Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)

The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death

Early ambulatory outpatient sequenced antiviral multidrug COVID-19 treatment (including for Delta or similar variants) for high-risk children and adolescents

During the past 19 months the global spread of the Severe Acute Respiratory Syndrome, Coronavirus2 (SARS-CoV-2 or COVID-19) has led to acute hospitalizations and death in primarily high-risk elderly and younger age groups who often present with comorbidities associated with increased risk. Otherwise, the virus is largely self-limiting in those infected outside of high-risk groups. Presently, the global community is confronting a predominant Delta variant of the virus, distinct from the initial variants, highly contagious and less virulent. The good news for high-risk populations is that early drug treatment (sequenced multi-drug treatment/SMDT) for all variants, has been shown to reduce the risk of hospitalization and death by as much as 85%. This paper is a combination of scientific research including clinical expert opinion of front-line doctors treating patients with COVID-19 and focuses on early treatments in children. The authors however, in support of the scientific literature recognize the risk of severe illness or death in the pediatric population is significantly low (statistical zero). Outlined are some of the key issues and pathophysiological principles that relate to the pediatric population with early infection. Therapeutic approaches based on these principles include 1) reduction of reinoculation, 2) combination antiviral anti-infective ‘repurposed’ therapy, 3) immunomodulation via oral/inhaled corticosteroids, 4) antiplatelet/antithrombotic/anticlotting therapy, and 5) administration of oxygen, monitoring, and telemedicine as needed. The key message is that as with adults, high-risk persons of any age, including the pediatric population, should not be left in a ‘wait-and-see’ mode whereby there is the potential for clinical decline; this, while effective, affordable, accessible, and safe treatments exist that could be administered in the pre-hospital phase. This paper should not in any way be taken as an indication or endorsement of elevated COVID-19 risk to pediatric populations, but rather as a proactive position in the rare instance a young child requires treatment. Future comparative effectiveness research comprised of high-quality and trustworthy observational study research and randomized controlled trials (especially study involving multiple therapeutic combinations/SMDT) will undoubtedly refine and clarify our clinical observations

Models for Hyperspectral Image Analysis: From Unmixing to Object-Based Classification

International audienceThe recent advances in hyperspectral remote sensing technology allow the simultaneous acquisition of hundreds of spectral wavelengths for each image pixel. This rich spectral information of the hyperspectral data makes it possible to discriminate different physical substances, leading to a potentially more accurate classification and thus opening the door to numerous new applications. Throughout the history of remote sensing research, numerous methods for hyperspectral image analysis have been presented. Depending on the spatial resolution of the images, specific mathematical models must be designed to effectively analyze the imagery. Some of these models operate at a sub-pixel level, trying to decompose a mixed spectral signature into its pure constituents, while others operate at a pixel or even object level, seeking to assign unique labels to every pixel or object in the scene. The spectral mixing of the measurements and the high dimensionality of the data are some of the challenging features of hyperspectral imagery. This chapter presents an overview of unmixing and classification methods, intended to address these challenges for accurate hyperspectral data analysis

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

ObjectivesAmong patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant.DesignSecondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722).SettingOne hundred-fifty-three ICUs in 13 countries.PatientsAltogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ).InterventionsNone.Measurements and main resultsTotal mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p p p p p p p p = 0.007).ConclusionsAmong STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions