Ruminants, particularly dairy and beef cattle, contribute to climate change through mostly enteric methane emissions. Several mitigating options have been proposed, including the feed additive ...3-nitrooxypropanol (3-NOP). The objectives of this study were to explain the variability in the mitigating effect of 3-NOP and to investigate the interaction between diet composition and 3-NOP dose, using meta-analytical approaches. Data from 13 articles (14 experiments) met the selection criteria for inclusion in the meta-analysis, and 48 treatment means were used for the analysis. Mean differences were calculated as 3-NOP treatment mean minus control treatment mean and then expressed as a percentage of the control mean. Three types of models were developed: (1) one including 3-NOP dose, overall mean, and individual covariate; (2) a combination of neutral detergent fiber (NDF), 3-NOP dose, and overall mean; and (3) one selected model from all combinations of up to 5 covariates, which were compared using a leave-one-out cross validation method. Models including only 3-NOP dose resulted in a significant reduction of 32.7%, 30.9%, and 32.6% for CH4 production (g/d), yield (g/kg dry matter intake), and intensity (g/kg energy-corrected milk), respectively, at an average 3-NOP dose of 70.5 mg/kg dry matter (DM). The greater the NDF content in the diet, the lower the reduction efficiency for a given 3-NOP dose. For 10 g/kg DM increase in NDF content from its mean (329 g of NDF/kg of DM) the 3-NOP effect on CH4 production was impaired by 0.633%, the 3-NOP effect on CH4 yield by 0.647%, and the 3-NOP effect on CH4 intensity by 0.723%. The analysis based on leave-one-out cross validation showed an increase in NDF and crude fat content reduces efficacy of 3-NOP and an increase in 3-NOP dose increases efficacy. A 1% (10 g/kg) DM decrease in dietary NDF content from its mean may increase the efficacy of 3-NOP in reducing CH4 production by 0.915%. A 1% (10 g/kg DM) decrease in dietary crude fat content from its mean enhances the efficacy of 3-NOP on CH4 production by 3.080% at a given dose and NDF level. For CH4 yield, next to 3-NOP dose, dietary NDF content and dietary crude fat content were included in the selected model, but also dietary starch content with an opposite direction to NDF and crude fat. The effect of 3-NOP dose on CH4 intensity was similar to its effect on CH4 production, whereas the effect of dietary NDF content was slightly lower. Expanding the previously published models with the newly available data published from trials since then improved model performance, hence demonstrating the value of regularly updating meta-analyses if a wider range of data becomes available.
An Algal Oil Containing EPA and DHA (AOCED) at ~50% was developed as a sustainable source of omega-3 fatty acids. AOCED was incorporated into extruded dry foods for dogs at 0, 0.75%, 1.5% and 3.0% ...levels (equivalent to 0, 7.5, 15 and 30 g/kg diet) on dry matter basis at the expense of chicken fat and fed to healthy female Beagle dogs starting at mating and throughout gestation and lactation. The offspring were fed their maternal corresponding diets for 26 weeks after weaning. AOCED-enriched diets were well tolerated by dogs in both generations and did not affect their overall health, physiological parameters, food consumption, body weights and body weight gains. There were no changes in hematology, clinical chemistry, and coagulation parameters in both generations of dogs fed the AOCED diets when compared to those in the control group. Plasma levels of DHA and EPA increased significantly and generally dose-dependently in both generations. The study demonstrated the safety of AOCED in dogs during gestation, lactation, and growth periods at dietary levels up to 3.0wt%, equivalent to 30 g/kg diet. AOCED's bioavailability as a source of DHA and EPA in dogs was demonstrated by the increased plasma concentrations of these nutritional lipids.
This study examined the value of endothelial shear stress (ESS) estimated in 3-dimensional quantitative coronary angiography (3D-QCA) models in detecting plaques that are likely to progress and cause ...events.
Cumulative evidence has shown that plaque characteristics and ESS derived from intravascular ultrasound (IVUS)−based reconstructions enable prediction of lesions that will cause cardiovascular events. However, the prognostic value of ESS estimated by 3D-QCA in nonflow limiting lesions is yet unclear.
