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András Südi,1 Balázs Sánta,2,3 Alpár Horváth,1,2 Gábor Tomisa,1 Zsolt Abonyi-Tóth,4,5 György Rokszin,4 Noémi Eszes,1 Veronika Müller,1 Lilla Tamási1 1Department of Pulmonology, Semmelweis University, Budapest, Hungary; 2Medical Department, Chiesi Hungary Kft, Budapest, Hungary; 3Department of Pulmonology, Szent Borbála County Hospital, Tatabanya, Hungary; 4Rx Target Kft, Budapest, Hungary; 5Department of Biostatistics, University of Veterinary Medicine, Budapest, HungaryCorrespondence: Lilla Tamási, Department of Pulmonology, Semmelweis University, Töm&odblac; Str. 25-29, Budapest, 1083, Hungary, Fax +36-1- 214-2498, Email tamasi.lilla@med.semmelweis-univ.huPurpose: COPD affects more than 300 million people worldwide, requiring inhalation treatment. Novel triple formulations of ICS, LABAs and LAMAs are becoming the mainstay of treatment, however there is still a lack of clinical evidence for personalized therapy.Patients and Methods: RATIONALE was a non-interventional, prospective, 52 week study, assessing the effectiveness of beclometasone/formoterol/glycopyrronium-bromide (BDP/FF/G), in symptomatic COPD patients, with moderate airflow obstruction. The study included 4 visits, where data on demographic parameters, exacerbations, symptoms, quality of life (based on the EQ-5D-3L questionnaire) and lung function were collected. Data on adherence to treatment, based on prescriptions filled was collected from the database of the National Health Insurance Fund, with the patients’ consent. The primary objective was the change of adherence to treatment during the study, compared to baseline.Results: Altogether 613 patients had been enrolled. Their average age was 64.56 years and 50.5% were female. The average CAT score was 20.86, and most patients had suffered minimum one exacerbation (82.2%). Average FEV1 was 59.6%. Most patients had some limitation in one or more dimensions of EQ-5D-3L, with an average visual analogue scale score (VAS) of 60.31. After 12 months of treatment, adherence improved significantly – proportion of patients in the highest adherence group increased from 29.8% to 69.7% (p< 0.001). The average CAT score improved by 7.02 points (95% CI 5.82– 8.21, p< 0.001). There was a significant improvement in all dimensions of EQ-5D-3L, with an average increase of 17.91 (95% CI 16.51– 19.31, p< 0.001) points in the VAS score. Exacerbation frequency also decreased significantly.Conclusion: Although limitations of observational studies are present, we observed that early introduction of fixed triple combination results in a marked improvement in adherence to treatment, symptom scores, exacerbation frequency and quality of life. The optimal choice of treatment is crucial for reaching the highest possible adherence.Keywords: COPD, fixed triple combination, inhalation treatment, quality of life

Abstract Background Therapeutic reference pricing (TRP) based on the WHO daily defined dose (DDD) is a method frequently employed for the cost-containment of pharmaceuticals. Our objective was to compare average drug use in the real world with DDD and to evaluate whether TRP based on DDD could result in cost savings on maintenance medication and the total direct health expenditures for asthma patients treated with Symbicort Turbuhaler (SYT) and Seretide Diskus (SED) in Hungary. Methods Real-world data were derived from the Hungarian National Health Insurance Fund database. Average doses and costs were compared between the high-dose and medium-dose SYT and SED groups. Multiple linear regressions were employed to adjust the data for differences in the gender and age distribution of patients. Results 27,779 patients with asthma were included in the analysis. Average drug use was lower than DDD in all groups, 1.38-1.95 inhalations in both SED groups, 1.28-1.97 and 1.74-2.49 inhalations in the medium and high-dose SYT groups, respectively. Although the cost of SED based on the DDD would be much lower than the cost of SYT in the medium-dose groups, no difference was found in the actual cost of the maintenance therapy. No significant differences were found between the groups in terms of total medical costs. Conclusions Cost-containment initiatives by payers may influence clinical decisions. TRP for inhalation asthma drugs raises special concern, because of differences in the therapeutic profile of pharmaceuticals and the lack of proven financial benefits after exclusion of the effect of generic price erosion. Our findings indicate that the presented TRP approach of asthma medications based on the daily therapeutic costs according to the WHO DDD does not result in reduced public healthcare spending in Hungary. Further analysis is required to show whether TRP generates additional expenditures by inducing switching costs and reducing patient compliance. Potential confounding factors may limit the generalisability of our conclusions.

Background: The nationwide HUN-CANCER EPI study examined cancer incidence and mortality rates in Hungary from 2011 to 2019., Methods: Using data from the National Health Insurance Fund (NHIF) and Hungarian Central Statistical Office (HCSO), our retrospective study analyzed newly diagnosed malignancies between Jan 1, 2011, and Dec 31, 2019. Age-standardized incidence and mortality rates were calculated for all and for different tumor types using both the 1976 and 2013 European Standard Populations (ESP)., Findings: The number of newly diagnosed cancer cases decreased from 60,554 to 56,675 between 2011-2019. Age-standardized incidence rates were much lower in 2018, than previously estimated (475.5 vs. 580.5/100,000 person-years [PYs] in males and 383.6 vs. 438.5/100,000 PYs in females; ESP 1976). All-site cancer incidence showed a mean annual decrease of 1.9% (95% CI: 2.4%-1.4%) in men and 1.0% (95% CI:1.42%-0.66%) in women, parallel to mortality trends (-1.6% in males and -0.6% in females; ESP 2013). In 2018, the highest age-standardized incidence rates were found for lung (88.3), colorectal (82.2), and prostate cancer (62.3) in men, and breast (104.6), lung (47.7), and colorectal cancer (45.8) in women. The most significant decreases in incidence rates were observed for stomach (4.7%), laryngeal (4.4%), and gallbladder cancers (3.5%), with parallel decreases in mortality rates (3.9%, 2.7% and 3.2%, respectively)., Interpretation: We found a lower incidence of newly diagnosed cancer cases for Hungary compared to previous estimates, and decreasing trends in cancer incidence and mortality, in line with global findings and the declining prevalence of smoking., Competing Interests: Authors ZKi, ZP, EG, MV, AB, TS, EK and KK were employed by the company MSD Pharma Hungary. ZV is an employee of Semmelweis University. Semmelweis University received a grant from MSD Pharma Hungary to contribute to this research. GR, VK, AB-T and IF are employees of RxTarget Ltd. and ZB is employed by Syntesia Ltd. where their contribution to this project was financially compensated. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study received funding from MSD Pharma Hungary. The funder had the following involvement with the study: study design, data collection and analysis, decision to publish, and preparation of the manuscript., (Copyright © 2024 Kiss, Szabó, Polgár, Horváth, Nagy, Fábián, Kovács, Surján, Barcza, Kenessey, Wéber, Wittmann, Molnár, Gyöngyösi, Benedek, Karamousouli, Abonyi-Tóth, Bertókné Tamás, Fürtős, Bogos, Moldvay, Gálffy, Tamási, Müller, Krasznai, Ostoros, Pápai-Székely, Maráz, Branyiczkiné Géczy, Hilbert, Tamás Berki, Rokszin and Vokó.)

