Darryl McGill

Over time, high-sensitivity TnT replaces NT-proBNP as the most powerful predictor of death in patients with dialysis-dependent chronic renal failure

BACKGROUND Cardiac biomarkers are emerging as a potentially powerful prognostic tool for renal-dialysis patients. The optimal biomarker and/or combination of biomarkers for predicting mortality remain uncertain. This study evaluates the prognostic value of the new high-sensitivity troponin T (TnT) assay compared to established biomarkers. METHODS All patients had blood sampled for prospective assessment of the prognostic value of traditional risk markers including albumin and CRP, and cardiac biomarkers BNP, NT-proBNP, TnT and TnI. Patients were closely monitored clinically. Mortality and morbidity outcomes were documented for a national morbidity and mortality database. Stored samples were subsequently used to measure TnT with a new high-sensitivity assay. RESULTS After a median of 30 months from blood collection, NT-proBNP was the most powerful predictor of all-cause mortality, along with albumin. After a median of 46.7 months the new high-sensitive TnT assay was the only cardiac biomarker predictive of all-cause mortality. TnT was detectable in all dialysis patients using the high-sensitive TnT assay with a cut-point of 24.15 ng/L below which all patients survived. CONCLUSIONS The new hs-TnT is the most powerful biomarker for prognostic classification for all-cause mortality of all the commonly used biomarkers for our renal-dialysis population. Our study also suggests that cardiac biomarkers have a different prognostic ability for different time frames with NT-proBNP being a better predictor for early mortality and troponin for later mortality.

Supervisor assessment of clinical and professional competence of medical trainees: a reliability study using workplace data and a focused analytical literature review

Even though rater-based judgements of clinical competence are widely used, they are context sensitive and vary between individuals and institutions. To deal adequately with rater-judgement unreliability, evaluating the reliability of workplace rater-based assessments in the local context is essential. Using such an approach, the primary intention of this study was to identify the trainee score variation around supervisor ratings, identify sampling number needs of workplace assessments for certification of competence and position the findings within the known literature. This reliability study of workplace-based supervisors’ assessments of trainees has a rater-nested-within-trainee design. Score variation attributable to the trainee for each competency item assessed (variance component) were estimated by the minimum-norm quadratic unbiased estimator. Score variance was used to estimate the number needed for a reliability value of 0.80. The trainee score variance for each of 14 competency items varied between 2.3% for emergency skills to 35.6% for communication skills, with an average for all competency items of 20.3%; the “Overall rating” competency item trainee variance was 28.8%. These variance components translated into 169, 7, 17 and 28 assessments needed for a reliability of 0.80, respectively. Most variation in assessment scores was due to measurement error, ranging from 97.7% for emergency skills to 63.4% for communication skills. Similar results have been demonstrated in previously published studies. In summary, overall supervisors’ workplace based assessments have poor reliability and are not suitable for use in certification processes in their current form. The marked variation in the supervisors’ reliability in assessing different competencies indicates that supervisors may be able to assess some with acceptable reproducibility; in this case communication and possibly overall competence. However, any continued use of this format for assessment of trainee competencies necessitates the identification of what supervisors in different institutions can reliably assess rather than continuing to impose false expectations from unreliable assessments.

Newer cardiac troponin I assays have similar performance to troponin T in patients with end-stage renal disease

Background: Troponin T is present in the blood of a majority of patients with endstage renal disease (ESRD) undergoing regular dialysis and presence of troponin T is a predictor of adverse outcome in these patients. With several new formulations of troponin I assays available, this study was performed to see whether these newer assays were able to detect troponin I in these patients more effectively than the older assays. Methods: One hundred and forty-three patients undergoing regular haemodialysis or peritoneal dialysis had plasma collected and troponin T and troponin I measured by a variety of assays. Results: The newer troponin I assays (Abbott Architect, Bayer Centaur and Beckman Accu-TnI) were able to detect troponin I (>75% of samples) as effectively as the Roche assay was able to detect troponin T, while other troponin I assays had a much lower rate of detection of troponin - DPC Immulite 2000 16% and Abbott AxSYM 35%. However, the troponin T assay had more samples detected at concentrations corresponding to an assay CV of 10% (59% of samples) than did the newer troponin I assays (highest on the Bayer Centaur at 37%). Conclusions: Newer assays demonstrate that troponin I is present in a similar number of samples as is troponin T, in the blood of patients with dialysis-dependent renal failure, and these newer troponin I assays identify patients at risk of experiencing a cardiac event.