This study analyzed baseline virtual histology (VH)-IVUS and angiographic data from 28 lipid-rich lesions (i.e., fibroatheromas) that caused major adverse cardiovascular events or required revascularization (MACE-R) at 5-year follow-up and 119 lipid-rich plaques from a control group that remained quiescent. The segments studied by VH-IVUS at baseline were reconstructed using 3D-QCA software. In the obtained geometries, blood flow simulation was performed, and the pressure gradient across the lipid-rich plaque and the mean ESS values in 3-mm segments were estimated. The additive value of these hemodynamic indexes in predicting MACE-R beyond plaque characteristics was examined.
MACE-R lesions were longer, had smaller minimum lumen area, increased plaque burden (PB), were exposed to higher ESS, and exhibited a higher pressure gradient. In multivariable analysis, PB (hazard ratio: 1.08; p = 0.004) and the maximum 3-mm ESS value (hazard ratio: 1.11; p = 0.001) were independent predictors of MACE-R. Lesions exposed to high ESS (>4.95 Pa) with a high-risk anatomy (minimal lumen area <4 mm2 and PB >70%) had a higher MACE-R rate (53.8%) than those with a low-risk anatomy exposed to high ESS (31.6%) or those exposed to low ESS who had high- (20.0%) or low-risk anatomy (7.1%; p < 0.001).
In the present study, 3D-QCA-derived local hemodynamic variables provided useful prognostic information, and, in combination with lesion anatomy, enabled more accurate identification of MACE-R lesions.
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This study sought to validate European Society of Cardiology guideline-endorsed high-risk features of stent-related recurrent ischemic events for the prediction of ischemic and bleeding outcomes ...including a stratification according to the PRECISE-DAPT score estimated bleeding risk.
The 2017 European Society of Cardiology–focused update on dual-antiplatelet therapy endorsed high-risk features of stent-related recurrent ischemic events. Because patients with high ischemic risk also have an increased bleeding risk, appropriate risk stratification for ischemic and bleeding events is crucial.
Between January 2009 and December 2015, a total of 10,236 consecutive patients undergoing clinically indicated percutaneous coronary intervention were prospectively included in the Bern PCI Registry. Guideline-endorsed high-risk features were retrospectively assessed. The primary ischemic endpoint was device-oriented composite endpoint (DOCE) (cardiac death, target-vessel myocardial infarction, and target lesion revascularization) at 1 year, and the primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) 3–5 at 1 year.
A total of 5,323 (52.0%) patients had at least 1 high-risk feature. Among patients with high-risk features, DOCE (12.3% vs. 5.5%; p < 0.001) and BARC 3–5 bleeding (4.9% vs. 2.2%; p < 0.001) occurred more frequently compared with those without. There was a graded risk increase for DOCE (0: 5.5%; 1 to 2: 11.3%; and ≥3: 16.7%; p < 0.001) and BARC 3–5 bleeding (0: 2.2%; 1 to 2: 4.5%; and ≥3: 6.6%; p < 0.001) as the number of high-risk features increased. High-PRECISE-DAPT score (≥25) was associated with an increased risk of DOCE and BARC 3–5 bleeding, irrespective of number of high-risk features.
The European Society of Cardiology guideline-endorsed high-risk features were associated with increased ischemic and bleeding risks following percutaneous coronary intervention in routine clinical practice. (CARDIOBASE Bern PCI Registry; NCT02241291)
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The Non-adherence Academic Research Consortium (NARC) has recently developed a consensus-based standardized classification for medication non-adherence in cardiovascular clinical trials. We aimed to ...assess the prevalence of NARC-defined self-reported non-adherence to P2Y12 inhibitors and its impact on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI).
