Computational modelling of cardiovascular pathophysiology to risk stratify commercial spaceflight.

For more than 60 years, humans have travelled into space. Until now, the majority of astronauts have been professional, government agency astronauts selected, in part, for their superlative physical fitness and the absence of disease. Commercial spaceflight is now becoming accessible to members of the public, many of whom would previously have been excluded owing to unsatisfactory fitness or the presence of cardiorespiratory diseases. While data exist on the effects of gravitational and acceleration (G) forces on human physiology, data on the effects of the aerospace environment in unselected members of the public, and particularly in those with clinically significant pathology, are limited. Although short in duration, these high acceleration forces can potentially either impair the experience or, more seriously, pose a risk to health in some individuals. Rather than expose individuals with existing pathology to G forces to collect data, computational modelling might be useful to predict the nature and severity of cardiovascular diseases that are of sufficient risk to restrict access, require modification, or suggest further investigation or training before flight. In this Review, we explore state-of-the-art, zero-dimensional, compartmentalized models of human cardiovascular pathophysiology that can be used to simulate the effects of acceleration forces, homeostatic regulation and ventilation-perfusion matching, using data generated by long-arm centrifuge facilities of the US National Aeronautics and Space Administration and the European Space Agency to risk stratify individuals and help to improve safety in commercial suborbital spaceflight.

Systematic review and meta-analysis of Murray's law in the coronary arterial circulation.

Murray's law has been viewed as a fundamental law of physiology. Relating blood flow ([Formula: see text]) to vessel diameter (D) ([Formula: see text]·âˆ·D3), it dictates minimum lumen area (MLA) targets for coronary bifurcation percutaneous coronary intervention (PCI). The cubic exponent (3.0), however, has long been disputed, with alternative theoretical derivations, arguing this should be closer to 2.33 (7/3). The aim of this meta-analysis was to quantify the optimum flow-diameter exponent in human and mammalian coronary arteries. We conducted a systematic review and meta-analysis of all articles quantifying an optimum flow-diameter exponent for mammalian coronary arteries within the Cochrane library, PubMed Medline, Scopus, and Embase databases on 20 March 2023. A random-effects meta-analysis was used to determine a pooled flow-diameter exponent. Risk of bias was assessed with the National Institutes of Health (NIH) quality assessment tool, funnel plots, and Egger regression. From a total of 4,772 articles, 18 were suitable for meta-analysis. Studies included data from 1,070 unique coronary trees, taken from 372 humans and 112 animals. The pooled flow diameter exponent across both epicardial and transmural arteries was 2.39 (95% confidence interval: 2.24-2.54; I2 = 99%). The pooled exponent of 2.39 showed very close agreement with the theoretical exponent of 2.33 (7/3) reported by Kassab and colleagues. This exponent may provide a more accurate description of coronary morphometric scaling in human and mammalian coronary arteries, as compared with Murray's original law. This has important implications for the assessment, diagnosis, and interventional treatment of coronary artery disease.

Evaluation of models of sequestration flow in coronary arteries-Physiology versus anatomy?

BACKGROUND: Myocardial ischaemia results from insufficient coronary blood flow. Computed virtual fractional flow reserve (vFFR) allows quantification of proportional flow loss without the need for invasive pressure-wire testing. In the current study, we describe a novel, conductivity model of side branch flow, referred to as 'leak'. This leak model is a function of taper and local pressure, the latter of which may change radically when focal disease is present. This builds upon previous techniques, which either ignore side branch flow, or rely purely on anatomical factors. This study aimed to describe a new, conductivity model of side branch flow and compare this with established anatomical models. METHODS AND RESULTS: The novel technique was used to quantify vFFR, distal absolute flow (Qd) and microvascular resistance (CMVR) in 325 idealised 1D models of coronary arteries, modelled from invasive clinical data. Outputs were compared to an established anatomical model of flow. The conductivity model correlated and agreed with the reference model for vFFR (r = 0.895, p < 0.0001; ＋0.02, 95% CI 0.00 to ＋ 0.22), Qd (r = 0.959, p < 0.0001; -5.2 mL/min, 95% CI -52.2 to ＋13.0) and CMVR (r = 0.624, p < 0.0001; ＋50 Woods Units, 95% CI -325 to ＋2549). CONCLUSION: Agreement between the two techniques was closest for vFFR, with greater proportional differences seen for Qd and CMVR. The conductivity function assumes vessel taper was optimised for the healthy state and that CMVR was not affected by local disease. The latter may be addressed with further refinement of the technique or inferred from complementary image data. The conductivity technique may represent a refinement of current techniques for modelling coronary side-branch flow. Further work is needed to validate the technique against invasive clinical data.

