An individualized digital twin of a patient for transdermal fentanyl therapy for chronic pain management.

Fentanyl transdermal therapy is a suitable treatment for moderate-to-severe cancer-related pain. The inter-individual variability of the patients leads to different therapy responses. This study aims to determine the effect of physiological features on the achieved pain relief. Therefore, a set of virtual patients was developed by using Markov chain Monte Carlo (MCMC) based on actual patient data. The members of this virtual population differ by age, weight, gender, and height. Tailored digital twins were developed using these correlated, individualized parameters to propose a personalized therapy for each patient. It was shown that patients of different ages, weights, and gender have significantly different fentanyl blood uptake, plasma fentanyl concentration, pain relief, and ventilation rate. In the digital twins, we included the virtual patients' response to the treatment, namely, pain relief. Therefore, the digital twin was able to adjust the therapy in silico to have more efficient pain relief. By implementing digital-twin-assisted therapy, the average pain intensity decreased by 16% compared to conventional therapy. The median time without pain increased by 23 h over 72 h. Therefore, the digital twin can be successfully used in individual control of transdermal therapy to reach higher pain relief and maintain steady pain relief. (Created with BioRender.com)

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Implementing physics-based digital patient twins to tailor the switch of oral morphine to transdermal fentanyl patches based on patient physiology.

Fentanyl transdermal patches are widely implemented for cancer-induced pain treatment due to the high potency of fentanyl and gradual drug release. However, transdermal fentanyl up-titration for opioid-naïve patients is difficult, which is why opioid treatment is often started with oral/iv morphine. Based on the daily dose of morphine, the initial dose of the fentanyl patch is decided upon. After reaching a stable level of pain, the switch is made from oral/iv morphine to transdermal fentanyl. There are standard calculation tools for transferring from oral/iv morphine to transdermal fentanyl, which is the same for all patients. By considering the variations in the physiology of the patients, a unique switching strategy cannot meet the needs of different patients. This study explores the outcome in terms of pain relief and minute ventilation during opioid therapy. For this, we used physics-based simulations on a virtually-generated population of patients, and we applied the same therapy to all patients. We could show that patients' physiology, such as gender, age, and weight, greatly impact the outcome of the therapy; as such, the correlation coefficient between pain intensity and age is 0.89, and the correlation coefficient between patient's weight and maximum plasma concentration of morphine and fentanyl is -0.98 and -0.97. Additionally, a different combination of the duration of overlap between morphine and fentanyl therapy with different doses of fentanyl was considered for the virtual patients to find the best opioid-switching strategy for each patient. We explored the impact of combining physiological features to determine the best-suited strategy for virtual patients. Our findings suggest that tailoring morphine and fentanyl therapy only based on a limited number of features is insufficient, and increasing the number of impactful physiological features positively influences the outcome of the therapy

How long and effective does a mask protect you from an infected person who emits virus-laden particles: By implementing one-dimensional physics-based modeling

SARS-CoV-2 spreads via droplets, aerosols, and smear infection. From the beginning of the COVID-19 pandemic, using a facemask in different locations was recommended to slow down the spread of the virus. To evaluate facemasks' performance, masks' filtration efficiency is tested for a range of particle sizes. Although such tests quantify the blockage of the mask for a range of particle sizes, the test does not quantify the cumulative amount of virus-laden particles inhaled or exhaled by its wearer. In this study, we quantify the accumulated viruses that the healthy person inhales as a function of time, activity level, type of mask, and room condition using a physics-based model. We considered different types of masks, such as surgical masks and filtering facepieces (FFPs), and different characteristics of public places such as office rooms, buses, trains, and airplanes. To do such quantification, we implemented a physics-based model of the mask. Our results confirm the importance of both people wearing a mask compared to when only one wears the mask. The protection time for light activity in an office room decreases from 7.8 to 1.4 h with surgical mask IIR. The protection time is further reduced by 85 and 99% if the infected person starts to cough or increases the activity level, respectively. Results show the leakage of the mask can considerably affect the performance of the mask. For the surgical mask, the apparent filtration efficiency reduces by 75% with such a leakage, which cannot provide sufficient protection despite the high filtration efficiency of the mask. The facemask model presented provides key input in order to evaluate the protection of masks for different conditions in public places. The physics-based model of the facemask is provided as an online application.ISSN:2296-256

A world of lies

This article reports two worldwide studies of stereotypes about liars. These studies are carried out in 75 different countries and 43 different languages. In Study 1, participants respond to the open-ended question "How can you tell when people are lying?" In Study 2, participants complete a questionnaire about lying. These two studies reveal a dominant pan-cultural stereotype: that liars avert gaze. The authors identify other common beliefs and offer a social control interpretation