Can the implementation of net gain requirements in England's planning system be applied to health?

This Personal View considers the relationship between spatial planning and health and the potential benefits of requiring health net gain from land use decisions and new developments. We explore how a health net gain objective could be applied in spatial planning policy and practice to improve people's health and wellbeing, using England's implementation of a biodiversity net gain objective as a model. This Personal View emphasises the need for a systems approach to the definition and strategic coordination of health gains, recognising the breadth of health determinants and inter-related economic, environmental, and social policy objectives. By considering the potential application of a net gain principle to health in spatial planning, we offer valuable insights into how the spatial planning system could be used to build the conditions of health creation. A road map is provided for exploration of health net gain in other national contexts in support of the operationalisation of global urban health initiatives.

Strategic COVID-19 vaccine distribution can simultaneously elevate social utility and equity.

Balancing social utility and equity in distributing limited vaccines is a critical policy concern for protecting against the prolonged COVID-19 pandemic and future health emergencies. What is the nature of the trade-off between maximizing collective welfare and minimizing disparities between more and less privileged communities? To evaluate vaccination strategies, we propose an epidemic model that explicitly accounts for both demographic and mobility differences among communities and their associations with heterogeneous COVID-19 risks, then calibrate it with large-scale data. Using this model, we find that social utility and equity can be simultaneously improved when vaccine access is prioritized for the most disadvantaged communities, which holds even when such communities manifest considerable vaccine reluctance. Nevertheless, equity among distinct demographic features may conflict; for example, low-income neighbourhoods might have fewer elder citizens. We design two behaviour-and-demography-aware indices, community risk and societal risk, which capture the risks communities face and those they impose on society from not being vaccinated, to inform the design of comprehensive vaccine distribution strategies. Our study provides a framework for uniting utility and equity-based considerations in vaccine distribution and sheds light on how to balance multiple ethical values in complex settings for epidemic control.

Assessment of the role of the Edinburgh dysphagia score in referral triage in a national service evaluation of the urgent suspected upper gastrointestinal cancer pathway.

BACKGROUND: The British Society of Gastroenterology has recommended the Edinburgh Dysphagia Score (EDS) to risk-stratify dysphagia referrals during the endoscopy COVID recovery phase. AIMS: External validation of the diagnostic accuracy of EDS and exploration of potential changes to improve its diagnostic performance. METHODS: A prospective multicentre study of consecutive patients referred with dysphagia on an urgent suspected upper gastrointestinal (UGI) cancer pathway between May 2020 and February 2021. The sensitivity and negative predictive value (NPV) of EDS were calculated. Variables associated with UGI cancer were identified by forward stepwise logistic regression and a modified Cancer Dysphagia Score (CDS) developed. RESULTS: 1301 patients were included from 19 endoscopy providers; 43% male; median age 62 (IQR 51-73) years. 91 (7%) UGI cancers were diagnosed, including 80 oesophageal, 10 gastric and one duodenal cancer. An EDS ≥3.5 had a sensitivity of 96.7 (95% CI 90.7-99.3)% and an NPV of 99.3 (97.8-99.8)%. Age, male sex, progressive dysphagia and unintentional weight loss >3 kg were positively associated and acid reflux and localisation to the neck were negatively associated with UGI cancer. Dysphagia duration <6 months utilised in EDS was replaced with progressive dysphagia in CDS. CDS ≥5.5 had a sensitivity of 97.8 (92.3-99.7)% and NPV of 99.5 (98.1-99.9)%. Area under receiver operating curve was 0.83 for CDS, compared to 0.81 for EDS. CONCLUSIONS: In a national cohort, the EDS has high sensitivity and NPV as a triage tool for UGI cancer. The CDS offers even higher diagnostic accuracy. The EDS or CDS should be incorporated into the urgent suspected UGI cancer pathway.

Shifting the Paradigm on Cannabis Safety.

