Can network science reveal structure in a complex healthcare system? A network analysis using data from emergency surgical services

Funder: Research Trainees Coordinating Centre; FundRef: http://dx.doi.org/10.13039/501100000659Introduction: Hospitals are complex systems and optimising their function is critical to the provision of high quality, cost effective healthcare. Metrics of performance have to date focused on the performance of individual elements rather than the whole system. Manipulation of individual elements of a complex system without an integrative understanding of its function is undesirable and may lead to counterintuitive outcomes and a holistic metric of hospital function might help design more efficient services. Objectives: We aimed to use network analysis to characterise the structure of the system of perioperative care for emergency surgical admissions in our tertiary care hospital. Design: We constructed a weighted directional network representation of the emergency surgical services using patient location data from electronic health records. Setting: A single-centre tertiary care hospital in the UK. Participants: We selected data from the retrospective electronic health record data of all unplanned admissions with a surgical intervention during their stay during a 3.5-year period, which resulted in a set of 16 500 individual admissions. Methods: We then constructed and analysed the structure of this network using established methods from network science such as degree distribution, betweenness centrality and small-world characteristics. Results: The analysis showed the service to be a complex system with scale-free, small-world network properties. We also identified such potential hubs and bottlenecks in the system. Conclusions: Our holistic, system-wide description of a hospital service may provide tools to inform service improvement initiatives and gives us insights into the architecture of a complex system of care. The implications for the structure and resilience of the service is that while being robust in general, the system may be vulnerable to outages at specific key nodes

In Silico Model of Critical Cerebral Oxygenation after Traumatic Brain Injury: Implications for Rescuing Hypoxic Tissue.

Cerebral oxygen delivery is central to the modern intensive care of patients with severe traumatic brain injury. Low brain tissue oxygen tension (PbtO2) results from microvascular collapse and diffusion limitation and is associated with adverse outcome. A number of therapies to improve oxygen delivery are known to be effective in improving PbtO2. Their relative effectiveness and microscopic regions of hypoxia, however, may exist/persist even in the presence of normal PbtO2. Unfortunately, there are no methods currently for assessing this quantitatively. We used an in silico (computational) simulation approach to understand the effect of common interventions on the microscopic distribution of brain tissue oxygen tension. We constructed a non-linear mathematical model of cerebral oxygen supply, diffusion, and consumption for a simplified geometry. Model parameters were chosen to agree with clinical parameters. We found that it was possible to create a plausible diffusion-limited scenario with a significant hypoxic fraction by increasing the mean diffusion distance. We found that increasing cerebral blood flow/blood oxygen content or suppressing the cerebral metabolic rate were most effective at improving PbtO2 and reduced the hypoxic fraction. Within the limitations of our modeling assumptions, increasing the arterial oxygen partial pressure was less effective and only improved PbtO2 by creating a region of hyperoxic tissue with no improvement in hypoxic fraction. The in silico simulations can be useful in understanding the likely physiological effect of complex treatments for which measurement techniques do not exist

Large-Scale Simulations of Reionization

We use cosmological simulations to explore the large-scale effects of reionization. Since reionization is a process that involves a large dynamic range - from galaxies to rare bright quasars - we need to be able to cover a significant volume of the universe in our simulation without losing hte important small scale effects from galaxies. Here we have taken an approach that uses clumping factors derived from small scale simulations to approximate the radiative transfer on the sub-cell scales. Using this technique, we can cover a simulation size up to $1280 h^{-1} Mpc$ with $10 h^{-1} Mpc$ cells. This allows us to construct synthetic spectra of quasars similar to observed spectra of SDSS quasars at high reshifts and compare them to the observational data. These spectra can then be analyzed for HII region sizes, the presence of the Gunn-Peterson trough and the Lyman-$\alpha$ forest.Comment: 25 page

The comparative abundance and behaviour of sharks in the Cayman Islands (BWI)

