Ana V. Pejcic

Risk factors for dysmenorrhea among young adult female university students.

OBJECTIVES The aim of this study was to investigate associated risk factors for dysmenorrhea in a sample of Serbian university students. METHODS A case-control study was conducted among undergraduate students (n = 288) attending lectures during 2014/2015 academic year at the Faculty of Medical Sciences, University of Kragujevac. RESULTS The only significant associations were between dysmenorrhea and age at menarche (OR adjusted = 0.74; 95% CI 0.58-0.95; p = 0.017), family history of dysmenorrhea (OR adjusted = 3.39; 95% CI 1.74-6.63; p = 0.000), duration of menstrual flow (OR adjusted = 1.52; 95% CI 1.16-1.99; p = 0.002) and smoking at least one cigarette a day (OR adjusted = 5.09; 95% CI 1.83-14.15; p = 0.002). The factors associated with dysmenorrhea were not interacting with each other. CONCLUSION Our results suggest that earlier age at menarche, longer duration of menstrual flow, prior family history of dysmenorrhea and smoking at least one cigarette a day are important risk factors associated with dysmenorrhea. Smoking cessation should be strongly encouraged.

Pharmaceutical expenditure dynamics in the Balkan countries

Extending to the south from central Europe into the Mediterranean Sea, the region of the Balkans includes the countries of Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Greece, Romania, Serbia, Slovenia, The Former Yugoslav Republic of Macedonia (FYR Macedonia), Montenegro, and the geographical/political region of European Turkey. Most Balkan states are middle-income countries, with the exception of Greece, Croatia, and Slovenia, which are all high-income countries. In addition, some of these countries are Member States of the European Union (EU): Greece since 1981, Slovenia since 2004, Bulgaria and Romania since 2007 and Croatia since 2013. All other Balkan countries are EU candidate countries, with the exception of Bosnia and Herzegovina, which is a potential candidate for EU membership. There are also differences in the performance of health systems among them. All countries in the past 20 years have been faced with different problems in financing healthcare and trying to implement different reforms in order to assure a sustainable and efficient healthcare system. During two and a half decades of health reform processes, the formerly massive hospital-centered system of the Post-Semashko countries (Albania, Bulgaria, Romania) and former Yugoslavia republics (Bosnia and Herzegovina, Croatia, Montenegro, Serbia, Slovenia and FYR Macedonia) have clearly been reshaped towards more preventive and efficient primary care, whereas, among the priorfree-market countries (Greece, Turkey) physician density increased the most. Among all Western Balkan countries, Bosnia and Herzegovina, consisting of the Federation of Bosnia and Herzegovina with its 10 cantons, Republic of Srpska and Brcko District, has the most complicated organization of health system financing and medicines reimbursement, leading to inequity in access to medicines among different administrative regions, which are covered by 12 different health insurance funds. Total health expenditure expressed as a percentage of gross domestic product and total expenditure on health per capita in terms of current purchase power parity in international

Growth of Global Publishing Output of Health Economics in the Twenty-First Century: A Bibliographic Insight

showed an obvious increase in most of the Balkan countries during 1995–2012.

Evaluation of brivaracetam: a new drug to treat epilepsy

Background Strong growth of interdisciplinary sciences might find exceptional example in academic health economics. We decided to observe the quantitative output in this science since the beginning of the twenty-first century. Methods Electronic search of the published literature was conducted in four different databases: one medical database—MEDLINE/PubMed, two general databases—Scopus/Elsevier and Web of Science (WoS), and one specialized health economic database—NHS Economic Evaluation Database (EED). The applied combination of key words was carefully chosen to cover the most commonly used terms in titles of publications dealing with conceptual areas of health economics. All bibliographic units were taken into account. Results Within the time horizon from January 1, 2000 to December 31, 2016, without language or limitations on bibliographic unit types, we identified an output ranging approximately from 60,345 to 88,246 records with applied search strategy in MEDLINE/PubMed, Scopus/Elsevier, and WoS. In NHS EED, we detected 14,761 records of economic evaluations of health interventions during the period in which database was maintained and regularly updated. With slightly more than one-third of the identified records, USA clearly dominates in this field. United Kingdom takes a strong second place with about 12% of identified records. Consistently, USA and UK universities are the most frequent among the top 15 affiliations/organizations of the authors of the identified records. Authors from Harvard University contributed to the largest number of the identified records. Conclusion There is a clear evidence of both the upward stream of blossoming in health economics publications and its acceleration. Based on this bibliographic data set, it is difficult to distinguish the actual impact growth of this output provided dominantly by academia with modest contribution by pharmaceutical/medicinal device industry and diverse national government-based agencies. Further insight into the citation track record of these individual publications could provide helpful upgrade and a perspective on ongoing development.

