Carbapenem-resistant Klebsiella pneumoniae in the Balkans: Clonal distribution and associated resistance determinants.

Carbapenems are considered to be among the last line antibiotics against extended-spectrum ß-lactamase producing Enterobacterales. Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been frequently reported and its spread in Europe is indisputable and poses an enormous threat to hospitalized patients which is of growing concern. This review aims to record prevalence of CRKP in the Balkan region and to review the current knowledge about this life-threatening pathogen. In this review, we summarize data about clinical isolates of carbapenem-resistant K. pneumoniae from Greece, Croatia, Romania, Bulgaria, Serbia, Slovenia, Montenegro, Bosnia-Herzegovina and Albania from published reports between 2000 and 2023. Among Balkan countries, Greece and Romania are the ones with the most reports about CRKP. Since 2007, KPCs are the dominant carbapenemases in both countries. KPC-2 and NDM-1-producing K. pneumoniae strains have been identified as the most frequent CRKP in Croatia, Bulgaria, Serbia, and Slovenia. OXA-48 enzyme has been identified in most Balkan countries. In addition, since 2018, CRKP sequence type 11 (ST11) seems to have replaced ST258 in Balkan Peninsula, while ST15 continues to thrive throughout the years. Not only efficacy of colistin against CRKP has decreased dramatically during the last ten years but colistin resistance mechanism is based on alterations of chromosomal mgrB gene, rather than the already known mcr genes.Moreover, ceftazidime-avibactam-resistant CRKP were detected mostly in Greece. Emergence of CRKP poses a severe threat to the Balkan countries. Due to the narrow therapeutic window, it is essential to prevent the spread of multiresistant K. pneumoniae strains.

Diagnostic psychiatric and somatic comorbidity in patients with depression in the Western Balkan countries.

INTRODUCTION: This paper aims to examine the frequency and significance of diagnostic comorbidity of psychiatric disorders and somatic diseases in a sample of patients with depression as well as present current psychopharmacological treatment of the patients in the sample. METHODS: The subjects in this study sample were 489 patients from the four Western Balkan countries with current primary diagnosis of major depression according to ICD 10. Comorbid psychiatric disorders and non-psychiatric illnesses were noted according to ICD 10 criteria during the diagnostic interview and analysed later. Additionally, the pharmacological treatment (existing and newly introduced) for each patient was noted and analysed later. RESULTS: At least one comorbid psychiatric disorder was present in 72.5% of patients. The most frequent were anxiety disorders (53.6%), specifically generalized anxiety disorder (20.2%); non-organic sleep disorders (50.7%), specifically insomnia (48.4%); and sexual dysfunctions (21.4%), specifically lack of sexual desire (20.2%). Comorbidity with any non-psychiatric illness was present in 80.3% of patients. The most frequent were circulatory system diseases (55.9%), specifically hypertension (45.9%); endocrine, nutritional and metabolic disorders (51.3%), specifically hyperlipidaemia (24.0%); and other non-psychiatric disorders (60.7%), specifically low back pain (22.7%). All patients received pharmacological treatment with different medications. Most patients received monotherapy or combination therapy of antidepressants, anxiolytics, antipsychotics and antiepileptics. The most frequently used antidepressants were escitalopram, sertraline, and duloxetine. The most frequently used anxiolytics were alprazolam and diazepam, the most used antiepileptic was pregabalin, and the most used antipsychotics were olanzapine, quetiapine, and aripiprazole. CONCLUSION: The results of the study confirm the results of previous research studies about the high prevalence of psychiatric and non-psychiatric comorbidities in patients with depression that were conducted in the past. It would be important if future studies could prove the importance of those comorbidities on clinical severity, choice of treatment, and its outcome in patients with depression.

Prevalence and associated factors of overweight and obesity among medical students from the Western Balkans (South-East Europe Region).