This thesis investigates the ecology of coastal sharks, in particular the Caribbean reef shark (Carcharhinus perezi), using data collected in the Cayman Islands from 2009 to 2019. Relative abundance was estimated by deploying 936 Baited Remote Underwater Video Systems (BRUVS) and individual shark behaviour monitored by recording the movement of 66 acoustically tagged Caribbean reef sharks. This work was complemented by information gathered on 24,442 dives by 69 SCUBA divers participating in a citizen science programme (the ‘Sharklogger Network’). Additionally, population sizes for two species were estimated through the application of mark-recapture models to the sighting histories of sharks individually identified on 557 BRUVS videos deployed between 2015 and 2018. The study recorded eight shark species of which Caribbean reef and Atlantic nurse shark (Ginglymostoma cirratum) were the most abundant, with estimated local coastal population sizes of 180 and 336 respectively. Immature and mature Caribbean reef, nurse, and hammerhead (Sphyrna) sharks were recorded throughout the year, suggesting resident breeding populations. Most Caribbean reef and nurse sharks showed relatively small home ranges (< 20 km) and high site-fidelity. However, some individuals showed maturity-based seasonal movements indicating a distinct mating and pupping season, with a few detected moving more than 100 km

ARDS subphenotypes: searching for Rorschach among the roentgenograms?

In 1967, Ashbaugh and colleagues first described acute respiratory distress syndrome (ARDS) - an acute illness, characterised by tachypnoea, hypoxaemia and loss of lung compliance occurring after a variety of pulmonary and non-pulmonary insults (including trauma, acute pancreatitis, viral pneumonitis)1. This concept is retained as the ARDS illness model within the current consensus definitions, with acute defined as within 7 days of insult, and hypoxaemia categorised using partial pressure of oxygen/fraction of inspired oxygen concentration (PaO2/FiO2 ratio) into mild (5 cm water2.MS-H is supported by the National Institute for Health Research Clinician Scientist Award (NIHR-CS-2016-16-011). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the UK National Institute for Health Research or the Department of Health. ACM is supported by an MRC Clinician Scientist Fellowship (MR/V006118/1)

The global variation of medical student engagement in teaching: Implications for medical electives.

INTRODUCTION: International medical electives, whereby undergraduates visit an institution in a country other than their own, are a common part of medical training. Visiting students are often asked to provide local teaching, which may be acceptable where the visitor is acting within the bounds of their own competency and the normal practices of both their home and host institutions. However, the extent to which teaching is an accepted student activity globally has not previously been described. This study aims to address this using an international survey approach. METHODS: A voluntary electronic survey, created using the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) framework, was distributed across established international medical student networks. This assessed the involvement of medical students in teaching and the educator training they receive, with the intention of comparing experiences between high-income countries (HICs) and low/middle-income countries (LMICs) to gauge the engagement of both "host" and "visiting" students. RESULTS: 443 students from 61 countries completed the survey, with an equal proportion of respondents from LMICs (49.4%, 219/443) and HICs (50.6%, 224/443). Around two thirds of students reported providing teaching whilst at medical school, with most reporting teaching numerous times a year, mainly to more junior medical students. There was with no significant difference between LMICs and HICs. Around 30 per cent of all medical students reported having received no teacher training, including 40 per cent of those already providing teaching. CONCLUSION: This study suggests that students are engaged in teaching globally, with no difference between HIC and LMIC contexts. However, students are underprepared to act as educators in both settings. Providing teaching as part of an elective experience may be ethically acceptable to both host and home institutions, but needs to be supported by formal training in delivering teaching.NIHR Global Health Research Group on Neurotraum

Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19

A growing number of patients with SARS-CoV-2 infections experience long-lasting symptoms. Even patients who suffered from a mild acute infection show a variety of persisting and debilitating neurocognitive, respiratory, or cardiac symptoms (Long-Covid syndrome), consequently leading to limitations in everyday life. Because data on health-related quality of life (HRQoL) is scarce, we aimed to characterize the impact of Long-Covid symptoms after a mild or moderate acute infection on HRQoL. In this observational study, outpatients seeking counseling in the interdisciplinary Post-Covid consultation of the University Hospital Zurich with symptoms persisting for more than 4 weeks were included. Patients who received an alternative diagnosis or suffered from a severe acute Covid-19 infection were excluded. St. George’s Respiratory Questionnaire (SGRQ), Euroquol-5D-5L (EQ-5D-5L), and the Short form 36 (SF-36) were distributed to assess HRQoL. 112 patients were included, 86 (76.8%) were female, median (IQR) age was 43 (32.0, 52.5) years with 126 (91, 180) days of symptoms. Patients suffered frequently from fatigue (81%), concentration difficulties (60%), and dyspnea (60%). Patients mostly stated impairment in performing usual activities and having pain/discomfort or anxiety out of the EQ-5D-5L. EQ index value and SGRQ activity score component were significantly lower in females. SF-36 scores showed remarkably lower scores in the physical health domain compared to the Swiss general population before and during the COVID-19 pandemic. Long-Covid syndrome has a substantial impact on HRQoL. Long-term surveillance of patients must provide clarity on the duration of impairments in physical and mental health.Trial registration: The study is registered on www.ClinicalTrials.gov, NCT04793269

