bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statin treatment and risk of recurrent venous thromboembolism: a nationwide cohort study
Authors: Nguyen Cu Dinh , Andersson Charlotte , Jensen Thomas Bo , Gjesing Anne , Schjerning Olsen Anne-Marie , Malta Hansen Carolina , Büller Harry , Torp-Pedersen Christian , Gislason Gunnar H 
Published: November 2013

ObjectivesStatins may decrease the risk of primary venous thromboembolism (VTE), that is, deep vein thrombosis (DVT) and pulmonary embolism (PE) but the effect of statins in preventing recurrent VTE is less clear. The aim of this study was therefore to investigate the association between statin therapy and risk of recurrent VTE.DesignA prospective cohort study.SettingAll hospitals in Denmark.ParticipantsAll patients with a hospital diagnosis of VTE in Denmark during 1997–2009 associated with a warfarin or heparin prescription were identified.Main outcome measuresAdjusted HR of recurrent hospitalised VTE (ie, fatal or non-fatal DVT or PE) associated with use of statins.Results44 330 patients with VTE were included in the study. Of these 3914 were receiving statin therapy at baseline. Patients receiving statins were older (68±11 compared to 62±18 years), had more comorbidity and used more medications. The incidence rate for recurrent VTE was 24.4 (95% CI 22.8 to 26.2) per 1000 person-years among statin users and 48.5 (95% CI 47.4 to 49.7) per 1000 person-years among non-statin users. Statin use was associated with a significantly lower risk of a recurrent VTE, adjusted HR 0.74 (95% CI 0.68 to 0.80), compared with no statin use. The association between statin use and risk of recurrent VTE was significantly affected by age. Among younger individuals (≤80 years), statin use was associated with lower risk of recurrent VTE, HR 0.70 (95% CI 0.65 to 0.76) whereas in older individuals (>80 years) statin use was significantly associated with higher risk of recurrent VTE, HR 1.28 (95% CI 1.02 to 1.60), p for interaction=<0.0001.ConclusionsStatin use was associated with a decreased risk of recurrent VTE.
Effectiveness and uptake of screening programmes for coronary heart disease and diabetes: a realist review of design components used in interventions
Authors: Holland Carol , Cooper Yvonne , Shaw Rachel , Pattison Helen , Cooke Richard 
Published: November 2013

ObjectiveTo evaluate behavioural components and strategies associated with increased uptake and effectiveness of screening for coronary heart disease and diabetes with an implementation science focus.DesignRealist review.Data sourcesPubMed, Web of Knowledge, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register and reference chaining. Searches limited to English language studies published since 1990.Eligibility criteriaEligible studies evaluated interventions designed to increase the uptake of cardiovascular disease (CVD) and diabetes screening and examined behavioural and/or strategic designs. Studies were excluded if they evaluated changes in risk factors or cost-effectiveness only.ResultsIn 12 eligible studies, several different intervention designs and evidence-based strategies were evaluated. Salient themes were effects of feedback on behaviour change or benefits of health dialogues over simple feedback. Studies provide mixed evidence about the benefits of these intervention constituents, which are suggested to be situation and design specific, broadly supporting their use, but highlighting concerns about the fidelity of intervention delivery, raising implementation science issues. Three studies examined the effects of informed choice or loss versus gain frame invitations, finding no effect on screening uptake but highlighting opportunistic screening as being more successful for recruiting higher CVD and diabetes risk patients than an invitation letter, with no differences in outcomes once recruited. Two studies examined differences between attenders and non-attenders, finding higher risk factors among non-attenders and higher diagnosed CVD and diabetes among those who later dropped out of longitudinal studies.ConclusionsIf the risk and prevalence of these diseases are to be reduced, interventions must take into account what we know about effective health behaviour change mechanisms, monitor delivery by trained professionals and examine the possibility of tailoring programmes according to contexts such as risk level to reach those most in need. Further research is needed to determine the best strategies for lifelong approaches to screening.
The economic burden of visual impairment and blindness: a systematic review
Authors: Köberlein Juliane , Beifus Karolina , Schaffert Corinna , Finger Robert P 
Published: November 2013

