Prevalence and inequality in persistent undiagnosed, untreated, and uncontrolled hypertension: Evidence from a cohort of older Mexicans

Hypertension is the leading risk factor for cardiovascular diseases (CVDs) and substantial gaps in diagnosis, treatment and control signal failure to avert premature deaths. Our aim was to estimate the prevalence and assess the socioeconomic distribution of hypertension that remained undiagnosed, untreated, and uncontrolled for at least five years among older Mexicans and to estimate rates of transition from those states to diagnosis, treatment and control. We used data from a cohort of Mexicans aged 50+ in two waves of the WHO Study on Global AGEing and adult health (SAGE) collected in 2009 and 2014. Blood pressure was measured, hypertension diagnosis and treatment self-reported. We estimated prevalence and transition rates over five years and calculated concentration indices to identify socioeconomic inequalities using a wealth index. Using probit models, we identify characteristics of those facing the greatest barriers in receiving hypertension care. More than 60 percent of individuals with full item response (N = 945) were classified as hypertensive. Over one third of those undiagnosed continued to be in that state five years later. More than two fifths of those initially untreated remained so, and over three fifths of those initially uncontrolled failed to achieve continued blood pressure control. While being classified as hypertensive was more concentrated among the rich, missing diagnosis, treatment and control were more prevalent among the poor. Men, singles, rural dwellers, uninsured, and those with overweight were more likely to have persistent undiagnosed, untreated, and uncontrolled hypertension. There is room for improvement in both hypertension diagnosis and treatment in Mexico. Clinical and public health attention is required, even for those who initially had their hypertension controlled. To ensure more equitable hypertension care and effectively prevent premature deaths, increased diagnosis and long-term treatment efforts should especially be directed towards men, singles, uninsured, and those with overweight.

Clinical significance of leptin in systemic lupus erythematosus

Objective: to study the frequency of hyperleptinemia in patients with systemic lupus erythematosus (SLE), its relationship with clinical and laboratory manifestations of the disease, drug therapy, and other metabolic disorders.Patients and methods. The cross-sectional study included 46 women with a definite diagnosis of SLE (median age 40 [31; 48] years) and disease duration 3.0 [0.9; 9.0] years. Glucocorticoids (GC) were received by 38 (83%) patients, hydroxychloroquine – by 35 (76%), immunosuppressants – by 10 (22%), biologic disease-modifying antirheumatic drugs – by 5 (11%). In all patients, fasting levels of glucose, leptin, apoliproprotein B (ApoB) and immunoreactive insulin were determined, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Concentration of leptin ≥11.1 ng/ml, ApoB – >1.6 mg/ml were considered an elevated level. HOMA-IR index ≥2.77 corresponded to the presence of insulin resistance (IR).Results and discussion. Hyperleptinemia was found in 34 (74%) patients with SLE, an increased level of ApoB – in 19 (41%), IR – in 10 (22%). In patients with hyperleptinemia, serositis, positivity for anti-double-stranded DNA (aDNA) and hypocomplementemia were less common, overweight and obesity were more frequent, the SLEDAI-2K index was lower, the aDNA level was lower, and the concentration of the C3 component of complement, insulin, HOMA-IR index, body mass index (BMI) and disease duration were higher (p<0.05 for all cases). BMI <25 kg / m2 had 26 (57%) women, 14 (54%) of whom had hyperleptinemia. In patients with BMI <25 kg / m2, we found a relationship between leptin concentration and disease duration (r=0.4, p=0.04), SLE activity according to SLEDAI-2K (r=-0.6, p=0.003), levels of aDNA (r=-0.6, p<0.001), C3 component of complement (r=0.5, p=0.01), maximum (r=0.7, p<0.001) and supporting (r=0,5, p=0.023) GC doses.In patients with BMI ≥25 kg/m2 (n=20), no such relationship was observed.Conclusion. Hyperleptinemia was found in the majority of women with SLE; elevated levels of ApoB and IR were much less common. Patients with hyperleptinemia are characterized by a longer duration and less activity of the disease, as well as the presence of overweight and obesity and an increase in the HOMA-IR index. In SLE patients with normal body weight, the concentration of leptin increased along with GC dose elevation.