(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer has become the leading cause of death in several countries. Our objective was to determine whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study comprised a nationwide analysis conducted in Hungary. The study population was divided into two groups: a type 2 diabetes mellitus group vs. a non-diabetic group. The primary outcome was the risk related to overall cancer incidence; a key secondary outcome was the overall incidence of cancer in distinct study years; and a further outcome was the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, p < 0.0001) in patients with diabetes as related to non-diabetic controls. The odds ratio was higher in males than in females [OR males : 2.76 (2.70-2.82) vs. OR females : 2.27 (2.22-2.33), p < 0.05 for male-to-female comparison]. The annual cancer incidence rate declined in non-diabetic controls, but not in patients with diabetes [-1.79% (-2.07--1.52%), p < 0.0001] vs. -0.50% (-1.12-+0.10%), p = 0.0991]. Several types of cancer showed a decreasing tendency in non-diabetic controls, but not in patients with type 2 diabetes. (4) Conclusions: Type 2 diabetes is associated with a higher risk of cancer. While the cancer incidence decreased for non-diabetic individuals with time, it remained unchanged in patients with T2DM.

Objective: Hungary has repeatedly been shown to have the highest cancer-related mortality and incidence in Europe. Despite lung cancer being the most abundant malignant diagnosis in Hungary, numerous concerns have been raised recently regarding the bias inherent to reported incidence estimates. Re-analysis of reimbursement claims has been suggested previously by our group as an alternative approach, offering revised figures of lung cancer incidence between 2011 and 2016. Leveraging on this methodology, we aimed at updating Hungarian lung cancer incidence estimates with an additional 5 years (2017-2021), including years affected by the COVID-19 pandemic. Additionally, we also attempted to improve the robustness of estimates by taking additional characteristics of the patient pathway into account., Methods: Lung cancer patients between 2011 and 2021 were identified based on reimbursement-associated ICD-10 codes, histology codes and time patterns. Multiple query architectures were tested for sensitivity and compared to official estimates of the Hungarian National Cancer Registry (HNCR). Epidemiological trends were estimated by Poisson-regression, corrected for age and sex., Results: A total of 89,948 lung cancer patients diagnosed in Hungary between 2011 and 2021 have been identified by our study. In 2019 alone, 7,887 patients were diagnosed according to our optimized query. ESP2013 standardized rate was estimated between 92.5/100,000 (2011) and 78.4/100,000 (2019). In 2019, standardized incidence was 106.8/100,000 for men and 59.7/100,000 for women. Up until the COVID-19 pandemic, lung cancer incidence was decreasing by 3.18% (2.1%-4.3%) yearly in men, while there was no significant decrease in women. Young age groups (40-49 and 50-59) featured the largest improvement, but women aged 60-79 are at an increasing risk for developing lung cancer. The COVID-19 pandemic resulted in a statistically significant decrease in lung cancer incidence, especially in the 50-59 age group (both sexes)., Conclusion: Our results show that using an optimized approach, re-analysis of reimbursement claims yields robust estimates of lung cancer incidence. According to this approach, the incidence rate of male lung cancer is declining in Hungary, in concordance with the trend observed for lung cancer mortality. Among women aged 60-79, the incidence of lung cancer has risen, requiring more attention in the near future., Competing Interests: GS, GH, ÉB, and KK are employees of MSD Pharma Hungary Ltd. ZV is an employee of Semmelweis University where his contribution to this project was financially compensated. ZKis is also an employee of MSD Pharma Hungary Ltd. and has an affiliation at the Second Department of Medicine and Nephrology-Diabetes Center, University of Pécs Medical School, Pécs, Hungary. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. The project was financed by MSD Pharma Hungary Ltd. VM has received consultation fees from AstraZeneca, Boehringer Ingelheim, Roche, Berlin-Chemie, Chiesi, BMS, Novartis, Actelion, Gilead, Pfizer, Richter, Lilly, Orion Pharma and Ipsen and served as PI for over 10 LC studies. LT is an employee of Semmelweis University. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gálffy, Szabó, Tamási, Müller, Moldvay, Sárosi, Kerpel-Fronius, Kardos, Csada, Pápai-Székely, Szász, Király, Hódi, Kovács, Balogh, Kovács, Darida, Buga, Rokszin, Abonyi-Tóth, Kiss, Vokó and Bogos.)

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Authors Zsolt Abonyi-T&oacute;th, Gy&ouml;rgy Rokszin and Ibolya F&aacute;bi&aacute;n are employed by RxTarget Ltd., Szolnok, Hungary. Zolt&aacute;n Kiss is also employed by MSD Pharma Hungary Ltd., but this provides no relevant conflict of interest for the current research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Background: The criteria for significant bronchodilator responsiveness (BDR) were published in 2005 by the European Respiratory Society/American Thoracic Society, which were revised in 2021, however, data on the agreement between these two recommendations in untreated patients with airflow limitation are missing., Aims: We aimed to study BDR to salbutamol (SABA) or ipratropium bromide (SAMA) in patients with suspected bronchial asthma or COPD at initial clinical presentation using the 2005 and 2021 criteria and explore clinical factors associated with BDR+., Methods: Symptomatic, treatment-naïve patients with expiratory airflow limitation ( n  = 105, 57 men, age (mean ± standard deviation): 65 ± 10 years) underwent BDR testing with 400 mcg salbutamol (day 1) or 80 mcg ipratropium bromide (day 2) and BDR was measured after 15 and 30 minutes. Clinical factors with risk for BDR+ were assessed with binomial logistic regression analysis., Results: We found a good agreement between the number of 2005-BDR+ and 2021-BDR+ patients at 15 and 30 minutes post-salbutamol and post-ipratropium (88.6-94.8%). More patients showed BDR+ after 30 minutes than following 15 minutes using either criterion. When results at 30 minutes are considered, the number of patients with 2005-BDR+ (82%) was higher than that of 2021-BDR+ (75%), with the proportion of SAMA+ patients being higher than that of SABA+ (2005: 70% vs. 49%, Fisher exact p  < 0.01; 2021: 64% vs. 41%, p  = 0.001). 2005-BDR+ and 2021-BDR+ to SABA were associated with decreasing pre-BD FEV 1 % predicted and the presence of cough. More patients with asthma were in the SABA+ group compared to the SAMA+ group (2005: 71% vs. 53%, Fischer exact p  = 0.04; 2021: 77% vs. 52%, p  = 0.02)., Conclusions: Fewer patients show BDR+ according to the 2021 criteria in comparison with the 2005 recommendations, and protocols for BDR testing may consider the assessment of response to both SABA and SAMA after 30 minutes., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Paratuberculosis (PTB) is a severe, slow-developing, untreatable disease of ruminants. Worldwide, the disease affects more than 50% of herds in the dairy industry, and causes substantial economic losses for dairy producers. Diagnostic tests show limited sensitivity, especially in the early stages of the disease. Our study aimed to investigate the seroprevalence of Mycobacterium avium ssp. paratuberculosis (MAP) in large-scale dairy herds in Hungary, in association with the self-reported presence or absence of screening and intervention measures against MAP transmission. We processed data from 42 large-scale Holstein Friesian farms in Hungary between 1 January 2018 and 31 December 2021. An average of 32,009 (min.: 31,702; max.: 32,207) animals were blood sampled yearly (127,372 in total during the four years), corresponding to 15% of the Hungarian dairy cattle population. All female cattle older than 2 years were blood sampled on the farms enroled in the study. The samples were tested using a commercial ELISA (IDEXX paratuberculosis screening Ab test). Farm managers were interviewed about their on-farm diagnostic and intervention approaches using a uniform questionnaire, including questions on the level of awareness, frequency of ELISA and PCR testing, and their strategies for culling adult animals and reducing transmission to newborn calves. By comparing the annual rate of change in seroprevalence and the amount of change observed during the four-year period, we concluded that test-and-cull strategies implemented in parallel with newborn calf management that aimed at preventing MAP transmission were superior to test-and-cull strategies alone; moreover, fortifying culling decision making via additional ELISA and PCR tests is superior to using a single ELISA result. For farms that carried out a complex program with both "test-and-cull" and proper newborn calf management, there was a proportional reduction in apparent seroprevalence at an average of 22.8% per year. Fifteen of the sampled farms had no measures in place to control paratuberculosis. On these farms, the seroprevalence increased by 12.1% per year on average.

