Implementing the treatment arm of a clinical trial often requires changes to healthcare practices. Barriers to such changes may undermine the delivery of the treatment making it more likely that the trial will demonstrate no treatment effect. The ‘Major outcomes with personalized dialysate temperature’ (MyTEMP) is a cluster-randomised trial to be conducted in 84 haemodialysis centres across Ontario, Canada to investigate whether there is a difference in major outcomes with an individualized dialysis temperature (IDT) of 0.5 °C below a patient’s body temperature measured at the beginning of each haemodialysis session, compared to a standard dialysis temperature of 36.5 °C. To inform how to deploy the IDT across many haemodialysis centres, we assessed haemodialysis physicians’ and nurses’ perceived barriers and enablers to IDT use. We developed two topic guides using the Theoretical Domains Framework (TDF) to assess perceived barriers and enablers to IDT ordering and IDT setting (physician and nurse behaviours, respectively). We recruited a purposive sample of haemodialysis physicians and nurses from across Ontario and conducted in-person or telephone interviews. We used directed content analysis to double-code transcribed utterances into TDF domains, and inductive thematic analysis to develop themes. We interviewed nine physicians and nine nurses from 11 Ontario haemodialysis centres. We identified seven themes of potential barriers and facilitators to implementing IDTs: (1) awareness of clinical guidelines and how IDT fits with local policies (knowledge; goals), (2) benefits and motivation to use IDT (beliefs about consequences; optimism; reinforcement; intention; goals), (3) alignment of IDTs with usual practice and roles (social/professional role and identity; nature of the behaviour; beliefs about capabilities), (4) thermometer availability/accuracy and dialysis machine characteristics (environmental context and resources), (5) impact on workload (beliefs about consequences; beliefs about capabilities), (6) patient comfort (behavioural regulation; beliefs about consequences; emotion), and (7) forgetting to prescribe or set IDT (memory, attention, decision making processes; emotion). There are anticipatable barriers to changing healthcare professionals’ behaviours to effectively deliver an intervention within a randomised clinical trial. A behaviour change framework can help to systematically identify such barriers to inform better delivery and evaluation of the treatment, therefore potentially increasing the fidelity of the intervention to increase the internal validity of the trial. These findings will be used to optimise the delivery of IDT in the MyTEMP trial and demonstrate how this approach can be used to plan intervention delivery in other clinical trials. ClinicalTrials.gov NCT02628366 . Registered November 16 2015.

The hepatic circulation is involved in adaptive systemic responses to circulatory stress. However, it is vulnerable to both chronic hypervolemia and cardiac dysfunction. The influence of hemodialysis (HD) and ultrafiltration (UF) upon liver water content has been understudied. We conducted a detailed pilot study to characterize the effects of HD upon liver water content and stiffness, referenced to peripheral fluid mobilization and total body water. We studied 14 established HD patients without liver disease. Magnetic resonance imaging (MRI) together with ultrasound-based elastography and bioimpedance assessment were employed to measure hepatic water content and stiffness, body composition, and water content in the calf pre- and post-HD. Mean UF volume was 8.13 ± 4.4 mL/kg/hr. Fluid removal was accompanied with effective mobilization of peripheral water (measured with MRI within the thigh) from 0.85 ± 0.21 g/mL to 0.83 ± 0.18 g/mL, and reduction in total body water (38.9 ± 9.4 L to 37.4 ± 8.6 L). However, directly-measured liver water content did not decrease (0.57 ± 0.1 mL/g to 0.79 ± 0.3 m L/g). Liver water content and IVC diameter were inversely proportional (r = − 0.57, p = 0.03), a relationship which persisted after dialysis. In contrast to the reduced total body water content, liver water content did not decrease post-HD, consistent with a diversion of blood to the hepatic circulation, in those with signs of greater circulatory stress. This novel observation suggests that there is a unique hepatic response to HD with UF and that the liver may play a more important role in intradialytic hypotension and fluid shifts than currently appreciated.

Background: Atrial fibrillation is a prevalent cardiac arrhythmia and may reduce cerebral blood perfusion augmenting the risk of dementia. We hypothesize that geometric variations in the cerebral arterial structure called the Circle of Willis (CoW) play an important role in influencing cerebral perfusion. The objective of this work was to develop a novel cardio-cerebral lumped parameter hemodynamic model to investigate the role of CoW variants on cerebral blood flow dynamics under atrial fibrillation conditions. Methods: A computational blood flow model was developed by coupling whole-body and detailed cerebral circulation descriptions, modified to represent six common variations of the CoW. Cerebral blood flow dynamics were simulated in common CoW variants, under control and imposed atrial fibrillation conditions. Risk was assessed based on the frequency of beat-wise hypoperfusion events, and sensitivity analysis was performed with respect to this model output. Results: It was found that the geometry of the CoW influenced the frequency of hypoperfusion events at different heart rates, with the variant missing a P1 segment having the highest risk. Sensitivity analysis revealed that intrinsic heart rate is most associated with the considered outcome. Conclusions: Our results suggest that CoW geometry plays an important role in influencing cerebral hemodynamics during atrial fibrillation. The presented study may assist in guiding our future clinical-imaging research.

