Homocysteine levels and treatment effect in the prospective study of pravastatin in the elderly at risk

Objectives: To assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine.<p></p> Design: A post hoc subanalysis in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), started in 1997, which is a double-blind, randomized, placebo-controlled trial with a mean follow-up of 3.2 years.<p></p> Setting: Primary care setting in two of the three PROSPER study sites (Netherlands and Scotland).<p></p> Participants: Individuals (n = 3,522, aged 70–82, 1,765 male) with a history of or risk factors for CVD were ranked in three groups depending on baseline homocysteine level, sex, and study site.<p></p> Intervention: Pravastatin (40 mg) versus placebo.<p></p> Measurements: Fatal and nonfatal CHD and mortality.<p></p> Results: In the placebo group, participants with a high homocysteine level (n = 588) had a 1.8 higher risk (95% confidence interval (CI) = 1.2–2.5, P = .001) of fatal and nonfatal CHD than those with a low homocysteine level (n = 597). The absolute risk reduction in fatal and nonfatal CHD with pravastatin treatment was 1.6% (95% CI = −1.6 to 4.7%) in the low homocysteine group and 6.7% (95% CI = 2.7–10.7%) in the high homocysteine group (difference 5.2%, 95% CI = 0.11–10.3, P = .046). Therefore, the number needed to treat (NNT) with pravastatin for 3.2 years for benefit related to fatal and nonfatal CHD events was 14.8 (95% CI = 9.3–36.6) for high homocysteine and 64.5 (95% CI = 21.4–∞) for low homocysteine.<p></p> Conclusion: In older persons at risk of CVD, those with high homocysteine are at highest risk for fatal and nonfatal CHD. With pravastatin treatment, this group has the highest absolute risk reduction and the lowest NNT to prevent fatal and nonfatal CHD.<p></p&gt

Blood pressure variability and cardiovascular risk in the PROspective study of pravastatin in the elderly at risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects

Wind Tunnel Test of Counter-Rotating Dual Rotor Wind Turbine With Double Rotational Armature Design

This study evaluates the performance of a counter-rotating dual rotor wind turbine (CR-DRWT) with 2 m2 rotor radius equipped with a double rotational armature in an open jet wind tunnel. With only one similar-sized design previously assessed in a wind tunnel, this study offers valuable validation material for the literature. Through wind tunnel testing, the CR-DRWT confirmed earlier findings in literature and achieved a 15% to 50% increase in power output and a 10% increase in efficiency (CP) compared to a single rotor configuration at higher wind speeds (> 7 m/s). Though these gains were not observed at lower wind speeds (4–7 m/s). The simplified mechanics of a double rotational armature show promise for SWTs, as financial viability depends on reducing LCOE through efficiency improvements that maximize energy capture. The design's maximum CP values were below those achieved in previous field tests at larger scale highlighting potential for improvement for smaller sized turbines. To further explore the aerodynamics of CR-DRWT's, computational fluid dynamics (CFD) simulations are recommended, as they could provide insights into optimizing flow dynamics around CR-DRWT's. Finally, the study emphasizes the need for precise pitch angle and rotational speed measurements to improve the value of future measurements

How learning style affects evidence-based medicine:a survey study

BACKGROUND: Learning styles determine how people manage new information. Evidence-based medicine (EBM) involves the management of information in clinical practice. As a consequence, the way in which a person uses EBM can be related to his or her learning style. In order to tailor EBM education to the individual learner, this study aims to determine whether there is a relationship between an individual's learning style and EBM competence (knowledge/skills, attitude, behaviour). METHODS: In 2008, we conducted a survey among 140 novice GP trainees in order to assess their EBM competence and learning styles (Accommodator, Diverger, Assimilator, Converger, or mixed learning style). RESULTS: The trainees' EBM knowledge/skills (scale 0-15; mean 6.8; 95%CI 6.4-7.2) were adequate and their attitudes towards EBM (scale 0-100; mean 63; 95%CI 61.3-64.3) were positive. We found no relationship between their knowledge/skills or attitudes and their learning styles (p = 0.21; p = 0.19). Of the trainees, 40% used guidelines to answer clinical questions and 55% agreed that the use of guidelines is the most appropriate way of applying EBM in general practice. Trainees preferred using evidence from summaries to using evidence from single studies. There were no differences in medical decision-making or in EBM use (p = 0.59) for the various learning styles. However, we did find a link between having an Accommodating or Converging learning style and making greater use of intuition. Moreover, trainees with different learning styles expressed different ideas about the optimal use of EBM in primary care. CONCLUSIONS: We found that EBM knowledge/skills and EBM attitudes did not differ with respect to the learning styles of GP trainees. However, we did find differences relating to the use of intuition and the trainees' ideas regarding the use of evidence in decision-making

