Measuring the impact of scientific publications and publication extenders: examples of novel approaches.

Different stakeholders, such as authors, research institutions, and healthcare professionals (HCPs) may determine the impact of peer-reviewed publications in different ways. Commonly-used measures of research impact, such as the Journal Impact Factor or the H-index, are not designed to evaluate the impact of individual articles. They are heavily dependent on citations, and therefore only measure impact of the overall journal or researcher respectively, taking months or years to accrue. The past decade has seen the development of article-level metrics (ALMs), that measure the online attention received by an individual publication in contexts including social media platforms, news media, citation activity, and policy and patent citations. These new tools can complement traditional bibliometric data and provide a more holistic evaluation of the impact of a publication. This commentary discusses the need for ALMs, and summarizes several examples - PlumX Metrics, Altmetric, the Better Article Metrics score, the EMPIRE Index, and scite. We also discuss how metrics may be used to evaluate the value of "publication extenders" - educational microcontent such as animations, videos and plain-language summaries that are often hosted on HCP education platforms. Publication extenders adapt a publication's key data to audience needs and thereby extend a publication's reach. These new approaches have the potential to address the limitations of traditional metrics, but the diversity of new metrics requires that users have a keen understanding of which forms of impact are relevant to a specific publication and select and monitor ALMs accordingly.

Different readers have different ways of deciding how important scientific articles are. The usual methods used to measure the impact of research, like the Journal Impact Factor or the H-index, are not meant to measure this for individual articles. These methods mainly look at how many times the articles are mentioned by others, and it can take a long time to see the impact.But in the past ten years, new tools called article-level metrics (ALMs) have been created. These tools measure how much attention an article gets online, like on social media, in the news, or when other researchers talk about it. ALMs are better at explaining how important a specific article is. They can work together with the usual methods to measure impact.This paper talks about why ALMs are important and gives examples of these tools, like PlumX Metrics, Altmetric, the Better Article Metrics score, the EMPIRE Index, and scite. It also explains how these tools can help us see the value of animations, videos, or summaries in simple language. These make it easier for more people to understand and learn from the articles.These new ways of measuring impact can help us see how important articles are in a more complete way. But because there are many different ways to measure this, it's important for users to understand which methods are relevant for a specific article and keep track of them.

Introducing the EMPIRE Index: A novel, value-based metric framework to measure the impact of medical publications.

Article-level measures of publication impact (alternative metrics or altmetrics) can help authors and other stakeholders assess engagement with their research and the success of their communication efforts. The wide variety of altmetrics can make interpretation and comparative assessment difficult; available summary tools are either narrowly focused or do not reflect the differing values of metrics from a stakeholder perspective. We created the EMPIRE (EMpirical Publication Impact and Reach Evaluation) Index, a value-based, multi-component metric framework for medical publications. Metric weighting and grouping were informed by a statistical analysis of 2891 Phase III clinical trial publications and by a panel of stakeholders who provided value assessments. The EMPIRE Index comprises three component scores (social, scholarly, and societal impact), each incorporating related altmetrics indicating a different aspect of engagement with the publication. These are averaged to provide a total impact score and benchmarked so that a score of 100 equals the mean scores of Phase III clinical trial publications in the New England Journal of Medicine (NEJM) in 2016. Predictor metrics are defined to estimate likely long-term impact. The social impact component correlated strongly with the Altmetric Attention Score and the scholarly impact component correlated modestly with CiteScore, with the societal impact component providing unique insights. Analysis of fresh metrics collected 1 year after the initial dataset, including an independent sample, showed that scholarly and societal impact scores continued to increase, whereas social impact scores did not. Analysis of NEJM 'notable articles' showed that observational studies had the highest total impact and component scores, except for societal impact, for which surgical studies had the highest score. The EMPIRE Index provides a richer assessment of publication value than standalone traditional and alternative metrics and may enable medical researchers to assess the impact of publications easily and to understand what characterizes impactful research.