Background: We developed a hemodynamic mathematical model of human circulation coupled to a virtual hemodialyzer. The model was used to explore mechanisms underlying our clinical observations involving hemodialysis. Methods: The model consists of whole body human circulation, baroreflex feedback control, and a hemodialyzer. Four model populations encompassing baseline, dialysed, therapeutic hypothermia treated, and simultaneous dialysed with hypothermia were generated. In all populations atrial fibrillation and renal failure as co-morbidities, and exercise as a treatment were simulated. Clinically relevant measurables were used to quantify the effects of each in silico experiment. Sensitivity analysis was used to uncover the most relevant parameters. Results: Relative to baseline, the modelled dialysis increased the population mean diastolic blood pressure by 5%, large vessel wall shear stress by 6%, and heart rate by 20%. Therapeutic hypothermia increased systolic blood pressure by 3%, reduced large vessel shear stress by 15%, and did not affect heart rate. Therapeutic hypothermia reduced wall shear stress by 15% in the aorta and 6% in the kidneys, suggesting a potential anti-inflammatory benefit. Therapeutic hypothermia reduced cardiac output under atrial fibrillation by 12% and under renal failure by 20%. Therapeutic hypothermia and exercise did not affect dialyser function, but increased water removal by approximately 40%. Conclusions: This study illuminates some mechanisms of the action of therapeutic hypothermia. It also suggests clinical measurables that may be used as surrogates to diagnose underlying diseases such as atrial fibrillation.

Purpose of review: Patients on hemodialysis have significantly higher rates of cardiovascular mortality resulting from a multitude of myocardial dysfunctions. Current imaging modalities allow independent assessment of cardiac morphology, contractile function, coronary arteries and cardiac perfusion. Techniques such as cardiac computed tomography (CT) imaging have been available for some time, but have not yet had widespread adoption because of technical limitations related to cardiac motion, radiation exposure and safety of contrast agents in kidney disease. Recent findings: Novel dynamic contrast-enhanced (DCE) CT imaging can be used to acquire high-resolution cardiac images, which simultaneously allow the assessment of coronary arteries and the quantitative measurement of myocardial perfusion. The advancement of recent CT scanners and cardiac protocols have allowed noninvasive imaging of the whole heart in a single imaging session with minimal cardiac motion artefact and exposure to radiation. Summary: DCE-CT imaging in clinical practice would allow comprehensive evaluation of the structure, function, and hemodynamics of the heart in a short, well tolerated scanning session. It is an imaging tool enabling the study of myocardial dysfunction in dialysis patients, who have greater cardiovascular risk than nonrenal cardiovascular disease populations, both at rest and under cardiac stress associated with hemodialysis itself.

Background: Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. Chronic exposure to intermittent hemodialysis may be a source of added stress to the cardiovascular system; intradialytic hypotension is a common complication of hemodialysis, and repeated events may lead to hemodynamic stress and ischemic injuries. Administration of non-pneumatic compression stockings to the lower limbs has demonstrated hemodynamic stabilizing effects in other settings and may provide similar benefits in the kidney disease population. Therefore, we conducted this pilot study assessing the feasibility and tolerability of the application of non-pneumatic compression stockings to patients with kidney disease. We also assessed the changes in hemodynamic measurements following the application of the compression stockings to explore the biological feasibility of this being an effective intervention for intradialytic hypotension. Methods: Fifteen individuals were enrolled in the study (5 healthy, 5 chronic kidney disease patients, and 5 dialysis patients). Outcomes including hemodynamic parameters such as cardiac output, peripheral vascular resistance, and blood pressure were measured using continuous pulse wave analysis. Changes in global longitudinal strain were measured via echocardiography. These outcome measurements were made before and after the application of compression stockings. Results: All study participants tolerated the compression garments well and without complication. Hemodynamic response to lower body compression caused varying effects on cardiac output, mean arterial pressure and global longitudinal strain. Some individuals saw large improvements in hemodynamic parameters while in others the opposite effect was observed. No consistent response was elicited. Conclusions: Application of compression stockings to patients with renal dysfunction is well-tolerated. However, significant variations in hemodynamic outcomes exist, and may be a barrier for larger scale trials without prior identification of specific patient characteristics indicating likely benefit from the application of external compression. Trial registration: ClinicalTrials.gov, Identifier: NCT02915627, Registration Date: Sept 27, 2016.