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1.
Geroscience ; 46(2): 2017-2031, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37798385

ABSTRACT

The demographic transition poses a significant challenge for health systems, especially in Central and Eastern European (CEE) countries, where the healthcare needs of aging populations are on the rise. This study aimed to describe and compare the health status and utilization of health services among the elderly residing in urban and rural areas of the most deprived region in Hungary. A comprehensive health survey was conducted in 2022, involving a randomly selected sample of 443 older adults (≥ 65 years) in Northeast Hungary. Multivariable logistic regression models adjusting for age, sex, education, financial status, chronic diseases, and activity limitations were used to investigate the association between type of residence and health service use. Among the study participants, 62.3% were female, 38.3% attained primary education, 12.5% reported a bad or very bad financial situation and 52.6% lived in urban areas. Overall, 24% of the elderly rated their health as very good or good (27.8% in urban and 19.7% in rural areas), while 57.8% (52.6% and 63.5% in urban and rural areas) reported limitations in daily activities. Compared to urban residents, rural residents reported lower rates of dentist visits (p = 0.006), specialist visits (p = 0.028), faecal occult blood testing (p < 0.001), colorectal cancer screening with colonoscopy (p = 0.014), and breast cancer screening (p = 0.035), and a higher rate of blood pressure measurement (p = 0.042). Multivariable models indicated that urban residence was positively associated with faecal occult blood testing (OR = 2.32, p = 0.014), but negatively associated with blood pressure (OR = 0.42, p = 0.017) and blood glucose measurements (OR = 0.48, p = 0.009). These findings highlight the influence of residence on health service utilization among older adults in Hungary. Further comprehensive studies are needed to better understand the health needs of the elderly population and to develop policies aimed at promoting healthy aging in CEE countries.


Subject(s)
Health Services , Patient Acceptance of Health Care , Humans , Female , Aged , Male , Urban Population , Hungary/epidemiology , Health Status
2.
PLoS Pathog ; 18(4): e1010402, 2022 04.
Article in English | MEDLINE | ID: mdl-35395059

ABSTRACT

Pulmonary infections caused by Bordetella pertussis used to be the prime cause of infant mortality in the pre-vaccine era and mouse models of pertussis pneumonia served in characterization of B. pertussis virulence mechanisms. However, the biologically most relevant catarrhal disease stage and B. pertussis transmission has not been adequately reproduced in adult mice due to limited proliferation of the human-adapted pathogen on murine nasopharyngeal mucosa. We used immunodeficient C57BL/6J MyD88 KO mice to achieve B. pertussis proliferation to human-like high counts of 108 viable bacteria per nasal cavity to elicit rhinosinusitis accompanied by robust shedding and transmission of B. pertussis bacteria to adult co-housed MyD88 KO mice. Experiments with a comprehensive set of B. pertussis mutants revealed that pertussis toxin, adenylate cyclase toxin-hemolysin, the T3SS effector BteA/BopC and several other known virulence factors were dispensable for nasal cavity infection and B. pertussis transmission in the immunocompromised MyD88 KO mice. In contrast, mutants lacking the filamentous hemagglutinin (FhaB) or fimbriae (Fim) adhesins infected the nasal cavity poorly, shed at low levels and failed to productively infect co-housed MyD88 KO or C57BL/6J mice. FhaB and fimbriae thus appear to play a critical role in B. pertussis transmission. The here-described novel murine model of B. pertussis-induced nasal catarrh opens the way to genetic dissection of host mechanisms involved in B. pertussis shedding and to validation of key bacterial transmission factors that ought to be targeted by future pertussis vaccines.


