Shared decision making for patients with kidney failure to improve end-of-life care: Development of the DESIRE intervention.

AIM: To describe the development of a shared decision making intervention for planning end-of-life care for patients with kidney failure, their relatives and health professionals in kidney services. BACKGROUND: End-of-life care conversations within standard disease management consultations are challenging for patients with kidney failure, their relatives and health professionals. End-of-life care planning is about making difficult decisions in advance, which is why health professionals need shared decision making skills to be able to initiate end-of-life conversations. Health professionals report needing more skills to raise the issue of end-of-life care options within consultations and patients want to be able to discuss issues important to them about future care plans. METHODS: The development design was guided by the UK Medical Research Council's framework and a user-centred approach was applied. Four workshops were conducted with end users. The Template for Intervention Description and Replication for Population Health and Policy interventions was used to shape which questions needed to be answered through the workshops and to present the intervention. The International Patient Decision Aid Standards (IPDAS) criteria set the standards to be achieved. RESULTS: Areas considered significant to a shared decision making intervention were training of health professionals, conversations about end-of-life care, planning and evaluation of the decisions, reporting decisions in health records and repetition of consultation. The development process went through 14 iterations. CONCLUSION: An intervention named DESIRE was developed that comprises: (1) a training programme for health professionals; (2) shared decision making conversations; and (3) a patient decision aid. The intervention met 30 out of 33 IPDAS criteria. IMPLICATIONS FOR PRACTICE: DESIRE is intended to support shared decision making about planning end-of-life care among patients with kidney failure, their relatives and health professionals. The study provides important tools for the stakeholders engaged that can be used within different models of care. IMPACT: What problem did the study address? International guidelines recommend health professionals involve patients with kidney failure in making decisions about end-of-life care, but there is variation in how this is implemented within and across kidney services. Furthermore, patients, relatives and health professionals find it challenging to initiate conversations about end-of-life care. What were the main findings? The study resulted in the development of a complex intervention, called DESIRE, about shared decision making and planning end-of-life care for patients with kidney failure, their relatives and health professionals in kidney services, including a training programme for health professionals, shared decision making conversations and a patient decision aid. Where and on whom will the research have an impact? The research contributes a shared decision making intervention to patients in the later stage of kidney failure, their relatives and health professionals. We believe that the DESIRE intervention could be introduced during consultations with health professionals at an earlier stage of the patient's illness trajectory, as well as being applied to other chronic diseases. REPORTING METHOD: This intervention development research is reported according to the GUIDance for the rEporting of intervention Development (GUIDED) checklist and the DEVELOPTOOLS Reporting Checklist. PATIENT OR PUBLIC CONTRIBUTION: Patients, relatives and health professionals have been involved throughout the research process as part of the research team and advisory board. For this study, the advisory board has particularly contributed to the development process of the DESIRE intervention by actively participating in the four workshops, in the iterations between the workshops and in the preparation of the manuscript.

Towards quantifying biomarkers for respiratory distress in preterm infants: Machine learning on mid infrared spectroscopy of lipid mixtures.

Neonatal respiratory distress syndrome (nRDS) is a challenging condition to diagnose which can lead to delays in receiving appropriate treatment. Mid infrared (IR) spectroscopy is capable of measuring the concentrations of two diagnostic nRDS biomarkers, lecithin (L) and sphingomyelin (S) with the potential for point of care (POC) diagnosis and monitoring. The effects of varying other lipid species present in lung surfactant on the mid IR spectra used to train machine learning models are explored. This study presents a lung lipid model of five lipids present in lung surfactant and varies each in a systematic approach to evaluate the ability of machine learning models to predict the lipid concentrations, the L/S ratio and to quantify the uncertainty in the predictions using the jackknife + -after-bootstrap and variant bootstrap methods. We establish the L/S ratio can be determined with an uncertainty of approximately ±0.3 mol/mol and we further identify the 5 most prominent wavenumbers associated with each machine learning model.

