Balancing scarce hospital resources during the COVID-19 pandemic using discrete-event simulation

COVID-19 has disrupted healthcare operations and resulted in large-scale cancellations of elective surgery. Hospitals throughout the world made life-altering resource allocation decisions and prioritised the care of COVID-19 patients. Without effective models to evaluate resource allocation strategies encompassing COVID-19 and non-COVID-19 care, hospitals face the risk of making sub-optimal local resource allocation decisions. A discrete-event-simulation model is proposed in this paper to describe COVID-19, elective surgery, and emergency surgery patient flows. COVID-19-specific patient flows and a surgical patient flow network were constructed based on data of 475 COVID-19 patients and 28,831 non-COVID-19 patients in Addenbrooke’s hospital in the UK. The model enabled the evaluation of three resource allocation strategies, for two COVID-19 wave scenarios: proactive cancellation of elective surgery, reactive cancellation of elective surgery, and ring-fencing operating theatre capacity. The results suggest that a ring-fencing strategy outperforms the other strategies, regardless of the COVID-19 scenario, in terms of total direct deaths and the number of surgeries performed. However, this does come at the cost of 50% more critical care rejections. In terms of aggregate hospital performance, a reactive cancellation strategy prioritising COVID-19 is no longer favourable if more than 7.3% of elective surgeries can be considered life-saving. Additionally, the model demonstrates the impact of timely hospital preparation and staff availability, on the ability to treat patients during a pandemic. The model can aid hospitals worldwide during pandemics and disasters, to evaluate their resource allocation strategies and identify the effect of redefining the prioritisation of patients.

     

Pathophysiology of Erectile Dysfunction

Physiology of erection and pathophysiology erectile dysfunction is reviewed. Analysis is obtained from basic and clinical research including animals studies, anatomical studies, and molecular and cellular research on corporal tissue obtained during penile prosthesis implantation. Supraspinal influences and spinal influence on penile erection has been learned from spinal cord injury patient. Corporal smooth muscle relaxation of penile arteries and corpus cavernosum leads to penile erection, results from parasympathetic/nonadrenergic noncholinergic neural pathway activation and simultaneous inhibition of sympathetic outflow. Anatomical studies taught understanding of the mechanism for restriction of blood outflow from the corpora cavernosa. The change of smooth muscle tone has emerged as a key factor in erection and detumescence. Many independent factors converge on the modulation of corporal smooth muscle tone. Neuronal and local neurotransmitter effects via gap junction, potassium channels, and calcium channel. A nitric oxide/cyclic guanosine monophosphate mechanism as well as cyclic aminomonophosphate has an important role in mediating the corporal smooth muscle relaxation necessary for erectile function. Erectile dysfunction can be due to vasculogenic, neurogenic, hormonal, veno-occlusive, psychogenic and/or pharmacogenic factors as well as alterations in the nitric oxide/cyclic guanosine monophosphate (cGMP) or cyclic aminophosphate (cAMP) pathway or other regulatory mechanisms including gap junction or ionic channel resulting in an imbalance in corporal smooth muscle contraction and relaxation. Our present knowledge of the hemodynamics, functional anatomy, neurophysiology, and neuropharmacology of penile erection and dysfunction at the cellular and molecular level has led to better understanding of physiology and pathophysiology of erectile dysfunction.     

Update on Corpus Cavernosum Smooth Muscle Contractile Pathways in Erectile Function: A Role for Testosterone?

IntroductionNormal erectile function (EF) involves a coordinated relaxation of the arteries that supply the penis and the corpus cavernosum smooth muscle (CCSM), resulting in expansion of the sinusoids and increased intracavernous pressure. But the CCSM spends the majority of its time in the contracted state which is mediated by norepinephrine released from nerve endings and other vasoconstrictors like endothelins released from the endothelium. These agents cause smooth muscle myosin (SMM) phosphorylation by elevating intracellular calcium. When calcium returns to basal levels, the calcium sensitivity increases and prevents myosin dephosphorylation, which involves the RhoA/Rho‐kinase (ROK) mechanism, thus maintaining force. Although mounting evidences demonstrate that androgens have a major influence on EF that is not just centrally mediated, this notion remains quite controversial.AimTo summarize the current knowledge on CCSM contractile pathways, the role they play in modulating EF, and the influence of androgens.MethodsThe article reviews the literature and contains some previously unpublished data on CCSM contraction signaling including the role that androgens are known to play in modulating these pathways.Main Outcome MeasuresData from peer‐reviewed publications and previously unpublished observations.ResultsIn addition to downregulation of many pro‐erectile molecular mechanisms, decreased testosterone (T) levels upregulate CCSM contractility, including hyperresponsiveness to α‐adrenergic agonists, increased SMM phosphorylation, alteration of SMM isoform composition, activation of RhoA/ROK signaling and modulation of sphingosine‐1‐phosphate regulation of CCSM tone.ConclusionsDecreased T levels upregulate CCSM contractile signaling. Meanwhile, it downregulates CCSM relaxation pathways synergizing to produce erectile dysfunction (ED). Although some urologists and researchers are still skeptical of the influence of androgens on penile erection, understanding these molecular control mechanisms as well as the influence that androgens have on these pathways should provide new evidence supporting the roles of androgens in EF and enhance the discovery of novel targets for drug development to treat ED. Zhang X, Melman A, and DiSanto ME. Update on corpus cavernosum smooth muscle contractile pathways in erectile function: A role for testosterone? J Sex Med 2011;8:1865–1879.