The global movement toward legalization of cannabis is resulting in an ever-increasing public perception that cannabis is safe. Cannabis is not the first drug to be available for nonmedical use, nor is it the first to have such an unfounded safety profile. The safety of long-term exposure to phytocannabinoids is misunderstood by, and under reported to, the general public. There is evidence to suggest that long-term use of recreational cannabis may be associated with an increased risk of undesirable side effects. This evidence warrants both appropriate caution from the general public and investment in further research by government and industry sectors that are profiting from the sale of these potent psychoactive agents. There is no doubt that these compounds have medical potential. However, in addition to the medical potential, we must also remain aware of the adverse health effects that are becoming synonymous with recreational cannabis use. This perspective highlights the privileged role that cannabis has as a perceived "safe drug" in society and summarizes some concerning side effects that are becoming associated with regular nonprescribed cannabis use.

Telestroke Assessment With Perfusion CT Improves the Diagnostic Accuracy of Stroke vs. Mimic.

Background and Purpose: CT perfusion (CTP) has been implemented widely in regional areas of Australia for telestroke assessment. The aim of this study was to determine if, as part of telestroke assessment, CTP provided added benefit to clinical features in distinguishing between strokes and mimic and between transient ischaemic attack (TIA) and mimic. Methods: We retrospectively analysed 1,513 consecutively recruited patients referred to the Northern New South Wales Telestroke service, where CTP is performed as a part of telestroke assessment. Patients were classified based on the final diagnosis of stroke, TIA, or mimic. Multivariate regression models were used to determine factors that could be used to differentiate between stroke and mimic and between TIA and mimic. Results: There were 693 strokes, 97 TIA, and 259 mimics included in the multivariate regression models. For the stroke vs. mimic model using symptoms only, the area under the curve (AUC) on the receiver operator curve (ROC) was 0.71 (95% CI 0.67-0.75). For the stroke vs. mimic model using the absence of ischaemic lesion on CTP in addition to clinical features, the AUC was 0.90 (95% CI 0.88-0.92). The multivariate regression model for predicting mimic from TIA using symptoms produced an AUC of 0.71 (95% CI 0.65-0.76). The addition of absence of an ischaemic lesion on CTP to clinical features for the TIA vs. mimic model had an AUC of 0.78 (95% CI 0.73-0.83) Conclusions: In the telehealth setting, the absence of an ischaemic lesion on CTP adds to the diagnostic accuracy in distinguishing mimic from stroke, above that from clinical features.

Assessment of the Validity of the Sinonasal Outcomes Test-22 in Pituitary Surgery: A Multicenter Prospective Trial.

OBJECTIVES/HYPOTHESIS: Sinonasal Outcomes Test-22 (SNOT-22) is used widely as a patient-reported sinonasal quality-of-life (QOL) instrument for endoscopic endonasal pituitary surgery. However, it has never been validated in this population. This study explores the psychometric validity of SNOT-22 to determine if it is a valid scale in patients undergoing endoscopic pituitary surgery. STUDY DESIGN: Multicenter prospective trial. METHODS: Adult patients (n = 113) with pituitary tumors undergoing endoscopic surgery were enrolled in a multicenter study. Patient-reported QOL was assessed using SNOT-22 and the Anterior Skull Base Nasal Inventory-12. Face validity, internal consistency, responsiveness to clinical change, test-retest reliability, and concurrent validity were determined using standard statistical methods. RESULTS: Internal consistency using Cronbach's alpha at baseline and 2 weeks postoperatively were 0.911 and 0.922, indicating SNOT-22 performed well as a single construct. Mean QOL scores were significantly worse at 2 weeks than baseline (16.4 ± 15.1 vs. 23.1 ± 16.4, P < .001), indicating the scale is responsive to clinical change. However, only 11/22 items demonstrated significant changes in mean scores at 2 weeks. Correlation between scores at 2 and 3 weeks was high, suggesting good test-retest reliability, r(107) = 0.75, P < .001. Factor analysis suggests the five-factor solution proposed for the SNOT-22 in rhinosinusitis patients is not valid in pituitary surgery patients. CONCLUSIONS: The SNOT-22 is a valid QOL instrument in patients undergoing endoscopic pituitary surgery. However, because it includes 22 items, can be applied only as a single construct, 50% of the items do not demonstrate changes after surgery, and is not as sensitive to change as other scales, shorter instruments developed specifically for this patient population may be preferable. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:E2757-E2763, 2021.