A Method to Measure Voxelotor Exposure in People with Sickle Cell Disease Using Capillary Zone Electrophoresis

Background: Voxelotor (Oxbryta®) is a small molecule that binds to the alpha chain of hemoglobin (Hb) and increases the affinity of Hb for oxygen which reduces sickle Hb polymerization. It was approved by the FDA in 2019 for the treatment of sickle cell disease (SCD). Currently, the only method available to estimate the concentration of voxelotor in the blood is to obtain exposure measurements which are only available in select research laboratories. A method to measure voxelotor at a standard laboratory would allow clinicians to assess compliance and may be useful in determining optimal dosing. Case studies have reported that voxelotor binding to Hb interferes with capillary zone electrophoresis (CZE). As previously reported, in CZE the characteristic peaks of hemoglobin A2 (HbA2) and hemoglobin F (HbF) split in the presence of voxelotor. Interestingly, it does not cause the hemoglobin S peak to split. We posited that we could use this split to estimate the presence of voxelotor and whole blood concentration. Biophysical measurements of voxelotor binding to Hb were also measured in these samples. Methods: Patients were enrolled prospectively in an IRB approved protocol. Voxelotor was initiated at 1500 mg daily on day 0 and samples were taken at day 0 (pre-dose), 14, 30, and 60. Samples had Hb variants quantified by CZE using the Capillarys 2 FlexPiercing Instrument (Sebia, Georgia). Hematology parameters were measured with the Sysmex XN-1000 automated analyzer (Sysmex, Illinois). To determine whole blood concentration of voxelotor, samples were sent to Worldwide Clinical Trials where a validated liquid chromatography-tandem mass spectrometry method was used. Voxelotor's interference with HbA2 on CZE is dependent on the HbF percentage, therefore samples from patients with SCD were combined into three pooled samples (5-10 samples per pool) of HbF percentages spanning 5-30%. Three hundred µL aliquots of each pool were spiked with voxelotor in DMSO in triplicate to different concentrations between 0 and 600 µMol/L and were incubated at room temperature for 1 hour before being tested with CZE. Samples were then analyzed for voxelotor interference resulting in split peaks of HbF and HbA2. HbA2 interference percent (%VarA2) was calculated as the reported value of the HbA2 split peak over the total HbA2 value (both split and parent peak) times 100. F% was used as directly reported by the instrument without consideration of voxelotor interference. Results were then analyzed in Excel (Data Analytics package) using a multiparameter regression to generate a line of best fit. To allow for logarithmic fit when examining the correlation of calculated concentration with increase in Hb due to voxelotor, samples with negative Hb rises were excluded and concentrations which resulted as negative values were changed to 0.01 µM. Results: Of 20 patients which have been enrolled to date, 9 patients have completed the study and their data was used for these analyses. Using the CZE method described above the concentration of voxelotor was quantifiable using the following equation. Equation 1: uM voxelotor = -99.13 + 7.10*%HbF +12.52*%VarA2 The calculated concentrations of voxelotor based on CZE results had a strong correlation with whole blood concentration (R 2 = 0.85, p &lt;0.001). (Figure 1) When calculated concentration was compared to change in Hb at days 14, 30, and 60 there was a significant positive logarithmic correlation between concentration and change in Hb (R 2=.56, p&lt;0.01). (Figure 2) Conclusions: Using equation 1, CZE can be used to detect the presence of voxelotor and estimate its whole blood concentration. This will allow clinicians to have a better understanding of how their patients are using voxelotor. Additionally, higher calculated whole blood concentrations correlated with higher increases in Hb. It was previously shown that patients who receive higher doses of voxelotor have on average larger increases in Hb. If it could be shown that increasing concentration in an individual on voxelotor is associated with an increased Hb for that individual, then our method could also be used to help clinicians select and adjust doses of voxelotor in a similar manner to how HbF is used in hydroxyurea dosing. Figure 1 Figure 1. Disclosures Curtis: GBT: Consultancy. Minniti: CSL Behring: Other: Endpoint adjudicator; Bluebird Bio: Other: Endpoint adjudicator; F. Hoffmann-La Roche: Consultancy; Chiesi: Consultancy; Novo Nordisk: Consultancy; Forma: Consultancy; Novartis: Consultancy; GBT: Consultancy. Ngyuen Dang: GBT: Current Employment. Pochron: GBT: Current Employment. Campbell: GBT: Research Funding; Sebia: Research Funding.

