Risk of exacerbation and mortality in asthma: a 10-year retrospective financial database analysis of the Hungarian Health Insurance Fund.

INTRODUCTION: Asthma is the most prevalent obstructive pulmonary disease, with drastically improved treatment options over the past decades. However, there is still a proportion of patients with suboptimal level of asthma control, leading to multiple hospitalisation due to severe acute exacerbation (SAE) and earlier death. In our study, we aimed to assess the risk of SAEs and mortality in patients who suffered an SAE. METHODS: The database of the National Health Insurance Fund was used to retrospectively analyse the data of all asthmatic patients who had been hospitalised for an SAE between 2009 and 2019. We used a competing risk model to analyse the effect of each exacerbation on the risk of further SAEs with age, sex, Charlson index and the number of severe and moderate exacerbations included as covariates. RESULT: Altogether, 9257 asthmatic patients suffered at least one exacerbation leading to hospitalisation during the study time. The majority (75.8%) were women, and the average age was 58.24 years. Most patients had at least one comorbidity. 3492 patients suffered at least one further exacerbation and 1193 patients died of any cause. In the competing risk model, each SAE increased the risk of further exacerbations (HR=2.078-7.026; p<0.0001 for each case) but not death. The risk of SAEs was also increased by age (HR=1.008) female sex (HR=1.102) and with the number of days of the first SAE (HR=1.007). CONCLUSIONS: Even though asthma is generally a well-manageable disease, there still are many patients who suffer SAEs that significantly increase the risk of further similar SAEs.

National and education-specific trends in life and health expectancies in Denmark 2004-2015.

BACKGROUND: Several studies have revealed widening of inequalities in life expectancy, but little is known about the recent changes in health expectancy nationally and between socioeconomic groups. This study examines dynamics of national and education-specific life expectancy and health expectancies at age 50 years in Denmark from 2004/2007 to 2015. METHODS: Nationwide register data on education and mortality were linked and combined with Danish health data from the Survey of Health, Ageing and Retirement in Europe and changes in life expectancy and three health expectancy indicators were estimated by Sullivan's method. RESULTS: From 2004 to 2015, national life expectancy at age 50 years increased by 2.4 years for men and 2.1 years for women. Simultaneously, after an initial rapid improvement from 2004 to 2007, the pace of progress in health expectancy decreased. From 2007 to 2015, the difference in life expectancy at age 50 years between men with long and short education increased from 4.3 to 5.0 years. For women, the corresponding increase in the life expectancy gap was less pronounced from 3.5 to 3.8 years. The educational gap in lifetime without long-term illness decreased from 4.6 years to 3.1 years for men and from 6.1 years to 4.6 years for women. On the contrary, the educational gap increased for lifetime without activity limitations and in self-rated good health. CONCLUSIONS: Previously observed improvements in health expectancy in Denmark slowed down despite continuing progress in life expectancy. This worrying change coincides with persistent educational inequalities in life expectancy and health expectancy and is a challenge to a sustainable social and health development in the future.

Deficiencies in the Recognition and Reporting of Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus; A Hungarian Nationwide Analysis.

Objectives: Recognition of chronic kidney disease (CKD) is crucial in type 2 diabetes mellitus (T2DM). We conducted a nationwide epidemiological study to evaluate T2DM-associated CKD in Hungary between 2016 and 2020. Methods: Annual incidence and prevalence rates of registered CKD amongst all pharmacologically treated T2DM patients were analyzed in different age-groups by the central database of the Hungarian Health Insurance Fund Management. Statistical methods included Poisson regression, Bonferroni test, Chi-square test. Results: We found 499,029 T2DM patients and 48,902 CKD patients in 2016, and 586,075 T2DM patients and 38,347 CKD patients in 2020. The majority of all prevalent T2DM and CKD patients were older (aged 60-69 years: 34.1% and 25.8%; ≥70 years: 36.1% and 64.4%, respectively). The annual incidence of T2DM and incidence rates of CKD in T2DM decreased in 2017-2020 (p < 0.001). The annual prevalence of T2DM increased (p < 0.01), the prevalence rates of CKD in T2DM were low and decreased from 9.8% to 6.5% in 2016-2020 (p < 0.001). Conclusion: Incidence and prevalence of T2DM-associated CKD decreased significantly in Hungary in 2016-2020. Lower prevalence rates of CKD may suggest under-recognition and/or under-reporting.

[Hyperbaric oxygen therapy in outpatient care]. / A túlnyomásos oxigénkezelés és helye az ambuláns ellátásban.