Too Many Cooks: Bayesian Inference for Coordinating Multi-Agent Collaboration.

Collaboration requires agents to coordinate their behavior on the fly, sometimes cooperating to solve a single task together and other times dividing it up into sub-tasks to work on in parallel. Underlying the human ability to collaborate is theory-of-mind (ToM), the ability to infer the hidden mental states that drive others to act. Here, we develop Bayesian Delegation, a decentralized multi-agent learning mechanism with these abilities. Bayesian Delegation enables agents to rapidly infer the hidden intentions of others by inverse planning. We test Bayesian Delegation in a suite of multi-agent Markov decision processes inspired by cooking problems. On these tasks, agents with Bayesian Delegation coordinate both their high-level plans (e.g., what sub-task they should work on) and their low-level actions (e.g., avoiding getting in each other's way). When matched with partners that act using the same algorithm, Bayesian Delegation outperforms alternatives. Bayesian Delegation is also a capable ad hoc collaborator and successfully coordinates with other agent types even in the absence of prior experience. Finally, in a behavioral experiment, we show that Bayesian Delegation makes inferences similar to human observers about the intent of others. Together, these results argue for the centrality of ToM for successful decentralized multi-agent collaboration.

From Genetics to Genomics: Facing the Liability Implications in Clinical Care.

Health care is transitioning from genetics to genomics, in which single-gene testing for diagnosis is being replaced by multi-gene panels, genome-wide sequencing, and other multi-genic tests for disease diagnosis, prediction, prognosis, and treatment. This health care transition is spurring a new set of increased or novel liability risks for health care providers and test laboratories. This article describes this transition in both medical care and liability, and addresses 11 areas of potential increased or novel liability risk, offering recommendations to both health care and legal actors to address and manage those liability risks.

Qualitative Assessment of the Effect of Continuous Positive Airway Pressure on the Nasal Cavity.

BACKGROUND: For patients with obstructive sleep apnea (OSA), there is a lack of knowledge regarding the impact of continuous positive airway pressure (CPAP) on the nasal cavity. There is a significant need for evidence-based recommendations regarding the appropriate use of CPAP following endoscopic sinus and skull base surgery. OBJECTIVE: The goal of this study is to translate a previously developed cadaveric model for evaluating CPAP pressures in the sinonasal cavity by showing safety in vivo and quantifying the effect of positive pressurized air flow on the nasal cavity of healthy individuals where physiologic effects are at play. METHODS: A previously validated cadaveric model using intracranial sensor catheters has proved to be a reliable technique for measuring sinonasal pressures. These sensors were placed in the nasal cavity of 18 healthy individuals. Pressure within the nose was recorded at increasing levels of CPAP. RESULTS: Overall, nasal cavity pressure was on average 85% of delivered CPAP. The amount of pressure delivered to the nasal cavity increased as the CPAP increased. The percentage of CPAP delivered was 77% for 5 cmH2O and increased to 89% at 20 cmH2O. There was a significant difference in mean intranasal pressures between all the levels of CPAP except 5 cmH2O and 8 cmH2O (P < .001). CONCLUSION: On average, only 85% of the pressure delivered by CPAP is transmitted to the nasal cavity. Higher CPAP pressures delivered a greater percentage of pressurized air to the nasal cavity floor. Our results are comparable to the cadaver model, which demonstrated similar pressure delivery even in the absence of anatomic factors such as lung compliance, nasal secretions, and edema. This study demonstrates the safety of using sensors in the human nasal cavity. This technology can also be utilized to evaluate the resiliency of various repair techniques for endoscopic skull base surgery with CPAP administration.

Addressing perceived economic obstacles to genetic testing as a way to mitigate disparities in family health history for adoptees.

