Outbreak of Invasive Group A Streptococcus in Children-Colorado, October 2022-April 2023.

BACKGROUND: In the fall of 2022, we observed a sharp rise in pediatric Invasive Group A Streptococcus (iGAS) hospitalizations in Colorado. We compared the epidemiology, clinical features, and patient outcomes in this outbreak to prior years. METHODS: Between October 2022 and April 2023, we prospectively identified and reviewed iGAS cases in hospitalized pediatric patients at Children's Hospital Colorado. Using laboratory specimen records, we also retrospectively compared the number of patients with sterile site GAS-positive cultures across three time periods: pre-COVID-19 (January 2015-March 2020), height of COVID-19 pandemic (April 2020-September 2022), and outbreak (October 2022-April 2023). RESULTS: Among 96 prospectively identified iGAS cases, median age was 5.7 years old; 66% were male, 70% previously healthy, 39% required critical care, and four patients died. Almost 60% had associated respiratory viral symptoms, 10% had toxic shock syndrome, and 4% had necrotizing fasciitis. Leukopenia, bandemia, and higher C-reactive protein values were laboratory findings associated with need for critical care. There were significantly more cases during the outbreak (9.9/month outbreak vs 3.9/month pre-pandemic vs 1.3/month pandemic), including more cases with pneumonia (28% outbreak vs 15% pre-pandemic vs 0% pandemic) and multifocal disease (17% outbreak vs 3% pre-pandemic vs 0% pandemic), P < .001 for all. CONCLUSIONS: Outbreak case numbers were almost triple the pre-pandemic baseline. The high percentage of cases with associated viral symptoms suggests a link to coinciding surges in respiratory viruses during this time. Invasive GAS can be severe and evolve rapidly; clinical and laboratory features may help in earlier identification of critically ill children.

Fairness and Risk: An Ethical Argument for a Group Fairness Definition Insurers Can Use.

Algorithmic predictions are promising for insurance companies to develop personalized risk models for determining premiums. In this context, issues of fairness, discrimination, and social injustice might arise: Algorithms for estimating the risk based on personal data may be biased towards specific social groups, leading to systematic disadvantages for those groups. Personalized premiums may thus lead to discrimination and social injustice. It is well known from many application fields that such biases occur frequently and naturally when prediction models are applied to people unless special efforts are made to avoid them. Insurance is no exception. In this paper, we provide a thorough analysis of algorithmic fairness in the case of insurance premiums. We ask what "fairness" might mean in this context and how the fairness of a premium system can be measured. For this, we apply the established fairness frameworks of the fair machine learning literature to the case of insurance premiums and show which of the existing fairness criteria can be applied to assess the fairness of insurance premiums. We argue that two of the often-discussed group fairness criteria, independence (also called statistical parity or demographic parity) and separation (also known as equalized odds), are not normatively appropriate for insurance premiums. Instead, we propose the sufficiency criterion (also known as well-calibration) as a morally defensible alternative that allows us to test for systematic biases in premiums towards certain groups based on the risk they bring to the pool. In addition, we clarify the connection between group fairness and different degrees of personalization. Our findings enable insurers to assess the fairness properties of their risk models, helping them avoid reputation damage resulting from potentially unfair and discriminatory premium systems.

How I Would have been Differently Treated. Discrimination Through the Lens of Counterfactual Fairness.

The widespread use of algorithms for prediction-based decisions urges us to consider the question of what it means for a given act or practice to be discriminatory. Building upon work by Kusner and colleagues in the field of machine learning, we propose a counterfactual condition as a necessary requirement on discrimination. To demonstrate the philosophical relevance of the proposed condition, we consider two prominent accounts of discrimination in the recent literature, by Lippert-Rasmussen and Hellman respectively, that do not logically imply our condition and show that they face important objections. Specifically, Lippert-Rasmussen's definition proves to be over-inclusive, as it classifies some acts or practices as discriminatory when they are not, whereas Hellman's account turns out to lack explanatory power precisely insofar as it does not countenance a counterfactual condition on discrimination. By defending the necessity of our counterfactual condition, we set the conceptual limits for justified claims about the occurrence of discriminatory acts or practices in society, with immediate applications to the ethics of algorithmic decision-making.

