We need better ways to help students avoid the harms of stress: Results of a meta-analysis on the effectiveness of school-based stress management interventions.

The level of psychological stress in children and adolescents has increased rapidly over the past decade. The aim of the present meta-analysis was to evaluate the effectiveness of school-based intervention programs targeting stress management and coping/resilience in school-aged children. The present study used more rigorous selection criteria than previous meta-analyses by only including randomized controlled trials to increase the validity of the meta-analysis. Fifty-five studies were selected for the analysis, including 66 comparisons in the case of stress and 47 comparisons in the case of coping/resilience outcomes. A meta-regression with robust variance estimation was used. Effects were calculated as the standardized mean difference (Hedges' g) between the intervention and control conditions at posttest. The results highlighted important methodological issues and the influence of outliers. Without outliers, the results indicated a small significant overall effect on stress (g = -0.15, p < .01) and coping/resilience (g = 0.14, p = .01). When outliers were included, the effect sizes markedly increased in both cases (gstress = -0.26, p = .022; gcoping/resilience = 0.30, p = .009). Stress management interventions were more effective if they were delivered by mental health professionals or researchers than by teachers. Coping/resilience interventions were more effective in older age groups, in selective samples, and if they included cognitive behavioral therapy. An explanation of the results and a detailed discussion of the limitations of the study and its implications for practice are considered.

Cost-Effectiveness of Lung Cancer Screening with Low-Dose Computed Tomography: Comparing Hungarian Screening Protocols with the US NLST.

We aimed to directly compare the cost-effectiveness of Hungarian (following the NELSON trial) and NLST screening protocols, two trials influencing lung-cancer-screening implementation internationally. A decision-analytic model analyzing the cost-effectiveness of Hungarian protocols was manipulated to reflect the protocols of the NLST, while maintaining features specific to the Hungarian healthcare setting. In the Hungarian protocol, there are three possible outcomes to the initial round of screening, positive, negative, and indeterminate, indicating an uncertain degree of suspicion for lung cancer. This protocol differs from the NLST, in which the only possible screening outcomes are positive or negative, with no indeterminate option. The NLST pathway for smokers aged 55-74 resulted in a EUR 43 increase in the total average lifetime costs compared to the Hungarian screening pathway and resulted in a lifetime gain of 0.006 QALYs. The incremental costs and QALYs yielded an ICER of 7875 EUR/QALY. Our results demonstrate that assigning any suspicious LDCT screen as a positive result (NLST protocol) rather than indeterminate (Hungarian protocol) can reduce patient uncertainty and yield a slight QALY gain that is worth the additional use of resources according to Hungary's willingness-to-pay threshold. A stratified analysis by age was also conducted, revealing decreasing cost-effectiveness when screening older cohorts. Our study provides insight into the cost-effectiveness, advantages, and disadvantages of various LDCT screening protocols for lung cancer and can assist other countries as they implement their screening programs.

Prospects of Food Taxes for Planetary Health: A Systematic Review of Modeling Studies.

OBJECTIVES: The aim of this study was to analyze the modeling methodologies of fiscal policies on food with health or environmental outcomes. BACKGROUND: Evidence suggests that fiscal policies on food can contribute to addressing the growing burden of noncommunicable diseases and climate change. These policies should be modeled in advance to see the implications for the environment and health. METHODS: A systematic review was conducted of studies that modeled fiscal policies on the food groups targeted by the EAT-Lancet Commission and examined their health or environmental outcomes. The Scopus and PubMed databases were searched on November 30, 2021. The records were double-screened and data on modeling methods were extracted from the included studies. RESULTS: A total of 55 studies were included in the review. The most frequently modeled interventions were fruit and vegetable subsidies (n = 19) and carbon taxes on food (n = 17). One study also included a consumer education campaign to enhance the effect of fiscal policy. The outcomes are highly sensitive to consumption change and price elasticities. None of the studies modeled the health effects of environmental outcomes. CONCLUSIONS: A model that covered all the relevant aspects of the issue was not found. Some parts were missing from all the included models. It is advisable to model the stability of the amount of diet consumed, either by keeping the amount of food in the diet stable or by taking a more conservative approach and keeping the consumed calories stable. It is preferable to keep the included diseases and environmental boundaries broad to have more valid outcome estimates on this complex issue. A more comprehensive understanding of fiscal policies would allow us to better anticipate the impact of our actions and inactions and thus could lead to more sophisticated measures taken by policymakers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. 2022 CRD42022291945/.