Being overweight and obese is associated with an elevated risk of developing noncommunicable diseases, which are the leading causes of mortality worldwide. It is a warning that global prevalence of overweight among university students ranges from 20 to 40%, which presents a significant public health problem. To date, there was no research conducted on medical students regarding the prevalence and associated factors of overweight and obesity in the countries of the Western Balkans (Slovenia, Croatia, Bosnia and Herzegovina, North Macedonia, and Serbia). The aim of this study was to determine the prevalence and potential demographic, socioeconomic, and health-related behavioral factors associated with overweight and obesity of medical students from Western Balkans. A cross-sectional study was conducted, surveying 2452 students from 14 medical faculties from 5 countries in the region. The prevalence of overweight was 12% and obesity was 2.3% among medical students from Western Balkans. Male gender and smoking status are significant positive predictors of overweight and obesity. Daily level of physical activity up to 1 h per day, going to preventive check-ups once a year or as a part of annual dormitory check-ups are associated with lower odds of being overweight and obese. By creating adequate public health educational programs, students can be influenced to acquire proper health-related lifestyle habits, which would lead to reducing the prevalence of overweight and obesity among the student population, as well as risk of developing noncommunicable diseases and improving the overall health of the population.

Global and local drivers of Echinococcus multilocularis infection in the western Balkan region.

The cestode, Echinococcus multilocularis, is one of the most threatening parasitic challenges in the European Union. Despite the warming climate, the parasite intensively spread in Europe's colder and warmer regions. Little is known about the expansion of E. multilocularis in the Balkan region. Ordinary least squares, geographically weighted and multi-scale geographically weighted regressions were used to detect global and local drivers that influenced the prevalence in red foxes and golden jackals in the southwestern part of Hungary. Based on the study of 391 animals, the overall prevalence exceeded 18% (in fox 15.2%, in jackal 21.1%). The regression models revealed that the wetland had a global effect (ß = 0.391, p = 0.006). In contrast, on the local scale, the mean annual precipitation (ß = 0.285, p = 0.008) and the precipitation seasonality (ß = - 0.211, p = 0.014) had statistically significant effects on the infection level. The geospatial models suggested that microclimatic effects might compensate for the disadvantages of a warmer Mediterranean climate. This study calls attention to fine-scale analysis and locally acting environmental factors, which can delay the expected epidemic fade-out. The findings of our study are suggested to consider in surveillance strategies.

COVID - 19 in two dialysis centers situated in two neighbouring states of the Western Balkans.

BACKGROUND: Bosnia and Herzegovina (BiH) and Serbia are countries in the Western Balkans that share parts of their social and political legacy from the former Yugoslavia, such as their health care system and the fact that they are not members of European Union. There are very scarce data on COVID - 19 pandemic from this region when compared to other parts of the world and even less is known about its impact on the provision of renal care or differences between countries in the Western Balkans. MATERIALS AND METHODS: This observational prospective study was conducted in two regional renal centres in BiH and Serbia, during the COVID - 19 pandemic. We obtained demographic and epidemiological data, clinical course and outcomes of dialysis and transplant patients with COVID - 19 in both units. Data were collected a via questionnaire for two consecutive time periods: February - June 2020 with a total number of 767 dialysis and transplant patients in the two centres, and July - December 2020 with a total number of 749 studied patients, corresponding to two of the largest waves of the pandemic in our region. Departmental policies and infection control measures in both units were also recorded and compared. RESULTS: For a period of 11 months, from February to December 2020, 82 patients on in-centre haemodialysis (ICHD), 11 peritoneal dialysis patients and 25 transplant patients who tested positive for COVID-19. In the first study period, the incidence of COVID - 19 positive in Tuzla was 1.3% among ICHD patients, and there were no positive peritoneal dialysis patients, or any transplant patients who tested positive. The incidence of COVID-19 was significantly higher in both centres in the second time period, which corresponds to the incidence in general population. Total deaths of COVID-19 positive patients was 0% in Tuzla and 45.5% in Nis during first, and 16.7% in Tuzla and 23.4% in Nis during the second period. There were notable differences in the national and local/departmental approach to the pandemic between the two centres. CONCLUSION: There was poor survival overall when compared to other regions of Europe. We suggest that this reflects the lack of preparedness of both of our medical systems for such situations. In addition, we describe important differences in outcome between the two centres. We emphasize the importance of preventative measures and infection control and highlight the importance of preparedness.