In this paper, we ask whether or not we can afford to realize the potential benefits of genetic testing as a screening tool for adoptees. Our method is to provide reasonable cost and savings estimates. We argue that the prospect of cost neutrality should be sufficient to explore the targeted screening for a population who will otherwise suffer an avoidable health disparity in access to inherited disease information. Our goal here is to establish that the investment needed to attain these benefits is not beyond our means.

iFuse Implant System for Treating Chronic Sacroiliac Joint Pain: A NICE Medical Technology Guidance.

Treatment and management of sacroiliac joint pain is often non-surgical, involving packages of care that can include analgesics, physiotherapy, corticosteroid injections and radiofrequency ablation. Surgical intervention is considered when patients no longer respond to conservative management. The iFuse Implant System is placed across the sacroiliac joint using minimally invasive surgery, stabilising the joint and correcting any misalignment or weakness that can cause chronic pain. The iFuse system was evaluated in 2018 by the UK National Institute for Health and Care Excellence (NICE) as part of the Medical Technologies Evaluation Programme (MTEP). Clinical evidence for iFuse suggests improved pain, Oswestry disability index (ODI) and quality of life compared to non-surgical management. The company (SI-Bone®) submitted two cost models indicating that iFuse was cost saving compared with open surgery and non-surgical management. Clinicians advised that non-surgical management was the most appropriate comparator and Cedar (a health technology research centre) made changes to the model to test the impact of higher acquisition and procedure costs. Cedar found iFuse to be cost incurring by approximately £560 per patient at 7 years. During the consultation period, the company reduced the cost of some iFuse consumables, and Cedar extended the time horizon to test the assumption that iFuse would become cost saving over time. These changes indicated that iFuse becomes cost saving at 8 years (approximately £129 per patient), after which the cost saving continues to increase. NICE published guidance in October 2018 recommending that the case for adoption of the iFuse system in the UK National Health Service (NHS) was supported by the evidence.

Genomic knowledge in the context of diagnostic exome sequencing: changes over time, persistent subgroup differences, and associations with psychological sequencing outcomes.

PURPOSE: People undergoing diagnostic genome-scale sequencing are expected to have better psychological outcomes when they can incorporate and act on accurate, relevant knowledge that supports informed decision making. METHODS: This longitudinal study used data from the North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing Study (NCGENES) of diagnostic exome sequencing to evaluate associations between factual genomic knowledge (measured with the University of North Carolina Genomic Knowledge Scale at three assessments from baseline to after return of results) and sequencing outcomes that reflected participants' perceived understanding of the study and sequencing, regret for joining the study, and responses to learning sequencing results. It also investigated differences in genomic knowledge associated with subgroups differing in race/ethnicity, income, education, health literacy, English proficiency, and prior genetic testing. RESULTS: Multivariate models revealed higher genomic knowledge at baseline for non-Hispanic Whites and those with higher income, education, and health literacy (p values < 0.001). These subgroup differences persisted across study assessments despite a general increase in knowledge among all groups. Greater baseline genomic knowledge was associated with lower test-related distress (p = 0.047) and greater perceived understanding of diagnostic genomic sequencing (p values 0.04 to <0.001). CONCLUSION: Findings extend understanding of the role of genomic knowledge in psychological outcomes of diagnostic exome sequencing, providing guidance for additional research and interventions.

Quantifying the dynamics of failure across science, startups and security.

