“How Is My Child’s Asthma?” Digital Phenotype and Actionable Insights for Pediatric Asthma

Background: In the traditional asthma management protocol, a child meets with a clinician infrequently, once in 3 to 6 months, and is assessed using the Asthma Control Test questionnaire. This information is inadequate for timely determination of asthma control, compliance, precise diagnosis of the cause, and assessing the effectiveness of the treatment plan. The continuous monitoring and improved tracking of the child’s symptoms, activities, sleep, and treatment adherence can allow precise determination of asthma triggers and a reliable assessment of medication compliance and effectiveness. Digital phenotyping refers to moment-by-moment quantification of the individual-level human phenotype in situ using data from personal digital devices, in particular, mobile phones. The kHealth kit consists of a mobile app, provided on an Android tablet, that asks timely and contextually relevant questions related to asthma symptoms, medication intake, reduced activity because of symptoms, and nighttime awakenings; a Fitbit to monitor activity and sleep; a Microlife Peak Flow Meter to monitor the peak expiratory flow and forced exhaled volume in 1 second; and a Foobot to monitor indoor air quality. The kHealth cloud stores personal health data and environmental data collected using Web services. The kHealth Dashboard interactively visualizes the collected data. Objective: The objective of this study was to discuss the usability and feasibility of collecting clinically relevant data to help clinicians diagnose or intervene in a child’s care plan by using the kHealth system for continuous and comprehensive monitoring of child’s symptoms, activity, sleep pattern, environmental triggers, and compliance. The kHealth system helps in deriving actionable insights to help manage asthma at both the personal and cohort levels. The Digital Phenotype Score and Controller Compliance Score introduced in the study are the basis of ongoing work on addressing personalized asthma care and answer questions such as, “How can I help my child better adhere to care instructions and reduce future exacerbation?” Methods: The Digital Phenotype Score and Controller Compliance Score summarize the child’s condition from the data collected using the kHealth kit to provide actionable insights. The Digital Phenotype Score formalizes the asthma control level using data about symptoms, rescue medication usage, activity level, and sleep pattern. The Compliance Score captures how well the child is complying with the treatment protocol. We monitored and analyzed data for 95 children, each recruited for a 1- or 3-month-long study. The Asthma Control Test scores obtained from the medical records of 57 children were used to validate the asthma control levels calculated using the Digital Phenotype Scores. Results: At the cohort level, we found asthma was very poorly controlled in 37% (30/82) of the children, not well controlled in 26% (21/82), and well controlled in 38% (31/82). Among the very poorly controlled children (n=30), we found 30% (9/30) were highly compliant toward their controller medication intake—suggesting a re-evaluation for change in medication or dosage—whereas 50% (15/30) were poorly compliant and candidates for a more timely intervention to improve compliance to mitigate their situation. We observed a negative Kendall Tau correlation between Asthma Control Test scores and Digital Phenotype Score as −0.509 (P\u3c.01). Conclusions: kHealth kit is suitable for the collection of clinically relevant information from pediatric patients. Furthermore, Digital Phenotype Score and Controller Compliance Score, computed based on the continuous digital monitoring, provide the clinician with timely and detailed evidence of a child’s asthma-related condition when compared with the Asthma Control Test scores taken infrequently during clinic visits

A 22-Week-Old Fetus with Nager Syndrome and Congenital Diaphragmatic Hernia due to a Novel SF3B4 Mutation.

Nager syndrome, or acrofacial dysostosis type 1 (AFD1), is a rare multiple malformation syndrome characterized by hypoplasia of first and second branchial arches derivatives and appendicular anomalies with variable involvement of the radial/axial ray. In 2012, AFD1 has been associated with dominant mutations in SF3B4. We report a 22-week-old fetus with AFD1 associated with diaphragmatic hernia due to a previously unreported SF3B4 mutation (c.35-2A>G). Defective diaphragmatic development is a rare manifestation in AFD1 as it is described in only 2 previous cases, with molecular confirmation in 1 of them. Our molecular finding adds a novel pathogenic splicing variant to the SF3B4 mutational spectrum and contributes to defining its prenatal/fetal phenotype

Digital phenotyping: Towards replicable findings with comprehensive assessments and integrative models in bipolar disorders

Background: Digital phenotyping promises to unobtrusively obtaining a continuous and objective input of symptomatology from patients\u27 daily lives. The prime example are bipolar disorders, as smartphone parameters directly reflect bipolar symptomatology. Empirical studies, however, have yielded inconsistent findings. We believe that three main shortcomings have to be addressed to fully leverage the potential of digital phenotyping: short assessment periods, rare outcome assessments, and an extreme fragmentation of parameters without an integrative analytical strategy. Methods: To demonstrate how to overcome these shortcomings, we conducted frequent (biweekly) dimensional and categorical expert ratings and daily self-ratings over an extensive assessment period (12 months) in 29 patients with bipolar disorder. Digital phenotypes were monitored continuously. As an integrative analytical strategy, we used structural equation modelling to build latent psychopathological outcomes (mania, depression) and latent digital phenotype predictors (sleep, activity, communicativeness). Outcomes: Combining gold-standard categorical expert ratings with dimensional self and expert ratings resulted in two latent outcomes (mania and depression) with statistically meaningful factor loadings that dynamically varied over 299 days. Latent digital phenotypes of sleep and activity were associated with same-day latent manic psychopathology, suggesting that psychopathological alterations in bipolar disorders relate to domains (latent variables of sleep and activity) and not only to specific behaviors (such as the number of declined incoming calls). The identification of latent psychopathological outcomes that dimensionally vary on a daily basis will enable to empirically determine which combination of digital phenotypes at which days prior to an upcoming episode are viable as digital prodromal predictors. (DIPF/Orig.

