Birthweight trends and their explanatory factors in Hungary between 1999 and 2018: an analysis of the Hungarian Tauffer registry.

BACKGROUND: The increasing birthweight trend stopped and even reversed in several high income countries in the last 20 years, however the reason for these changes is not well characterized. We aimed to describe birthweight trends of term deliveries in Hungary between 1999 and 2018 and to investigate potential maternal and foetal variables that could drive these changes. METHODS: We analysed data from the Hungarian Tauffer registry, a compulsory anonymized data collection of each delivery. We included all singleton term deliveries in 1999-2018 (n = 1,591,932). We modelled birthweight trends separately in 1999-2008 and 2008-2018 in hierarchical multiple linear regression models adjusted for calendar year, newborn sex, maternal age, gestational age at delivery, and other important determinants. RESULTS: Median birthweights increased from 3250/3400 g (girl/boy) to 3300/3440 g from 1999 to 2008 and decreased to 3260/3400 g in 2018. When we adjusted for gestational age at delivery the increase in the first period became more pronounced (5.4 g/year). During the second period, similar adjustment substantially decreased the rate of decline from 2.5 to 1.4 g/year. Further adjustment for maternal age halved the rate of increase to 2.4 g/year in the first period. During the second period, adjustment for maternal age had little effect on the estimate. CONCLUSIONS: Our findings of an increasing birthweight trend (mostly related to the aging of the mothers) in 1999-2008 may forecast an increased risk of cardiometabolic diseases in offsprings born in this period. In contrast, the decreasing birthweight trends after 2008 may reflect some beneficial effects on perinatal morbidity. However, the long-term effect cannot be predicted, as the trend is mostly explained by the shorter pregnancies.

Birthweights showed an increase followed by a decrease in several high income countries in the last 20 years, however the reasons for these changes is not well described. Thus, we aimed to investigate birthweight trends and their potential explanatory factors in Hungary between 1999 and 2018. We used registry data of all deliveries from Hungary in 1999­2018 (n = 1 591 932). Birthweights increased from 3250/3400 g (girl/boy) to 3300/3440 g from 1999 to 2008 and decreased to 3260/3400 g until 2018. Maternal age explained approximately half of increase in the first period, while a substantial part of the decrease in the second period was explained by the presence of shorter pregnancies. The increasing birthweights in 1999­2008 may forecast an increased risk of cardiometabolic diseases in offsprings born in this period. In contrast, the decreasing birthweight trends after 2008 may reflect some beneficial effects on perinatal morbidity. However, its long-term consequences cannot be predicted, as the trend is mostly explained by the shorter pregnancies.

Spontaneous and Treatment-Related Changes of Serum Calcitonin in Medullary Thyroid Cancer: Long-Term Experience in a Patient With Multiple Endocrine Neoplasia Type 2B.

PURPOSE: Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. METHODS: The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). RESULTS: Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. CONCLUSION: This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.

Proposal of a novel cardiovascular risk prediction score in lupus nephritis.

Introduction: Patients with systemic lupus erythematosus are prone to develop cardiovascular disease (CVD), and have increased morbidity and mortality. Methods: We conducted a retrospective analysis on lupus nephritis patients to assess the occurrence and predictors of major adverse cardiovascular events (MACE). Data were collected from patients who underwent kidney biopsy between 2005 and 2020. Statistical analysis was performed to unveil correlations. Results: 91 patients were analyzed in this period, with a mean age of 37.3 ± 12.3 years and 86% being female. The mean follow-up time was 62 ± 48 months. 15.38% of the patients underwent at least one MACE. Two patients deceased of CVD. Increased age (35.81 ± 11.14 vs 45.5 ± 15.11 years, p=0.012) entailed a higher occurrence of MACEs. Neutrophil count (5.15 ± 2.83 vs 7.3 ± 2.99 Giga/L, p=0.001) was higher, whereas diastolic blood pressure (DBP) was lower (89.51 ± 10.96 vs 78.43 ± 6.9 mmHg, p<0.001) at the time of the biopsy in patients with MACE. Age, neutrophil count, and DBP proved to be independent predictors of MACEs. We propose a new model (CANDE - Cardiovascular risk based on Age, Neutrophil count, and Diastolic blood pressure Estimation score) calculated from these variables, which predicts the probability of MACE occurrence. Conclusion: This study underscores the importance of actively screening for cardiovascular risks in this vulnerable patient population. Age, neutrophil count, and diastolic blood pressure have been established as independent risk factors for MACE in lupus nephritis. The CANDE score derived from these parameters may serve as a prompt, cost-effective, and easily accessible estimation tool for assessing the likelihood of major adverse cardiovascular risk. These findings emphasize the necessity for comprehensive management strategies addressing both immune dysregulation and cardiovascular risk factors in systemic lupus erythematosus to mitigate adverse outcomes.