The popularity of seafoods is high due to their superb dietary properties and healthy composition. However, it is crucial to understand whether they adequately contribute to our essential nutritional needs. Small amounts of essential metals are indispensable in the human body to proper physiological functioning; their deficiency can manifest in various sets of symptoms that can only be eliminated with their intake during treatment or nutrition. However, the excessive consumption of metals can induce undesirable effects, or even toxicosis. Shellfish, oyster, and squid samples were collected directly from a fish market. After sample preparation, the concentration of essential metals (cobalt, chromium, copper, manganese, molybdenum, nickel, and zinc) was detected by Inductively Coupled Plasma Optical Emission Spectrometry. The results were analyzed statistically using ANOVA and two-sample t -tests. The average concentration of the investigated essential elements and the calculated burden based on the consumption were below the Recommended Dietary Allowances and Tolerable Upper Intake Levels. Based on these results, the trace element contents of the investigated seafoods do not cover the necessary recommended daily intake of them, but their consumption poses no health hazard due to their low levels.

Objective: The approval of immunotherapy (I-O) for the treatment of late-stage non-small cell lung cancer (NSCLC) opened new perspectives in improving survival outcomes. However, survival data have not yet been provided from the period of the Covid-19 pandemic. The aims of our study were to assess and compare survival outcomes of patients with advanced LC receiving systemic anticancer treatment (SACT) before and after the approval of immunotherapy in Hungary, and to examine the impact of pandemic on survival outcomes using data from the Hungarian National Health Insurance Fund (NHIF) database., Methods: This retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with advanced stage lung cancer (LC) (ICD-10 C34) between 1 January 2011 and 31 December 2021 and received SACT treatment without LC-related surgery. Survival rates were evaluated by year of diagnosis, sex, age, and LC histology., Results: In total, 35,416 patients were newly diagnosed with advanced LC and received SACT during the study period (mean age at diagnosis: 62.1-66.3 years). In patients with non-squamous cell carcinoma, 3-year survival was significantly higher among those diagnosed in 2019 vs. 2011-2012 (28.7% [95% CI: 26.4%-30.9%] vs. 14.45% [95% CI: 13.21%-15.69%], respectively). In patients with squamous cell carcinoma, 3-year survival rates were 22.3% (95% CI: 19.4%-25.2%) and 13.37% (95% CI: 11.8%-15.0%) in 2019 and 2011-2012, respectively, the change was statistically significant. Compared to 2011-2012, the hazard ratio of survival change for non-squamous cell carcinoma patients was 0.91, 0.82, and 0.62 in 2015-2016, 2017-2018, and 2019, respectively (p<0.001 for all cases). In the squamous cell carcinoma group, corresponding hazard ratios were 0.93, 0.87, and 0.78, respectively (p<0.001 for all cases). Survival improvements remained significant in both patient populations during the Covid-19 pandemic (2020-2021). No significant improvements were found in the survival of patients with small cell carcinoma. Platinum-based chemotherapy was the most common first-line treatment in all diagnostic periods, however, the proportion of patients receiving first- or second-line immunotherapy significantly increased during the study period., Conclusion: 3-year survival rates of NSCLC almost doubled among patients with non-squamous cell carcinoma and significantly improved at squamous cell carcinoma over the past decade in Hungary. Improvements could potentially be attributable by the introduction of immunotherapy and were not offset by the Covid-19 pandemic., Competing Interests: GH, KKn, TS, ZP and KKo are employees of MSD Pharma Hungary Ltd. ZV is an employee of Semmelweis University where their contribution to this project was financially compensated. ZKis is also employee of MSD Pharma Hungary Ltd., and has affiliation at Second Department of Medicine and Nephrology-Diabetes Center, University of Pécs Medical School, Pécs, Hungary. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. ZB is employee of Syntesia Ltd. and her contribution to this project was financially compensated. The program is financed by MSD Pharma Hungary Ltd. VM has received consultation fees from Astraeneca, Boehringer Ingelheim, Roche, Berlin-Chemie, Chiesi, BMS, Novartis, Actelion, Gilead, Pfizer, Richter, Lilly, Orion Pharma and Ipsen and served as PI for over 10 LC studies. LT is employee of Semmelweis University. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kiss, Gálffy, Müller, Moldvay, Sárosi, Pápai-Székely, Csada, Kerpel-Fronius, Király, Szász, Hódi, Polányi, Kovács, Karamousouli, Knollmajer, Szabó, Berta, Vokó, Rokszin, Abonyi-Tóth, Barcza, Tamási and Bogos.)

Background: Preterm birth remains a significant burden to families, health systems and societies. The aim was to quantify the incremental prematurity-related public health expenditure in Hungary and to estimate the potential impact of a decrease in the prevalence of prematurity on the public payer's spending., Methods: Over a 6-year time horizon, public financing data of inpatient, outpatient and pharmaceutical care for children born at ≥ 25 weeks of gestation in 2009/2010 were retrieved from the Hungarian National Health Insurance Fund database. In descriptive analysis, the public payer's spending was given as cost/capita. The impact of a decrease in prematurity prevalence was specified as the total budget impact. An exchange rate of 294 Hungarian forint/Euro was applied., Results: A total of 93,124 children (including 8.6% who were premature babies) were included in the analysis. A strong negative relationship was shown between gestational age and per capita cost. The 6-year cost of care for the cohort born at 26 weeks of gestation (28,470 Euro per capita) was 24 times higher than that for the cohort born at 40 weeks. First-year inpatient spending accounted for the largest proportion of total health care spending across all gestational ages. All investigated prematurity complications (retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular cerebral bleeding and leukomalacia) resulted in additional significant incremental spending. If 70% of pregnancies ending with preterm birth could be prolonged by 1 week, the savings would be almost 7.0 million Euros in the first 6 years of life., Conclusion: This comprehensive analysis of prematurity-related health care spending confirmed that premature infants have much higher costs for care than those born at term in Hungary. These quantitative outcomes can provide essential inputs for the cost-effectiveness analysis of medical technologies and public health interventions that can decrease the prevalence of premature birth., Trial Registration: Not applicable., (© 2023. The Author(s).)

A healthy udder is important for economical and hygienic milk production. In this study we determined the teat parameters, measured during milking, in the presence of mastitis and after its recovery. The length of the streak canal, the area of the teat end and the area of the pars papillaris of 52 Holstein-Friesian cows were examined by ultrasound before, immediately after, and two hours after milking. Pars papillaris size before milking was higher in the presence of disease (P = 0.011), but was larger before and two hours after milking (P = 0.047 and P = 0.024) with more severe mastitis. During mastitis and recovery, the dimensions of the streak canal (P=0.056-0.934) and teat end (P=0.156-0.420) did not differ from each other. The obtained results show that during mastitis, coagulated milk dilates the pars papillaris better (P=0.011) than the higher milk production of the cured cow. After more severe mastitis, regeneration of the pars papillaris as well as post-milking regeneration also takes place more slowly. The size and size changes of the streak canal and teat end are not affected by the presence or healing of the udder inflammation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Reproductive disorders caused by porcine reproductive and respiratory syndrome virus-1 are not yet fully characterized. We report QuPath-based digital image analysis to count inflammatory cells in 141 routinely, and 35 CD163 immunohistochemically stained endometrial slides of vaccinated or unvaccinated pregnant gilts inoculated with a high or low virulent PRRSV-1 strain. To illustrate the superior statistical feasibility of the numerical data determined by digital cell counting, we defined the association between the number of these cells and endometrial, placental, and fetal features. There was strong concordance between the two manual scorers. Distributions of total cell counts and endometrial and placental qPCR results differed significantly between examiner1's endometritis grades. Total counts' distribution differed significantly between groups, except for the two unvaccinated. Higher vasculitis scores were associated with higher endometritis scores, and higher total cell counts were expected with high vasculitis/endometritis scores. Cell number thresholds of endometritis grades were determined. A significant correlation between fetal weights and total counts was shown in unvaccinated groups, and a significant positive correlation was found between these counts and endometrial qPCR results. We revealed significant negative correlations between CD163+ counts and qPCR results of the unvaccinated group infected with the highly virulent strain. Digital image analysis was efficiently applied to assess endometrial inflammation objectively.

