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Background: The COVID-19 pandemic has a large impact worldwide and is known to particularly affect the older population. This paper outlines the protocol for external validation of prognostic models predicting mortality risk after presentation with COVID-19 in the older population. These prognostic models were originally developed in an adult population and will be validated in an older population (≥70 years of age) in three healthcare settings: the hospital setting, the primary care setting, and the nursing home setting. Methods: Based on a living systematic review of COVID-19 prediction models, we identified eight prognostic models predicting the risk of mortality in adults with a COVID-19 infection (five COVID-19 specific models: GAL-COVID-19 mortality, 4C Mortality Score, NEWS2+ model, Xie model, and Wang clinical model and three pre-existing prognostic scores: APACHE-II, CURB65, SOFA). These eight models will be validated in six different cohorts of the Dutch elder population, three hospital cohorts, two primary care cohorts, and a nursing home cohort. All prognostic models will be validated in hospital setting while the GAL-COVID-19 mortality model will be validated in hospital, primary care, and nursing home settings. The study will include individuals ≥70 years of age with a highly suspected or PCR-confirmed COVID-19 infection from March 2020 to December 2020 (and up to December 2021 in a sensitivity analysis). The predictive performance will be evaluated in terms of discrimination, calibration, and decision curves for each of the COVID-19 prognostic models in each cohort individually. For prognostic models with indications of miscalibration, an intercept update will be performed after which predictive performance will be re-evaluated. Discussion:Insight into the performance of existing prognostic models in one of the most vulnerable populations clarifies the extent to which tailoring of COVID-19 prognostic models is needed when models are applied to the older population. Such insight will be important for possible future waves of the COVID-19 pandemic or future pandemics.

Highlights • Especially the frail elderly show a high number of severe COVID-19. • Viral shedding may be increased in elderly patients. • Early identification is complicated due to atypical disease presentation. • Applying hygiene measures in patients with cognitive disorders is challenging. • The cardiorespiratory reserve is decreased increasing the risk of complications. • The aging immune system has a pro-inflammatory tendency, exaggerated by SARS-CoV-2., Importance: Among COVID-19 cases, especially the (frail) elderly show a high number of severe infections, hospital admissions, complications, and death. The highest mortality is found between 80 and 89 years old. Why do these patients have a higher risk of severe COVID-19? In this narrative review we address potential mechanisms regarding viral transmission, physical reserve and the immune system, increasing the severity of this infection in elderly patients. Observations: First, the spread of COVID-19 may be enhanced in elderly patients. Viral shedding may be increased, and early identification may be complicated due to atypical disease presentation and limited testing capacity. Applying hygiene and quarantine measures, especially in patients with cognitive disorders including dementia, can be challenging. Additionally, elderly patients have a decreased cardiorespiratory reserve and are more likely to have co-morbidity including atherosclerosis, rendering them more susceptible to complications. The aging innate and adaptive immune system is weakened, while there is a pro-inflammatory tendency. The effects of SARS-CoV-2 on the immune system on cytokine production and T-cells, further seem to aggravate this pro-inflammatory tendency, especially in patients with cardiovascular comorbidity, increasing disease severity. Conclusions and relevance: The combination of all factors mentioned above contribute to the disease severity of COVID-19 in the older patient. While larger studies of COVID-19 in elderly patients are needed, understanding the factors increasing disease severity may improve care and preventative measures to protect the elderly patient at risk for (severe) COVID-19 in the future.

The Initial Systolic Time Interval (ISTI), obtained from the electrocardiogram (ECG) and impedance cardiogram (ICG), is considered to be a measure for the time delay between the electrical and mechanical activity of the heart and reflects an early active period of the cardiac cycle. The clinical relevance of this time interval is subject of study. This paper introduces a method using ISTI to evaluate and predict the circulatory response to fluid administration in patients after coronary artery bypass graft surgery and presents preliminary results of a pilot study by comparing ISTI with cardiac output (CO) responsiveness. Also the use of the pulse transit time (PTT), earlier recommended for this purpose, was investigated. The results showed an inverse relationship between ISTI and CO at all moments of fluid administration and also an inverse relationship between the changes ΔISTI and ΔCO before and after full fluid administration. No relationships between PTT and CO or ΔPTT and ΔCO were found. It is concluded that ISTI is dependent upon preload, and that ISTI has the potential to be used as a clinical parameter assessing preload.

