Fixed-dose combination therapy (polypill) for the prevention of cardiovascular disease.

CLINICAL QUESTION: Is fixed-dose combination therapy (polypill) that combines antiplatelet, blood pressure-lowering, and cholesterol-lowering medications into a single pill associated with improved cardiovascular disease (CVD) risk factors or reduced all-cause mortality or fatal and nonfatal CVD events? Is the polypill associated with an increase in adverse events? BOTTOM LINE: Polypills are associated with greater reductions in systolic blood pressure and total cholesterol compared with usual care, placebo, or active comparators, but also with a 19% higher risk of any adverse event. Due to limited power from available evidence, the association of polypills with all-cause mortality or fatal and nonfatal CVD events is uncertain

Estimation of Canadian manure and fertilizer nitrogen application rates for crops at the soil polygon level using the CANB v2.0 model

Non-Peer ReviewedIn response to national environmental and climate change modeling projects such as agri-environmental indicators, greenhouse gases, carbon sequestration and policy scenarios, fertilizer N and manure nitrogen N application rates were estimated for individual crops at the Soil Landscapes of Canada (SLC) polygon scale (1:1 million). This database provides an estimate of the actual amount of N applied per crop and per hectare, based on provincial fertilization recommendations, manure production levels of each type of livestock and reported amounts of fertilizer sold. The database is being incorporated into ongoing programs related to Kyoto accounting of greenhouse gas emissions, environmental performance and policy formulation at Agriculture and Agri-Food Canada. A standardized Canadian Agricultural Nitrogen Budget (CANB v2.0) model was developed to calculate the agri-environmental indicators Residual Soil Nitrogen (RSN) and Indicator of Risk of Water Contamination by Nitrogen (IROWC-N). CANB is a national-level model that operates on 3500 SLC polygons using generalized soil, landscape, climate, and Census of Agriculture socioeconomic data. It is designed to provide a regional update on the soil N balance for each of the census years of 1981, 1986, 1991, 1996, 2001 and into the future. The database and model have the capability to calculate a number of different components of the nutrient balance, including the inputs of fertilizer N, manure N, biological N and atmospheric N and N the removals of N in the harvested proportion of the crop and via nitrogenous gas emissions. This paper describes the procedures to estimate fertilizer N and manure N inputs for each crop within each polygon. It includes: (i) the compilation of soil-specific N application rates from provincial extension guidelines, (ii) the calculation of total manure N production from animal numbers and excretion rates, (iii) the calculation of available manure N after storage and handling losses, and (iv) the recommended and adjusted nitrogen application rates. Adjustments were made to account for the amount of inorganic N in the manure applied to the various crops. The adjusted nitrogen rate data was also reconciled with the provincial fertilizer sales data

Fixed-dose combination therapy for the prevention of cardiovascular disease.

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of fixed-dose combination therapy on optimising CVD risk factors and reducing CVD fatal and non-fatal events for both primary and secondary prevention of CVD. Details of CVD events and risk factors included are listed in the methods. We will also determine any adverse events associated with taking fixed-dose combination therapy. This will include studies conducted in both developed and developing regions of the world

Total Haskell is Reasonable Coq

We would like to use the Coq proof assistant to mechanically verify properties of Haskell programs. To that end, we present a tool, named hs-to-coq, that translates total Haskell programs into Coq programs via a shallow embedding. We apply our tool in three case studies -- a lawful Monad instance, "Hutton's razor", and an existing data structure library -- and prove their correctness. These examples show that this approach is viable: both that hs-to-coq applies to existing Haskell code, and that the output it produces is amenable to verification.Comment: 13 pages plus references. Published at CPP'18, In Proceedings of 7th ACM SIGPLAN International Conference on Certified Programs and Proofs (CPP'18). ACM, New York, NY, USA, 201

