Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives.

Lipophilicity, a significant physicochemical parameter of bioactive molecules, along with absorption, distribution, metabolism, excretion parameters and toxicity risk, was investigated for 32 thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives with anti-inflammatory potential. The experimental lipophilicity study was carried out by reversed-phase thin-layer chromatography in a binary isopropanol-water mobile phase, and the obtained results were compared with the theoretical lipophilicity parameters estimated by various computational methods. Strong correlations were found between the experimental retention factors and calculated partition coefficients. A modified Petra/Osiris/Molinspiration analysis was performed on the previously synthesized compounds, using SwissADME, Osiris and Molinspiration web tools. The predicted in silico parameters highlighted the most promising compounds as potential drug candidates. The compounds showed good gastrointestinal absorption, moderate activity according to the bioactivity score (values situated between -1.25 and -0.06), and a safe toxicity profile. The results obtained in this study will contribute to lipophilicity studies and other future studies focused on modulating new drug candidates starting from thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives, which are important heterocycles in medicinal chemistry.

Utilization of psychotropic medicines in Romania during 1998-2018.

Background: Mental disorders can have a significant impact on patients' life, including economic, social and individual consequences, and psychotropic medication is essential to treat these conditions. Psychotropic drug utilization studies contribute to a clearer picture of the management of these conditions. Data published from Romania on this topic is limited. The present study aims to characterize the utilization patterns of anxiolytics, antidepressants (ADs), and antipsychotics (APs) in Romania during 1998-2018. Methods: Drug utilization data were provided by Management Center for Documentation, Information and Marketing (CEGEDIM) Romania and quantitative data for each psychotropic medicine were converted to total defined daily doses (DDDs) and to DDD/1000inhabitants/day (DDD/TID). The total use of medicines in DDD/TID was computed in order to obtain the drug utilization 90% (DU90%) segment. Results: An increasing trend in total utilization of psychotropic medicines in Romania started in 2004. Anxiolytics use was predominant until 2013 and the yearly anxiolytic use over the entire study period remained between 10 and 15 DDD/TID. Diazepam lost popularity over time in detriment of the utilization of other anxiolytic benzodiazepines, such as alprazolam and lorazepam. ADs utilization markedly increased during the study period (the average annual growth rate was 13.66% starting 1999). Selective serotonin reuptake inhibitors (SSRIs) became present on the 2008 DU90% and was the dominant class of ADs, with sertraline being the most prescribed, followed by escitalopram and paroxetine. APs utilization showed an increasing trend from 2003 until 2018. Atypical APs became present on the 2008 DU90%, while typical APs were no longer included in the 2018 DU90%. Among atypical APs, olanzapine was the main agent prescribed, and starting 2010 was followed by quetiapine and risperidone. The uptake of APs long-acting formulations became more evident during the last analyzed years (2015-2018). Conclusion: We observed an increasing utilization of APs and a more prominent increase in ADs utilization in Romania during 1998-2018. The anxiolytic prescribing remained nearly stable during this time. Further research can bring more information on the various factors influencing psychotropic utilization in Romania.

Effectiveness and Protection Duration of Anti-COVID-19 Vaccinations among Healthcare Personnel in Cluj-Napoca, Romania.

The anti-COVID-19 vaccines, developed for use during the pandemic period, must be evaluated for effectiveness in order to coordinate the vaccination program. Therefore, this study aimed to measure the anti-COVID-19 vaccine effectiveness (VE) and duration of protection against symptomatic forms of infection among healthcare personnel who were professionally exposed to the SARS-CoV-2 virus. A prospective cohort study, which was conducted in a university hospital between January 2021 and April 2022, compared immunologically naïve and previously infected personnel who were vaccinated, revaccinated, or unvaccinated. The VE was measured based on survival rates constructed with the actuarial method, using 30 day intervals. Among the 783 subjects that were included in the study, those that were vaccinated showed a decrease in VE from 90.98% (95% confidence intervals (CI): 74.87-96.77) in the first 30 days to 69.95% (95% CI: 40.29-84.87) at 60 days after vaccination. The VE for revaccinated personnel was 93.27% (95% CI: 77.53-97.99) at 60 days and 86.54% (95% CI: 75.59-92.58) at 90 days after revaccination. For previously infected personnel, protection against reinfection was 94.03% (95% CI: 79.41-98.27) at 420 days and 82.08% (95% CI: 53.93-93.03) at 450 days after revaccination. The highest VE for preventing the symptomatic forms of COVID-19 was observed in the revaccinated, but only for a 3-month duration. Better protection against reinfection was provided by revaccination after passing through infection.

