COVID-19 scenario modelling for the mitigation of capacity-dependent deaths in intensive care

Managing healthcare demand and capacity is especially difficult in the context of the COVID-19 pandemic, where limited intensive care resources can be overwhelmed by a large number of cases requiring admission in a short space of time. If patients are unable to access this specialist resource, then death is a likely outcome. In appreciating these ‘capacity-dependent’ deaths, this paper reports on the clinically-led development of a stochastic discrete event simulation model designed to capture the key dynamics of the intensive care admissions process for COVID-19 patients. With application to a large public hospital in England during an early stage of the pandemic, the purpose of this study was to estimate the extent to which such capacity-dependent deaths can be mitigated through demand-side initiatives involving non-pharmaceutical interventions and supply-side measures to increase surge capacity. Based on information available at the time, results suggest that total capacity-dependent deaths can be reduced by 75% through a combination of increasing capacity from 45 to 100 beds, reducing length of stay by 25%, and flattening the peak demand to 26 admissions per day. Accounting for the additional ‘capacity-independent’ deaths, which occur even when appropriate care is available within the intensive care setting, yields an aggregate reduction in total deaths of 30%. The modelling tool, which is freely available and open source, has since been used to support COVID-19 response planning at a number of healthcare systems within the UK National Health Service

The value of triage during periods of intense COVID-19 demand: simulation modelling study

Background: During the COVID-19 pandemic many intensive care units have been overwhelmed by unprecedented levels of demand. Notwithstanding ethical considerations, the prioritisation of patients with better prognoses may support a more effective use of available capacity in maximising aggregate outcomes. This has prompted various proposed triage criteria, although in none of these has an objective assessment been made in terms of impact on number of lives and life-years saved. Design: An open source computer simulation model was constructed for approximating the intensive care admission and discharge dynamics under triage. The model was calibrated from observational data for 9505 patient admissions to UK intensive care units. In order to explore triage efficacy under various conditions, scenario analysis was performed using a range of demand trajectories corresponding to differing non-pharmaceutical interventions.Results: Triaging patients at the point of expressed demand had negligible effect on deaths but reduces life-years lost by up to 8.4% (95% CI: 2.6% to 18.7%). Greater value may be possible through ‘reverse triage’, i.e. promptly discharging any patient not meeting the criteria if admission cannot otherwise be guaranteed for one that does. Under such policy, life-years lost can be reduced by 11.7% (2.8% to 25.8%), which represents 23.0% (5.4% to 50.1%) of what is operationally feasible with no limit on capacity and in absence of improved clinical treatments.Conclusions: The effect of simple triage is limited by a trade-off between reduced deaths within intensive care (due to improved outcomes) and increased deaths resulting from declined admission (due to lower throughput given the longer lengths of stay of survivors). Improvements can be found through reverse triage, at the expense of potentially complex ethical considerations.<br/

Effect of dietary fatty acid composition on depot fat and exercise performance in a migrating songbird, the red-eyed vireo

Most migrating birds accumulate lipid stores as their primary source of energy for fueling long distance flights. Lipid stores of birds during migration are composed of mostly unsaturated fatty acids; whether such a fatty acid composition enhances exercise performance of birds is unknown. We tested this hypothesis by measuring metabolic rate at rest and during intense exercise in two groups of red-eyed vireos, a long-distance migratory passerine, fed either a diet containing 82% unsaturated fat (82%U), or one containing 58% unsaturated fat (58%U). Vireos fed the 82%U diet had fat stores containing (77%) unsaturated fatty acids, whereas vireos fed the 58% U diet had fat stores containing less (66%) unsaturated fatty acids. Blood metabolites measured prior to and immediately following exercise confirmed that vireos were metabolizing endogenous fat during intense exercise. Mass-specific resting metabolic rate (RMR) was similar for vireos fed the 58%U diet (2.75±0.32 ml O2 g–1 h–1) and for vireos fed the 82%U diet (2.30±0.30 ml O2 g–1 h–1). However, mass-specific peak metabolic rate (MRpeak) was 25% higher in vireos fed the 58%U diet (28.55±1.47 ml O2 g–1 h–1) than in vireos fed the 82%U diet (21.50±1.76 ml O2 g–1 h–1). Such whole-animal energetic effects of fatty acid composition of birds suggest that the energetic cost of migration in birds may be affected by the fatty acid composition of the diet