Prevalence and determinants of diagnosed and undiagnosed diabetes in Hungary based on the nationally representative cross-sectional H-UNCOVER study.

AIMS: To estimate prevalence of diagnosed (dDM) and undiagnosed diabetes (uDM) in Hungary and investigate determinants of uDM. METHODS: Data was obtained from the nationally representative H-UNCOVER study. As laboratory measurements were available for 11/19 Hungarian counties, n = 5,974/17,787 people were eligible. After exclusions, 5,673 (representing 4,976,097 people) were included. dDM was defined by self-reporting, while uDM as negative self-reporting and elevated fasting glucose (≥7 mmol/l) and/or HbA1c (≥48 mmol/mol). Logistic regression for complex samples was used to calculate comparisons between dDM and uDM adjusted for age and BMI. RESULTS: Diabetes prevalence was 12.0 %/11.9 % (women/men, 95 %CI:10.7-13.4 %/10.7-13.2 %), while 2.2 %/2.8 % (1.7-2.8 %/2.2-3.6 %) of women/men were uDM. While the proportion of uDM vs. dDM was similar for women ≥ 40, men in their forties had the highest odds for uDM. Neither unemployment (women/men OR:0.58 [0.14-2.45]/0.50 [0.13-1.92]), nor education level (tertiary vs. primary; women/men OR: 1.16 [0.53-2.56]/ 0.53 [0.24-1.18]) were associated with uDM. The risk of uDM was lower in both sexes with chronic morbidities. CONCLUSIONS: We report higher prevalence of diabetes and undiagnosed diabetes than previous Hungarian estimates. The finding that socioeconomic factors are not associated to uDM suggests that universal health care could provide equitable access to diabetes diagnosis.

Population-level norm values by EQ-5D-3L in Hungary - a comparison of survey results from 2022 with those from 2000.

PURPOSE: Although population norms of the EQ-5D-3L instrument had been available in Hungary since 2000, their evaluation was based on a United Kingdom (UK) value set. Our objective was to estimate the population norms for EQ-5D-3L by using the new Hungarian value set available since 2020, to extend the scope to adolescents, and to compare with norms from 2000. METHODS: A cross sectional EQ-5D-3L survey representative of the Hungarian population was conducted in 2022. The EQ-5D-3L dimensional responses were analyzed by age and sex and compared with the survey from 2000, by estimating population frequencies with their 95% confidence intervals; index values were evaluated by both value sets. RESULTS: Altogether, 11,910 respondents, aged 12 or more (578 between 12 and 17), completed the EQ-5D-3L. There was a notable improvement in reporting problems for both sexes (age 35-64) regarding the pain/discomfort and anxiety/depression compared to 2000. Below the age 44, both sexes had an EQ-5D-3L index plateau of 0.98, while above the age 55, men tended to have numerically higher index values compared to women, with the difference increasing with older age. Improvement in dimensional responses were also translated to numerically higher index values for both sexes between ages 18 and 74 compared to 2000. Multivariate regression analysis showed that higher educational attainment, lower age, larger household size, and active occupational status were associated with higher index values. CONCLUSION: Over the past 22 years, there was a large improvement in HRQoL of the middle-aged to elderly men and women in Hungary.

Health states can be described by a combination of statements of health-related quality of life measures. 'Value sets' are numerical expressions of how preferred a health state is. The provision of population-level health-related quality of life estimates (also known as 'population norms') are expected to improve the precision of patient-level clinical decision making, and health economic and public health studies. However, preference towards these health states is influenced by culture, resulting in differences across populations. While responses for the EQ-5D-3L instrument for adults have been available in Hungary since 2000, the evaluation of these responses was based on a 'value set' from the United Kingdom, rather than a Hungarian one.This research, utilizing the newly introduced Hungarian 'value set' (available since 2020) for the EQ-5D-3L instrument, offers a larger sample size, inclusion of adolescents and potentially improved sampling compared to the prior research conducted in 2000. Comparison of the two surveys allows us to estimate changes in both dimensional responses and overall health-related quality of life of the population over a 20-year time horizon, while we also compare the impact of different 'value sets' on health-related quality of life assessment. A large EQ-5D-3L improvement was observed in middle-aged-to-elderly people.