Determination of 226Ra in TENORM Sample Considering Radon Leakage Correction

Background: Phosphogypsum is material produced as a byproduct in fertilizer industry and is generally used for building materials. This material may contain enhanced radium-226 (226Ra) activity concentration compared to its natural concentration that may lead to indoor radon accumulation. Therefore, an accurate measurement method is proposed in this study to determine 226Ra activity concentration in phosphogypsum sample, considering the potential radon leakage from the sample container.Materials and Methods: The International Atomic Energy Agency (IAEA) phosphogypsum reference material was used as a sample in this study. High-purity germanium (HPGe) gamma spectrometry was used to measure the activity concentration of the 226Ra decay products, i.e., 214Bi and 214Pb. Marinelli beakers sealed with three different sealing methods were used as sample containers. Due to the potential leakage of radon from the Marinelli beaker (MB), correction to the activity concentration resulted in gamma spectrometry is needed. Therefore, the leaked fraction of radon escaped from the sample container was calculated and added to the gamma spectrometry measured values.Results and Discussion: Total activity concentration of 226Ra was determined by summing up the activity concentration from gamma spectrometry measurement and calculated concentration from radon leakage correction method. The results obtained from 214Bi peak were 723.4 ± 4.0 Bq· kg-1 in MB1 and 719.2 ± 3.5 Bq· kg-1 in MB2 that showed about 5% discrepancy compared to the certified activity. Besides, results obtained from 214Pb peak were 741.9 ± 3.6 Bq· kg-1 in MB1 and 740.1 ± 3.4 Bq· kg-1 in MB2 that showed about 2% difference compared to the certified activity measurement of 226Ra concentration activity.Conclusion: The results show that radon leakage correction was calculated with insignificant discrepancy to the certified values and provided improvement to the gamma spectrometry. Therefore, measuring 226Ra activity concentration in TENORM (technologically enhanced naturally occurring radioactive material) sample using radon leakage correction can be concluded as a convenient and accurate method that can be easily conducted with simple calculation.

THERMODIFFUSION SATURATION OF THE SURFACE LAYERS OF α-TITANIUM BY OXYGEN, NITROGEN, CARBON

The purpose of the study is to analytically assess the depth of the gas-saturated zone in the case of a single-component diffusion saturation of alpha-titanium with nitrogen, oxygen and carbon from a rarefied controlled gas environment. Results. Based on the analysis of the literature data, the work schematically shows the interaction of alpha titanium with the elements of implementation and presents the processes with the corresponding parameters that characterize. It is shown that the surface impurity concentration is equal to the equilibrium concentration and is established instantly and does not depend on time. Consequently, with the proposed generalized nonstationary boundary condition in the absence of diffusion of impurities into the volume of the metal, the time dependence of its surface concentration is given, determined by the intensity of surface processes. The dependence of the relative change in the microhardness in the diffusion zone of titanium due to dissolved nitrogen (without taking into account the contribution of nitride inclusions) is presented. Analytically calculated concentration profiles of nitrogen generally correlate well with the distribution of the corresponding relative changes in microhardness in the surface layer. Analytical calculations of the concentration profiles of oxygen, nitrogen and carbon in titanium at a saturation temperature of 700 °C are presented. Practical value. The results obtained will make it possible to preliminarily estimate the size of the fortified near-surface layer depending on the parameters of chemical-thermal treatment and select the optimal parameters of thermal diffusion treatment to ensure the formation of reinforced layers on products made of alpha-titanium based on elements of interstitial in order to increase the functional properties.

