Potential implications of coronary artery calcium testing for guiding aspirin use among asymptomatic individuals with diabetes.

ObjectiveIt is unclear whether coronary artery calcium (CAC) is effective for risk stratifying patients with diabetes in whom treatment decisions are uncertain.Research design and methodsOf 44,052 asymptomatic individuals referred for CAC testing, we studied 2,384 individuals with diabetes. Subjects were followed for a mean of 5.6 ± 2.6 years for the end point of all-cause mortality.ResultsThere were 162 deaths (6.8%) in the population. CAC was a strong predictor of mortality across age-groups (age <50, 50-59, ≥60), sex, and risk factor burden (0 vs. ≥1 additional risk factor). In individuals without a clear indication for aspirin per current guidelines, CAC stratified risk, identifying patients above and below the 10% risk threshold of presumed aspirin benefit.ConclusionsCAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention

Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and Multivessel Disease

BACKGROUND: The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain.   OBJECTIVES: CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only.   METHODS: After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months.   RESULTS: Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups.   CONCLUSIONS: In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival. (Complete Versus Lesion-only Primary PCI Pilot Study [CvLPRIT]; ISRCTN70913605)

Association Between Modifiable Risk Factors and Pharmaceutical Expenditures Among Adults With Atherosclerotic Cardiovascular Disease in the United States: 2012–2013 Medical Expenditures Panel Survey

Background Atherosclerotic cardiovascular disease (ASCVD) causes most deaths in the United States and accounts for the highest healthcare spending. The association between the modifiable risk factors (MRFs) of ASCVD and pharmaceutical expenditures are largely unknown. Methods and Results We examined the association between MRFs and pharmaceutical expenditures among adults with ASCVD using the 2012 and 2013 Medical Expenditure Panel Survey. A 2‐part model was used while accounting for the survey\u27s complex design to obtain nationally representative results. All costs were adjusted to 2013 US dollars using the gross domestic product deflator. The annual total pharmaceutical expenditure among those with ASCVD was $71.6 billion, 33$519 [95% confidence interval (CI), $12–918; P=0.011]), dyslipidemia ($631 [95% CI, $168–1094; P=0.008]), hypertension: ($1078 [95% CI, $697–1460; P\u3c0.001)], and diabetes mellitus ($2006 [95% CI, $1470–2542]). Compared with those with optimal MRFs (0–1), those with average MRFs (2–3) spent an average of$1184 (95% CI, $805–1564; P\u3c0.001) more on medications, and those with poor MRFs (≥4) spent$2823 (95% CI, $2338–3307; P\u3c0.001) more. Conclusions Worsening MRFs were proportionally associated with higher annual pharmaceutical expenditures among patients with established ASCVD regardless of non‐ASCVD comorbidity. In‐depth studies of the roles played by other factors in this association can help reduce medication‐related expenditures among ASCVD patients

Economic Impact of Moderate‐Vigorous Physical Activity Among Those With and Without Established Cardiovascular Disease: 2012 Medical Expenditure Panel Survey

Background Physical activity (PA) has an established favorable impact on cardiovascular disease (CVD) outcomes and quality of life. In this study, we aimed to estimate the economic effect of moderate‐vigorous PA on medical expenditures and utilization from a nationally representative cohort with and without CVD. Methods and Results The 2012 Medical Expenditure Panel Survey data were analyzed. Our study population was limited to noninstitutionalized US adults ≥18 years of age. Variables of interest included CVD (coronary artery disease, stroke, heart failure, dysrhythmias, or peripheral artery disease) and cardiovascular modifiable risk factors (CRFs; hypertension, diabetes mellitus, hypercholesterolemia, smoking, and/or obesity). Two‐part econometric models were utilized to study cost data; a generalized linear model with gamma distribution and link log was used to assess expenditures per capita. The final study sample included 26 239 surveyed individuals. Overall, 47% engaged in moderate‐vigorous PA ≥30 minutes, ≥5 days/week, translating to 111.5 million adults in the United States stratifying by CVD status; 32% reported moderate‐vigorous PA among those with CVD versus 49% without CVD. Generally, participants reporting moderate‐vigorous PA incurred significantly lower health care expenditures and resource utilization, displaying a step‐wise lower total annual health care expenditure as moving from CVD to non‐CVD (and each CRF category). Conclusions Moderate‐vigorous PA ≥30 minutes, ≥5 days/week is associated with significantly lower health care spending and resource utilization among individuals with and without established CVD

Cigarette smoking worsens systemic inflammation in persons with metabolic syndrome