Cigarette Smoking among Medical Students from the Western Balkan.

University student's smoking is a significant public health problem. It is estimated that, globally, every fifth medical student is a smoker. So far, no research dealing with cigarette smoking among medical students has been conducted in the countries of the Western Balkans. The aim of this study was to examine the prevalence and risk factors of cigarette smoking among Western Balkans medical students. A cross-sectional study was conducted among 2452 students from 14 medical faculties in the Western Balkans (Republic of Slovenia, Republic of Croatia, Bosnia and Herzegovina, Republic of North Macedonia and Republic of Serbia). The data were gathered through an online survey. There were significantly more non-smokers than smokers among medical students. Only gender and parents smoking status were statistically significantly associated with students smoking status. The smokers were more often male students, who lived in urban areas prior their studies, and whose parents were both smokers. With the aim of monitoring and enhancing student population health, it is necessary for public health activists and health officials to continually survey the students' smoking status in order to recognize the smoking influencing factors, and form and take on appropriate activities to improve the prevention of cigarette smoking among students, as well as motivate those who smoke to give up smoking, which would contribute to improving the health of the student population.

New cases of human dirofilariosis on the Balkan Peninsula - "Masked intruders" uncovered by a surgeon.

Dirofilaria spp. nematodes are accidental parasites of humans causing mild to serious, superficial or visceral infections. Superficial dirofilariosis is rather common in Europe and is typically manifested as subcutaneous form. Herein we report 46 new cases of human dirofilariosis (19 patients with subcutaneous, 18 patients with ocular, 4 patients wih genital, 2 patients with submucosal, 2 patients with pulmonary and 1 patient with intramuscular form of infection) that were recorded from the beginning of 2015 to May 2021 on the Balkan Peninsula with a goal to update the prevalence of this parasitosis and point out potential problems in diagnosis and treatment. Besides, given the high possibility of misinterpretation as tumor, our second aim was to encourage the inclusion of this pathogen in the differential diagnosis of subcutaneous nodules. Although quite common forms, subcutaneous and ocular dirofilariosis can be very often misdiagnosed in clinical practice due to the absence of specific clinical manifestations. Therefore, raising awareness of clinicians about this zoonosis is needed as well as closer collaboration between physicians and veterinarians.

Systematic Review: Re-emergence of human leishmaniasis in the Balkans.

OBJECTIVE: To provide an updated overview of the leishmaniasis epidemiology in the Balkans, as this region presents "blank space" on the map of leishmaniasis knowledge in Europe. METHODS: Following the PRISMA guideline, literature on the presence and circulation of human leishmaniasis in Balkan countries was screened in PubMed, Google Scholar, Science Direct, Scopus, Web of Science, Matica Srpska Library and the National Library of Serbia. RESULTS: Sixty nine publications from 1919 until September 2020 were reviewed. Historical records indicate that leishmaniasis was previously present mainly in the southern parts of the Balkans, while newer data demonstrate its northward spread. CONCLUSIONS: Human leishmaniasis is re-emerging in the Balkans and in some areas is already widespread.

Impact of multimorbidity and polypharmacy on the management of patients with atrial fibrillation: insights from the BALKAN-AF survey.

