Utilization of geospatial distribution in the measurement of study cohort representativeness.

OBJECTIVE: The ability to apply results from a study to a broader population remains a primary objective in translational science. Distinct from intrinsic elements of scientific rigor, the extrinsic concept of generalization requires there be alignment between a study cohort and population in which results are expected to be applied. Widespread efforts have been made to quantify representativeness of a study cohorts. These techniques, however, often consider the study and target cohorts as monolithic collections that can be directly compared. Overlooking known impacts to health from socio-demographic and environmental factors tied to individual's geographical location, and potentially obfuscating misalignment in underrepresented population subgroups. This manuscript introduces several measures to account for geographic information in the measurement of cohort representation. METHODS: Metrics were defined across two themes. First, measures of recruitment, to assess a study cohort is drawn at an expected rate and in an expected geographical pattern with respect to individuals in a reference cohort. Quantifying the coverage and spread across the distinct geographic regions comprising the target population. Second, measures of individual characteristics, to assess if the study cohort accurately reflects the sociodemographic, clinical, and geographic diversity observed across a reference cohort. Employing intra-individual measures of distance and aggregate measures of alignment designed to account for geospatial proximity of individuals. RESULTS: As an empirical demonstration, methods are applied to an active clinical study examining asthma in Black and African American patients at a US Midwestern pediatric hospital. Results illustrate how areas of over- and under-recruitment can be identified and contextualized in light of study recruitment patterns. At an individual-level, highlighting the ability to identify a subset of features for which the study cohort closely resembled the broader population. In addition to an opportunity to dive deeper into misalignments, to identify study cohort members that are in some way distinct from the communities for which they are expected to represent. CONCLUSION: Together, these metrics provide a comprehensive spatial assessment of a study cohort with respect to a broader target population. Such an approach offers researchers a toolset by which to target expected generalization of results derived from a given study.

Clarification of adverse drug reactions by a pharmacovigilance team results in increased antibiotic re-prescribing at a freestanding United States children's hospital.

Documentation of adverse drug reactions (ADRs) is a key factor in guiding future prescribing. However, incomplete documentation is common and often fails to distinguish implicated drugs as true allergies. This in turn leads to unnecessary avoidance of implicated drug classes and may result in sub-optimal prescribing. Pharmacovigilance (PV) programs utilize a systematic approach to clarify ADR documentation and are known to improve patient safety. Yet it remains unclear if PV alters prescribing. Or, if the existence of the ADR documentation itself continues to prompt avoidance of implicated drugs. To address this, our work presents a retrospective cohort study assessing if clarification of antibiotic ADRs by a hospital-wide PV team was associated with future, safe, re-prescribing at a freestanding pediatric hospital in the midwestern United States. First, we compared the likelihood of future prescribing in an antibiotic class with an active ADR, as compared to alternative drug classes, between PV-clarified and non-clarified patients. Second, we assessed differences in adverse event rates 30-days after future prescribing based on PV clarification status. For robustness, analyses were performed on patients with ADRs in four antibiotic classes: penicillin-based beta-lactams (n = 45,642), sulfonamides/trimethoprim (n = 5,329), macrolides (n = 3,959), and glycopeptides (n = 622). Results illustrate that clarification of an ADR by PV was associated with an increased odds of future prescribing in the same drug class (Odds Ratio [95%-CI]): penicillin-based beta-lactams (1.59 [1.36-1.89]), sulfonamides/trimethoprim (2.29 [0.89-4.91]), macrolides (0.77 [0.33-1.61]), and glycopeptide (1.85 [1.12-3.20]). Notably, patients clarified by PV experienced no increase in the rate of adverse events within 30-days following the prescribing of antibiotics in the same class as an active ADR. Overall, this study provides strong evidence that PV reviews safely increase the rate of re-prescribing antibiotics even in the presence of an existing implicated drug ADR.

Complex trait associations in rare diseases and impacts on Mendelian variant interpretation.