ObjectivesVisual impairment and blindness (VI&B) cause a considerable and increasing economic burden in all high-income countries due to population ageing. Thus, we conducted a review of the literature to better understand all relevant costs associated with VI&B and to develop a multiperspective overview.DesignSystematic review: Two independent reviewers searched the relevant literature and assessed the studies for inclusion and exclusion criteria as well as quality.Eligibility criteria for included studiesInterventional, non-interventional and cost of illness studies, conducted prior to May 2012, investigating direct and indirect costs as well as intangible effects related to visual impairment and blindness were included.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement approach to identify the relevant studies. A meta-analysis was not performed due to the variability of the reported cost categories and varying definition of visual impairment.ResultsA total of 22 studies were included. Hospitalisation and use of medical services around diagnosis and treatment at the onset of VI&B were the largest contributor to direct medical costs. The mean annual expenses per patient were found to be US$ purchasing power parities (PPP) 12 175–14 029 for moderate visual impairment, US$ PPP 13 154–16 321 for severe visual impairment and US$ PPP 14 882–24 180 for blindness, almost twofold the costs for non-blind patients. Informal care was the major contributor to other direct costs, with the time spent by caregivers increasing from 5.8 h/week (or US$ PPP 263) for persons with vision >20/32 up to 94.1 h/week (or US$ PPP 55 062) for persons with vision ≤20/250. VI&B caused considerable indirect costs due to productivity losses, premature mortality and dead-weight losses.ConclusionsVI&B cause a considerable economic burden for affected persons, their caregivers and society at large, which increases with the degree of visual impairment. This review provides insight into the distribution of costs and the economic impact of VI&B.
Impact of faecal haemoglobin concentration on colorectal cancer mortality and all-cause death
Authors: Chen Li-Sheng , Yen Amy Ming-Fang , Fraser Callum G , Chiu Sherry Yueh-Hsia , Fann Jean Ching-Yuan , Wang Po-En , Lin Sheng-Che , Liao Chao-Sheng , Lee Yi-Chia , Chiu Han-Mo , Chen Hsiu-Hsi 
Published: November 2013

ObjectiveTo assess the effect of an incremental increase in faecal haemoglobin (f-Hb) concentration on colorectal cancer (CRC) mortality and all-cause death.DesignWe conducted an observational study of cohorts over time based on two population-based CRC screening programmes.SettingTwo cities of Taiwan.Participants1233 individuals with CRC (217 prevalent cases and 1016 incident cases) and 2640 with colorectal adenoma (1246 prevalent cases and 1394 incident cases) found in the two cohorts of 59 767 and 125 976 apparently healthy individuals, aged 40 years and above, who had been invited to participate in screening since 2001 and 2003, respectively.Main outcome measuresDeath from CRC and all-cause death ascertained by following up from the entire two cohorts over time until 2009.ResultsThe effect of an incremental increase in f-Hb on the risk for CRC mortality was noted, increasing from a slightly increased risk for the category of f-Hb of 20–49 ng Hb/mL (adjusted HR (aHR)=1.09; 95% CI 0.68 to 1.75) to 11.67 (95% CI 7.71 to 17.66) for the group with f-Hb≥450 ng Hb/mL as compared with the group considered baseline with f-Hb of 1–19 ng Hb/mL (p<0.001). A similar but less marked increasing trend was found for all-cause mortality, aHR increasing from 1.15 (95% CI 1.07 to 1.24) for the group with f-Hb of 20–49 ng Hb/mL to 1.67 (95% CI 1.54 to 2.07) for the group with f-Hb≥450 ng Hb/mL.ConclusionsWe substantiated the impacts of an incremental increase in f-Hb on the risk for death from CRC and all-cause death, consistently showing a significant gradient relationship. Both discoveries suggest that f-Hb may not only make contribution to facilitating individually tailored screening for CRC but also can be used as a significant predictor for life expectancy.
A degenerating PDE system for phase transitions and damage
Authors: Rocca Elisabetta , Rossi Riccarda 
Published: November 2013

