Opposite trends in incidence of breast cancer in young and old female cohorts in Hungary and the impact of the Covid-19 pandemic: a nationwide study between 2011-2020.

Background: This nationwide study examined breast cancer (BC) incidence and mortality rates in Hungary between 2011-2019, and the impact of the Covid-19 pandemic on the incidence and mortality rates in 2020 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Methods: Our nationwide, retrospective study included patients who were newly diagnosed with breast cancer (International Codes of Diseases ICD)-10 C50) between Jan 1, 2011 and Dec 31, 2020. Age-standardized incidence and mortality rates (ASRs) were calculated using European Standard Populations (ESP). Results: 7,729 to 8,233 new breast cancer cases were recorded in the NHIF database annually, and 3,550 to 4,909 all-cause deaths occurred within BC population per year during 2011-2019 period, while 2,096 to 2,223 breast cancer cause-specific death was recorded (CSO). Age-standardized incidence rates varied between 116.73 and 106.16/100,000 PYs, showing a mean annual change of -0.7% (95% CI: -1.21%-0.16%) and a total change of -5.41% (95% CI: -9.24 to -1.32). Age-standardized mortality rates varied between 26.65-24.97/100,000 PYs (mean annual change: -0.58%; 95% CI: -1.31-0.27%; p=0.101; total change: -5.98%; 95% CI: -13.36-2.66). Age-specific incidence rates significantly decreased between 2011 and 2019 in women aged 50-59, 60-69, 80-89, and ≥90 years (-8.22%, -14.28%, -9.14%, and -36.22%, respectively), while it increased in young females by 30.02% (95%CI 17,01%- 51,97%) during the same period. From 2019 to 2020 (in first COVID-19 pandemic year), breast cancer incidence nominally decreased by 12% (incidence rate ratio [RR]: 0.88; 95% CI: 0.69-1.13; 2020 vs. 2019), all-cause mortality nominally increased by 6% (RR: 1.06; 95% CI: 0.79-1.43) among breast cancer patients, and cause-specific mortality did not change (RR: 1.00; 95%CI: 0.86-1.15). Conclusion: The incidence of breast cancer significantly decreased in older age groups (≥50 years), oppositely increased among young females between 2011 and 2019, while cause-specific mortality in breast cancer patients showed a non-significant decrease. In 2020, the Covid-19 pandemic resulted in a nominal, but not statistically significant, 12% decrease in breast cancer incidence, with no significant increase in cause-specific breast cancer mortality observed during 2020.

Significant improvement in melanoma survival over the last decade: A Hungarian nationwide study between 2011 and 2019.

BACKGROUND: Recent real-world studies have reported significant improvements in the survival of malignant melanoma in the past few years, mainly as a result of modern therapies. However, long-term survival data from Central Eastern European countries such as Hungary are currently lacking. METHODS: This nationwide, retrospective study examined melanoma survival in Hungary between 2011-2019 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Crude overall survival and age-standardized 5-year net survival as well as the association between age, sex and survival were calculated. RESULTS: Between 2011 and 2019, 22,948 newly diagnosed malignant melanoma cases were recorded in the NHIF database (47.89% male, mean age: 60.75 years (SD: ±16.39)). Five-year overall survival was 75.40% (women: 80.78%; men: 69.52%). Patients diagnosed between 2017-2019 had a 20% lower risk of mortality compared to patients diagnosed between 2011-2012 (HR 0.80, 95% CI 0.73-0.89; p < 0.0001). Age-standardized 5-year net survival rates in 2011-2014 and 2015-2019 were 90.6% and 95.8%, respectively (women: 93.1% and 98.4%, men: 87.8% and 92.7%, respectively). The highest age-standardized 5-year net survival rates were found in the 0-39 age cohort (94.6% in the 2015-2019 period). CONCLUSION: Hungary has similar melanoma survival rates to Western European countries. Based on net survival, the risk of dying of melanoma within 5 years was cut by more than half (55%) during the study period, which coincides with the successful implementation of awareness campaigns and the wide availability of modern therapies.

Improving Quality Indicator of Melanoma Management - Change of Melanoma Mortality-to-Incidence Rate Ratio Based on a Hungarian Nationwide Retrospective Study.