The study was performed on 10 female and 10 male wild boars (Sus scrofa) after shooting during the regular hunting season to investigate the concentration of metals in the muscle and fat tissue. The concentrations of essential and non-essential elements were determined (arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), mercury (Hg), and zinc (Zn)) using inductively coupled plasma optical emission spectrometry. The concentrations of As, Hg, and Cd were below the limit of detection (As, Hg: < 0.5 mg/kg, Cd: < 0.05 mg/kg) in every tissue sample of both sexes. The lead was detected as 0.36 ± 0.16 mg/kg and 0.22 ± 0.06 mg/kg in the muscle of females and males, respectively, showing a significant difference between the sexes (p = 0.0184). The measured concentration of Cr was 0.14 ± 0.08 mg/kg and 0.13 ± 0.06 mg/kg, and that of copper was 1.22 ± 0.14 mg/kg and 1.06 ± 0.16 mg/kg in the muscle of females and males, respectively. The same tendency was observed in the case of copper content of fat tissues (female: 0.13 ± 0.10 mg/kg; male: 0.13 ± 0.04 mg/kg; p = 0.2707). Manganese concentration of muscle was 0.45 ± 0.30 mg/kg (female) and 1.36 ± 0.96 mg/kg (male), and that of fat tissue was 0.32 ± 0.22 mg/kg (female) and 0.74 ± 0.75 mg/kg (male). The Zn was detected as 56.75 ± 7.86 mg/kg and 1.83 ± 0.76 mg/kg in the muscle and fat of females and 52.12 ± 11.51 mg/kg and 1.94 ± 0.57 mg/kg in males, respectively. Based on data, the consumption of fat and muscle tissues of the wild boars tested can be food toxicologically objectionable, mainly due to the lead content, and thus pose a risk to frequent consumers of this type of game meat., (© 2022. The Author(s).)

Objective: The Hungarian Undiagnosed Lung Cancer (HULC) study aimed to explore the potential reasons for missed LC (lung cancer) diagnosis by comparing healthcare and socio-economic data among patients with post-mortem diagnosed LC with those who were diagnosed with LC during their lives., Methods: This nationwide, retrospective study used the databases of the Hungarian Central Statistical Office (HCSO) and National Health Insurance Fund (NHIF) to identify patients who died between January 1, 2019 and December 31, 2019 and were diagnosed with lung cancer post-mortem (population A) or during their lifetime (population B). Patient characteristics, socio-economic factors, and healthcare resource utilization (HCRU) data were compared between the diagnosed and undiagnosed patient population., Results: During the study period, 8,435 patients were identified from the HCSO database with LC as the cause of death, of whom 1,203 (14.24%) had no LC-related ICD (International Classification of Diseases) code records in the NHIF database during their lives (post-mortem diagnosed LC population). Post-mortem diagnosed LC patients were significantly older than patients diagnosed while still alive (mean age 71.20 vs. 68.69 years, p<0.001), with a more pronounced age difference among female patients (difference: 4.57 years, p<0.001), and had significantly fewer GP (General Practitioner) and specialist visits, X-ray and CT scans within 7 to 24 months and 6 months before death, although the differences in GP and specialist visits within 7-24 months did not seem clinically relevant. Patients diagnosed with LC while still alive were more likely to be married (47.62% vs. 33.49%), had higher educational attainment, and had more children, than patients diagnosed with LC post-mortem., Conclusions: Post-mortem diagnosed lung cancer accounts for 14.24% of total lung cancer mortality in Hungary. This study provides valuable insights into patient characteristics, socio-economic factors, and HCRU data potentially associated with a high risk of lung cancer misdiagnosis., Competing Interests: Authors ZK, AV, KKn, MV, KKo, AB, IKö, EK and ZP are employed by MSD Pharma Hungary Ltd. ZV is employed by Semmelweis University where his contribution to this project was financially compensated. KB, JM and GyO are employees of National Korányi Institute of Pulmonology and have received speaker honorarium from MSD Hungary. GabG is employee of Oncology Center of Törökbálint and has received speaker honorarium from MSD Hungary. ZsB is employee of Syntesia Ltd. and her contribution to this project was financially compensated. The programme is financed by MSD Pharma Hungary Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kiss, Bogos, Tamási, Ostoros, Müller, Bittner, Sárosi, Vastag, Knollmajer, Várnai, Kovács, Berta, Köveskuti, Karamousouli, Rokszin, Abonyi-Tóth, Barcza, Kenessey, Weber, Nagy, Freyler-Fadgyas, Szócska, Szegner, Hilbert, Géczy, Surján, Moldvay, Vokó, Gálffy and Polányi.)

Background and objectives: In the last couple of years, pharmacological management of patients with type 2 diabetes mellitus (T2DM) have been markedly renewed. The aim of this study was to analyse the changes in prescribing patterns of antidiabetic drugs for treating patients with T2DM in Hungary between 2015 and 2020. Material and Methods: In this retrospective, nationwide analysis, we used the central database of the National Health Insurance Fund. We present annual numbers and their proportion of T2DM patients with different treatment regimens. Results: In the period of 2015−2020, the number of incident cases decreased from 60,049 to 29,865, while prevalent cases increased from 682,274 to 752,367. Patients with metformin (MET) monotherapy had the highest prevalence (31% in 2020). Prevalence of insulin (INS) monotherapy continuously but slightly decreased from 29% to 27% while that of sulfonylurea (SU) monotherapy markedly decreased from 37% to 20%. Dipeptidyl peptidase (DPP-4) inhibitors remained popular in 2020 as monotherapy (5%), in dual combination with MET (12%) and in triple combination with MET and SU (5%). The prevalence of patients with sodium-glucose co-transporter-2 (SGLT-2) inhibitors increased from 1% to 4% in monotherapy, from <1% to 6% in dual combination with MET, and from <1% to 2% in triple oral combination with MET and SU or DPP-4-inhibitors. The prevalence of patients using glucagon-like peptide-1 receptor agonists (GLP-1-RAs) also increased but remained around 1−2% both in monotherapy and combinations. For initiating antihyperglycaemic treatment, MET monotherapy was the most frequently used regime in 2020 (50%), followed by monotherapy with SUs (16%) or INS (10%). After initial MET monotherapy, the incidence rates of patients with add-on GLP-1-RAs (2%, 3%, and 4%) and those of add-on SGLT-2 inhibitors (4%, 6%, and 8%) slowly increased in the subsequent 24, 48, and 72 months, respectively. Conclusions: In the period of 2015−2020, we documented important changes in trends of antihyperglycaemic therapeutic patterns in patients with T2DM which followed the new scientific recommendations but remained below our expectations regarding timing and magnitude. More efforts are warranted to implement new agents with cardiovascular/renal benefits into therapeutic management in time, in a much larger proportion of T2DM population, and without delay.