Hyperbaric oxygen therapy, or high pressure oxygen therapy, is a highly specialised branch of medicine. Applications and results date back to the 1960s and it has been used, researched and developed ever since. During the treatment, patients breathe 100% oxygen in a pressurised chamber. For clinical purposes, as defined, the pressure must equal or exceed 1.4 atmosphera absolute, most of the cases typically higher (2.0-2.5 atmosphera absolute). Oxygen dissolves by pressure in body fluids, transported by circulation to all tissues. Cellular regeneration and tissue processes are induced by both the increased oxygen supply and the intermittent change in tissue partial oxygen pressure associated with treatment. The effect can be used in the treatment of many diseases, usually as part of a complex treatment plan. Additional advantage is that it is a non-invasive and pain-free therapy. Evidence-based indications and general baseline usage are regulated by the European Underwater and Baromedical Society through the European Committee of Hyperbaric Medicine, in accordance with the principles of evidence-based medicine. The authors describe three cases in their publication where hyperbaric oxygen therapy significantly contributed to the success of overall treatment. Orv Hetil. 2023; 164(25): 993-996.

Correction to: Changes in socioeconomic differentials in old age life expectancy in four Nordic countries: the impact of educational expansion and education-specific mortality.

[This corrects the article DOI: 10.1007/s10433-022-00698-y.].

Changes in socioeconomic differentials in old age life expectancy in four Nordic countries: the impact of educational expansion and education-specific mortality.

Overall progress in life expectancy (LE) depends increasingly on survival in older ages. The birth cohorts now reaching old age have experienced considerable educational expansion, which is a driving force for the social change and social inequality. Thus, this study examines changes in old age LE by educational attainment in the Nordic countries and aims to find out to what extent the change in national LEs is attributable to education-specific mortality and the shifting educational composition. We used national register data comprising total 65 + populations in Denmark, Finland, Norway and Sweden to create period life tables stratified by five-year age groups (65-90 +), sex and educational attainment. Difference in LE between 2001 and 2015 was decomposed into the contributions of mortality changes within each educational group and changes in educational composition. Increasing LE at all ages and in all educational groups coincided with persistent and growing educational inequalities in all countries. Most of the gains in LE at age 65 could be attributed to decreased mortality (63-90%), especially among those with low education, the largest educational group in most countries. The proportion of the increase in LE attributable to improved education was 10-37%, with the highest contributions recorded for women in Norway and Sweden. The rising educational levels in the Nordic countries still carry potential for further gains in national LEs. However, the educational expansion has contributed to uneven gains in LE between education groups, which poses a risk for the future increase of inequalities in LE. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00698-y.

What should be the baseline when calculating excess mortality? New approaches suggest that we have underestimated the impact of the COVID-19 pandemic and previous winter peaks.

Excess mortality has been used to measure the impact of COVID-19 over time and across countries. But what baseline should be chosen? We propose two novel approaches: an alternative retrospective baseline derived from the lowest weekly death rates achieved in previous years and a within-year baseline based on the average of the 13 lowest weekly death rates within the same year. These baselines express normative levels of the lowest feasible target death rates. The excess death rates calculated from these baselines are not distorted by past mortality peaks and do not treat non-pandemic winter mortality excesses as inevitable. We obtained weekly series for 35 industrialized countries from the Human Mortality Database for 2000-2020. Observed, baseline and excess mortalities were measured by age-standardized death rates. We assessed weekly and annual excess death rates driven by the COVID-19 pandemic in 2020 and those related to seasonal respiratory infections in earlier years. There was a distinct geographic pattern with high excess death rates in Eastern Europe followed by parts of the UK, and countries of Southern and Western Europe. Some Asia-Pacific and Scandinavian countries experienced lower excess mortality. In 2020 and earlier years, the alternative retrospective and the within-year excess mortality figures were higher than estimates based on conventional metrics. While the latter were typically negative or close to zero in years without extraordinary epidemics, the alternative estimates were substantial. Cumulation of this "usual" excess over 2-3 years results in human losses comparable to those caused by COVID-19. Challenging the view that non-pandemic seasonal winter mortality is inevitable would focus attention on reducing premature mortality in many countries. As SARS-CoV-2 is unlikely to be the last respiratory pathogen with the potential to cause a pandemic, such measures would also strengthen global resilience in the face of similar threats in the future.

The short-term mortality fluctuation data series, monitoring mortality shocks across time and space.