Childhood Obesity and the Cryptic Language of the Microbiota: Metabolomics' Upgrading.

The growing obesity epidemic in childhood is increasingly concerning for the related physical and psychological consequences, with a significant impact on health care costs in both the short and the long term. Nonetheless, the scientific community has not yet completely clarified the complex metabolic mechanisms underlying body weight alterations. In only a small percentage of cases, obesity is the result of endocrine, monogenic, or syndromic causes, while in much more cases, lifestyle plays a crucial role in obesity development. In this context, the pediatric age appears to be of considerable importance as prevention strategies together with early intervention can represent important therapeutic tools not only to counteract the comorbidities that increasingly affect children but also to hinder the persistence of obesity in adulthood. Although evidence in the literature supporting the alteration of the microbiota as a critical factor in the etiology of obesity is abundant, it is not yet fully defined and understood. However, increasingly clear evidence is emerging regarding the existence of differentiated metabolic profiles in obese children, with characteristic metabolites. The identification of specific pathology-related biomarkers and the elucidation of the altered metabolic pathways would therefore be desirable in order to clarify aspects that are still poorly understood, such as the consequences of the interaction between the host, the diet, and the microbiota. In fact, metabolomics can characterize the biological behavior of a specific individual in response to external stimuli, offering not only an eventual effective screening and prevention strategy but also the possibility of evaluating adherence and response to dietary intervention.

Multi-institutional experience with COVID-19 convalescent plasma in children.

BACKGROUND AND OBJECTIVES: Convalescent COVID-19 plasma (CCP) was developed and used worldwide as a treatment option by supplying passive immunity. Adult studies suggest administering high-titer CCP early in the disease course of patients who are expected to be antibody-negative; however, pediatric experience is limited. We created a multi-institutional registry to characterize pediatric patients (<18 years) who received CCP and to assess the safety of this intervention. METHODS: A REDCap survey was distributed. The registry collected de-identified data including demographic information (age, gender, and underlying conditions), COVID-19 disease features and concurrent treatments, CCP transfusion and safety events, and therapy response. RESULTS: Ninety-five children received CCP: 90 inpatients and 5 outpatients, with a median age of 10.2 years (range 0-17.9). They were predominantly Latino/Hispanic and White. The most frequent underlying medical conditions were chronic respiratory disease, immunosuppression, obesity, and genetic syndromes. CCP was primarily given as a treatment (95%) rather than prophylaxis (5%). Median total plasma dose administered and transfusion rates were 5.0 ml/kg and 2.6 ml/kg/h, respectively. The transfusions were well-tolerated, with 3 in 115 transfusions reporting mild reactions. No serious adverse events were reported. Severity scores decreased significantly 7 days after CCP transfusion or at discharge. Eighty-five patients (94.4%) survived to hospital discharge. All five outpatients survived to 60 days. CONCLUSIONS: CCP was found to be safe and well-tolerated in children. CCP was frequently given concurrently with other COVID-19-directed treatments with improvement in clinical severity scores ≥7 days after CCP, but efficacy could not be evaluated in this study.

Risk Factors for Venous Thromboembolic Events in Children With Acute Musculoskeletal Infections.

