Brian Regan

Molecular imprinting is a rapidly growing area of interest involving the synthesis of artificial recognition elements that enable the separation of analyte from a sample matrix and its determination. Traditionally, this approach can be successfully applied to small analyte (<1.5 kDa) separation/ extraction, but, more recently it is finding utility in biomimetic sensors. These sensors consist of a recognition element and a transducer similar to their biosensor counterparts, however, the fundamental distinction is that biomimetic sensors employ an artificial recognition element. Molecularly imprinted polymers (MIPs) employed as the recognition elements in biomimetic sensors contain binding sites complementary in shape and functionality to their target analyte. Despite the growing interest in molecularly imprinting techniques, the commercial adoption of this technology is yet to be widely realised for blood sample analysis. This review aims to assess the applicability of this technology for the point-of-care testing (POCT) of cardiovascular disease-related biomarkers. More specifically, molecular imprinting is critically evaluated with respect to the detection of cardiac biomarkers indicative of acute coronary syndrome (ACS), such as the cardiac troponins (cTns). The challenges associated with the synthesis of MIPs for protein detection are outlined, in addition to enhancement techniques that ultimately improve the analytical performance of biomimetic sensors. The mechanism of detection employed to convert the analyte concentration into a measurable signal in biomimetic sensors will be discussed. Furthermore, the analytical performance of these sensors will be compared with biosensors and their potential implementation within clinical settings will be considered. In addition, the most suitable application of these sensors for cardiovascular assessment will be presented.

Measurement is the basis for assessing potential improvements in healthcare quality. Measures may be classified into four categories: volume, structure, outcome, and process (VSOP). Measures of each type should be used with a full understanding of their cost and benefit. Although volume and structure measures are easily collected, impact on healthcare results is not always clear. Process measures are generally more difficult and expensive to collect, and the relationship between process and outcomes is only recently being explored. Knowledge of measure types and relationships among them, as well as emerging evidence on the role of patient satisfaction, must be used to guide improvements and ultimately for demonstrating value in healthcare.

Arteriosclerosis is an important age-dependent disease that encompasses atherosclerosis, in-stent restenosis (ISR), pulmonary hypertension, autologous bypass grafting and transplant arteriosclerosis. Endothelial dysfunction and the proliferation of vascular smooth muscle cell (vSMC)-like cells is a critical event in the pathology of arteriosclerotic disease leading to intimal-medial thickening (IMT), lipid retention and vessel remodelling. An important aspect in guiding clinical decision-making is the detection of biomarkers of subclinical arteriosclerosis and early cardiovascular risk. Crucially, relevant biomarkers need to be good indicators of injury which change in their circulating concentrations or structure, signalling functional disturbances. Extracellular vesicles (EVs) are nanosized membraneous vesicles secreted by cells that contain numerous bioactive molecules and act as a means of intercellular communication between different cell populations to maintain tissue homeostasis, gene regulation in recipient cells and the adaptive response to stress. This review will focus on the emerging field of EV research in cardiovascular disease (CVD) and discuss how key EV signatures in liquid biopsies may act as early pathological indicators of adaptive lesion formation and arteriosclerotic disease progression. EV profiling has the potential to provide important clinical information to complement current cardiovascular diagnostic platforms that indicate or predict myocardial injury. Finally, the development of fitting devices to enable rapid and/or high-throughput exosomal analysis that require adapted processing procedures will be evaluated.

Cardiac biomarkers are frequently measured to provide guidance on the well-being of a patient in relation to cardiac health with many assays having been developed and widely utilised in clinical assessment. Effectively treating and managing cardiovascular disease (CVD) relies on swiftly responding to signs of cardiac symptoms, thus providing a basis for enhanced patient management and an overall better health outcome. Ultra-sensitive cardiac biomarker detection techniques play a pivotal role in improving the diagnostic capacity of an assay and thus enabling a better-informed decision. However, currently, the typical approach taken within healthcare depends on centralised laboratories performing analysis of cardiac biomarkers, thus restricting the roll-out of rapid diagnostics. Point-of-care testing (POCT) involves conducting the diagnostic test in the presence of the patient, with a short turnaround time, requiring small sample volumes without compromising the sensitivity of the assay. This technology is ideal for combatting CVD, thus the formulation of ultra-sensitive assays and the design of biosensors will be critically evaluated, focusing on the feasibility of these techniques for point-of-care (POC) integration. Moreover, there are several key factors, which in combination, contribute to the development of ultra-sensitive techniques, namely the incorporation of nanomaterials for sensitivity enhancement and manipulation of labelling methods. This review will explore the latest developments in cardiac biomarker detection, primarily focusing on the detection of cardiac troponin I (cTnI). Highly sensitive detection of cTnI is of paramount importance regarding the rapid rule-in/rule-out of acute myocardial infarction (AMI). Thus the challenges encountered during cTnI measurements are outlined in detail to assist in demonstrating the drawbacks of current commercial assays and the obstructions to standardisation. Furthermore, the added benefits of introducing multi-biomarker panels are reviewed, several key biomarkers are evaluated and the analytical benefits provided by multimarkers-based methods are highlighted.

BACKGROUND: Little is known about the actual treatment of patients with chronic obstructive pulmonary disease (COPD), either in the inpatient or outpatient settings. We hypothesized that there are substantial opportunities for improvement in adherence with current guidelines and recommendations. METHODS: We reviewed the medical records of all patients hospitalized with acute exacerbation of COPD between January 2005 and December 2006 at 5 New York City hospitals. RESULTS: There were 1285 unique patients with 1653 hospitalizations. Of these 1653, 83% were for patients with a prior history of COPD and 368 (22%) represented repeat admissions during our study period. The majority were treated during their hospitalization with a combination of systemic steroids (85%), bronchodilators (94%) and antibiotics (80%). There were 59 deaths (3.6%). Smoking cessation counseling was offered to 48% of active smokers. Influenza and pneumococcal vaccines were administered to half of eligible patients. On discharge, only 46.0% were prescribed maintenance bronchodilators and 24% were not prescribed any inhaled therapy. Even in the 226 unique patients (17.6%) readmitted at least once during course of the study, on discharge only 44.7% were prescribed maintenance bronchodilators and 23% were not prescribed any regular inhaled therapy. CONCLUSIONS: Patients hospitalized with acute exacerbation of COPD generally receive adequate hospital care, but there may be opportunities to improve care pharmacologically and with smoking cessation counseling and vaccination during and after hospitalization.