Subject(s)
Adhesins, Bacterial , Bordetella pertussis , Whooping Cough , Adenylate Cyclase Toxin , Adhesins, Bacterial/metabolism , Animals , Bordetella pertussis/genetics , Disease Models, Animal , Humans , Mice , Mice, Inbred C57BL , Myeloid Differentiation Factor 88 , Nasal Cavity/microbiology , Pertussis Vaccine , Virulence Factors, Bordetella/genetics , Whooping Cough/transmission
3.
J Pers Med ; 12(3)2022 Mar 03.
Article in English | MEDLINE | ID: mdl-35330387

ABSTRACT

Governments are increasingly looking to vaccination to provide a path out of the COVID-19 pandemic. Hungary offers an example to investigate whether social inequalities compromise what a successful vaccine program can achieve. COVID-19 morbidity, mortality, and vaccination coverage were characterized by calculation of indirectly standardized ratios in the Hungarian population during the third pandemic wave at the level of municipalities, classified into deprivation quintiles. Then, their association with socioeconomic deprivation was assessed using ecological regression. Compared to the national average, people living in the most deprived municipalities had a 15-24% lower relative incidence of confirmed COVID-19 cases, but a 17-37% higher relative mortality and a 38% lower vaccination coverage. At an ecological level, COVID-19 mortality showed a strong positive association with deprivation and an inverse association with vaccination coverage (RRVaccination = 0.86 (0.75-0.98)), but the latter became non-significant after adjustment for deprivation (RRVaccination = 0.95 (0.84-1.09), RRDeprivation = 1.10 (1.07-1.14)). Even what is widely viewed as one of the more successful vaccine roll outs was unable to close the gap in COVID-19 mortality during the third pandemic wave in Hungary. This is likely to be due to the challenges of reaching those living in the most deprived municipalities who experienced the highest mortality rates during the third wave.

4.
Int J Mol Sci ; 22(21)2021 Oct 28.
Article in English | MEDLINE | ID: mdl-34769101

ABSTRACT

The whooping cough agent, Bordetella pertussis, secretes an adenylate cyclase toxin-hemolysin (CyaA, ACT, or AC-Hly) that catalyzes the conversion of intracellular ATP to cAMP and through its signaling annihilates the bactericidal activities of host sentinel phagocytes. In parallel, CyaA permeabilizes host cells by the formation of cation-selective membrane pores that account for the hemolytic activity of CyaA. The pore-forming activity contributes to the overall cytotoxic effect of CyaA in vitro, and it has previously been proposed to synergize with the cAMP-elevating activity in conferring full virulence on B. pertussis in the mouse model of pneumonic infection. CyaA primarily targets myeloid phagocytes through binding of their complement receptor 3 (CR3, integrin αMß2, or CD11b/CD18). However, with a reduced efficacy, the toxin can promiscuously penetrate and permeabilize the cell membrane of a variety of non-myeloid cells that lack CR3 on the cell surface, including airway epithelial cells or erythrocytes, and detectably intoxicates them by cAMP. Here, we used CyaA variants with strongly and selectively enhanced or reduced pore-forming activity that, at the same time, exhibited a full capacity to elevate cAMP concentrations in both CR3-expressing and CR3-non-expressing target cells. Using B. pertussis mutants secreting such CyaA variants, we show that a selective enhancement of the cell-permeabilizing activity of CyaA does not increase the overall virulence and lethality of pneumonic B. pertussis infection of mice any further. In turn, a reduction of the cell-permeabilizing activity of CyaA did not reduce B. pertussis virulence any importantly. These results suggest that the phagocyte-paralyzing cAMP-elevating capacity of CyaA prevails over the cell-permeabilizing activity of CyaA that appears to play an auxiliary role in the biological activity of the CyaA toxin in the course of B. pertussis infections in vivo.


Subject(s)
Adenylate Cyclase Toxin/metabolism , Bordetella pertussis/pathogenicity , Whooping Cough/metabolism , Animals , Bordetella pertussis/physiology , Cell Membrane Permeability , Cyclic AMP/metabolism , Female , Host-Pathogen Interactions , Humans , Mice , Mice, Inbred BALB C , Phagocytes/metabolism , Phagocytes/microbiology , Sheep , Virulence , Whooping Cough/microbiology , Whooping Cough/pathology
5.
Psychiatr Hung ; 36(3): 417-424, 2021.
Article in Hungarian | MEDLINE | ID: mdl-34738533

ABSTRACT

David Lynch with his work 'Eraserhead' dove deep into the existential regions of the human psyche and brought back the product which he states to be 'his most spiritual film'. Three main factors (the psychobiography, the theories of psychoanalysis and the works of Lipot Szondi) helped me establish the theoretical fundament for the exploration of the trauma-induced state of coercion through the symbolism of the film. The established interrelations will give us a new perspective on Lynch's works and biography, and may give us a chance to take a closer look at the dynamics of the state coercion.


