, enalapril, diclofenac, amlodipine, acetylsalicylic acid, pantoprazole, paracetamol and bromazepam. Conclusions. The overall drug utilisation in the hospital was modest and almost equal in 2016 compared to 2011. Besides the leading consumption of vitamin B12 and thioctic acid, this study points out some interesting prescribing patterns, such as predominant use of diclofenac over ibuprofen, and overuse of proton pump inhibitors. There is a need for educative interventions among physicians in order to improve their prescribing practice.

Background/Aim. The era of direct-acting antiviral (DAA) regimen in the treatment of chronic hepatitis C virus (HCV) started in 2011. The aim of this study was to assess the antiviral efficacy and safety of DAA regimen, ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) + dasabuvir (DSV) + ribavirin (RBV), in patients with chronic HCV infection, genotype 1. Methods. The real-life data were collected. The study was multicentric and included seven infectious diseases and hepatology departments in Serbia. A total of 21 patients were enrolled in the OBV/PTV/r + DSV + RBV early access program, 20 of which were previously treated with pegylated interferon + RBV, while 1 was treatment-naive. All patients received the adequate doses of these antiviral drugs. RBV was not given to the patients with HCV genotype 1b infection according to the therapeutic protocol. For the majority of patient, the treatment duration lasted for 12 weeks. For the patients with liver cirrhosis, who were infected with HCV genotype 1a, the duration of treatment was 24 weeks. Viremia was assessed at four points in time: at baseline, 4 weeks after the treatment beginning (rapid viral response, RVR), 12 or 24 weeks after the treatment beginning (end of treatment response ? ETR) and 12 weeks after the end of treatment (sustained viral response ? SVR). SVR, as a confirmation of the absence of HCV was considered as endpoint of successful treatment. Results. Complete RVR, ETR and SVR were achieved in 64.71%, 85.71% and 95.24% of the patients, respectively. Only 3 patients had mild adverse effects which did not required dose reduction. Conclusion. The treatment of the patients with a chronic HCV infection with OBV/PTV/r + DSV + RBV resulted in excellent antiviral activity and tolerability.