Nation-Wide Survey Assessing the Knowledge and Attitudes of Romanian Pharmacists Concerning Pharmacogenetics.

Background: Pharmacogenetics (PGx) is an important component of personalized medicine that has the potential to improve medicines' effectiveness and safety. However, despite progress in technology and availability, PGx testing application into patient-care in Eastern Europe countries, has been slow. Objectives: Our aim was to describe knowledge and attitudes of Romanian pharmacists concerning PGx, and identify potential factors limiting PGx implementation. Method: An anonymous, web-based questionnaire was distributed to Romanian pharmacists registered in the National Pharmacists' Association (NPA) via an official e-mail sent by NPA representatives. Results: A total of 1,058 pharmacists completed the questionnaires, resulting in a response rate of 7.6%. Pharmacists were predominantly female (90.1%), younger than 49 years (87.5%) and mostly worked in community pharmacies (80.2%). Most pharmacists (64.8%) had a knowledge score between 30 and 49 points out of 60, and (75.4%) had attitude scores between 9 and 7 out of 10. Attitude and knowledge scores positively correlated. Conclusion: Despite performing fairly well on general questions regarding PGx, Romanian pharmacists may lack in-depth knowledge, which can affect their readiness to discuss PGx information with patients or other healthcare professionals. High pricing was considered an important impediment in PGx implementation.

Safety of Antibiotics in Hospitalized Children in Romania: A Prospective Observational Study.

Antibiotics are among the most prescribed drugs in pediatric inpatients and are frequently associated with adverse drug reactions (ADRs) in children. This study aimed to assess the frequency and type of ADRs related to the use of antibiotics in pediatric inpatients through a prospective observational study, conducted over 6 months, covering the winter and spring seasons when the incidence of infections peaks in Romania. ADRs were evaluated for causality, avoidability and severity. Among the 266 included children, 25 (9.4%) experienced 30 ADRs. ADR frequency tended to be higher in ≤2-year-olds (13 of 25, 52.0%) than in other age categories. Gastrointestinal and hematological ADRs were most frequently observed. Diarrhea was the most common ADR associated with antibiotics (8 of 30, 26.7%). Ceftriaxone (16 of 30, 53.3%), cefuroxime, ceftazidime and azithromycin (3 of 30, 10.0% each) were most commonly responsible for ADRs. After causality assessment, 2 (6.7%) ADRs were considered definite, 12 (40.0%) probable and 16 (53.3%) possible. One ADR was classified as definitely avoidable and one as possibly avoidable. Seven children required treatment for ADRs. Antibiotic treatment was discontinued in 4 children. Antibiotics frequently caused ADRs in ≤ 2-year-olds and were commonly associated with gastrointestinal symptoms. Close monitoring of antibiotic-associated ADRs remains important in the pediatric population.

Artificial Intelligence and Antibiotic Discovery.

Over recent decades, a new antibiotic crisis has been unfolding due to a decreased research in this domain, a low return of investment for the companies that developed the drug, a lengthy and difficult research process, a low success rate for candidate molecules, an increased use of antibiotics in farms and an overall inappropriate use of antibiotics. This has led to a series of pathogens developing antibiotic resistance, which poses severe threats to public health systems while also driving up the costs of hospitalization and treatment. Moreover, without proper action and collaboration between academic and health institutions, a catastrophic trend might develop, with the possibility of returning to a pre-antibiotic era. Nevertheless, new emerging AI-based technologies have started to enter the field of antibiotic and drug development, offering a new perspective to an ever-growing problem. Cheaper and faster research can be achieved through algorithms that identify hit compounds, thereby further accelerating the development of new antibiotics, which represents a vital step in solving the current antibiotic crisis. The aim of this review is to provide an extended overview of the current artificial intelligence-based technologies that are used for antibiotic discovery, together with their technological and economic impact on the industrial sector.

