Expert elicitation to inform a cost effectiveness analysis of screening for renal cancer: methodological and practical considerations

Background: Population screening for renal cell carcinoma (RCC) using ultrasound has the potential to improve survival outcomes; however a cost-effectiveness analysis (CEA) has yet to be performed. Due to the lack of existing evidence, we performed structured expert elicitation to derive unknown quantities to inform the CEA. Objectives: To elicit the cancer stage distribution (proportion of individuals with each stage of cancer) for different RCC screening scenarios and the annual transition probabilities for undiagnosed disease becoming diagnosed in the NHS. Methods: The study design and reporting adhered to the Reporting Guidelines for the Use of Expert Judgement in Model-Based Economic Evaluations. The elicitation was conducted face-to-face or via telephone between each individual expert and the facilitator, aided by online material. For multinomial data, Connor Mosimann and modified Connor Mosimann distributions were fitted for each expert and for all experts combined using mathematical linear pooling. Results: A total of 24 clinical experts were invited, and 71% participated (7 urologists, 6 oncologists, 4 radiologists). The modified Connor Mosimann distribution provided the best fit for the majority of elicited quantities. Greater uncertainty was noted for the elicited transition probabilities compared to the elicited stage distributions. Conclusion: We performed the first expert elicitation of RCC screening parameters, crucial information which will inform the CEA of screening. Additionally, the elicited quantities may enable future health economic evaluations assessing the value of diagnostic tools and pathways in RCC

Incidence of arrhythmias and heart rate variability in wild-type rats exposed to social stress

Psychological stressors of different natures can induce different shifts of autonomic control on cardiac electrical activity, with either a sympathetic or a parasympathetic prevalence. Arrhythmia occurrence, R-R interval variability, and plasma catecholamine elevations were measured in male wild-type rats exposed to either a social stressor (defeat) or a nonsocial challenge (restraint). Electrocardiograms were telemetrically recorded, and blood samples were withdrawn through jugular vein catheters from normal, freely moving animals. Defeat produced a much higher incidence of arrhythmias (mostly ventricular premature beats), which were mainly observed in the 60-s time periods after attacks. The social challenge also induced a much stronger reduction of average R-R interval, a lower R-R interval variability (as estimated by the time-domain parameters standard deviation of mean R-R interval duration, coefficient of variance, and root mean square of successive differences in R-R interval duration), and higher elevations of venous plasma catecholamines compared with restraint. These autonomic and/or neuroendocrine data indicate that a social stressor such as defeat is characterized by both a higher sympathetic activation and a lower parasympathetic antagonism compared with a nonsocial restraint challenge, which results in a higher risk for ventricular arrhythmias

Incidence of arrhythmias and heart rate variability in wild-type rats exposed to social stress

Psychological stressors of different natures can induce different shifts of autonomic control on cardiac electrical activity, with either a sympathetic or a parasympathetic prevalence. Arrhythmia occurrence, R-R interval variability, and plasma catecholamine elevations were measured in male wild-type rats exposed to either a social stressor (defeat) or a nonsocial challenge (restraint). Electrocardiograms were telemetrically recorded, and blood samples were withdrawn through jugular vein catheters from normal, freely moving animals. Defeat produced a much higher incidence of arrhythmias (mostly ventricular premature beats), which were mainly observed in the 60-s time periods after attacks. The social challenge also induced a much stronger reduction of average R-R interval, a lower R-R interval variability (as estimated by the time-domain parameters standard deviation of mean R-R interval duration, coefficient of variance, and root mean square of successive differences in R-R interval duration), and higher elevations of venous plasma catecholamines compared with restraint. These autonomic and/or neuroendocrine data indicate that a social stressor such as defeat is characterized by both a higher sympathetic activation and a lower parasympathetic antagonism compared with a nonsocial restraint challenge, which results in a higher risk for ventricular arrhythmias.

Impact of mitral regurgitation in patients with acute heart failure: insights from the RELAX-AHF-2 trial

Aims The impact of mitral regurgitation (MR) in patients hospitalized for acute heart failure (AHF) is not well established. We assessed the role of MR in patients enrolled in the Relaxin in Acute Heart Failure 2 (RELAX-AHF-2) trial.Methods and results Patients enrolled in RELAX-AHF-2 with available data regarding MR status were included in this analysis. Baseline characteristics, in-hospital data, and clinical outcomes through 180-day follow-up were evaluated. The impact of moderate/severe MR was assessed. Among 6420 AHF patients with known MR status, 1810 patients (28.2%) had moderate/severe MR. Compared to patients with no/mild MR, those with moderate/severe MR were more likely to have history of heart failure (HF), prior HF hospitalization, more comorbidities, symptoms/signs of HF, lower left ventricular ejection fraction and higher N-terminal pro-B-type natriuretic peptide levels. Moderate/severe MR was associated with longer length of hospital stay, higher rates of residual dyspnoea, increased jugular venous pressure through the index hospitalization and a higher unadjusted risk of the composite of cardiovascular (CV) death or rehospitalization for HF/renal failure (RF) through 180 days (crude hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.03-1.27, p = 0.01). The association between moderate/severe MR and poorer outcomes was not maintained in a multivariable model including several covariates of interest (adjusted HR 1.03, 95% CI 0.91-1.17, p = 0.65). Similar findings were observed for HF/RF rehospitalization alone.Conclusions In patients with AHF, moderate/severe MR was associated with a worse clinical profile but did not have an independent prognostic impact on clinical outcomes

Trajectories of Changes in Renal Function in Patients with Acute Heart Failure

Background: Changes in renal function have been associated with differential outcomes in patients with acute heart failure (HF). However, individual trajectories of changes in renal function are unknown, and it is unclear whether they relate to different clinical characteristics and clinical outcomes. Our aim was to investigate the prognostic importance of individual trajectories of change in renal function in acute HF. Methods: This was a retrospective, observational analysis from the double-blind, randomized, placebo-controlled PROTECT trial in patients with acute HF. We identified and internally validated 8 different renal trajectories among 1897 patients by visual inspection of inhospital serum creatinine changes. The primary outcome measure was all-cause mortality at 180 days. Mean age was 70 ± 12 years; 70% were male, and mean baseline estimated glomerular filtration rate was 49.0 mL/min/1.73m2. Results: A total of 8 different trajectories was established. The most prevalent trajectories were an inhospital bump (19.0%), a sustained increase (17.6%) and a dip (14.5%) in serum creatinine. Overall, the clinical characteristics of patients in different trajectories were remarkably similar. Crude 180-day mortality rates ranged from 12.0% in the trajectory, with no significant changes to 18.3% in the trajectory of sustained increase without significant differences. Overall, after multivariable adjustment, there was no trajectory of changes in renal function that was associated with significantly better or worse outcomes. Conclusions: Trajectories of changes in renal function in acute HF differ considerably on the patient level. Despite these differences, clinical characteristics and outcomes were similar, therefore, questioning the prognostic importance of changes in renal function in acute HF