The Bland-Altman Limits of Agreement is a popular and widespread means of analyzing the agreement of two methods, instruments, or raters in quantitative outcomes. An agreement analysis could be ...reported as a stand-alone research article but it is more often conducted as a minor quality assurance project in a subgroup of patients, as a part of a larger diagnostic accuracy study, clinical trial, or epidemiological survey. Consequently, such an analysis is often limited to brief descriptions in the main report. Therefore, in several medical fields, it has been recommended to report specific items related to the Bland-Altman analysis. The present study aimed to identify the most comprehensive and appropriate list of items for such an analysis. Seven proposals were identified from a MEDLINE/PubMed search, three of which were derived by reviewing anesthesia journals. Broad consensus was seen for the a priori establishment of acceptability benchmarks, estimation of repeatability of measurements, description of the data structure, visual assessment of the normality and homogeneity assumption, and plotting and numerically reporting both bias and the Bland-Altman Limits of Agreement, including respective 95% confidence intervals. Abu-Arafeh et al. provided the most comprehensive and prudent list, identifying 13 key items for reporting (Br. J. Anaesth. 2016, 117, 569-575). An exemplification with interrater data from a local study accentuated the straightforwardness of transparent reporting of the Bland-Altman analysis. The 13 key items should be applied by researchers, journal editors, and reviewers in the future, to increase the quality of reporting Bland-Altman agreement analyses.
Purpose
To conduct a systematic review of articles on PET imaging of carotid atherosclerosis with emphasis on clinical usefulness and comparison with other imaging modalities.
Methods
Research ...articles reporting carotid artery PET imaging with different radiotracers until 30 November 2018 were systematically searched for in Medline/PubMed, Scopus, Embase, Google Scholar, and Cochrane Library. Duplicates were removed, and editorials, case studies, and investigations on feasibility or reproducibility of PET imaging and of patients with end-stage diseases or immunosuppressive medications were omitted. After quality assessment of included articles using Joanna Briggs Institute checklists, all eligible articles were reviewed.
Results
Of 1718 primary hits, 53 studies comprising 4472 patients, aged 47–91 years (78.8% males), were included and grouped under the following headlines: diagnostic performance, risk factors, laboratory findings, imaging modalities, and treatment.
18
F-fluorodeoxyglucose (FDG) (49/53) and
18
F-sodium fluoride (NaF) (5/53) were the most utilized tracers to visualize carotid wall inflammation and microcalcification, respectively. Higher carotid FDG uptake was demonstrated in patients with than without symptomatic carotid atherosclerosis. Normal carotid arteries presented with the lowest FDG uptake. In symptomatic atherosclerosis, carotid arteries ipsilateral to a cerebrovascular event had higher FDG uptake than the contralateral carotid artery. FDG uptake was significantly associated with age, male gender, and body mass index in healthy individuals, and in addition with arterial hypertension, hypercholesterolemia, and diabetes mellitus in patients. Histological assessment indicated a strong correlation between microcalcification and NaF uptake in symptomatic patients. Histological evidence of calcification correlated inversely with FDG uptake, which was associated with increased macrophage and CD68 count, both accounting for increased local inflammatory response.
Conclusion
FDG-PET visualizes the inflammatory part of carotid atherosclerosis enabling risk stratification to a certain degree, whereas NaF-PET seems to indicate long-term consequences of ongoing inflammation by demonstrating microcalcification allowing discrimination of atherosclerotic from normal arteries and suggesting clinically significant carotid atherosclerosis.
Purpose
We examined the literature to elucidate the role of 18F-sodium fluoride (NaF)-PET in atherosclerosis.
Methods
Following a systematic search of PubMed/MEDLINE, Embase, and Cochrane Library ...included articles underwent subjective quality assessment with categories low, medium, and high. Of 2811 records, 1780 remained after removal of duplicates. Screening by title and abstract left 41 potentially eligible full-text articles, of which 8 (about the aortic valve (
n
= 1), PET/MRI feasibility (
n
= 1), aortic aneurysms (
n
= 1), or quantification methodology (
n
= 5)) were dismissed, leaving 33 published 2010–2012 (
n
= 6), 2013–2015 (
n
= 11), and 2016–2018 (
n
= 16) for analysis.
Results
They focused on coronary (
n
= 8), carotid (
n
= 7), and femoral arteries (
n
= 1), thoracic aorta (
n
= 1), and infrarenal aorta (
n
= 1). The remaining 15 studies examined more than one arterial segment. The literature was heterogeneous: few studies were designed to investigate atherosclerosis, 13 were retrospective, 9 applied both FDG and NaF as tracers, 24 NaF only. Subjective quality was low in one, medium in 13, and high in 19 studies. The literature indicates that NaF is a very specific tracer that mimics active arterial wall microcalcification, which is positively associated with cardiovascular risk. Arterial NaF uptake often presents before CT-calcification, tends to decrease with increasing density of CT-calcification, and appears, rather than FDG-avid foci, to progress to CT-calcification. It is mainly surface localized, increases with age with a wide scatter but without an obvious sex difference. NaF-avid microcalcification can occur in fatty streaks, but the degree of progression to CT-calcification is unknown. It remains unknown whether medical therapy influences microcalcification. The literature held no therapeutic or randomized controlled trials.
