877 research outputs found
Do VERTIS-CV trial results question a class-effect of cardiovascular protection with sodium-glucose cotransporter 2 inhibitors?
VERTIS-CV was planned according to the Food and Drug
Administration (FDA) former guidelines to assess the CV safety of
new glucose-lowering drugs (recently updated to evaluate safety more
broadly). Therefore, this study was originally designed and powered to
show non-inferiority of ertugliflozin compared to placebo with respect
to CV outcomes in high-risk patients with type 2 diabetes. From this
point of view, the ‘mission’ was accomplished since VERTIS-CV results
showed non-inferiority of ertugliflozin compared to placebo.
However, based on previous studies showing positive effects of other
SGLT2i on CV and renal outcomes, the VERTIS-CV protocol had
been amended to reflect a doubling of the original sample size and inclusion of efficacy objectives for superiority
Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials
Objective: To assess the effects of selective cyclo-oxygenase-2 (COX 2) inhibitors and traditional non-steroidal anti-inflammatory drugs (NSAIDs) on the risk of vascular events. Design: Meta-analysis of published and unpublished tabular data from randomised trials, with indirect estimation of the effects of traditional NSAIDs. Data sources: Medline and Embase (January 1966 to April 2005); Food and Drug Administration records; and data on file from Novartis, Pfizer, and Merck. Review methods: Eligible studies were randomised trials that included a comparison of a selective COX 2 inhibitor versus placebo or a selective COX 2 inhibitor versus a traditional NSAID, of at least four weeks' duration, with information on serious vascular events (defined as myocardial infarction, stroke, or vascular death). Individual investigators and manufacturers provided information on the number of patients randomised, numbers of vascular events, and the person time of follow-up for each randomised group. Results: In placebo comparisons, allocation to a selective COX 2 inhibitor was associated with a 42% relative increase in the incidence of serious vascular events (1.2%/year v 0.9%/year; rate ratio 1.42, 95% confidence interval 1.13 to 1.78; P = 0.003), with no significant heterogeneity among the different selective COX 2 inhibitors. This was chiefly attributable to an increased risk of myocardial infarction (0.6%/year v 0.3%/year; 1.86, 1.33 to 2.59; P = 0.0003), with little apparent difference in other vascular outcomes. Among trials of at least one year's duration (mean 2.7 years), the rate ratio for vascular events was 1.45 (1.12 to 1.89; P = 0.005). Overall, the incidence of serious vascular events was similar between a selective COX 2 inhibitor and any traditional NSAID (1.0%/year v 0.9/%year; 1.16, 0.97 to 1.38; P = 0.1). However, statistical heterogeneity (P = 0.001) was found between trials of a selective COX 2 inhibitor versus naproxen (1.57, 1.21 to 2.03) and of a selective COX 2 inhibitor versus non-naproxen NSAIDs (0.88, 0.69 to 1.12). The summary rate ratio for vascular events, compared with placebo, was 0.92 (0.67 to 1.26) for naproxen, 1.51 (0.96 to 2.37) for ibuprofen, and 1.63 (1.12 to 2.37) for diclofenac. Conclusions: Selective COX 2 inhibitors are associated with a moderate increase in the risk of vascular events, as are high dose regimens of ibuprofen and diclofenac, but high dose naproxen is not associated with such an excess
An innovative AAL system based on neural networks and IoT-aware technologies to improve the quality of life in elderly people
Nowadays more and more elderly people need support in daily activities. This is due to the increase of cognitive diseases and other conditions which lead the elderly to not being self-sufficient. Considering this, providing an Ambient Assisted Living system could improve significantly people life quality and could support caregivers' tasks. The combination of Ambient Assisted Living systems and information and communication technologies achieve this purpose perfectly. They exploit internet of things and artificial intelligence paradigms to make daily challenges easier for people with neurodegenerative diseases. This work melds technologies mentioned above providing a smart system for elderly to manage goods and fill in shopping lists. It was possible using software, hardware, and cloud systems combined with a neural network aimed to recognise products. The proposed system has been validated both from a functional point of view through a proof-of-concept and quantitatively by a performance analysis of its components
