Study of clinical experience with different approaches to controlled ovarian hyperstimulation: a focus on safety and efficacy.

OBJECTIVES: Current retrospective cohort study analyses clinical database records of 4792 assisted reproduction procedures to assess the significance of target effectiveness endpoints from a safety perspective. METHODS: Stimulation protocols with urinary, recombinant or combination of both types gonadotrophin preparations are compared according to the following primary endpoints: incidence of ovarian hyperstimulation syndrome (OHSS), cycle cancellation, follicle count, induced estradiol values, clinical pregnancy achieved and cycles reached embryo transfer/freezing. We have investigated the incidence of cases evaluated as 'risky for OHSS' by secondary efficacy endpoints (exogenous gonadotrophin exposure, luteinising hormone and progesterone values, oocyte yield, eggs with normal maturation). The following statistical methods were applied: descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test, Pearson chi-square test, Fisher's exact test, binary logistic regression. RESULTS: Only 16 cases (0.42%) of moderate and delayed OHSS were established. Three hundred and seven (8.6%) stimulation cycles have been cancelled, principally among urinary protocols. Although the clinical pregnancy rate does not differ significantly in compared groups, punctured follicle count, oocyte yield and progesterone level were higher for recombinant preparations, followed by combined and urinary protocols. Follicle count, mean estradiol and luteinising hormone levels are within the 'safe window' for all investigated groups, associated with minimised risk of stimulation cancellation. The mean follicle-stimulating hormone (FSH) dose was highest in urinary protocols at the same duration of stimulation compared with recombinant products. The younger age, bigger follicle count, oocytes yield, mature oocytes count, percentage of fertilised oocytes, more embryos transferred and the later day of embryo transfer are critical for both assisted reproduction techniques (ART) success rate and the safety profile of sterility treatment. CONCLUSIONS: Safety surveillance of ART exceeds the incidence of OHSS. Suboptimal effectiveness of stimulation protocols may also jeopardise the well-being of ART patients. Gonadotrophin exposure, induced values of sex hormones, and quantity and quality of extracted oocytes should be considered to minimise any unintended suffering of treated couples.

Pilot Study of Pharmacists' Attitudes towards and Expectations for Remuneration of Valueadded Pharmacy Services (VAPS) in Bulgaria.

INTRODUCTION: Value-added pharmacy services (VAPS) are additional services to the traditional pharmacy activities, which do not in-clude dispensing of medicinal products and professional consultation. These services have cost reduction effect on the healthcare system and add value to the work of the pharmacist as a healthcare professional. AIM: To assess the pharmacists' attitudes and expectations towards the remuneration of value-added pharmacy services (VAPS) in Bulgaria. MATERIALS AND METHODS: A cross-sectional study including pharmacists working in community pharmacies was carried out between August 2018 and October 2018. A web-based 15-item questionnaire was developed. The questionnaire was distributed to all members of the Bulgarian Pharmaceutical Union (n=5165). Two hundred thirty-three questionnaires were filled in and returned (response rate of 4.5%). Data were processed by SPSS v. 24.0. RESULTS: Over 51% of the community pharmacies in Bulgaria offer VAPS, mainly measuring blood pressure (67.4%) and blood glucose (12.9%). Over two-thirds of the pharmacists considered charging a remuneration fee for blood pressure measurement irrelevant. About 30.5% of those who held the opposite opinion proposed that the fee charged should not be higher than EUR 2.56. Over 44% of the re-spondents proposed that the fee for blood glucose measurement should not be higher than the same amount. Most pharmacists (98.3%) supported the idea of charging a remuneration fee for injections and influenza vaccination in a pharmacy. CONCLUSION: The study shows that pharmacists in Bulgaria are ready to offer VAPS, but additional remuneration for the services should be provided.

Regulatory Requirements for Food Supplements in the European Union and Bulgaria.

Data provided by the European Commission show that public expenditures for food supplements have been constantly increasing over the last decade. The aim of the present study was to analyze the major food supplements regulations in the European Union and in Bulgaria. Relevant publications were searched and found in MEDLINE/PubMed, Scopus Database, Web of Knowledge, and in Internet-based search with predefined keywords. Numerous authors support the opinion that there is a real risk that low quality products may be distributed in countries with poor production control. Bulgarian national legislation have 6 regulations with different legal force for provision of healthy and safe food supplements on the market. Currently, the European Community is concerned about food products, including FS, launched on the market because the citizens require reliable protection of their health. This concern provoked the European Parliament and the Council to undertake a number of legislative initiatives in the field of production and control of food products. It is necessary to set more precise quality and safety criteria in future strategies associated with those products.