Background Emerging data suggests that the combination of smoking and metabolic syndrome (MetS) markedly increases cardiovascular disease risk well beyond that of either condition. In this study we assess if this interaction can be explained by an additive increase in the risk of systemic inflammation by MetS and cigarette smoking. Methods We evaluated 5,503 healthy non-diabetic Brazilian subjects (mean age of 43 ± 10 years, 79% males). Participants were divided into sub-groups of smokers and non-smokers with or without MetS. High-sensitivity C reactive protein (hs-CRP) was measured to assess degree of underlying inflammation. Results Overall (19%) had hs-CRP \u3e 3 mg/L. In adjusted regression analyses, compared to non-smokers, there was a 0.19 mg/L (95% CI: 0.05, 0.32) increase in hs-CRP among smokers in the entire population and 0.63 mg/L (95% CI: 0.26, 1.01) increase among smokers with MetS while there was no significant increase among smokers without MetS (β = 0.09 95% CI: -0.05, 0.24). In a fully adjusted logistic regression model, smokers compared to non-smokers were 55% more likely to have elevated hs-CRP in the entire population (OR 1.55, 95% CI: 1.25, 1.92) and more than twice as likely to have elevated hs-CRP if they had MetS ( OR 2.05, 95% CI: 1.40, 3.01) while the risk was non-significant among those without MetS (OR = 1.29, 95% CI: 0.98, 1.69). Conclusion The study demonstrates an additive effect of cigarette smoking on the risk of systemic inflammation in MetS thus highlighting the need for determining smoking status among those with MetS and aggressively targeting smoking cessation in this population

Computational infrared and Raman spectra by hybrid QM/MM techniques: a study on molecular and catalytic material systems

Vibrational spectroscopy is one of the most well-established and important techniques for characterizing chemical systems. To aid the interpretation of experimental infrared and Raman spectra, we report on recent theoretical developments in the ChemShell computational chemistry environment for modelling vibrational signatures. The hybrid quantum mechanical and molecular mechanical approach is employed, using density functional theory for the electronic structure calculations and classical forcefields for the environment. Computational vibrational intensities at chemical active sites are reported using electrostatic and fully polarizable embedding environments to achieve more realistic vibrational signatures for materials and molecular systems, including solvated molecules, proteins, zeolites and metal oxide surfaces, providing useful insight into the effect of the chemical environment on the signatures obtained from experiment. This work has been enabled by the efficient task-farming parallelism implemented in ChemShell for high-performance computing platforms.  This article is part of a discussion meeting issue 'Supercomputing simulations of advanced materials'

Multiscale QM/MM modelling of catalytic systems with ChemShell

Hybrid quantum mechanical/molecular mechanical (QM/MM) methods are a powerful computational tool for the investigation of all forms of catalysis, as they allow for an accurate description of reactions occurring at catalytic sites in the context of a complicated electrostatic environment. The scriptable computational chemistry environment ChemShell is a leading software package for QM/MM calculations, providing a flexible, high performance framework for modelling both biomolecular and materials catalysis. We present an overview of recent applications of ChemShell to problems in catalysis and review new functionality introduced into the redeveloped Python-based version of ChemShell to support catalytic modelling. These include a fully guided workflow for biomolecular QM/MM modelling, starting from an experimental structure, a periodic QM/MM embedding scheme to support modelling of metallic materials, and a comprehensive set of tutorials for biomolecular and materials modelling

CMIP and ATP2C2 Modulate Phonological Short-Term Memory in Language Impairment

Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 × 10−7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 × 10−5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition

Computational infrared and Raman spectra by hybrid QM/MM techniques: a study on molecular and catalytic material systems

Vibrational spectroscopy is one of the most well-established and important techniques for characterizing chemical systems. To aid the interpretation of experimental infrared and Raman spectra, we report on recent theoretical developments in the ChemShell computational chemistry environment for modelling vibrational signatures. The hybrid quantum mechanical and molecular mechanical approach is employed, using density functional theory for the electronic structure calculations and classical forcefields for the environment. Computational vibrational intensities at chemical active sites are reported using electrostatic and fully polarizable embedding environments to achieve more realistic vibrational signatures for materials and molecular systems, including solvated molecules, proteins, zeolites and metal oxide surfaces, providing useful insight into the effect of the chemical environment on the signatures obtained from experiment. This work has been enabled by the efficient task-farming parallelism implemented in ChemShell for high-performance computing platforms. This article is part of a discussion meeting issue ‘Supercomputing simulations of advanced materials’

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London