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Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.

Single ventricle patients, including those with hypoplastic left heart syndrome (HLHS), typically undergo three palliative heart surgeries culminating in the Fontan procedure. HLHS is associated with high rates of morbidity and mortality, and many patients develop arrhythmias, electrical dyssynchrony, and eventually ventricular failure. However, the correlation between ventricular enlargement and electrical dysfunction in HLHS physiology remains poorly understood. Here we characterize the relationship between growth and electrophysiology in HLHS using computational modeling. We integrate a personalized finite element model, a volumetric growth model, and a personalized electrophysiology model to perform controlled in silico experiments. We show that right ventricle enlargement negatively affects QRS duration and interventricular dyssynchrony. Conversely, left ventricle enlargement can partially compensate for this dyssynchrony. These findings have potential implications on our understanding of the origins of electrical dyssynchrony and, ultimately, the treatment of HLHS patients., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Medical Instruments & Bio-Inspired Technology

Many drugs interact with ion channels in the cells of our heart and trigger heart rhythm disorders with potentially fatal consequences. Computational modeling can provide mechanistic insight into the onset and propagation of drug-induced arrhythmias, but the effect of drugs on the mechanical performance of the heart remains poorly understood. Here we establish a multiphysics framework that integrates the biochemical, electrical, and mechanical effects of drugs, from cellular excitation to cardiac contraction. For the example of the drug dofetilide, we show that drug concentrations of 5x and 8x increase the heart rate to 122 and 114 beats per minute, increase myofiber stretches by 5%, and decrease overall tissue relaxation by 6%. This results in inter-ventricular and atrial-ventricular dyssynchronies and changes in cardiac output by - 2.5 % and +7%. Our results emphasize the need for multiphysics modeling to better understand the mechanical implications of drug-induced arrhythmias. Knowing how different drug concentrations affect the performance of the heart has important clinical implications in drug safety evaluation and personalized medicine., Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public., Medical Instruments & Bio-Inspired Technology