Subject(s)
Coercion , Psychoanalysis , History, 20th Century , Humans , Male , Psychoanalysis/history , Psychotherapy
6.
BMJ Glob Health ; 6(9)2021 09.
Article in English | MEDLINE | ID: mdl-34518205

ABSTRACT

INTRODUCTION: We describe COVID-19 morbidity, mortality, case fatality and excess death in a country-wide study of municipalities in Hungary, exploring the association with socioeconomic status. METHODS: The spatial distribution of morbidity, mortality and case fatality was mapped using hierarchical Bayesian smoothed indirectly standardised ratios. Indirectly standardised ratios were used to evaluate the association between deprivation and the outcome measures. We looked separately at morbidity and mortality in the 10 districts with the highest and 10 districts with the lowest share of Roma population. RESULTS: Compared with the national average, the relative incidence of cases was 30%-36% lower in the most deprived quintile but the relative mortality and case fatality were 27%-32% higher. Expressed as incidence ratios relative to the national average, the most deprived municipalities had a relative incidence ratio of 0.64 (CI: 0.62 to 0.65) and 0.70 (CI: 0.69 to 0.72) for males and females, respectively. The corresponding figures for mortality were 1.32 (CI: 1.20 to 1.44) for males and 1.27 (CI: 1.16 to 1.39) for females and for case fatality 1.27 (CI: 1.16 to 1.39) and 1.32 (CI: 1.20 to 1.44) for males and females, respectively. The excess death rate (per 100 000) increased with deprivation levels (least deprived: 114.12 (CI: 108.60 to 119.84) and most deprived: 158.07 (CI: 149.30 to 167.23)). The 10 districts where Roma formed the greatest share of the population had an excess mortality rate 17.46% higher than the average for the most deprived quintile. CONCLUSIONS: Those living in more deprived municipalities had a lower risk of being identified as a confirmed COVID-19 case but had a higher risk of death. An inverse association between trends in morbidity and mortality by socioeconomic conditions should be a cause for concern and points to the need for responses, including those involving vaccination, to pay particular attention to inequalities and their causes.


Subject(s)
COVID-19 , Bayes Theorem , Female , Humans , Hungary/epidemiology , Male , Pandemics , Risk Factors , SARS-CoV-2 , Socioeconomic Factors
7.
Article in English | MEDLINE | ID: mdl-33668088

ABSTRACT

This study was designed to characterize the spatial distribution of metformin medication used as first-line monotherapy for prevention of T2DM in relationship with the socioeconomic status (level of deprivation) and T2DM mortality at district level in a nationwide cross-sectional ecological study for the first time in a European country, Hungary. Risk analysis was used to estimate the relationships between socioeconomic status, characterized by tertiles of deprivation index, and mortality caused by diabetes, and metformin medication (both prescription and redemption) for the years of 2018 and 2019 at the district level. The spatial distribution of districts with a higher relative frequency of metformin prescriptions and redemptions showed a positive correlation with socio-economic deprivation. Significant association between the relatively high T2DM mortality and the highest level of deprivation could also be detected, but less-deprived regions with high T2DM mortality and low metformin utilization could also be identified. Although the statistical associations detected in this ecological study do not indicate a causal relationship, it is reasonable to suppose that the underuse of metformin medication may contribute to the unfavourable T2DM mortality in certain regions. Our findings underline the need for more effective preventive services including metformin medication to decrease T2DM morbidity and mortality burden.


Subject(s)
Diabetes Mellitus, Type 2 , Metformin , Cross-Sectional Studies , Europe , Humans , Hungary , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Social Class
8.
Article in English | MEDLINE | ID: mdl-33504113

ABSTRACT

The aim of this study was to investigate how amenable mortality and related ambulance services differ on a county level in Hungary. The differences in mortality rates and ambulance services could identify counties where stronger ambulance services are needed. The datasets for 2018 consisted of county level aggregated data of citizens between the ages 15-64. The study examined how both the mortality rates and the ambulance rescue deliveries differ from the national average. The analyses were narrowed down to disease groups, such as acute myocardial infarction, hemorrhagic and ischemic stroke. Inequalities were identified regarding the distribution of number of ambulance deliveries, several counties had rates more than double that of the national average. For both mortality and ambulance services some of the counties had significantly better results and others had significantly worse compared to the national average. In Borsod-Abaúj-Zemplén county's case, hemorrhagic stroke mortality was significantly higher (1.73 [1.35-2.11]), while ambulance deliveries were significantly lower (0.58 [0.40-0.76]) compared to the national average. The research has shown that regarding the investigated mortality rates and ambulance services there are considerable differences between the counties in Hungary. In this regard policy makers should implement policies to tackle these discrepancies.