Bidirectional brain-body interactions during natural story listening.

Narratives can synchronize neural and physiological signals between individuals, but the relationship between these signals, and the underlying mechanism, is unclear. We hypothesized a top-down effect of cognition on arousal and predicted that auditory narratives will drive not only brain signals but also peripheral physiological signals. We find that auditory narratives entrained gaze variation, saccade initiation, pupil size, and heart rate. This is consistent with a top-down effect of cognition on autonomic function. We also hypothesized a bottom-up effect, whereby autonomic physiology affects arousal. Controlled breathing affected pupil size, and heart rate was entrained by controlled saccades. Additionally, fluctuations in heart rate preceded fluctuations of pupil size and brain signals. Gaze variation, pupil size, and heart rate were all associated with anterior-central brain signals. Together, these results suggest bidirectional causal effects between peripheral autonomic function and central brain circuits involved in the control of arousal.

Decisional needs in people with kidney failure, their relatives and health professionals about end-of-life care options: A qualitative interview study.

AIM: To investigate the decisional needs in Denmark of people with kidney failure, relatives, and health professionals when planning end-of-life care. DESIGN: A qualitative interview study. METHODS: Individual semi-structured interviews were carried out with people with kidney failure, relatives and health professionals from November 2021 to June 2022. Malterud's systematic text condensation was used to analyse transcripts. RESULTS: A total of 13 patients, 10 relatives, and 12 health professionals were interviewed. Overall, four concepts were agreed on: (1) Talking about end of life is difficult, (2) Patients and relatives need more knowledge and information, (3) Health professionals need more tools and training, and (4) Experiencing busyness as a barrier to conversations about end of life. CONCLUSION: People with kidney failure, relatives, and health professionals shared certain decisional needs while also having some different decisional needs about end-of-life care. To meet these various needs, end-of-life conversations should be systematic and organized according to the patients' needs and wishes. IMPACT: Non-systematic end-of-life care decision-making processes limit patients' involvement. Patients and relatives need more knowledge about end-of-life care, and health professionals need more competences and time to discuss decisional needs. A shared decision-making intervention for people with kidney failure when making end-of-life care decisions will be developed. REPORTING METHOD: This empirical qualitative research is reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. PATIENT OR PUBLIC CONTRIBUTION: Patients, relatives, and health professionals have been involved throughout the research process as part of the research team and advisory board. The patients are people with kidney failure and the relatives are relatives of a person with kidney failure. For this study, the advisory board has particularly contributed to the validation of the invitation letter for participation, the interview guides and the preparation of the manuscript.

Respiratory Syncytial Virus Maternal Vaccination in Infants below 6 Months of Age: Meta-Analysis of Safety, Immunogenicity, and Efficacy.

INTRODUCTION: Severe respiratory syncytial virus (RSV) disease is most prevalent during infancy, particularly in those born prematurely, who benefit least from maternal antibody transfers. Maternal immunization is an attractive prevention leading to vaccine clinical trials. This meta-analysis aimed to evaluate recent maternal RSV vaccine trials. METHODS: Following PRISMA-P guidelines for systematic reviews and registered at https://www.crd.york.ac.uk/prospero, this study shortlisted six randomized clinical trials of suitable quality from four databases. Meta-analysis evaluated vaccine safety, immunogenicity, and efficacy in infants and their mothers. RESULTS: From random-effects and fixed-effects meta-analysis between trial and control arms, the maternal post-vaccination geometric antibody (Ab) titers showed pooled standard mean differences (SMDs [95% CI]) at delivery of (4.14 [2.91-5.37]), (3.95 [2.79-5.11]), and (12.20 [7.76, 16.64]) for RSV neutralizing Ab A, B, and F IgG, respectively. Vaccine administration was more likely than placebo to cause local pain, erythema, swelling, and systemic myalgia. Furthermore, the Ab levels in infants at birth showed pooled SMDs of each RSV A (3.9 [2.81-4.99]), RSV B (1.86 [1.09-2.62]), and RSV F IgG (2.24 [1.24-3.23]). The overall reduction of RSV-related lower respiratory tract infections and hospitalizations in the first 6 months of life was 52% and 48%, respectively. CONCLUSIONS: Not only does antenatal RSV vaccination look safe and immunogenic in vaccinated mothers, but it also reliably provides effective antibody levels in infants and diminishes RSV-related severe disease in infants under 6 months of age.