OBJECTIVE: We investigated the impact of multimorbidity and polypharmacy on the management of atrial fibrillation (AF) patients in clinical practice and assessed factors associated with polypharmacy and oral anticoagulation (OAC) use in AF patients with multimorbidity and polypharmacy. METHODS: A 14-week prospective study of consecutive non-valvular AF patients was performed in seven Balkan countries. RESULTS: Of 2712 consecutive patients, 2263 patients (83.4%) had multimorbidity (AF + ≥2 concomitant diseases) and 1505 patients (55.5%) had polypharmacy. 1416 (52.2%) patients had both multimorbidity and polypharmacy. Overall, 1164 (82.2%) patients received OAC, 200 (14.1%) patients received antiplatelet drugs alone and 52 (3.7%) patients had no antithrombotic therapy (AT). Non-emergency centre and paroxysmal AF were significantly associated with OAC non-use in patients with multimorbidity, whilst age ≥80 years and non-emergency centre were identified to be independent predictors of OAC non-use in patients with polypharmacy. CONCLUSIONS: Multimorbidity and polypharmacy were common among AF patients in our study. AT was suboptimal and approximately 18% of multimorbid patients with polypharmacy were not anticoagulated. Pattern of AF and non-emergency centre were associated with OAC non-use in AF patients with multimorbidity, whilst non-emergency centre and age ≥80 years were associated with OAC non-use in AF patients with polypharmacy. Key Message Multimorbidity and polypharmacy are common among patients with AF. Antithrombotic therapy was suboptimal in AF patients with multimorbidity and polypharmacy. Approximately, 18% of multimorbid patients with polypharmacy were not anticoagulated.

Characteristics and outcomes of critically ill patients with influenza A (H1N1) in the Western Balkans during the 2019 post-pandemic season.

Background: This study looked at the characteristics and outcomes of critically ill patients with confirmed influenza A (H1N1) pdm09 infection in the Western Balkans in the post-pandemic period. Materials and Methods: This retrospective observational study of medical records and associated data collected during the post-pandemic period included all mechanically ventilated adult patients of two university-affiliated hospitals of the Western Balkans between 1 January and 31 March 2019 who had influenza A (H1N1) pdm09 infection confirmed by real-time reverse transcriptase-polymerase chain reaction from nasopharyngeal swab specimens and respiratory secretions. Results: The study included 89 patients, 49 males (55.1%), aged 56.09 ± 12.64 years. The median time from shift from hospital time to intensive care unit was 1 day (range: 1-2). In the post-pandemic period, cases observed in this study were found to have the following comorbidities: cardiovascular diseases in 44 (49.4%) patients and diabetes in 21 (23.6%) patients. Thirty-one patients (34.8%) in this study were obese. All 89 patients (100%) experienced some degree of acute respiratory distress syndrome, and 39 (44%) had multiorgan failure. Eighty-three patients (93%) were intubated and mechanically ventilated, 6 (7%) received non-invasive mechanical ventilation, 12 (13%) were treated with vvECMO and 36 (40%) received renal replacement therapy. Vasoactive support was needed by 56 (63%) patients. The median duration of mechanical ventilation was 9 (6-15.5) days. The hospital mortality rate was 44%. Conclusion: Critically ill patients with confirmed influenza A (H1N1) pdm09 infection in the post-pandemic season were older, required vasoactive drugs more often, and there was a trend of higher survival compared to H1N1 infection patients in the previous pandemic seasons.

Tigecycline susceptibility of multidrug-resistant Acinetobacter baumannii from intensive care units in the western Balkans.

Tigecycline can be effective to treat infections of carbapenem-resistant Acinetobacter baumannii (CRAB) however, no interpretive criteria have been approved so far. The objectives of this study were to evaluate the proportion of CRAB isolates and to compare gradient test with a broth microdilution (BMD) method for tigecycline susceptibility testing of A. baumannii.This study included 349 multidrug-resistant (MDR) Acinetobacter spp. collected from Serbia, Montenegro, Bosnia and Herzegovina in 2016 and 2017. Antibiotic susceptibility testing was performed by disk diffusion, VITEK2, gradient, ComASP Colistin. Tigecycline susceptibilities were interpreted according to breakpoints of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA).Majority of the tested isolates were CRAB (92.8%). Tigecycline MIC50/MIC90 values were 4/8 µg/mL by BMD and 0.5/4 µg/mL by gradient test. Essential agreement for BMD and gradient test amounted to 65.1%. With EUCAST breakpoints, categorical agreement (CA) was achieved in 38% isolates. Major discordance (MD-false susceptibility/resistance) and minor discordance (mD-false categorization involving intermediate results) were observed in 10% and 57% A. baumannii, respectively. With FDA breakpoints, CA, MD and mD were observed in 44%, 16% and 47% isolates, respectively. Colistin resistance was 2.1%.The study highlights a high proportion of CRAB and several discordances between BMD and gradient test which may lead to inappropriate therapy.

