Raqeeb, Haastrup, and Evans: Seeking Consistency through a Distributive Justice-Based Approach to Limitation of Treatment in the Context of Dispute.

When is life-sustaining treatment not in the best interests of a minimally conscious child? This is an extremely difficult question that incites seemingly intractable debate. And yet, it is the question courts in England and Wales have set out to answer in disputes about appropriate medical treatment for children.

Clinical Spectroscopy: Lost in Translation?

This Focal Point Review paper discusses the developments of biomedical Raman and infrared spectroscopy, and the recent strive towards these technologies being regarded as reliable clinical tools. The promise of vibrational spectroscopy in the field of biomedical science, alongside the development of computational methods for spectral analysis, has driven a plethora of proof-of-concept studies which convey the potential of various spectroscopic approaches. Here we report a brief review of the literature published over the past few decades, with a focus on the current technical, clinical, and economic barriers to translation, namely the limitations of many of the early studies, and the lack of understanding of clinical pathways, health technology assessments, regulatory approval, clinical feasibility, and funding applications. The field of biomedical vibrational spectroscopy must acknowledge and overcome these hurdles in order to achieve clinical efficacy. Current prospects have been overviewed with comment on the advised future direction of spectroscopic technologies, with the aspiration that many of these innovative approaches can ultimately reach the frontier of medical diagnostics and many clinical applications.

Non-hyperaemic assessment of coronary ischaemia: application of machine learning techniques.

Aims: Hyperaemic and non-hyperaemic pressure ratios (NHPR) are routinely used to identify significant coronary lesions. Machine learning (ML) techniques may help better understand these indices and guide future practice. This study assessed the ability of a purpose-built ML algorithm to classify coronary ischaemia during non-hyperaemia compared with the existing gold-standard technique (fractional flow reserve, FFR). Further, it investigated whether ML could identify components of coronary and aortic pressure cycles indicative of ischaemia. Methods and results: Seventy-seven coronary vessel lesions (39 FFR defined ischaemia, 53 patients) with proximal and distal non-hyperaemic pressure waveforms and FFR values were assessed using supervised and unsupervised learning techniques in combination with principal component analysis (PCA). Fractional flow reserve measurements were obtained from the right coronary artery (13), left anterior descending (46), left circumflex (11), left main (1), obtuse marginal (2), and diagonal (4). The most accurate supervised learning classification utilized whole-cycle aortic with diastolic distal blood pressure waveforms, yielding a classification accuracy of 86.9% (sensitivity 86.8%, specificity 87.2%, positive predictive value 86.8%, negative predictive value 87.2%). Principal component analysis showed subtle variations in coronary pressures at the start of diastole have significant relation to ischaemia, and whole-cycle aortic pressure data are important for determining ischaemia. Conclusions: Our ML algorithm classifies significant coronary lesions with accuracy similar to previous studies comparing time-domain NHPRs with FFR. Further, it has identified characteristics of pressure waveforms that relate to function. These results provide an application of ML to ischaemia requiring only standard data from non-hyperaemic pressure measurements.

Assessing Rationing Decisions through the Principle of Proportionality.

Rationing policies necessarily discriminate, as they must identify bases on which to discriminate between patients in order to prioritise. Treatments may provide a greater benefit to some people than others and this may be a morally relevant difference that justifies discrimination. But it is difficult to identify when a reduced capacity to benefit from treatment is a sufficient basis deny a person access to treatment. We argue that a clearer test is required to hold governments to account. Discriminatory policies should be assessed by incorporating the principle of utility into the proportionality test. This would mean that discriminatory policies could only be justified if the benefit to the community in discriminating outweighed the cost to the individual of being discriminated against.

Early economic evaluation to guide the development of a spectroscopic liquid biopsy for the detection of brain cancer.