Counterfactual Explanations via Locally-guided Sequential Algorithmic Recourse

Counterfactuals operationalised through algorithmic recourse have become a powerful tool to make artificial intelligence systems explainable. Conceptually, given an individual classified as y -- the factual -- we seek actions such that their prediction becomes the desired class y' -- the counterfactual. This process offers algorithmic recourse that is (1) easy to customise and interpret, and (2) directly aligned with the goals of each individual. However, the properties of a "good" counterfactual are still largely debated; it remains an open challenge to effectively locate a counterfactual along with its corresponding recourse. Some strategies use gradient-driven methods, but these offer no guarantees on the feasibility of the recourse and are open to adversarial attacks on carefully created manifolds. This can lead to unfairness and lack of robustness. Other methods are data-driven, which mostly addresses the feasibility problem at the expense of privacy, security and secrecy as they require access to the entire training data set. Here, we introduce LocalFACE, a model-agnostic technique that composes feasible and actionable counterfactual explanations using locally-acquired information at each step of the algorithmic recourse. Our explainer preserves the privacy of users by only leveraging data that it specifically requires to construct actionable algorithmic recourse, and protects the model by offering transparency solely in the regions deemed necessary for the intervention.Comment: 7 pages, 5 figures, 3 appendix page

Migration- and exercise-induced changes to flight muscle size in migratory birds and association with \u3cem\u3eIGF1\u3c/em\u3e and \u3cem\u3emyostatin\u3c/em\u3e mRNA expression

Seasonal adjustments to muscle size in migratory birds may result from preparatory physiological changes or responses to changed workloads. The mechanisms controlling these changes in size are poorly understood. We investigated some potential mediators of flight muscle size (myostatin and insulin-like growth factor, IGF1) in pectoralis muscles of wild wintering or migrating white-throated sparrows (Zonotrichia albicollis), captive white-throated sparrows that were photoperiod manipulated to be in a `wintering\u27 or `migratory\u27 (Zugunruhe) state, and captive European starlings (Sturnus vulgaris) that were either exercised for 2 weeks in a wind tunnel or untrained. Flight muscle size increased in photo-stimulated `migrants\u27 and in exercised starlings. Acute exercise but not long-term training caused increased expression of IGF1, but neither caused a change in expression of myostatin or its metalloprotease activator TLL1. Photo-stimulated `migrant\u27 sparrows demonstrated increased expression of both myostatin and IGF1, but wild sparrows exhibited no significant seasonal changes in expression of either myostatin or IGF1. Additionally, in both study species we describe several splice variants of myostatin that are shared with distantly related bird species. We demonstrate that their expression patterns are not different from those of the typical myostatin, suggesting that they have no functional importance and may be mistakes of the splicing machinery. We conclude that IGF1 is likely to be an important mediator of muscle phenotypic flexibility during acute exercise and during endogenous, seasonal preparation for migration. The role of myostatin is less clear, but its paradoxical increase in photo-stimulated `migrants\u27 may indicate a role in seasonal adjustments of protein turnover

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure

Prophylactic Embolization of the Cystic Artery Before Radioembolization: Feasibility, Safety, and Outcomes

PurposeTo evaluate the safety and efficacy of two different methods of proximal cystic artery embolization in patients undergoing yttrium-90 radioembolization.Materials and methodsForty-six patients had cystic artery embolization performed immediately before yttrium-90 radioembolization, either by using Gelfoam pledgets (n = 35) or coils (n = 11). Clinical symptomatology during the admission and angiographic findings at 1-month follow-up were retrospectively reviewed. Rates of collateralization or recanalization of the cystic artery were compared, as well as the frequency of postprocedural abdominal pain and need for cholecystectomy.ResultsTechnical success was achieved in all patients, and there were no procedural complications related to cystic artery embolization. Of the 11 coil-embolized patients, 5 (45%) demonstrated collateralization of the cystic artery at 1 month, and 1 (9%) demonstrated recanalization of the cystic artery. Of the 35 Gelfoam-embolized cases, 2 (6%) had collateralized at 1 month, and 14 (40%) had recanalized. Two patients (one from each group) had self-limited right upper quadrant pain after the procedure, and one patient in the coil embolization group required cholecystectomy.ConclusionProximal cystic artery embolization is safe and feasible and may be performed during liver-directed embolotherapy to minimize the exposure of the gallbladder to particulate, chemoembolic, or radioembolic agents