Sex differences in coronary microvascular resistance measured by a computational fluid dynamics model.

Background: Increased coronary microvascular resistance (CMVR) is associated with coronary microvascular dysfunction (CMD). Although CMD is more common in women, sex-specific differences in CMVR have not been demonstrated previously. Aim: To compare CMVR between men and women being investigated for chest pain. Methods and results: We used a computational fluid dynamics (CFD) model of human coronary physiology to calculate absolute CMVR based on invasive coronary angiographic images and pressures in 203 coronary arteries from 144 individual patients. CMVR was significantly higher in women than men (860 [650-1,205] vs. 680 [520-865] WU, Z = -2.24, p = 0.025). None of the other major subgroup comparisons yielded any differences in CMVR. Conclusion: CMVR was significantly higher in women compared with men. These sex-specific differences may help to explain the increased prevalence of CMD in women.

The Complementary Value of Absolute Coronary Flow in the Assessment of Patients with Ischaemic Heart Disease (the COMPAC-Flow Study).

Fractional flow reserve (FFR) is the current gold-standard invasive assessment of coronary artery disease (CAD). FFR reports coronary blood flow (CBF) as a fraction of a hypothetical and unknown normal value. Although used routinely to diagnose CAD and guide treatment, how accurately FFR predicts actual CBF changes remains unknown. Here we compared fractional CBF with the absolute CBF (aCBF in mL/min), measured with a computational method during standard angiography and pressure-wire assessment, on 203 diseased arteries (143 patients). We found a substantial correlation between the two measurements (r 0.89, Cohen's Kappa 0.71). Concordance between fractional and absolute CBF reduction was high when FFR was >0.80 (91%), but reduced when FFR was ≤0.80 (81%), 0.70-0.80 (68%) and, particularly 0.75-0.80 (62%). Discordance was associated with coronary microvascular resistance, vessel diameter and mass of myocardium subtended, all factors to which FFR is agnostic. Assessment of aCBF complements FFR, and may be valuable to assess CBF, particularly in cases within the FFR 'grey-zone'.

Virtual (Computed) Fractional Flow Reserve: Future Role in Acute Coronary Syndromes.

The current management of acute coronary syndromes (ACS) is with an invasive strategy to guide treatment. However, identifying the lesions which are physiologically significant can be challenging. Non-invasive imaging is generally not appropriate or timely in the acute setting, so the decision is generally based upon visual assessment of the angiogram, supplemented in a small minority by invasive pressure wire studies using fractional flow reserve (FFR) or related indices. Whilst pressure wire usage is slowly increasing, it is not feasible in many vessels, patients and situations. Limited evidence for the use of FFR in non-ST elevation (NSTE) ACS suggests a 25% change in management, compared with traditional assessment, with a shift from more to less extensive revascularisation. Virtual (computed) FFR (vFFR), which uses a 3D model of the coronary arteries constructed from the invasive angiogram, and application of the physical laws of fluid flow, has the potential to be used more widely in this situation. It is less invasive, fast and can be integrated into catheter laboratory software. For severe lesions, or mild disease, it is probably not required, but it could improve the management of moderate disease in 'real time' for patients with non-ST elevation acute coronary syndromes (NSTE-ACS), and in bystander disease in ST elevation myocardial infarction. Its practicability and impact in the acute setting need to be tested, but the underpinning science and potential benefits for rapid and streamlined decision-making are enticing.

Study Design Features Associated with Patient Attrition in Studies of Traumatic Brain Injury: A Systematic Review.