Identifying and Validating Networks of Oncology Biomarkers Mined From the Scientific Literature.

Biomarkers, as measurements of defined biological characteristics, can play a pivotal role in estimations of disease risk, early detection, differential diagnosis, assessment of disease progression and outcomes prediction. Studies of cancer biomarkers are published daily; some are well characterized, while others are of growing interest. Managing this flow of information is challenging for scientists and clinicians. We sought to develop a novel text-mining method employing biomarker co-occurrence processing applied to a deeply indexed full-text database to generate time-interval-delimited biomarker co-occurrence networks. Biomarkers across 6 cancer sites and a cancer-agnostic network were successfully characterized in terms of their emergence in the published literature and the context in which they are described. Our approach, which enables us to find publications based on biomarker relationships, identified biomarker relationships not known to existing interaction networks. This search method finds relevant literature that could be missed with keyword searches, even if full text is available. It enables users to extract relevant biological information and may provide new biological insights that could not be achieved by individual review of papers.

Progress and controversies: treating obesity and insulin resistance in the context of hypertension.

Improvements in hypertension treatment and control are challenged by the increasing incidence of metabolic risk factors for hypertension, in particular, obesity and insulin resistance. Such risk factors can increase the severity of hypertension and can interact via a multitude of hormonal and inflammatory pathways. Their presence may affect antihypertensive agent choice with regard to antihypertensive efficacy as well as potential synergistic or antagonistic effects on inflammatory status and progression to diabetes. Furthermore, an increasing number of pharmacologic options are available to promote weight loss and insulin sensitivity that may affect blood pressure directly and indirectly. This review considers the metabolic basis for the complex interactions of hypertension with obesity and insulin resistance, and it assesses the clinical evidence for an impact of weight loss and insulin-sensitizing treatment on blood pressure. Awareness of these pathophysiologic interrelations and their implications for treatment are likely to be of increasing importance for successful blood pressure management.

Cardiovascular high-risk patients--treat to protect, but whom?

Current guidelines for the prevention of coronary heart disease emphasize the importance of global cardiovascular risk, which requires the evaluation and treatment of multiple risk factors. Cardiovascular risk can be stratified with the Framingham algorithm, which produces a numerical score related to the presence of risk factors, such as hypertension, dyslipidemia, and smoking. However, this algorithm is not generally applicable to European countries, particularly for those countries where the risk for cardiovascular disease is low. The SCORE (Systematic COronary Risk Evaluation) project has produced risk charts that are based on cholesterol, blood pressure, and age for low-risk European countries (Belgium, France, Greece, Italy, Luxembourg, Spain, and Switzerland) and high-risk countries. Assessments of end-organ damage can provide further prognostic information, particularly in intermediate-risk patients, but the value of including additional biomarkers in risk stratification remains to be confirmed. Risk for coronary heart disease is high or very high in more than 50% of hypertensive patients. Risk appears to be underestimated in clinical practice, particularly in those patients at highest risk. Major intervention trials with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have shown that these agents reduce the risk for cardiovascular events in patients at all levels of risk, with the greatest benefits seen in those at highest risk.

No HOPE without proof: do ARBs meet the standard for cardiovascular protection?

Blockade of the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) plays an important role in the protection and prevention of cardiovascular disease. The Heart Outcomes Prevention Evaluation (HOPE) study established the significant effect of ACE inhibition on cardiovascular morbidity and mortality beyond blood pressure control. Smaller studies have demonstrated the efficacy of ARBs. In addition, a recent analysis from the Blood Pressure Lowering Treatment Trialists' Collaboration showed that ARB-based and ACE inhibitor-based treatment regimens were comparable in terms of the odds ratio for stroke and heart failure, independent of blood pressure reduction. There is an emerging body of evidence to suggest that a combination approach to RAS blockade with an ARB and an ACE inhibitor may further improve cardiovascular outcome compared with monotherapy with either agent alone. The large-scale ONgoing Telmisartan Alone or in combination with Ramipril Global Endpoint Trial (ONTARGET), comparing high-dose ramipril (HOPE study dosage) with telmisartan or a combination of the two, should provide important insight into the benefits of RAS blockade intervention. The results of ONTARGET are anticipated to be available in 2008.