Evidence for trans-generational medication in nature

Ecology Letters (2010) 13: 1485–1493Parasites pose a serious threat to host fitness, and natural selection should favour host traits that reduce infection or disease symptoms. Here, we provide the first evidence of trans-generational medication, in which animals actively use medicine to mitigate disease in their offspring. We studied monarch butterflies and their virulent protozoan parasites, and found that neither caterpillars nor adult butterflies could cure themselves of disease. Instead, adult butterflies preferentially laid their eggs on toxic plants that reduced parasite growth and disease in their offspring caterpillars. It has often been suggested that sick animals may use medication to cure themselves of disease, but evidence for the use of medication in nature has so far been scarce. Our results provide evidence that infected animals may indeed use medicine as a defence against parasites, and that such medication may target an individual’s offspring rather than the individual itself.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79381/1/j.1461-0248.2010.01537.x.pd

Healthy Eating Index and Alternate Healthy Eating Index among Haitian Americans and African Americans with and without Type 2 Diabetes

Ethnicities within Black populations have not been distinguished in most nutrition studies. We sought to examine dietary differences between African Americans (AA) and Haitian Americans (HA) with and without type 2 diabetes using the Healthy Eating Index, 2005 (HEI-05), and the Alternate Healthy Eating Index (AHEI). The design was cross-sectional N = 471 (225 AA, 246 HA) and recruitment was by community outreach. The eating indices were calculated from data collected with the Harvard food-frequency questionnaire. African Americans had lower HEI-05 scores β = −10.9 (−8.67, 13.1); SE = 1.12, P < .001 than HA. Haitian American females and AA males had higher AHEI than AA females and HA males, respectively, (P = .006) adjusting for age and education. Participants with diabetes had higher adherence to the HEI-05 β = 3.90 (1.78, 6.01), SE = 1.08, P < .001 and lower adherence to the AHEI β = −9.73 (16.3, −3.19), SE = 3.33, P = .004, than participants without diabetes. The findings underscore the importance of disaggregating ethnicities and disease state when assessing diet

Relationship of Optimism and Suicidal Ideation in Three Groups of Patients at Varying Levels of Suicide Risk

Optimism has been associated with reduced suicidal ideation, but there have been few studies in patients at high suicide risk. We analyzed data from three study populations (total N=319) with elevated risk of suicide: (1) patients with a recent acute cardiovascular event, (2) patients hospitalized for heart disease who had depression or an anxiety disorder, and (3) patients psychiatrically hospitalized for suicidal ideation or following a suicide attempt. For each study we analyzed the association between optimism (measured by the Life-Orientation Test-Revised) and suicidal ideation, and then completed an exploratory random effects meta-analysis of the findings to synthesize this data. The meta-analysis of the three studies showed that higher levels of self-reported optimism were associated with a lower likelihood of suicidal ideation (odds ratio [OR]=.89, 95% confidence interval [CI]=.85-.95, z=3.94, pz=3.57, pz=3.61,

Calcium carbonate-calcium phosphate mixed cement compositions for bone reconstruction

The feasibility of making calcium carbonate-calcium phosphate (CaCO3-CaP) mixed cements, comprising at least 40 % (w/w) CaCO3 in the dry powder ingredients, has been demonstrated. Several original cement compositions were obtained by mixing metastable crystalline calcium carbonate phases with metastable amorphous or crystalline calcium phosphate powders in aqueous medium. The cements set within at most 1 hour at 37°C in atmosphere saturated with water. The hardened cement is microporous and exhibits weak compressive strength. The setting reaction appeared to be essentially related to the formation of a highly carbonated nanocrystalline apatite phase by reaction of the mestastable CaP phase with part or almost all of the metastable CaCO3 phase. The recrystallization of metastable CaP varieties led to a final cement consisting of a highly carbonated poorly crystalline apatite (PCA) analogous to bone mineral associated with various amounts of vaterite and/or aragonite. The presence of controlled amounts of CaCO3 with a higher solubility than the apatite formed in the well-developed calcium phosphate cements might be of interest to increase resorption rates in biomedical cement and favor its replacement by bone tissue. Cytotoxicity testing revealed excellent cytocompatibility of CaCO3-CaP mixed cement compositions

Physico-chemical and thermochemical studies of the hydrolytic conversion of amorphous tricalcium phosphate into apatite

