Changes in Plasma Copeptin Levels during Hemodialysis:Are the Physiological Stimuli Active in Hemodialysis Patients?

Plasma levels of copeptin, a surrogate marker for the vasoconstrictor hormone arginine vasopressin (AVP), are increased in hemodialysis patients. Presently, it is unknown what drives copeptin levels in hemodialysis patients. We investigated whether the established physiological stimuli for copeptin release, i.e. plasma osmolality, blood volume and mean arterial pressure (MAP), are operational in hemodialysis patients.One hundred and eight prevalent, stable hemodialysis patients on a thrice-weekly dialysis schedule were studied during hemodialysis with constant ultrafiltration rate and dialysate conductivity in this observational study. Plasma levels of copeptin, sodium, MAP, and blood volume were measured before, during and after hemodialysis. Multivariate analysis was used to determine the association between copeptin (dependent variable) and the physiological stimuli plasma sodium, MAP, excess weight as well as NT-pro-BNP immediately prior to dialysis and between copeptin and changes of plasma sodium, MAP and blood volume with correction for age, sex and diabetes during dialysis treatment.Patients were 63 ± 15.6 years old and 65% were male. Median dialysis vintage was 1.6 years (IQR 0.7-4.0). Twenty-three percent of the patients had diabetes and 82% had hypertension. Median predialysis copeptin levels were 141.5 pmol/L (IQR 91.0-244.8 pmol/L). Neither predialysis plasma sodium levels, nor NT-proBNP levels, nor MAP were associated with predialysis copeptin levels. During hemodialysis, copeptin levels rose significantly (p<0.01) to 163.0 pmol/L (96.0-296.0 pmol/L). Decreases in blood volume and MAP were associated with increases in copeptin levels during dialysis, whereas there was no significant association between the change in plasma sodium levels and the change in copeptin levels.Plasma copeptin levels are elevated predialysis and increase further during hemodialysis. Volume stimuli, i.e. decreases in MAP and blood volume, rather than osmotic stimuli, are associated with change in copeptin levels during hemodialysis

Device-measured physical activity and cardiometabolic health: the Prospective Physical Activity, Sitting, and Sleep (ProPASS) consortium

Background and Aims: Physical inactivity, sedentary behaviour (SB), and inadequate sleep are key behavioural risk factors of cardiometabolic diseases. Each behaviour is mainly considered in isolation, despite clear behavioural and biological interdependencies. The aim of this study was to investigate associations of five-part movement compositions with adiposity and cardiometabolic biomarkers.Methods: Cross-sectional data from six studies (n = 15 253 participants; five countries) from the Prospective Physical Activity, Sitting and Sleep consortium were analysed. Device-measured time spent in sleep, SB, standing, light-intensity physical activity (LIPA), and moderate-vigorous physical activity (MVPA) made up the composition. Outcomes included body mass index (BMI), waist circumference, HDL cholesterol, total:HDL cholesterol ratio, triglycerides, and glycated haemoglobin (HbA1c). Compositional linear regression examined associations between compositions and outcomes, including modelling time reallocation between behaviours.Results: The average daily composition of the sample (age: 53.7 ± 9.7 years; 54.7% female) was 7.7h sleeping, 10.4h sedentary, 3.1h standing, 1.5h LIPA, and 1.3h MVPA. A greater MVPA proportion and smaller SB proportion were associated with better outcomes. Reallocating time from SB, standing, LIPA, or sleep into MVPA resulted in better scores across all outcomes. For example, replacing 30min of SB, sleep, standing, or LIPA with MVPA was associated with-0.63 (95% confidence interval-0.48,-0.79),-0.43 (-0.25,-0.59),-0.40 (-0.25,-0.56), and-0.15 (0.05,-0.34) kg/m2 lower BMI, respectively. Greater relative standing time was beneficial, whereas sleep had a detrimental association when replacing LIPA/MVPA and positive association when replacing SB. The minimal displacement of any behaviour into MVPA for improved cardiometabolic health ranged from 3.8 (HbA1c) to 12.7 (triglycerides) min/day. Conclusions: Compositional data analyses revealed a distinct hierarchy of behaviours. Moderate-vigorous physical activity demonstrated the strongest, most time-efficient protective associations with cardiometabolic outcomes. Theoretical benefits from reallocating SB into sleep, standing, or LIPA required substantial changes in daily activity.</p

Device-measured physical activity and cardiometabolic health: the Prospective Physical Activity, Sitting, and Sleep (ProPASS) consortium