Titanium dioxide (TiO2) is a well-known photocatalytic compound that can be used to effectively reduce the presence of pathogens in human and animal hospitals via ROS release. The aim of this study was to investigate the efficacy of a polymer-based composite layer containing TiO2 and zinc oxide (ZnO) against Escherichia coli (E. coli) of animal origin. We showed that the photocatalyst coating caused a significant (p < 0.001) reduction in pathogen numbers compared to the control with an average reduction of 94% over 30 min. We used six light sources of different wattages (4 W, 7 W, 9 W, 12 W, 18 W, 36 W) at six distances (35 cm, 100 cm, 150 cm, 200 cm, 250 cm, 300 cm). Samples (n = 2160) were taken in the 36 settings and showed no significant difference in efficacy between light intensity and distance. We also investigated the influence of organic contaminant that resulted in lower activity as well as the effect of a water jet and a high-pressure device on the antibacterial activity. We found that the latter completely removed the coating from the surface, which significantly (p < 0.0001) reduced its antibacterial potential. As a conclusion, light intensity and distance does not reduce the efficacy of the polymer, but the presence of organic contaminants does.

Objective: This study aimed to examine the characteristics of the lung cancer (LC) patient pathway in Hungary during a 6-years period. Methods: This nationwide, retrospective study included patients newly diagnosed with LC (ICD-10 C34) between January 1, 2011, and December 31, 2016, using data from the National Health Insurance Fund (NHIF) of Hungary. The following patient pathway intervals were examined: system, diagnostic and treatment interval by age, gender, tumor type, study year and first-line LC therapy. Results: During the 6-years study period, 17,386 patients had at least one type of imaging (X-ray or CT/MRI) prior to diagnosis, and 12,063 had records of both X-ray and CT/MRI. The median system interval was 64.5 days, and it was 5 days longer among women, than in men (68.0 vs. 63.0 days). The median system interval was significantly longer in patients with adenocarcinoma compared to those with squamous cell carcinoma or small cell lung cancer (70.4 vs. 64.0 vs. 48.0 days, respectively). Patients who received surgery as first-line treatment had significantly longer median system intervals compared to those receiving chemotherapy (81.4 vs. 62.0 days). The median system interval significantly increased from 62.0 to 66.0 days during the 6-years study period. Conclusion: The LC patient pathway significantly increased in Hungary over the 6-years study period. There were no significant differences in the length of the whole LC patient pathway according to age, however, female sex, surgery as first-line treatment, and adenocarcinoma were associated with longer system intervals., Competing Interests: ZK, AV, ZP, ZN-E, KK, and MV are employees of MSD Pharma Hungary Ltd. MV is a research fellow at Semmelweis University. KH is a research fellow at Eötvös Loránd University. BN and ZV are employees at Eötvös Loránd University where their contribution to this project was financially compensated. KB and GO are employees of National Korányi Institute of Pulmonology and have received speaker honorarium from MSD Hungary. GG is employee of Oncology Center of Törökbálint and has received speaker honorarium from MSD Hungary. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. ZB is employee of Syntesia Ltd. and her contribution to this project was financially compensated. The programme is financed by MSD Pharma Hungary Ltd. JM was supported by the Hungarian Brain research Program (grant 2017-1.2.1-NKP-2017-00002), and the Hungarian NRDI Office (grant K-129065). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from MSD Pharma Hungary Ltd. The funder had the following involvement with the study: development of study design, data collection, data analysis, interpretation of data, the writing of this article and the decision to submit it for publication., (Copyright © 2021 Kiss, Bogos, Tamási, Ostoros, Müller, Urbán, Bittner, Sárosi, Vastag, Polányi, Nagy-Erdei, Knollmajer, Várnai, Nagy, Horváth, Rokszin, Abonyi-Tóth, Barcza, Moldvay, Gálffy and Vokó.)

Objective: Hungary has one of the highest incidences and mortality rates of lung cancer (LC), therefore the objective of this study was to analyse and compare LC incidence and mortality rates between the main Hungarian regions. Methods: This nationwide, retrospective study used data from the National Health Insurance Fund and included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between Jan 1, 2011 and Dec 31, 2016. Age-standardized incidence and mortality rates were calculated and compared for the main regions. Results: The highest incidence rate in males was recorded in Northern Hungary (146.8/100,000 person-years [PY]), while the lowest rate was found in Western Transdanubia (94.7/100,000 PY in 2011). All rates showed a declining trend between 2011 and 2016, with the largest decrease in the Northern Great Plain (-20.0%; p = 0.008). LC incidence and mortality rates in women both showed a rising tendency in all regions of Hungary, reaching the highest in Central Hungary (59.86/100,000 PY in 2016). Lung cancer incidence and mortality rates in males correlated with the level of education and smoking prevalence ( p = 0.006 and p = 0.01, respectively) in the regions. A correlation with GDP per capita and Health Development Index (HDI) index could also be observed in the Hungarian regions, although these associations were not statistically significant. No correlations could be detected between these parameters among females. Conclusion: This analysis revealed considerable differences in the epidemiology of LC between the 7 main Hungarian regions. LC incidence and mortality rates significantly correlated with smoking and certain socioeconomic factors in men, but not in women. Further research is needed to explain the regional differences., Competing Interests: ZB was employed by the company Syntesia Medical Communications Ltd. AV, ZK, ZP, ZN-E, AD and KK are employees of MSD Pharma Hungary Ltd. KH is a research fellow at Eötvös Loránd University, employed in the framework of a joint research programme of Eötvös Loránd and MSD Pharma Hungary Ltd. MV and PS are research fellows at Semmelweis University, employed in the framework of a joint research programme of Semmelweis University and MSD Pharma Hungary Ltd. BN and ZV are employees of Eötvös Loránd University where their contribution to this project was financially compensated. KB, JM and GO are employees of National Korányi Institute of Pulmonology, GG is an employee of Oncology Center of Törökbálint, LT and VM are employees of Semmelweis University, LU is an employee of Gyógyintézet, NB is an employee of University of Debrecen, VS is an employee of University of Pécs, where their contribution to this project was not financially compensated. GR and ZA-T are employees of RxTarget Ltd where their contribution to this project was financially compensated. The programme is financed by MSD Pharma Hungary Ltd. JM was supported by the Hungarian Brain Research Program (grant 2017-1.2.1-NKP-2017-00002), and the Hungarian NRDI Office (grant K-129065). The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from MSD Pharma Hungary Ltd. The funder had the following involvement with the study: development of study design, data collection, data analysis, interpretation of data, the writing of this article and the decision to submit it for publication., (Copyright © 2021 Gálffy, Vastag, Bogos, Kiss, Ostoros, Müller, Urbán, Bittner, Sárosi, Polányi, Nagy-Erdei, Daniel, Knollmajer, Várnai, Szegner, Vokó, Nagy, Horváth, Rokszin, Abonyi-Tóth, Pozsgai, Barcza, Moldvay and Tamási.)