A randomized controlled trial of nebulized surfactant for the treatment of severe COVID-19 in adults (COVSurf trial).

SARS-CoV-2 directly targets alveolar epithelial cells and can lead to surfactant deficiency. Early reports suggested surfactant replacement may be effective in improving outcomes. The aim of the study to assess the feasibility and efficacy of nebulized surfactant in mechanically ventilated COVID-19 patients. Patients were randomly assigned to receive open-labelled bovine nebulized surfactant or control (ratio 3-surfactant: 2-control). This was an exploratory dose-response study starting with 1080 mg of surfactant delivered at 3 time points (0, 8 and 24 h). After completion of 10 patients, the dose was reduced to 540 mg, and the frequency of nebulization was increased to 5/6 time points (0, 12, 24, 36, 48, and an optional 72 h) on the advice of the Trial Steering Committee. The co-primary outcomes were improvement in oxygenation (change in PaO2/FiO2 ratio) and ventilation index at 48 h. 20 patients were recruited (12 surfactant and 8 controls). Demographic and clinical characteristics were similar between groups at presentation. Nebulized surfactant administration was feasible. There was no significant improvement in oxygenation at 48 h overall. There were also no differences in secondary outcomes or adverse events. Nebulized surfactant administration is feasible in mechanically ventilated patients with COVID-19 but did not improve measures of oxygenation or ventilation.

Systematic analysis and characterization of long non-coding RNA genes in inflammatory bowel disease.

The cases of inflammatory bowel disease (IBD) are increasing rapidly around the world. Due to the multifactorial causes of IBD, there is an urgent need to understand the pathogenesis of IBD. As such, the usage of high-throughput techniques to profile genetic mutations, microbiome environments, transcriptome and proteome (e.g. lipidome) is increasing to understand the molecular changes associated with IBD, including two major etiologies of IBD: Crohn disease (CD) and ulcerative colitis (UC). In the case of transcriptome data, RNA sequencing (RNA-seq) technique is used frequently. However, only protein-coding genes are analyzed, leaving behind all other RNAs, including non-coding RNAs (ncRNAs) to be unexplored. Among these ncRNAs, long non-coding RNAs (lncRNAs) may hold keys to understand the pathogenesis of IBD as lncRNAs are expressed in a cell/tissue-specific manner and dysregulated in a disease, such as IBD. However, it is rare that RNA-seq data are analyzed for lncRNAs. To fill this gap in knowledge, we re-analyzed RNA-seq data of CD and UC patients compared with the healthy donors to dissect the expression profiles of lncRNA genes. As inflammation plays key roles in the pathogenesis of IBD, we conducted loss-of-function experiments to provide functional data of IBD-specific lncRNA, lung cancer associated transcript 1 (LUCAT1), in an in vitro model of macrophage polarization. To further facilitate the lncRNA research in IBD, we built a web database, IBDB (https://ibd-db.shinyapps.io/IBDB/), to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in IBD patients compared with healthy donors.

Systematic Analysis of Long Non-Coding RNAs in Inflammasome Activation in Monocytes/Macrophages.