Subject(s)
Myocardial Infarction , Stroke , Adolescent , Adult , Ambulances , Humans , Hungary/epidemiology , Middle Aged , Young Adult
10.
Article in English | MEDLINE | ID: mdl-32961765

ABSTRACT

This work was designed to investigate antithrombotic drug utilization and its link with the socioeconomic characteristics of specific population groups in Hungary by a comparative analysis of data for prescriptions by general practitioners and the redeemed prescriptions for antithrombotic drugs. Risk analysis capabilities were applied to estimate the relationships between socioeconomic status, which was characterized by quintiles of a multidimensional composite indicator (deprivation index), and mortality due to thromboembolic diseases as well as antithrombotic medications for the year 2016 at the district level in Hungary. According to our findings, although deprivation is a significant determinant of mortality due to thromboembolic diseases, clusters can be identified that represent exemptions to this rule: an eastern part of Hungary, consisting of two highly deprived counties, had significantly lower mortality than the country average; by contrast, the least-deprived northwestern part of the country, consisting of five counties, had significantly higher mortality than the country average. The fact that low socioeconomic status in general and poor adherence to antithrombotic drugs irrespective of socioeconomic status were associated with increased mortality indicates the importance of more efficient control of preventive medication and access to healthcare in all districts of the country to reduce mortality due to thromboembolic diseases.


Subject(s)
Drug Prescriptions , Fibrinolytic Agents , Socioeconomic Factors , Cross-Sectional Studies , Humans , Hungary , Practice Patterns, Physicians' , Social Class
11.
Sci Rep ; 10(1): 10761, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32612167

ABSTRACT

The Hungarian Pediatric Oncology Network provides centralized treatment and population-based registration for cases of childhood cancer since 1973. We collected and analized data on late mortality, secondary malignancies and cardiac diseases in survivors (> 5 years) of childhood cancer to evaluate long-term risks. We extracted all solid tumour cases (3,650 followed up for 5-39.3 years, diagnosis: 1973-2008) from the database of the Hungarian Childhood Cancer Registry and checked against the Population Registry. Among the 301 patients who died after 5 years (8.2%) the most common causes of death were progression of primary cancer (52.5%), secondary malignancies (16%) and cardiovascular diseases (8%). Late mortality rates (SMR, total: 35,006 pyrs) showed highly elevated risk of death (SMR: 10.7 95% CI 9-12.4) for the second 5 years of follow up and moderately elevated risk for 10-year survivors (SMR: 3.5 95% CI 3-4.1). Marked differences were detected in the pattern of causes of death between diagnostic groups of primary cancer; with highest risks beyond 10 years for CNS tumours, Hodgkin disease, osteosarcoma and advanced stage neuroblastoma. The longstanding mortality risk for 5-year survivors underlines the need for tailored long-term follow-up and monitoring of late consequences according to the context of different primary diseases of childhood cancer.


Subject(s)
Cancer Survivors , Hodgkin Disease/mortality , Neoplasms/mortality , Neuroblastoma/mortality , Osteosarcoma/mortality , Adolescent , Adult , Cause of Death , Child , Child, Preschool , Disease Progression , Female , Hodgkin Disease/diagnosis , Humans , Hungary/epidemiology , Infant , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasms/diagnosis , Neoplasms, Second Primary , Neuroblastoma/diagnosis , Osteosarcoma/diagnosis , Registries , Risk , Treatment Outcome , Young Adult
12.
Viruses ; 12(7)2020 06 30.
Article in English | MEDLINE | ID: mdl-32629880