BACKGROUND AND OBJECTIVES: Venous thromboembolic events (VTE) complicate acute hematogenous musculoskeletal infections (MSKIs) among hospitalized children. However, there is limited guidance for which specific MSKI patients are at the greatest VTE risk. This study aimed to identify VTE risk factors for children hospitalized with MSKIs. METHODS: A retrospective chart review was performed of children hospitalized with MSKIs at a single quaternary care pediatric hospital during a 9-year period. Patients with chronic MSKIs, non-hematogenous infections, or significant contributing comorbidities were excluded. Demographic and clinical characteristics were compared between patients with and without VTE using forward stepwise conditional multivariable logistic regression to identify VTE risk factors. RESULTS: Among 335 included patients, 7 (2.1%) developed a VTE. There was no difference in age, sex, or obesity rates for those with or without VTE. Patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and/or critical illness were more likely to develop a VTE with summative adjusted odds ratios of 31.7 and 26.4, respectively. In addition, patients with VTEs had longer hospitalizations (median 4.7 vs. 12.8 d, P <0.001), longer courses of intravenous antimicrobials (median 3.7 vs. 13.5 d, P =0.001), and longer time to fever resolution (median 25.7 vs. 162 h, P =0.004). CONCLUSIONS: VTE prevalence among children with acute MSKIs is low. MRSA infection and critical illness significantly increase the risk for VTE development in these patients. Future prospective studies are needed to determine if VTEs in high-risk MSKI patients can be prevented.

Outcomes of Critically Ill Children With Acute Lymphoblastic Leukemia and Cytokine Release Syndrome Due to Chimeric Antigen Receptor T Cell Therapy: US, Multicenter PICU, Cohort Database Study.

OBJECTIVES: Cytokine release syndrome (CRS) is a potentially lethal toxicity associated with chimeric antigen receptor T cell therapy for pediatric acute lymphoblastic leukemia (ALL). Outcomes after critical illness due to severe CRS are poorly described. Our aim was to characterize critical illness outcomes across a multicenter cohort of PICU patients with ALL and CRS. DESIGN: Multicenter retrospective cohort study. SETTING: Twenty-one PICUs contributing data to Virtual Pediatric Systems, LLC (January 2020-December 2021). PATIENTS: PICU patients with ALL or unclassified leukemia and CRS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 55 patients; 34 (62%) were 12 years or older, 48 (87%) were admitted from a hospital inpatient ward, and 23 (42%) received advanced organ failure support or monitoring. Fifty-one survived to PICU discharge (93%) including 19 of 23 (83%) who received advanced organ failure support or monitoring defined as receipt of noninvasive or invasive ventilation, cardiopulmonary resuscitation, extracorporeal membrane oxygenation, continuous renal replacement therapy, or placement of a tracheostomy, arterial catheter, hemodialysis catheter, or intracranial catheter. Twelve patients (22%) received invasive ventilation, nine of whom survived to PICU discharge. Two of four patients who received continuous renal replacement therapy and one of three patients who required cardiopulmonary resuscitation survived to PICU discharge. Lengths of PICU stay were median 3.0 days (interquartile range, 1.4-7.8 d) among PICU survivors, 7.8 (5.4-11.1) among those receiving advanced organ failure support or monitoring, and 7.2 days (interquartile range, 2.9-14.7 d) among nonsurvivors. Of the 51 patients who survived to PICU discharge, 48 (94%) survived the hospitalization. CONCLUSIONS: PICU patients with CRS frequently received a high level of support, and the majority survived their PICU stay and hospitalization. Additional multicenter investigations of severe CRS are necessary to inform evidence-based practice.

Serum lactate is associated with increased illness severity in immunocompromised pediatric hematology oncology patients presenting to the emergency department with fever.