Deciphering the human antibody response against Burkholderia pseudomallei during melioidosis using a comprehensive immunoproteome approach

IntroductionThe environmental bacterium Burkholderia pseudomallei causes the often fatal and massively underreported infectious disease melioidosis. Antigens inducing protective immunity in experimental models have recently been identified and serodiagnostic tools have been improved. However, further elucidation of the antigenic repertoire of B. pseudomallei during human infection for diagnostic and vaccine purposes is required. The adaptation of B. pseudomallei to very different habitats is reflected by a huge genome and a selective transcriptional response to a variety of conditions. We, therefore, hypothesized that exposure of B. pseudomallei to culture conditions mimicking habitats encountered in the human host might unravel novel antigens that are recognized by melioidosis patients.Methods and resultsIn this study, B. pseudomallei was exposed to various stress and growth conditions, including anaerobiosis, acid stress, oxidative stress, iron starvation and osmotic stress. Immunogenic proteins were identified by probing two-dimensional Western blots of B. pseudomallei intracellular and extracellular protein extracts with sera from melioidosis patients and controls and subsequent MALDI-TOF MS. Among B. pseudomallei specific immunogenic signals, 90 % (55/61) of extracellular immunogenic proteins were identified by acid, osmotic or oxidative stress. A total of 84 % (44/52) of intracellular antigens originated from the stationary growth phase, acidic, oxidative and anaerobic conditions. The majority of the extracellular and intracellular protein antigens were identified in only one of the various stress conditions. Sixty-three immunoreactive proteins and an additional 38 candidates from a literature screening were heterologously expressed and subjected to dot blot analysis using melioidosis sera and controls. Our experiments confirmed melioidosis-specific signals in 58 of our immunoproteome candidates. These include 15 antigens with average signal ratios (melioidosis:controls) greater than 10 and another 26 with average ratios greater than 5, including new promising serodiagnostic candidates with a very high signal-to-noise ratio.ConclusionOur study shows that a comprehensive B. pseudomallei immunoproteomics approach, using conditions which are likely to be encountered during infection, can identify novel antibody targets previously unrecognized in human melioidosis

Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based Study.

Pan-immunoglobulin assays can simultaneously detect IgG, IgM and IgA directed against the receptor binding domain (RBD) of the S1 subunit of the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 S1-RBD Ig). In this work, we aim to evaluate a quantitative SARS-CoV-2 S1-RBD Ig electrochemiluminescence immunoassay (ECLIA) regarding analytical, diagnostic, operational and clinical characteristics. Our work takes the form of a population-based study in the principality of Liechtenstein, including 125 cases with clinically well-described and laboratory confirmed SARS-CoV-2 infection and 1159 individuals without evidence of coronavirus disease 2019 (COVID-19). SARS-CoV-2 cases were tested for antibodies in sera taken with a median of 48 days (interquartile range, IQR, 43-52) and 139 days (IQR, 129-144) after symptom onset. Sera were also tested with other assays targeting antibodies against non-RBD-S1 and -S1/S2 epitopes. Sensitivity was 97.6% (95% confidence interval, CI, 93.2-99.1), whereas specificity was 99.8% (95% CI, 99.4-99.9). Antibody levels linearly decreased from hospitalized patients to symptomatic outpatients and SARS-CoV-2 infection without symptoms (p < 0.001). Among cases with SARS-CoV-2 infection, smokers had lower antibody levels than non-smokers (p = 0.04), and patients with fever had higher antibody levels than patients without fever (p = 0.001). Pan-SARS-CoV-2 S1-RBD Ig in SARS-CoV-2 infection cases significantly increased from first to second follow-up (p < 0.001). A substantial proportion of individuals without evidence of past SARS-CoV-2 infection displayed non-S1-RBD antibody reactivities (248/1159, i.e., 21.4%, 95% CI, 19.1-23.4). In conclusion, a quantitative SARS-CoV-2 S1-RBD Ig assay offers favorable and sustained assay characteristics allowing the determination of quantitative associations between clinical characteristics (e.g., disease severity, smoking or fever) and antibody levels. The assay could also help to identify individuals with antibodies of non-S1-RBD specificity with potential clinical cross-reactivity to SARS-CoV-2