Increased thromboxane biosynthesis is associated with poststroke dementia
BACKGROUND AND PURPOSE: It has been suggested that daily intake of aspirin
is associated with a reduction of cognitive decline, both in normal and in
demented subjects, but the mechanism is unclear. We have therefore studied
the relationship between thromboxane (TX) A(2) biosynthesis, as reflected
by the urinary excretion of 11-dehydro-TXB(2), and the presence of
dementia in patients after acute stroke. METHODS: Patients from the
Rotterdam Stroke Databank were screened for dementia between 3 and 9
months after stroke. Patients had a full neurological examination,
neuropsychological screening, and, if indicated, extensive
neuropsychological examination. Criteria used for the diagnosis of
dementia were from the Diagnostic and Statistical Manual of Mental
Disorders, Third Edition (Revised). Urine samples were taken at the time
of screening. Urinary 11-dehydro-TXB(2) was measured by means of a
previously validated radioimmunoassay. RESULTS: Dementia was diagnosed in
71 patients, and urine samples were available for 62. Median value (range)
of 11-dehydro-TXB(2) was 399 (89 to 2105) pmol/mmol creatinine for
demented patients versus 273 (80 to 1957) for 69 controls with stroke but
without dementia (P=0.013). No difference was found between 44 patients
with vascular dementia, 404 (89 to 2105) pmol/mmol creatinine, and 18
patients with Alzheimer's disease plus cerebrovascular disease, 399 (96 to
1467) pmol/mmol creatinine (P=0.68). In a stepwise logistic regression
analysis, in which possible confounders such as use of antiplatelet
medication, cardiovascular risk factors, and type of stroke were taken
into account, increased urinary excretion of 11-dehydro-TXB(2) remained
independently related to the presence of dementia (OR 1.12, 95% CI 1.03 to
1.22 per 100 pmol/mmol creatinine). The difference in metabolite excretion
rates between demented and nondemented patients was most prominent within
the subgroup of ischemic stroke patients who received aspirin (P<0.01).
CONCLUSIONS: Increased thromboxane biosynthesis in the chronic phase after
stroke is associated with the presence of but not the type of poststroke
dementia. It is particularly apparent in patients on aspirin, thereby
suggesting the involvement of extraplatelet sources of TXA(2) production
in this setting
Platelet activation and lipid peroxidation in patients with acute ischemic stroke
BACKGROUND AND PURPOSE: Both platelet activation and lipid peroxidation are potential sources of vasoactive eicosanoids that can be produced via the cyclooxygenase pathway, ie, thromboxane (TX) A2, or by free radical-catalyzed peroxidation of arachidonic acid, ie, isoprostanes. We investigated the biosynthesis of TXA2 and F2-isoprostanes, as reflected by the urinary excretion of 11-dehydro-TXB2 and 8-epi-prostaglandin (PG) F2 alpha respectively, in 62 consecutive patients (30 men, 32 women; mean age, 67 +/- 14 years) with acute ischemic stroke.
METHODS: At least two consecutive 6-hour urine samples were obtained during the first 72 hours after onset of symptoms. Urinary eicosanoids were measured by previously described radioimmunoassays.
RESULTS: Repeated periods of enhanced thromboxane biosynthesis were found in 52% of patients. Urinary 11-dehydro-TXB2 averaged 221 +/- 207 (mean +/- SD; n = 197; range, 13 to 967) pmol/mmol creatinine in 30 patients treated with cyclooxygenase inhibitors (mostly aspirin) at the time of study versus 392 +/- 392 (n = 186; range, 26 to 2533) in 32 untreated patients (P .05). The correlation between the two metabolites was moderate in both untreated patients (r = .41, P < .001) and patients with cyclooxygenase inhibitors (r = .31, P < .001). In a multiple regression analysis, increased thromboxane production was independently associated with severity of stroke on admission, atrial fibrillation, and treatment with cyclooxygenase-inhibiting drugs.