ABSTRACT

COVID-19 epidemic has been suppressed in Hungary due to timely non-pharmaceutical interventions, prompting a considerable reduction in the number of contacts and transmission of the virus. This strategy was effective in preventing epidemic growth and reducing the incidence of COVID-19 to low levels. In this report, we present the first epidemiological and statistical analysis of the early phase of the COVID-19 outbreak in Hungary. Then, we establish an age-structured compartmental model to explore alternative post-lockdown scenarios. We incorporate various factors, such as age-specific measures, seasonal effects, and spatial heterogeneity to project the possible peak size and disease burden of a COVID-19 epidemic wave after the current measures are relaxed.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Disease Outbreaks , Pneumonia, Viral/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19 , Child , Child, Preschool , Coronavirus Infections/mortality , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Disease Outbreaks/prevention & control , Female , Humans , Hungary/epidemiology , Infant , Infant, Newborn , Male , Middle Aged , Models, Statistical , Pandemics/prevention & control , Pneumonia, Viral/mortality , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Quarantine , Risk Factors , SARS-CoV-2 , Sex Factors , Young Adult
13.
BMJ Open ; 9(7): e024957, 2019 07 23.
Article in English | MEDLINE | ID: mdl-31340955

ABSTRACT

OBJECTIVE: The study was designed to explore the development of the general practitioner (GP) shortage in primary care and its characteristics in Hungary. DESIGN: Longitudinal follow-up study over the decade 2007-2016. METHODS: Analyses were performed on changes in number, age and sex of GPs by practice type (adult, paediatric and mixed), as well as on their geographical distribution and migration between areas characterised by deprivation index (DI) at municipality level. The association between deprivation and vacancy for GPs was studied by risk analysis. The number of population underserved was defined by DI quintile. SETTING AND SUBJECTS: The study involved all general practices and GPs in the period examined. MAIN OUTCOME MEASURE: It is showed that the number of general practices with unfilled GP posts was increasing exponentially, mainly in the most deprived areas of the country. RESULTS: A decrease in the number of GPs in all types of practices, especially in mixed (by 7.7%; p<0.001) and paediatric (by 6.5%; p<0.001) ones, was shown; the number of adult practices with unfilled GP posts doubled, while the number of paediatric practices with a vacancy for a paediatrician more than tripled. The average age of GPs was increased by 3.7 years (p<0.001) in adult, by 5.4 years (p<0.001) in paediatric and by 4.2 years (p<0.001) in mixed practices. In 2007, 52.27% (95% CI 51.03 to 53.5) of the GPs were women, and this rate increased to 56.19% (95% CI 54.93 to 57.44) by the end of the decade. An exponential association between relative vacancy rate and deprivation was confirmed. As a result of the migration of GPs, in the most deprived areas, the number of GPs decreased by 8.43% (95% CI 5.86 to 10.99). CONCLUSIONS: The workforce crisis in Hungarian primary care is progressively deepening and resulting in more severe inequity in access to healthcare.


Subject(s)
General Practitioners/supply & distribution , Health Workforce/trends , Pediatricians/supply & distribution , Primary Health Care/statistics & numerical data , Adult , Age Distribution , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Hungary , Longitudinal Studies , Male , Middle Aged , Sex Distribution
14.
Sci Rep ; 9(1): 6342, 2019 04 19.
Article in English | MEDLINE | ID: mdl-31004084

ABSTRACT

Rhabdomyosarcomas (RMS) are a heterogeneous group of mesodermal tumors, the most common sub-types are embryonal (eRMS) and alveolar (aRMS) rhabdomyosarcoma. Immunohistochemical analysis revealed c-Myb expression in both eRMS and aRMS. c-Myb has been reported to be often associated with malignant human cancers. We therefore investigated the c-Myb role in RMS using cellular models of RMS. Specific suppression of c-Myb by a lentiviral vector expressing doxycycline (Dox)-inducible c-Myb shRNA inhibited proliferation, colony formation, and migration of the eRMS cell line (RD), but not of the aRMS cell line (RH30). Upon c-Myb knockdown in eRMS cells, cells accumulated in G0/G1 phase, the invasive behaviour of cells was repressed, and elevated levels of myosin heavy chain, marker of muscle differentiation, was detected. Next, we used an RD-based xenograft model to investigate the role of c-Myb in eRMS tumorigenesis in vivo. We found that Dox administration did not result in efficient suppression of c-Myb in growing tumors. However, when c-Myb-deficient RD cells were implanted into SCID mice, we observed inefficient tumor grafting and attenuation of tumor growth during the initial stages of tumor expansion. The presented study suggests that c-Myb could be a therapeutic target in embryonal rhabdomyosarcoma assuming that its expression is ablated.