The NLRP3 inflammasome plays a pivotal role in regulating inflammation and immune responses. Its activation can lead to an inflammatory response and pyroptotic cell death. This is beneficial in the case of infections, but excessive activation can lead to chronic inflammation and tissue damage. Moreover, while most of the mammalian genome is transcribed as RNAs, only a small fraction codes for proteins. Among non-protein-coding RNAs, long non-coding RNAs (lncRNAs) have been shown to play key roles in regulating gene expression and cellular processes. They interact with DNA, RNAs, and proteins, and their dysregulation can provide insights into disease mechanisms, including NLRP3 inflammasome activation. Here, we systematically analyzed previously published RNA sequencing (RNA-seq) data of NLRP3 inflammasome activation in monocytes/macrophages to uncover inflammasome-regulated lncRNA genes. To uncover the functional importance of inflammasome-regulated lncRNA genes, one inflammasome-regulated lncRNA, ENSG00000273124, was knocked down in an in vitro model of macrophage polarization. The results indicate that silencing of ENSG00000273124 resulted in the up-regulation tumor necrosis factor (TNF), suggesting that this lncRNA might be involved in pro-inflammatory response in macrophages. To make our analyzed data more accessible, we developed the web database InflammasomeDB.

An open-access dataset of naturalistic viewing using simultaneous EEG-fMRI.

In this work, we present a dataset that combines functional magnetic imaging (fMRI) and electroencephalography (EEG) to use as a resource for understanding human brain function in these two imaging modalities. The dataset can also be used for optimizing preprocessing methods for simultaneously collected imaging data. The dataset includes simultaneously collected recordings from 22 individuals (ages: 23-51) across various visual and naturalistic stimuli. In addition, physiological, eye tracking, electrocardiography, and cognitive and behavioral data were collected along with this neuroimaging data. Visual tasks include a flickering checkerboard collected outside and inside the MRI scanner (EEG-only) and simultaneous EEG-fMRI recordings. Simultaneous recordings include rest, the visual paradigm Inscapes, and several short video movies representing naturalistic stimuli. Raw and preprocessed data are openly available to download. We present this dataset as part of an effort to provide open-access data to increase the opportunity for discoveries and understanding of the human brain and evaluate the correlation between electrical brain activity and blood oxygen level-dependent (BOLD) signals.

DoxoDB: A Database for the Expression Analysis of Doxorubicin-Induced lncRNA Genes.

Cancer and cardiovascular disease are the leading causes of death worldwide. Recent evidence suggests that these two life-threatening diseases share several features in disease progression, such as angiogenesis, fibrosis, and immune responses. This has led to the emergence of a new field called cardio-oncology. Doxorubicin is a chemotherapy drug widely used to treat cancer, such as bladder and breast cancer. However, this drug causes serious side effects, including acute ventricular dysfunction, cardiomyopathy, and heart failure. Based on this evidence, we hypothesize that comparing the expression profiles of cells and tissues treated with doxorubicin may yield new insights into the adverse effects of the drug on cellular activities. To test this hypothesis, we analyzed published RNA sequencing (RNA-seq) data from doxorubicin-treated cells to identify commonly differentially expressed genes, including long non-coding RNAs (lncRNAs) as they are known to be dysregulated in diseased tissues and cells. From our systematic analysis, we identified several doxorubicin-induced genes. To confirm these findings, we treated human cardiac fibroblasts with doxorubicin to record expression changes in the selected doxorubicin-induced genes and performed a loss-of-function experiment of the lncRNA MAP3K4-AS1. To further disseminate the analyzed data, we built the web database DoxoDB.

Patient involvement interventions for patients with kidney failure making end-of-life care decisions: a scoping review.

