Annual epidemiological and health insurance disease burden of hip osteoarthritis in Hungary based on nationwide data.

BACKGROUND: Health services utilization related to hip osteoarthritis imposes a significant burden on society and health care systems. Our aim was to analyse the epidemiological and health insurance disease burden of hip osteoarthritis in Hungary based on nationwide data. METHODS: Data were extracted from the nationwide financial database of the National Health Insurance Fund Administration (NHIFA) of Hungary for the year 2018. The analysed data included annual patient numbers, prevalence, and age-standardized prevalence per 100,000 population in outpatient care, health insurance costs calculated for age groups and sexes for all types of care. Patients with hip osteoarthritis were identified using code M16 of the International Classification of Diseases (ICD), 10th revision. Age-standardised prevalence rates were calculated using the European Standard Population 2013 (ESP2013). RESULTS: Based on patient numbers of outpatient care, the prevalence per 100,000 among males was 1,483.7 patients (1.5%), among females 2,905.5 (2.9%), in total 2,226.2 patients (2.2%). The age-standardised prevalence was 1,734.8 (1.7%) for males and 2,594.8 (2.6%) for females per 100,000 population, for a total of 2,237.6 (2.2%). The prevalence per 100,000 population was higher for women in all age groups. In age group 30-39, 40-49, 50-59, 60-69 and 70 + the overall prevalence was 0.2%, 0.8%, 2.7%, 5.0% and 7.7%, respectively, describing a continuously increasing trend. In 2018, the NHIFA spent 42.31 million EUR on the treatment of hip osteoarthritis. Hip osteoarthritis accounts for 1% of total nationwide health insurance expenditures. 36.8% of costs were attributed to the treatment of male patients, and 63.2% to female patients. Acute inpatient care, outpatient care and chronic and rehabilitation inpatient care were the main cost drivers, accounting for 62.7%, 14.6% and 8.2% of the total health care expenditure for men, and 51.0%, 20.0% and 11.2% for women, respectively. The average annual treatment cost per patient was 3,627 EUR for men and 4,194 EUR for women. CONCLUSIONS: The prevalence of hip osteoarthritis was 1.96 times higher (the age-standardised prevalence was 1.5 times higher) in women compared to men. Acute inpatient care was the major cost driver in the treatment of hip osteoarthritis. The average annual treatment cost per patient was 15.6% higher for women compared to men.

[Quality of life in acute ischaemic stroke patients treated with recanalisation]. / Rekanalizációs beavatkozással kezelt, akut ischaemiás stroke-os betegek életminosége.

Background and purpose:

Stroke is a serious health problem that has a significant impact on health-related quality of life. Despite the increasing popularity of measuring quality of life among patients, it is not routinely measured in clinical practice, and therefore little is known about how well clinical measures reflect quality of life after stroke. The aim of this study was to investigate the quality of life of patients with acute ischaemic stroke.

For the prospective study, patients diagnosed with acute ischemic stroke at the Neurology Clinic of the Clinical Center of the University of Pécs were selected through convenience sampling between June 2022 and May 2023. Based on the treatments, patients were divided into three groups: mechanical thrombectomy (MT), intravenous thrombolysis (IVT), and standard care (SC). Modified Rankin Scale (Pre-mRS, Follow-up mRS), NIH Stroke Scale (NIHSS), and European Quality of Life 5 Dimensions Scale (EQ-5D-5L) were used in the research. Descriptive statistics, paired T-tests, Wilcoxon tests, McNemar tests and Pearson correlation analysis were applied for the analysis (SPSS 25.0; p <0.05).

A total of 198 participants (115 males, 83 females) took part in the study (MT: 50, IVT: 69, SC: 79). The Pre-mRS and follow-up mRS values indicate that the majority of patients in all three groups fell into the mild category (Pre-mRS: 176 participants; 88%, follow-up mRS: 158 participants; 80%). There was a significant improvement in NIHSS scores in all three groups (IVT: 4.36 vs. 1.57, p<0.001; MT: 8.98 vs. 4.50, p<0.001; SC: 4.38 vs. 2.84, p<0.001). The EQ-5D-5L value also significantly increased for all groups (IVT: 0.82 vs. 0.88, p<0.001; MT: 0.63 vs. 0.73, p<0.001, SC: 0.76 vs. 0.80, p=0.014). Patients admitted with lower NIHSS values reported better quality of life at the end of our study (r: -0.43451).