Survival of propionic acidemia patients with liver transplant.

Propionic acidemia (PA) is a rare metabolic disorder affecting amino acid metabolism. Liver transplantation improves some outcomes, but the impact on long-term survival remains unclear. A systematic literature review and survival analysis, identifying 94 PA patients who underwent transplantation, revealed a survival probability of 62% at age 33; while median survival was estimated at 40 years. These findings highlight a substantial survival deficit of PA patients compared to the general population despite liver transplantation.

Decreasing incidence and mortality of lung cancer in Hungary between 2011 and 2021 revealed by robust estimates reconciling multiple data sources.

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.

Breast cancer stage and molecular subtype distribution: real-world insights from a regional oncological center in Hungary.

OBJECTIVE: Examining the distribution of breast cancer (BC) stage and molecular subtype among women aged below (< 45 years), within (45-65 years), and above (> 65 years) the recommended screening age range helps to understand the screening program's characteristics and contributes to enhancing the effectiveness of BC screening programs. METHODS: In this retrospective study, female patients with newly diagnosed BC from 2010 to 2020 were identified. The distribution of cases in terms of TNM stages, severity classes, and subtypes was analysed according to age groups. RESULTS: A total of 3282 women diagnosed with BC were included in the analysis. Among these cases 51.4% were detected outside the screening age group, and these were characterized by a higher TNM stage compared to those diagnosed within the screening age band. We observed significantly higher relative frequency of advanced BC in the older age group compared to both the screening age population and women younger than 45 years (14.9% vs. 8.7% and 7.7%, P < 0.001). HR-/HER2- and HER+ tumours were relatively more frequent among women under age 45 years (HR-/HER2-: 23.6%, HER2+: 20.5%) compared to those within the screening age range (HR-/HER2-: 13.4%, HER2+: 13.9%) and the older age group (HR-/HER2-: 10.4%, HER2+: 11.5%). CONCLUSIONS: The findings of our study shed light on potential areas for the improvement of BC screening programs (e.g., extending screening age group, adjusting screening frequency based on molecular subtype risk status) in Hungary and internationally, as well.

Effectiveness of educational interventions for healthcare workers on vaccination dialogue with older adults: a systematic review.

BACKGROUND: Healthcare workers (HCW) significantly influence older adults' vaccine acceptance. This systematic review aimed to identify effective educational interventions for HCWs that could enhance their ability to engage in a dialogue with older adults on vaccination. METHODS: Medline, Scopus, Cochrane library and grey literature were searched for comparative studies investigating educational interventions concerning older adult vaccinations. The search encompassed all languages and publication years. Analysis was performed on the outcomes 'vaccines offered or ordered' and 'vaccination rates'. Whenever feasible, a sub-analysis on publication year was conducted. Methodological limitations were assessed using the RoB 2 for RCTs and the GRADE checklist for non-randomized studies. Study outcomes were categorized according to the four-level Kirkpatrick model (1996) for effectiveness: reaction, learning, behaviour, and results. RESULTS: In total, 48 studies met all inclusion criteria. Most studies included reminder systems signalling HCWs on patients due for vaccination. Other interventions included seminars, academic detailing and peer-comparison feedback. Four articles reporting on the reaction-level indicated that most HCWs had a favourable view of the intervention. Two of the six articles reporting on the learning-level observed positive changes in attitude or knowledge due to the intervention. Seventeen studies reported on the behaviour-level. An analysis on eleven out of seventeen studies focusing on vaccines 'ordered' or 'offered' outcomes suggested that tailored reminders, particularly those implemented before 2000, were the most effective. Out of 34 studies reporting on the result-level, 24 were eligible for analysis on the outcome 'vaccination rate', which showed that compared to usual care, multicomponent interventions were the most effective, followed by tailored reminders, especially those predating 2000. Nonetheless, tailored reminders often fell short compared to other interventions like standing orders or patient reminders. In both the behaviour-level and result-level 'education only' interventions frequently underperformed relative to other interventions. Seventeen out of the 27 RCTs, and seven of the 21 non-randomized studies presented a low-to-medium risk for bias in the studies' findings. CONCLUSIONS: Tailored reminders and multicomponent interventions effectively assist HCWs in addressing vaccines with older adults. However, education-only interventions appear to be less effective compared to other interventions rates, attitude, knowledge.