Transposition and implementation of EU rare disease policy in Eastern Europe

ABSTRACT Introduction: High prevalence of therapy-resistant epilepsy demands development of anticonvulsants with new mechanisms of action. Brivaracetam is an analogue of levetiracetam which binds to the synaptic vesicle protein 2A (SV2A) and decreases release of excitatory neurotransmitters. Areas covered: Relevant published studies were searched for by predefined strategy in MEDLINE, EBSCO and SCINDEKS electronic databases. Brivaracetam is effective as adjunctive therapy for uncontrolled partial-onset seizures with or without secondary generalization in patients 16 years and older with epilepsy. It reduces baseline-adjusted focal seizure frequency per week from 7.3 to 12.8% over placebo. Adverse events rate in patients with brivaracetam is not higher than in patients with placebo. Expert opinion: Brivaracetam is an important step forward in the treatment of therapy-resistant partial-onset seizures with or without secondary generalization. Its development was systematic and targeted. Due to its efficacy and excellent safety profile, it is likely that brivaracetam will be often prescribed. In future, efficacy and safety of brivaracetam should be tested in monotherapy settings and also in the first-line therapy of partial-onset seizures.

Risk factors for potential drug-drug interactions in intensive care unit patients

ABSTRACT Introduction: А series of European Union (EU) political decisions have made rare diseases one of the cornerstones of the common European health policy. Adopted in 2009, Council Recommendation on an action in the field of rare diseases aimed to serve as a policy-making guideline. However, the implementation report, which followed it, neither performed detailed cross-country comparison, nor assessed the impact of the policies. Areas covered: A 10-indicator set was elaborated to structure the review and to describe rare disease activities in 14 Eastern European countries. Expert commentary: Taking into account all indicators, EU member states outperform candidate and potential candidate countries in terms of rare disease policy planning and implementation. Hungary is the top performer, followed by Bulgaria and Czech Republic. Non-EU countries form the bottom tier, with Serbia being the best ranked among them. While EU adhesion is a major facilitator for planning and adopting rare disease policies, local stakeholders are the triggering factor for their successful implementation. European reference networks are likely to be the future of rare disease activities in the EU. They need to synchronize and closely collaborate with all important EU projects in the field of rare diseases if they are to achieve their objectives.

Alcohol Beverage Household Expenditure, Taxation and Government Revenues in Broader European WHO Region

Purpose: To determine risk factors for each severity‐based category of potential drug‐drug interactions (DDIs) encountered at intensive care unit (ICU) patients. Methods: This was a retrospective cohort analysis of patients treated at the ICU of the Clinical Center Kragujevac, a public tertiary care hospital in Kragujevac, Serbia. Three interaction checkers were used to reveal drug‐drug interactions: Medscape, Epocrates and Micromedex. Results: The study included 201 patients, 66.19 ± 16.11 years of age. Average number of DDIs per patient ranged from 10.49 ± 8.80 (Micromedex) to 29.43 ± 21.51 (Medscape). Antiarrhythmic or anticonvulsant drug prescription, Charlson Comorbidity Index, male sex, length of hospitalization, number of drugs or therapeutic groups prescribed and surgery increased the risk of DDIs in ICU patients, while presence of delirium or dementia and transfer from emergency department to ICU protected against. Conclusions: The rate of the DDIs in ICU patients at a tertiary care hospital is high, and adversely influenced by number of drugs or drug groups prescribed per patient, antiarrhythmic or anticonvulsant drug prescription, comorbidities, length of hospitalization and surgery. On the other hand, presence of cognitive deficit and transfer from emergency department to ICU protect ICU patients from the DDIs. Highlights:The rate of the DDIs in ICU patients at a tertiary care hospital is high.Drug related risk factors for DDIs: antiarrhythmics, anticonvulsants, number of prescribed drugs and therapeutic groups.Patient related risk factors for DDIs: higher Charlson Comorbidity Index, male sex, length of hospitalization and surgery.Presence of delirium or dementia and transfer from emergency department to ICU seem to protect against DDIs.The most frequently detected DDI was between midazolam and tramadol.

