Vesela Radonjic

Antibiotic use in eastern Europe: a cross-national database study in coordination with the WHO Regional Office for Europe

BACKGROUND There are no reliable data on antibiotic use in non-European Union (EU) southern and eastern European countries and newly independent states. We aimed to collect valid, representative, comparable data on systemic antimicrobial use in these non-EU countries of the WHO European region. METHODS Validated 2011 total national wholesale antibiotic-use data of six southern and eastern European countries and regions and seven newly independent states were analysed in accordance with the WHO anatomical therapeutic chemical (ATC)/defined daily doses (DDD) method and expressed in DDD/1000 inhabitants per day (DID). FINDINGS Total (outpatients and hospital care) antibiotic use ranged from 15·3 DID for Armenia to 42·3 DID for Turkey. Co-amoxiclav was mainly used in Georgia (42·9% of total antibiotic use) and Turkey (30·7%). Newly independent states used substantial quantities of ampicillin and amoxicillin (up to 55·9% of total antibiotic use in Azerbaijan). Montenegro and Serbia were the highest consumers of macrolides (15·8% and 19·5% of total antibiotic use, respectively), mainly azithromycin. Parenteral antibiotic treatment is common practice: 46·4% of total antibiotic use in Azerbaijan (mainly ampicillin; 5·3 DID) and 31·1% of total antibiotic use in Tajikistan (mainly ceftriaxone; 4·7 DID). INTERPRETATION This study provides publicly available total antibiotic-use data for 13 non-EU countries and areas of the WHO European region. These data will raise awareness of inappropriate antibiotic use and stimulate policy makers to develop action plans. The established surveillance system provides a method to develop quality indicators of antibiotic use and to assess the effect of policy and regulatory actions. FUNDING Netherlands Ministry of Health, Welfare, and Sport, and EU.

Contractile effects of endothelins on isolated ampullar segment of human oviduct in luteal phase of menstrual cycle

Endothelin-1 induces contractions of human oviduct ampullar segment in follicular phase of menstrual cycle, acting on ET(A) receptors. The aim of our study was to investigate effects of endothelin-1, endothelin-2 and endothelin-3 on isolated ampullar segment of human oviducts, taken from the patients in luteal phase of menstrual cycle. Fallopian tubes were taken from 20 female patients (one tube from each patient) during abdominal hysterectomy with adnexectomy, due to extensive uterine fibroids. The oviduct ampulla was mounted in an organ bath longitudinally, and the tension of the isolated preparation was recorded with the isometric transducer. Endothelin-1 produced concentration-dependent tonic contraction of the isolated ampullar segment (EC(50)=6.80 +/- 1.2 x 10(-10)M), and concentration-dependent inhibition of its rhythmic contractions (EC(50)=7.86 +/- 2.3 x 10(-10)M). Endothelin-2 produced concentration-dependent tonic contraction of the isolated ampullar segment (EC(50)=4.56 +/- 0.3 x 10(-10)M), without affecting its rhythmic contractions. Endothelin-3 did not affect either tone or rhythmic contractions of the isolated preparations. Selective antagonist for ET(A) receptor subtype, BQ 123, produced inhibition of endothelin-1 effects on both tone (pA(2)=9.50) and spontaneous rhythmic contractions (pA(2)=10.73), while selective antagonist for ET(B) receptor subtype, BQ 788, produced only inhibition of endothelin-1 effects on tone (pA(2)=9.61), while the effect of endothelin-1 on spontaneous rhythmic contractions remained unaffected. The results of our study suggest that in the luteal phase both ET(A) and ET(B) receptors regulate tone, and only ET(A) receptors regulate rhythmic activity of human oviducts ampullar segment.

Evaluation of brivaracetam: a new drug to treat epilepsy

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.

Systemic antimycotic and antifungal use in eastern Europe: a cross-national database study in coordination with the WHO Regional Office for Europe

*Corresponding author. Laboratory of Medical Microbiology, Vaccine IFax: +32-3-265-2526; E-mail: niels.adriaenssens@uantwerpen.be†Members are listed in the Acknowledgements section.Keywords:

Experience with developing antibiotic stewardship programmes in Serbia: potential model for other Balkan countries?