In this paper, we analyze a PDE system arising in the modeling of phase transition and damage phenomena in thermoviscoelastic materials. The resulting evolution equations in the unknowns ϑ (absolute temperature), u (displacement), and χ (phase/damage parameter) are strongly nonlinearly coupled. Moreover, the momentum equation for u contains χ-dependent elliptic operators, which degenerate at the pure phases (corresponding to the values χ = 0 and χ = 1), making the whole system degenerate. That is why, we have to resort to a suitable weak solvability notion for the analysis of the problem: it consists of the weak formulations of the heat and momentum equation, and, for the phase/damage parameter χ, of a generalization of the principle of virtual powers, partially mutuated from the theory of rate-independent damage processes. To prove an existence result for this weak formulation, an approximating problem is introduced, where the elliptic degeneracy of the displacement equation is ruled out: in the framework of damage models, this corresponds to allowing for partial damage only. For such an approximate system, global-in-time existence and well-posedness results are established in various cases. Then, the passage to the limit to the degenerate system is performed via suitable variational techniques.
Plasma S100A8/A9 Correlates With Blood Neutrophil Counts, Traditional Risk Factors, and Cardiovascular Disease in Middle-Aged Healthy Individuals
Authors: Cotoi Ovidiu S. , Dunér Pontus , Ko Nayoung , Hedblad Bo , Nilsson Jan , Björkbacka Harry , Schiopu Alexandru 
Published: November 2013

Objective—
The S100 alarmins A8, A9, and A8/A9, secreted by activated neutrophils and monocytes/macrophages, are involved in the pathogenesis of various inflammatory diseases. S100A8/A9 has previously been linked to atherogenesis and cardiovascular (CV) disease. We investigated whether S100A8, A9, and A8/A9 correlate with carotid artery disease and CV risk in apparently healthy individuals.

Approach and Results—
We measured baseline S100A8, A9, and A8/A9 in 664 individuals aged 63 to 68 years, with no previous history of CV disease, randomly selected from the Malmö Diet and Cancer population cohort. We examined the correlations between S100 proteins and circulating cell populations, plasma cytokines, carotid artery disease, and incidence of CV events during a median follow-up period of 16.2 years. We found that plasma S100A8/A9 concentration is positively influenced by circulating neutrophil numbers, smoking, body mass index, glycosylated hemoglobin A1c, and low-density lipoprotein. High-density lipoprotein was negatively associated with S100A8/A9. S100A8/A9 and the neutrophil counts were positively correlated with intima-media area in the common carotid artery, independently of age, sex, and CV risk factors. S100A8/A9 and circulating neutrophils presented similar associations with the incidence of coronary events (hazard ratio [95% confidence interval] per 1 SD: 1.28 [1.03–1.59] and 1.26 [1.04–1.53], respectively) and CV death (1.34 [1.06–1.71] and 1.59 [1.33–1.90], respectively). These relationships were mainly supported by strong associations in women, which were independent of traditional risk factors. There were no independent relationships between S100A8 and S100A9, and CV disease.

Conclusions—
Our study supports the value of S100A8/A9 as a potentially important link between neutrophils, traditional CV risk factors, and CV disease.
Importance of Evaluating Cell Cholesterol Influx With Efflux in Determining the Impact of Human Serum on Cholesterol Metabolism and Atherosclerosis
Authors: Weibel Ginny L. , Drazul-Schrader Denise , Shivers Debra K. , Wade Alisha N. , Rothblat George H. , Reilly Muredach P. , de la Llera-Moya Margarita 
Published: November 2013

Objective—
Cholesterol efflux relates to cardiovascular disease but cannot predict cellular cholesterol mass changes. We asked whether influx and net flux assays provide additional insights.

Approach and Results—

Adapt a bidirectional flux assay to cells where efflux has clinical correlates and examine the association of influx, efflux, and net flux to serum triglycerides (TGs). Apolipoprotein B–depleted (high-density lipoprotein-fraction) serum from individuals with unfavorable lipids (median [interquartile range]; high-density lipoprotein-cholesterol=39 [32–42], low-density lipoprotein-cholesterol=109 [97–137], TGs=258 [184–335] mg/dL; n=13) promoted greater ATP-binding cassette transporter A1–mediated [1,2-
3H
] cholesterol efflux (3.8±0.3%/4 hour versus 1.2±0.4%/4 hour;
P
<0.0001) from cyclic 3’,5’-amp(CTP-amp)-treated J774 macrophages than from individuals with favorable lipids (high-density lipoprotein-cholesterol=72 [58–88], low-density lipoprotein-cholesterol=111 [97–131], TGs=65 [56–69] mg/dL; n=10). Thus, high TGs associated with more ATP-binding cassette transporter A1 acceptors. Efflux of cholesterol mass (μg free cholesterol/mg cell protein per 8 hour) to serum was also higher (7.06±0.33 versus 5.83±0.48;
P
=0.04). However, whole sera from individuals with unfavorable lipids promoted more influx (5.14±0.65 versus 2.48±0.85;
P
=0.02) and lower net release of cholesterol mass (1.93±0.46 versus 3.36±0.47;
P
=0.04). The pattern differed when mass flux was measured using apolipoprotein B–depleted serum rather than serum. Although individuals with favorable lipids tended to have greater influx than those with unfavorable lipids, efflux to apolipoprotein B–depleted serum was markedly higher (6.81±0.04 versus 2.62±0.14;
P
<0.0001), resulting in an efflux:influx ratio of ≈3-fold. Thus both serum and apolipoprotein B–depleted serum from individuals with favorable lipids promoted greater net cholesterol mass release despite increased ATP-binding cassette transporter A1–mediated efflux in samples of individuals with high TGs/unfavorable lipids.