Anticoagulant therapy, anti-platelet agents and gastrointestinal endoscopy.

Background: The increasing use of anticoagulant therapy and anti‐platelet agents in the primary and secondary prevention of cardiovascular, cerebrovascular and venous thromboembolic disease has increased the need for guidelines for managing these agents prior to gastrointestinal endoscopy, particularly if therapeutic manoeuvres are required. The continuation of anticoagulant therapy increases the risk of haemorrhagic complications of gastrointestinal endoscopy. Temporary suspension of anticoagulant therapy exposes the patient to the risk of thromboembolism associated with the underlying condition requiring anticoagulant treatment.

Shorter Ischaemic Time and Improved Survival with Pre-hospital STEMI Diagnosis and Direct Transfer for Primary PCI

BACKGROUND We sought to determine if our regional program for pre-hospital STEMI diagnosis and direct transfer for primary PCI (PPCI) was associated with shorter ischaemic times and improved survival compared with ED diagnosis. METHODS STEMI diagnosis was made at the scene by pre-hospital ECG or in local EDs depending on patient presentation. Ambulance ECGs were transmitted to our ED for cath lab activation. Patient variables and outcomes at 12 months were recorded. RESULTS We treated 782 consecutive patients with PPCI during January 2008-June 2013. Cath lab activation was initiated prior to hospital arrival (pre-hospital) in 24% of cases and by ED in 76% of cases. Median total ischaemic time was 154 min for pre-hospital and 211 minutes for ED patients (p<0.0001). Mortality at 12 months was 7.9% in the ED group compared with 3.7% in the pre-hospital group (p=0.036). On multivariate Cox regression analysis including baseline and procedural variables, pre-hospital activation remained an independent predictor of mortality (HR 0.45, 95% CI 0.20-1.0, p=0.03). CONCLUSIONS Pre-hospital diagnosis of STEMI and direct transfer to the cath lab reduced total ischaemic time by 57 minutes and mortality by >50% following PPCI. Further efforts are needed to increase the proportion of STEMI patients treated using this strategy.

Symptom-to-Balloon Time is a Strong Predictor of Adverse Events Following Primary Percutaneous Coronary Intervention: Results From the Australian Capital Territory PCI Registry

BACKGROUND Notwithstanding improvements in door-to-balloon time, adverse event rates after primary PCI have remained steady. We analysed the effect of symptom-to-balloon (STB) time, a reflection of total ischaemic time, on major adverse cardiovascular events (MACE) and explored predictors of prolonged STB time. METHODS The study population included 1002 consecutive patients (22.4% women) with a mean age of 62.3±13.2 years, who underwent primary PCI during 2008-2014. Groups were compared for STB ≤ and >240min. Primary endpoint was one-year MACE, a composite of death, reinfarction, stent thrombosis or target vessel revascularisation. RESULTS Symptom-to-balloon time was available in 893 patients of which 588 (65.8%) had STB ≤240min and 305 (34.2%) had STB >240min. The incidence of one-year MACE increased significantly in a stepwise manner with increasing STB time (p for trend=0.003). Symptom-to-balloon time was an independent predictor of one-year MACE along with age >70 years, final TIMI flow <3, three vessel disease, cardiogenic shock and out-of-hospital cardiac arrest. We also performed a multivariate analysis to determine predictors of delayed treatment. Predictors of STB time >240min were age >70 years, female gender, diabetes, absence of prehospital catheter laboratory activation and presentation to a non-PCI centre. CONCLUSION Incidence of MACE was strongly correlated with STB time and STB time was an independent predictor of MACE. We have identified specific subgroups with prolonged STB times (age >70, female gender, diabetes, absence of prehospital activation and presentation to a non-PCI centre). This information should inform future studies and strategies to minimise delays in these subgroups for improved outcomes.

Construct validation of judgement-based assessments of medical trainees’ competency in the workplace using a “Kanesian” approach to validation