At 30 days, significant improvement was observed in MT, IVT and SC groups when measured with EQ-5D-5L, but the extent of improvement was highest in the MT group.

The long-term effect of generic price competition on the Hungarian statin market.

BACKGROUND: Generic competition is a vital health policy tool used in regulating the pharmaceutical market. Drug group HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase) inhibitors, widely known as "statins," was the first drug group in Hungary in which generic prescriptions became mandatory. Our aim is to analyze the changes in the retail and wholesale margins through the generic competition regarding "statins". METHODS: Data was derived from the nationwide pharmaceutical database of the Hungarian National Health Insurance Fund Administration, the only health care financing agency in Hungary. We observed the turnover data regarding the HMG-CoA-reductase inhibitor "statins" from 2010 through 2019. As the drugs under review have a fixed price point in Hungary, we effectively calculated the margins. RESULTS: In 2010, the consumer expenditure of statins was 30.7 billion HUF ($148 million), which decreased by 59%, to 12.5 billion HUF ($42.9 million) in 2019. In 2010, the annual health insurance reimbursement of statins was 23.7 billion HUF ($114 million), which underwent a 63% decrease to 8.6 billion HUF ($29.7 million) in 2019. In 2010, the DOT turnover was 287 million days, and it increased to above 346 million days for 2019, which reflects a 20% increase over the past nine years. The monthly retail margins decreased from 334 million HUF ($1.6 million), (January, 2010) to 176 million HUF ($0.61 million), (December, 2019). The monthly wholesale margins decreased from 96.3 million HUF ($0.46 million), (January, 2010) to 41.4 million HUF ($0.14 million), (December, 2019). The most significant downturn in margins was due to the introduction of the first two blind bids. The combined DOT turnover in reference to the examined 43 products consistently increased. CONCLUSIONS: The decline in retail and wholesale margin and in health insurance expenditures was largely due to a reduction in the consumer price of generic medicines. DOT turnover of statins also increased significantly.

Progressive chromogenic anti-factor Xa assay and its use in the classification of antithrombin deficiencies.

BACKGROUND: Antithrombin (AT) is a slow-acting progressive inhibitor of activated clotting factors, particularly thrombin and activated factor X (FXa). However, the presence of heparin or heparan sulfate accelerates its effect by several magnitudes. AT deficiency, a severe thrombophilia, is classified as type I (quantitative) and type II (qualitative) deficiency. In the latter case mutations may influence the reactive site, the heparin binding-site (HBS) and exert pleiotropic effect. Heterozygous type II-HBS deficiency is a less severe thrombophilia than other heterozygous subtypes. However, as opposed to other subtypes, it also exists in homozygous form which represents a very high risk of venous thromboembolism. METHODS: A modified anti-FXa chromogenic AT assay was developed which determines both the progressive (p) and the heparin cofactor (hc) activities, in parallel. The method was evaluated and reference intervals were established. The usefulness of the assay in detecting type II-HBS AT deficiency was tested on 78 AT deficient patients including 51 type II-HBS heterozygotes and 18 homozygotes. RESULTS: Both p-anti-FXa and hc-anti-FXa assays showed excellent reproducibility and were not influenced by high concentrations of triglyceride, bilirubin and hemoglobin. Reference intervals for p-anti-FXa and hc-anti-FXa AT activities were 84%-117% and 81%-117%, respectively. Type II-HBS deficient patients demonstrated low (heterozygotes) or very low (homozygotes) hc-anti-FXa activity with normal or slightly decreased p-anti-FXa activity. The p/hc ratio clearly distinguished wild type controls, type II-HBS heterozygotes and homozygotes. CONCLUSIONS: Concomitant determination of p-anti-FXa and hc-anti-FXa activities provides a reliable, clinically important diagnosis of type II-HBS AT deficiency and distinguishes between homozygotes and heterozygotes.