Human achievements are often preceded by repeated attempts that fail, but little is known about the mechanisms that govern the dynamics of failure. Here, building on previous research relating to innovation1-7, human dynamics8-11 and learning12-17, we develop a simple one-parameter model that mimics how successful future attempts build on past efforts. Solving this model analytically suggests that a phase transition separates the dynamics of failure into regions of progression or stagnation and predicts that, near the critical threshold, agents who share similar characteristics and learning strategies may experience fundamentally different outcomes following failures. Above the critical point, agents exploit incremental refinements to systematically advance towards success, whereas below it, they explore disjoint opportunities without a pattern of improvement. The model makes several empirically testable predictions, demonstrating that those who eventually succeed and those who do not may initially appear similar, but can be characterized by fundamentally distinct failure dynamics in terms of the efficiency and quality associated with each subsequent attempt. We collected large-scale data from three disparate domains and traced repeated attempts by investigators to obtain National Institutes of Health (NIH) grants to fund their research, innovators to successfully exit their startup ventures, and terrorist organizations to claim casualties in violent attacks. We find broadly consistent empirical support across all three domains, which systematically verifies each prediction of our model. Together, our findings unveil detectable yet previously unknown early signals that enable us to identify failure dynamics that will lead to ultimate success or failure. Given the ubiquitous nature of failure and the paucity of quantitative approaches to understand it, these results represent an initial step towards the deeper understanding of the complex dynamics underlying failure.

Intracellular dynamics of superparamagnetic iron oxide nanoparticles for magnetic particle imaging.

Superparamagnetic iron oxide nanoparticles (SPIONs) are a foundational platform for a variety of biomedical applications. Of particular interest is Magnetic Particle Imaging (MPI), which is a growing area of research and development due to its advantages including high resolution and sensitivity with positive contrast. There has been significant work in the area of in vivo optimization of SPIONs for MPI as well as their biodistribution in and clearance from the body. However, little is known about the dynamics of SPIONs following cellular internalization which may limit their usefulness in a variety of potential imaging and treatment applications. This work shows a clear 20% decrease in magnetic performance of SPIONs, as observed by Magnetic Particle Spectroscopy (MPS), after internalization and systematic consideration of applicable factors that affect SPION signal generation, including microstructure, environment, and interparticle interactions. There is no observed change to SPION microstructure after internalization, and the surrounding environment plays little to no role in magnetic response for the SPIONs studied here. Interparticle interactions described by dipole-dipole coupling of SPIONs held close to one another after internalization are shown to be the dominant cause of decreased magnetic performance in cells. These conclusions were drawn from transmission electron microscopy (TEM) image analysis at relevant length scales, experimentally prepared and characterized SPIONs in varied environmental conditions, and theoretical modeling with Monte Carlo simulations.

Large teams develop and small teams disrupt science and technology.

One of the most universal trends in science and technology today is the growth of large teams in all areas, as solitary researchers and small teams diminish in prevalence1-3. Increases in team size have been attributed to the specialization of scientific activities3, improvements in communication technology4,5, or the complexity of modern problems that require interdisciplinary solutions6-8. This shift in team size raises the question of whether and how the character of the science and technology produced by large teams differs from that of small teams. Here we analyse more than 65 million papers, patents and software products that span the period 1954-2014, and demonstrate that across this period smaller teams have tended to disrupt science and technology with new ideas and opportunities, whereas larger teams have tended to develop existing ones. Work from larger teams builds on more-recent and popular developments, and attention to their work comes immediately. By contrast, contributions by smaller teams search more deeply into the past, are viewed as disruptive to science and technology and succeed further into the future-if at all. Observed differences between small and large teams are magnified for higher-impact work, with small teams known for disruptive work and large teams for developing work. Differences in topic and research design account for a small part of the relationship between team size and disruption; most of the effect occurs at the level of the individual, as people move between smaller and larger teams. These results demonstrate that both small and large teams are essential to a flourishing ecology of science and technology, and suggest that, to achieve this, science policies should aim to support a diversity of team sizes.

Thopaz+ Portable Digital System for Managing Chest Drains: A NICE Medical Technology Guidance.

