Electronic health records to facilitate clinical research

Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research

Association of Chronic Obstructive Pulmonary Disease with Morbidity and Mortality in Patients with Peripheral Artery Disease: Insights from the EUCLID Trial

Background: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lower extremity peripheral artery disease (PAD) and suffering PAD-related morbidity and mortality. However, the effect and burden of COPD on patients with PAD is less well defined. This post hoc analysis from EUCLID aimed to analyze the risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with PAD and concomitant COPD compared with those without COPD, and to describe the adverse events specific to patients with COPD.Methods: EUCLID randomized 13,885 patients with symptomatic PAD to monotherapy with either ticagrelor or clopidogrel for the prevention of MACE. In this analysis, MACE, MALE, mortality, and adverse events were compared between groups with and without COPD using unadjusted and adjusted Cox proportional hazards model.Results: Of the 13,883 patients with COPD status available at baseline, 11% (n=1538) had COPD. Patients with COPD had a higher risk of MACE (6.02 vs 4.29 events/100 patient-years; pConclusion: In patients with comorbid PAD and COPD, the risks of MACE, respiratory-related adverse events, and premature study drug discontinuation were higher when compared with patients without COPD.</div

Electronic health records to facilitate clinical research

Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research.</p

AINTEGUMENTA and the D-type cyclin CYCD3;1 regulate root secondary growth and respond to cytokinins

Higher plant vasculature is characterized by two distinct developmental phases. Initially, a well-defined radial primary pattern is established. In eudicots, this is followed by secondary growth, which involves development of the cambium and is required for efficient water and nutrient transport and wood formation. Regulation of secondary growth involves several phytohormones, and cytokinins have been implicated as key players, particularly in the activation of cell proliferation, but the molecular mechanisms mediating this hormonal control remain unknown. Here we show that the genes encoding the transcription factor AINTEGUMENTA (ANT) and the D-type cyclin CYCD3;1 are expressed in the vascular cambium of Arabidopsis roots, respond to cytokinins and are both required for proper root secondary thickening. Cytokinin regulation of ANT and CYCD3 also occurs during secondary thickening of poplar stems, suggesting this represents a conserved regulatory mechanism.Peer reviewe

Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch.

Silver birch (Betula pendula) is a pioneer boreal tree that can be induced to flower within 1 year. Its rapid life cycle, small (440-Mb) genome, and advanced germplasm resources make birch an attractive model for forest biotechnology. We assembled and chromosomally anchored the nuclear genome of an inbred B. pendula individual. Gene duplicates from the paleohexaploid event were enriched for transcriptional regulation, whereas tandem duplicates were overrepresented by environmental responses. Population resequencing of 80 individuals showed effective population size crashes at major points of climatic upheaval. Selective sweeps were enriched among polyploid duplicates encoding key developmental and physiological triggering functions, suggesting that local adaptation has tuned the timing of and cross-talk between fundamental plant processes. Variation around the tightly-linked light response genes PHYC and FRS10 correlated with latitude and longitude and temperature, and with precipitation for PHYC. Similar associations characterized the growth-promoting cytokinin response regulator ARR1, and the wood development genes KAK and MED5A

Shift-down in growth rate rather than high cell density induces toxic shock syndrome toxin-1 gene expression in Staphylococcus aureus

A luciferase-based reporter system for the expression of the toxic shock syndrome toxin-1 gene (tst) of Staphylococcus aureus FRI 1187 was used in continuous culture to determine whether high cell density on transient shift-down or shift-up of specific growth rate (μ) induced expression of tst. Little expression occurred at steady state at a low dilution rate (D) and in a transient period of increasing μ. However, a rapid and approximately 130-fold increase in expression occurred during a transient shift-down of μ. These findings suggest reduction of μ is a key element in the control of tst expressio

The harms of smoking and benefits of smoking cessation in women compared with men with type 2 diabetes: An observational analysis of the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial

Objectives: In general populations, the adverse effects of smoking on coronary risk have been demonstrated to be greater in women than in men; whether this is true for individuals with diabetes is unclear. Design: Cohort study. Setting: 20 countries worldwide participating in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron modified release Controlled Evaluation) trial. Participants: 11 140 patients with type 2 diabetes aged ≥55 years and in cardiovascular risk at the time of randomisation. Primary and secondary outcome measures: Major cardiovascular events (death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction (MI)), all cardiovascular events (major cardiovascular event or peripheral arterial disease or transient ischaemic attack), and all-cause mortality. Secondary outcome measures were major coronary events (fatal and non-fatal MI), major cerebrovascular events (fatal and non-fatal stroke), nephropathy (new or worsening renal disease), and all cancer. Results: At baseline, 6466 (56% women) participants were never-smokers, 1550 (28% women) were daily smokers and 3124 (21% women) were former smokers. Median follow-up time was 5 years. In Cox regression models after multiple adjustments, compared with never smoking, daily smoking was associated with increased risk of all primary and secondary outcomes with the exception of major cerebrovascular disease. Only for major coronary events was there any evidence of a stronger effect in women than in men (ratio of the adjusted HRs women:men; 1.64 (0.83 to 3.26) p=0.08)

The impact of level of education on vascular events and mortality in patients with type 2 diabetes mellitus: Results from the ADVANCE study

Aims The relationship between educational level and the risk of all-cause mortality is well established, whereas the association with vascular events in individuals with type 2 diabetes is not well described. Any association may reflect a link with common cardiovascular or lifestyle-based risk factors. Methods The relationships between the highest level of educational attainment and major cardiovascular events, microvascular complications and all-cause mortality were explored in a cohort of 11,140 individuals with type 2 diabetes. Completion of formal education before the age of 16 was categorized as a low level of education. Regional differences between Asia, East Europe and Established Market Economies were also assessed. Results During a median of 5 years of follow up, 1031 (9%) patients died, 1147 (10%) experienced a major cardiovascular event and 1136 (10%) a microvascular event. After adjustment for baseline characteristics and risk factors, individuals with lower education had an increased risk of cardiovascular events (hazard ratio (HR) 1.31, 95% CI 1.16–1.48, p < 0.0001), microvascular events (HR 1.23, 95% CI 1.08–1.39, p = 0.0013) and all-cause mortality (HR 1.34, 95% CI 1.18–1.52, p < 0.0001). In regional analyses the increased risk of studied outcomes associated with lower education was weakest in Established Market Economies and strongest in East Europe. Conclusions A low level of education is associated with an increased risk of vascular events and death in patients with type 2 diabetes, independently of common lifestyle associated cardiovascular risk factors. The effect size varies between geographical regions

AINTEGUMENTA and the D-type cyclin CYCD3;1 regulate root secondary growth and respond to cytokinins

Higher plant vasculature is characterized by two distinct developmental phases. Initially, a well-defined radial primary pattern is established. In eudicots, this is followed by secondary growth, which involves development of the cambium and is required for efficient water and nutrient transport and wood formation. Regulation of secondary growth involves several phytohormones, and cytokinins have been implicated as key players, particularly in the activation of cell proliferation, but the molecular mechanisms mediating this hormonal control remain unknown. Here we show that the genes encoding the transcription factor AINTEGUMENTA (ANT) and the D-type cyclin CYCD3;1 are expressed in the vascular cambium of Arabidopsis roots, respond to cytokinins and are both required for proper root secondary thickening. Cytokinin regulation of ANT and CYCD3 also occurs during secondary thickening of poplar stems, suggesting this represents a conserved regulatory mechanism