OBJECTIVES: An early economic evaluation to inform the translation into clinical practice of a spectroscopic liquid biopsy for the detection of brain cancer. Two specific aims are (1) to update an existing economic model with results from a prospective study of diagnostic accuracy and (2) to explore the potential of brain tumor-type predictions to affect patient outcomes and healthcare costs. METHODS: A cost-effectiveness analysis from a UK NHS perspective of the use of spectroscopic liquid biopsy in primary and secondary care settings, as well as a cost-consequence analysis of the addition of tumor-type predictions was conducted. Decision tree models were constructed to represent simplified diagnostic pathways. Test diagnostic accuracy parameters were based on a prospective validation study. Four price points (GBP 50-200, EUR 57-228) for the test were considered. RESULTS: In both settings, the use of liquid biopsy produced QALY gains. In primary care, at test costs below GBP 100 (EUR 114), testing was cost saving. At GBP 100 (EUR 114) per test, the ICER was GBP 13,279 (EUR 15,145), whereas at GBP 200 (EUR 228), the ICER was GBP 78,300 (EUR 89,301). In secondary care, the ICER ranged from GBP 11,360 (EUR 12,956) to GBP 43,870 (EUR 50,034) across the range of test costs. CONCLUSIONS: The results demonstrate the potential for the technology to be cost-effective in both primary and secondary care settings. Additional studies of test use in routine primary care practice are needed to resolve the remaining issues of uncertainty-prevalence in this patient population and referral behavior.

Ethnic differences in coronary anatomy, left ventricular mass and CT-derived fractional flow reserve.

BACKGROUND: Studies have observed higher incidence of cardiovascular mortality in South Asians (SA), and lower prevalence in East Asians (EA), compared with Caucasians. These observations are not entirely explained by ethnic differences in cardiovascular risk factors and mechanistic factors such as variations in cardiac anatomy and physiology may play a role. This study compared ethnic differences in CT-assessed left ventricular (LV) mass, coronary anatomy and non-invasive fractional flow reserve (FFRCT). METHODS: Three-hundred symptomatic patients (age 59 ± 7.9, male 51%) underwent clinically-mandated CT-coronary-angiography (CTA) were matched for age, gender, BMI and diabetes (100 each ethnicity). Assessment of coronary stenosis, luminal dimensions and vessel dominance was performed by independent observers. LV mass, coronary luminal volume and FFRCT were quantified by blinded core-laboratory. A sub-analysis was performed on patients (n = 187) with normal/minimal disease (0-25% stenosis). RESULTS: Stenosis severity was comparable across ethnic groups. EA demonstrated less left-dominant circulation (2%) compared with SA (8.2%) and Caucasians (10.1%). SA compared with EA and Caucasians demonstrated smallest indexed LV mass, coronary luminal volumes and dimensions. EA compared with Caucasians had comparable indexed LV mass, coronary luminal dimensions and highest luminal volumes. The latter was driven by higher prevalence of right-dominance including larger and longer right posterior left ventricular artery. FFRCT in the left anterior descending artery (LAD) was lowest in SA (0.87) compared with EA (0.89; P = 0.009) and Caucasians (0.89; P < 0.001), with no difference in other vessels. All observed differences were consistent in patients with minimal disease. CONCLUSION: This single-centre study identified significant ethnic differences in CT-assessed LV mass, coronary anatomy and LAD FFRCT. These hypotheses generating results may provide a mechanistic explanation for ethnic differences in cardiovascular outcomes and require validation in larger cohorts.

Quantitative and Qualitative Coronary Plaque Assessment Using Computed Tomography Coronary Angiography: A Comparison With Intravascular Ultrasound.

BACKGROUND: To compare computed tomography coronary angiography (CTCA) with intravascular ultrasound (IVUS) in quantitative and qualitative plaque assessment. METHODS: Patients who underwent IVUS and CTCA within 3 months for suspected coronary artery disease were retrospectively studied. Plaque volumes on CTCA were quantified manually and with automated-software and were compared to IVUS. High-risk plaque features were compared between CTCA and IVUS. RESULTS: There were 769 slices in 32 vessels (27 patients). Manual plaque quantification on CTCA was comparable to IVUS per slice (mean difference of 0.06±0.07, p=0.44; Bland-Altman 95% limits of agreement -2.19-2.08 mm3, bias of -0.06mm3) and per vessel (3.1mm3 ± -2.85mm3, p=0.92). In contrast, there was significant difference between automated-software and IVUS per slice (2.3±0.09mm3, p<0.001; 95% LoA -6.78 to 2.25mm3, bias of -2.2mm3) and per vessel (33.04±10.3 mm3, p<0.01). The sensitivity, specificity, positive and negative predictive value of CTCA to detect plaques that had features of echo-attenuation on IVUS was 93.3%, 99.6%, 93.3% and 99.6% respectively. The association of ≥2 high-risk plaque features on CTCA with echo attenuation (EA) plaque features on IVUS was excellent (86.7%, 99.6%, 92.9% and 99.2%). In comparison, the association of high-risk plaque features on CTCA and plaques with echo-lucency on IVUS was only modest. CONCLUSION: Plaque volume quantification by manual CTCA method is accurate when compared to IVUS. The presence of at least two high-risk plaque features on CTCA is associated with plaque features of echo attenuation on IVUS.