Occurrence of Pesticide Residues in Spanish Honey Measured by QuEChERS Method Followed by Liquid and Gas Chromatography–Tandem Mass Spectrometry

In the current study, the QuEChERS extraction method with slight modifications, followed by liquid and gas chromatography–tandem mass spectrometry, was applied for the determination of 399 pesticide residues in 91 raw honey samples from northeastern Spain. The quality control procedure established in Document No. SANTE/12682/2019 was successfully followed: the responses in reagent blank and blank honey samples were below 30% of the reporting limit (0.01 mg kg−1) for all analysed compounds, the correlation coefficients (R2) were higher than 0.99 in most calibration curves, the deviation of back-calculated concentration from the true concentration was below ±20% (using the standard of 50 μg L−1 concentration), and the recoveries of spiked samples on matrix were within the range of 70–120% for almost all analytes. Only chlorfenvinphos (2–7.8 ng/g) and coumaphos (8.8–37 ng/g) were detected in 13 samples, and neither were observed to exceed their maximum residue limits (MRLs). Dietary risk assessment for pesticide residues in honey above their lowest calibrated level (LCL) was performed, and two different age groups, adults and infants, were considered as populations at risk. The contribution of honey lay far below the acceptable daily intake (ADI) for both pesticide residues. Therefore, according to our results, honey is unlikely to pose concerns for consumer health in terms of its contribution to dietary long-term exposure. However, to maintain the level of compliance, pesticide residues in honey should be continuously monitored.

COVID-19 and Unmet Healthcare Needs of Older People: Did Inequity Arise in Europe?

Background: The disruption in healthcare provision due to the COVID-19 pandemic forced many non-urgent medical treatments and appointments to be postponed or denied, which is expected to have huge impact on non-acute health conditions, especially in vulnerable populations such as older people. Attention should be paid to equity issues related to unmet needs during the pandemic. Methods: We calculated concentration indices to identify income-related inequalities and horizontal inequity in unmet needs due to postponed and denied healthcare in people over 50 during COVID-19, using data from the Survey on Health, Ageing and Retirement in Europe (SHARE). Results: Very few countries show significant income-related inequalities in postponed, rescheduled or denied treatments and medical appointments, usually favouring the rich. Only Estonia, Italy and Romania show a significant horizontal inequity (HI) in postponed healthcare, which apparently favours the poor. Significant pro-rich inequity in denied healthcare is found in Italy, Poland and Greece. Conclusions: Although important income-related horizontal inequity in unmet needs of European older adults during the early waves of the COVID-19 pandemic is not evident for most countries, some of them have to carefully monitor barriers to healthcare access. Delays in diagnosis and treatments may ultimately translate into adverse health outcomes, reduced quality of life and, even, widen socio-economic health inequalities among older people.

Will mandatory audit firm rotation reduce audit market concentration in South Africa?

Purpose: Deconcentrating the audit market was one of the stated objectives of the proposed mandatory audit firm rotation (MAFR) ruling in South Africa. With MAFR being a contentious topic, this study aimed to explore the possible effect of MAFR on audit market concentration in South Africa in anticipation of the implementation thereof in 2023.Design/methodology/approach: A sample of 415 South African listed companies was studied for the period 2010–2018. Data were mainly captured from annual reports. Descriptive statistics and significance testing were performed on calculated concentration ratios and identified audit firm rotations.Findings/results: South African audit market concentration mirrored empirical evidence from most developed countries – with Big 4 audit firms dominating the audit market, whilst a monopoly within the Big 4 audit firm grouping was also evident. Based on observed audit firm concentration and audit firm rotation behaviour, it was anticipated that MAFR might further increase audit market concentration. A concerning result was the sheer scale of audit firm rotations to be carried out in anticipation of MAFR in 2023.Practical implications: This study identified the impairment of audit quality and increased costs as possible unintended consequences of MAFR in South Africa.Originality/value: This study contributed to the limited body of knowledge on the possible effect of MAFR in South Africa. This study proposed alternatives to MAFR and recommended areas for future research to support evidence-based decisions on remedies to address audit quality and audit market concentration in South Africa.