Emerging evidence implicates common genetic variation - aggregated into polygenic scores (PGS) - impacting the onset and phenotypic presentation of rare diseases. In this study, we quantified individual polygenic liability for 1,151 previously published PGS in a cohort of 2,374 probands enrolled in the Genomic Answers for Kids (GA4K) rare disease study, revealing widespread associations between rare disease phenotypes and PGSs for common complex diseases and traits, blood protein levels, and brain and other organ morphological measurements. We observed increased polygenic burden in probands with variants of unknown significance (VUS) compared to unaffected carrier parents. We further observed an enrichment in overlap between diagnostic and candidate rare disease genes and large-effect PGS genes. Overall, our study supports and expands on previous findings of complex trait associations in rare disease phenotypes and provides a framework for identifying novel candidate rare disease genes and in understanding variable penetrance of candidate Mendelian disease variants.

Hepatic artery thrombosis and use of anticoagulants and antiplatelet agents in pediatric liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) is a reported complication of 5%-10% of pediatric liver transplantations, rates 3-4 times that seen in adults. Early HAT (seen within 14 days after transplant) can lead to severe allograft damage and possible urgent re-transplantation. In this report, we present our analysis of HAT in pediatric liver transplant from a national clinical database and examine the association of HAT with anticoagulant or antiplatelet medication administered in the post-operative period. METHODS: Data were obtained from the Pediatric Health Information System database maintained by the Children's Hospital Association. For each liver transplant recipient identified in a 10-year period, diagnosis, demographic, and medication data were collected and analyzed. RESULTS: Our findings showed an average rate of HAT of 6.3% across 31 centers. Anticoagulant and antiplatelet medication strategies varied distinctly among and even within centers, likely due to the fact there are no consensus guidelines. Notably, in centers with similar medication usage, HAT rates continue to vary. At the patient level, use of aspirin within the first 72 h of transplantation was associated with a decreased risk of HAT, consistent with other reports in the literature. CONCLUSION: We suggest that concerted efforts to standardize anticoagulation approaches in pediatric liver transplant may be of benefit in the prevention of HAT. A prospective multi-institutional study of regimen-possibly including aspirin-following transplantation could have significant value.

SSSH: Responsive soothing bassinet feasibility study for infants with congenital heart disease after cardiac surgery.

PURPOSE: For infants with congenital heart disease (CHD) requiring surgery, prolonged hospital stays, intermittent caregiver visitation, and constrained unit staffing ratios present barriers to adequately address post-operative stressors and associated need to retain cognitive and physiological reserves. Similar patients requiring high-engagement interventions, such as hospitalized infants with neonatal abstinence syndrome, have found success in utilizing responsive bassinets to soothe infants and save floor nurses' time. However, it remains unclear if such technology can be leveraged in the CHD population given their complex hemodynamics, feeding intolerance, and monitoring requirements. METHODS: This multidisciplinary feasibility study evaluated responsive bassinet use in a cohort of infants with CHD <6 months of age in a medical-surgical unit at a midwestern children's hospital. Specifically assessing 1) implementation requirements, challenges, and potential of utilizing the device, together with 2) ability to perform bedside monitoring (monitoring) and 3) measuring physiologic trends during use. RESULTS: Between 11/2020-1/2022, nine infants utilized a responsive bassinet over 599 h (mean 13, range 4-26 days per infant). No increase in monitoring alarms and accurate vital signs monitoring during bassinet activity were noted with appropriate physiologic responses for infants with single ventricle and biventricular surgeries. CONCLUSIONS: Feasibility of introducing new technology into care, and successful use of its functionality for soothing was found to be plausible for infants with CHD. PRACTICE IMPLICATIONS: After cardiac surgery, infants with CHD have need for interventions to reduce stress. Use of a soothing bassinet has the potential to aid in doing so without interference with monitoring requirements.

Associations of Home Monitoring Data to Interventional Catheterization for Infants with Recurrent Coarctation of the Aorta and Hypoplastic Left Heart Syndrome.