Objective: Lung cancer is one of the most common cancers worldwide and its survival is still poor. The objective of our study was to estimate long-term survival of Hungarian lung cancer patients at first time based on a nationwide review of the National Health Insurance Fund database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between January 1, 2011 and December 31, 2016. Survival rates were evaluated by year of diagnosis, patient gender and age, and morphology of lung cancer. Results: 41,854 newly diagnosed lung cancer patients were recorded. Mean age at diagnosis varied between 64.7 and 65.9 years during study period. One- and 5-year overall survival rates for the total population were 42.2 and 17.9%, respectively. Survival was statistically associated with gender, age and type of lung cancer. Female patients ( n = 16,362) had 23% better survival (HR: 0.77, 95% confidence interval (CI): 0.75-0.79; p < 0.001) than males ( n = 25,492). The highest survival rates were found in the 20-49 age cohort (5Y = 31.3%) and if the cancer type was adenocarcinoma (5Y = 20.5%). We measured 5.3% improvement (9.2% adjusted) in lung cancer survival comparing the period 2015-2016 to 2011-2012 (HR: 0.95 95% CI: 0.92-0.97; p = 0.003), the highest at females <60 year (0.86 (adjusted HR was 0.79), interaction analysis was significant for age and histology types. Conclusion: Our study provided long-term Lung cancer survival data in Hungary for the first time. We found a 5.3% improvement in 5-year survival in 4 years. Women and young patients had better survival. Survival rates were comparable to-and at the higher end of-rates registered in other East-Central European countries (7.7%-15.7%)., Competing Interests: ZK, AV, ZN-E, and AD are employees of MSD Pharma Hungary Ltd. KH is a research fellow at Eötvös Loránd University. BN and ZV are employees of Eötvös Loránd University where their contribution to this project was financially compensated. KB and GO are employees of National Korányi Institute of Pulmonology and have received speaker honorarium from MSD Hungary. GG is employee of Oncology Center of Törökbálint and has received speaker honorarium from MSD Hungary. LT and VM are employees of Semmelweis University. LU is employee of Mátra Gyógyintézet. NB is employee of University of Debrecen. VS is employee of University of Pécs. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. ZB is employee of Syntesia Ltd. and her contribution to this project was financially compensated. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bogos, Kiss, Tamási, Ostoros, Müller, Urbán, Bittner, Sárosi, Vastag, Polányi, Nagy-Erdei, Daniel, Vokó, Nagy, Horváth, Rokszin, Abonyi-Tóth, Barcza, Gálffy and Moldvay.)

Objective: No assessment was conducted describing the age and gender specific epidemiology of lung cancer (LC) prior to 2018 in Hungary, thus the objective of this study was to appraise the detailed epidemiology of lung cancer (ICD-10 C34) in Hungary based on a retrospective analysis of the National Health Insurance Fund database. Methods: This longitudinal study included patients aged ≥20 years with LC diagnosis (ICD-10 C34) between January 1, 2011 and December 31, 2016. Patients with different cancer-related codes 6 months before or 12 months after LC diagnosis or having any cancer treatment other than lung cancer protocols were excluded. Results: Lung cancer incidence and mortality increased with age, peaking in the 70-79 age group (375.0/100,000 person-years) among males, while at 60-69 age group for females (148.1/100,000 person-years). The male-to-female incidence rate ratio reached 2.46-3.01 ( p < 0.0001) among the 70-79 age group. We found 2-11% decrease in male incidence rate at most age groups, while a significant 1-3% increase was observed in older females (>60) annually during the study period. Conclusion: This nationwide epidemiology study demonstrated that LC incidence and mortality in Hungary decreased in younger male and female population, however we found significant increase of incidence in older female population, similar to international trends. Incidence rates peaked in younger age-groups compared to Western countries, most likely due to higher smoking prevalence in these cohorts, while lower age LC incidence could be attributed to higher competing cardiovascular risk resulting in earlier mortality in smoking population., Competing Interests: ZK, AV, and ZN-E, and AD are employees of MSD Pharma Hungary Ltd. KH is a research fellow at Eötvös Loránd University. BN and ZV are employees of Eötvös Loránd University where their contribution to this project was financially compensated. KB and GO are employees of National Korányi Institute of Pulmonology and have received speaker honorarium from MSD Hungary. GG is employee of Oncology Center of Törökbálint and has received speaker honorarium from MSD Hungary, LT and VM are employees of Semmelweis University and they declare have no conflict of interest, LU is employee of MG and he declares have no conflict of interest, NB is employee of University of Debrecen and she declares have no conflict of interest, VS is employee of University of Pécs and she declares have no conflict of interest. GR and ZA-T are employees of RxTarget Ltd. where their contribution to this project was financially compensated. ZB is employees of Synthesia Ltd. And her contribution to this project was financially compensated. The authors declare that this study received funding from MSD Pharma Hungary Ltd. The funder had the following involvement with the study: study design, data collection and analysis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tamási, Horváth, Kiss, Bogos, Ostoros, Müller, Urbán, Bittner, Sárosi, Vastag, Polányi, Nagy-Erdei, Daniel, Nagy, Rokszin, Abonyi-Tóth, Moldvay, Vokó and Gálffy.)

Objective: This study examined cumulative excess mortality in European countries in the year of the Covid-19 pandemic and characterized the dynamics of the pandemic in different countries, focusing on Hungary and the Central and Eastern European region. Methods: Age-standardized cumulative excess mortality was calculated based on weekly mortality data from the EUROSTAT database, and was compared between 2020 and the 2016-2019 reference period in European countries. Results: Cumulate weekly excess mortality in Hungary was in the negative range until week 44. By week 52, it reached 9,998 excess deaths, corresponding to 7.73% cumulative excess mortality vs. 2016-2019 ( p -value = 0.030 vs. 2016-2019). In Q1, only Spain and Italy reported excess mortality compared to the reference period. Significant increases in excess mortality were detected between weeks 13 and 26 in Spain, United Kingdom, Belgium, Netherland and Sweden. Romania and Portugal showed the largest increases in age-standardized cumulative excess mortality in the Q3. The majority of Central and Eastern European countries experienced an outstandingly high impact of the pandemic in Q4 in terms of excess deaths. Hungary ranked 11th in cumulative excess mortality based on the latest available data of from the EUROSTAT database. Conclusion: Hungary experienced a mortality deficit in the first half of 2020 compared to previous years, which was followed by an increase in mortality during the second wave of the COVID-19 pandemic, reaching 7.7% cumulative excess mortality by the end of 2020. The excess was lower than in neighboring countries with similar dynamics of the pandemic., Competing Interests: Krisztina Bogos, Anna Kerpel Fronius, Gabriella Temesi, Jenő Elek, Ildikó Madurka, Zsuzsanna Cselkó, Péter Csányi are employees of National Korányi Institute of Pulmonology. György Rokszin and Zsolt Abonyi‐Tóth are employees of RxTarget Ltd. Zsófia Barcza is employee of Syntesia Ltd. Zoltan Kiss is a PhD fellow in 2nd Department of Medicine and Nephrological Center of University of Pécs. Judit Moldvay was supported by the Hungarian Brain research Program (grant 2017‐1.2.1‐NKP‐2017‐00002), and the Hungarian NRDI Office (grant K‐129065)., (Copyright © 2021 Bogos, Kiss, Kerpel Fronius, Temesi, Elek, Madurka, Cselkó, Csányi, Abonyi-Tóth, Rokszin, Barcza and Moldvay.)

In the international publications, in the last decades, incidence and mortality of lung cancer was the highest in Hungary in the ranking of European countries and even worldwide, despite the fact that no lung cancer incidence data were reported from Hungary until 2019. In the studies published by our working group at the end of 2019 and in the first half of 2020, we were the first to publish Hungarian lung cancer incidence and mortality data based on research on the NEAK database. The results of this study showed a significant, 25-30% lower incidence of lung cancer in Hungary than the previously reported data. Based on these findings, it was determined that the previously reported Hungarian lung cancer incidence and mortality data can be compiled due to different methodological applications of inadequately calculated results, and Hungarian lung cancer incidence and mortality are equally high, but not higher than the average in Central European countries. In addition, a decrease in the incidence and mortality of male lung cancer was measured between 2011 and 2016, while increasing values were found for women.