Implementing chlamydia screening: what do women think? A systematic review of the literature

BACKGROUND: Chlamydia trachomatis is a common sexually transmitted infection that can have serious consequences. It is universally agreed that screening for chlamydia infection should be offered to sexually active young women. We undertook a literature review to document the views, attitudes and opinions of women about being screened, tested and diagnosed with Chlamydia trachomatis. METHODS: Online databases (MEDLINE, Meditext, PsycINFO, Web of Science) and reference lists searched up to August 2005. Search terms: chlamydia, attitude, attitude to health, interview, qualitative, women. Eligibility criteria: about chlamydia, included women, involved interviews/surveys/focus groups, looked at women's views/opinions/attitudes, published in English. Thematic analysis identified the main and recurrent themes emerging from the literature. We compared our thematic analysis with the Theory of Planned Behaviour to provide a model that could assist in planning chlamydia screening programs. RESULTS: From 561 identified articles, 25 fulfilled inclusion criteria and were reviewed. 22: USA, UK; 3: Holland, Sweden, Australia. Major themes identified: need for knowledge and information, choice and support; concerns about confidentiality, cost, fear, anxiety and stigma. Women are more likely to find chlamydia screening/testing acceptable if they think chlamydia is a serious, common condition which can cause infertility and if they understand that chlamydia infection can be asymptomatic. Women want a range of options for chlamydia testing including urine tests, self-administered swabs, pelvic exams and clinician-collected swabs, home-testing and community-based testing. Tests should be free, easy and quick. Women want support for dealing with the implications of a chlamydia diagnosis, they feel chlamydia diagnoses need to be normalised and destigmatised and they want assistance with partner notification. Women need to know that their confidentiality will be maintained. CONCLUSION: Our review found that women from various countries and ethnic backgrounds share similar views regarding chlamydia screening, testing and diagnosis. The acknowledged importance of women's views in planning an effective chlamydia screening program is expanded in this review which details the nature and complexity of such views and considers their likely impact

Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity

Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes were evaluated by mining GWAS datasets. eQTL analysis identified 1,971 and 2,078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2, were identified in both tissues. 62.1% of top cis-eSNPs were within ±50kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes, (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu) and identified genetically-regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes

Gender Differences in Aspirin use Among Adults With Coronary Heart Disease in the United States

BACKGROUND: Aspirin reduces mortality for men and women with coronary heart disease (CHD). Previous research suggests women with acute coronary syndromes receive less aggressive care, including less frequent early administration of aspirin. The presence of gender differences in aspirin use for secondary prevention is less clear. OBJECTIVE: To determine if a gender difference exists in the use of aspirin for secondary prevention among individuals with CHD. DESIGN: We analyzed data from the nationally representative 2000–2002 Medical Expenditure Panel Surveys to determine the prevalence of regular aspirin use among men and women with CHD. PARTICIPANTS: Participants, 1,869, 40 years and older who reported CHD or prior myocardial infarction. RESULTS: Women were less likely than men to use aspirin regularly (62.4% vs 75.6%, p < .001) even after adjusting for demographic, socioeconomic and clinical characteristics (adjusted OR = 0.62, 95% CI, 0.48–0.79). This difference narrowed but remained significant when the analysis was limited to those without self-reported contraindications to aspirin (79.8% vs 86.4%, P = .002, adjusted OR = 0.68, 95% CI, 0.48–0.97). Women were more likely than men to report contraindications (20.5% vs 12.5%, P < .001). Differences in aspirin use were greater between women and men with private health insurance (61.8% vs 79.0%, P < .001, adjusted OR = 0.48, 95% CI, 0.35–0.67) than among those with public coverage (62.5% vs 70.7%, P = .04, adjusted OR = 0.74, 95% CI, 0.50–1.11) (P < .001 for gender–insurance interaction). CONCLUSION: We found a gender difference in aspirin use among patients with CHD not fully explained by differences in patient characteristics or reported contraindications. These findings suggest a need for improved secondary prevention of cardiovascular events for women with CHD