The post-Norwood interstage period for infants with hypoplastic left heart syndrome is a high-risk time with 10-20% of infants having a complication of recurrent coarctation of the aorta (RCoA). Many interstage programs utilize mobile applications allowing caregivers to submit home physiologic data and videos to the clinical team. This study aimed to investigate if caregiver-entered data resulted in earlier identification of patients requiring interventional catheterization for RCoA. Retrospective home monitoring data were extracted from five high-volume Children's High Acuity Monitoring Program®-affiliated centers (defined as contributing > 20 patients to the registry) between 2014 and 2021 after IRB approval. Demographics and caregiver-recorded data evaluated include weight, heart rate (HR), oxygen saturation (SpO2), video recordings, and 'red flag' concerns prior to interstage readmissions. 27% (44/161) of infants required interventional catheterization for RCoA. In the 7 days prior to readmission, associations with higher odds of RCoA included (mean bootstrap coefficient, [90% CI]) increased number of total recorded videos (1.65, [1.07-2.62]) and days of recorded video (1.62, [1.03-2.59]); increased number of total recorded weights (1.66, [1.09-2.70]) and days of weights (1.56, [1.02-2.44]); increasing mean SpO2 (1.55, [1.02-2.44]); and increased variation and range of HR (1.59, [1.04-2.51]) and (1.71, [1.10-2.80]), respectively. Interstage patients with RCoA had increased caregiver-entered home monitoring data including weight and video recordings, as well as changes in HR and SpO2trends. Identifying these items by home monitoring teams may be beneficial in clinical decision-making for evaluation of RCoA in this high-risk population.

Rehabilitation Outcomes in Children With Acute Flaccid Myelitis From 2014 to 2019: A Multicenter Retrospective Review.

BACKGROUND: Acute flaccid myelitis (AFM) is a childhood illness characterized by sudden-onset weakness impairing function. The primary goal was to compare the motor recovery patterns of patients with AFM who were discharged home or to inpatient rehabilitation. Secondary analyses focused on recovery of respiratory status, nutritional status, and neurogenic bowel and bladder in both cohorts. METHODS: Eleven tertiary care centers in the United States performed a retrospective chart review of children with AFM between January 1, 2014, and October 1, 2019. Data included demographics, treatments, and outcomes on admission, discharge, and follow-up visits. RESULTS: Medical records of 109 children met inclusion criteria; 67 children required inpatient rehabilitation, whereas 42 children were discharged directly home. The median age was 5 years (range 4 months to 17 years), and the median time observed was 417 days (interquartile range = 645 days). Distal upper extremities recovered better than the proximal upper extremities. At acute presentation, children who needed inpatient rehabilitation had significantly higher rates of respiratory support (P < 0.001), nutritional support (P < 0.001), and neurogenic bowel (P = 0.004) and bladder (P = 0.002). At follow-up, those who attended inpatient rehabilitation continued to have higher rates of respiratory support (28% vs 12%, P = 0.043); however, the nutritional status and bowel/bladder function were no longer statistically different. CONCLUSIONS: All children made improvements in strength. Proximal muscles remained weaker than distal muscles in the upper extremities. Children who qualified for inpatient rehabilitation had ongoing respiratory needs at follow-up; however, recovery of nutritional status and bowel/bladder were similar.

Characterization of a Vigorous sucking style in early infancy and its predictive value for weight gain and eating behaviors at 12 months.

This study sought to identify sucking profiles among healthy, full-term infants and assess their predictive value for future weight gain and eating behaviors. Pressure waves of infant sucking were captured during a typical feeding at age 4 months and quantified via 14 metrics. Anthropometry was measured at 4 and 12 months, and eating behaviors were measured by parent report via the Children's Eating Behavior Questionnaire-Toddler (CEBQ-T) at 12 months. Sucking profiles were created using a clustering approach on the pressure wave metrics, and utility of these profiles was assessed for predicting which infants will have weight-for-age (WFA) percentile changes from ages 4-12 months that exceed thresholds of 5, 10, and 15 percentiles, and for estimating each CEBQ-T subscale score. Among 114 infants, three sucking profiles were identified: Vigorous (51%), Capable (28%), and Leisurely (21%). Sucking profiles were found to improve estimation of change in WFA from 4 to 12 months and 12-month maternal-reported eating behaviors above infant sex, race/ethnicity, birthweight, gestational age, and pre-pregnancy body mass index alone. Infants with a Vigorous sucking profile gained significantly more weight during the study period than infants with a Leisurely profile. Infant sucking characteristics may aid in predicting which infants may be at greater risk of obesity, and therefore sucking profiles deserve more investigation.

