A three-parameter langmuir-type model for fitting standard curves of sandwich enzyme immunoassays with special attention to the α-fetoprotein assay

In a simplified approach to the reaction kinetics of enzyme-linked immunoassays, a Langmuir-type equation y = [ax/(b + x)] + c was derived. This model proved to be superior to logit-log and semilog models in the curve-fitting of standard curves. An assay for α-fetoprotein developed in our laboratory with a sensitivity of 2 g/liter and a between-day coefficient of variation of about 15% was used for comparison of the different models. The proposed model has the advantage that it is based on the law of mass action and that blank determinations can be included in the calculation of the curves without giving a disproportionate bias

Effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients (CONFIDENCE): protocol for a multicentre randomised controlled trial.

BACKGROUND: Fluid therapy is a common intervention in critically ill patients. It is increasingly recognised that deresuscitation is an essential part of fluid therapy and delayed deresuscitation is associated with longer invasive ventilation and length of intensive care unit (ICU) stay. However, optimal timing and rate of deresuscitation remain unclear. Lung ultrasound (LUS) may be used to identify fluid overload. We hypothesise that daily LUS-guided deresuscitation is superior to deresuscitation without LUS in critically ill patients expected to undergo invasive ventilation for more than 24 h in terms of ventilator free-days and being alive at day 28. METHODS: The "effect of lung ultrasound-guided fluid deresuscitation on duration of ventilation in intensive care unit patients" (CONFIDENCE) is a national, multicentre, open-label, randomised controlled trial (RCT) in adult critically ill patients that are expected to be invasively ventilated for at least 24 h. Patients with conditions that preclude a negative fluid balance or LUS examination are excluded. CONFIDENCE will operate in 10 ICUs in the Netherlands and enrol 1000 patients. After hemodynamic stabilisation, patients assigned to the intervention will receive daily LUS with fluid balance recommendations. Subjects in the control arm are deresuscitated at the physician's discretion without the use of LUS. The primary endpoint is the number of ventilator-free days and being alive at day 28. Secondary endpoints include the duration of invasive ventilation; 28-day mortality; 90-day mortality; ICU, in hospital and total length of stay; cumulative fluid balance on days 1-7 after randomisation and on days 1-7 after start of LUS examination; mean serum lactate on days 1-7; the incidence of reintubations, chest drain placement, atrial fibrillation, kidney injury (KDIGO stadium ≥ 2) and hypernatremia; the use of invasive hemodynamic monitoring, and chest-X-ray; and quality of life at day 28. DISCUSSION: The CONFIDENCE trial is the first RCT comparing the effect of LUS-guided deresuscitation to routine care in invasively ventilated ICU patients. If proven effective, LUS-guided deresuscitation could improve outcomes in some of the most vulnerable and resource-intensive patients in a manner that is non-invasive, easy to perform, and well-implementable. TRIAL REGISTRATION: ClinicalTrials.gov NCT05188092. Registered since January 12, 2022

Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)

Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients (17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5–11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4–17.2). Multivariate analyses identify viral loads above 7 log10 RNA copies/mL (odds ratio [OR] of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions

Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study

BACKGROUND: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. METHODS: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. RESULTS: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. DISCUSSION: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research