Conclusion
The literature was heterogeneous and with few clear cut messages. NaF-PET is a new approach to detect and quantify microcalcification in early-stage atherosclerosis. NaF uptake correlates with cardiovascular risk factors and appears to be a good measure of the body’s atherosclerotic burden, potentially suited also for assessment of anti-atherosclerotic therapy.
Abstract Background The classification of myocardial infarction into 5 types was introduced in 2007. The prognostic impact of this universal definition, with particular focus on type 2 myocardial ...infarction, has not been studied prospectively in unselected hospital patients. Methods During a 1-year period, all hospitalized patients having cardiac troponin I measured were considered. The diagnosis of a myocardial infarction was according to the universal definition, and specified criteria were used in the classification of type 2 myocardial infarction. Follow-up was at least 1 year, with mortality as the end point. Results A total of 3762 consecutive patients were studied, of whom 488 (13%) had a myocardial infarction. In 119 patients a type 2 myocardial infarction was diagnosed. After a median of 2.1 years (interquartile range, 1.6-2.5 years), 150 patients had died, with a mortality rate of 49% (58/119) in those with type 2 myocardial infarction and 26% (92/360) in those with type 1 myocardial infarction ( P < .0001). In a multivariable Cox regression analysis the following variables were independently associated with mortality: current or prior smoker, high age, prior myocardial infarction, type 2 myocardial infarction, hypercholesterolemia, high p-creatinine, and diabetes mellitus. The multivariable-adjusted hazard ratio for type 2 myocardial infarction was 2.0 (95% confidence interval, 1.3-3.0). With shock as the only exception, mortality was independent of the triggering conditions leading to type 2 myocardial infarction. Conclusions Mortality in patients with type 2 myocardial infarction is high, reaching approximately 50% after 2 years. Further descriptive and survival studies are needed to improve the scientific evidence on which treatment of type 2 myocardial infarction is based.
•Both Gwet's AC1 and Cohen's kappa compare the observed agreement rate with a comparator, but they use conceptually completely different comparators.•Gwet's AC1 and Cohens's kappa behave completely ...different with respect to the influence of the prevalence of positive ratings and with respect to possible values in the case of independence between the raters.•These fundamental differences suggest that Gwet's AC1 is not a substitute for Cohen's kappa.
Gwet's AC1 has been proposed as an alternative to Cohen's kappa in evaluating the agreement between two binary ratings. This approach is becoming increasingly popular, and researchers have been criticized for still using Cohen's kappa. However, a rigorous discussion of properties of Gwet's AC1 is still missing. In this paper several basic properties of Gwet's AC1 are investigated and compared with those of Cohen's kappa, in particular the dependence on the prevalence of positive ratings for a given agreement rate and the behaviour in case of no association or maximal disagreement. Both approaches compare the observed agreement rate with a comparative number. Cohen's kappa uses an expected agreement rate as comparator, whereas Gwet's AC1 uses an expected disagreement rate. Consequently, for a fixed agreement rate, Gwet's AC1 increases with increasing difference of the prevalence of positive ratings from 0.5. In contrast, Cohen's kappa decreases. Gwet's AC1 can take positive and negative values in the case of no association between the two raters, whereas Cohen's kappa is 0. Due to these fundamental differences, Gwet's AC1 should not be seen as a substitute for Cohen's kappa. In particular, the verbal classification of kappa values by Landis & Koch should not be applied to Gwet's AC1.
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Purpose
To examine the diagnostic accuracy of spectral CT pulmonary angiography (S-CTPA) using ventilation-perfusions lung scintigraphy (V/Q-scan) as a reference standard in the diagnosis of acute or ...chronic pulmonary embolism (APE/CPE) and chronic thromboembolic pulmonary hypertension (CTEPH).
Methods
PubMed, Embase, Scopus, and Web of Science were searched for the period from 1 Jan 2006 to 7 Feb 2019; eligible studies had > 10 patients over 18 years old, a diagnostic outcome of PE or CTEPH, and used V/Q scan as a reference standard. Bias and applicability were assessed using QUADAS-2 tools. Sensitivities, specificities, and predictive values were noted or calculated from available information. Meta-analysis employed a fixed-effects model of Mantel and Haenszel. Heterogeneity was assessed with
I
-squared statistics.