The conversion of amorphous tricalcium phosphate with different hydration ratio into apatite in water at 25 °C has been studied by microcalorimetry and several physical–chemical methods. The hydrolytic transformation was dominated by two strong exothermic events. A fast, relatively weak, wetting process and a very slow but strong heat release assigned to a slow internal rehydration and the crystallization of the amorphous phase into an apatite. The exothermic phenomenon related to the rehydration exceeded the crystalline transformation enthalpy. Rehydration occurred before the conversion of the amorphous phase into apatite and determined the advancement of the hydrolytic reaction. The apatitic phases formed evolved slightly with time after their formation. The crystallinity increased whereas the amount of HPO4 2− ion decreased. These data allow a better understanding of the behavior of biomaterials involving amorphous phases such as hydroxyapatite plasma-sprayed coating

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide, yet ASCVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of ASCVD. OBJECTIVES: To determine the effect of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal ASCVD events, and adverse events. We also sought to determine the effect of fixed-dose combination therapy on blood pressure, lipids, adherence, discontinuation rates, health-related quality of life, and costs. SEARCH METHODS: We updated our previous searches in September 2016 of CENTRAL, MEDLINE, Embase, ISI Web of Science, and DARE, HTA, and HEED. We also searched two clinical trials registers in September 2016. We used no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure-lowering and one lipid-lowering component versus usual care, placebo, or an active drug comparator for any treatment duration in adults 18 years old or older, with no restrictions on presence or absence of pre-existing ASCVD. DATA COLLECTION AND ANALYSIS: Three review authors independently selected studies for inclusion and extracted the data for this update. We evaluated risk of bias using the Cochrane 'Risk of bias' assessment tool. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 ≥ 50%). We used the GRADE approach to evaluate the quality of evidence. MAIN RESULTS: In the initial review, we identified nine randomised controlled trials with a total of 7047 participants and four additional trials (n = 2012 participants; mean age range 62 to 63 years; 30% to 37% women) were included in this update. Eight of the 13 trials evaluated the effects of fixed-dose combination (FDC) therapy in populations without prevalent ASCVD, and the median follow-up ranged from six weeks to 23 months. More recent trials were generally larger with longer follow-up and lower risk of bias. The main risk of bias was related to lack of blinding of participants and personnel, which was inherent to the intervention. Compared with the comparator groups (placebo, usual care, or active drug comparator), the effects of the fixed-dose combination treatment on mortality (FDC = 1.0% versus control = 1.0%, RR 1.10, 95% CI 0.64 to 1.89,  I2 = 0%, 5 studies, N = 5300) and fatal and non-fatal ASCVD events (FDC = 4.7% versus control = 3.7%, RR 1.26, 95% CI 0.95 to 1.66, I2 = 0%, 6 studies, N = 4517) were uncertain (low-quality evidence). The low event rates for these outcomes and indirectness of evidence for comparing fixed-dose combination to usual care versus individual drugs suggest that these results should be viewed with caution. Adverse events were common in both the intervention (32%) and comparator (27%) groups, with participants randomised to fixed-dose combination therapy being 16% (RR 1.16, 95% CI 1.09 to 1.25, 11 studies, 6906 participants, moderate-quality evidence) more likely to report an adverse event . The mean differences in systolic blood pressure between the intervention and control arms was -6.34 mmHg (95% CI -9.03 to -3.64, 13 trials, 7638 participants, moderate-quality evidence). The mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.61 mmol/L (95% CI -0.88 to -0.35, 11 trials, 6565 participants, low-quality evidence) and -0.70 mmol/L (95% CI -0.98 to -0.41, 12 trials, 7153 participants, moderate-quality evidence), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 80% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multidrug strategy by 44% (26% to 65%) compared with usual care (4 trials, 3835 participants, moderate-quality evidence). AUTHORS' CONCLUSIONS: The effects of fixed-dose combination therapy on all-cause mortality or ASCVD events are uncertain. A limited number of trials reported these outcomes, and the included trials were primarily designed to observe changes in ASCVD risk factor levels rather than clinical events, which may partially explain the observed differences in risk factors that were not translated into differences in clinical outcomes among the included trials. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, active comparator, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing, longer-term trials of fixed-dose combination therapy will help demonstrate whether short-term changes in risk factors might be maintained and lead to expected differences in clinical events based on these changes