The COVID-19 pandemic has revealed substantial coverage and quality gaps in existing international and national statistical monitoring systems. It is striking that obtaining timely, accurate, and comparable across countries data in order to adequately respond to unexpected epidemiological threats is very challenging. The most robust and reliable approach to quantify the mortality burden due to short-term risk factors is based on estimating weekly excess deaths. This approach is more reliable than monitoring deaths with COVID-19 diagnosis or calculating incidence or fatality rates affected by numerous problems such as testing coverage and comparability of diagnostic approaches. In response to the emerging data challenges, a new data resource on weekly mortality has been established. The Short-term Mortality Fluctuations (STMF, available at www.mortality.org ) data series is the first international database providing open-access harmonized, uniform, and fully documented data on weekly all-cause mortality. The STMF online vizualisation tool provides an opportunity to perform a quick assessment of the excess weekly mortality in one or several countries by means of an interactive graphical interface.

Method for reconstructing mortality by educational groups.

BACKGROUND: The lack of classification by educational attainment in death and population exposure data at older ages is an important constraint for studying changes and patterns of mortality disparities by education in Denmark and Sweden. The missing educational distribution of population also restricts analyses aiming at estimating contributions of compositional change to the improvements in national longevity. This study proposes a transparent approach to solve the two methodological issues allowing to obtain robust education-specific mortality estimates and population weights. METHODS: Using nonparametric approach, we redistribute the unknown cases and extrapolate the mortality curves of these sub-populations with the help of population-level data on an aggregate level from the Human Mortality Database. RESULTS: We present reconstructed and harmonized education-specific abridged and complete life tables for Sweden and Denmark covering 5-year-long periods from 1991-1995 to 2011-2015. The newly estimated life tables are in good agreement with the national life tables and show plausible age- and education-specific patterns. The observed changes in life expectancy by education suggest about the widening longevity gap between the highest and lowest educated for males and females in both countries. CONCLUSIONS: The proposed simple and transparent method can be applied in similar country-specific cases showing large proportions of missing education or other socio-economic characteristics at older ages.

An open-sourced, web-based application to analyze weekly excess mortality based on the Short-term Mortality Fluctuations data series.

The COVID-19 pandemic stimulated the interest of scientists, decision makers and the general public in short-term mortality fluctuations caused by epidemics and other natural or man-made disasters. To address this interest and provide a basis for further research, in May 2020, the Short-term Mortality Fluctuations data series was launched as a new section of the Human Mortality Database. At present, this unique data resource provides weekly mortality death counts and rates by age and sex for 38 countries and regions. The main objective of this paper is to detail the web-based application for visualizing and analyzing the excess mortality based on the Short-term Mortality Fluctuation data series. The application yields a visual representation of the database that enhances the understanding of the underlying data. Besides, it enables the users to explore data on weekly mortality and excess mortality across years and countries. The contribution of this paper is twofold. First, to describe a visualization tool that aims to facilitate research on short-term mortality fluctuations. Second, to provide a comprehensive open-source software solution for demographic data to encourage data holders to promote their datasets in a visual framework.

Comments on: A functional polymorphism rs10830963 in melatonin receptor 1B associated with the risk of gestational diabetes mellitus.

We have read with great interest the accepted manuscript of the meta-analysis performed by Huang, et al. titled "A functional polymorphism rs10830963 in melatonin receptor 1B associated with the risk of gestational diabetes mellitus" published online in the 2019 December 6 issue of Bioscience Reports (https://doi.org/10.1042/BSR20190744). We do agree with the authors' final conclusion that such a meta-analysis should eventually confirm that the MTNR1B rs10830963 G allele is significantly associated with increased risk of gestational diabetes mellitus (GDM) development in pregnant populations with Asian and European ancestry. However we have surprisingly found that our genetic association study (PLoS One (2017), https://doi.org/10.1371/journal.pone.0169781) was included in this meta-analysis, but with mistakenly calculated odds ratios (OR). Therefore we would suggest to use the correct OR values based on our original publication that were already indicating a high genetic effect size for the MTNR1B rs10830963 risk variant on GDM development.

Utilization of acute vascular imaging and neurointervention for acute ischaemic stroke patients in 20 Hungarian stroke centers.