BACKGROUND AND AIMS: Physical inactivity, sedentary behaviour (SB), and inadequate sleep are key behavioural risk factors of cardiometabolic diseases. Each behaviour is mainly considered in isolation, despite clear behavioural and biological interdependencies. The aim of this study was to investigate associations of five-part movement compositions with adiposity and cardiometabolic biomarkers. METHODS: Cross-sectional data from six studies (n = 15 253 participants; five countries) from the Prospective Physical Activity, Sitting and Sleep consortium were analysed. Device-measured time spent in sleep, SB, standing, light-intensity physical activity (LIPA), and moderate-vigorous physical activity (MVPA) made up the composition. Outcomes included body mass index (BMI), waist circumference, HDL cholesterol, total:HDL cholesterol ratio, triglycerides, and glycated haemoglobin (HbA1c). Compositional linear regression examined associations between compositions and outcomes, including modelling time reallocation between behaviours. RESULTS: The average daily composition of the sample (age: 53.7 ± 9.7 years; 54.7% female) was 7.7 h sleeping, 10.4 h sedentary, 3.1 h standing, 1.5 h LIPA, and 1.3 h MVPA. A greater MVPA proportion and smaller SB proportion were associated with better outcomes. Reallocating time from SB, standing, LIPA, or sleep into MVPA resulted in better scores across all outcomes. For example, replacing 30 min of SB, sleep, standing, or LIPA with MVPA was associated with -0.63 (95% confidence interval -0.48, -0.79), -0.43 (-0.25, -0.59), -0.40 (-0.25, -0.56), and -0.15 (0.05, -0.34) kg/m2 lower BMI, respectively. Greater relative standing time was beneficial, whereas sleep had a detrimental association when replacing LIPA/MVPA and positive association when replacing SB. The minimal displacement of any behaviour into MVPA for improved cardiometabolic health ranged from 3.8 (HbA1c) to 12.7 (triglycerides) min/day. CONCLUSIONS: Compositional data analyses revealed a distinct hierarchy of behaviours. Moderate-vigorous physical activity demonstrated the strongest, most time-efficient protective associations with cardiometabolic outcomes. Theoretical benefits from reallocating SB into sleep, standing, or LIPA required substantial changes in daily activity

Prehospital Stroke Triage:A Modeling Study on the Impact of Triage Tools in Different Regions

Background and purpose: Direct transportation to a thrombectomy-capable intervention center is beneficial for patients with ischemic stroke due to large vessel occlusion (LVO), but can delay intravenous thrombolytics (IVT). The aim of this modeling study was to estimate the effect of prehospital triage strategies on treatment delays and overtriage in different regions. Methods: We used data from two prospective cohort studies in the Netherlands: the Leiden Prehospital Stroke Study and the PRESTO study. We included stroke code patients within 6 h from symptom onset. We modeled outcomes of Rapid Arterial oCclusion Evaluation (RACE) scale triage and triage with a personalized decision tool, using drip-and-ship as reference. Main outcomes were overtriage (stroke code patients incorrectly triaged to an intervention center), reduced delay to endovascular thrombectomy (EVT), and delay to IVT. Results: We included 1798 stroke code patients from four ambulance regions. Per region, overtriage ranged from 1-13% (RACE triage) and 3-15% (personalized tool). Reduction of delay to EVT varied by region between 24 ± 5 min (n = 6) to 78 ± 3 (n = 2), while IVT delay increased with 5 (n = 5) to 15 min (n = 21) for non-LVO patients. The personalized tool reduced delay to EVT for more patients (25 ± 4 min [n = 8] to 49 ± 13 [n = 5]), while delaying IVT with 3-14 min (8-24 patients). In region C, most EVT patients were treated faster (reduction of delay to EVT 31 ± 6 min (n = 35), with RACE triage and the personalized tool. Conclusions: In this modeling study, we showed that prehospital triage reduced time to EVT without disproportionate IVT delay, compared to a drip-and-ship strategy. The effect of triage strategies and the associated overtriage varied between regions. Implementation of prehospital triage should therefore be considered on a regional level.</p

Value-based healthcare in ischemic stroke care: Case-mix adjustment models for clinical and patient-reported outcomes

Background: Patient-Reported Outcome Measures (PROMs) have been proposed for benchmarking health care quality across hospitals, which requires extensive case-mix adjustment. The current study's aim was to develop and compare case-mix models for mortality, a functional outcome, and a patient-reported outcome measure (PROM) in ischemic stroke care. Methods: Data from ischemic stroke patients, admitted to four stroke centers in the Netherlands between 2014 and 2016 with available outcome information (N = 1022), was analyzed. Case-mix adjustment models were developed for mortality, modified Rankin Scale (mRS) scores and EQ-5D index scores with respectively binary logistic, proportional odds and linear regression models with stepwise backward selection. Predictive ability of these models was determined with R-squared (R2) and area-under-The-receiver-operating-characteristic-curve (AUC) statistics. Results: Age, NIHSS score on admission, and heart failure were the only common predictors across all three case-mix adjustment models. Specific predictors for the EQ-5D index score were sex (β = 0.041), socio-economic status (β =-0.019) and nationality (β =-0.074). R2-values for the regression models for mortality (5 predictors), mRS score (9 predictors) and EQ-5D utility score (12 predictors), were respectively R2 = 0.44, R2 = 0.42 and R2 = 0.37. Conclusions: The set of case-mix adjustment variables for the EQ-5D at three months differed considerably from the set for clinical outcomes in stroke care. The case-mix adjustment variables that were specific to this PROM were sex, socio-economic status and nationality. These variables should be considered in future attempts to risk-Adjust for PROMs during benchmarking of hospitals