AIM Antimicrobial resistance and inappropriate use of antibiotics in children are important issues. Consequently, there is a need to develop comprehensive stewardship programs even in hospitals with limited resources starting with childrens hospitals. METHODS Retrospective observational analysis of antimicrobial utilization and resistance patterns over 5 years in a tertiary care childrens hospital in Serbia. RESULTS Cumulative antimicrobial resistance decreased but was still high, with high cumulative resistance rates among the most widely used antibiotics in the hospital. Total antibiotic use decreased from 2010 to 2014 although there was still high prescribing of reserved antibiotics. CONCLUSION Concerns with inappropriate use and high resistance rates among some antibiotics used in the hospital are being used to develop guidance on future antibiotic use in this hospital, building on the recently introduced antibiotic stewardship program, as well as encourage other hospitals in Serbia to review their policies.

A rating instrument for fear of hospitalisation

AIMS AND OBJECTIVES To develop and validate a reliable instrument that can measure fear of hospitalisation experienced by outpatients. BACKGROUND After having a diagnosis established, some patients experience sense of fear, unpleasantness and embarrassment due to the possibility to be admitted to a hospital. Currently, there is no available instrument for measuring fear of hospitalisation. DESIGN Cross-sectional study for assessing reliability and validity of a questionnaire. METHOD The questionnaire with 17 items and answers according to the Likert scale was developed during two brainstorming sessions of the research team. Its reliability, validity and temporal stability were tested on the sample of 330 outpatients. The study was multicentric, involving patients from seven cities and three countries. RESULTS Fear of hospitalisation scale showed satisfactory reliability, when rated both by the investigators (Cronbachs alpha .799) and by the patients themselves (Cronbachs alpha .760). It is temporally stable, and both divergent and convergent validity tests had good results. Factorial analysis revealed three domains: fear of being injured, trust to medical staff and fear of losing privacy or autonomy. CONCLUSIONS This study developed new reliable and valid instrument for measuring fear of hospitalisation. RELEVANCE TO CLINICAL PRACTICE Identification of patients with high level of fear of hospitalisation by this instrument should help clinicians to administer measures which may decrease fear and prevent avoidance of healthcare utilisation.

Antimicrobial Medicines Consumption in Eastern Europe and Central Asia – an Updated Cross-National Study and Assessment of Quantitative Metrics for Policy Action

Introduction: Surveillance of antimicrobial medicines consumption is central to improving their use and reducing resistance rates. There are few published data on antibiotic consumption in Eastern Europe and Central Asia. To address this, 18 non-European Union (EU) countries and territories contribute to the WHO Regional Office for Europe (WHO Europe) Antimicrobial Medicines Consumption (AMC) Network. Objectives: (i) Analyze 2015 consumption of J01 class antibacterials for systemic use from 16 AMC Network members; (ii) compare results with 2011 data and 2015 ESAC-Net estimates; (iii) assess consumption against suggested indicators; (iv) evaluate the impact of planned changes to defined daily doses (DDDs) in 2019 for some commonly used antibiotics; and (v) consider the utility of quantitative metrics of consumption for policy action. Methods: Analysis methods are similar to ESAC-Net for EU countries. The Anatomical Therapeutic Chemical (ATC) classification and DDD methodology were used to calculate total consumption (DDD/1000 inhabitants/day [DID]), relative use measures (percentages), extent of use of WHO Watch and Reserve group antibiotics and impact of DDD changes. Findings: Total J01 consumption in 2015 ranged 8.0–41.5 DID (mean 21.2 DID), generally lower than in 2011 (6.4–42.3 DID, mean 23.6 DID). Beta-lactam penicillins, cephalosporins, and quinolones represented 16.2–56.6, 9.4–28.8, and 7.5–24.6% of total J01 consumption, respectively. Third-generation cephalosporins comprised up to 90% of total cephalosporin consumption in some countries. Consumption of WHO Reserve antibiotics was very low; Watch antibiotics comprised 17.3–49.5% of total consumption (mean 30.9%). Variability was similar to 2015 ESAC-Net data (11.7–38.3 DID; mean 22.6 DID). DDD changes in 2019 impact both total and relative consumption estimates: total DIDs reduced on average by 12.0% (7.3–35.5 DID), mostly due to reduced total DDDs for commonly used penicillins; impact on rankings and relative use estimates were modest. Discussion: Quantitative metrics of antibiotic consumption have value. Improvements over time reflect national activities, however, changes in total volumes may conceal shifts to less desirable choices. Relative use measures targeting antibiotics of concern may be more informative. Some, including WHO Watch and Reserve classifications, lend themselves to prescribing targets supported by guidelines and treatment protocols.