Using a standardized questionnaire administered at 1 year after PCI, we assessed the 4 NARC-defined non-adherence levels including type, decision-maker, reasons, and timing within the Bern PCI registry. The primary endpoint was the patient-oriented composite endpoint (POCE) defined as a composite of death, myocardial infarction, stroke, and any revascularization at 1 year. The recommended P2Y12 inhibitor duration was 12 months. Among 3,896 patients, P2Y12 inhibitor non-adherence was observed in 647 (17%) patients. Discontinuation was permanent in the majority of patients (84%). The decision was mainly driven by a physician (94%), and rarely by patients (6%). The most frequent reason was risk profile change (43%), followed by unlisted reasons (25%), surgery (17%), and adverse events (14%). Non-adherence occurred early (<30 days) in 21%, late (30-180 days) in 45%, and very late (>180 days) in 33%. The majority of POCE events (n = 421/502, 84%) occurred during adherence to the prescribed P2Y12 inhibitor. Permanent discontinuation, doctor-driven non-adherence, and risk profile change emerged as independent predictors for POCE.
In real-world PCI population treated with 1-year DAPT, non-adherence was observed in nearly one-fifth of patients. Non-adherence to P2Y12 inhibitors was associated with worse clinical outcomes, while the risk was related to underlying contexts.
NCT02241291.
Leishmaniasis is endemic in 98 countries with an estimated 350 million people at risk and approximately 2 million cases annually. Brazil is one of the most severely affected countries.
We applied ...Bayesian geostatistical negative binomial models to analyze reported incidence data of cutaneous and visceral leishmaniasis in Brazil covering a 10-year period (2001-2010). Particular emphasis was placed on spatial and temporal patterns. The models were fitted using integrated nested Laplace approximations to perform fast approximate Bayesian inference. Bayesian variable selection was employed to determine the most important climatic, environmental, and socioeconomic predictors of cutaneous and visceral leishmaniasis.
For both types of leishmaniasis, precipitation and socioeconomic proxies were identified as important risk factors. The predicted number of cases in 2010 were 30,189 (standard deviation SD: 7,676) for cutaneous leishmaniasis and 4,889 (SD: 288) for visceral leishmaniasis. Our risk maps predicted the highest numbers of infected people in the states of Minas Gerais and Pará for visceral and cutaneous leishmaniasis, respectively.
Our spatially explicit, high-resolution incidence maps identified priority areas where leishmaniasis control efforts should be targeted with the ultimate goal to reduce disease incidence.
The purpose of this study was to evaluate ischemic and bleeding outcomes of unselected cancer patients undergoing percutaneous coronary intervention (PCI).
The number of cancer patients undergoing ...PCI is increasing despite concerns regarding ischemic and bleeding risks.
Between 2009 and 2017, consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Cancer-specific data including type, date of initial diagnosis, and health status at index PCI were collected. We performed propensity score matching to adjust for baseline differences between patients with and without cancer. The primary ischemic endpoint was the device-oriented composite endpoint (cardiac death, target vessel myocardial infarction, target lesion revascularization) at 1 year, and the primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) 2 to 5 at 1 year.
Among 13,647 patients, 1,368 (10.0%) had an established diagnosis of cancer. The 3 leading cancer types were prostate (n = 294), gastrointestinal tract (n = 188), and hematopoietic (n = 177). At index PCI, 179 (13.1%) patients were receiving active cancer treatment. In matched analysis, there was no significant difference in device-oriented composite endpoint (11.5% vs. 10.2%; p = 0.251), whereas cardiac death and BARC 2 to 5 bleeding occurred more frequently among patients with cancer compared with those without cancer (6.8% vs. 4.5%; p = 0.010 and 8.0% vs. 6.0%; p = 0.026, respectively). Cancer diagnosis within 1 year before PCI emerged as an independent predictor for cardiac death and BARC 2 to 5 bleeding at 1 year.
Cancer patients carry an increased risk of cardiac mortality that was not associated with stent-related ischemic events among patients undergoing PCI in routine clinical practice. Higher risk of bleeding in cancer patients undergoing PCI deserves particular attention. (CARDIOBASE Bern PCI Registry; NCT02241291)
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