Results
Four hundred ninety-three unique records were identified. Following screening by title, 53 studies were included in the abstract and full-text assessment. A total of six articles were included; four were suitable for a meta-analysis. Pooled sensitivity was 94.2% (95% CI, 88.3–100%), pooled specificity was 88.5% (95% CI, 81.3–95.6%), and positive and negative predictive values were 87.8% (95% CI, 80.3–95.4%) and 94.5% (95% CI, 89.3–99.7%), respectively.
Conclusion
Data on S-CTPA for PE/CTEPH remains promising, but limited; only small studies with methodological issues are available. Evidence is best for CPE/CTEPH whereas no firm conclusions are possible for APE. There is a need for larger, prospective studies with a robust composite reference standard including state-of-the-art CTPA and V/Q-scans.
Key Points
• S-CTPA has high sensitivity and specificity for perfusion defects in patients with PE or CPETH.
• Methodological issues and diversity of reference standards were found in the small number of included studies.
• There is a need for larger prospective studies with more robust composite reference standards.
Bland–Altman limits of agreement are very popular in method comparison studies on quantitative outcomes. However, a straightforward application of Bland–Altman analysis requires roughly normally ...distributed differences, a constant bias, and variance homogeneity across the measurement range. If one or more assumptions are violated, a variance-stabilizing transformation (e.g., natural logarithm, square root) may be sufficient before Bland–Altman analysis can be performed. Sometimes, fractional polynomial regression has been used when the choice of variance-stabilizing transformation was unclear and increasing variability in the differences was observed with increasing mean values. In this case, regressing the absolute differences on a function of the average and applying fractional polynomial regression to this end were previously proposed. This review revisits a previous inter-rater agreement analysis on the Agatston score for coronary calcification. We show the inappropriateness of a straightforward Bland–Altman analysis and briefly describe the nonparametric limits of agreement of the original investigation. We demonstrate the application of fractional polynomials, use the Stata packages fp and fp_select, and discuss the use of degree-2 (the default setting) and degree-3 fractional polynomials. Finally, we discuss conditions for evaluating the appropriateness of nonstandard limits of agreement.
Objective
The benefit of FDG-PET/CT in follow-up of patients treated with adjuvant immunotherapy after resection of high-risk malignant melanoma (MM) is debated. This study evaluated the diagnostic ...accuracy and clinical impact of FDG-PET/CT for diagnosing MM recurrence during the first year after surgery.
Methods
We retrospectively included 124 patients with resected high-risk MM, who received adjuvant immunotherapy and follow-up FDG-PET/CT. Clinical information and AJCC-8 stage was obtained from patients’ medical records. Recurrence was verified by biopsy/progression on a subsequent scan leading to change of treatment. Non-recurrence was assumed when no metastases were observed until the subsequent follow-up scan. Incidence of recurrence, sensitivity, specificity, positive and negative predictive values (PPV and NPV) were outcome measures.
Results
Incidence rate of MM recurrence was 0.27 95% CI 0.17–0.37 per person-year during the first-year. Recurrence was detected in 13 patients (10%) at 3-month FDG-PET/CT, in 10 patients (8.1%) at 6 months, 1 patient (0.8%) at 9 months, 3 patients (2.4%) at 12 months. The overall sensitivity, specificity, PPV, and NPV were 97% 86–99, 82% 78–86, 39% 29–50, and 99% 98–99, respectively. The PPV trended towards higher values as disease stage increased. At the 3-month scan, the majority of actions derived from positive findings were surgery or earlier expedition of the subsequent follow-up scan.
Conclusion
The high rate of recurrence in patients with high-risk MM treated with adjuvant immunotherapy emphasizes the need for follow-up. The potential harm by a moderately low specificity reflecting a high number of false-positive results must be weighed against the benefit of early detection of recurrence.
The area under the receiver operating characteristics curve is a popular measure of the overall discriminatory power of a continuous variable used to indicate the presence of an outcome of interest, ...such as disease or disease progression. In clinical practice, the use of cut-off points as benchmark values for further treatment planning is greatly appreciated, despite the loss of information that such a dichotomization implies. Optimal cut-off points are often derived from fixed sample size studies, and the aim of this study was to investigate the convergence behavior of optimal cut-off points with increasing sample size and to explore a heuristic and path-based algorithm for cut-off point determination that targets stagnating cut-off point values. To this end, the closest-to-(0,1) criterion in receiver operating characteristics curve analysis was used, and the heuristic and path-based algorithm aimed at cut-off points that deviated less than 1% from the cut-off point of the previous iteration. Such a heuristic determination stopped after only a few iterations, thereby implicating practicable sample sizes; however, the result was, at best, a rough estimate of an optimal cut-off point that was unbiased and positively and negatively biased for a prevalence of 0.5, smaller than 0.5, and larger than 0.5, respectively.
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