After the publication of this work [1] it was brought to our attention that there was an error in Table two (Table 1 here) of the article, in which the table columns were misaligned. The correct version of the table is included here: Table 1 Composition of bodyl fluids (in mmol/L)

ObjectiveIn this narrative review, an overview is given of the pros and cons of various crystalloid fluids used for infusion during initial resuscitation or maintenance phases in adult hospitalized patients. Special emphasis is given on dose, composition of fluids, presence of buffers (in balanced solutions) and electrolytes, according to recent literature. We also review the use of hypertonic solutions.MethodsWe extracted relevant clinical literature in English specifically examining patient-oriented outcomes related to fluid volume and type.ResultsA restrictive fluid therapy prevents complications seen with liberal, large-volume therapy, even though restrictive fluid loading with crystalloids may not demonstrate large hemodynamic effects in surgical or septic patients. Hypertonic solutions may serve the purpose of small volume resuscitation but carry the disadvantage of hypernatremia. Hypotonic solutions are contraindicated in (impending) cerebral edema, whereas hypertonic solutions are probably more helpful in ameliorating than in preventing this condition and improving outcome. Balanced solutions offer a better approach for plasma composition than unbalanced ones, and the evidence for benefits in patient morbidity and mortality is increasing, particularly by helping to prevent acute kidney injury.ConclusionsIsotonic and hypertonic crystalloid fluids are the fluids of choice for resuscitation from hypovolemia and shock. The evidence that balanced solutions are superior to unbalanced ones is increasing. Hypertonic saline is effective in mannitol-refractory intracranial hypertension, whereas hypotonic solutions are contraindicated in this condition.

OBJECTIVES: Haemodynamic parameters for predicting fluid responsiveness in intensive care patients are invasive, technically challenging or not universally applicable. We compared the initial systolic time interval (ISTI), a non-invasive measure of the time interval between the electrical and mechanical activities of the heart measured by impedance cardiography, with invasively measured haemodynamic parameters in predicting fluid responsiveness after cardiac surgery. METHODS: Thirty-two clinically hypovolemic patients admitted to the intensive care unit after coronary artery bypass surgery received 500 ml of gelatine solution in two volume loading steps of 250 ml at an infusion rate of 1000 ml/h. Haemodynamic and biochemical measurements were done at baseline and 15 min after each volume loading step with continuous recording of the impedance cardiogram and electrocardiogram. RESULTS: Forty-four percentage (n = 14) of patients showed a stroke volume (SV) index increase >10%. ISTI predicted fluid responsiveness with an optimum threshold of >153 ms (P = 0.023) and a sensitivity of 71% and specificity of 78%. The predictive values of ISTI did not differ from those of arterial pressure or SV at baseline. A decrease of ISTI of =8.3 ms predicted fluid responsiveness with the highest positive predictive value (88%, P = 0.004) among the variables, and absence thereof virtually excluded fluid responsiveness (specificity 94%). CONCLUSIONS: Non-invasively measured ISTI is able to predict and monitor fluid responsiveness after cardiac surgery non-inferiorly to invasively measured haemodynamic indices. © The Author 2013. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

The objective of the study is to develop a non-invasive method to optimize the assessment of cardiac preload and therapeutic fluid administration after coronary artery bypass surgery. Previous studies have reported that the pre-ejection period (PEP), obtained from the electro-cardiogram (ECG) and from the invasively measured arterial pressure Pa, can be used for this assessment as it is dependent on the cardiac preload. The Initial Systolic Time Interval (ISTI), obtained non-invasively by simultaneous measurement of the Electro-CardioGram (ECG) and Impedance CardioGram (ICG), is expected to depend on the cardiac preload as well. 16 patients, admitted to the Intensive Care Unit after coronary artery bypass surgery and presumably hypovolaemic, were measured during administration of 2×250 ml of an isosmotic colloidal fluid solution. The parameters PEP and ISTI were determined before and after the administrations and compared with the change in cardiac output (CO), obtained by a thermodilution technique. Preliminary results show significant relationships between ISTI and CO and between changes in both of these variables before and after fluid administration.