OBJECTIVE: The objective of this review was to investigate and map empirical evidence of patient involvement interventions to support patients with kidney failure making end-of-life care decisions in kidney services. INTRODUCTION: Clinical guidance integrating end-of-life care within kidney failure management pathways varies. Advance care planning interventions aimed at involving patients with kidney failure in their end-of-life care planning are established in some countries. However, there is limited evidence of the other types of patient involvement interventions integrated within services to support patients with kidney failure in making decisions about their end-of-life care. INCLUSION CRITERIA: This scoping review included studies exploring patient involvement interventions evaluated for patients with kidney failure considering end-of-life care, their relatives, and/or health professionals in kidney services. Studies of children under the age of 18 years were excluded. METHODS: The review was informed by JBI methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review guidelines. MEDLINE, Scopus, Embase, and CINAHL were searched for full-text studies in English, Danish, German, Norwegian, or Swedish. Two independent reviewers assessed the literature against the inclusion criteria. A relational analysis framework was used to synthesize the data extracted from the included studies, and to investigate and map different patient involvement interventions. RESULTS: The search identified 1628 articles, of which 33 articles met the inclusion criteria. A total of 23 interventions were described. Interventions targeted patients (n=3); health professionals (n=8); patients and health professionals (n=5); and patients, relatives, and health professionals (n=7). Intervention components included patient resources (eg, information, patient decision aids), consultation resources (eg, advance care planning, shared decision-making), and practitioner resources (eg, communication training). Patient involvement interventions were delivered within hospital-based kidney services. CONCLUSIONS: The review identified several ways to support patients with kidney failure to be involved in end-of-life care decisions. Future interventions may benefit from adopting a complex intervention framework to engage multiple stakeholders in the research and design of an intervention for shared decision-making between patients with kidney failure, their relatives, and health professionals about integrating end-of-life care options into their kidney disease management pathway.

Multiomics links global surfactant dysregulation with airflow obstruction and emphysema in COPD.

Rationale: Pulmonary surfactant is vital for lung homeostasis as it reduces surface tension to prevent alveolar collapse and provides essential immune-regulatory and antipathogenic functions. Previous studies demonstrated dysregulation of some individual surfactant components in COPD. We investigated relationships between COPD disease measures and dysregulation of surfactant components to gain new insights into potential disease mechanisms. Methods: Bronchoalveolar lavage proteome and lipidome were characterised in ex-smoking mild/moderate COPD subjects (n=26) and healthy ex-smoking (n=20) and never-smoking (n=16) controls using mass spectrometry. Serum surfactant protein analysis was performed. Results: Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, surfactant protein (SP)-B, SP-A and SP-D concentrations were lower in COPD versus controls (log2 fold change (log2FC) -2.0, -2.2, -1.5, -0.5, -0.7 and -0.5 (adjusted p<0.02), respectively) and correlated with lung function. Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D, napsin A and CD44 inversely correlated with computed tomography small airways disease measures (expiratory to inspiratory mean lung density) (r= -0.56, r= -0.58, r= -0.45, r= -0.36, r= -0.44, r= -0.37, r= -0.40 and r= -0.39 (adjusted p<0.05)). Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D and NAPSA inversely correlated with emphysema (% low-attenuation areas): r= -0.55, r= -0.61, r= -0.48, r= -0.51, r= -0.41, r= -0.31 and r= -0.34, respectively (adjusted p<0.05). Neutrophil elastase, known to degrade SP-A and SP-D, was elevated in COPD versus controls (log2FC 0.40, adjusted p=0.0390), and inversely correlated with SP-A and SP-D. Serum SP-D was increased in COPD versus healthy ex-smoking volunteers, and predicted COPD status (area under the curve 0.85). Conclusions: Using a multiomics approach, we demonstrate, for the first time, global surfactant dysregulation in COPD that was associated with emphysema, giving new insights into potential mechanisms underlying the cause or consequence of disease.

T2DB: A Web Database for Long Non-Coding RNA Genes in Type II Diabetes.

Type II diabetes (T2D) is a growing health problem worldwide due to increased levels of obesity and can lead to other life-threatening diseases, such as cardiovascular and kidney diseases. As the number of individuals diagnosed with T2D rises, there is an urgent need to understand the pathogenesis of the disease in order to prevent further harm to the body caused by elevated blood glucose levels. Recent advances in long non-coding RNA (lncRNA) research may provide insights into the pathogenesis of T2D. Although lncRNAs can be readily detected in RNA sequencing (RNA-seq) data, most published datasets of T2D patients compared to healthy donors focus only on protein-coding genes, leaving lncRNAs to be undiscovered and understudied. To address this knowledge gap, we performed a secondary analysis of published RNA-seq data of T2D patients and of patients with related health complications to systematically analyze the expression changes of lncRNA genes in relation to the protein-coding genes. Since immune cells play important roles in T2D, we conducted loss-of-function experiments to provide functional data on the T2D-related lncRNA USP30-AS1, using an in vitro model of pro-inflammatory macrophage activation. To facilitate lncRNA research in T2D, we developed a web application, T2DB, to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in T2D patients compared to healthy donors or subjects without T2D.

