Changes in the prevalence, treatment and control of hypertension in Germany? : a clinical-epidemiological study of 50.000 primary care patients

INTRODUCTION: Medical societies have developed guidelines for the detection, treatment and control of hypertension (HTN). Our analysis assessed the extent to which such guidelines were implemented in Germany in 2003 and 2001. METHODS: Using standardized clinical diagnostic and treatment appraisal forms, blood pressure levels and patient questionnaires for 55,518 participants from the cross-sectional Targets and Essential Data for Commitment of Treatment (DETECT) study (2003) were analyzed. Physician's diagnosis of hypertension (HTN(doc)) was defined as coding hypertension in the clinical appraisal questionnaire. Alternative definitions used were physician's diagnosis or the patient's self-reported diagnosis of hypertension (HTN(doc,pat)), physician's or patient's self-reported diagnosis or a BP measurement with a systolic BP≥140 mmHg and/or a diastolic BP≥90 (HTN(doc,pat,bp)) and diagnosis according to the National Health and Nutrition Examination Survey (HTN(NHANES)). The results were compared with the similar German HYDRA study to examine whether changes had occurred in diagnosis, treatment and adequate blood pressure control (BP below 140/90 mmHg) since 2001. Factors associated with pharmacotherapy and control were determined. RESULTS: The overall prevalence rate for hypertension was 35.5% according to HTN(doc) and 56.0% according to NHANES criteria. Among those defined by NHANES criteria, treatment and control rates were 56.0% and 20.3% in 2003, and these rates had improved from 55.3% and 18.0% in 2001. Significant predictors of receiving antihypertensive medication were: increasing age, female sex, obesity, previous myocardial infarction and the prevalence of comorbid conditions such as coronary heart disease (CHD), hyperlipidemia and diabetes mellitus (DM). Significant positive predictors of adequate blood pressure control were CHD and antihypertensive medication. Inadequate control was associated with increasing age, male sex and obesity. CONCLUSIONS: Rates of treated and controlled hypertension according to NHANES criteria in DETECT remained low between 2001 and 2003, although there was some minor improvement

Insights into the Electronic Structure of a U(IV) Amido and U(V) Imido Complex

Reaction of the N-heterocylic carbene ligand $^{i}$PrIm (L$^{1}$) and lithium bis(trimethylsilyl)amide (TMSA) as a base with UCl$_{4}$ resulted in U(IV) and U(V) complexes. Uranium\u27s +V oxidation state in (HL$^{1}$)$_{2}$[U(V)(TMSI)Cl$_{5}$] (TMSI=trimethylsilylimido) (2) was confirmed by HERFD-XANES measurements. Solid state characterization by SC-XRD and geometry optimisation of [U(IV)(L$^{1}$)$_{2}$(TMSA)Cl$_{3}$] (1) indicated a silylamido ligand mediated inverse trans influence (ITI). The ITI was examined regarding different metal oxidation states and was compared to transition metal analogues by theoretical calculations

Cardiovascular risk prediction - a systems medicine approach

Background Guidelines for the prevention of cardiovascular disease (CVD) have recommended the assessment of the total CVD risk by risk scores. Current risk algorithms are low in sensitivity and specificity and they have not incorporated emerging risk markers for CVD. We suggest that CVD risk assessment can be still improved. We have developed a long-term risk prediction model of cardiovascular mortality in patients with stable coronary artery disease (CAD) based on newly available machine learning and on an extended dataset of new biomarkers.Methods 2953 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study were included. 184 laboratory and 21 demographic markers were ranked according to their contribution to risk of cardiovascular (CV) mortality using different data mining approaches. A self-learning bioinformatics workflow, including seven different machine learning algorithms, was developed for CV risk prediction. The study population was stratified into patients with and without significant CAD. Thereby, significant CAD was defined as a lumen narrowing of 50 or more in at least one of the coronary segments or a history of definite myocardial infarction. The machine learning models in both subpopulations were compared with established CV risk assessment tools.Results After a follow-up of 10 years, 603 (20.4%) patients died of cardiovascular causes. 95% patients without CAD deceased within ten years and 247 (13.2 %) patients with CAD within 5 years. Overall and in patients without CAD, NT-proBNP (N-terminal pro B-type natriuretic peptide), TnT (Troponin T), estimated cystatin c based GFR (glomerular filtration rate) and age were the highest ranked predictors, while in patients with CAD, NT-proBNP, GFR, CT-proAVP (C-terminal pro arginine vasopressin) and TNT were highest predictive. In the comparison with the FRS, PROCAM and ESC risk scores, the machine learning workflow produced more accurate and robust CV mortality prediction in patients without CAD. Equivalent CV risk prediction was obtained in the CAD subpopulation in comparison with the Marschner risk score. Overall, the existing algorithms in general tend to assign more patients into the medium risk groups, while the machine learning algorithms tend to have a clearer risk/no risk assignment. The framework is available upon request.Conclusion We have developed a fully automated and self-validating computational framework of machine learning techniques using an extensive database of clinical, routinely and non-routinely measured laboratory data. Our framework predicts long-term CV mortality at least as accurate as existing CVD risk scores. A combination of four highly ranked biomarkers and the random forest approach showed the best predictive results. Moreover, a dynamic computational model has several advantages over static CVD risk prediction tools: it is freeware, transparent, variable, transferable and expandable to any population, types of events and time frames

