Sick leaves among healthy pregnant Croatian healthcare workers during the COVID-19 pandemic due to loopholes in the occupational safety system.

The aim of this study was to explore occupational safety in pregnant Croatian healthcare workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic. To this end we composed an anonymous questionnaire that included pregnancy data, risk assessment and mitigation, and workplace intervention and distributed it to HCWs through social media of their groups and associations. The study includes a total of 173 respondents (71.1 % physicians, 19.7 % nurses, 9.2 % other HCWs) diagnosed with pregnancy in 2020 and 2021. Employers were notified about HCWs' pregnancy at the eighth (IQR 7.0-11.0) week of pregnancy, which delayed workplace risk assessment and mitigation beyond the first trimester. Only 19.6 % of the participants had the risk assessed and mitigated, mostly on their own initiative (76.5 %). After notifying employers about pregnancy, 37.0 % of participants opted for temporary work incapacity (TWI) due to "pregnancy complications" despite healthy pregnancy, 16.8 % were granted a pregnant worker's paid leave at the expense of the employer, while 5.8 % continued to work at the same workplace. Nurses used the TWI benefit more frequently than physicians (58.8 % vs 30.1 %, P=0.004). Our findings suggest that occupational safety of pregnant HCWs in Croatia lacks clear-cut and transparent strategies to protect pregnant HCWs, forcing them to misuse the healthcare system.

Spectrum and Frequency of BRAF Mutations in Skin Melanomas in the Dalmatian Region of Croatia.