Development of high-throughput ATR-FTIR technology for rapid triage of brain cancer.

Non-specific symptoms, as well as the lack of a cost-effective test to triage patients in primary care, has resulted in increased time-to-diagnosis and a poor prognosis for brain cancer patients. A rapid, cost-effective, triage test could significantly improve this patient pathway. A blood test using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy for the detection of brain cancer, alongside machine learning technology, is advancing towards clinical translation. However, whilst the methodology is simple and does not require extensive sample preparation, the throughput of such an approach is limited. Here we describe the development of instrumentation for the analysis of serum that is able to differentiate cancer and control patients at a sensitivity and specificity of 93.2% and 92.8%. Furthermore, preliminary data from the first prospective clinical validation study of its kind are presented, demonstrating how this innovative technology can triage patients and allow rapid access to imaging.

Application of the DILEMMA score to improve lesion selection for invasive physiological assessment.

OBJECTIVES: We sought to assess the validity of the DILEMMA score against instantaneous wave-free ratio (iFR) and evaluate its utility in rationalizing the number of patients referred for invasive physiological assessment. BACKGROUND: The DILEMMA score is a validated angiographic scoring tool incorporating minimal lumen diameter, lesion length and subtended myocardial area that has been shown to predict the functional significance of lesions as assessed by fractional flow reserve (FFR). METHODS: Patients in the DEFINE-FLAIR study who had coronary stenosis of intermediate severity were randomized to either FFR or iFR. DILEMMA score was calculated retrospectively on a subset of this cohort by operators blinded to FFR or iFR values. RESULTS: Three hundred and forty-six lesions (181 assessed by FFR; 165 by iFR) from 259 patients (mean age 66.0 years, 79% male) were included. A DILEMMA score ≤ 2 had a negative predictive value of 96.3% and 95.7% for identifying lesions with FFR >0.80 and iFR >0.89, respectively. A DILEMMA score ≥ 9 had a positive predictive value of 88.9% and 100% for identifying lesions with FFR ≤0.80 and iFR ≤0.89, respectively. The receiver operating characteristic area under the curve values for DILEMMA score to predict FFR ≤0.80 and iFR ≤0.89 were 0.83 (95% CI 0.77-0.90) and 0.82 (0.75-0.89) respectively. A DILEMMA score ≤ 2 or ≥9 occurred in 172 of the 346 lesions (49.7%). CONCLUSIONS: Using DILEMMA score in patients with coronary stenosis of intermediate severity may reduce the need for pressure wire use, offering potential cost-savings and minimizing the risks associated with invasive physiological lesion assessment.

Diagnostic accuracy of ASLA score (a novel CT angiographic index) and aggregate plaque volume in the assessment of functional significance of coronary stenosis.