Introduction: Determining which febrile pediatric hematology/oncology (PHO) patients will decompensate from severe infection is a significant challenge. Serum lactate is a well-established marker of illness severity in general adult and pediatric populations, however its utility in PHO patients is unclear given that chemotherapy, organ dysfunction, and cancer itself can alter lactate metabolism. In this retrospective analysis, we studied the association of initial serum lactate in febrile immunosuppressed PHO patients with illness severity, defined by the incidence of clinical deterioration events (CDE) and invasive bacterial infection (IBI) within 48 hours. Methods: Receiver operating characteristic (ROC) curves were reported using initial lactate within two hours of arrival as the sole predictor for CDE and IBI within 48 hours. Using a generalized estimating equations (GEE) approach, the association of lactate with CDE and IBI within 48 hours was tested in univariate and multivariable analyses including covariates based on Quasi-likelihood under Independence Model Criterion (QIC). Additionally, the association of lactate with secondary outcomes (i.e., hospital length of stay (LOS), intensive care unit (PICU) admission, PICU LOS, non-invasive infection) was assessed. Results: Among 897 encounters, 48 encounters had ≥1 CDE (5%), and 96 had ≥1 IBI (11%) within 48 hours. Elevated lactate was associated with increased CDE in univariate (OR 1.77, 95%CI: 1.48-2.12, p<0.001) and multivariable (OR 1.82, 95%CI: 1.43-2.32, p<0.001) analyses, longer hospitalization (OR 1.15, 95%CI: 1.07-1.24, p<0.001), increased PICU admission (OR 1.68, 95%CI: 1.41-2.0, p<0.001), and longer PICU LOS (OR 1.21, 95%CI: 1.04-1.4, p=0.01). Elevated lactate was associated with increased IBI in univariate (OR 1.40, 95%CI: 1.16-1.69, p<0.001) and multivariable (OR 1.49, 95%CI: 1.23-1.79, p<0.001) analyses. Lactate level was not significantly associated with increased odds of non-invasive infection (p=0.09). The QIC of the model was superior with lactate included for both CDE (305 vs. 325) and IBI (563 vs. 579). Conclusions: These data demonstrated an independent association of elevated initial lactate level and increased illness severity in febrile PHO patients, suggesting that serum lactate could be incorporated into future risk stratification strategies for this population.

A Multicenter, Prospective, Observational, Cohort-Controlled Study of Clinical Outcomes Following Coronavirus Disease 2019 (COVID-19) Convalescent Plasma Therapy in Hospitalized Patients With COVID-19.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial. METHODS: From April through August 2020, hospitalized patients with COVID-19 at 16 participating hospitals in Colorado were enrolled and treated with CCP and compared with hospitalized patients with COVID-19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial, given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated hospitalized patients with COVID-19 were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality. RESULTS: A total of 542 hospitalized patients with COVID-19 were enrolled at 16 hospitals across the region. A total of 468 hospitalized patients with COVID-19 were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared with controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. CONCLUSIONS: These data show that treatment of hospitalized patients with COVID-19 treated with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality.

Highway to (Digital) Surveillance: When Are Clients Coerced to Share Their Data with Insurers?

Clients may feel trapped into sharing their private digital data with insurance companies to get a desired insurance product or premium. However, private insurance must collect some data to offer products and premiums appropriate to the client's level of risk. This situation creates tension between the value of privacy and common insurance business practice. We argue for three main claims: first, coercion to share private data with insurers is pro tanto wrong because it violates the autonomous choice of a privacy-valuing client. Second, we maintain that irrespective of being coerced, the choice of accepting digital surveillance by insurers makes it harder for the client to protect his or her autonomy (and to act spontaneously and authentically). The violation of autonomy also makes coercing customers into digital surveillance pro tanto morally wrong. Third, having identified an economically plausible process involving no direct coercion by insurers, leading to the adoption of digital surveillance, we argue that such an outcome generates further threats against autonomy. This threat provides individuals with a pro tanto reason to prevent this process. We highlight the freedom dilemma faced by regulators who aim to prevent this outcome by constraining market freedoms and argue for the need for further moral and empirical research on this question.

Transparency as design publicity: explaining and justifying inscrutable algorithms.