Mutation of the BRAF oncogene is one of the most common mutations detected in human neoplasia, occurring in 40-60% of all cutaneous melanoma. BRAF is a serine/threonine protein kinase which is an essential part of the mitogen-activated protein kinase (MAPK) pathway. It is physiologically activated by RAS, but in mutated form, due to molecular conformational change, BRAF becomes constitutively active with subsequent persistent activation of downstream cytoplasmic and nuclear proteins (MEK, ERK, ETS), which finally leads to gene expression that promotes cell growth and survival. Inhibition of the altered MAPK pathway by BRAF inhibitors and combined BRAF/MEK inhibitors in BRAF mutated melanoma has become a standard therapeutic approach (1,2). We recently reported the frequency and clinicopathological features of BRAF V600E mutated melanomas in the Dalmatian region of Croatia. This report included 80 cutaneous melanomas with BRAF analyses performed at our institution until the second half of 2017, using a kit which detected only BRAF V600E mutation (3). From the second half of 2017, we started using a kit which detects several types of BRAF mutations along with NRAS mutation. The aim of this report was to determine the spectrum and frequency of different BRAF mutations in a group of skin melanomas in the Dalmatian region of Croatia and to comment on the relationship between type of BRAF mutation and therapeutic response to MAPK pathway inhibition. The analysis included 179 patients with stage 3 and stage 4 cutaneous melanoma with known BRAF/NRAS mutational status. The paraffin blocks were forwarded from four Dalmatian hospitals (Split: 139 cases, Zadar: 17 cases, Sibenik: 13 cases, Dubrovnik: 10 cases). BRAF/NRAS mutation analysis was performed at the Institute of Pathology, Clinical Hospital Center Split, Croatia, in the period from the second half of 2017 to the end of 2022. For DNA extraction analysis, hematoxylin and eosin stained slides from each submitted sample were reviewed by a pathologist, and tumor tissue was identified for analysis. For all tissue specimens, DNA was extracted from sections (10 mm thick) using the cobas® DNA Sample Preparation Kit (Roche Molecular Diagnostics), following the manufacturer's protocol. The amount of genomic DNA was quantified using the Qubit® 2.0 Fluorometer (Life Technologies) and adjusted to a fixed concentration to be added to the amplification/detection mixture. For mutation analysis, the target DNA was amplified and detected on the cobas z 480 analyzer using the amplification and detection reagents provided in the Roche BRAF/NRAS mutation test (LSR) kit, according to the manufacturer's protocol. The test results were reported as follows: BRAF exon 11 mutation detected, BRAF V600E/E2/D mutation detected, BRAF V600K mutation detected, BRAF V600R mutation detected, BRAF K601E mutation detected, NRAS (G12X, G13X, A18T, Q61X, other NRAS Ex3/4) mutation detected, mutation not detected, or invalid result (no result was obtained on the cobas test). BRAF mutation was observed in 87 patients (48.6%), NRAS mutation was found in 27 patients (15.1%), while 65 patients (36.3%) were without BRAF/NRAS mutation (Table 1). In the group of BRAF mutated melanomas, 61 cases (70.1%) had V600E/E2/D mutation, 20 cases (23%) had V600K mutation, 3 cases (3.4%) had exon 11 mutation, 2 cases (2.3%) had V600R mutation, and 1 case (1.2%) had K601E mutation (Table 2). The observed frequency of BRAF mutated melanomas in this study was similar to the frequency reported in our previous study (48.6% and 47.5%, respectively) (3). The vast majority were BRAF V600 mutations, while BRAF non-V600 mutations were rare (95.4% and 4.6%, respectively). In the group of BRAF V600 mutations, V600E/E2/D mutations predominated, followed by V600K mutations, while V600R mutations were rare. Greaves et al. reported similar frequency of BRAF V600 mutations in a group of 499 BRAF-mutated cutaneous melanomas, with V600E/E2/D mutations observed in 77.2% cases, followed by V600K mutations observed in 17.2% cases, and V600R mutations observed in 2.6% cases (4). BRAF non-V600 mutations (exon 11 and K601E mutations) were rarely observed in this study, confirming the findings of other authors (4,5). A three-class system of BRAF mutations was recently proposed that takes into account the differences in their kinase activity, with class I containing mutants with high kinase activity and high response rate to BRAF and BRAF/MEK inhibitors. Class II BRAF mutations have lower kinase activity than class I mutants, but higher than wild-type BRAF, showing resistance to BRAF inhibitor monotherapy and sensitivity to MEK and BRAF/MEK inhibitors. Finally, class III BRAF mutations are characterized by low kinase activity and low response rate to targeted therapy (6). BRAF V600 mutations belong to class I mutations, which means that the large majority of BRAF-positive melanomas in this study (95.4%) were sensitive to targeted therapy. However, the sensitivity to targeted therapy is different among different class I BRAF mutations. While large randomized controlled trials on combined BRAF/MEK inhibition showed good overall response (63-68%) and improvement of progression-free survival (PFS) and overall survival (OS) for the melanomas with most prevalent V600E and V600K mutations, Menzer et al. showed lower response rate to MAPK pathway inhibition (45%) in the group of metastatic melanomas with BRAF V600 mutations other than V600E/K. The overall response rate to MAPK pathway inhibition in the same group of melanomas with BRAF non-V600 mutations (class II and III mutations) was only 18% (7). In our group of BRAF mutated skin metastatic melanomas, we found only 6 cases (6.9%) with expected lower response rate to MAPK pathway inhibition: 2 cases with V600R mutation (class I non-V600E/K mutation), 1 case with K601E mutation (class II mutation), and 3 cases with exon 11 mutation (class II and III mutations).

Polypharmacy and potentially inappropriate prescribing of benzodiazepines in older nursing home residents.

INTRODUCTION: Previous research has raised concerns about high prevalence of drug-related problems, polypharmacy and inappropriate benzodiazepine prescribing in nursing homes (NHs) and confirmed lack of studies from Central and South-Eastern Europe. The aim of our study was to determine the prevalence and characteristics of polypharmacy, hyperpolypharmacy and inappropriate benzodiazepine prescribing in NH residents in Croatia. METHODS: Data from 226 older NH residents from five Croatian NHs were collected using the InterRAI Long-Term Care Facilities assessment form. The prevalence and determinants of polypharmacy/hyperpolypharmacy and patterns of inappropriate benzodiazepine prescribing were documented. RESULTS: The prevalence of polypharmacy (49.6%) and hyperpolypharmacy (25.7%) among NH residents was high. In our study, 72.1% of NH residents were prescribed at least one psychotropic agent, 36.7% used 2-3 psychotropics and 6.6% used 4+ psychotropics. Among benzodiazepine users (55.8%), 28% of residents were prescribed benzodiazepines in higher than recommended geriatric doses, 75% used them for the long term and 48% were prescribed concomitant interacting medications. The odds of being prescribed polypharmacy/hyperpolypharmacy were significantly higher for older patients with polymorbidity (6+ disorders, proportional odds ratio (POR) = 19.8), type II diabetes (POR = 5.2), ischemic heart disease (POR = 4.6), higher frailty (Clinical Frailty Scale (CFS ≥5); POR = 4.3) and gastrointestinal problems (POR = 4.8). CONCLUSIONS: Our research underscores the persistent challenge of inappropriate medication use and drug-related harms among older NH residents, despite existing evidence and professional campaigns. Effective regulatory and policy interventions, including the implementation of geriatrician and clinical pharmacy services, are essential to address this critical issue and ensure optimal medication management for vulnerable NH populations.

