Machine Learning Model Based on Transthoracic Bioimpedance and Heart Rate Variability for Lung Fluid Accumulation Detection: Prospective Clinical Study

BACKGROUND: Accumulation of excess body fluid and autonomic dysregulation are clinically important characteristics of acute decompensated heart failure. We hypothesized that transthoracic bioimpedance, a noninvasive, simple method for measuring fluid retention in lungs, and heart rate variability, an assessment of autonomic function, can be used for detection of fluid accumulation in patients with acute decompensated heart failure. OBJECTIVE: We aimed to evaluate the performance of transthoracic bioimpedance and heart rate variability parameters obtained using a fluid accumulation vest with carbon black-polydimethylsiloxane dry electrodes in a prospective clinical study (System for Heart Failure Identification Using an External Lung Fluid Device; SHIELD). METHODS: We computed 15 parameters: 8 were calculated from the model to fit Cole-Cole plots from transthoracic bioimpedance measurements (extracellular, intracellular, intracellular-extracellular difference, and intracellular-extracellular parallel circuit resistances as well as fitting error, resonance frequency, tissue heterogeneity, and cellular membrane capacitance), and 7 were based on linear (mean heart rate, low-frequency components of heart rate variability, high-frequency components of heart rate variability, normalized low-frequency components of heart rate variability, normalized high-frequency components of heart rate variability) and nonlinear (principal dynamic mode index of sympathetic function, and principal dynamic mode index of parasympathetic function) analysis of heart rate variability. We compared the values of these parameters between 3 participant data sets: control (n=32, patients who did not have heart failure), baseline (n=23, patients with acute decompensated heart failure taken at the time of admittance to the hospital), and discharge (n=17, patients with acute decompensated heart failure taken at the time of discharge from hospital). We used several machine learning approaches to classify participants with fluid accumulation (baseline) and without fluid accumulation (control and discharge), termed with fluid and without fluid groups, respectively. RESULTS: Among the 15 parameters, 3 transthoracic bioimpedance (extracellular resistance, R0; difference in extracellular-intracellular resistance, R0 - Rinfinity, and tissue heterogeneity, alpha) and 3 heart rate variability (high-frequency, normalized low-frequency, and normalized high-frequency components) parameters were found to be the most discriminatory between groups (patients with and patients without heart failure). R0 and R0 - Rinfinity had significantly lower values for patients with heart failure than for those without heart failure (R0: P=.006; R0 - Rinfinity: P=.001), indicating that a higher volume of fluids accumulated in the lungs of patients with heart failure. A cubic support vector machine model using the 5 parameters achieved an accuracy of 92% for with fluid and without fluid group classification. The transthoracic bioimpedance parameters were related to intra- and extracellular fluid, whereas the heart rate variability parameters were mostly related to sympathetic activation. CONCLUSIONS: This is useful, for instance, for an in-home diagnostic wearable to detect fluid accumulation. Results suggest that fluid accumulation, and subsequently acute decompensated heart failure detection, could be performed using transthoracic bioimpedance and heart rate variability measurements acquired with a wearable vest. Emily Ensom, Eric Ding, Anna Hayes, Jarno Riistama, Chad Darling, David McManus, Ki H. Chon. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 27.08.2020

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Point-of-care technologies in heart, lung, blood and sleep disorders from the Center for Advancing Point-of-Care Technologies

Recent advancements in point-of-care technologies have transformed care for patients with heart, lung, blood, and sleep disorders by providing rapid, cost-effective, and accessible solutions to challenges in the detection and management of many health conditions. However, major barriers exist throughout the technology development process that inhibit the actualization of many promising and potentially successful ideas. The Center for Advancing Point of Care Technologies has established a system for supporting further innovation in this field and bridging the gap between initial idea conception and implementation. We highlight current and emerging point-of-care technologies throughout the development spectrum and emphasize the need for a needs-driven model of health technology development that involve appropriate stakeholders in the process

Effect of Amoxicillin dose and treatment duration on the need for antibiotic re-treatment in children with Community-Acquired Pneumonia: The CAP-IT randomized clinical trial

Importance: The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear. Objective: To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days. Design, Setting, and Participants: Multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019. Interventions: Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401). Main Outcomes and Measures: The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates. Results: Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI -∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI -∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P =.63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P =.04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P =.03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, -∞ to10%]; P value for interaction =.18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, -∞ to 7.4%]; P value for interaction =.73). Conclusions and Relevance: Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings. Trial Registration: ISRCTN Identifier: ISRCTN76888927