CONCLUSIONS: We conclude that during the first few days after an acute ischemic stroke (1) platelet activation occurs repeatedly in a cyclooxygenase-dependent fashion; (2) platelet activation is not associated with concurrent changes in isoprostane biosynthesis; (3) platelet activation is independently associated with stroke severity and atrial fibrillation; and (4) isoprostane biosynthesis is largely independent of platelet cyclooxygenase activity
NSAID Use Selectively Increases the Risk of Non-Fatal Myocardial Infarction: A Systematic Review of Randomised Trials and Observational Studies
Recent clinical trials and observational studies have reported increased coronary events associated with non steroidal anti-inflammatory drugs (NSAIDs). There appeared to be a disproportionate increase in non-fatal versus fatal events, however, numbers of fatal events in individual studies were too small, and event rates too low, to be meaningful.We undertook a pooled analysis to investigate the effect of NSAIDs on myocardial infarction (MI) risk with the specific aim to differentiate non-fatal from fatal events.We searched Pubmed (January, 1990 to March, 2010) for observational studies and randomised controlled trials that assessed the effect of NSAIDs (traditional or selective COX-2 inhibitors [coxibs]) on MI incidence separately for fatal and non-fatal events. Summary estimates of relative risk (RR) for non-fatal and fatal MIs were calculated with a random effects model.NSAID therapy carried a RR of 1.30 (95% CI, 1.20-1.41) for non-fatal MI with no effect on fatal MI (RR 1.02, 95% CI, 0.89-1.17) in six observational studies. Overall, the risk increase for non-fatal MI was 25% higher (95% CI, 11%-42%) than for fatal MI. The two studies that included only individuals with prior cardiovascular disease presented risk estimates for non-fatal MI on average 58% greater (95% CI, 26%-98%) than those for fatal MI. In nine randomised controlled trials, all investigating coxibs, the pooled RR estimate for non-fatal MI was 1.61 (95% CI, 1.04-2.50) and 0.86 (95% CI 0.51-1.47) for fatal MIs.NSAID use increases the risk of non-fatal MI with no substantial effect on fatal events. Such differential effects, with potentially distinct underlying pathology may provide insights into NSAID-induced coronary pathology. We studied the association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of myocardial infarction (MI), separating non-fatal from fatal events, summarizing the evidence from both observational studies and randomised controlled trials. An increased risk of non-fatal MI was clearly found in both types of studies while use of NSAID did not confer an increased risk of fatal MI. Our findings provide support for the concept that thrombi generated under NSAID treatment could be different from spontaneous thrombi
GIS based Integration and Analysis of multiple source Information for Non-Proliferation Studies
In recent years the volume and variety of information that needs to be analysed in the context of non-proliferation have been increasing continuously Therefore, an integrated, all-source information analysis is paramount for an efficient and effective monitoring of the Non-Proliferation Treaty (NPT). The ¿Treaty Monitoring¿ workpackage of the LIMES research project addressed this issue by developing an integrated platform supporting the non-proliferation image analyst in verifying treaty compliance. The main benefits of the platform are (i) integrating information from multiple sources and time-frames, including satellite imagery, site models, open source information, reports, etc; (ii) improved information management using a GIS-based platform and (iii) enhanced methodologies for satellite image analysis. The platform components facilitate the analysis by highlighting changes and anomalies, which are potentially safeguards-relevant and by providing quantitative measurements which are not readily available from the images. It improves the efficiency and effectiveness of the information assessment by providing all-source integration capabilities, which allow to easily access supporting collateral information (e.g. Open Source information) from an image analysis task, an vice versa. The paper presents the components of the integration platform and the results of the demonstration which monitored the construction of a nuclear reactor in Olkiluoto, Finland.JRC.E.9-Nuclear security (Ispra
Oxidative Stress and Platelet Activation in Homozygous Homocystinuria
Background
—
Severe hyperhomocysteinemia due to cystathionine β-synthase deficiency (CβSD) is associated with early atherothrombotic vascular disease. Homocysteine may exert its effects by promoting oxidative damage. In the present study, we investigated whether in vivo formation of 8-iso-prostaglandin (PG) F
2α
, a platelet-active product of arachidonic acid peroxidation, is enhanced in CβSD and whether it correlates with in vivo platelet activation, as reflected by thromboxane (TX) metabolite excretion.
Methods and Results
—
Urine and blood samples were obtained from patients with homozygous CβSD (n=13) and age-matched healthy subjects. Urinary 8-iso-PGF
2α
excretion was significantly higher in CβSD patients than in control subjects (640±384 versus 213±43 pg/mg creatinine;
P
=0.0015) and correlated with plasma homocysteine (ρ=0.398,
P
=0.0076). Similarly, urinary 11-dehydro-TXB
2
excretion was enhanced in CβSD (1166±415 versus 324±72 pg/mg creatinine;
P
=0.0015) and correlated with urinary 8-iso-PGF
2α
(ρ=0.362,
P
=0.0153). Vitamin E supplementation (600 mg/d for 2 weeks) was associated with a statistically significant increase in its plasma levels (from 16.6±4.6 to 40.4±8.7 μmol/L,
P
=0.0002) and with reductions in 8-iso-PGF
2α
(from 790±159 to 559±111 pg/mg creatinine,
P
=0.018) and 11-dehydro-TXB
2
(from 1273±383 to 913±336 pg/mg creatinine,
P
=0.028). A statistically significant inverse correlation was found between urinary 8-iso-PGF
2α
and plasma vitamin E levels (ρ=−0.745,
P
=0.0135).
Conclusions
—
The results of the present study suggest that enhanced peroxidation of arachidonic acid to form bioactive F
2
-isoprostanes may represent an important mechanism linking hyperhomocysteinemia and platelet activation in CβSD patients. Moreover, they provide a rationale for dose-finding studies of vitamin E supplementation in this setting
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