Background: There are few papers comparing complications of type 1 diabetes with those of a similarly young age with type 2 diabetes. The aim of our nationwide study was to compare the risks of mortality and morbidities between the two types of diabetes (age ≤ 40)., Methods: We identified all young adult patients with type 1 diabetes who were recorded in the database of the Hungarian National Health Insurance Fund between 2001 and 2014 (n = 11 863) and compared them with a population of similar age with young adult type 2 diabetes (n = 47 931). The incidence of all-cause mortality, myocardial infarction, stroke, any type of cancer, diabetic ketoacidosis, and hypoglycemia was followed from the onset of diabetes to the date of death or end of study period., Results: The risks of all-cause mortality were significantly higher in patients with type 1 compared with patients with type 2 diabetes (hazard ratio, 95%CI; 2.17, 1.95-2.41; P < .0001). The risks of myocardial infarction (0.90, 0.71-1.13; P = 0.36) and stroke (1.06, 0.87-1.29; P = .582) were not significantly different in type 1 compared with type 2. In contrast, the risk of cancer (1.35, 1.15-1.59; P = .0003), dialysis (2.20, 1.76-2.75; P < .0001), hypoglycemia (7.70, 6.45-9.18; P < .0001), and ketoacidosis (22.12, 19.60-25.00; P < .0001) was higher among patients with type 1 compared with those with type 2 diabetes., Conclusions: A comparatively higher incidence of diabetic ketoacidosis and hypoglycemia and higher risk of cancer and dialysis in patients with type 1 diabetes than in those with type 2 may play a role in the higher risk of mortality., (© 2019 The Authors Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.)

Objective: While Hungary is often reported to have the highest incidence and mortality rates of lung cancer, until 2018 no nationwide epidemiology study was conducted to confirm these trends. The objective of this study was to estimate the occurrence of lung cancer in Hungary based on a retrospective review of the National Health Insurance Fund (NHIF) database. Methods: Our retrospective, longitudinal study included patients aged ≥20 years who were diagnosed with lung cancer (ICD-10 C34) between 1 Jan 2011 and 31 Dec 2016. Age-standardized incidence and mortality rates were calculated using both the 1976 and 2013 European Standard Populations (ESP). Results: Between 2011 and 2016, 6,996 - 7,158 new lung cancer cases were recorded in the NHIF database annually, and 6,045 - 6,465 all-cause deaths occurred per year. Age-adjusted incidence rates were 115.7-101.6/100,000 person-years among men (ESP 1976: 84.7-72.6), showing a mean annual change of - 2.26% ( p = 0.008). Incidence rates among women increased from 48.3 to 50.3/100,000 person-years (ESP 1976: 36.9-38.0), corresponding to a mean annual change of 1.23% ( p = 0.028). Age-standardized mortality rates varied between 103.8 and 97.2/100,000 person-years (ESP 1976: 72.8-69.7) in men and between 38.3 and 42.7/100,000 person-years (ESP 1976: 27.8-29.3) in women. Conclusion: Age-standardized incidence and mortality rates of lung cancer in Hungary were found to be high compared to Western-European countries, but lower than those reported by previous publications. The incidence of lung cancer decreased in men, while there was an increase in incidence and mortality among female lung cancer patients., (Copyright © 2019 Bogos, Kiss, Gálffy, Tamási, Ostoros, Müller, Urbán, Bittner, Sárosi, Vastag, Polányi, Nagy-Erdei, Vokó, Nagy, Horváth, Rokszin, Abonyi-Tóth and Moldvay.)

Introduction: The aim of the present study was to assess changes in the incidence and prevalence of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in children and adolescents in Hungary during the period 2001 to 2016 in order to provide nationwide population-based epidemiology data on diabetes in youths aged 0-18 years., Material and Methods: This was a retrospective cohort study of Hungarian children and adolescents aged 18 years or younger. Pharmacologically treated diabetes cases were obtained through a population-based registry of the Hungarian National Health Insurance Fund. Time series analysis was used to evaluate the changing patterns of the incidence and prevalence for type 1 and type 2 diabetes covering a 16-year period., Results: During the study period, 6,138 and 1,997 new T1DM and T2DM cases were observed, respectively. Newly diagnosed T2DM cases accounted for 24.5% of all incident diabetes cases. Incidence of T1DM increased from 16/100,000 to 23/100,000 ( R 2 = 0.7681; p < 0.0001). The male-to-female ratio among newly diagnosed T1DM patients did not change over the study period. Prevalence of T1DM rose from 114/100,000 to 209/100,000 ( R 2 = 0.9909; p < 0.0001). The prevalent T1DM cases showed significant male predominance in every year ( p < 0.05). Incidence of T2DM decreased from 8/100,000 to 5/100,000 ( R 2 = 0.4977; p < 0.0014). The overall prevalence of T2DM did not change significantly. Prevalent T2DM cases showed significant female predominance in every year ( p < 0.0001). A significant decrease in male-to female ratio was observed among newly diagnosed T2DM cases over the study period ( p < 0.0001)., Conclusions: According to these population-based Hungarian data of children and adolescents with diabetes, T1DM is still the most common form and its frequency continues to rise, affecting more males than females. A high proportion of patients have T2DM, affecting more females than males, but the occurrence of medically treated cases is not increasing. The decrease in male-to-female ratio in newly diagnosed T2DM cases needs further investigations., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

The length of the streak canal and the area of the teat end were studied by ultrasound during the dry period in 40 Holstein-Friesian cows. In the first week, the values of these teat parameters decreased significantly (P < 0.05) and this did not change significantly until the middle of the dry period. In the last month of gestation, the length of the streak canal was significantly reduced (P < 0.05), while the area of the teat end did not decrease significantly (P > 0.05). At each of the five examination times, a very strong positive correlation (r = 0.85-0.94) was found between the two teat parameters. In healthy cows, the streak canal and the area of teat end, both of which are part of the udder's defence system, can regenerate sufficiently during the dry period, minimising the risk of contamination through the streak canal and the development of mastitis. If the regeneration of this defence system fails, the chances of infection through the streak canal increase.

Aims: Incidence and prevalence of Type 2 diabetes mellitus (T2DM) vary in different regions. Long-term nationwide epidemiological data are useful to assess trends over time. The aim of the study was to analyze the epidemiological changes of pharmacologically treated T2DM among people aged over 18 years in Hungary between 2001 and 2016., Methods: Annual incidence, prevalence and all-cause mortality rate of pharmacologically treated T2DM patients were evaluated from 2001 to 2016 using the central database of the National Institute of Health Insurance Fund Management. Data were adjusted to age using the 2013 European Standard Population., Results: Incident rate of pharmacologically treated T2DM decreased from 931.6 cases/100,000 person-years to 350.7 cases/100,000 person-years resulting in a -62.4% change (annual average change: -6.46% [95% CI: -7.64%; -5.67%]) between 2001 and 2016. The prevalence rate continuously increased from 4949.9 cases/100,000 persons in 2001 to the highest rate (8135.0 cases/100,000 persons) in 2011, which plateaued during the next 3 years and slightly decreased thereafter. Standardized all-cause mortality rate in people with T2DM decreased between 2001 and 2016 by 11.9% (annual average change: -0.84% [95% CI: -1.22%; -0.39%])., Conclusions: Despite a clearly decreasing incidence of pharmacologically treated T2DM in patients aged over 18 years, the prevalence rate increased from 2001 to 2011 followed by a 3-year-long plateau and a slight decrease thereafter. These long-term trends with the reduced mortality rate may indicate favorable effects of health promotional activities for preventing and treating T2DM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aim of this study was to analyze the impact of reproductive management practices on fertility in primiparous and multiparous dairy cows and to identify the differences by parity. Data on reproductive performance and management of cows were gathered from 34 large commercial Holstein-Friesian dairy herds in Hungary. Individual data on 23 781 cows that calved in the studied herds in 2014 were collected from the national milk recording database and used to calculate the reproductive indices. Farm managers and veterinarians were interviewed in person from May 22 to November 6, 2015 using a questionnaire to collect information about reproductive management practices. The data were statistically analyzed by mixed-effects models. Our results showed that the use of a voluntary waiting period (VWP) was linked to a greater increase in calving-to-conception interval (CCI, P < 0.05) and a greater decline in the chance of pregnancy at 200 days in milk (P200, P < 0.001) in multiparous cows. Estrus synchronization was related to a larger reduction in days-to-first service (DFS, P < 0.001), breeding interval (IBI, P < 0.05), and CCI ( P < 0.01) and a greater improvement in P200 ( P < 0.001) in primiparous cows. Early pregnancy diagnosis and pregnancy recheck improved IBI ( P < 0.01 for both practices), CCI ( P < 0.01 and P < 0.001, respectively), and P200 ( P < 0.001 for both practices) to a larger extent in primiparous than in multiparous cows. In conclusion, estrus synchronization, early pregnancy diagnosis, and pregnancy recheck led to a greater improvement in fertility in primiparous cows than in multiparous cows.