Bat Bites and Rabies PEP in the Croatian Reference Centre for Rabies 1995-2020.

Seroprevalence of lyssaviruses in certain bat species has been proven in the Republic of Croatia, but there have been no confirmed positive bat brain isolates or human fatalities associated with bat injuries/bites. The study included a retrospective analysis of bat injuries/bites, post-exposure prophylaxis (PEP) and geographic distribution of bat injuries in persons examined at the Zagreb Antirabies Clinic, the Croatian Reference Centre for Rabies. In the period 1995-2020, we examined a total of 21,910 patients due to animal injuries, of which 71 cases were bat-related (0.32%). Of the above number of patients, 4574 received rabies PEP (20.87%). However, for bat injuries, the proportion of patients receiving PEP was significantly higher: 66 out of 71 patients (92.95%). Of these, 33 received only the rabies vaccine, while the other 33 patients received the vaccine with human rabies immunoglobulin (HRIG). In five cases, PEP was not administered, as there was no indication for treatment. Thirty-five of the injured patients were biologists or biology students (49.29%). The bat species was confirmed in only one of the exposure cases. This was a serotine bat (Eptesicus serotinus), a known carrier of Lyssavirus hamburg. The results showed that the bat bites were rather sporadic compared to other human injuries caused by animal bites. All bat injuries should be treated as if they were caused by a rabid animal, and according to WHO recommendations. People who come into contact with bats should be strongly advised to be vaccinated against rabies. Entering bat habitats should be done with caution and in accordance with current recommendations, and nationwide surveillance should be carried out by competent institutions and in close collaboration between bat experts, epidemiologists and rabies experts.

Referrals For Gender-Affirming Hormone Treatment in Croatia's National Network for Transgender Healthcare.

A network of healthcare professionals specializing in transgender care was established in Croatia in 2011, and legal advancements were subsequently made in 2014. Both achievements made gender transition more transparent and thus more attainable in Croatia. This observational study was conducted to assess the number of transgender individuals initiating gender-affirming hormone treatment (GAHT) in Croatia and describes trends in age and sex assigned at birth. Between 2011 and 2022, a total of 111 transgender individuals initiated GAHT. Within the cohort, 52 were assigned male at birth (AMAB) and 59 were assigned female at birth (AFAB). The overall annual incidence rate of transgender individuals initiating GAHT was 0.52 per 100,000 age-adjusted individuals. There was a statistically significant increase (p < 0.01) in transgender individuals commencing GAHT before the COVID-19 pandemic. Furthermore, a rising trend toward masculinizing rather than feminizing treatment was identified (p < 0.05), particularly among younger transgender individuals. The COVID-19 pandemic disrupted these trends in 2020, except for the trend of initiating therapy at a younger age (p < 0.01). The annual incidence and age distribution trends of transgender individuals initiating GAHT in Croatia closely mirrored those in other European countries, with a higher prevalence of individuals assigned female at birth. The study underscores a significant rise in the number of individuals initiating gender-affirming hormone treatment, emphasizing the need for proper legal regulation and healthcare system response.

Impact of the number of therapy lines on survival in advanced gastric and esophagogastric adenocarcinoma - a real-world retrospective analysis from Croatia.