Effectiveness of SARS-CoV-2 primary vaccines and boosters in patients with type 2 diabetes mellitus in Hungary (HUN-VE 4 Study).

INTRODUCTION: Type 2 diabetes mellitus is a risk factor for severe COVID-19 infection and is associated with increased risk of complications. The present study aimed to investigate effectiveness and persistence of different COVID vaccines in persons with or without diabetes during the Delta wave in Hungary. RESEARCH DESIGN AND METHODS: Data sources were the national COVID-19 registry data from the National Public Health Center and the National Health Insurance Fund on the total Hungarian population. The adjusted incidence rate ratios and corresponding 95% CIs were derived from a mixed-effect negative binomial regression model. RESULTS: A population of 672 240 cases with type 2 diabetes and a control group of 2 974 102 non-diabetic persons free from chronic diseases participated. Unvaccinated elderly persons with diabetes had 2.68 (95% CI 2.47 to 2.91) times higher COVID-19-related mortality rate as the 'healthy' controls. Primary immunization effectively equalized the risk of COVID-19 mortality between the two groups. Vaccine effectiveness declined over time, but the booster restored the effectiveness against mortality to over 90%. The adjusted vaccine effectiveness of the primary Pfizer-BioNTech against infection in the 14-120 days of postvaccination period was 71.6 (95% CI 66.3 to 76.1)% in patients aged 65-100 years with type 2 diabetes and 64.52 (95% CI 59.2 to 69.2)% in the controls. Overall, the effectiveness tended to be higher in individuals with diabetes than in controls. The booster vaccines could restore vaccine effectiveness to over 80% concerning risk of infection (eg, patients with diabetes aged 65-100 years: 89.1 (88.1-89.9)% with Pfizer-on-Pfizer, controls 65-100 years old: 86.9 (85.8-88.0)% with Pfizer-on-Pfizer, or patients with diabetes aged 65-100 years: 88.3 (87.2-89.2)% with Pfizer-on-Sinopharm, controls 65-100 years old: 87.8 (86.8-88.7)% with Pfizer-on-Sinopharm). CONCLUSIONS: Our data suggest that people with type 2 diabetes may have even higher health gain when getting vaccinated as compared with non-diabetic persons, eliminating the marked, COVID-19-related excess risk of this population. Boosters could restore protection.

The Semmelweis Study: a longitudinal occupational cohort study within the framework of the Semmelweis Caring University Model Program for supporting healthy aging.

The Semmelweis Study is a prospective occupational cohort study that seeks to enroll all employees of Semmelweis University (Budapest, Hungary) aged 25 years and older, with a population of 8866 people, 70.5% of whom are women. The study builds on the successful experiences of the Whitehall II study and aims to investigate the complex relationships between lifestyle, environmental, and occupational risk factors, and the development and progression of chronic age-associated diseases. An important goal of the Semmelweis Study is to identify groups of people who are aging unsuccessfully and therefore have an increased risk of developing age-associated diseases. To achieve this, the study takes a multidisciplinary approach, collecting economic, social, psychological, cognitive, health, and biological data. The Semmelweis Study comprises a baseline data collection with open healthcare data linkage, followed by repeated data collection waves every 5 years. Data are collected through computer-assisted self-completed questionnaires, followed by a physical health examination, physiological measurements, and the assessment of biomarkers. This article provides a comprehensive overview of the Semmelweis Study, including its origin, context, objectives, design, relevance, and expected contributions.

Frailty prevalence in 42 European countries by age and gender: development of the SHARE Frailty Atlas for Europe.