GWAS META-analysis followed by MENDELIAN randomisation revealed potential control mechanisms for circulating α-klotho levels

The protein α-Klotho acts as transmembrane co-receptor for fibroblast growth factor 23 (FGF23) and is a key regulator of phosphate homeostasis. However, α-Klotho also exists in a circulating form, with pleiotropic, but incompletely understood functions and regulation. Therefore, we undertook a genome-wide association study (GWAS) meta-analysis followed by Mendelian randomization (MR) of circulating α-Klotho levels. Plasma α-Klotho levels were measured by enzyme-linked immunosorbent assay (ELISA) in the Ludwigshafen Risk and Cardiovascular Health and Avon Longitudinal Study of Parents and Children (mothers) cohorts, followed by a GWAS meta-analysis in 4376 individuals across the two cohorts. Six signals at five loci were associated with circulating α-Klotho levels at genome-wide significance (P 9% of the variation in circulating α-Klotho levels. MR analyses revealed no causal relationships between α-Klotho and renal function, FGF23-dependent factors such as vitamin D and phosphate levels, or bone mineral density. The screening for genetic correlations with other phenotypes followed by targeted MR suggested causal effects of liability of Crohn’s disease risk [Inverse variance weighted (IVW) beta = 0.059 (95% confidence interval 0.026, 0.093)] and low-density lipoprotein cholesterol levels [−0.198 (−0.332, −0.063)] on α-Klotho. Our GWAS findings suggest that two enzymes involved in post-translational modification, B4GALNT3 and CHST9, contribute to genetic influences on α-Klotho levels, presumably by affecting protein turnover and stability. Subsequent evidence from MR analyses on α-Klotho levels suggest regulation by mechanisms besides phosphate-homeostasis and raise the possibility of cross-talk with FGF19- and FGF21-dependent pathways, respectively. Significance statement: α-Klotho as a transmembrane protein is well investigated along the endocrine FGF23-α-Klotho pathway. However, the role of the circulating form of α-Klotho, which is generated by cleavage of transmembrane α-Klotho, remains incompletely understood. Genetic analyses might help to elucidate novel regulatory and functional mechanisms. The identification of genetic factors related to circulating α-Klotho further enables MR to examine causal relationships with other factors. The findings from the first GWAS meta-analysis of circulating α-Klotho levels identified six genome-wide significant signals across five genes. Given the function of two of the genes identified, B4GALNT3 and CHST9, it is tempting to speculate that post-translational modification significantly contributes to genetic influences on α-Klotho levels, presumably by affecting protein turnover and stability

Benthic silicon cycling in the Arctic Barents Sea: a reaction–transport model study

Over recent decades the highest rates of water column warming and sea ice loss across the Arctic Ocean have been observed in the Barents Sea. These physical changes have resulted in rapid ecosystem adjustments, manifesting as a northward migration of temperate phytoplankton species at the expense of silica-based diatoms. These changes will potentially alter the composition of phytodetritus deposited at the seafloor, which acts as a biogeochemical reactor and is pivotal in the recycling of key nutrients, such as silicon (Si). To appreciate the sensitivity of the Barents Sea benthic system to the observed changes in surface primary production, there is a need to better understand this benthic–pelagic coupling. Stable Si isotopic compositions of sediment pore waters and the solid phase from three stations in the Barents Sea reveal a coupling of the iron (Fe) and Si cycles, the contemporaneous dissolution of lithogenic silicate minerals (LSi) alongside biogenic silica (BSi), and the potential for the reprecipitation of dissolved silicic acid (DSi) as authigenic clay minerals (AuSi). However, as reaction rates cannot be quantified from observational data alone, a mechanistic understanding of which factors control these processes is missing. Here, we employ reaction–transport modelling together with observational data to disentangle the reaction pathways controlling the cycling of Si within the seafloor. Processes such as the dissolution of BSi are active on multiple timescales, ranging from weeks to hundreds of years, which we are able to examine through steady state and transient model runs. Steady state simulations show that 60 % to 98 % of the sediment pore water DSi pool may be sourced from the dissolution of LSi, while the isotopic composition is also strongly influenced by the desorption of Si from metal oxides, most likely Fe (oxyhydr)oxides (FeSi), as they reductively dissolve. Further, our model simulations indicate that between 2.9 % and 37 % of the DSi released into sediment pore waters is subsequently removed by a process that has a fractionation factor of approximately −2 ‰, most likely representing reprecipitation as AuSi. These observations are significant as the dissolution of LSi represents a source of new Si to the ocean DSi pool and precipitation of AuSi an additional sink, which could address imbalances in the current regional ocean Si budget. Lastly, transient modelling suggests that at least one-third of the total annual benthic DSi flux could be sourced from the dissolution of more reactive, diatom-derived BSi deposited after the surface water bloom at the marginal ice zone. This benthic–pelagic coupling will be subject to change with the continued northward migration of Atlantic phytoplankton species, the northward retreat of the marginal ice zone and the observed decline in the DSi inventory of the subpolar North Atlantic Ocean over the last 3 decades.</p