Stroke prevention in elderly patients with non-valvular atrial fibrillation in the BALKAN-AF survey.

BACKGROUND: Atrial fibrillation (AF) is common amongst the elderly, but this group tends to be suboptimally treated. Limited data are available on the stroke prevention strategies in the elderly, especially in the Balkan region. AIM: We investigated the use of oral anticoagulant therapy (OAC) amongst elderly AF patients in clinical practice in the Balkan region. METHOD: A 12-week prospective snapshot survey (2014-2015) of consecutive non-valvular AF patients was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia. Data were collected via an electronic case report form. RESULTS: Of 2671 patients, 418 (15.6%) were ≥80 years old. Overall, OAC was used in 1965 patients (73.6%). Compared with younger patients, the elderly (age ≥ 80) had a higher mean CHA2 DS2 -VASc score (3.22 ± 1.71 vs 4.89 ± 1.35, P < .001) and more often a HAS-BLED score of ≥3 (n = 198 [47.0%] vs n = 625 [27.3%], P < .001), but were less likely to receive OAC (n = 269 [64.4%] vs n = 1696 [75.3%], odds ratio [OR] 0.91; 95%CI 0.86-0.97, P = .003). There was no significant association between OAC use and mean CHA2 DS2 -VASc (OR 0.86; 95%CI 0.75-1.00, P = .053) or HAS-BLED score (OR 1.21; 95%CI 0.81-1.81, P = .349) in the elderly. CONCLUSION: In the BALKAN-AF Survey, elderly AF patients were less likely to receive the guideline-adherent treatment despite their less favourable risk profile. Since OAC nonuse among the elderly was not associated with increased HAS-BLED score, factors other than patients' risk profile could influence the implementation of guideline-adherent treatment for thromboprophylaxis in the elderly AF patients.

An update on Toscana virus distribution, genetics, medical and diagnostic aspects.

BACKGROUND: Toscana virus is an arbovirus transmitted by sand flies within the Mediterranean area where it can cause febrile illness and neuroinvasive infections during the seasonal circulation period of the vector. Although it is an important cause of meningitis and encephalitis, it remains a neglected virus with limited published data, as demonstrated by <250 peer-reviewed articles since the 1970s. OBJECTIVE: The last review article on Toscana virus was published in 2012. The aim was to compile peer-reviewed articles to provide an updated review highlighting recent findings to complement previous review articles. SOURCES: PubMed database was searched using the 'Toscana virus' keyword from 2010 to present. A total of 152 articles were retrieved and identified studies were assessed for novel information on virus genetics, and geographic and medical aspects compared with existing knowledge reported in previous review articles. CONTENT: Studies addressing medical, veterinary and entomological aspects have provided evidence that Toscana virus is present in North Africa, in the Balkan Peninsula, and in most of the Mediterranean islands. Besides the two previously recognized genetic lineages, a novel evolutionary lineage has been identified in the Balkan Peninsula. Co-circulation of two genetic lineages has been demonstrated in France, in Turkey and in Croatia. In addition to meningitis and meningo-encephalitis, which have been reported for 40 years, various neuroinvasive forms have been recently reported such as Guillain-Barré syndrome, hydrocephalus, myositis, fasciitis, polymyeloradiculopathy, deafness and facial paralysis. IMPLICATION: Because it is endemic in countries bordering the Mediterranean, physicians should include Toscana virus in the differential diagnosis of patients presenting with febrile illness and/or neurological manifestations.