Comparative frailty prevalence data across European countries is sparse due to heterogeneous measurement methods. The Survey of Health, Ageing and Retirement (SHARE) initiative conducted interviews with probability sampling of non-institutionalized elderly people in several European countries. Previous frailty analyses of SHARE datasets were limited to initial SHARE countries and did not provide age- and gender-stratified frailty prevalence. Our aim was to provide age- and gender-stratified frailty prevalence estimates in all European countries, with predictions where necessary. From 29 SHARE participating countries, 311,915 individual surveys were analyzed. Frailty prevalence was estimated by country and gender in 5-year age bands using the SHARE Frailty Instrument and a frailty index. Association of frailty prevalence with age, gender, and GDP per capita (country-specific economic indicator for predictions) was investigated in multivariate mixed logistic regression models with or without multiple imputation. Female gender and increasing age were significantly associated with higher frailty prevalence. Higher GDP per capita, with or without purchasing power parity adjustment, was significantly associated with lower frailty prevalence in the 65-79 age groups in all analyses. Observed and predicted data on frailty rates by country are provided in the interactive SHARE Frailty Atlas for Europe. Our study provides age- and gender-stratified frailty prevalence estimates for all European countries, revealing remarkable between-country heterogeneity. Higher frailty prevalence is strongly associated with lower GDP per capita, underlining the importance of investigating transferability of evidence across countries at different developmental levels and calling for improved policies to reduce inequity in risk of developing frailty across European countries.

Roadmap to improve the organized cancer screening programs - The case of colorectal cancer screening in Montenegro.

BACKGROUND: Implementation of organized cancer screening programs comes with many challenges and barriers, which may inhibit the achievement of the screening activities' desired benefits. In this paper we outline a plan for improving the colorectal cancer (CRC) screening system in Montenegro. METHODS: We formulated a roadmap, which was generally defined as a country-specific strategic plan to improve cancer screening programs. The roadmap development was an iterative, step-by-step process. First, we described the current screening program, then identified and described key barriers, and finally proposed actions to overcome them. Multiple sources of information (e.g., documents, expert opinions) were collected and processed by local and international stakeholders. RESULTS: The CRC screening program was implemented between 2013-2019 by gradually increasing the invitation of the target population. Key barriers of the implementation were defined: 1) Lack of colonoscopy capacity in the northern part of the country; 2) Inadequate information technology systems; 3) Inadequate public promotion of screening. The defined actions were related to overcoming lack of available resources (e.g., financial, human and technological), to improve the policy environment and the knowledge, and to facilitate information sharing. CONCLUSION: The collaboration between local stakeholders of CRC screening and researchers experienced in planning and evaluating screening programs resulted in the first comprehensive description of CRC screening in Montenegro, detailed understanding of key barriers that emerged during implementation and a carefully designed list of actions. The implementation of these actions and the evaluation of whether barriers were solved will be captured in the upcoming period by maintaining this collaboration.

Effectiveness and waning of protection with the BNT162b2 vaccine against the SARS-CoV-2 Delta variant in immunocompromised individuals.

Introduction: In Hungary, the HUN-VE 3 study determined the comparative effectiveness of various primary and booster vaccination strategies during the Delta COVID-19 wave. That study included more than 8 million 18-100-year-old individuals from the beginning of the pandemic. Immunocompromised (IC) individuals have increased risk for COVID-19 and disease course might be more severe in them. In this study, we wished to estimate the risk of SARS-CoV-2 infection and COVID-19 related death in IC individuals compared to healthy ones and the effectiveness of the BNT162b2 vaccine by reassessing HUN-VE 3 data. Patients and methods: Among the 8,087,988 individuals undergoing follow-up from the onset of the pandemic in the HUN-VE 3 cohort, we selected all the 263,116 patients with a diagnosis corresponding with IC and 6,128,518 controls from the second wave, before vaccinations started. The IC state was defined as two occurrences of corresponding ICD-10 codes in outpatient or inpatient claims data since 1 January, 2013. The control group included patients without chronic diseases. The data about vaccination, SARS-CoV-2 infection and COVID-19 related death were obtained from the National Public Health Center (NPHC) during the Delta wave. Cases of SARS-CoV-2 infection were reported on a daily basis using a centralized system via the National Public Health Center (NPHC). Results: Out of the 263,116 IC patients 12,055 patients (4.58%) and out of the 6,128,518 healthy controls 202,163 (3.30%) acquired SARS-CoV-2 infection. Altogether 436 IC patients and 2141 healthy controls died in relation to COVID-19. The crude incidence rate ratio (IRR) of SARS-CoV-2 infection was 1.40 (95%CI: 1.37-1.42) comparing IC patients to healthy controls. The crude mortality rate ratio was 4.75 (95%CI: 4.28-5.27). With respect to SARS-CoV-2 infection, interestingly, the BNT162b2 vaccine was more effective in IC patients compared to controls. Primary vaccine effectiveness (VE) was higher in IC patients compared to controls and the booster restored VE after waning. VE regarding COVID-19 related death was less in IC patients compared to healthy individuals. Booster vaccination increased VE against COVID-19-related death in both IC patients and healthy controls. Conclusion: There is increased risk of SARS-CoV-2 infection and COVID-19 related mortality in IC patient. Moreover, booster vaccination using BNT162b2 might restore impaired VE in these individuals.