Comparative analysis of the quality of life regarding patients who underwent hip replacement in public versus private hospitals in Hungary.

The study aimed to investigate the impact of hip replacement surgery on the quality of life and to compare the outcomes by sociodemographic and surgical data in Hungarian public and private hospitals. Patients were selected at the Department of Orthopaedics (Clinical Centre, University of Pécs) and at the Da Vinci Private Clinic in Pécs. Patients completed the SF-36 and Oxford Hip Score (OHS) questionnaires before the surgery, 6 weeks and 3 months later. We also evaluated socio-demographic data, disease and surgical conditions. The research involved 128 patients, 60 patients in public, 68 patients in private hospital. Despite the different sociodemographic characteristics and surgical outcomes of public and private healthcare patients, both groups had significantly improved the quality of life 3 months after hip replacement surgery measured by OHS and SF-36 physical health scores (p < 0.001). In the mental health score, only the patients of the private health sector showed a significant improvement (p < 0.001). The extent of improvement did not differ between the two healthcare sectors according to the OHS questionnaire (p = 0.985). While the SF-36 physical health score showed a higher improvement for public patients (p = 0.027), the mental health score showed a higher improvement for private patients (p = 0.015).

Assessing the per Capita Food Supply Trends of 38 OECD Countries between 2000 and 2019-A Joinpoint Regression Analysis.

Food supply has an impact on the prevalence of diet-related non-communicable diseases. We aimed to analyze the protein, fat (g/capita/day) and calorie (kcal/capita/day) supply from 2000 to 2019 as derived from the OECD Health Statistics database. A joinpoint regression was used to examine the number and location of breakpoints in the time series. The annual percent change (APC) was calculated using Joinpoint 4.9.0.0. The per capita daily kcal per nutrient was calculated for each country and the resulting percentage distributions were compared to the acceptable macronutrient distribution ranges. Protein, fat and calorie supplies have increased significantly between 2000 and 2019. Each started to show a much steeper, positive change between 2012 and 2014 (APCfat: 1.0; 95%CI: 0.8-1.1; APCprotein: 0.5; 95%CI: 0.3-0.6; APCkcal: 0.4; 95%CI: 0.3-0.5). In terms of the composition of the daily calorie intake per capita, the overall share of fat (+4.9%) and protein (+1.0%) increased between 2000 and 2019. We found significant differences among countries and also an increasing and optimal proportion of consumed protein per total calorie in all countries over the last two decades. We concluded that several countries have access to fat availability above the optimal level, which deserves particular attention from health policy makers in the fight against obesity and diet-related diseases.

Prevalence and Annual Health Insurance Cost of Endometriosis in Hungary-A Nationwide Study Based on Routinely Collected, Real-World Health Insurance Claims Data.

Endometriosis is a disease that is often diagnosed late and that may lead to significant reduction in quality of life and serious complications (e.g., infertility). We aimed to assess the prevalence and the annual, nationwide health insurance treatment cost of endometriosis in Hungary using a quantitative, descriptive, cross-sectional method, focusing on the year 2019. We used claims data obtained from the Hungarian National Health Insurance Fund Administration (NHIFA). Patient numbers, total and age-specific prevalence, annual health insurance expenditure, and the distribution of costs across age groups were determined. The NHIFA spent a total of HUF 619.95 million (EUR 1.91 million) on endometriosis treatment. The highest number of patients and prevalence (10,058 women, 197.3 per 100,000) were found in outpatient care. In acute inpatient care, prevalence was substantially lower (23.5 per 100,000). Endometriosis, regardless of its type, affects 30-39-year-olds in the highest number: 4397 women (694.96 per 100,000) in this age group were affected in 2019. The average annual health insurance expenditure per capita was EUR 189.45. In addition to early detection and diagnosis of endometriosis, it is of pivotal importance to provide adequate therapy to reduce costs and reduce the burden on the care system.