Shared decision-making and planning end-of-life care for patients with end-stage kidney disease: a protocol for developing and testing a complex intervention.

BACKGROUND: Internationally, it has been stressed that advance care planning integrated within kidney services can lead to more patients being involved in decisions for end-of-life care. In Denmark, there is no systematic approach to advance care planning and end-of-life care interventions within kidney services. A shared decision-making intervention for planning end-of-life care may support more effective treatment management between patients with end-stage kidney disease, their relatives and the health professionals. The purpose of this research is to find evidence to design a shared decision-making intervention and test its acceptability to patients with end-stage kidney disease, their relatives, and health professionals in Danish kidney services. METHODS: This research project will be conducted from November 2020 to November 2023 and is structured according to the UK Medical Research Council framework for complex intervention design and evaluation research. The development phase research includes mixed method surveys. First, a systematic literature review synthesising primary empirical evidence of patient-involvement interventions for patients with end-stage kidney disease making end-of-life care decisions will be conducted. Second, interview methods will be carried out with patients with end-stage kidney disease, relatives, and health professionals to identify experiences of involvement in decision-making and decisional needs when planning end-of-life care. Findings will inform the co-design of the shared decision-making intervention using an iterative process with our multiple-stakeholder steering committee. A pilot test across five kidney units assessing if the shared decision-making intervention is acceptable and feasible to patients, relatives, and health professionals providing services to support delivery of care in kidney services. DISCUSSION: This research will provide evidence informing the content and design of a shared decision-making intervention supporting patient-professional planning of end-of-life care for patients with end-stage kidney disease, and assessing its acceptability and feasibility when integrated within Danish kidney units. This research is the first step to innovating the involvement of patients in end-of-life care planning with kidney professionals.

Psychological inoculation can reduce susceptibility to misinformation in large rational agent networks.

The unchecked spread of misinformation is recognized as an increasing threat to public, scientific and democratic health. Online networks are a contributing cause of this spread, with echo chambers and polarization indicative of the interplay between the search behaviours of users and reinforcement processes within the system they inhabit. Recent empirical work has focused on interventions aimed at inoculating people against misinformation, yielding success on the individual level. However, given the evolving, dynamic information context of online networks, important questions remain regarding how such inoculation interventions interact with network systems. Here we use an agent-based model of a social network populated with belief-updating users. We find that although equally rational agents may be assisted by inoculation interventions to reject misinformation, even among such agents, intervention efficacy is temporally sensitive. We find that as beliefs disseminate, users form self-reinforcing echo chambers, leading to belief consolidation-irrespective of their veracity. Interrupting this process requires 'front-loading' of inoculation interventions by targeting critical thresholds of network users before consolidation occurs. We further demonstrate the value of harnessing tipping point dynamics for herd immunity effects, and note that inoculation processes do not necessarily lead to increased rates of 'false-positive' rejections of truthful communications.

Systematic Analysis of Long Non-Coding RNA Genes in Nonalcoholic Fatty Liver Disease.