Conclusions—
When considering the efficiency of serum specimens to modulate cell cholesterol content, both influx and efflux need to be measured.
Clinical-Grade Human Neural Stem Cells Promote Reparative Neovascularization in Mouse Models of Hindlimb Ischemia
Authors: Katare Rajesh , Stroemer Paul , Hicks Caroline , Stevanato Lara , Patel Sara , Corteling Randolph , Miljan Erik , Vishnubhatla Indira , Sinden John , Madeddu Paolo 
Published: November 2013

Objective—
CTX0E03 (CTX) is a clinical-grade human neural stem cell (hNSC) line that promotes angiogenesis and neurogenesis in a preclinical model of stroke and is now under clinical development for stroke disability. We evaluated the therapeutic activity of intramuscular CTX hNSC implantation in murine models of hindlimb ischemia for potential translation to clinical studies in critical limb ischemia.

Approach and Results—

Immunodeficient (CD-1 Fox
nu/nu
) mice acutely treated with hNSCs had overall significantly increased rates and magnitude of recovery of surface blood flow (laser Doppler), limb muscle perfusion (fluorescent microspheres,
P
<0.001), and capillary and small arteriole densities in the ischemic limb (fluorescence immunohistochemistry, both
P
<0.001) when compared with the vehicle-treated group. Hemodynamic and anatomic improvements were dose related and optimal at a minimum dose of 3×10
5
cells. Dose-dependent improvements in blood flow and increased vessel densities by hNSC administration early after ischemia were confirmed in immunocompetent CD-1 and streptozotocin-induced diabetic mice, together with marked reductions in the incidence of necrotic toes (
P
<0.05). Delayed administration of hNSCs, 7 days after occlusion, produced restorative effects when comparable with acute treatment of 35 days after hindlimb ischemia. Histological studies in hindlimb ischemia immunocompetent mice for the first 7 days after treatment revealed short-term hNSC survival, transient elevation of early host muscle inflammatory, and angiogenic responses and acceleration of myogenesis.

Conclusions—
hNSC therapy represents a promising treatment option for critical limb ischemia.
Genome-Wide Interaction Study Identifies
RCBTB1
as a Modifier for Smoking Effect on Carotid Intima-Media Thickness
Authors: Wang Liyong , Rundek Tatjana , Beecham Ashley , Hudson Barry , Blanton Susan H. , Zhao Hongyu , Sacco Ralph L. , Dong Chuanhui 
Published: November 2013

Objective—
Carotid intima-media thickness (cIMT), a marker for atherosclerosis, is affected by smoking and has substantial interindividual variation. We sought to identify the genetic moderators influencing the effect of smoking on cIMT.

Approach and Results—

With a multistage design using 722 379 single nucleotide polymorphisms (SNP), a genome-wide interaction study was performed in a discovery sample of 669 Hispanics, followed by replication in 589 subjects (264 Hispanics, 172 non-Hispanic blacks, 153 non-Hispanic whites). Assuming an additive genetic model, regression analysis was performed to test for smoking–SNP interaction on cIMT while controlling for age, sex, and the top 3 principal components of ancestry. The strongest interaction in Hispanics was found with a synonymous splicing SNP (rs3751383) in exon 9 of
RCBTB1
(
P
=2.5e
−6
in discovery sample;
P
=0.01 in the Hispanic replication sample;
P
<8.8e
−9
in the combined Hispanic sample). Stratification analysis in the combined Hispanic sample showed that smoking had no effect on cIMT among rs3751383 G homozygote (
P
=0.15), a moderate effect among rs3751383 heterozygote (
P
=0.01), and a strong effect among rs3751383 A homozygote (
P
=2.1e
−7
). A consistent trend was observed in the non-Hispanic white and black data sets, leading to an interaction effect of
P
<2.9e
−9
in the meta-analysis of all 1258 subjects.