Subject(s)
Carcinogenesis/metabolism , G1 Phase , Gene Expression Regulation, Neoplastic , Proto-Oncogene Proteins c-myb/metabolism , Resting Phase, Cell Cycle , Rhabdomyosarcoma, Embryonal/metabolism , Animals , Carcinogenesis/genetics , Carcinogenesis/pathology , Cell Line, Tumor , Gene Knockdown Techniques , Mice , Proto-Oncogene Proteins c-myb/genetics , Rhabdomyosarcoma, Embryonal/genetics , Rhabdomyosarcoma, Embryonal/pathology
15.
J Clin Hypertens (Greenwich) ; 20(10): 1473-1484, 2018 10.
Article in English | MEDLINE | ID: mdl-30302936

ABSTRACT

Patients with grade 2-3 essential hypertension and postplacebo mean clinic systolic blood pressure (SBP) 160-190 mm Hg and 24-hour SBP 140-175 mm Hg by ambulatory blood pressure monitoring (ABPM) received 40 mg azilsartan medoxomil (AZL-M) monotherapy for 4 weeks. "Nonresponders" were then randomized to 8 weeks of double-blind treatment with AZL-M 40 mg, AZL-M/chlortalidone (CLD) 40/25, or AZL-M/CLD 40/12.5 mg. After 8 weeks, mean clinic SBP change was -21.1 (±1.04) mm Hg for AZL-M/CLD 40/25 mg, -15.8 (±1.08) mm Hg for AZL-M/CLD 40/12.5 mg, and -6.4 (±1.05) mm Hg for AZL-M 40 mg (P < 0.001 for both AZL-M/CLD vs AZL-M, ANCOVA). Drug discontinuation rates were 8.9% (AZL-M/CLD 40/25 mg), 7.5% (AZL-M 40 mg), and 3.9% (AZL-M/CLD 40/12.5 mg). Creatinine increased in 8.1% (AZL-M/CLD 40/25), 3.1% (AZL-M/CLD 40/12.5 mg), and 3.0% (AZL-M 40 mg) of patients. AZL-M/CLD was effective and well tolerated in patients not achieving blood pressure targets with AZL-M.


Subject(s)
Benzimidazoles/therapeutic use , Chlorthalidone/therapeutic use , Drug Therapy, Combination/methods , Essential Hypertension/drug therapy , Oxadiazoles/therapeutic use , Aged , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , Blood Pressure/drug effects , Blood Pressure/physiology , Blood Pressure Monitoring, Ambulatory/methods , Chlorthalidone/administration & dosage , Chlorthalidone/adverse effects , Essential Hypertension/classification , Essential Hypertension/epidemiology , Essential Hypertension/ethnology , Female , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Oxadiazoles/administration & dosage , Oxadiazoles/adverse effects , Sodium Chloride Symporter Inhibitors/therapeutic use , Systole
16.
J Renin Angiotensin Aldosterone Syst ; 19(3): 1470320318795000, 2018.
Article in English | MEDLINE | ID: mdl-30175930