The largest solid organ in humans, the liver, performs a variety of functions to sustain life. When damaged, cells in the liver can regenerate themselves to maintain normal liver physiology. However, some damage is beyond repair, which necessitates liver transplantation. Increasing rates of obesity, Western diets (i.e., rich in processed carbohydrates and saturated fats), and cardiometabolic diseases are interlinked to liver diseases, including non-alcoholic fatty liver disease (NAFLD), which is a collective term to describe the excess accumulation of fat in the liver of people who drink little to no alcohol. Alarmingly, the prevalence of NAFLD extends to 25% of the world population, which calls for the urgent need to understand the disease mechanism of NAFLD. Here, we performed secondary analyses of published RNA sequencing (RNA-seq) data of NAFLD patients compared to healthy and obese individuals to identify long non-coding RNAs (lncRNAs) that may underly the disease mechanism of NAFLD. Similar to protein-coding genes, many lncRNAs are dysregulated in NAFLD patients compared to healthy and obese individuals, suggesting that understanding the functions of dysregulated lncRNAs may shed light on the pathology of NAFLD. To demonstrate the functional importance of lncRNAs in the liver, loss-of-function experiments were performed for one NAFLD-related lncRNA, LINC01639, which showed that it is involved in the regulation of genes related to apoptosis, TNF/TGF, cytokine signaling, and growth factors as well as genes upregulated in NAFLD. Since there is no lncRNA database focused on the liver, especially NAFLD, we built a web database, LiverDB, to further facilitate functional and mechanistic studies of hepatic lncRNAs.

The metabolic syndrome is frequent in children and adolescents with type 1 diabetes compared to healthy controls.

OBJECTIVE: There is a rise in overweight and obesity among children and adolescents with type 1 diabetes (T1D) in parallel with the rise in the metabolic syndrome (MetS) among children and adolescents. The aim of the study was to describe the prevalence and characteristics of MetS in children and adolescents with T1D compared to their healthy counterparts. RESEARCH DESIGN AND METHODS: The study includes two Danish cohorts; (i) the Copenhagen cross sectional cohort 2016 of 277 children and adolescents with T1D that attend the pediatric outpatient clinic at a large hospital in greater Copenhagen and (ii) the CHAMPS-study DK which is a population-based cohort study of Danish children and adolescents (control cohort). Participants were categorized to have MetS if at least two of the following criteria were met: (i) systolic and/or diastolic blood pressure ≥ 90th percentile, (ii) waist circumference ≥90th percentile, and (iii) triglyceride ≥90th percentile and/or HDL ≤10th percentile. RESULTS: The prevalence of children with Mets in the T1D cohort was higher than in the control cohort (p = 0.002). Moreover, participants with T1D had MetS at a lower level of BMI (p < 0.001) and waist circumference (p < 0.001) than participants with MetS from the control cohort (z-scores = 0.90 and 1.51). Participants with MetS were younger than the other T1D participants (median 12.8 [9.9,14.8] vs. median 14.6 [11.2,16.9] years, p = 0.006). CONCLUSIONS: Children and adolescents with T1D have an increased risk of MetS compared to healthy controls and clinicians and caretakers should consider early prevention and health promotion strategies.

Prediction of Neonatal Respiratory Distress Biomarker Concentration by Application of Machine Learning to Mid-Infrared Spectra.

The authors of this study developed the use of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) combined with machine learning as a point-of-care (POC) diagnostic platform, considering neonatal respiratory distress syndrome (nRDS), for which no POC currently exists, as an example. nRDS can be diagnosed by a ratio of less than 2.2 of two nRDS biomarkers, lecithin and sphingomyelin (L/S ratio), and in this study, ATR-FTIR spectra were recorded from L/S ratios of between 1.0 and 3.4, which were generated using purified reagents. The calibration of principal component (PCR) and partial least squares (PLSR) regression models was performed using 155 raw baselined and second derivative spectra prior to predicting the concentration of a further 104 spectra. A three-factor PLSR model of second derivative spectra best predicted L/S ratios across the full range (R2: 0.967; MSE: 0.014). The L/S ratios from 1.0 to 3.4 were predicted with a prediction interval of +0.29, -0.37 when using a second derivative spectra PLSR model and had a mean prediction interval of +0.26, -0.34 around the L/S 2.2 region. These results support the validity of combining ATR-FTIR with machine learning to develop a point-of-care device for detecting and quantifying any biomarker with an interpretable mid-infrared spectrum.