BACKGROUND: Visual assessment of diameter-stenosis on Computed Tomography Coronary Angiography (CTCA) lacks specificity to determine functional significance of coronary artery stenosis. Percent-aggregate plaque volume (%APV) and ASLA score, which incorporates Area of Stenosis, Lesion length, and area of myocardium subtended estimated by APPROACH score (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease) have been described to predict lesion specific ischaemia in focal lesions with intermediate stenosis. METHODS AND RESULTS: Included were 81 patients (mean age 64.7 ±â€¯9 years, 62% male; 94 vessels) who underwent 320- detector-row CTCA, invasive coronary angiography and fractional-flow-reserve (FFR). We examined vessels with wide range of diameter stenosis (mid to severe) and with multiple lesions. Invasive FFR of ≤0.8 was considered functionally significant. The first 54 patients (62 vessels) formed the derivation cohort. ASLA score was the best predictor of FFR ≤ 0.8 (AUC 0.83, p < 0.001) compared to %APV (0.72), CT >50% (0.76), APPROACH score (0.79), area-stenosis (0.73), diameter-stenosis (0.74), minimum-luminal-diameter (0.74), minimal-luminal-area (0.72), and lesion-length (0.67). ASLA score and not %APV, provided incremental predictive value when added to CT > 50 [(NRI 0.71, p = 0.005) vs. (NRI 0.01, p = 0.96)]. In the validation cohort of 27 patients (32 vessels), the ASLA score (AUC 0.85) was again a better predictor of FFR ≤ 0.8 compared to %APV (0.71), CT > 50% (0.66) and other CT indices. The AUC of ASLA score was superior to CTCA>50% (p = 0.001). CONCLUSION: ASLA score is a novel predictor of functional significance of coronary stenosis and adds incremental predictive value to CT > 50 but %APV did not.

Coronary computed tomography angiography for the assessment of chest pain: current status and future directions.

Chest pain is one of the most common presenting symptoms leading to presentation to medical clinics and Emergency Departments worldwide. Defining the nature and etiology of chest pain can pose a diagnostic dilemma for clinicians, despite the availability of several diagnostic algorithms and guidelines to assist them in evaluating these patients. Most investigations in patients with acute chest pain are initially performed to either exclude or diagnose and manage potentially life-threatening conditions such as acute coronary syndrome, pulmonary embolism and aortic dissection. In cases of stable chest pain syndromes, the focus shifts to determining the presence, extent and severity of coronary artery disease. In recent years, coronary computed tomography angiography (CCTA) is being increasingly used worldwide in the assessment of both stable and acute chest pain syndromes. This review evaluates the current evidence regarding the clinical utility of CCTA in the stable and acute chest pain settings and outlines the latest advances in CCTA techniques, including functional assessment of coronary stenoses, and their potential clinical application to improve patient care in a cost-effective manner.

Assessment of the geometric interaction between the Lotus transcatheter aortic valve prosthesis and the native ventricular aortic interface by 320-multidetector computed tomography.

OBJECTIVES: This study sought to assess the geometric interaction between the Lotus Valve System transcatheter aortic prosthesis (Boston Scientific, Natick, Massachusetts) and the native aortoventricular interface using multidetector computed tomography (MDCT). BACKGROUND: The interaction between transcatheter aortic valve prostheses and native anatomy is variable, although potentially predictable. The Lotus transcatheter device uses a novel mechanical means of expansion, the effect of which on native anatomic geometry has not previously been described. METHODS: Forty patients treated with the Lotus prosthesis were enrolled. The patients underwent 320-MDCT imaging before and after implantation. Prosthesis dimensions and relevant interaction parameters, including circularity and expansion, were assessed. The degree of paraprosthetic regurgitation (PAR) and prosthesis gradient were measured by transthoracic echocardiography at the same time points. RESULTS: The mean baseline annular eccentricity index (EI) was 0.21 ± 0.06 and left ventricular outflow tract EI was 0.31 ± 0.09. The deployed prostheses had high rates of circularity with a mean EI across all device segments of 0.06 ± 0.04. In noncircular device deployment, an EI >0.1 was identified in 25% of prostheses and was associated with greater native annular eccentricity at baseline compared with circular devices (0.24 ± 0.04 vs. 0.19 ± 0.06; p = 0.01). The median percent of expansion was 97.5 ± 3.8% in the inflow portion of the prosthesis. Twenty-five percent of prostheses were <90% expanded in at least 1 segment with a numerical, but not statistically significant, association between oversizing and underexpansion. No correlation was found between device underexpansion and the mean transprosthesis gradient or between noncircularity and PAR. CONCLUSIONS: The Lotus prosthesis results in nearly full device expansion and circularization of the native basal plane. Awareness of the anatomic interaction between this unique device and the native architecture may help in the formulation of appropriate device-specific sizing algorithms.