Digital phenotyping: towards replicable findings with comprehensive assessments and integrative models in bipolar disorders

Background: Digital phenotyping promises to unobtrusively obtaining a continuous and objective input of symptomatology from patients’ daily lives. The prime example are bipolar disorders, as smartphone parameters directly reflect bipolar symptomatology. Empirical studies, however, have yielded inconsistent findings. We believe that three main shortcomings have to be addressed to fully leverage the potential of digital phenotyping: short assessment periods, rare outcome assessments, and an extreme fragmentation of parameters without an integrative analytical strategy. Methods: To demonstrate how to overcome these shortcomings, we conducted frequent (biweekly) dimensional and categorical expert ratings and daily self-ratings over an extensive assessment period (12 months) in 29 patients with bipolar disorder. Digital phenotypes were monitored continuously. As an integrative analytical strategy, we used structural equation modelling to build latent psychopathological outcomes (mania, depression) and latent digital phenotype predictors (sleep, activity, communicativeness). Outcomes: Combining gold-standard categorical expert ratings with dimensional self and expert ratings resulted in two latent outcomes (mania and depression) with statistically meaningful factor loadings that dynamically varied over 299 days. Latent digital phenotypes of sleep and activity were associated with same-day latent manic psychopathology, suggesting that psychopathological alterations in bipolar disorders relate to domains (latent variables of sleep and activity) and not only to specific behaviors (such as the number of declined incoming calls). The identification of latent psychopathological outcomes that dimensionally vary on a daily basis will enable to empirically determine which combination of digital phenotypes at which days prior to an upcoming episode are viable as digital prodromal predictors

Digital phenotype of mood disorders: A conceptual and critical review

BackgroundMood disorders are commonly diagnosed and staged using clinical features that rely merely on subjective data. The concept of digital phenotyping is based on the idea that collecting real-time markers of human behavior allows us to determine the digital signature of a pathology. This strategy assumes that behaviors are quantifiable from data extracted and analyzed through digital sensors, wearable devices, or smartphones. That concept could bring a shift in the diagnosis of mood disorders, introducing for the first time additional examinations on psychiatric routine care.ObjectiveThe main objective of this review was to propose a conceptual and critical review of the literature regarding the theoretical and technical principles of the digital phenotypes applied to mood disorders.MethodsWe conducted a review of the literature by updating a previous article and querying the PubMed database between February 2017 and November 2021 on titles with relevant keywords regarding digital phenotyping, mood disorders and artificial intelligence.ResultsOut of 884 articles included for evaluation, 45 articles were taken into account and classified by data source (multimodal, actigraphy, ECG, smartphone use, voice analysis, or body temperature). For depressive episodes, the main finding is a decrease in terms of functional and biological parameters [decrease in activities and walking, decrease in the number of calls and SMS messages, decrease in temperature and heart rate variability (HRV)], while the manic phase produces the reverse phenomenon (increase in activities, number of calls and HRV).ConclusionThe various studies presented support the potential interest in digital phenotyping to computerize the clinical characteristics of mood disorders

Recent Advances in Asthma Research and Treatments

This book provides an insightful and analytical look at several aspects related to asthma. Written by experts in the field, chapters cover such topics as asthma phenotypes and current biological treatments, anaphylactic reactions in radiology procedures, asthma and COVID-19, mobile apps for both patients and providers, the function of non-coding RNAs in asthma mediated by Th2 cells, and the roles of B7 and semaphorin molecules. The book provides readers the information they need to get a clear understanding of asthma, its phenotypes, treatment biologics, COVID-19 effects, digital care frameworks, epigenetics, and costimulators/immune checkpoints

Neuropsychiatric correlates of power state in smartphone use

Schizophrenia is a complex and devastating illness with heterogeneous symptoms, late diagnosis, and excess early mortality. It is also associated with comorbidities including substance abuse, depression, anxiety, and sleep problems, that have adverse effects on the individual over the entire course of the disease. While effects of these comorbidities have been identified in the literature, few studies have involved longitudinal assessments and reproducible data collection in large populations. Recent smartphone research tools have been developed that provide better access to patients and can enable a real-world snapshot of a person’s mental state. In addition, these tools use the phone’s sensors to construct a digital phenotype of an individual, with the potential to detect changes in symptoms and cognition on a moment-by-moment basis. Previous studies report associations between anxiety and smartphone use, but most involve cross-sectional data and cohorts of healthy controls completing paper and pencil scales. A recent smartphone study collected day-to-day symptomatology, cognition, and phone usage data and discovered that the association between anxiety and smartphone use is more complex than originally thought