Antithrombin deficiency and its laboratory diagnosis.

Antithrombin (AT) belongs to the serpin family and is a key regulator of the coagulation system. AT inhibits active clotting factors, particularly thrombin and factor Xa; its absence is incompatible with life. This review gives an overview of the protein and gene structure of AT, and attempts to explain how glucosaminoglycans, such as heparin and heparan sulfate accelerate the inhibitory reaction that is accompanied by drastic conformational change. Hypotheses on the regulation of blood coagulation by AT in physiological conditions are discussed. Epidemiology of inherited thrombophilia caused by AT deficiency and its molecular genetic background with genotype-phenotype correlations are summarized. The importance of the classification of AT deficiencies and the phenotypic differences of various subtypes are emphasized. The causes of acquired AT deficiency are also included in the review. Particular attention is devoted to the laboratory diagnosis of AT deficiency. The assay principles of functional first line laboratory tests and tests required for classification are discussed critically, and test results expected in various AT deficiency subtypes are summarized. The reader is provided with a clinically oriented algorithm for the correct diagnosis and classification of AT deficiency, which could be useful in the practice of routine diagnosis of thrombophilia.

A new ELISA method for the measurement of total α2-plasmin inhibitor level in human body fluids.

The ever-increasing research efforts to develop new antithrombotic therapies have led to the reassessment of the role of alpha-2-plasmin inhibitor (α2-PI) in pathological conditions. In particular, experimental stroke studies have suggested correlation between increased free α2-PI level and mortality. However there are only a small number of well-characterized and specific assays available for the measurements of free α2-PI. In plasma α2-PI undergoes both N- and/or C-terminal cleavages resulting four isoforms with modified susceptibility to FXIII catalyzed cross-linking to fibrin and/or loss of plasmin(ogen) binding. Present paper describes a new sandwich ELISA method for the determination of free total α2-PI in plasma and other body fluids. A newly generated biotinylated monoclonal antibody recognizes and captures all the four N- and/or C-terminally modified isoforms of α2-PI while HRPO-labeled polyclonal anti-α2-PI antibody detects the captured antigen. Performing the 2-step assay in streptavidin-coated microplate can be completed within three hours. The assay is well reproducible, total (within laboratory) imprecision in the normal, pathological and very low ranges were 7.4%, 9.1% and < 19%, respectively. When examining the plasma samples of 197 healthy volunteers, 100 acute ischemic stroke patients and 102 patients with venous thrombosis, strong correlation was observed between total α2-PI antigen levels and α2-PI activity for each group. Using the assay a reference interval of 45-86 mg/L was established for total α2-PI mass concentration in the plasma. α2-PI levels were also measured in cerebrospinal fluid samples of 47 individuals the median value and range was 132 (36-379) µg/L. In conclusion, our ELISA enables accurate and fast measurement of total free α2-PI in human body fluids.

Factor XIII levels and factor XIII B subunit polymorphisms in patients with venous thromboembolism.

BACKGROUND: The association of plasma factor XIII (FXIII) level with venous thromboembolism (VTE) is still controversial and the effect of sex and FXIII B subunit (FXIII-B) polymorphisms in this respect have not been explored. OBJECTIVES: 1/ To determine FXIII activity and antigen levels in patients with a history of VTE and how they are influenced by sex and FXIII-B polymorphisms. 2/ To explore the association of FXIII levels and FXIII-B polymorphisms with the risk of VTE. METHODS: 218 VTE patients and equal number of age and sex matched controls were enrolled in the study. FXIII activity was measured by ammonia release assay; FXIII-A2B2 and FXIII-B levels were determined by ELISAs. FXIII-B polymorphisms were identified by RT-PCR using melting point analysis. RESULTS: Adjusted FXIII activity and FXIII-A2B2 antigen levels were significantly higher in females with a history of VTE than in the respective controls. FXIII-B levels were significantly lower in male VTE patients than in controls. FXIII-A2B2 antigen levels in the upper tertile increased the risk of VTE in females (adjusted OR: 2.52; CI: 1.18-5.38). Elevated FXIII-B antigen level had a protective effect only in males (adjusted OR: 0.19; CI: 0.08-0.46). FXIII-B Intron K c.1952+144 C>G polymorphism significantly lowered FXIII activity, FXIII-A2B2 and FXIII-B antigen levels in both groups. FXIII-B polymorphisms did not influence the risk of VTE. CONCLUSIONS: In VTE patients the changes of FXIII level and their effect on the risk of VTE show considerable sex-specific differences. Intron K polymorphism results in decreased FXIII levels, but does not influence the risk of VTE.