BackgroundEvaluations of clinical assessments that use judgement-based methods have frequently shown them to have sub-optimal reliability and internal validity evidence for their interpretation and intended use. The aim of this study was to enhance that validity evidence by an evaluation of the internal validity and reliability of competency constructs from supervisors’ end-of-term summative assessments for prevocational medical trainees.MethodsThe populations were medical trainees preparing for full registration as a medical practitioner (74) and supervisors who undertook ≥2 end-of-term summative assessments (n = 349) from a single institution. Confirmatory Factor Analysis was used to evaluate assessment internal construct validity. The hypothesised competency construct model to be tested, identified by exploratory factor analysis, had a theoretical basis established in workplace-psychology literature. Comparisons were made with competing models of potential competency constructs including the competency construct model of the original assessment. The optimal model for the competency constructs was identified using model fit and measurement invariance analysis. Construct homogeneity was assessed by Cronbach’s α. Reliability measures were variance components of individual competency items and the identified competency constructs, and the number of assessments needed to achieve adequate reliability of R > 0.80.ResultsThe hypothesised competency constructs of “general professional job performance”, “clinical skills” and “professional abilities” provides a good model-fit to the data, and a better fit than all alternative models. Model fit indices were χ2/df = 2.8; RMSEA = 0.073 (CI 0.057-0.088); CFI = 0.93; TLI = 0.95; SRMR = 0.039; WRMR = 0.93; AIC = 3879; and BIC = 4018). The optimal model had adequate measurement invariance with nested analysis of important population subgroups supporting the presence of full metric invariance. Reliability estimates for the competency construct “general professional job performance” indicated a resource efficient and reliable assessment for such a construct (6 assessments for an R > 0.80). Item homogeneity was good (Cronbach’s alpha = 0.899). Other competency constructs are resource intensive requiring ≥11 assessments for a reliable assessment score.ConclusionInternal validity and reliability of clinical competence assessments using judgement-based methods are acceptable when actual competency constructs used by assessors are adequately identified. Validation for interpretation and use of supervisors’ assessment in local training schemes is feasible using standard methods for gathering validity evidence.

Tolvaptan for Heart Failure in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis

BACKGROUND Heart failure (HF) is frequently associated with renal impairment. Tolvaptan is reported to be effective in treating congestion in HF without significant electrolyte loss compared to conventional diuretics. However, the safety and efficacy of its use in patients with chronic kidney disease (CKD) is uncertain. This systematic review and meta-analysis evaluated the efficacy and safety outcomes of tolvaptan for HF management in patients with CKD, with a focus at a physiologic basis related to safety. METHODS We searched for observational studies and randomised clinical trials (RCTs) that assessed the effects of tolvaptan against placebo or standard care in adult patients with HF and CKD. Our protocol was registered with PROSPERO (number CRD42017052775). RESULTS Seventeen studies were included in the qualitative review and six in the meta-analysis involving 1597 patients. Tolvaptan was associated with an increase in sodium concentration. No significant differences in change of eGFR and serum creatinine were found between tolvaptan and control groups. Urine flow rate appears to increase significantly with tolvaptan compared to baseline (p<0.0001). The meta-analysis demonstrated no heterogeneity between studies but the possibility of publication bias due to incomplete reporting in excluded studies and lack of RCTs. CONCLUSIONS The safety profile of tolvaptan appears acceptable for patients with HF and CKD. There is evidence for an improvement in serum sodium and reduction in body water without deterioration in renal function. Further research is needed to elucidate the long-term benefits of tolvaptan as an adjunct or alternative to diuretics in such patients.

Fractal analysis of heart rate variability as a predictor of mortality: A systematic review and meta-analysis

Previous studies have suggested benefits of applying fractal analysis to intervals between R waves in electrocardiography as an additional prognostic marker. The aim of this study was to investigate whether fractal analysis can provide an independent predictor of cardiac mortality or all-cause mortality. Prognostic cohort studies reporting fractal heart rate variability results from 24-h Holter monitor recordings were selected for comparison. Populations were subdivided into four groups-post-myocardial infarction, left ventricular dysfunction, other cardiac, and non-cardiac patients-and analysed using ANOVA, Forest plots (using pooled mean difference), and Funnel plots. The most significant mean differences were recorded in short-term fractal self-similarity (α1) (-0.17, 95% CI [-0.21, -0.13], p < 0.00001) and the traditional measure called standard deviation of NN intervals (SDNN) (-13.31, 95% CI [-18.89, -7.73], p < 0.00001) between the deceased and survivor groups. Fractal measures of long-term fractal self-similarity (α2), 1/f scaling (β), and traditional heart rate variability measures of high frequency to low frequency ratio show promise. This review indicated that fractal measure α1 and traditional measure SDNN could be potential predictors of mortality, but require further assessment to determine appropriate thresholds for clinical significance and additional targeted prognostic studies to properly define their applicability as prognostic markers. Therefore, clinicians should interpret fractal and traditional measures with caution since such measures have yet to be fully described as biomarkers for clinical application.