The aim of the study was to conduct a retrospective database analysis to understand the current treatment patterns and outcomes to plan potential improvements in therapy delivery and patient selection. The electronic patient medical records of 225 patients with advanced gastric and esophagogastric adenocarcinoma treated at two Croatian high-volume tertiary centers from January 2018 to December 2021 were analyzed. Patients ineligible for chemotherapy (66 of 291, 22.7%) due to poor general condition or co-morbidities were not included in the study. The median overall survival (OS) for the whole cohort was 11.0 months (95% confidence interval (CI) 9.7-12.0). Of the 225 patients who received first-line therapy, 47.6%, 16.9%, and 3.1% received second-, third-, and fourth-line therapy, respectively. Survival correlated significantly with the number of treatment lines received (p<0.001), with a median OS from diagnosis of 7.8 (95% CI 6.6-9.4), 12.0 (95% CI 10.0-14.0), and 20.0 months (95% CI 18.0-23.0) for patients receiving 1, 2, and ≥3 lines of treatment, respectively. This study confirmed the positive impact of the number of chemotherapy lines on OS. This highlights the importance of the ratio of patients receiving multiple lines of therapy as well as the availability of new and effective drugs in real-life clinical practice. The selection of optimal therapy for each patient in the first-line therapy is important because a significant number of patients do not receive second-line therapy.

The mediating role of depressive, anxiety, and physical symptoms on work ability index in employed women with breast cancer: a prospective study from Croatia.

AIM: To explore the relationship between the current work ability index (WAI) and depressive and anxiety symptoms in breast cancer (BC) patients and the role of depressive, anxiety, and physical symptoms in mediating this relationship. METHODS: This prospective study enrolled 83 employed women with BC. At baseline assessment (in the first three months following BC diagnosis) and follow-up assessment (one year after baseline), participants completed the WAI, Beck Depression Inventory-II, State-Trait Anxiety Inventory, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire with a breast cancer-specific module. Mediation analyses were conducted to explore the mechanism by which depressive, anxiety, and physical symptoms influenced the relationship between WAI and depressive and anxiety symptoms. RESULTS: WAI was negatively associated with depressive and anxiety symptoms. The effect of baseline depressive and trait anxiety symptoms on WAI at follow-up was mediated by both depressive and trait anxiety symptoms, as well as by physical symptoms at follow-up. The effect of baseline state anxiety symptoms on WAI at follow-up was mediated only by state anxiety symptoms at follow-up. CONCLUSIONS: Baseline depressive and anxiety symptoms affect WAI at follow-up not only through persisting depressive and anxiety symptoms observed at follow-up but also through physical symptoms at follow-up. This indicates that efforts aimed at improving psychological health may result in simultaneous improvements in both psychological and physical health, as well as the resulting WAI.

Sex Ratio at Birth after Concurrent Events of Earthquakes and the COVID-19 Pandemic in Croatia.

The sex ratio at birth (ratio of males to females) has been known to be affected by exogenous shocks such as wars, pollution, natural catastrophes, economic crises, and others. Among these stressful events, both earthquakes and the COVID-19 pandemic have been reported to lower the sex ratio at birth. In this article, a rather unusual situation of two episodes of simultaneous events of COVID-19 lockdown and earthquakes approximately nine months apart (March and December of 2020) is investigated to assess whether they were associated with a bias in sex ratio at birth 3-5 months later (in utero loss) and 9 months later (loss at conception) in Croatia. The monthly time series of sex ratio at birth, total number of births, and total number of both male and female births from January 2010 to December 2021 were analyzed. Seasonally adjusted autoregressive moving-average models were used to estimate the functional form of the time series from January 2010 to February 2020. These results were used to predict the future values of the series until December 2021 and to compare them with the actual values. For all series used, there was no indication of deviation from the values predicted by the models, neither for 3-5 months nor for 9 months after the COVID-19 lockdown and earthquake events. The possible mechanisms of the absence of bias, such as the threshold of the stressful events and its localized reach, as well as the statistical methods employed, are discussed.

Detection of Macrolide and/or Fluoroquinolone Resistance Genes in Mycoplasma genitalium Strains Isolated from Men in the Northwest Region of Croatia in 2018-2023.