Expert Opinion on Current Trends in the Use of Insulin in the Management of People with Type 2 Diabetes from the South-Eastern European Region and Israel.

Despite the availability of various antihyperglycaemic therapies and comprehensive guidelines, glycaemic control in diabetes management has not improved significantly during the last decade in the real-world clinical setting. Treatment inertia arising from a complex interplay among patient-, clinician- and healthcare-system-related factors is the prime reason for this suboptimal glycaemic control. Also, the key factor leading to inadequate glycaemic levels remains limited communication between healthcare professionals (HCPs) and people with type 2 diabetes (PwT2D). Early insulin administration has several advantages including reduced glucotoxicity, high efficacy and preserved ß-cell mass/function, leading to lowering the risk of diabetes complications. The current publication is based on consensus of experts from the South-Eastern European region and Israel who reviewed the existing evidence and guidelines for the treatment of PwT2D. Herein, the experts emphasised the timely use of insulin, preferably second-generation basal insulin (BI) analogues and intensification using basal-plus therapy, as the most-potent glucose-lowering treatment choice in the real-world clinical setting. Despite an increase in the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), the experts urged timely insulin initiation for inadequate glycaemic control in PwT2D. Furthermore, the combination of BI and GLP-1 RA addressing both fasting plasma glucose and post-prandial excursions as a free- or fixed-ratio combination was identified to reduce treatment complexity and burden. To minimise discontinuation and improve adherence, the experts reiterated quality, regular interactions and discussions between HCPs and PwT2D/carers for their involvement in the diabetes management decision-making process. Clinicians and HCPs should consider the opinions of the experts in accordance with the most recent recommendations for diabetes management.

Diagnosis rates, therapeutic characteristics, lifestyle, and cancer screening habits of patients with diabetes mellitus in a highly deprived region in Hungary: a cross-sectional analysis.

Introduction: Low socioeconomic status affects not only diagnosis rates and therapy of patients with diabetes mellitus but also their health behavior. Our primary goal was to examine diagnosis rates and therapy of individuals with diabetes living in Ormánság, one of the most deprived areas in Hungary and Europe. Our secondary goal was to examine the differences in lifestyle factors and cancer screening participation of patients with diagnosed and undiagnosed diabetes compared to healthy participants. Methods: Our study is a cross-sectional analysis using data from the "Ormánság Health Program". The "Ormánság Health Program" was launched to improve the health of individuals in a deprived region of Hungary. Participants in the program were coded as diagnosed diabetes based on diagnosis by a physician as a part of the program, self-reported diabetes status, and self-reported prescription of antidiabetic medication. Undiagnosed diabetes was defined as elevated blood glucose levels without self-reported diabetes and antidiabetic prescription. Diagnosis and therapeutic characteristics were presented descriptively. To examine lifestyle factors and screening participation, patients with diagnosed and undiagnosed diabetes were compared to healthy participants using linear regression or multinomial logistic regression models adjusted for sex and age. Results: Our study population consisted of 246 individuals, and 17.9% had either diagnosed (n=33) or undiagnosed (n=11) diabetes. Metformin was prescribed in 75.8% (n=25) of diagnosed cases and sodium-glucose cotransporter-2 inhibitors (SGLT-2) in 12.1% (n=4) of diagnosed patients. After adjustment, participants with diagnosed diabetes had more comorbidities (adjusted [aOR]: 3.50, 95% confidence interval [95% CI]: 1.34-9.18, p<0.05), consumed vegetables more often (aOR: 2.49, 95% CI: 1.07-5.78, p<0.05), but desserts less often (aOR: 0.33, 95% CI: 0.15-0.75, p<0.01) than healthy individuals. Patients with undiagnosed diabetes were not different in this regard from healthy participants. No significant differences were observed for cancer screening participation between groups. Conclusions: To increase recognition of diabetes, targeted screening tests should be implemented in deprived regions, even among individuals without any comorbidities. Our study also indicates that diagnosis of diabetes is not only important for the timely initiation of therapy, but it can also motivate individuals in deprived areas to lead a healthier lifestyle.

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.

Genetic and environmental determinants of bone quality: a cross-sectional analysis of the Hungarian Twin Registry.