INTRODUCTION: The incidence of melanoma has been increasing in the last decades. A retrospective Hungarian epidemiological study provided real-world data on incidence and mortality rates. There have been changing trends in incidence in Hungary in the last decade and mortality decreased, shifting mortality-to-incidence rate ratios (MIR). MIR is an indicator of cancer management quality. OBJECTIVES: Our aim is to show the changes of melanoma MIR in Hungary between 2011 and 2018 and to compare the real-world evidence-based results of our Hungarian nationwide retrospective study with other European countries. METHODS: MIR is calculated from the age-specific standardized incidence and mortality rates from our study. Annual MIR values are presented for the total population and for both sexes between 2011 and 2018, along with 95% confidence intervals. Comparison with European countries are shown for 2012 and 2018 based on the GLOBOCAN database and Eurostat health care expenditure per capita data. RESULTS: MIR decreased by 0.035 during the study years. The decrease was same in both sexes (0.031). Male had higher MIRs in all study years. In both 2012 and 2018, Hungarian MIR in both sexes was lower than the European Union average (males: 0.192 vs. 0.212 and 0.148 vs. 0.174 respectively, women: 0.107 vs. 0.129 and 0.083 vs. 0.107 respectively). DISCUSSION: Hungarian mortality-to-incidence ratio is the lowest in Central and Eastern Europe and is close to the level of Western and Northern European countries. The results are driven by the high number of new diagnosed melanoma cases.

Changing Trends in Melanoma Incidence and Decreasing Melanoma Mortality in Hungary Between 2011 and 2019: A Nationwide Epidemiological Study.

BACKGROUND: The incidence of malignant melanoma has continually increased during the past few decades, however, certain reports suggest a recent change in trends. The aim of our study was to examine the epidemiology of melanoma in Hungary. METHODS: This nationwide, retrospective, longitudinal study included melanoma patients diagnosed between 1 January 2009 and 31 December 2019 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary. Age-standardized incidence and cause-specific mortality rates were calculated. RESULTS: We identified 2,426 and 2,414 new melanoma cases in 2011 and in 2019. Age-standardized incidence rates were higher in males and varied between 28.28 and 34.57/100,000 person-years (PYs), and between 22.63 and 26.72/100,000 PYs in females. We found 16.14 and 18.82% increases in male and female incidence rates from 2011 to 2015 (p=0.067 and p<0.001, respectively), and 12.77 and 11.35% decreases from 2015 to 2019 (p=0.062 and p=0.004, respectively). The change of incidence trends (2011-2015 vs. 2015-2019) was significant in females (p=0.002) and in the total melanoma population (p=0.011), but not in the male population (p=0.063). A 16.55% (95% CI: -27.07 to -4.59; p=0.013) decrease in mortality rates was found in the overall melanoma population. CONCLUSIONS: We observed a significant trend change in melanoma incidence in the female and total melanoma population, and a significant decrease in mortality in the total melanoma population. These changes may be attributed to intensive melanoma awareness campaigns as well as to the increase in screening and access to modern therapies.

[Vaccine hesitancy among primary healthcare professionals in Hungary]. / Védooltásokkal kapcsolatos kételyek és elkötelezettség a magyarországi egészségügyi alapellátásban dolgozók körében.

Introduction: The attitude to immunization and the issue of vaccine hesitancy in health care workers (HCWs) have been studied in a former survey performed by ECDC (European Centre for Disease Prevention and Control). Aim: Our aim was to study the immunization attitude of primary care paediatricians, general practitioners and primary care nurses in Hungary. Method: We studied vaccine hesitancy in HCWs by way of a questionnaire, developed on the basis of a recent similar survey by ECDC in four countries. The online survey has been performed between May and July 2017. Altogether 765 questionnaires have been returned: 189 primary care paediatricians, 375 general practitioners working in adult or mixed practices, and 201 primary care nurses. The sample has been weighted to the country-specific features - e.g., location of the practice, residence and age of the HCWs - within each of the three groups, so from this aspect it can be considered representative. Results: Our results did not differ substantially from the international ECDC data. Approximately 2/3 of the primary care doctors and about 50% of the primary care nurses were convinced of the benefit and value of vaccines. Data on vaccine hesitancy were consolingly low, though the data on recommended vaccines were somewhat higher compared to the age related/NIP (National Immunization Plan) vaccines. The well-known vaccine scares - e.g., autism-MMR, etc., known also from the literature - could hardly been detected, and it can be explained by the voluntary participation in the study. The least supported vaccine is BCG, while the highest hesitancy rates are related to MMR in Hungary. Conclusion: The need to improve immunization-related communication among primary HCWs could clearly been detected - both in gradual and in post-gradual training programs. Orv Hetil. 2019; 160(48): 1904-1914.

Decreased vasoconstrictor responses in remote cerebral arteries after focal brain ischemia and reperfusion in the rat, in vitro.