Regulation of plasma factor XIII levels in healthy individuals; a major impact by subunit B intron K c.1952+144 C>G polymorphism.

BACKGROUND: The regulation of plasma factor XIII (FXIII) levels in healthy individuals has been only partially explored. The identification of major non-genetic and genetic regulatory factors might provide important information on the contribution of FXIII to the risk of cardio/cerebrovascular diseases. OBJECTIVES: To determine the effect of age, smoking, BMI, fibrinogen concentration on plasma FXIII activity, complex FXIII antigen (FXIII-A2B2) and total FXIII-B subunit (tFXIII-B) level, to correlate FXIII-B level with the other two FXIII parameters and to assess the variation of FXIII levels in carriers of major FXIII subunit polymorphisms. METHODS: 268 healthy individuals were enrolled in the study. FXIII activity was measured by the ammonia release assay; FXIII-A2B2 and tFXIII-B were determined by ELISAs. FXIII-A p.Val34Leu, FXIII-B p.His95Arg and FXIII-B intron K c.1952+144 C>G polymorphisms were identified by RT-PCR using melting point analysis with fluorescence resonance energy transfer detection. RESULTS: All investigated FXIII parameters showed significant positive correlation with age and fibrinogen level; gender and BMI influenced only tFXIII-B. A highly significant positive correlation was demonstrated between tFXIII-B and the other FXIII parameters. FXIII-A p.Val34Leu polymorphism had only slight, if any effect on FXIII levels. The FXIII-B Arg95 allele moderately increased all three FXIII parameters, but the effect became statistically significant only after adjustment. The FXIII-B intron K G allele drastically decreased FXIII levels, and it seemed to be in synergism with the FXIII-A Leu34 allele. CONCLUSIONS: Plasma FXIII levels are subjected to multifactorial regulation, in which age, fibrinogen level and FXIII-B intron K polymorphism are major determinants.

The superiority of anti-FXa assay over anti-FIIa assay in detecting heparin-binding site antithrombin deficiency.

OBJECTIVES: Antithrombin is a progressive inhibitor of active factor X (FXa) and thrombin (FIIa). Its effect is 500- to 1,000-fold accelerated by heparin or heparan sulfate. Heterozygous type I (quantitative) and most type II (qualitative) antithrombin deficiencies highly increase the risk of venous thromboembolism (VTE), while homozygous mutations are lethal. The functional defect affecting the heparin-binding site confers moderate risk of VTE to heterozygous and high risk of VTE to homozygous individuals. METHODS: Antithrombin activity assays based on the inhibition of FIIa and FXa were compared for their efficiency in detecting heparin-binding site defects. RESULTS: With a single exception, in heterozygotes for heparin-binding site defects (n = 20), anti-FIIa activities remained in the reference interval, while anti-FXa activities were uniformly decreased. In individuals who were homozygous for heparin-binding site mutations (n = 9), anti-FIIa activities were in the range of 48% to 80%; the range of anti-FXa activities was 9% to 25%. Anti-FIIa and anti-FXa activities in type I deficiencies and type II pleiotropic deficiency did not differ significantly. CONCLUSIONS: Anti-FXa antithrombin assay is recommended as a first-line test to detect type II heparin-binding site antithrombin deficiency.