There is abundant evidence that bone mineral content is highly heritable, while the heritability of bone quality (i.e. trabecular bone score [TBS] and quantitative ultrasound index [QUI]) is rarely investigated. We aimed to disentangle the role of genetic, shared and unique environmental factors on TBS and QUI among Hungarian twins. Our study includes 82 twin (48 monozygotic, 33 same-sex dizygotic) pairs from the Hungarian Twin Registry. TBS was determined by DXA, QUI by calcaneal bone ultrasound. To estimate the genetic and environmental effects, we utilized ACE-variance decomposition. For the unadjusted model of TBS, an AE model provided the best fit with > 80% additive genetic heritability. Adjustment for age, sex, BMI and smoking status improved model fit with 48.0% of total variance explained by independent variables. Furthermore, there was a strong dominant genetic effect (73.7%). In contrast, unadjusted and adjusted models for QUI showed an AE structure. Adjustments improved model fit and 25.7% of the total variance was explained by independent variables. Altogether 70-90% of the variance in QUI was related to additive genetic influences. We found a strong genetic heritability of bone quality in unadjusted models. Half of the variance of TBS was explained by age, sex and BMI. Furthermore, the adjusted model suggested that the genetic component of TBS could be dominant or an epistasis could be present. In contrast, independent variables explained only a quarter of the variance of QUI and the additive heritability explained more than half of all the variance.

Effect of school lockdown due to the COVID-19 pandemic on screen time among adolescents in Hungary: a longitudinal analysis.

Introduction: Studies indicate that due to school lockdown during the Coronavirus Disease 2019 (COVID-19) pandemic, screen time increased more steeply than pre-pandemic years. The aim of our study was to examine changes in screen time and its components (screen time spent on videos, games, homework, and other activities) of adolescents affected by COVID-19 school closures compared to controls from pre-pandemic years and to assess the effect of family structure and family communication. Methods: Two sets of ninth-grader boys and girls transitioning into 10th grade were included in the analysis. The 'pre-COVID classes' (controls) completed the baseline survey in February 2018 and the follow-up survey in March 2019. 'COVID classes' (cases) completed the baseline survey in February 2020 (1 month before the COVID-19-related school lockdowns) and the follow-up survey in March 2021. Linear mixed models stratified by sex were built to assess the change in screen time over one year adjusted for family structure and communication. Results: Our study population consisted of 227 controls (128 girls, 99 boys) and 240 cases (118 girls, 122 boys). Without COVID-19, overall screen time did not change significantly for boys, but there was a decrease in screen time for gaming by 0.63 h, which was accompanied by an increase of 1.11 h in screen time for other activities (consisting mainly of social media and communication). Because of the pandemic, all components increased by 1.44-2.24 h in boys. Girls' screen time and its components remained stable without school lockdown, while it increased for videos and homework by 1.66-2.10 h because of school lockdown. Living in a single-parent household was associated with higher, while better family communication resulted in lower screen time. Discussion: Our results indicate that COVID-19-related school lockdowns modified the age-specific increase in screen time for boys and girls as well. This trend, however, may be counterbalanced by improving communication between family members.

Cost-Effectiveness of Bariatric Surgery in Patients Living with Obesity and Type 2 Diabetes.

Aims: The favourable effects of bariatric surgeries on body weight reduction and glucose control have been demonstrated in several studies. Additionally, the cost-effectiveness of bariatric surgeries has been confirmed in several analyses. The aim of the current analysis was to demonstrate the cost-effectiveness of bariatric surgeries in obese patients with type 2 diabetes in Hungary compared to conventional diabetes treatments based on economic modelling of published clinical trial results. Materials and Methods: Patients entered the simulation model at the age of 45 with body mass index (BMI) ≥ 30 kg/m2 and type 2 diabetes. The model was performed from the public payer's perspective, comparing sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) procedures to conventional care of diabetes. The results were provided separately for three BMI categories. Results: The base-case analysis demonstrated that both surgery types were dominant; i.e., they saved 17 064 to 24 384 Euro public payer expenditures and resulted in improved health outcomes (1.36 to 1.50 quality-adjusted life years gain (QALY)) in the three BMI categories. Bariatric surgeries extended the life expectancy and the disease-free survival times of all the investigated diabetes complications. All the scenario analyses confirmed the robustness of the base-case analysis, such that bariatric surgeries remained dominant compared to conventional diabetes treatments. Conclusion: The results of this cost-effectiveness analysis highlight the importance of bariatric surgeries as alternatives to conventional diabetes treatments in the obese population. Therefore, it is strongly recommended that a wider population has access to these surgeries in Hungary.