Comparison of diagnostic accuracy of combined assessment using adenosine stress computed tomography perfusion + computed tomography angiography with transluminal attenuation gradient + computed tomography angiography against invasive fractional flow reserve.

OBJECTIVES: The goal of this study was to compare the diagnostic accuracy of combined computed tomography perfusion (CTP) + computed tomography angiography (CTA), transluminal attenuation gradient by 320-detector row computed tomography (TAG320) + CTA, and CTP + TAG320 + CTA (multidetector computed tomography-integrated protocol [MDCT-IP]) assessment in predicting significant fractional flow reserve (FFR). BACKGROUND: CTA has limited specificity for predicting functionally significant stenoses. Novel CT techniques, including adenosine stress CTP and TAG320, may improve the diagnostic accuracy of CTA. METHODS: CTA, CTP, and TAG320 were assessed using 320-detector row MDCT. Patients who underwent CTA, CTP, and FFR assessment on invasive coronary angiography were included. CTP was assessed using the visual perfusion assessment. TAG320 was defined as the linear regression coefficient between luminal attenuation and axial distance. A TAG320 cutoff value of -15.1 HU/10 mm as previously described was defined as significant. Functionally significant coronary stenosis was defined as FFR ≤0.8. RESULTS: The cohort included 75 patients (age 64.1 ± 10.8 years, 52 men) and 44 (35%) FFR-significant vessels. In 127 vessels, CTA predicted FFR-significant stenosis with 89% sensitivity and 65% specificity compared with MDCT-IP, which showed 88% sensitivity and 83% specificity. In 97 vessels in which the results of all techniques were available, TAG320 + CTA (area under the curve [AUC] = 0.844) and CTP + CTA (AUC = 0.845) had comparable per-vessel diagnostic accuracy (p = 0.98). The diagnostic accuracy of MDCT-IP (AUC = 0.91) was superior to TAG320 + CTA or CTP + CTA (p = 0.01). CONCLUSIONS: In vessels without significant calcification or artefact, TAG320 + CTA and CTP + CTA provide comparable diagnostic accuracy for functional assessment of coronary artery stenosis. MDCT-IP may provide the best diagnostic accuracy for functional assessment of coronary artery stenosis.

Increasing access to chronic disease self-management programs in rural and remote communities using telehealth.

OBJECTIVE: This study examined whether a telehealth chronic disease self-management program (CDSMP) would lead to improvements in self-efficacy, health behaviors, and health status for chronically ill adults living in Northern Ontario, Canada. Two telehealth models were used: (1) single site, groups formed by participants at one telehealth site; and (2) multi-site, participants linked from multiple sites to form one telehealth group, as a strategy to increase access to the intervention for individuals living in rural and remote communities. SUBJECTS AND METHODS: Two hundred thirteen participants diagnosed with heart disease, stroke, lung disease, or arthritis attended the CDSMP at a preexisting Ontario Telemedicine Network studio from September 2007 to June 2008. The program includes six weekly, peer-facilitated sessions designed to help participants develop important self-management skills to improve their health and quality of life. Baseline and 4-month follow-up surveys were administered to assess self-efficacy beliefs, health behaviors, and health status information. Results were compared between single- and multi-site delivery models. RESULTS: Statistically significant improvements from baseline to 4-month follow-up were found for self-efficacy (6.6±1.8 to 7.0±1.8; p<0.001), exercise behavior, cognitive symptom management, communication with physicians, role function, psychological well-being, energy, health distress, and self-rated health. There were no statistically significant differences in outcomes between single- and multi-site groups. CONCLUSIONS: Improvements in self-efficacy, health status, and health behaviors were equally effective in single- and multi-site groups. Access to self-management programs could be greatly increased with telehealth using single- and multi-site groups in rural and remote communities.

Current and evolving clinical applications of multidetector cardiac CT in assessment of structural heart disease.