Understanding deprescribing of preventive cardiovascular medication: a Q-methodology study in patients

Patients with low cardiovascular disease (CVD) risk potentially use preventive cardiovascular medication unnecessarily. Our aim was to identify various viewpoints and beliefs concerning the preventive CVD management of patients with low CVD risk using preventive cardiovascular medication. Furthermore, we investigated whether certain viewpoints were related to a preference for deprescription or the continuation of preventive cardiovascular medication

OPTIMSM: FPGA hardware accelerator for Zero-Knowledge MSM

The Multi-Scalar Multiplication (MSM) is the main barrier to accelerating Zero-Knowledge applications. In recent years, hardware acceleration of this algorithm on both FPGA and GPU has become a popular research topic and the subject of a multi-million dollar prize competition (ZPrize). This work presents OPTIMSM: Optimized Processing Through Iterative Multi-Scalar Multiplication. This novel accelerator focuses on the acceleration of the MSM algorithm for any Elliptic Curve (EC) by improving upon the Pippenger algorithm. A new iteration technique is introduced to decouple the required buckets from the window size, resulting in fewer EC computations for the same on-chip memory resources. Furthermore, we combine known optimizations from the literature for the first time to achieve additional latency improvements. Our enhanced MSM implementation significantly reduces computation time, achieving a speedup of up to $\times 12.77$ compared to recent FPGA implementations. Specifically, for the BLS12-381 curve, we reduce the computation time for an MSM of size $2^{24}$ to 914 ms using a single compute unit on the U55C FPGA or to 231 ms using four U55C devices. These results indicate a substantial improvement in efficiency, paving the way for more scalable and efficient Zero-Knowledge proof systems

OPTIMSM: FPGA hardware accelerator for Zero-Knowledge MSM

The Multi-Scalar Multiplication (MSM) is the main barrier to accelerating Zero-Knowledge applications. In recent years, hardware acceleration of this algorithm on both FPGA and GPU has become a popular research topic and the subject of a multi-million dollar prize competition (ZPrize). This work presents OPTIMSM: Optimized Processing Through Iterative Multi-Scalar Multiplication. This novel accelerator focuses on the acceleration of the MSM algorithm for any Elliptic Curve (EC) by improving upon the Pippenger algorithm. A new iteration technique is introduced to decouple the required buckets from the window size, resulting in fewer EC computations for the same on-chip memory resources. Furthermore, we combine known optimizations from the literature for the first time to achieve additional latency improvements. Our enhanced MSM implementation significantly reduces computation time, achieving a speedup of up to x12.77 compared to recent FPGA implementations. Specifically, for the BLS12-381 curve, we reduce the computation time for an MSM of size 224 to 914 ms using a single compute unit on the U55C FPGA or to 231 ms using four U55C devices. These results indicate a substantial improvement in efficiency, paving the way for more scalable and efficient Zero-Knowledge proof systems

Risk stratification and treatment effect of statins in secondary cardiovascular prevention in old age: additive value of N-terminal pro-B-type natriuretic peptide

Background To date, no validated risk scores exist for prediction of recurrence risk or potential treatment effect for older people with a history of a cardiovascular event. Therefore, we assessed predictive values for recurrent cardiovascular disease of models with age and sex, traditional cardiovascular risk markers, and ‘SMART risk score’, all with and without addition of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Treatment effect of pravastatin was assessed across low and high risk groups identified by the best performing models. Design and methods Post-hoc analysis in 2348 participants (age 70–82 years) with a history of cardiovascular disease within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. Composite endpoint was a recurrent cardiovascular event/cardiovascular mortality. Results The models with age and sex, traditional risk markers and SMART risk score had comparable predictive values (area under the curve (AUC) 0.58, 0.61 and 0.59, respectively). Addition of NT-proBNP to these models improved AUCs with 0.07 (p for difference ((pdiff)) = 0.003), 0.05 (pdiff = 0.009) and 0.06 (pdiff < 0.001), respectively. For the model with age, sex and NT-proBNP, the hazard ratio for the composite endpoint in pravastatin users compared with placebo was 0.67 (95% confidence interval 0.49–0.90) for those in the highest third of predicted risk and 0.91 (0.57–1.46) in the lowest third, number needed to treat 12 and 115 (pdiff = 0.038) respectively. Conclusion In secondary cardiovascular prevention in old age addition of NT-proBNP improves prediction of recurrent cardiovascular disease, cardiovascular mortality and treatment effect of pravastatin. A minimal model including age, sex and NT-proBNP predicts as accurately as complex risk models including NT-proBNP