Access to orphan drugs – comparison across Balkan countries

Health Economics and Pharmacoeconomics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia, 2 Federal Research Institute for Public Health Organization and Information (CNIIOIZ), Ministry of Health, Moscow, Russia, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria, 4 Yeshiva University, New York, NY, USA, 5 Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

Authors’ reply to Rare diseases in Romania – a response to ‘Transposition and implementation of EU rare diseases policy in Eastern Europe’

The aim of this study was to compare orphan drug access in a sample of Balkan countries: five EU Member States (Bulgaria, Croatia, Greece, Romania, Slovenia) and two EU Candidates (Serbia, Montenegro). The comparative analysis was based on a cross-sectional study and included medicinal products with an active orphan designation and market authorisation on January 1, 2017. Access to orphan drugs is an ongoing challenge in these countries. Three clusters of countries were identified in terms of orphan drug access: Greece and Slovenia, making the top tier, Romania, Bulgaria, and Croatia, being in the middle, and EU Candidates, Serbia and Montenegro, forming the bottom tier, where a substantial number of EU market approved orphan drugs was not even registered. Available public health resources and market size are probably among the contributing factors for such inequalities. Sizeable part of EMA market authorised orphan medicinal products is not even priced in the Balkan countries. This is a serious issue, which is putting rare disease patients from this region in a particularly vulnerable situation. There is a need for further improvement in accessibility of orphan drugs in the Balkan countries. Cross-border collaboration in the field of pricing, health technology assessment, and reimbursement negotiation of orphan drugs may help to address these challenges.

Expenditure trends of orphan drugs in Serbia: 8-Year analysis of orphan drug market in Serbia

We readwith great interest the response by Emilia Severin and we would like to thank her for the detailed overview of rare disease policy-making in Romania [1]. Indeed, for the past decade all Eastern European countries have made substantial progress in this field. Romania has been an example of effective multistakeholder rare disease collaboration at national level, with the Romanian national alliance for rare diseases playing amajor role in these activities. We would like to put stress on the methodology of our study and in particular on the definition and primary reference source used for the indicator of national plan/strategy for rare diseases [2]. Under our approach, a national plan/strategy for rare diseases has to be (1) formally adopted and (2) government-funded plan/strategy, (3) consisting of specific priorities. These three criteria – formal adoption, public funding, and specific priorities – are based on the EUROPLAN Project’s ‘Selecting indicators to evaluate the achievements of RD initiatives’ [3]. The website of the Directorate-General for Health and Food Safety (DG SANTE) of the European Commission was searched for existing national plans for rare diseases in Eastern European countries. In fact, DG SANTE has established a detailed collection of rare disease documents on its Internet site in order to boost the dissemination and adoption of such policies. Under the Council’s Recommendation on an action in the field of rare diseases, the European Commission required Member States to regularly report on rare disease policy progress, with this information usually published on the DG SANTE’s rare disease web page [4]. As the official health policy directory of the European Union, DG SANTE is considered the most credible and up-to-date information source for rare disease policy activities in Europe. In the case of Romania, our final conclusion was based on the following considerations. First, оn DG SANTE’s web page the data for Romania indicate ‘Romanian National Plan for Rare Diseases 2010–2014 (Draft)’ [4]. This information clearly shows that this policy document cannot be regarded as officially adopted by the Romanian Government. Furthermore, the hyperlink provided is no longer working and we could not assess the plan itself. RD-Action, as suggested by Emilia Severin’s response as a reference source for the official European position on this issue, is a joint action, funded by the European Union’s Health Programme 2014–2020. This is a project activity and its disclaimer states that its deliverables cannot be considered to reflect the views of the European Commission and/or DG SANTE or any other body of the European Union [5]. Second and more importantly, we explored the official documents available on the web page of the Romanian Ministry of Health in order to check and better understand the current state of this draft plan. We found and analyzed Romania’s National Health Strategy 2014–2020 [6]. Indeed, rare diseases are listed as a public health sub-priority in this document under Axis 3 (Prevention of non-communicable diseases), which is clearly stated in our published article (‘Still, rare disease activities are included in the Romania’s National Health Strategy 2014–2020, as a part of axis of prevention of non-communicable diseases’ [2]). However, a sub-priority is not an equivalent to a formally adopted specific national plan for rare diseases. This is a part of an overall health strategy and such documents exist virtually in all jurisdictions in the world. Furthermore, chronic non-communicable diseases are now a universal health policy priority in all countries. Rare diseases do make part of this broad field. But it does not automatically mean that each country with a health strategy has a separate national plan to tackle rare diseases. In conclusion, as we were not able to clearly identify a formally adopted specific document from Romania, entitled ‘National plan for rare diseases’, and Emilia Severin did not provide such references either, we believe the findings and recommendations of our study are correct and in accordance with the methodology presented.