The effects of brain ischemia and reperfusion on smooth muscle function in remote cerebral and peripheral arteries are hardly known. Maximum vasoconstrictions (E(max)) caused by 120mmol/l KCl and 5-HT in endothelium-denuded ring preparations were measured in ischemic and control cerebral arteries of rats after a 1-h right middle cerebral artery occlusion followed by 0-min (I/NR) or 2-3-min (I/SR) reperfusion, and in peripheral arteries after I/SR. Surprisingly, vasoconstrictions to 5-HT and 120mmol/lK(+) were attenuated in remote brain vessels after I/SR, i.e. in the contralateral middle cerebral artery and the basilar artery, while I/NR depressed E(max) of 5-HT and high KCl only in the ischemic middle cerebral artery. Pretreatment with N-(2-mercaptopropionyl) glycine (MPG, 100mg/kg i.p.), a free radical scavenger, fully prevented the impairment of vasomotor function in the middle cerebral artery on both sides after I/SR. Moreover, vasomotor functions were normal in the coronary, renal and pulmonary arteries after I/SR. In conclusion, focal cerebral ischemia and reperfusion impaired vasoconstrictor responses in remote brain arteries of rats by a mechanism involving free radicals. The lack of similar effects in peripheral vessels indicates poor defence of brain arteries against remote injury caused by reactive oxygen species-dependent mechanisms.

Therapeutic time window of neuroprotection by non-competitive AMPA antagonists in transient and permanent focal cerebral ischemia in rats.

EGIS-8332 and GYKI 53405 are selective, non-competitive AMPA (2-amino-3[3-hydroxy-5-methyl-4-isoxazolyl] propionic acid) antagonists that effectively protected against tissue injury caused by global and focal cerebral ischemia in laboratory animals. This study evaluated the therapeutic time window of neuroprotection by EGIS-8332 and GYKI 53405 in permanent and transient middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. Infarct size was measured by TTC staining 48 h after permanent MCAO (electrocoagulation), and 24 h after reperfusion following a 1-h transient MCAO carried out using the intraluminal filament technique. Treatment with EGIS-8332 (10 mg/kg, i.p.) 60 or 120 min after permanent MCAO, decreased infarct size by 30% and 36%, respectively, and the effect of GYKI 53405 (10 mg/kg, i.p.) was similar (30% and 33%, respectively; p<0.01 all). Neither compound was effective if administered 180 or 240 min after permanent MCAO. Both EGIS-8332 and GYKI 53405 (20 mg/kg, i.p.) reduced the core and total (core plus penumbra) volumes of tissue injury in the whole brain and the cerebral cortex when administered 120 or 180 min after transient MCAO. The compounds did not alter tissue damage in the striatum. No neuroprotective effect was obtained at 240 min after transient MCAO. In conclusion, the therapeutic time window of neuroprotection by EGIS-8332 and GYKI 53405 was 2 h in permanent and 3 h in transient focal cerebral ischemia in rats. The results suggest that treatment with non-competitive AMPA antagonists can only be expected to produce a neuroprotective action in humans if administered shortly after the appearance of stroke symptoms.

Use of TTC staining for the evaluation of tissue injury in the early phases of reperfusion after focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: 2,3,5-Triphenyltetrazolium chloride (TTC) staining measures tissue viability used to evaluate infarct size. The goal of this study was to compare viability of neuronal tissue during the early phases of ischemia-reperfusion assessed either by perfusion of the brain with TTC solution transcardially, in vivo, or by staining brain slices, in vitro. METHODS: The middle cerebral artery was occluded for 1 h in male SPRD rats and then reperfused for 0, 1, 4, 8, 16 and 24 h. Ischemic damage was evaluated by TTC staining, in vivo and in vitro, and by histology (Luxol Fast Blue and Fluoro-Jade staining, electron microscopy). RESULTS: Core volume of tissue injury measured in vivo was large at 0 h and steadily decreased by 50% (p<0.001) up to 16 h, but substantially increased from 16 to 24 h of reperfusion. In contrast, a significant core volume appeared at 4 h only, in vitro, and gradually increased up to 24 h. Core volume was larger in vivo than in vitro at all times except at 16 h when the opposite was observed. Evans blue administered intracardially stained TTC-negative areas at 1 and 24 h. Histology covered the evolution of serious tissue injury but also demonstrated some morphologically preserved neurons in the infracted area at 24 h. CONCLUSIONS: Formation of formazan from TTC can depend on both the staining method and the metabolic burden of the brain tissue causing uncertainties in the volume of ischemia-induced brain injury measured by TTC staining.