Association between congenital heart disease and parenteral nutrition-associated liver disease in neonates: A retrospective cohort study.

OBJECTIVE: Infants receiving parenteral nutrition (PN) are at increased risk of PN-associated liver disease (PNALD), which can lead to hepatic fibrosis. Congenital heart disease (CHD) represents a risk factor for hepatic fibrosis, so this study sought to better understand whether infants with CHD were at elevated risk of PNALD when receiving long-term PN. STUDY DESIGN: This study includes a retrospective cohort of infants at a level IV neonatal intensive care unit from 2010 to 2020 who received long-term PN during the first 8 weeks of life. A time-varying Cox survival model was used to model risk of PNALD between infants with and without CHD, adjusted for demographics, surgical intervention, and PN exposure, using a 5000-iteration bootstrap estimation. Secondary analyses evaluated risk against discrete CHD diagnoses, and sensitivity analysis was performed on the magnitude and quantity of direct bilirubin laboratory measurements making up the PNALD definition. RESULTS: Neonates with CHD were found to be at higher risk for PNALD during or soon after long-term PN exposure. A pattern of increasing association strength with increasing bilirubin threshold suggests infants with CHD may also experience higher degrees of injury. CONCLUSIONS: This work offers a step in understanding how diagnoses can be factored into neonate PN prescription. Future work will explore modifications in lipid profiles and timing to mitigate risk in patients with CHD.

Machine Learning Algorithm Improves the Prediction of Transplant Hepatic Artery Stenosis or Occlusion: A Single-Center Study.

ABSTRACT: The aim of this study was to determine if machine learning can improve the specificity of detecting transplant hepatic artery pathology over conventional quantitative measures while maintaining a high sensitivity.This study presents a retrospective review of 129 patients with transplanted hepatic arteries. We illustrate how beyond common clinical metrics such as stenosis and resistive index, a more comprehensive set of waveform data (including flow half-lives and Fourier transformed waveforms) can be integrated into machine learning models to obtain more accurate screening of stenosis and occlusion. We present a novel framework of Extremely Randomized Trees and Shapley values, we allow for explainability at the individual level.The proposed framework identified cases of clinically significant stenosis and occlusion in hepatic arteries with a state-of-the-art specificity of 65%, while maintaining sensitivity at the current standard of 94%. Moreover, through 3 case studies of correct and mispredictions, we demonstrate examples of how specific features can be elucidated to aid in interpreting driving factors in a prediction.This work demonstrated that by utilizing a more complete set of waveform data and machine learning methodologies, it is possible to reduce the rate of false-positive results in using ultrasounds to screen for transplant hepatic artery pathology compared with conventional quantitative measures. An advantage of such techniques is explainability measures at the patient level, which allow for increased radiologists' confidence in the predictions.

Data-Driven Nurse Staffing in the Neonatal Intensive Care Unit.

ABSTRACT: The challenge of nurse staffing is amplified in the acute care neonatal intensive care unit (NICU) setting, where a wide range of highly variable factors affect staffing. A comprehensive overview of infant factors (severity, intensity), nurse factors (education, experience, preferences, team dynamics), and unit factors (structure, layout, shift length, care model) influencing pre-shift NICU staffing is presented, along with how intra-shift variability of these and other factors must be accounted for to maintain effective and efficient assignments. There is opportunity to improve workload estimations and acuity measures for pre-shift staffing using technology and predictive analytics. Nurse staffing decisions affected by intra-shift factor variability can be enhanced using novel care models that decentralize decision-making. Improving NICU staffing requires a deliberate, systematic, data-driven approach, with commitment from nurses, resources from the management team, and an institutional culture prioritizing patient safety.

Corticosteroid response predicts bronchopulmonary dysplasia status at 36 weeks in preterm infants treated with dexamethasone: A pilot study.