In this paper we argue that transparency of machine learning algorithms, just as explanation, can be defined at different levels of abstraction. We criticize recent attempts to identify the explanation of black box algorithms with making their decisions (post-hoc) interpretable, focusing our discussion on counterfactual explanations. These approaches to explanation simplify the real nature of the black boxes and risk misleading the public about the normative features of a model. We propose a new form of algorithmic transparency, that consists in explaining algorithms as an intentional product, that serves a particular goal, or multiple goals (Daniel Dennet's design stance) in a given domain of applicability, and that provides a measure of the extent to which such a goal is achieved, and evidence about the way that measure has been reached. We call such idea of algorithmic transparency "design publicity." We argue that design publicity can be more easily linked with the justification of the use and of the design of the algorithm, and of each individual decision following from it. In comparison to post-hoc explanations of individual algorithmic decisions, design publicity meets a different demand (the demand for impersonal justification) of the explainee. Finally, we argue that when models that pursue justifiable goals (which may include fairness as avoidance of bias towards specific groups) to a justifiable degree are used consistently, the resulting decisions are all justified even if some of them are (unavoidably) based on incorrect predictions. For this argument, we rely on John Rawls's idea of procedural justice applied to algorithms conceived as institutions.

Trust does not need to be human: it is possible to trust medical AI.

In his recent article 'Limits of trust in medical AI,' Hatherley argues that, if we believe that the motivations that are usually recognised as relevant for interpersonal trust have to be applied to interactions between humans and medical artificial intelligence, then these systems do not appear to be the appropriate objects of trust. In this response, we argue that it is possible to discuss trust in medical artificial intelligence (AI), if one refrains from simply assuming that trust describes human-human interactions. To do so, we consider an account of trust that distinguishes trust from reliance in a way that is compatible with trusting non-human agents. In this account, to trust a medical AI is to rely on it with little monitoring and control of the elements that make it trustworthy. This attitude does not imply specific properties in the AI system that in fact only humans can have. This account of trust is applicable, in particular, to all cases where a physician relies on the medical AI predictions to support his or her decision making.

Multidisciplinary Guidance Regarding the Use of Immunomodulatory Therapies for Acute Coronavirus Disease 2019 in Pediatric Patients.

BACKGROUND: Immune-mediated lung injury and systemic hyperinflammation are characteristic of severe and critical coronavirus disease 2019 (COVID-19) in adults. Although the majority of severe acute respiratory syndrome coronavirus 2 infections in pediatric populations result in minimal or mild COVID-19 in the acute phase of infection, a small subset of children develop severe and even critical disease in this phase with concomitant inflammation that may benefit from immunomodulation. Therefore, guidance is needed regarding immunomodulatory therapies in the setting of acute pediatric COVID-19. This document does not provide guidance regarding the recently emergent multisystem inflammatory syndrome in children (MIS-C). METHODS: A multidisciplinary panel of pediatric subspecialty physicians and pharmacists with expertise in infectious diseases, rheumatology, hematology/oncology, and critical care medicine was convened. Guidance statements were developed based on best available evidence and expert opinion. RESULTS: The panel devised a framework for considering the use of immunomodulatory therapy based on an assessment of clinical disease severity and degree of multiorgan involvement combined with evidence of hyperinflammation. Additionally, the known rationale for consideration of each immunomodulatory approach and the associated risks and benefits was summarized. CONCLUSIONS: Immunomodulatory therapy is not recommended for the majority of pediatric patients, who typically develop mild or moderate COVID-19. For children with severe or critical illness, the use of immunomodulatory agents may be beneficial. The risks and benefits of such therapies are variable and should be evaluated on a case-by-case basis with input from appropriate specialty services. When available, the panel strongly favors immunomodulatory agent use within the context of clinical trials. The framework presented herein offers an approach to decision-making regarding immunomodulatory therapy for severe or critical pediatric COVID-19 and is informed by currently available data, while awaiting results of placebo-controlled randomized clinical trials.

How to fairly incentivise digital contact tracing.