Mycoplasma genitalium (M. genitalium) poses a significant public health challenge due to its association with non-gonococcal urethritis (particularly in men) and antimicrobial resistance. However, despite the prevalence of M. genitalium infections and the rise in resistance rates, routine testing and surveillance remain limited. This is the first study from Croatia that aimed to assess the prevalence and trends of resistance in M. genitalium strains isolated from male individuals by detecting macrolide and fluoroquinolone resistance genes. The study also aimed to explore the factors associated with resistance and changes in resistance patterns over time. Urine samples collected from male individuals in the Zagreb County and northwest region of Croatia between 2018 and 2023 were tested for M. genitalium with the use of molecular methods. Positive samples were subjected to DNA extraction and multiplex tandem polymerase chain reaction (MT-PCR) targeting genetic mutations associated with macrolide (23S rRNA gene) and fluoroquinolone (parC gene) resistance. Of the 8073 urine samples tested from 6480 male individuals (and following the exclusion of repeated specimens), we found that the prevalence of M. genitalium infection was 2.2%. Macrolide resistance was observed in 60.4% of strains, while fluoroquinolone resistance was found in 19.2%. Co-resistance to both antibiotics was present in 18.2% of cases. A statistically significant increase in fluoroquinolone resistance was noted over the study period (p = 0.010), but this was not evident for azithromycin resistance (p = 0.165). There were no statistically significant differences in resistance patterns between age groups, whereas re-testing of patients revealed dynamic changes in resistance profiles over time. The high burden of macrolide resistance and increasing fluoroquinolone resistance underscore the urgent need for comprehensive resistance testing and surveillance programs. The implementation of resistance-guided treatment strategies, along with enhanced access to molecular diagnostics, is pivotal for effectively managing M. genitalium infections.

The Influence of the COVID-19 Pandemic on Hospitalizations for Ambulatory Care-Sensitive Conditions in Split-Dalmatia County, Croatia.

Background and Objectives: We aimed to explore whether the COVID-19 pandemic influenced hospitalizations for ambulatory care-sensitive conditions (ACSCs) in Split-Dalmatia County, Croatia. Materials and Methods: We performed a cross-sectional comparative study using two different time periods, the pre-pandemic (from March 2019 to February 2020) and the pandemic period (from March 2020 to February 2021), to explore the possible influences that the COVID-19 pandemic had on hospitalizations for ACSCs. The ACSCs were classified into the categories of vaccine-preventable, chronic, and acute disease. The indicators were statistically analyzed. Results: During the pandemic, a decrease in the total number of hospitalizations and ACSC hospitalizations was recorded. The relative risk for having any ACSC hospitalization in the pandemic period compared to the pre-pandemic period was 0.67 (95% CI, 0.64-0.71; p = 0). The risk reduction was seen in all three categories of vaccine-preventable ACSCs, chronic disease, and acute disease. Large reductions were found in the relative risk of hospitalization for COPD and asthma. Considering the mode of discharge, there was a statistically significantly higher risk of ACSCs with fatal outcomes during the pandemic than in the pre-pandemic period (relative risk 1.31; 95% CI, 1.01-1.7; p = 0.0197). Conclusions: The results of this study show that the COVID-19 pandemic influenced the total number of hospitalizations as well as hospitalizations relating to ACSCs. Certainly, one of the reasons for these changes was due to organizational changes in the working of the entire health system due to the COVID-19 pandemic.

Prevalence of risk factors for development of cardiovascular diseases in urban and rural areas of Eastern Croatia: a cross-sectional study.

OBJECTIVE: Cardiovascular diseases are the leading global cause of death. Due to the disparities in cardiovascular risk factors between rural and urban populations, this study aims to assess the differences in the prevalence of risk factors in urban and rural areas of eastern Croatia. METHODS: The cross-sectional study included 280 participants (140 from urban and 140 from rural areas) registered at studied general practice offices. Methods included e-health records, questionnaire, physical examination methods, and blood sampling for laboratory tests. RESULTS: The most common risk factors among participants were elevated total cholesterol (83.6%), elevated LDL cholesterol (81.8%), increased body mass index (75.0%), increased waist-hip ratio (82.9%), increased waist circumference (63.2%), and arterial hypertension (70.1%). The rural participants had a significantly higher prevalence of arterial hypertension (p = 0.023), increased body mass index (p = 0.004), increased waist circumference (p = 0.004), increased waist-hip ratio (p < 0.001), and increased LDL cholesterol (p = 0.029), while the urban participants had a significantly higher prevalence of insufficient physical activity (p < 0.001). CONCLUSIONS: In the examined sample, the prevalence of cardiovascular risk factors is generally high. Participants from rural areas are significantly more susceptible to cardiovascular risk factors than participants from urban areas.