CFD analysis of asymmetric mixing at different inlet configurations of a split-and-recombine micro mixer

In the scope of the ENPRO II initiative (Energy Efficiency and Process Intensification for the Chemical Industry), a major challenge of process intensification of polymer synthesis in continuous systems is fouling. Pre-mixing is a key aspect to prevent fouling and is achieved through milli and micro structured devices (Bayer et al. 1). While equal volume flow ratios are well investigated in milli and micro systems, asymmetric mixing tasks have received less attention. This paper investigates the dependency of mixing phenomena on different flow rate ratios and modified inlet geometries. A split-and-recombine (SAR) mixer is modified by means of an injection capillary to facilitate the asymmetric mixing task. Asymmetric volume flows of ratios between 1:15 and 1:60 are investigated; the velocity ratios range from 0.5 to 2. The setup is simulated with the Computational Fluid Dynamics (CFD) tool ANSYS®;Fluent. The species equation is solved directly without the use of micro mixing models. The simulation is validated by means of a concentration field in a mixing Tee using Laser-Induced Fluorescence (LIF) with a Confocal Laser Scanning Microscope (CLSM). The three dimensional flow structures and the mixing quality are analyzed as a measure for micro mixing. The calculated concentration fields show good agreement with the experimental results and reveal the secondary flow structures and chaotic advection within the channel. The injection of the small feed stream is found to be very efficient when drawn into the secondary structures, increasing the potential of diffusive mixing. CFD simulations help to understand and locate such structures and improve the mixing performance.

Change in full immunization inequalities in Indian children 12–23 months: an analysis of household survey data

Background India has made substantial progress in improving child health in recent years. However, the country continues to account for a large number of vaccine preventable child deaths. We estimated wealth-related full immunization inequalities in India. We also calculated the degree to which predisposing, reinforcing, and enabling factors contribute to these inequalities. Methods We used data from the two rounds of a large nationally representative survey done in all states in India in 2005–06 (n = 9582) and 2015–16 (n = 49,284). Full immunization status was defined as three doses of diphtheria-tetanus-pertussis vaccine, three doses of polio vaccine, one dose of Bacillus Calmette–Guérin vaccine, and one dose of measles vaccine in children 12–23 months. We compared full immunization coverage by wealth quintiles using descriptive statistics. We calculated concentration indices for full immunization coverage at the national and state levels. Using predisposing, reinforcing, and enabling factors associated with full immunization status identified from the literature, we applied a generalized linear model (GLM) framework with a binomial distribution and an identity link to decompose the concentration index. Results National full immunization coverage increased from 43.65% in 2005–06 to 62.46% in 2015–16. Overall, full immunization coverage in both 2005–06 and 2015–16 in all states was lowest in children from poorer households and improved with increasing socioeconomic status. The national concentration index decreased from 0.36 to 0.13 between the two study periods, indicating a reduction in poor-rich inequality. Similar reductions were observed for most states, except in states where inequalities were already minimal (i.e., Tamil Nadu) and in some northeastern states (i.e., Meghalaya and Manipur). In 2005–06, the contributors to wealth-related full immunization inequality were antenatal care, maternal education, and socioeconomic status. The same factors contributed to full immunization inequality in 2015–16 in addition to difficulty reaching a health facility. Conclusions Immunization coverage and wealth-related equality have improved nationally and in most states over the last decade in India. Targeted, context-specific interventions could help address overall wealth-related full immunization inequalities. Intensified government efforts could help in this regard, particularly in high-focus states where child mortality remains high.