Multidetector computed tomography (CT) has an established role in the evaluation of selected patients suspected of having coronary disease; however, in addition to coronary assessment, multidetector CT can be used to evaluate numerous noncoronary structures in the same examination. In particular, the use of multidetector CT to provide pulmonary and cardiac venous anatomic information prior to electrophysiology procedures is well established, and its important role in the periprocedural evaluation of patients undergoing percutaneous procedures, such as transcatheter aortic valve replacement and left atrial appendage device occlusion, is being increasingly recognized. Such advances have resulted in multidetector CT being increasingly used as a complementary imaging technique to echocardiography and magnetic resonance imaging for the comprehensive evaluation of cardiac structure and function in particular clinical situations. This review provides an overview of the noncoronary cardiac structures that can be evaluated with multidetector CT, and outlines the established appropriate clinical uses of multidetector CT in the assessment of structural heart disease, as well as evolving periprocedural clinical applications.

Assessment of left ventricular volumes, ejection fraction and regional wall motion with retrospective electrocardiogram triggered 320-detector computed tomography: a comparison with 2D-echocardiography.

Left ventricular (LV) volumes, ejection fraction (LVEF) and regional wall motion (LVRWM) have important treatment and prognostic implications in patients with coronary artery disease. We sought to determine the accuracy of 320-row multidetector computed tomography (MDCT) for the assessment of LV volumes, LVEF and LVRWM, using 2D-echocardiography as the reference standard. We evaluated 50 consecutive patients (mean age 60 ± 14 years, 66% male) who underwent 320-detector MDCT (dose-modulated retrospective electrocardiogram-triggering) and 2D-echocardiography within 14 days for investigation of known or suspected coronary artery disease. Two blinded readers measured LV volumes on MDCT and visually assessed LVRWM with a 3-point scale using a 17-segment model. A separate experienced echocardiologist, blinded to MDCT findings, assessed LVRWM on 2D-echocardiograms and determined LV volumes and LVEF using Simpson's biplane method. 2D-echocardiography served as the reference standard. Mean LVEF was 59 ± 9% (range 26-75%) on 2D-echocardiography and 60 ± 9% (range 27-76%) on MDCT. Using linear regression analysis, MDCT agreed very well with 2D-echocardiography for assessment of LVEDV (r(2) = 0.88; P < 0.001), LVESV (r(2) = 0.95; P < 0.001) and LVEF (r(2) = 0.90; P < 0.001). Mean differences (±standard deviation) of 14 ± 13 ml, 5 ± 7 ml and 1 ± 3% were observed between MDCT and 2D-echocardiography for LVEDV, LVESV and LVEF, respectively. On 2D-echocardiography, 81/850 (9.5%) segments had abnormal LVRWM. Agreement for assessment of LVRWM between 2D-echocardiography and MDCT was excellent (96%, k = 0.76). Accurate assessment of LV volumes, LVEF and LVRWM is feasible with 320-detector MDCT, with MDCT demonstrating slightly larger LV volumes than 2D-echocardiography.

Prevalence, detection, and management of the metabolic syndrome in patients with acute myocardial infarction: role of an obesity-centric definition.

Background. We sought to determine and compare the prevalence of the Metabolic Syndrome (MS) in patients with acute myocardial infarction (AMI) utilizing the new International Diabetes Federation (IDF) definition with the older National Cholesterol Education Program (NCEP) definition. We also examined the clinical utility of MS in this context. Methods. A total of 107 consecutive patients with AMI were prospectively evaluated for MS. Fasting lipids obtained at admission and fasting glucose at discharge were used. A postdischarge folder audit verified rates of discharge coding and implementation of specific management strategies for MS. Results. Baseline patient characteristics included: mean age 59 +/- 13 years; males 80%; diabetes 19%; mean BMI 29.7 +/- 8.4 kg/m(2). MS prevalence was 54% by the IDF definition and 49% by the NCEP definition, with good agreement between definitions: kappa = 0.664, P < .001. Factors predictive of MS after multivariate analysis included: hypertension, fasting glucose, waist circumference, and serum HDL (all P < .05). Despite the high prevalence, MS was recognized at discharge in only 1 patient, and referral for exercise and/or weight-loss programs was undertaken in 5 patients. Conclusion. There is a high prevalence of MS utilizing contemporary definitions in patients with AMI: 54% by the IDF definition and 49% by NCEP criteria. Despite the high prevalence, MS was under-recognized and under-treated in this population.