Fueling an epidemic of non-communicable disease in the Balkans: a nutritional survey of Bosnian adults.

OBJECTIVES: Dietary surveys are essential for guiding national efforts to reduce the burden of non-communicable disease, but individual-level dietary data are lacking in many low- and middle-income countries. We aimed to estimate the prevalence of inadequate and excessive intakes of specific nutrients in Bosnia and Herzegovina. METHODS: A dietary survey among 853 adults using two 24-h recalls. RESULTS: The majority of men (73%) and women (66%) were overweight/obese, and > 50% of participants had elevated blood pressure. Low intakes of N-3 polyunsaturated fatty acids, specifically α-linolenic acid (men: 94.4 mg/day among, women: 96.6 mg/day) and DHA + EPA (men: 18.2 mg/day, women: 16.0 mg/day), low fiber intake (women: 21.5 g/day), and high sodium (men: 3244 mg/day, women: 2291 mg/) and saturated fatty acids intakes (men: 29.2 g/day) were reported. There was also a suggestion of low intakes of vitamins A, B6, C and D (in both sexes), and of riboflavin, folate, B12 and calcium (in women). CONCLUSIONS: Our findings provide initial evidence on the Bosnian population's dietary habits and identify aspects that need attention. As the survey evolves into a continuing surveillance system, it will allow evaluation of dietary changes over time.

Molecular identification of Puumala orthohantavirus in Bulgaria.

In Bulgaria, only Dobrava orthohantavirus has been detected in patients and in rodents. In order to elucidate possible Puumala orthohantavirus (PUUV) circulation, 131 bank voles (Myodes glareolus) were captured. PUUV RNA was detected in 14 (10.7%). Partial L segment sequences were recovered from six M. glareolus. Phylogenetic analysis showed that all PUUV sequences from this study clustered together among the Alpe-Adrian lineage. It is the first genetic evidence of the virus circulation in a Balkan country outside north-western Balkans. The findings in this study extended the known edge of virus distribution towards Southeastern Europe.

A generic framework for spatial quantitative risk assessments of infectious diseases: Lumpy skin disease case study.

The increase in availability of spatial data and the technological advances to handle such data allow for subsequent improvements in our ability to assess risk in a spatial setting. We provide a generic framework for quantitative risk assessments of disease introduction that capitalizes on these new data. It can be adopted across multiple spatial scales, for any pathogen, method of transmission or location. The framework incorporates the risk of initial infection in a previously uninfected location due to registered movement (e.g., trade) and unregistered movement (e.g., daily movements of wild animals). We discuss the steps of the framework and the data required to compute it. We then outline how this framework is applied for a single pathway using lumpy skin disease as a case study, a disease which had an outbreak in the Balkans in 2016. We calculate the risk of initial infection for the rest of Europe in 2016 due to trade. We perform the risk assessment on 3 spatial scales-countries, regions within countries and individual farms. We find that Croatia (assuming no vaccination occurred) has the highest mean probability of infection, with Italy, Hungary and Spain following. Including import detection of infected trade does reduce risk but this reduction is proportionally lower for countries with highest risk. The risk assessment results are consistent across the spatial scales, while in addition, at the finer spatial scales, it highlights specific areas or individual locations of countries on which to focus surveillance.

Low levels of modern contraceptive use and associated factors in the Western Balkans.