ABSTRACT

INTRODUCTION: We measured the effects of azilsartan medoxomil co-administered with chlorthalidone 25 mg in stage 2 hypertension. METHODS: Azilsartan medoxomil 40 or 80 mg plus chlorthalidone were compared with placebo plus chlorthalidone once daily in a randomized, double-blind, 6-week trial. The primary endpoint was change from baseline in 24-hour mean systolic blood pressure by ambulatory blood pressure monitoring. RESULTS: Patients ( N=551; mean age 59 years; 51.7% men) were randomly assigned to placebo plus chlorthalidone ( n=184), azilsartan medoxomil 40 mg plus chlorthalidone ( n=185), or azilsartan medoxomil 80 mg plus chlorthalidone ( n=182). Baseline systolic blood pressures were similar among groups. After 6 weeks, least squares mean (standard error) reductions with azilsartan medoxomil 40 mg and 80 mg plus chlorthalidone were similar in magnitude (-31.7 (1.0) and -31.3 (1.0) mmHg, respectively), but greater than chlorthalidone alone (-15.9 (1.0) mmHg). Hypotension and serum creatinine elevations were more frequent with azilsartan medoxomil plus chlorthalidone than chlorthalidone alone (reversed with drug discontinuation). Notably, plasma potassium reduction of 0.43 meq/L with chlorthalidone was attenuated to 0.13 and 0.05 meq/L by azilsartan medoxomil 40 mg and 80 mg, respectively. CONCLUSION: Azilsartan medoxomil 40 mg or 80 mg plus chlorthalidone 25 mg was significantly more efficacious than chlorthalidone alone in reducing blood pressure and was well tolerated. Clinicaltrial.gov , https://clinicaltrials.gov/ct2/show/NCT00591773 , NCT00591773.


Subject(s)
Benzimidazoles/adverse effects , Benzimidazoles/therapeutic use , Chlorthalidone/adverse effects , Chlorthalidone/therapeutic use , Oxadiazoles/adverse effects , Oxadiazoles/therapeutic use , Blood Pressure/drug effects , Blood Pressure Monitoring, Ambulatory , Diastole/drug effects , Drug Therapy, Combination , Female , Humans , Hypertension/drug therapy , Hypertension/physiopathology , Male , Middle Aged , Systole/drug effects , Treatment Outcome
17.
Front Pharmacol ; 9: 839, 2018.
Article in English | MEDLINE | ID: mdl-30123128

ABSTRACT

The wide life expectancy gap between the old and new member states of the European Union is most strongly related to the high rate of premature mortality caused by cardiovascular diseases (CVDs). To learn more about the background of this gap, the relationship of socioeconomic status (SES) with CVD mortality, morbidity and the utilization of antihypertensive drugs was studied in Hungary, a Central-Eastern European country with an extremely high relative risk of premature CVD mortality. Risk analysis capabilities were used to estimate the relationships between SES, which was characterized by tertiles of a multidimensional composite indicator (the deprivation index) and CVD burden (mortality and morbidity) as well as the antihypertensive medications at the district level in Hungary. The excess risks caused by premature mortality from CVDs showed a strong correlation with deprivation using the Rapid Inquiry Facility. The distribution of prevalence values related to these diseases was found to be similar, but in the areas of highest deprivation, where the prevalence of chronic ischaemic heart diseases and cerebrovascular diseases was found to be higher than the national average by 30 and 20%, the prevalence of hypertension exceeded the national average by only 4%. A linear association between the relative frequency of prescriptions/redemptions and deprivation for most antihypertensive drugs, except angiotensinogen receptor blockers, was shown. More intense screening for hypertension is proposed to improve the control of CVDs in countries affected by high disease burden.

18.
J Clin Hypertens (Greenwich) ; 20(4): 694-702, 2018 04.
Article in English | MEDLINE | ID: mdl-29504252

ABSTRACT

An open-label, long-term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in hypertensive participants with stage 3 chronic kidney disease. Initial therapy was AZL-M/CLD 20/12.5 mg (n = 77) or OLM/HCTZ 20/12.5 mg (n = 76), but could be up-titrated (AZL-M/CLD to 40/25 mg; OLM/HCTZ to 40/25 mg [US] or 20/25 mg [Europe]) with other agents added during weeks 4-52. Primary endpoint was proportion of participants with ≥ 1 adverse event (AE) through week 52. Baseline demographics were similar. AEs did not differ between groups (88.3%, AZL-M/CLD vs 76.3%, OLM/HCTZ; P = .058). AZL-M/CLD showed greater systolic BP reductions after initial dosing (P = .037) but not during long-term follow-up (P = .588). A greater proportion of participants up-titrated to the highest dose with OLM/HCTZ (48.7%) vs AZL-M/CLD (29.9%) (P = .021) and were taking additional antihypertensive medications (26.3% vs 16.9%). Both AZL-M/CLD and OLM/HCTZ showed similar efficacy and tolerability.