Cardiac and vascular protection: the potential of ONTARGET.

Cardiovascular risk is determined by multiple risk factors. Blockade of the renin-angiotensin system is an important approach to the prevention of cardiovascular events. In the largest angiotensin receptor blocker cardiovascular outcome study to date, the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) program will compare the efficacy of therapy with telmisartan and ramipril, in reducing cardiovascular events in patients at high risk (history of coronary artery disease, stroke or transient ischemic attack, peripheral artery disease, or diabetes with evidence of end-organ damage). Recruited patients (n = 31,546) will be followed up for a period of 6 years, and more than 150,000 patient-years of data will be recorded. The primary endpoint is a composite of cardiovascular death, stroke, acute myocardial infarction, and hospitalization for congestive heart failure; secondary endpoints focus on reductions in newly diagnosed heart failure, new-onset type 2 diabetes, cognitive decline, atrial fibrillation, and nephropathy. In addition, an ambulatory blood pressure monitoring substudy will be conducted to assess the effect of treatment on endpoints after adjustment for 24-hour blood pressure values. Other substudies of the treatment effects on erectile dysfunction, blood markers, arterial stiffness, oral glucose tolerance, and the progression of target organ damage are also planned. The results of the ONTARGET program are due in 2008, and the findings are expected to have important clinical implications for the management of patients at high cardiovascular risk.

Targeting cardiovascular protection: the concept of dual renin-angiotensin system control.

The renin-angiotensin system plays a key role in the regulation of blood pressure, and blockade of this system now forms a central part of strategies to reduce the risk for cardiovascular events in high-risk patients. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been shown to be effective in lowering blood pressure and reducing the risk for cardiovascular events, but both classes of drug have some limitations. Plasma concentrations of angiotensin II increase during ACE-inhibitor therapy in some patients, partly as a result of the production of angiotensin II via non-ACE pathways; furthermore, elevated aldosterone concentrations can occur in a significant proportion of patients. ARBs block the deleterious effects of angiotensin II at angiotensin type 1 receptors irrespective of the origin of the peptide, but the beneficial effects of kinins may be diminished. ARB therapy results in activation of angiotensin type 2 receptors, resulting in potentially beneficial anti-inflammatory, antithrombotic, and antiproliferative effects, but the clinical significance of these effects remains controversial. Some ARBs, particularly telmisartan, have been shown to act as partial agonists of peroxisome proliferator-activated receptor gamma, thereby increasing insulin sensitivity. Combination therapy with ACE inhibitors and ARBs offers the potential for effective blood pressure control, decreased aldosterone production, enhanced kinin activity, and increased insulin sensitivity. The potential clinical benefits of this approach in high-risk patients are currently being investigated in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), which is comparing therapy using a combination of telmisartan plus ramipril with the use of each drug in monotherapy.

Prospects for renovascular protection by more aggressive renin-angiotensin system control.

Risk factors such as hypertension or diabetes result in a continuum of renal damage. Without intervention, initial subclinical endothelial damage progresses to incipient disease, identified by microalbuminuria. Glomerular filtration rate declines, macroalbuminuria develops, and eventually end-stage renal disease (ESRD) emerges. Because of the interrelationship between cardiovascular and renal disease and their common pathophysiologies involving angiotensin II, many patients die of cardiovascular disease before renal replacement therapy is needed. Blood pressure control is key to renoprotection, but blood pressure-independent mechanisms are also implicated. Targeting the renin-angiotensin system (RAS) using angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) is a logical approach to managing all at-risk patients. In advanced nephropathy, therapy aims at retarding progression to ESRD. For incipient nephropathy, ideal therapy should bring about microalbuminuria regression. In patients at risk of renal damage, preventing early target-organ damage is essential. Although evidence of ACE inhibitor benefit is limited, data show that ARBs provide renoprotection throughout the continuum and that this may be related to their cardioprotective effects. More aggressive RAS targeting by combination blockade is under investigation. Telmisartan is an ARB that delays progression of incipient and overt diabetic nephropathy and brings about regression from microalbuminuria to normoalbuminuria in hypertensive and normotensive patients. The ultimate proof of benefit will come from the ONTARGET trial, which will evaluate the cardiovascular and renal protective effects of the combination of telmisartan and ramipril.