The Thopaz+ portable digital system was evaluated by the Medical Technologies Advisory Committee (MTAC) of the National Institute for Health and Care Excellence (NICE). The manufacturer, Medela, submitted a case for the adoption of Thopaz+ that was critiqued by Cedar, on behalf of NICE. Due to a lack of clinical evidence submitted by the manufacturer, Cedar carried out its own literature search. Clinical evidence showed that the use of Thopaz+ led to shorter drainage times, a shorter hospital stay, lower rates of chest drain re-insertion and higher patient satisfaction compared to conventional chest drainage when used in patients following pulmonary resection. One comparative study of the use of Thopaz+ in patients with spontaneous pneumothorax was identified and showed shorter drainage times and a shorter length of hospital stay compared to conventional drainage. No economic evidence was submitted by the manufacturer, but a simple decision tree model was included. The model was improved by Cedar and showed a cost saving of £111.33 per patient when Thopaz+ was used instead of conventional chest drainage in patients following pulmonary resection. Cedar also carried out a sub-group analysis of the use of Thopaz+ instead of conventional drainage in patients with pneumothorax where a cost saving of £550.90 was observed. The main cost driver for the model and sub-group analysis was length of stay. The sub-group analysis was based on a single comparative study. However, the MTAC received details of an unpublished audit of Thopaz+ which confirmed its efficacy in treating patients with pneumothorax. Thopaz+ received a positive recommendation in Medical Technologies Guidance 37.

Skill discrepancies between research, education, and jobs reveal the critical need to supply soft skills for the data economy.

Rapid research progress in science and technology (S&T) and continuously shifting workforce needs exert pressure on each other and on the educational and training systems that link them. Higher education institutions aim to equip new generations of students with skills and expertise relevant to workforce participation for decades to come, but their offerings sometimes misalign with commercial needs and new techniques forged at the frontiers of research. Here, we analyze and visualize the dynamic skill (mis-)alignment between academic push, industry pull, and educational offerings, paying special attention to the rapidly emerging areas of data science and data engineering (DS/DE). The visualizations and computational models presented here can help key decision makers understand the evolving structure of skills so that they can craft educational programs that serve workforce needs. Our study uses millions of publications, course syllabi, and job advertisements published between 2010 and 2016. We show how courses mediate between research and jobs. We also discover responsiveness in the academic, educational, and industrial system in how skill demands from industry are as likely to drive skill attention in research as the converse. Finally, we reveal the increasing importance of uniquely human skills, such as communication, negotiation, and persuasion. These skills are currently underexamined in research and undersupplied through education for the labor market. In an increasingly data-driven economy, the demand for "soft" social skills, like teamwork and communication, increase with greater demand for "hard" technical skills and tools.

ENDURALIFE-Powered Cardiac Resynchronisation Therapy Defibrillator Devices for Treating Heart Failure: A NICE Medical Technology Guidance.

ENDURALIFE™-powered cardiac resynchronisation therapy defibrillator (CRT-D) devices were the subject of an evaluation by the National Institute for Health and Care Excellence, through its Medical Technologies Evaluation Programme, for the treatment of heart failure. Boston Scientific (manufacturer) submitted a case for the adoption of the technology, claiming that it has a longer battery life resulting in a longer time to CRT-D replacement. Other claimed benefits were fewer complications associated with replacement procedures, fewer hospital admissions, less time spent in hospital and reduced demand on cardiology device implantation rooms. The submission was critiqued by Cedar, an external assessment centre. The submitted clinical evidence showed that ENDURALIFE-powered devices implanted during the period 2008-2010 were superior, in terms of longevity, to other devices at that time. Submitted economic evidence indicated that, because of a reduction in the need for replacement procedures, ENDURALIFE-powered devices were cost saving when compared to comparator devices. Cedar highlighted uncertainty of the applicability of the clinical evidence to devices marketed today. The Medical Technologies Advisory Committee noted that this was unavoidable due to the follow-up time required to study battery life. Clinical experts noted that increased battery life is an important patient benefit. However, centres use devices from multiple manufacturers to negate pressure on clinical services in the event of a major device recall. The clinical and economic evidence showed benefits to the patient, and further analysis requested by the committee suggested that ENDURALIFE-powered CRT-Ds may save between £2120 and £5627 per patient over 15 years through a reduction in the need for replacement procedures. ENDURALIFE-powered CRT-D devices received a positive recommendation in Medical Technologies Guidance 33.