BACKGROUND AND PURPOSE: Acute mortality rate of stroke in Hungary is significantly higher than in Western Europe, which is likely to be partially attributable to suboptimal treatment. METHODS: We examined the use of acute vascular imaging and mechanical thrombectomy for acute ischaemic stroke patients. We collected data on 20 consecutive patients from Hungarian stroke centers before 31st August 2016. RESULTS: Out of the reported 410 patients, 166 (40.4%) underwent CT angiography and 44 (10.7%) had mechanical thrombectomy. CONCLUSION: Only about 1/3 of acute ischaemic stroke patients eligible for thrombectomy actually had it. The underlying reasons include long onset-to-door time, low utilization of acute vessel imaging and a limited neuro-intervention capacity needing improvement.

Reduced GLP-1 response to a meal is associated with the CTLA4 rs3087243 G/G genotype.

Although insulitis is the characteristic main feature of type 1 diabetes mellitus (T1DM), many aspects of ß cell loss still remain elusive. Immune dysregulation and alterations in the dipeptidyl-peptidase-4-incretin system might have a role in disease development, but their connection is poorly understood. We assessed the associations of a few selected, immunologically relevant single nucleotide gene variants with the DPP-4-incretin system in individuals with T1DM and in healthy controls. Prandial plasma (total, active) GLP-1 levels, serum DPP-4 activity, CD25 and CTLA-4 expression of T cells and DPP4 rs6741949, CTLA4 rs3087243, CD25 rs61839660 and PTPN2 rs2476601 SNPs were assessed in 33 T1DM patients and 34 age-, gender-, BMI-matched non-diabetic controls without a family history of T1DM. CTLA-4 expression was lower in the Foxp3+CD25+ regulatory T cells from individuals homozygous for the CTLA4 rs3087243-G variant compared to those who carry an A allele. Prandial plasma total GLP-1 levels 45 min after a standardized meal were reduced in individuals homozygous for the CTLA4 rs3087243 G major allele compared to A allele carriers both in the entire study population (with statistical power over 90%) and within the T1DM group. Here we report for the first time a reduced total prandial GLP-1 plasma concentration in individuals with the CTLA4 rs3087243 G/G genotype. One may speculate that immune response-related L cell damage might possibly explain this novel association.

The MTNR1B rs10830963 Variant in Interaction with Pre-Pregnancy BMI is a Pharmacogenetic Marker for the Initiation of Antenatal Insulin Therapy in Gestational Diabetes Mellitus.

The rs10830963 variant of the Melatonin Receptor 1B (MTNR1B) gene is associated with the development of gestational diabetes mellitus (GDM). We hypothesized that carrying the rs10830963/G risk allele had effect on antenatal insulin therapy (AIT) initiation in GDM in a body mass index (BMI)-dependent manner. Design: In this post hoc analysis the MTNR1B rs10830963 genotype and the clinical data of 211 Caucasian GDM patients were assessed. As a first step, a pre-pregnancy BMI threshold was determined where the effect of MTNR1B rs10830963/G allele carrying on AIT initiation was the most significant using logistic regression. Maternal age adjusted real-life odds ratios (OR) values were calculated. The chi-square test was also used to calculate the p value and 10.000 bootstrap simulations were performed in each case to re-assess the statistical power and the OR. Carrying the MTNR1B rs10830963/G allele increased the odds of AIT initiation (OR = 5.2, p = 0.02 [χ² test], statistical power = 0.53) in GDM patients with pre-pregnancy BMI ≥ 29 kg/m². The statistical power reached 0.77, when the pre-pregnancy BMI cutoff of 27 kg/m² was used and the genetic effect on AIT initiation was still significant, but only using the logistic regression model. Carrying the MTNR1B rs10830963/G risk allele-in interaction with pre-pregnancy BMI-is likely be considered as a candidate pharmacogenetic marker of antenatal insulin therapy initiation and should be further assessed in precision medicine trials in GDM.

Adequate life-expectancy reconstruction for adult human mortality data.

Mortality information of populations is aggregated in life tables that serve as a basis for calculation of life expectancy and various life disparity measures. Conventional life-table methods address right-censoring inadequately by assuming a constant hazard in the last open-ended age group. As a result, life expectancy can be substantially distorted, especially in the case when the last age group in a life table contains a large proportion of the population. Previous research suggests addressing censoring in a gamma-Gompertz-Makeham model setting as this framework incorporates all major features of adult mortality. In this article, we quantify the difference between gamma-Gompertz-Makeham life expectancy values and those published in the largest publicly available high-quality life-table databases for human populations, drawing attention to populations for which life expectancy values should be reconsidered. We also advocate the use of gamma-Gompertz-Makeham life expectancy for three reasons. First, model-based life-expectancy calculation successfully handles the problem of data quality or availability, resulting in severe censoring due to the unification of a substantial number of deaths in the last open-end age group. Second, model-based life expectancies are preferable in the case of data scarcity, i.e. when data contain numerous age groups with zero death counts: here, we provide an example of hunter-gatherer populations. Third, gamma-Gompertz-Makeham-based life expectancy values are almost identical to the ones provided by the major high-quality human mortality databases that use more complicated procedures. Applying a gamma-Gompertz-Makeham model to adult mortality data can be used to revise life-expectancy trends for historical populations that usually serve as input for mortality forecasts.