Conclusions—

Our study represents the first genome-wide smoking–SNP interaction study of cIMT and identifies
RCBTB1
as a modifier of the smoking effect on cIMT. Testing for gene–environment interactions can help uncover genetic factors that contribute to the interindividual variation in response to the same environmental exposure.
Genetic Influences on Trajectories of Systolic Blood Pressure Across Childhood and Adolescence
Authors: Howe Laura D. , Parmar Priyakumari G. , Paternoster Lavinia , Warrington Nicole M. , Kemp John P. , Briollais Laurent , Newnham John P. , Timpson Nicholas J. , Smith George Davey , Ring Susan M. , Evans David M. , Tilling Kate , Pennell Craig E. , Beilin Lawrie J. , Palmer Lyle J. , Lawlor Debbie A. 
Published: November 2013

Background—
Blood pressure (BP) tends to increase across childhood and adolescence, but the genetic influences on rates of BP change are not known. Potentially important genetic influences could include genetic variants identified in genome-wide association studies of adults as being associated with BP, height, and body mass index. Understanding the contribution of these genetic variants to changes in BP across childhood and adolescence could yield understanding into the life course development of cardiovascular risk.

Methods and Results—
Pooling data from 2 cohorts (the Avon Longitudinal Study of Parents and Children [n=7013] and the Western Australian Pregnancy Cohort [n=1459]), we examined the associations of allelic scores of 29 single-nucleotide polymorphisms (SNPs) for adult BP, 180 height SNPs, and 32 body mass index SNPs, with trajectories of systolic BP (SBP) from 6 to 17 years of age, using linear spline multilevel models. The allelic scores of BP and body mass index SNPs were associated with SBP at 6 years of age (per-allele effect sizes, 0.097 mm Hg [SE, 0.039 mm Hg] and 0.107 mm Hg [SE, 0.037 mm Hg]); associations with age-related changes in SBP between 6 and 17 years of age were of small magnitude and imprecisely estimated. The allelic score of height SNPs was only weakly associated with SBP changes. No sex or cohort differences in genetic effects were observed.

Conclusions—
Allelic scores of BP and body mass index SNPs demonstrated associations with SBP at 6 years of age with a similar magnitude but were not strongly associated with changes in SBP with age between 6 and 17 years. Further work is required to identify variants associated with changes with age in BP.
Long-Term Coffee Consumption and Risk of Cardiovascular Disease
Authors: Ding Ming , Bhupathiraju Shilpa N. , Satija Ambika , van Dam Rob M. , Hu Frank B. 
Published: November 2013

Background—
Considerable controversy exists on the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose–response relationship of long-term coffee consumption with CVD risk.

Methods and Results—

PubMed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1 279 804 participants and 36 352 CVD cases. A nonlinear relationship of coffee consumption with CVD risk was identified (
P
for heterogeneity=0.09,
P
for trend <0.001,
P
for nonlinearity <0.001). Compared with the lowest category of coffee consumption (median, 0 cups per day), the relative risk of CVD was 0.95 (95% confidence interval, 0.87–1.03) for the highest category (median, 5 cups per day) category, 0.85 (95% confidence interval, 0.80–0.90) for the second highest category (median, 3.5 cups per day), and 0.89 (95% confidence interval, 0.84–0.94) for the third highest category (median, 1.5 cups per day). Looking at separate outcomes, coffee consumption was nonlinearly associated with both coronary heart disease (
P
for heterogeneity=0.001,
P
for trend <0.001,
P
for nonlinearity <0.001) and stroke (
P
for heterogeneity=0.07,
P
for trend <0.001,
P
for nonlinearity <0.001;
P
for trend differences >0.05) risks.

Conclusions—
A nonlinear association between coffee consumption and CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with elevated CVD risk.