OBJECTIVES: The objective of this research was to determine modern contraceptive use (MCU) and explore factors associated with MCU in the Western Balkans. METHODS: Multiple Indicator Cluster Survey (MICS) data from Bosnia and Herzegovina, Kosovo, Macedonia, Montenegro and Serbia, including the datasets from Roma settlements, were merged. Bivariate and multivariate analyses were used to assess which factors were associated with MCU among married women aged 15-49 in the region. RESULTS: Among the 11,381 women surveyed, 13.75% reported MCU and 23.74% justified domestic violence. While bivariate analysis indicated that women who expressed justification of domestic violence were less likely to report MUC, this was not the case after adjusting for sociodemographic factors. Multivariate analysis showed that Roma were less likely than non-Roma to engage in MCU. Additionally, increased education, increased wealth, and urban residency were significantly associated with increased likelihood of MCU. CONCLUSION: The results highlight the need for more attention from research, programming and policy communities in order to better understand and address the overall problematically low level of MCU and factors associated with low MCU. More efforts are needed to address the disparities in MCU among Roma women and women of lower socioeconomic status.

How common is Balkan endemic nephropathy among immigrants in endemic regions?

PURPOSE: In the early 1970s, a number of authors described the development of Balkan endemic nephropathy (BEN) in immigrants in endemic regions. The aim of this study was to examine whether immigrants in endemic regions are suffering from BEN today. METHODS: The study involved 193 residents of two endemic regions divided into three groups: two groups of native residents-(1) members of BEN families, (2) members of non-BEN families, and (3) immigrants, who had moved from non-affected settlements to the endemic regions of Kolubara (38 years ago) or Semberia (20 years ago). All persons were subjected to an interview, objective examination, kidney ultrasound, and laboratory analysis to detect the presence of BEN consensus diagnostic criteria. RESULTS: The number of immigrants with BEN biomarkers outside cutoff values was significantly lower than for BEN family members. Five BEN family members met diagnostic criteria for BEN and four for suspected BEN. Although five non-BEN family members had different combinations of BEN biomarkers, all of them had diseases other than BEN in which these biomarkers also occurred. None of the immigrants met the criteria for BEN. Nevertheless, one descendant of an immigrant, a 78-year-old male, whose mother was from a non-BEN family in the Kolubara district, exhibited all the criteria for BEN: alpha1-microglobulinuria, chronic renal failure, and anemia. CONCLUSION: While 30 years ago, BEN was reported equally among immigrants and natives, currently it is diagnosed in some BEN family members in the eighth decade of life, but extremely rarely in immigrants also in old age.

'Are The Times A-Changin'? Trends in adolescent substance use in Europe.

AIMS: To estimate temporal trends in adolescents' current cigarette, alcohol and cannabis use in Europe by gender and region, test for regional differences and evaluate regional convergence. DESIGN AND SETTING: Five waves of the European School Survey Project on Alcohol and Other Drugs (ESPAD) from 28 countries between 1999 and 2015. Countries were grouped into five regions [northern (NE), southern (SE), western (WE), eastern Europe (EE) and the Balkans (BK)]. PARTICIPANTS: A total of 223 814 male and 211 712 female 15-16-year-old students. MEASUREMENTS: Daily cigarette use, weekly alcohol use, monthly heavy episodic drinking (HED) and monthly cannabis use. Linear and quadratic trends were tested using multi-level mixed-effects logistic regression; regional differences were tested using pairwise Wald tests; mean absolute differences (MD) of predicted prevalence were used for evaluating conversion. FINDINGS: Daily cigarette use among boys in EE showed a declining curvilinear trend, whereas in all other regions a declining linear trend was found. With the exception of BK, trends of weekly drinking decreased curvilinear in both genders in all regions. Among girls, trends in WE, EE and BK differed from trends in NE and SE. Monthly HED showed increasing curvilinear trends in all regions except in NE (both genders), WE and EE (boys each). In both genders, the trend in EE differed from the trend in SE. Trends of cannabis use increased in both genders in SE and BK; differences were found between the curvilinear trends in EE and BK. MD by substance and gender were generally somewhat stable over time. CONCLUSIONS: Despite regional differences in prevalence of substance use among European adolescents from 1999 to 2015, trends showed remarkable similarities, with strong decreasing trends in cigarette use and moderate decreasing trends in alcohol use. Trends of cannabis use only increased in southern Europe and the Balkans. Trends across all substance use indicators suggest no regional convergence.