Optical Patterning in Photoresponsive Azobenzene-Based Waterborne Coatings

Reversible photoresponsive waterborne dispersions can be directly applied in the paint and printing industry and have several potential applications such as in rewritable optical patterns, security labeling, and sensing. However, the synthesis of such dispersions and application as waterborne coatings has rarely been reported. In this work, photoresponsive polymer dispersions containing light-responsive azobenzene were prepared by resin-stabilized emulsion polymerization. The aqueous dispersions consist of core/shell type polymer particles, where the resin forms the shell around the polymer core. The photoresponsive azobenzene was incorporated into the resin shell (azo-in-shell) or polymer core (azo-in-core). Waterborne coatings were easily prepared by applying the dispersions on glass or paperboard. The photoresponsive behavior of the azobenzene in the dispersions and coatings shows fast and reversible isomerization and a similar half-life of the cis-azobenzene regardless of its surrounding matrix in the coating, dispersion, or solution. Optical patterns were reversibly imprinted in the coatings on paperboard, which remain visible for several hours at room temperature and several weeks when stored in the freezer. The water barrier properties of the azobenzene-containing coatings on paperboard were unaffected by the addition of the azobenzene moieties and isomerization state. Our results reveal a class of photoresponsive azobenzene waterborne coatings that can be easily applied on different substrates

Traditional Cardiovascular Risk Factors Strongly Underestimate the 5-Year Occurrence of Cardiovascular Morbidity and Mortality in Spinal Cord Injured Individuals

Objectives: To explore whether traditional models of cardiovascular disease (CVD) risk prediction correctly predict CVD events across a median 5.7-year follow-up period in individuals with spinal cord injury (SCI) and whether adding SCI-related characteristics (ie, lesion level) to the prediction model can improve the prognostic value. Design: Retrospective analysis of patient records. Setting: Observation at the start of active rehabilitation of participants in a multicenter cohort study, "Restoration of (Wheelchair) Mobility in SCI Rehabilitation," in the Netherlands. Participants: Patients with SCI (N=200) The patients were 74% men, aged 40 +/- 14 years, and with an American Spinal Injury Association (ASIA) impairment score of A through D. Forty percent had tetraplegia, and 69% were motor complete. Interventions: Risk profiling/not applicable. Main Outcome Measures: Survival status and cardiovascular morbidity and mortality qwere obtained from medical records. Five-year Framingham Risk Scores (FRS) and the FRS ability to predict events assessed using receiver operating characteristic (ROC) curves with corresponding areas under the curve (AUC) and 95% confidence intervals (CI). Kaplan-Meier curves and the log-rank test were used to assess the difference in clinical outcome between participants with an FRS score lower or higher than the median FRS score for the cohort. SCI-related factors associated with CVD events, ASIA impairment, motor completeness, level of injury, and sports participation before injury were explored using univariate and multivariate Cox proportional hazard regression. Results: The median 5-year FRS was 1.36%. Across a median follow-up period of 5.7 years, 39 developed a CVD event, including 10 fatalities. Although the FRS markedly underestimated the true occurrence of CVD events, the Kaplan-Meier curves and the log-rank test showed that the risk ratio for individuals with an FRS score less than the median FRS (eg, low risk) versus a score greater than the median FRS (high risk) was 3.2 (95% CI, 1.6-6.5; P=.001). Moreover, ROC with corresponding AUCs suggests acceptable accuracy of the FRS to identify individuals with increased risk for future CVD events (ROC AUC of 0.71; 95% CI, 0.62-0.82). Adding ASIA impairment (0.74; 95% CI, 0.66-0.82), motor impairment (0.74; 95% CI, 0.66-0.83), level of injury (0.72; 95% CI, 0.63-0.81), or active engagement in sport before injury (0.72; 95% CI, 0.630.88) to the FRS did not improve the level of discrimination. Conclusions: Our 5.7-year retrospective study reveals that cardiovascular risk factors and risk models markedly underestimate the true risk for CVD events in individuals with SCI. Nonetheless, these markers successfully distinguish between SCI individuals at high versus low risk for future CVD events. Our data may have future clinical implications, both related to (cutoff values of) CVD risk factors, but also for (earlier) prescription of (non)pharmacologic strategies against CVD in SCI individuals. (C) 2020 by the American Congress of Rehabilitation Medicin