IMPORTANCE: A major barrier to therapeutic development in neonates is a lack of standardized drug response measures that can be used as clinical trial endpoints. The ability to quantify treatment response in a way that aligns with relevant downstream outcomes may be useful as a surrogate marker for new therapies, such as those for bronchopulmonary dysplasia (BPD). OBJECTIVE: To construct a measure of clinical response to dexamethasone that was well aligned with the incidence of severe BPD or death at 36 weeks' postmenstrual age. DESIGN: Retrospective cohort study. SETTING: Level IV Neonatal Intensive Care Unit. PARTICIPANTS: Infants treated with dexamethasone for developing BPD between 2010 and 2020. MAIN OUTCOME(S) AND MEASURE(S): Two models were built based on demographics, changes in ventilatory support, and partial pressure of carbon dioxide (pCO2 ) after dexamethasone administration. An ordinal logistic regression and regularized binary logistic model for the composite outcome were used to associate response level to BPD outcomes defined by both the 2017 BPD Collaborative and 2018 Neonatal Research Network definitions. RESULTS: Ninety-five infants were treated with dexamethasone before 36 weeks. Compared to the baseline support and demographic data at the time of treatment, changes in ventilatory support improved ordinal model sensitivity and specificity. For the binary classification, BPD incidence was well aligned with risk levels, increasing from 16% to 59%. CONCLUSIONS AND RELEVANCE: Incorporation of response variables as measured by changes in ventilatory parameters and pCO2 following dexamethasone administration were associated with downstream outcomes. Incorporating drug response phenotype into a BPD model may enable more rapid development of future therapeutics.

Vaping, Perceptions of Vaping, and Plans to Quit Among E-cigarette Users in the United States and the United Kingdom.

INTRODUCTION: Government and health organizations in the United States and the United Kingdom have taken different stances on e-cigarettes policy. To explore the potential effects of these policies, we describe e-cigarette user characteristics, intentions to quit, and perceived attitudes toward vaping. METHODS: We used the online crowdsourcing platform Prolific to conduct a cross-sectional survey of current vapers in both countries. Measures were drawn from international surveys. RESULTS: The sample included 1044 vapers (524 United Kingdom; 520 United States) with a mean age of 34. Samples differed by gender (United States: 57% male vs 45% in United Kingdom), race (United States: 79% White vs 90% in United Kingdom) and employment (United States: 73% employed vs 79% in United Kingdom). UK respondents were more likely than US respondents to be ever smokers (89% vs 71%, p < .0001); be daily vapers (69% vs 53%, p < .0001) and to use e-cigarettes to quit smoking (75% vs 65%, p < .0007). Most vapers in the United Kingdom and the United States want to stop vaping (62% vs 61%; p < .9493), but US respondents plan to quit significantly sooner (odds ratio 0.47, p < .0004). Attitudes differed as well. Over half (56%) of UK respondents reported their government-approved e-cigarette use, and 24% felt health care providers had positive views on e-cigarettes versus 29% and 13% from the United States, respectively (p < .0004 for both). CONCLUSIONS: Plans for quitting and perceptions regarding e-cigarettes differ markedly between demographically similar groups of vapers in the two countries. Future research should determine whether e-cigarette cessation for adults should be a public health goal, and if so, identify effective ways to stop. IMPLICATIONS: The contribution of this study is that it describes differences in behaviors and attitudes of vapers recruited through the same research platform and adjusted to account for minor demographic differences across country samples. For clinicians, these findings suggest that most vapers would welcome assistance in quitting. For researchers and policymakers, findings suggest that government policy regarding nicotine devices might influence behaviors and attitudes related to use and also that future research is needed to determine effective ways to quit.

Will Apple devices' passive atrial fibrillation detection prevent strokes? Estimating the proportion of high-risk actionable patients with real-world user data.