Digital apps using Bluetooth to log proximity events (henceforth, digital contact tracing) are increasingly supported by technologists and governments. By and large, the public debate on this matter focuses on privacy, with experts from both law and technology offering very concrete proposals and participating to a lively debate. Far less attention is paid to effective incentives and their fairness. This paper aims to fill this gap by offering a practical, workable solution for a promising incentive, justified by the ethical principles of non-maleficence, beneficence, autonomy and justice. This incentive is a free phone optimised for running such app.

Accuracy of Bedside Ultrasound Femoral Vein Diameter Measurement by PICU Providers.

OBJECTIVES: Perform a needs assessment by evaluating accuracy of PICU provider bedside ultrasound measurement of femoral vein diameter prior to utilization of the catheter-to-vein ratio for central venous catheter size selection. DESIGN: Prospective observational cohort study. SETTING: PICU within a quaternary care children's hospital. PATIENTS: PICU patients greater than 30 days and less than 6 years without a femoral central venous catheter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Gold-standard femoral vein diameter measurements were made by a radiologist, sonographer, or bedside ultrasound expert. PICU providers then repeated the femoral vein diameter measurements, and results were compared by Bland-Altman analysis with a priori accuracy goal of limits of agreement ± 15%. Among recruited patients (n = 27), the median age was 1.1 years (interquartile range 0.5-2.3 yr), weight was 9.0 kg (interquartile range 7.0-11.5 kg), and reference femoral vein diameter was 0.36 cm (interquartile range 0.28-0.45 cm). Providers performed 148 femoral vein diameter measurements and did not meet goal accuracy when compared with the reference measurement with a bias of 4% (95% of limits of agreement -62% to 70%). A majority of patients would have a catheter-to-vein ratio greater than 0.5 using either age-based central venous catheter size selection criterion (14/27) or the provider bedside ultrasound femoral vein diameter measurement (18/27). CONCLUSIONS: PICU provider measurement of femoral vein diameter by bedside ultrasound is inaccurate when compared with expert reference measurement. Central venous catheter size selection based on age or PICU provider femoral vein diameter measurement can lead to a catheter-to-vein ratio greater than 0.5 and potentially increase the risk of catheter-associated venous thromboembolism. Structured bedside ultrasound training with assessment of accuracy is necessary prior to implementation of venous thromboembolism reduction efforts based on catheter-to-vein ratio recommendations.

A comparison of different methods of red blood cell leukoreduction and additive solutions on the accumulation of neutrophil-priming activity during storage.

BACKGROUND: Three methods of leukoreduction (LR) are used worldwide: filtration, buffy coat removal (BCR), and a combination of the previous two methods. Additionally, there are a number of additive solutions (ASs) used to preserve red blood cell (RBC) function throughout storage. During RBC storage, proinflammatory activity accumulates; thus, we hypothesize that both the method of LR and the AS affect the accumulation of proinflammatory activity. STUDY DESIGN AND METHODS: Ten units of whole blood were drawn from healthy donors, the RBC units were isolated, divided in half by weight, and leukoreduced by: 1) BCR, 2) filtration, or 3) BCR and filtration (combination-LR); stored in bags containing AS-3 per AABB criteria; and sampled weekly. The supernatants were isolated and frozen (-80°C). RBC units drawn from healthy donors into AS-1-, AS-3-, or AS-5-containing bags were also stored and sampled weekly, and the supernatants were isolated and frozen. The supernatants were assayed for neutrophil (PMN)-priming activity and underwent proteomic analyses. RESULTS: Filtration and combination LR decreased priming activity accumulation versus buffy coat LR, although the accumulation of priming activity was not different during storage. Combination LR increased hemolysis versus filtration via proteomic analysis. Priming activity from AS-3 units was significant later in storage versus AS-1- or AS-5-stored units. CONCLUSIONS: Although both filtration and combination LR decrease the accumulation of proinflammatory activity versus buffy coat LR, combination LR is not more advantageous over filtration, has increased costs, and may cause increased hemolysis. In addition, AS-3 decreases the early accumulation of PMN-priming activity during storage versus AS-1 or AS-5.