Treating to protect: current cardiovascular treatment approaches and remaining needs.

Current best practice to reduce cardiovascular disease involves evaluating patients' global cardiovascular risk profiles and devising treatment strategies accordingly. Despite the proven efficacy of this approach, very few physicians are adequately assessing risk, and consequently patients are failing to achieve desired treatment targets. Modifying lifestyle factors, such as diet, exercise, and cessation of smoking, remains one of the simplest and most potent means of reducing risk. Newly emerging evidence suggests that moderate physical activity (such as brisk walking for 30 minutes a day), eg, by raising levels of circulating endothelial progenitor cells, improves endothelial function and enhances vascular repair. However, patients remain remarkably reluctant to lifestyle changes, even in the face of overt, life-threatening disease. Statin treatment reduces cardiovascular morbidity and death in both primary and secondary prevention studies. However, over 90% of adults at high risk for coronary heart disease fail to achieve target low-density lipoprotein cholesterol levels in spite of statin therapy. Similarly, only about 37% of patients with hypertension meet blood pressure targets. Antihypertensive drugs achieve different levels of cardioprotection. Mounting evidence links regimens containing beta-blockers or diuretics with higher incidence of type 2 diabetes. In contrast, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers appear to confer extra protection on target organs on top of blood pressure reduction. The ONTARGET Trial Program is designed to clarify the importance of this effect. Educating patients, raising physicians' awareness, and implementing effective and safe treatment regimens are all necessary steps to bring about the much-needed improvements in cardiac health outcomes.

Optimal management of lipids in diabetes and metabolic syndrome.

Patients with diabetes or metabolic syndrome frequently have higher triglycerides, lower high-density lipoprotein (HDL) cholesterol, and more particles containing apolipoprotein B (ApoB); this combination contributes significantly to their cardiovascular risk. Optimal management of dyslipidemia and increased atherosclerotic risk requires a fundamental understanding of diabetic dyslipidemia, the clinical evidence for different interventional strategies, and the potential benefit of achieving therapeutic targets. For this review, we considered guidelines, recent reviews, and clinical trial results. The features of dyslipidemia in type 2 diabetes and the metabolic syndrome are linked metabolically and are related to central adiposity and insulin resistance. Levels of ApoB and HDL cholesterol are particularly important markers of risk. Guidelines broadly agree that low-density lipoprotein (LDL) cholesterol should be reduced below population average levels. Additional or secondary strategies in patients with diabetes or the metabolic syndrome are to decrease non-HDL cholesterol, ApoB and/or LDL particle concentration, to increase HDL cholesterol, and to reduce triglycerides. Lifestyle changes and statins are the bedrock of treatment, although second-line treatment using fibrates or niacin will likely benefit many patients with residual risk. Ezetimibe, too, has a favorable effect on lipid profile and inflammatory biomarkers of risk. Dyslipidemia in type 2 diabetes and metabolic syndrome has a distinct profile, suggesting the need for a tailored therapy that targets the key features of lowered HDL cholesterol and raised triglycerides, in addition to the primary antiatherogenic strategy of lowering ApoB-containing lipoproteins, such as LDL. With the prominent failure of some recent intervention trials, new therapeutic strategies-particularly safe and effective means to raise HDL-are needed to manage dyslipidemia in this high-risk population.