Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events in people with prior coronary heart ...disease, but large trials of omega-3 fatty acids have produced conflicting results.
To conduct a meta-analysis of all large trials assessing the associations of omega-3 fatty acid supplements with the risk of fatal and nonfatal coronary heart disease and major vascular events in the full study population and prespecified subgroups.
This meta-analysis included randomized trials that involved at least 500 participants and a treatment duration of at least 1 year and that assessed associations of omega-3 fatty acids with the risk of vascular events.
Aggregated study-level data were obtained from 10 large randomized clinical trials. Rate ratios for each trial were synthesized using observed minus expected statistics and variances. Summary rate ratios were estimated by a fixed-effects meta-analysis using 95% confidence intervals for major diseases and 99% confidence intervals for all subgroups.
The main outcomes included fatal coronary heart disease, nonfatal myocardial infarction, stroke, major vascular events, and all-cause mortality, as well as major vascular events in study population subgroups.
Of the 77 917 high-risk individuals participating in the 10 trials, 47 803 (61.4%) were men, and the mean age at entry was 64.0 years; the trials lasted a mean of 4.4 years. The associations of treatment with outcomes were assessed on 6273 coronary heart disease events (2695 coronary heart disease deaths and 2276 nonfatal myocardial infarctions) and 12 001 major vascular events. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800 mg/d) had no significant associations with coronary heart disease death (rate ratio RR, 0.93; 99% CI, 0.83-1.03; P = .05), nonfatal myocardial infarction (RR, 0.97; 99% CI, 0.87-1.08; P = .43) or any coronary heart disease events (RR, 0.96; 95% CI, 0.90-1.01; P = .12). Neither did randomization to omega-3 fatty acid supplementation have any significant associations with major vascular events (RR, 0.97; 95% CI, 0.93-1.01; P = .10), overall or in any subgroups, including subgroups composed of persons with prior coronary heart disease, diabetes, lipid levels greater than a given cutoff level, or statin use.
This meta-analysis demonstrated that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events. It provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease.
Aspirin is widely used for cardioprotection with its antiplatelet effects due to the blocking of thromboxane A2 production. However, it has been suggested that platelet abnormalities in those with ...diabetes prevent adequate suppression with once daily aspirin.
In the ASCEND randomized double-blind trial of aspirin 100 mg once daily versus placebo in participants with diabetes but no history of cardiovascular disease, suppression was assessed by measuring 11-dehydro-thromboxane B2 excretion in urine (U-TXM) in a randomly selected sample of 152 participants (76 aspirin arm, 74 placebo arm), plus 198 (93 aspirin arm, 105 placebo arm) adherent to study drugs and selected to maximize the numbers ingesting their last tablet 12-24 h before urine sampling. U-TXM was assayed using a competitive ELISA assay in samples mailed a mean of 2 years after randomization, with time since taking last aspirin/placebo tablet recorded at the time of sample provision. Effective suppression (U-TXM < 1500 pg/mg creatinine) and percentage reductions in U-TXM by aspirin allocation were compared.
In the random sample, U-TXM was 71% (95% CI 64-76%) lower among aspirin vs placebo-allocated participants. Among adherent participants in the aspirin arm, U-TXM was 72% (95% CI 69-75%) lower than in the placebo arm and 77% achieved effective suppression overall. Suppression was similar among those who ingested their last tablet more than 12 h before urine sampling with levels in the aspirin arm 72% (95% CI 67-77%) lower than in the placebo arm and 70% achieving effective suppression.
Daily aspirin significantly reduces U-TXM in participants with diabetes, including at 12-24 h after ingestion.
ISRCTN ISRCTN60635500. Registered on 1 Sept 2005; ClinicalTrials.gov NCT00135226. Registered on 24 Aug 2005.
Background
Continuous glucose monitoring (CGM) for diabetes combines noninvasive glucose biosensors, continuous monitoring, cloud computing, and analytics to connect and simulate a hospital setting ...in a person’s home. CGM systems inspired analytics methods to measure glycemic variability (GV), but existing GV analytics methods disregard glucose trends and patterns; hence, they fail to capture entire temporal patterns and do not provide granular insights about glucose fluctuations.
Objective
This study aimed to propose a machine learning–based framework for blood glucose fluctuation pattern recognition, which enables a more comprehensive representation of GV profiles that could present detailed fluctuation information, be easily understood by clinicians, and provide insights about patient groups based on time in blood fluctuation patterns.
Methods
Overall, 1.5 million measurements from 126 patients in the United Kingdom with type 1 diabetes mellitus (T1DM) were collected, and prevalent blood fluctuation patterns were extracted using dynamic time warping. The patterns were further validated in 225 patients in the United States with T1DM. Hierarchical clustering was then applied on time in patterns to form 4 clusters of patients. Patient groups were compared using statistical analysis.
Results
In total, 6 patterns depicting distinctive glucose levels and trends were identified and validated, based on which 4 GV profiles of patients with T1DM were found. They were significantly different in terms of glycemic statuses such as diabetes duration (P=.04), glycated hemoglobin level (P<.001), and time in range (P<.001) and thus had different management needs.
Conclusions
The proposed method can analytically extract existing blood fluctuation patterns from CGM data. Thus, time in patterns can capture a rich view of patients’ GV profile. Its conceptual resemblance with time in range, along with rich blood fluctuation details, makes it more scalable, accessible, and informative to clinicians.