OBJECTIVE: Utilizing integrated electronic health record (EHR) and consumer-grade wearable device data, we sought to provide real-world estimates for the proportion of wearers that would likely benefit from anticoagulation if an atrial fibrillation (AFib) diagnosis was made based on wearable device data. MATERIALS AND METHODS: This study utilized EHR and Apple Watch data from an observational cohort of 1802 patients at Cedars-Sinai Medical Center who linked devices to the EHR between April 25, 2015 and November 16, 2018. Using these data, we estimated the number of high-risk patients who would be actionable for anticoagulation based on (1) medical history, (2) Apple Watch wear patterns, and (3) AFib risk, as determined by an existing validated model. RESULTS: Based on the characteristics of this cohort, a mean of 0.25% (n = 4.58, 95% CI, 2.0-8.0) of patients would be candidates for new anticoagulation based on AFib identified by their Apple Watch. Using EHR data alone, we find that only approximately 36% of the 1802 patients (n = 665.93, 95% CI, 626.0-706.0) would have anticoagulation recommended even after a new AFib diagnosis. DISCUSSION AND CONCLUSION: These data suggest that there is limited benefit to detect and treat AFib with anticoagulation among this cohort, but that accessing clinical and demographic data from the EHR could help target devices to the patients with the highest potential for benefit. Future research may analyze this relationship at other sites and among other wearable users, including among those who have not linked devices to their EHR.

Utility of the 13 C-pantoprazole breath test as a CYP2C19 phenotyping probe for children.

The 13 C-pantoprazole breath test (PAN-BT) is a safe, noninvasive, in vivo CYP2C19 phenotyping probe for adults. Our objective was to evaluate PAN-BT performance in children, with a focus on discriminating individuals who, according to guidelines from the Clinical Pharmacology Implementation Consortium (CPIC), would benefit from starting dose escalation versus reduction for proton pump inhibitors (PPIs). Children (n = 65, 6-17 years) genotyped for CYP2C19 variants *2, *3, *4, and *17 received a single oral dose of 13 C-pantoprazole. Plasma concentrations of pantoprazole and its metabolites, and changes in exhaled 13 CO2 (termed delta-over-baseline or DOB), were measured 10 times over 8 h using high performance liquid chromatography with ultraviolet detection and spectrophotometry, respectively. Pharmacokinetic parameters of interest were generated and DOB features derived using feature engineering for the first 180 min postadministration. DOB features, age, sex, and obesity status were used to run bootstrap analysis at each timepoint (Ti ) independently. For each iteration, stratified samples were drawn based on genotype prevalence in the original cohort. A random forest was trained, and predictive performance of PAN-BT was evaluated. Strong discriminating ability for CYP2C19 intermediate versus normal/rapid metabolizer phenotype was noted at DOBT30 min (mean sensitivity: 0.522, specificity: 0.784), with consistent model outperformance over a random or a stratified classifier approach at each timepoint (p < 0.001). With additional refinement and investigation, the test could become a useful and convenient dosing tool in clinic to help identify children who would benefit most from PPI dose escalation versus dose reduction, in accordance with CPIC guidelines.

Heart Rate Recovery Following Exercise Testing in Pediatric Patients with Acyanotic Repaired Congenital Heart Disease.

Attenuated heart rate recovery (HRR) following peak exercise has been shown to be a predictor of mortality in populations of adults with Fontan palliation, coronary artery disease, heart failure, and heart transplantation. However, few have studied HRR in children and adolescents with congenital heart disease (CHD). This case-control study compared HRR patterns from exercise stress testing in children and adolescents with and without repaired acyanotic CHD (raCHD). Retrospective analysis included patients aged 10-18 years who had exercise testing between 2007 and 2017. The raCHD cohort included patients with Tetralogy of Fallot, transposition of the great arteries, coarctation, truncus arteriosus, atrioventricular septal defect, pulmonary outflow obstruction, aortic stenosis and/or insufficiency, or septal defects. Those in the control cohort were matched for age, sex, BMI, peak METs achieved, and peak heart rate (HR). HR at 1-min intervals throughout the 10-min recovery period and HRR patterns were analyzed. The study included n = 584 individuals (raCHD: n = 146), median age 14 years old, 67.1% male. The cohorts had similar resting and peak HRs. Linear mixed-effects models (LMM) suggested statistically significant cohort-by-time interaction for HR in exercise recovery, with the largest mean difference at minute-6 (2.9 bpm, p = 0.008). When comparing lesion types, LMM found no cohort or cohort-by-time interaction. While minute-6 of exercise recovery was statistically significant, the difference was 2.9 bpm and may not have clinical significance. These results suggest that HRR in pediatric raCHD patients should not vary from their healthy peers, and an attenuated HRR may not be directly attributed to underlying raCHD.