Practical tool to assess reliability of web-based medicines information.

AIM: Information disseminated by medicines information systems is not always easy to apply. Nowadays internet provides access to enormous volume and range of health information that was previously inaccessible both for medical specialists and consumers. The aim of this study is to assess internet as a source of drug and health related information and to create test methodology to evaluate the top 10 visited health-related web-sites in Bulgaria. METHODS: Using existing scientific methodologies for evaluation of web sources, a new algorithm of three-step approach consisting of score-card validation of the drug-related information in the 10 most visited Bulgarian web-sites was created. RESULTS: In many cases the drug information in the internet sites contained errors and discrepancies. Some of the published materials were not validated; they were out-of-date and could cause confusion for consumers. CONCLUSION: The quality of the online health information is a cause for considerable information noise and threat to patients' safety and rational drug use. There is a need of monitoring the drugs information available online in order to prevent patient misinformation and confusion that could lead to medication errors and abuse.

Physicians' knowledge and attitude towards adverse event reporting system and result to intervention--randomized nested trial among Bulgarian physicians.

AIM: To identify the factors that influence physicians' under-reporting in Bulgaria and their attitude towards adverse event reporting system and to estimate the role of self-education by providing educational materials. METHODS: A randomized nested trial among physicians-general practitioners and specialists in Bulgaria was conducted by a validated questionnaire in order to evaluate their knowledge and attitude towards adverse event reporting system. One month after the intervention the participants were re-visited and were asked to answer the same questions again in order to estimate the change in their knowledge and attitude towards pharmacovigilance system and to obtain their evaluation for the materials provided. RESULTS: The response rate was 91. Fifty seven (46.3%) physicians were not familiar with the pharmacovigilance system. The most common reason for non-reporting adverse drug reactions (ADRs) was uncertainty concerning the relationship between the suspected drug and ADRs, the ADRs were already known and the fact that the physician was not aware where they should report. Although 103 (83.7%) respondents in the entry survey and by 102 (82.9%) of those participating in the exit survey consider ADRs reporting as their obligation (p more than 0.05), only 50 (40.7%) and 31 (25.2%), respectively answered that they had ever reported ADRs; 109 (88.6%) of the surveyed physicians assessed the provided educational materials as useful for them. CONCLUSION: The physicians in Bulgaria have poor knowledge for the pharmacovigilance system; however self-education leads to a better knowledge and positive attitude towards ADRs reporting system. National drug regulatory authority should play a more active role in improving physicians' adherence to the ADRs reporting systems and the developed educational pack can be used in nationwide campaign.

Study of obligations defined in agreements between parties involved in clinical trials of medicinal products in Bulgaria.

AIM: To analyse and assess the legislative and contractual obligations of the parties involved in the conduct of clinical trials, with identification of the needs for comprehensive contractual regulation of their rights and responsibilities. METHODS: This survey has been carried out by means of review, analysis of comprehensiveness, comparative legislative analysis and assessment of compliance with the legislation of sample of investigator and site agreements governing the process of conducting clinical trials. RESULTS: The survey comprises analyses of contractual relations between the sponsor of the study and the investigator, and between the sponsor of the study and the trial site, respectively, relevant to clinical trials which are actually conducted in Bulgaria at the time of and following the survey. Comparative method based on pre-defined structured indices was employed to outline the major variances in the volume of responsibilities and obligations of the said parties to the clinical trial, as regulated by the investigator and site agreements. The analysis of comprehensiveness showed evident omissions in the regulation of relations and interactions between the parties to the agreements. CONCLUSION: The detailed contractual regulation providing for the statutory obligations and responsibilities of the parties involved in the conduct of clinical trials is a good guarantee for proper understanding of the obligations of each party and for compliance with their relevant responsibilities in view of protecting the rights of the participants in the clinical trials - patients or healthy volunteers.

Safety assessment of newly marketed herbal medicines--methodological approach (Ginkgo biloba example in Bulgaria).

This study presents a proposal for the methodological approach for postmarketing safety profile assessment based on sales data and information for adverse drug reactions of newly introduced herbal medicinal products in the market. The study covers all herbal medicinal products containing dry extract of Ginkgo biloba leaves allowed for sale in Bulgaria. The methodological approach we create should be used for the establishment of the national herbal drugs policy complying with the recent European regulatory changes and specificity of the therapeutic practice in the country.