Monitoring HPV Prevalence and Risk Cofactors for Abnormal Cytology in the Post-Vaccination Period among Croatian Women.

The incidence and mortality rate of cervical cancer in Croatia remains a health challenge despite screening efforts. Besides the persistent infection with HPV, the development of cancer is also associated with some cofactors. The goal of this study was to assess circulating HPV genotypes and risk factors for the development of cervical precancer after almost 16 years from the onset of HPV vaccination in Croatia. In this study, a total of 321 women attending gynecological care were evaluated. Relevant medical and demographic information, including cytology, were collected. HPV genotyping was performed by PCR. Comparing the HPV types found in circulation in the pre-vaccination (1999-2015) and post-vaccination periods (2020-2023), a statistically significant reduction in HPV 31 was noted, while the overall prevalence increased in the post-vaccination period. Besides the expected HPV positivity as a risk factor, the history of smoking was associated with LSIL or worse cytology at enrollment. For the first time, this population study revealed a statistically significant shift in the HPV genotype in the post-vaccination period, as well as the confirmation of risk factors for the development of abnormal cytology among Croatian women.

The role of longevity-related genetic variant interactions as predictors of survival after 85 years of age.

Genome-wide association studies and candidate gene studies have identified several genetic variants that might play a role in achieving longevity. This study investigates interactions between pairs of those single nucleotide polymorphisms (SNPs) and their effect on survival above the age of 85 in a sample of 327 Croatian individuals. Although none of the SNPs individually showed a significant effect on survival in this sample, 14 of the 359 interactions tested (between SNPs not in LD) reached the level of nominal significance (p<0.05), showing a potential effect on late-life survival. Notably, SH2B3 rs3184504 interacted with different SNPs near TERC, TP53 rs1042522 with different SNPs located near the CDKN2B gene, and CDKN2B rs1333049 with different SNPs in FOXO3, as well as with LINC02227 rs2149954. The other interaction pairs with a possible effect on survival were FOXO3 rs2802292 and ERCC2 rs50871, IL6 rs1800795 and GHRHR rs2267723, LINC02227 rs2149954 and PARK7 rs225119, as well as PARK7 rs225119 and PTPN1 rs6067484. These interactions remained significant when tested together with a set of health-related variables that also had a significant effect on survival above 85 years. In conclusion, our results confirm the central role of genetic regulation of insulin signalling and cell cycle control in longevity.

Seroepidemiology of Herpes Simplex Viruses Type 1 and 2 in Pregnant Women in Croatia.

Background and Objectives: Herpes simplex viruses (HSV-1 and HSV-2) are one of the most widespread causes of human viral infections. In Croatia, only two published studies have analyzed the seroprevalence of HSV infections in childbearing-aged and pregnant women (2005-2010), while more recent data are lacking. This study aimed to analyze the prevalence and risk factors for HSV-1 and HSV-2 infections among pregnant women in Croatia in the period from 2011 to 2021. Materials and Methods: This study included 667 pregnant women aged 16-45 years submitted for HSV-1 and HSV-2 serology testing. Serum samples were initially screened for HSV-1 and HSV-2 IgM and IgG antibodies using a commercial ELISA test with a confirmation of HSV-2-positive samples using an immunoblot assay. Results: The overall IgG seroprevalence rates were 69.9% for HSV-1 and 3.8% for HSV-2. A significant gradual increase in the HSV-2 seroprevalence with age was observed from 0.5% in participants under 30 years to 8.3% in participants above 40 years. The HSV-1 seroprevalence was stable up to 40 years (70.0 and 68.3%, respectively), with an increase to 86.1%, but this difference did not reach statistical significance. Area of residence (urban or suburban/rural), geographic region (continental or coastal), and obstetric history (normal pregnancy or unfavorable obstetric history) were not associated with HSV-1 and HSV-2 seroprevalence. Older age was found to be a significant risk factor for HSV-2 seropositivity in both univariate and multivariate risk analysis. Conclusions: HSV-1 infection is widely prevalent among pregnant women with a stable trend over time. However, a declining trend in the HSV-2 seroprevalence was observed compared to 2005-2010. Serological screening in pregnant women is important in identifying seronegative women who are susceptible to HSV infection as well as seropositive women who are at risk for genital herpes recurrence during delivery.