Objective: In recent decades several studies reported significant changes in the mortality and morbidity of patients with type 2 diabetes. In this Hungarian nationwide study, we assessed the changes of mortality and cardiovascular risks comparing a group of patient diagnosed during the two periods of 2001-2004 and 2010-2013. Research Design and Methods: We identified patients with type 2 diabetes recorded in the database of the Hungarian National Health Insurance Fund aiming to assess changes of risks for all-cause mortality, myocardial infarction, and stroke during the follow-up periods of 48 months. Results: We included 274,109 patients with newly diagnosed type 2 diabetes between 2001 and 2004, while only 152,678 in the 2010-2013 period. The risk of all-cause mortality at the beginning of the follow-up was not different comparing 2010-2013 to 2001-2004 (HR 1.03), and a mild but significant decrease could be detected (HR 0.87) after 48 months. A lower risk for myocardial infarction was documented in the second month after the diagnosis of diabetes (HR 0.67), which remained constant during the study period and almost the same after 48 months (HR 0.73). On the contrary, our study verified a slightly increased risk for stroke close to the diagnosis [HR 1.06 (1.00-1.13)] and a decreased one [HR 0.72 (0.69-0.79)] at the end of the study. Conclusions: An increased risk for stroke followed by a sharp decrease, and an unchanged risk for myocardial infarction in the Hungarian population with type 2 diabetes possibly resulted in a mild decrease of all-cause mortality between 2001 and 2013.

As a result of the increase in herd size and the intensification of production, the complexity of reproductive management has been growing in dairy herds. The aim of our study was to examine the associations of management practices and reproductive performance in Holstein cows on large commercial dairy farms. Management practices applied to cows were surveyed between 22 May and 6 November 2015 in 34 large Holstein-Friesian dairy herds in Hungary. Individual data of 23 784 cows that calved between 1 January 2014 and 31 December 2014 in the surveyed herds were gathered. Associations between the management practices and the reproductive parameters were analyzed by mixed effects models. Regarding heat abatement we found that ventilation with sprinklers was associated with the shortest breeding interval (P0.05) results to lack of heat stress protection. It was also revealed, that lack of a well-established voluntary waiting period (VWP) or a VWP shorter than 50 days was associated with less days to first service (P<0.01), shorter breeding interval (P<0.01) and calving to conception interval (P<0.05), as well as higher odds of carrying a calf by 200 days in milk (P<0.01) compared with those using a VWP of at least 50 days. Those farms that applied transrectal ultrasonography were more likely to use ventilation with sprinklers (P<0.05), hormonal synchronization (P<0.01) and to perform early pregnancy diagnosis followed by pregnancy recheck (P<0.05). The application of transrectal ultrasonography with one of the aforementioned practices was associated with reduced days to first service (P<0.05), shorter breeding interval (P<0.05) and higher odds of pregnancy at 200 days in milk (P<0.05). Our study highlights the management practices most closely related to improved reproductive performance, which are, therefore, suggested to be applied on dairy farms, considering the local circumstances of the individual farms.

Introduction: Adequate persistence to antidiabetic treatment is highly important to achieve proper glycemic control. In this study we evaluate the persistence to treatment with dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists in a nationwide cohort of patients with type 2 diabetes., Methods: Using a central database in Hungary, we analyzed the persistence to the treatment with dipeptidyl peptidase-4 inhibitors (n = 59,900), sodium-glucose co-transporter-2 inhibitors (n = 26,052), and glucagon-like peptide-1 receptor agonists (n = 17,332) at treatment intensification between 2014 and 2016. We also compared the persistence of dipeptidyl peptidase-4 inhibitors (n = 9163) and sodium-glucose co-transporter-2 inhibitors (n = 1257) in initial therapy to that of metformin (n = 79,305) or sulfonylureas (n = 29,057). The rates of persistence to treatment and risk of non-persistence are reported., Results: The persistence rates of dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists at treatment intensification were 69.6%, 67.8%, and 66.3% at year 1 which decreased to 57.3%, 56.8%, and 52.1% by year 2, respectively. The risk of non-persistence was higher by 6.6% (95% CI 3.6-9.6) for sodium-glucose co-transporter-2 inhibitors and by 8.3% (95% CI 5.0-11.5) for glucagon-like peptide-1 receptor agonists as compared to dipeptidyl peptidase-4 inhibitors. Novel oral antidiabetic drugs in fixed versus free add-on combinations with metformin had higher persistence. The persistence to treatment with novel oral antidiabetic drugs in initial therapy was better (dipeptidyl peptidase-4 inhibitors, 59.6% and 47.6%; sodium-glucose co-transporter-2 inhibitors, 61.9% and 47.0%) than that of initial monotherapy with metformin (47.0% and 39.1%) or sulfonylureas (52.4% and 41.8%) at years 1 and 2, respectively., Conclusion: Analysis of persistence of treatment with novel glucose-lowering medications revealed differences between drug classes, favoring dipeptidyl peptidase-4 inhibitors vs. sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Persistence data of novel antihyperglycemic agents may be useful for guiding the decision at initiation of antidiabetic treatment., Funding: Hungarian Diabetes Association. Plain language summary available for this article.

Background: The excess risks of mortality and cardiovascular morbidity among patients with type 2 diabetes mellitus (T2DM) is well known. In this nationwide study, we assessed risks of mortality and cardiovascular events comparing patients with T2DM and matched controls., Methods: We identified patients with T2DM in a retrospective cohort study using the database of the National Health Insurance Fund between 1 January 2010 and 31 December, 2013. Controls were randomly included and matched according to age, gender, and zip code of residence. Patients were divided into subgroups according to age decades for outcome analyses., Results: During the mean follow-up period of 2.3 years, 152,678 patients with T2DM and 305,356 matched controls were included. Patients with T2DM showed significantly higher risk for all-cause mortality (HR 1.26, 95% CI 1.22-1.29, p < 0.0001), myocardial infarction (HR 1.81, 95% CI 1.69-1.94, p < 0.0001) and stroke (HR 1.40, 95% CI 1.35-1.46, p < 0.0001) compared to matched controls. The higher risk associated with T2DM for mortality, myocardial infarction and stroke differed significantly between age groups (p interaction  < 0.05 for all outcomes) with significantly higher risk observed in younger patients., Conclusions: The risk of cardiovascular outcomes and all-cause mortality is significantly higher in patients with T2DM. Notably, the relative hazard increases with decreasing age suggesting that younger patients with T2DM should receive more attention for cardiovascular prevention.