Subject(s)
Benzimidazoles/administration & dosage , Chlorthalidone/administration & dosage , Hydrochlorothiazide/administration & dosage , Hypertension/drug therapy , Olmesartan Medoxomil/administration & dosage , Oxadiazoles/administration & dosage , Renal Insufficiency, Chronic/complications , Aged , Benzimidazoles/adverse effects , Chlorthalidone/adverse effects , Drug Therapy, Combination/adverse effects , Female , Humans , Hydrochlorothiazide/adverse effects , Male , Middle Aged , Olmesartan Medoxomil/adverse effects , Oxadiazoles/adverse effects , Treatment Outcome
19.
Clin Hypertens ; 24: 2, 2018.
Article in English | MEDLINE | ID: mdl-29445520

ABSTRACT

BACKGROUND: This was a phase 3, randomized, double-blind, placebo-controlled study. METHODS: Adult Korean patients with essential hypertension and a baseline mean sitting clinic systolic blood pressure (scSBP) ≥150 and ≤180 mmHg were randomized to 6-week treatment with placebo (n = 65), azilsartan medoxomil (AZL-M) 40 mg (n = 132), or AZL-M 80 mg (n = 131). The primary endpoint was the change from baseline to week 6 in trough scSBP. RESULTS: The least-squares mean (standard error) change from baseline in trough scSBP in the placebo, AZL-M 40-mg, and 80-mg groups at week 6 were - 8.8 (2.00), - 22.1 (1.41), and - 23.7 (1.40) mmHg, respectively (p < 0.001 for AZL-M 40 and 80 mg vs placebo). No clinically meaningful heterogeneity in efficacy was observed between subgroups (age, sex, diabetes status) and the overall population. Treatments were well tolerated and adverse events were similar between groups. CONCLUSIONS: Results of this study confirm a positive benefit-risk profile of AZL-M for essential hypertension in Korean adults. TRIAL REGISTRATION: Clinicaltrial.gov; identifier number: NCT02203916. Registered July 28, 2014 (retrospectively registered).

20.
BMJ Open ; 7(7): e015527, 2017 Jul 28.
Article in English | MEDLINE | ID: mdl-28756383

ABSTRACT

OBJECTIVE: To examine the UK practice patterns in treating newly diagnosed hypertension and to determine whether subgroups of high-risk patients are more or less likely to follow particular therapeutic protocols and to reach blood pressure goals. DESIGN: Retrospective cohort study. SETTING: This study examined adults in The Health Improvement Network (THIN) UK general practice medical records database who were initiated on medication for hypertension. PARTICIPANTS: 48 131 patients with essential hypertension diagnosed between 2008 and 2010 who were registered with a participating practice for a minimum of 13 months prior to, and 6 months following, initiation of therapy. We excluded patients with gestational hypertension or secondary hypertension. Patients were classified into risk groups based on blood pressure readings and comorbid conditions. PRIMARY AND SECONDARY OUTCOME MEASURES: Odds of receiving single versus fixed or free-drug combination therapy and odds of achieving blood pressure control were assessed using multivariable logistic regression. RESULTS: The vast majority of patients (95.8%) were initiated on single drug therapy. Patients with high cardiovascular risk (patients with grade 2-3 hypertension or those with high normal/grade 1 hypertension plus at least one cardiovascular condition pretreatment) had a statistically significant benefit of starting immediately on combination therapy when blood pressure control was the desired goal (OR: 1.23; 95% CI: 1.06 to 1.42) but, surprisingly, were less likely than patients with no risk factors to receive combination therapy (OR: 0.53; 95% CI: 0.47 to 0.59). CONCLUSIONS: Our results suggest that combination therapy may be indicated for patients with high cardiovascular risk, who accounted for 60.6% of our study population. The National Institute for Health and Care Excellence guideline CG34 of 2006 (in effect during the study period) recommended starting with single drug class therapy for most patients, and this advice does seem to have been followed even in cases where a more aggressive approach might have been considered.


Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , General Practice , Hypertension/prevention & control , Adult , Aged , Comorbidity , Databases, Factual , Female , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Male , Medication Adherence , Middle Aged , Practice Guidelines as Topic , Retrospective Studies , Risk Factors , United Kingdom/epidemiology
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