Epidemiology of Bartonella henselae infection in pet and stray cats in Croatia with risk factors analysis.

BACKGROUND: Cats are the primary reservoirs of the bacterium Bartonella henselae, the main cause of cat-scratch disease in humans. The main vector of the bacterium is the cat flea, Ctenocephalides felis. In southeastern Europe, data are lacking on the prevalence of B. henselae infection in cats, the strains of B. henselae involved and the risk factors associated with the infection. METHODS: Blood samples collected in ethylenediaminetetraacetic acid-containing tubes from 189 domestic cats (156 pet cats and 33 stray cats) from Zagreb, the capital city of Croatia, and 10 counties throughout Croatia were cultured for Bartonella spp. Following culture, bacterial isolates were genotyped at eight loci after using PCR to amplify 16S ribosomal RNA (rRNA) and the internal transcribed spacer region between the 16S and 23S rRNA sequences. Univariate and multivariate logistic regression were used to identify risk factors for B. henselae infection in cats. RESULTS: Bartonella spp. was detected in 31 cats (16.4%), and subsequent genotyping at the eight loci revealed B. henselae in all cases. Thirty complete multilocus sequence typing profiles were obtained, and the strains were identified as four sequence types that had been previously reported, namely ST5 (56.7%), ST6 (23.3%), ST1 (13.3%) and ST24 (3.3%), as well as a novel sequence type, ST33 (3.3%). The univariate analysis revealed a significantly higher risk of B. henselae infection in cats residing in coastal areas of Croatia (odds ratio [OR] 2.592, 95% confidence interval [CI] 1.150-5.838; P = 0.0191) and in cats with intestinal parasites (OR 3.207, 95% CI 1.088-9.457; P = 0.0279); a significantly lower risk was identified in cats aged > 1 year (OR 0.356, 95% CI 0.161-0.787; P = 0.0247) and in cats sampled between April and September (OR 0.325, 95% CI 0.147-0.715; P = 0.005). The multivariate analysis that controlled for age showed a positive association with the presence of intestinal parasites (OR 4.241, 95% CI 1.243-14.470; P = 0.0119) and coastal residence (OR 2.567, 95% CI 1.114-5.915; P = 0.0216) implying increased risk of infection, and a negative association with sampling between April and September (OR 0.379, 95% CI 0.169-0.848; P = 0.018) implying a decreased risk of infection. After controlling for the season, an increased risk of infection remained for the coastal region (OR 2.725, 95% CI 1.200-6.186; P = 0.012). CONCLUSIONS: Bartonella henselae is prevalent throughout Croatia and is a public health threat. Environmental and host factors can significantly affect the risk of infection, and these should be explored in more detail. The presence of intestinal parasites highlights the need to eliminate the flea vector, Ctenocephalides felis, as the most effective approach to control infections in cats and humans.

Levels of depression, anxiety and subjective happiness among health sciences students in Croatia: a multi-centric cross-sectional study.

