Exploring causal interactions between blood pressure and RR interval at the respiratory frequency

The mechanisms underlying the relationship between RR interval and systolic arterial pressure (SAP) variability at the respiratory frequency are still object of discussion. In this study, the information on directionality provided by causal cross-spectral analysis was exploited to infer possible influences of respiration on cardiovascular parameters variability. The ability of causal analysis to account for directionality in RR-SAP interrelationships in presence of respiratory exogenous effects was first tested on model simulations. Hence, real data measured on healthy subjects during spontaneous and paced breathing at 0.25 Hz were analysed. The results obtained in real data were consistent with simulations, thus supporting the hypothesis of different influences of respiration on SAP and RR interval variability under different physiological conditions

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Feasibility of cuff-free measurement of systolic and diastolic arterial blood pressure

We validated a prototype cuff-free device for noninvasive estimation of blood pressure (BP). The system assumed a linear relation between BP values and the inverse of arterial blood pulse transit time, measured as time interval between the R wave on the electrocardiograph and the onset of the peripheral pulse wave on a finger plethysmogram. Thirty-three healthy subjects were analyzed at rest and during increasing stress exercise. To estimate subject-specific linear model parameters, the system was calibrated ad personam with reference to BP measures obtained by a cuff sphygmomanometer. High correlation values (R(2) = 0.89 and 0.78 for systolic and diastolic BP, respectively) and differences consistent with clinical requirements (mean discrepancy of -0.058 and -0.25 mm Hg; 95% confidence interval of -13.0 to +12.9 mm Hg and -11.3 to +10.8 mm Hg, for systolic and diastolic BP, respectively) were observed between device and reference measurements. Calibration parameter stability and accuracy level were confirmed in a midterm evaluation, 30 days after calibration. These findings suggest the suitability of the device for noninvasive BP monitoring and its potentiality for clinical applications. Improvements can be achieved by further investigation of the calibration procedure and sensor placement

Causal transfer function analysis to describe closed loop interactions between cardiovascular and cardiorespiratory variability signals

Although the concept of transfer function is intrinsically related to an input-output relationship, the traditional and widely used estimation method merges both feedback and feedforward interactions between the two analyzed signals. This limitation may endanger the reliability of transfer function analysis in biological systems characterized by closed loop interactions. In this study, a method for estimating the transfer function between closed loop interacting signals was proposed and validated in the field of cardiovascular and cardiorespiratory variability. The two analyzed signals x and y were described by a bivariate autoregressive model, and the causal transfer function from x to y was estimated after imposing causality by setting to zero the model coefficients representative of the reverse effects from y to x. The method was tested in simulations reproducing linear open and closed loop interactions, showing a better adherence of the causal transfer function to the theoretical curves with respect to the traditional approach in presence of non-negligible reverse effects. It was then applied in ten healthy young subjects to characterize the transfer functions from respiration to heart period (RR interval) and to systolic arterial pressure (SAP), and from SAP to RR interval. In the first two cases, the causal and non-causal transfer function estimates were comparable, indicating that respiration, acting as exogenous signal, sets an open loop relationship upon SAP and RR interval. On the contrary, causal and traditional transfer functions from SAP to RR were significantly different, suggesting the presence of a considerable influence on the opposite causal direction. Thus, the proposed causal approach seems to be appropriate for the estimation of parameters, like the gain and the phase lag from SAP to RR interval, which have a large clinical and physiological relevance

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use

The value of open-source clinical science in pandemic response: lessons from ISARIC

International audienc