Measuring lung mechanics of expiratory tidal breathing with non-invasive breath occlusion

Background and objective: Lung mechanics measurements provide clinically useful information about disease progression and lung health. Currently, there are no commonly practiced methods to non-invasively measure both resistive and elastic lung mechanics during tidal breathing, preventing the important information provided by lung mechanics from being utilised. This study presents a novel method to easily assess lung mechanics of spontaneously breathing subjects using a dynamic elastance, single-compartment lung model. Methods: A spirometer with a built-in shutter was used to occlude expiration during tidal breathing, creating exponentially decaying flow when the shutter re-opened. The lung mechanics measured were respiratory system elastance and resistance, separated from the exponentially decaying flow, and interrupter resistance calculated at shutter closure. Progressively increasing resistance was added to the spirometer mouthpiece to simulate upper airway obstruction. The lung mechanics of 17 healthy subjects were successfully measured through spirometry. Results: N = 17 (8 female, 9 male) healthy subjects were recruited. Measured decay rates ranged from 5 to 42/s, subjects with large variation of decay rates showed higher muscular breathing effort. Lung elastance measurements ranged from 3.9 to 21.2 cmH -2 2 O/L, with no clear trend between change in elastance and added resistance. Resistance calculated from decay rate and elastance ranged from 0.15 to 1.95 cmH -2 2 Os/L. These very small resistance values are due to the airflow measured originating from low-resistance areas in the centre of airways. Occlusion resistance measurements were as expected for healthy subjects, and increased as expected as resistance was added. Conclusions: This test was able to identify reasonable dynamic lung elastance and occlusion resistance values, providing new insight into expiratory breathing effort. Clinically, this lung function test could impact current practice. It does not require high levels of cooperation from the subject, allowing a wider cohort of patients to be assessed more easily. Additionally, this test can be simply implemented in a small standalone device, or with standard lung function testing equipment

Low testosterone levels predict all-cause mortality and cardiovascular events in women: a prospective cohort study in German primary care patients

Objective: Although associations between testosterone and cardiovascular (CV) morbidity in women have been proposed, no large prospective study has evaluated potential associations between testosterone and mortality in women. The objective was to determine whether baseline testosterone levels in women are associated with future overall or CV morbidity and mortality. Design: Prospective cohort study with a 4.5-year follow-up period. Methods: From a representative sample of German primary care practices, 2914 female patients between 18 and 75 years were analyzed for the main outcome measures: CV risk factors, CV diseases, and all-cause mortality. Results: At baseline, the study population was aged 57.96±14.37 years with a mean body mass index of 26.71±5.17 kg/m2. No predictive value of total testosterone for incident CV risk factors or CV diseases was observed in logistic regressions. Patients with total testosterone levels in the lowest quintile Q1, however, had a higher risk to die of any cause or to develop a CV event within the follow-up period compared to patients in the collapsed quintiles Q2–Q5 in crude and adjusted Cox regression models (all-cause mortality: Q2–Q5 versus Q1: crude hazard ratios (HR) 0.49, 95% confidence interval (CI) 0.33–0.74; adjusted HR 0.62, 95% CI 0.42–0.939; CV events: Q2–Q5 versus Q1: crude HR 0.54, 95% CI 0.38–0.77; adjusted HR 0.68, 95% CI 0.48–0.97). Kaplan–Meier curves revealed similar data. Conclusions: Low baseline testosterone in women is associated with increased all-cause mortality and incident CV events independent of traditional risk factors

Rigorous analysis of numerical methods: a comparative study

For any photonic device simulation, the accuracy of the numerical solution not only depends on the methods being used but also on the discretization parameters used in that numerical method. In this work, Finite Element Method and Finite Difference Time Domain Method based on Maxwell’s equations were used to simulate optical waveguides and directional couplers. As the solution accuracy may also depend on the index contrast used in such photonic devices, the characteristics of low-index contrast Germanium doped Silica and high-index contrast Silicon Nanowire Waveguides were analyzed, evaluated and benchmarked. Numerical results to benchmark Directional Couplers are also reported in this paper