Life expectancy versus lifespan inequality: A smudge or a clear relationship?

Interest in inequality, including lifespan inequality, is growing. Several studies, using various measures of variation in the length of life, reveal that as life expectancy increases, lifespan inequality tends to decrease, albeit with considerable variation across populations and over time. The aim of this article is to understand why the strength of the relationship between life expectancy and lifespan inequality varies across publications. Results differ in large part because they are based on different data sources. In addition, some measures show more smudginess than others. All the analyses presented here support the basic finding of a strong relationship between life expectancy and lifespan inequality.

Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development.

CONTEXT: Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). OBJECTIVE: We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. METHODS: 960 pregnant women (after dropouts 820: case/control: m99'WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m'99WHO criteria based on standard OGTT values. RESULTS: The most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m'99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT. CONCLUSIONS: We confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99'WHO and the IADPSG GDM diagnostic criteria.

The emergence of longevous populations.

The human lifespan has traversed a long evolutionary and historical path, from short-lived primate ancestors to contemporary Japan, Sweden, and other longevity frontrunners. Analyzing this trajectory is crucial for understanding biological and sociocultural processes that determine the span of life. Here we reveal a fundamental regularity. Two straight lines describe the joint rise of life expectancy and lifespan equality: one for primates and the second one over the full range of human experience from average lifespans as low as 2 y during mortality crises to more than 87 y for Japanese women today. Across the primate order and across human populations, the lives of females tend to be longer and less variable than the lives of males, suggesting deep evolutionary roots to the male disadvantage. Our findings cast fresh light on primate evolution and human history, opening directions for research on inequality, sociality, and aging.

Fumonisin measurement from maize samples by high-performance liquid chromatography coupled with corona charged aerosol detector.

Fumonisins are a class of mycotoxins produced mainly by Fusarium species, which is primary fungal contaminant of the maize and maize-derived products around the world. The B-series fumonisins (FB1, FB2 and FB3) are the most abundant and toxic constituent; thus, their levels are regulated generally worldwide. In this study, we developed a reliable method for the measurement of fumonisin FB1, FB2 and FB3 mycotoxins from maize samples without the time-consuming derivatization step using a high-performance liquid chromatograph coupled with corona charged aerosol detector. The detection and quantitation limit of the whole method were 0.02 and 0.04 mg/kg for each fumonisins, respectively. The detection linearity was tested in the calibration range of 2 orders of magnitude and the recoveries from the spiked samples were determined. The developed method proved to be sufficient to measure the maximum residue levels of fumonisins, which are specified in European Union and United States in maize and maize-based products.

Efflux transport of serum amyloid P component at the blood-brain barrier.

Serum amyloid P component (SAP), a member of the innate immune system, does not penetrate the brain in physiological conditions; however, SAP is a stabilizing component of the amyloid plaques in neurodegenerative diseases. We investigated the cerebrovascular transport of human SAP in animal experiments and in culture blood-brain barrier (BBB) models. After intravenous injection, no SAP could be detected by immunohistochemistry or ELISA in healthy rat brains. Salmonella typhimurium lipopolysaccharide injection increased BBB permeability for SAP and the number of cerebral vessels labeled with fluorescein isothiocyanate (FITC)-SAP in mice. Furthermore, when SAP was injected to the rat hippocampus, a time-dependent decrease in brain concentration was seen demonstrating a rapid SAP efflux transport in vivo. A temperature-dependent bidirectional transport of FITC-SAP was observed in rat brain endothelial monolayers. The permeability coefficient for FITC-SAP was significantly higher in abluminal to luminal (brain to blood) than in the opposite direction. The luminal release of FITC-SAP from loaded endothelial cells was also significantly higher than the abluminal one. Our data indicate the presence of BBB efflux transport mechanisms protecting the brain from SAP penetration. Damaged BBB integrity due to pathological insults may increase brain SAP concentration contributing to development of neurodegenerative diseases.