Drug utilisation study of antidiabetic medication during 2012-2019 in Romania.

BACKGROUND: To analyse the antidiabetic medication (ADM) market trends in Romania and to describe the utilisation of the new ADMs (glucagon-like peptide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase-4 inhibitors [DPP-4i] and sodium-glucose transport protein 2 inhibitors [SGLT-2i]). METHODS: We conducted an analysis of pharmacy claims data from IQVIA Romania. We analysed the reimbursed prescriptions that included at least one ADM as defined daily doses (DDDs)/1000 inhabitants/day and the number of prescriptions. RESULTS: The total number of ADMs DDDs/1000/day increased by 54.33% from 2012 (48.08) to 2019 (74.20). Biguanides, sulfonylureas and insulin were the most prescribed each year, with an increasing utilisation trend. In 2019 metformin represented 37.69% of the total market share, followed by sulfonylureas (29.94%) and insulin (23.93%). The newer antidiabetics uptake was low. In 2019 the number of DDDs/1000 inhabitants/day was 2.03 for DDP-4i, 2.39 for GLP-1 RA and 1.6 for SGLT2i. CONCLUSIONS: An overall trend of market increase was found for ADMs from 2012 to 2019, corresponding to the increasing prevalence of diabetes in Romania. Although the use of DPP-4i, GLP-1 RA and SGLT2i have increased steadily, the uptake remained low, with no more than 12.61% of the market share (alone or as fixed combinations with metformin or insulin) in 2019.

Potential Role of Propolis in the Prevention and Treatment of Metabolic Diseases.

Propolis is a resinous mixture with a complex chemical composition, produced by honeybees and stingless bees from a variety of vegetal sources. In the last decades, propolis was extensively researched, multiple studies confirming its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. More recently, due to an exponential increase in the number of patients with metabolic diseases, there is also a growing interest in the study of antidiabetic, antihyperlipidemic, and anti-obesity effects of propolis. The aim of this review was to evaluate the potential role of propolis in the prevention and treatment of metabolic diseases like diabetes mellitus, dyslipidemia, and obesity. The preclinical in vivo and in vitro pharmacological models investigating antidiabetic, antihyperlipidemic, and anti-obesity effects of propolis were reviewed with a focus on the putative mechanisms of actions of several chemical constituents. Additionally, the available clinical studies and an evaluation of the safety profile of propolis were also presented.

Influence of COVID-19 on Health-Related Quality of Life and the Perception of Being Vaccinated to Prevent COVID-19: An Approach for Community Pharmacists from Romania and Bulgaria.

Community pharmacists are essential front-line health workers, involved in relieving the COVID-19 burden. Their health-related quality of life status needs to be assessed, as lower levels could affect their functioning. In order to evaluate the current status of community pharmacists' quality of life from Romania and Bulgaria during the COVID-19 pandemic, and to identify factors associated with their decision on being vaccinated to prevent COVID-19, an online survey involving 395 community pharmacists was conducted from 15th July 2020 to 15th August 2020. The 15D instrument was used for quality-of-life assessment. The pharmacists' recommendations for vitamin C and D intake during the COVID-19 pandemic were also analyzed in order to promote future training programs for community pharmacists. Descriptive statistics, comparative analyses between pharmacists from Romania and Bulgaria, and multiple correlation analyses were performed on the collected data. Significant differences were observed for the level of quality of life between the two groups of pharmacists according to their age; smaller values, directly correlated with their age (total 15D score and age: Spearman r = 0.168, p = 0.022), were obtained for Bulgarian pharmacists regarding sleeping, usual activities, mental function, discomfort and symptoms, depression, distress. The perception of being vaccinated did not differ between Romanian and Bulgarian pharmacists, as almost 50% agreed to vaccination (p = 0.7542). Their willingness to vaccinate was correlated with vitamin D usage (p = 0.0134), rather than with vitamin C (p = 0.4157). No other significant associations were found between willingness to get vaccinated to prevent COVID-19 and other characteristics (age, gender, income, quality-of-life markers). Evidence-based interventions are required to enhance the health-related quality of life of community pharmacists involved in the first line of the COVID-19 pandemic.