Discrete Heart Rate Values or Continuous Streams? Representation, Variability, and Meaningful Use of Vital Sign Data.

Documentation and review of patient heart rate are a fundamental process across a myriad of clinical settings. While historically recorded manually, bedside monitors now provide for the automated collection of such data. Despite the availability of continuous streaming data, patients' charts continue to reflect only a subset of this information as snapshots recorded throughout a hospitalization. Over the past decade, prominent works have explored the implications of such practices and established fundamental differences in the alignment of discrete charted vitals and steaming data captured by monitoring systems. Limited work has examined the temporal properties of these differences, how they manifest, and their relation to clinical applications. The work presented in this article addresses this disparity, providing evidence that differences between charting techniques extend to measures of variability. Our results demonstrate how variability manifests with respect to temporal elements of charting timing and how it can facilitate personalized care by contextualizing deviations in magnitude. This work also highlights the utility of variability metrics with relation to clinical measures including associations to severity scores and a case study utilizing complex variability metrics derived from the complete set of monitor data.

Examining Response to Negative Life Events Through Fitness Tracker Data.

Negative life events, such as the death of a loved one, are an unavoidable part of life. These events can be overwhelmingly stressful and may lead to the development of mental health disorders. To mitigate these adverse developments, prior literature has utilized measures of psychological responses to negative life events to better understand their effects on mental health. However, psychological changes represent only one aspect of an individual's potential response. We posit measuring additional dimensions of health, such as physical health, may also be beneficial, as physical health itself may be affected by negative life events and measuring its response could provide context to changes in mental health. Therefore, the primary aim of this work was to quantify how an individual's physical health changes in response to negative life events by testing for deviations in their physiological and behavioral state (PB-state). After capturing post-event, PB-state responses, our second aim sought to contextualize changes within known factors of psychological response to negative life events, namely coping strategies. To do so, we utilized a cohort of professionals across the United States monitored for 1 year and who experienced a negative life event while under observation. Garmin Vivosmart-3 devices provided a multidimensional representation of one's PB-state by collecting measures of resting heart rate, physical activity, and sleep. To test for deviations in PB-state following negative life events, One-Class Support Vector Machines were trained on a window of time prior to the event, which established a PB-state baseline. The model then evaluated participant's PB-state on the day of the life event and each day that followed, assigning each day a level of deviance relative to the participant's baseline. Resulting response curves were then examined in association with the use of various coping strategies using Bayesian gamma-hurdle regression models. The results from our objectives suggest that physical determinants of health also deviate in response to negative life events and that these deviations can be mitigated through different coping strategies. Taken together, these observations stress the need to examine physical determinants of health alongside psychological determinants when investigating the effects of negative life events.

Identifying HbA1c trajectories and modifiable risk factors of trajectories in 5- to 9-year-olds with recent-onset type 1 diabetes from the United States.

OBJECTIVE: To explore glycated haemoglobin (HbA1c) patterns in 5- to 9-year-olds in the recent-onset period of type 1 diabetes and identify parent psychosocial factors that may predict children's HbA1c trajectory using a prospective, longitudinal design. RESEARCH DESIGN AND METHODS: We measured family demographics and parent psychosocial factors at baseline. We collected HbA1c levels from children every 3 months for up to 30 months. Deriving several features around HbA1c trends, we used k-means clustering to group trajectories and linear and logistic regressions to identify parent psychosocial predictors of children's HbA1c trajectories. RESULTS: The final cohort included 106 families (48 boys, mean child age 7.50 ± 1.35 years and mean diabetes duration 4.71 ± 3.19 months). We identified four unique HbA1c trajectories in children: high increasing, high stable, intermediate increasing and low stable. Compared to a low stable trajectory, increasing parent-reported hypoglycaemia fear total score was associated with decreased odds of having a high stable or intermediate increasing trajectory. Increasing parent-reported diabetes-specific family conflict total score was associated with increased odds of having a high stable or intermediate increasing trajectory. CONCLUSIONS: We are the first to identify distinct HbA1c trajectories in 5- to 9-year-olds with recent-onset type 1 diabetes as well as parent psychosocial factors that may predict high stable or increasing trajectories and could represent future treatment targets.