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 changes in advanced lung cancer survival during the past decade in Hungary: impact of modern immunotherapy and the COVID-19 pandemic.

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.

Systematic literature review of the epidemiology of glycogen storage disease type 1a.

Glycogen storage disease (GSD) type 1a is an inherited autosomal recessive metabolic disease caused by a deficiency in glucose-6-phosphatase activity. The objectives of this research were to systematically review the published literature on the epidemiology of GSD 1a and to assess the performance of reported epidemiology measures in a simulation model. In this systematic literature review 2,539 record titles and abstracts were screened. Of these, only 11 studies contained relevant data on GSD 1a disease epidemiology. Reported disease frequency ranged from 0.085/100,000 to 10.3/100,000 newborns when considering all the GSD literature. When this was narrowed to GSD 1 and GSD 1a, the range was tightened to 0.25-3.02/100,000 and 0.085-4.9/100,000 newborns, respectively. Most of the identified studies counted the number of diagnoses in a defined period and related to the number of births in the same (Dx method) or different time period (DoB method). The simulation model results indicate that in most of the situations, the Dx method provides a closer estimate to the true disease incidence than the DoB method. Despite the scarcity of epidemiology data, the results of this systematic review strongly support that GSD 1a and its parent disease groups (GSD and GSD 1) are rare diseases.

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.

Cardioprotective efficacy of limb remote ischaemic preconditioning in rats: discrepancy between a meta-analysis and a three-centre in vivo study.

AIMS: Remote ischaemic preconditioning (RIPC) is a robust cardioprotective intervention in preclinical studies. To establish a working and efficacious RIPC protocol in our laboratories, we performed randomized, blinded in vivo studies in three study centres in rats, with various RIPC protocols. To verify that our experimental settings are in good alignment with in vivo rat studies showing cardioprotection by limb RIPC, we performed a systematic review and meta-analysis. In addition, we investigated the importance of different study parameters. METHODS AND RESULTS: Male Wistar rats were subjected to 20-45 min cardiac ischaemia followed by 120 min reperfusion with or without preceding RIPC by 3 or 4 × 5-5 min occlusion/reperfusion of one or two femoral vessels by clamping, tourniquet, or pressure cuff. RIPC did not reduce infarct size (IS), microvascular obstruction, or arrhythmias at any study centres. Systematic review and meta-analysis focusing on in vivo rat models of myocardial ischaemia/reperfusion injury with limb RIPC showed that RIPC reduces IS by 21.28% on average. In addition, the systematic review showed methodological heterogeneity and insufficient reporting of study parameters in a high proportion of studies. CONCLUSION: We report for the first time the lack of cardioprotection by RIPC in rats, assessed in individually randomized, blinded in vivo studies, involving three study centres, using different RIPC protocols. These results are in discrepancy with the meta-analysis of similar in vivo rat studies; however, no specific methodological reason could be identified by the systematic review, probably due to the overall insufficient reporting of several study parameters that did not improve over the past two decades. These results urge for publication of more well-designed and well-reported studies, irrespective of the outcome, which are required for preclinical reproducibility, and the development of clinically translatable cardioprotective interventions.