BACKGROUND: Previous studies have shown that symptoms of depression and anxiety were highly prevalent among health sciences students. This may lead to other professional and personal difficulties and a decrease in individuals' well-being. This study aimed to analyze levels of depression, anxiety and subjective happiness among health sciences students in Croatia. METHODS: We conducted a cross-sectional study in 10 higher education institutions in Croatia during March 2023. Eligible participants were health sciences students. Participants filled out an online survey consisting of sociodemographic questions and validated scales for determining the levels of depression (9-question Patient Health Questionnaire, PHQ-9), anxiety (General Anxiety Disorder 7-item scale, GAD-7), and happiness (Subjective Happiness Scale, SHS). RESULTS: Of 7460 invited students, 2137 students participated in the study (29% response rate). There were 41.4% of students that exhibited at least mild depressive symptoms, with 8% of students exhibiting moderately severe symptoms and 1.8% severe depressive symptoms. Mild anxiety was found in 36.8%, moderate anxiety in 23.9% and severe anxiety in 15.8% of students. The median SHS score was 19 (15.25-22). Women students had significantly higher levels of depression (p < 0.001) and anxiety (p < 0.001) than their men peers. Students in earlier study years showed higher levels of depression, anxiety and lower levels of subjective happiness compared to those in later study years. Students with lower self-assessed financial status had higher levels of depression (p < 0.001) and anxiety (p < 0.001). Students that failed an academic year had higher levels of depression (p < 0.001), but lower levels of anxiety (p = 0.005). CONCLUSION: In this study, we have shown that health sciences students exhibit high levels of depression and anxiety, at rates exceeding those in the general population reported in other studies. Our results may help educational institutions to put greater effort into the battle against mental health stigma, foster acceptance of mental health issues and encourage students to seek help when needed. Adequate mental health services are needed at universities to promote timely diagnosis and treatment of mental health problems.

Increased number of cryptosporidiosis cases with travel history to Croatia might be related to swimming pools, Germany, 2023.

In August and September 2023, an unusually high number of cryptosporidiosis cases identified by routine German surveillance had travelled to Croatia (n = 23). Nine cases had stayed in the same camping resort and seven further cases had stayed at other camping sites within 15 km. Based on our standardised questionnaires, the most likely source of infection was swimming pools (93%). Further environmental investigations on site might reveal potential common sources of contamination that could be targeted by control measures.

Bloodstream Infections in Pediatric Oncology Patients: Bacterial Pathogen Distribution and Antimicrobial Susceptibility at the University Hospital Centre Zagreb, Croatia-A 5-Year Analysis.

The epidemiology of bacterial pathogens causing bloodstream infections (BSIs) in pediatric hematology/oncology patients is changing and resistance to antimicrobial agents is globally spread. We retrospectively assessed demographic, clinical, and microbiologic data of BSIs during a 5-year period at a pediatric hematology/oncology unit from January 1, 2017, to December 31, 2021, at the University Hospital Centre Zagreb, Zagreb, Croatia. In 66 pediatric patients with malignancies, 93 BSI episodes were registered and 97 bacterial isolates were cultured. The Gram-positive versus Gram-negative ratio was 67 (69.1%) versus 30 (30.9%). Coagulase-negative staphylococci (48; 49.6%) were the most frequent isolates, followed by Enterobacterales (17; 17.5%) and Staphylococcus aureus (6; 6.2%). Multidrug resistance isolates included extended spectrum ß-lactamase producers (n=3). Resistance rates to piperacillin/tazobactam, cefepime, and meropenem in Gram-negative isolates were 15.4%, 14.3%, and 0.0%, respectively. Gram-positive bacteria are the most common cause of BSI in our patients. Resistance rates to piperacillin/tazobactam and cefepime in Gram-negative isolates make meropenem a better choice for empirical antimicrobial treatment. As national and hospital data may differ, the surveillance of pathogen distribution and antimicrobial susceptibility in pediatric hematology/oncology wards is necessary to adjust empirical treatment accordingly.

SPATIAL AND SOCIAL ASPECTS OF THE 1918-1919 PANDEMIC FLU IN SPLIT / Prostorna i socijalna obiljezja pandemijske gripe 1918. - 1919. u Splitu

The Spanish flu pandemic is considered the largest and most dangerous epidemic at the beginning of the 20th century affecting most of the world today. The Spanish flu pandemic did not bypass the territory of Croatia (at the time, Croatia was part of the Austro-Hungarian Monarchy), nor its southern coastal region of Dalmatia and the city of Split. Using the example of the city Split, the paper analyses the spatial and demographic determinants of population mortality from the Spanish flu between 1918 and 1919, i.e., from March 1918 to April 1919. The paper is based on the data of the Church Death registers kept in the Archbishop's Archives in Split and newspaper articles. The analysis of the spatial distribution of mortality within urban settlements showed that the number of deaths per urban settlement