The roles of Pseudomonas aeruginosa polysaccharides (Pel, Psl, alginate) in reverse osmosis (RO) membrane biofouling and nitric oxide (NO) induced dispersal were investigated. While mutants deficient ...in Psl formed significantly lower biofilm (total cell and polysaccharide) biovolumes than the PAO1 wild-type on glass surfaces, total cell biovolumes were similar during fouling of RO membranes. However, biofilms of the Psl deficient mutants exhibited a striated pattern, leaving large areas of membrane unfouled and contained up to 70% less polysaccharide and 24% less protein than the wild-type. Membranes fouled by the psl mutants exhibited a 69% reduction in the rate of biofouling (pressure rise over a given period), while the pel and alginate mutants were similar to the wild-type, suggesting functional differences in the polysaccharides. Overproduction of alginate by a PDO300 mutant increased the biofouling rate (59%) relative to wild-type, highlighting the ability of this polysaccharide to promote biofilm adherence and increase hydraulic resistance to permeate flow in an RO system. These results emphasize the importance of attachment specific polysaccharides for bacteria when fouling industrial RO membranes. When exposed to NO, dispersal of the PDO300 mutant biofilm was 25% lower than the wild-type, whilst dispersal of the alginate deficient mutant was 11% greater. Alginate thus appears to play an important role in NO induced dispersal of PAO1 biofilms.
•The role of PAO1 polysaccharides, Psl, Pel and Alg, in RO membrane biofouling was investigated.•A lack of Psl led to a striated biofilm, reducing the biofouling rate and the increase in TMP.•Overproduction of alginate increased the biofouling rate and accelerated the TMP rise.•Alginate overproduction reduced nitric oxide induced dispersal of PAO1 biofilms.•Biofouling was strongly dependent on individual polysaccharides and their physical properties.
Alpha-dioxygenase (α-DOX) enzymes catalyse the oxygenation of fatty acids to yield a newly identified group of oxylipins that play a role in protecting tissues from oxidative damage and cell death. ...In tomato (Lycopersicon esculentum Mill.) α-DOX was identified as salt-regulated by differential display of mRNA, and is represented by a small gene family comprising at least three members: LEα-DOX1, -2, and -3 of which only LEα-DOX1 was salt-responsive. The enhancement of LEα-DOX1 expression in roots by salt, wounding and challenge with Pythium aphanidermatum (Edson) Fitzp. suggests that α-DOX-generated oxylipins may mediate the response of roots to these environmental stresses. In roots, LEα-DOX1 was abscisic acid (ABA)-responsive. However, in the ABA-deficient mutant flacca salt-responsive expression was equivalent to that in the wild type. Similarly, in roots exposed to fluridone (FLU) salt up-regulated expression; however, in this case salt-responsive LEα-DOX1 expression was greater than that in roots that were not exposed to FLU. A possible explanation for this is provided by the role of ABA in suppressing ethylene accumulation in osmotically stressed roots. The ethylene-generating agent ethephon and precursor 1-aminocyclopropane-1-carboxylic acid markedly elevated LEα-DOX1 expression, and this enhanced expression was suppressed by ABA. LEα-DOX1 expression in salt-stressed roots was not markedly affected by AVG indicating that ABA may be responsible for enhanced α-DOX expression in salt-treated roots.
A multicenter, randomized trial involving participants with diabetes and no evident cardiovascular disease at trial entry showed that aspirin led to a lower risk of serious vascular events than ...placebo but also caused a higher risk of major bleeding.
In this trial involving patients with diabetes without evidence of cardiovascular disease, the risk of serious vascular events was similar in those who received n−3 fatty acid supplements and those ...who received placebo.
Adults with vascular disease were treated with a statin to lower LDL cholesterol and were assigned to receive either extended-release niacin plus laropiprant or placebo. Niacin–laropiprant did not ...significantly reduce the risk of major vascular events and increased the risk of serious adverse events.
Patients with cardiovascular disease remain at substantial risk for major vascular events despite current approaches to treatment of risk factors.
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Observational data indicate that the low-density lipoprotein (LDL) cholesterol level is strongly positively associated with the risk of coronary heart disease and that the high-density lipoprotein (HDL) cholesterol level is strongly inversely associated.
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High-dose niacin decreases the LDL cholesterol level and increases the HDL cholesterol level, as well as lowering triglyceride and lipoprotein(a) levels and blood pressure.
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,
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Current guidelines recommend that niacin therapy be considered for reducing cardiovascular risk,
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,
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and its use in the United States has been . . .
The use of aspirin for the secondary prevention of cardiovascular disease (CVD) is firmly established, and the proportional reductions in heart attacks and strokes appear to be similar in people with ...and without diabetes. Uncertainty remains about the role of antiplatelet treatments for primary prevention of CVD, and guidelines vary in their recommendations. It has also been hypothesized that long-term aspirin can prevent gastro-intestinal and other cancers.
Observational studies suggest associations between higher intakes of omega-3 fatty acids (FA) and lower rates of CVD, but there is no large-scale randomized evidence to support using prophylactic omega-3 FA supplementation in primary prevention.
ASCEND is a randomized trial assessing whether 100 mg daily aspirin safely prevents CVD and cancer in patients with diabetes without known arterial disease. It is also assessing whether supplementation with 1 g omega-3 FA daily prevents CVD. This paper describes the methods and baseline characteristics of the randomized participants.
Between 2005 and 2011, using mail-based methods, 15,480 people with diabetes were randomized to aspirin versus placebo and, in a factorial design, to omega-3 FA supplementation versus placebo. Blood and urine samples were collected to allow baseline stratification by biochemical prognostic variables (e.g. HbA1c, blood lipids). Follow-up is for a median of at least 7 years.
Demonstrating that prophylactic aspirin safely reduces the risk of CVD or cancer in the primary prevention setting, or that omega-3 FA supplementation prevents CVD, would be relevant to hundreds of millions of people worldwide who are currently not receiving such therapies. The results of ASCEND will be reported in 2018.
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