Loss to follow-up or patient attrition is common in longitudinal studies of traumatic brain injury (TBI). Lack of understanding exists between the relation of study design and patient attrition. This review aimed to identify features of study design that are associated with attrition. We extended the analysis of a previous systematic review on missing data in 195 TBI studies using the Glasgow Outcome Scale Extended (GOSE) as an outcome measure. Studies that did not report attrition or had heterogeneous methodology were excluded, leaving 148 studies. Logistic regression found seven of the 14 design features studied to be associated with patient attrition. Four features were associated with an increase in attrition: greater follow-up frequency (odds ratio [OR]: 1.2, 95% confidence interval [CI]: 1.0-1.3), single rather than multi-center design (OR: 1.6, 95% CI: 1.2-2.2), enrollment of exclusively mild TBI patients (OR: 2.8, 95% CI: 1.6-4.9), and collection of the GOS by post or telephone without face-to-face contact (OR: 1.6, 95% CI:1.1-2.4). Conversely, two features were associated with a reduction in attrition: recruitment in an acute care setting defined as the ward or intensive care unit (OR: 0.58, 95% CI: 0.47-0.72) and a greater duration of time between injury and follow-up (OR: 0.93, 95% CI: 0.88-0.99). This review highlights design features that are associated with attrition and could be considered when planning for patient retention. Further work is needed to establish the mechanisms between the observed associations and potential remedies.

Handling of Missing Outcome Data in Traumatic Brain Injury Research: A Systematic Review.

Traumatic brain injury (TBI) research commonly measures long-term functional outcome, but studies often suffer from missing data as patients are lost to follow-up. This review assesses the extent and handling of missing outcome data in the TBI literature and provides a practical guide for future research. Relevant electronic databases were searched from January 1, 2012 to October 27, 2017 for TBI studies that used the Glasgow Outcome Scale or Glasgow Outcome Scale-Extended (GOS/GOSE) as an outcome measure. Studies were screened and data extracted in line with Cochrane guidance. A total of 195 studies, 21 interventional, 174 observational, with 104,688 patients were included. Using the reported follow-up rates in a mixed model, on average 91% of patients were predicted to return to follow-up at 6 months post-injury, 84% at 1 year, and 69% at 2 years. However, 36% of studies provided insufficient information to determine the number of subjects at each time-point. Of 139 studies that did report missing outcome data, only 50% attempted to identify why data were missing, with just 4 reporting their assumption on the "missingness mechanism." The handling of missing data was heterogeneous, with the most common method being its exclusion from analysis. These results confirm substantial variability in the standard of reporting and handling of missing outcome data in TBI research. We conclude that practical guidance is needed to facilitate meaningful and accurate study interpretation, and therefore propose a framework for the handling of missing outcome data in future TBI research.

Prevalence of hepatitis C among psychiatric patients in the public sector.

OBJECTIVE: This study estimated the seroprevalence of hepatitis C virus in a public-sector psychiatric hospital. METHOD: Patients admitted between Jan. 1, 1998, and Dec. 30, 2000, were routinely screened for hepatitis C virus antibody on admission. RESULTS: A total of 133 (8.5%) of 1,556 patients admitted were positive for the hepatitis C virus. Aminotransferase levels were elevated but rarely abnormal among patients positive for the hepatitis C virus. Hepatitis B surface antibody was found in 27.8% of the patients positive for the hepatitis C virus. These patients were more likely to receive a diagnosis of psychoactive substance use disorder but no other psychiatric diagnoses. CONCLUSIONS: The prevalence of hepatitis C virus is high among psychiatric patients in the public sector. Much needs to be learned about the role of universal screening and effective techniques for primary prevention and antiviral treatment in this population.

Laboratory investigation of an E. coli O157:H7 outbreak associated with swimming in Battle Ground Lake, Vancouver, Washington.

Escherichia coli O157:H7 has been associated with a number of waterborne outbreaks, but it has never been recovered from an implicated environment. This paper reports on an August 1999 outbreak of E. coli O157:H7 associated with swimming in Battle Ground Lake in Clark Country, Washington. E. coli O157:H7 was isolated from duck feces, as well as from two water samples. The authors used pulsed-field gel electrophoresis to compare these isolates with patient isolates for genetic homology. All the isolates yielded the same restriction fragment patterns. In addition, using polymerase chain reaction, the authors found patient isolates and environmental isolates to have the same virulence factors (Stx, eaeA, and hly).