Clinical validation of digital biomarkers for pediatric patients with asthma and cystic fibrosis - Potential for clinical trials and clinical care

2021 ◽  
pp. 2100208
Author(s):  
Matthijs D. Kruizinga ◽  
Esmée Essers ◽  
Frederik E. Stuurman ◽  
Yalçin Yavuz ◽  
Marieke L. de Kam ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cystic Fibrosis ◽  
Heart Rate ◽  
Clinical Trials ◽  
Clinical Care ◽  
Clinical Validation ◽  
Healthy Children ◽  
Children With Asthma ◽  
Digital Biomarkers ◽  
Lower Physical Activity

BackgroundDigital biomarkers are a promising novel method to capture clinical data in a home-setting. However, clinical validation prior to implementation is of vital importance. The aim of this study was to clinically validate physical activity, heart rate, sleep and FEV1 as digital biomarkers measured by a smartwatch and portable spirometer in children with asthma and cystic fibrosis (CF).MethodsThis was a prospective cohort study including 60 children with asthma and 30 children with CF (age 6–16). Participants wore a smartwatch, performed daily spirometry at home and completed a daily symptom questionnaire for 28-days. Physical activity, heart rate, sleep and FEV1 were considered candidate digital endpoints. Data from 128 healthy children was used for comparison. Reported outcomes were compliance, difference between patients and controls, correlation with disease-activity and potential to detect clinical events. Analysis was performed with linear mixed effect models.ResultsMedian compliance was 88%. On average, patients exhibited lower physical activity and FEV1 compared to healthy children, whereas the heart rate of children with asthma was higher compared to healthy children. Days with a higher symptom score were associated with lower physical activity for children with uncontrolled asthma and CF. Furthermore, FEV1 was lower and (nocturnal) heart rate was higher for both patient groups on days with more symptoms. Candidate biomarkers and showed a distinct pattern before- and after a pulmonary exacerbation.ConclusionPortable spirometer- and smartwatch-derived digital biomarkers show promise as candidate endpoints for use in clinical trials or clinical care in pediatric lung disease.

scholarly journals Towards remote monitoring in pediatric care and clinical trials—Tolerability, repeatability and reference values of candidate digital endpoints derived from physical activity, heart rate and sleep in healthy children

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244877
Author(s):  
M. D. Kruizinga ◽  
N. van der Heide ◽  
A. Moll ◽  
A. Zhuparris ◽  
Y. Yavuz ◽  
...  
Keyword(s):  
Physical Activity ◽  
Heart Rate ◽  
Clinical Trials ◽  
Reference Values ◽  
Pediatric Care ◽  
Portable Devices ◽  
Healthy Children ◽  
Blood Pressure Monitor ◽  
Pressure Monitor ◽  
Wide Range

Background Digital devices and wearables allow for the measurement of a wide range of health-related parameters in a non-invasive manner, which may be particularly valuable in pediatrics. Incorporation of such parameters in clinical trials or care as digital endpoint could reduce the burden for children and their parents but requires clinical validation in the target population. This study aims to determine the tolerability, repeatability, and reference values of novel digital endpoints in healthy children. Methods Apparently healthy children (n = 175, 46% male) aged 2–16 were included. Subjects were monitored for 21 days using a home-monitoring platform with several devices (smartwatch, spirometer, thermometer, blood pressure monitor, scales). Endpoints were analyzed with a mixed effects model, assessing variables that explained within- and between-subject variability. Endpoints based on physical activity, heart rate, and sleep-related parameters were included in the analysis. For physical-activity-related endpoints, a sample size needed to detect a 15% increase was calculated. Findings Median compliance was 94%. Variability in each physical activity-related candidate endpoint was explained by age, sex, watch wear time, rain duration per day, average ambient temperature, and population density of the city of residence. Estimated sample sizes for candidate endpoints ranged from 33–110 per group. Daytime heart rate, nocturnal heart rate and sleep duration decreased as a function of age and were comparable to reference values published in the literature. Conclusions Wearable- and portable devices are tolerable for pediatric subjects. The raw data, models and reference values presented here can be used to guide further validation and, in the future, clinical trial designs involving the included measures.

scholarly journals Applicability of a Web-Based, Individualized Exercise Intervention in Patients With Liver Disease, Cystic Fibrosis, Esophageal Cancer, and Psychiatric Disorders: Process Evaluation of 4 Ongoing Clinical Trials (Preprint)

2017 ◽  
Author(s):  
Daniel Pfirrmann ◽  
Nils Haller ◽  
Yvonne Huber ◽  
Patrick Jung ◽  
Klaus Lieb ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cystic Fibrosis ◽  
Clinical Trials ◽  
Liver Disease ◽  
Activity Level ◽  
Daily Routine ◽  
Intervention Period ◽  
Web Based ◽  
Significant Change ◽  
Disease Specific

BACKGROUND In the primary and secondary prevention of civilization diseases, regular physical activity is recommended in international guidelines to improve disease-related symptoms, delay the progression of the disease, or to enhance postoperative outcomes. In the preoperative context, there has been a paradigm shift in favor of using preconditioning concepts before surgery. Web-based interventions seem an innovative and effective tool for delivering general information, individualized exercise recommendations, and peer support. OBJECTIVE Our first objective was to assess feasibility of our Web-based interventional concept and analyze similarities and differences in a sustained exercise implementation in different diseases. The second objective was to investigate the overall participants’ satisfaction with our Web-based concept. METHODS A total of 4 clinical trials are still being carried out, including patients with esophageal carcinoma scheduled for oncologic esophagectomy (internet-based perioperative exercise program, iPEP, study), nonalcoholic fatty liver disease (hepatic inflammation and physical performance in patients with nonalcoholic steatohepatitis, HELP, study), depression (exercise for depression, EXDEP, study), and cystic fibrosis (cystic fibrosis online mentoring for microbiome, exercise, and diet, COMMED, study). During the intervention period, the study population had access to the website with disease-specific content and a disease-specific discussion forum. All participants received weekly, individual tailored exercise recommendations from the sports therapist. The main outcome was the using behavior, which was obtained by investigating the log-in rate and duration. RESULTS A total of 20 participants (5 from each trial) were analyzed. During the intervention period, a regular contact and a consequent implementation of exercise prescription were easily achieved in all substudies. Across the 4 substudies, there was a significant decrease in log-in rates (P<.001) and log-in durations (P<.001) over time. A detailed view of the different studies shows a significant decrease in log-in rates and log-in durations in the HELP study (P=.004; P=.002) and iPEP study (P=.02; P=.001), whereas the EXDEP study (P=.58; P=.38) and COMMED study (P=.87; P=.56) showed no significant change over the 8-week intervention period. There was no significant change in physical activity within all studies (P=.31). Only in the HELP study, the physical activity level increased steadily over the period analyzed (P=.045). Overall, 17 participants (85%, 17/20) felt secure and were not scared of injury, with no major differences in the subtrials. CONCLUSIONS The universal use of the Web-based intervention appears to be applicable across the heterogonous collectives of our study patients with regard to age and disease. Although the development of physical activity shows only moderate improvements, flexible communication and tailored support could be easily integrated into patients’ daily routine. CLINICALTRIAL iPEP study: ClinicalTrials.gov NCT02478996; https://clinicaltrials.gov/ct2/show/NCT02478996 (Archived by WebCite at http://www.webcitation.org/6zL1UmHaW); HELP study: ClinicalTrials.gov NCT02526732; http://www.webcitation.org/6zJjX7d6K (Archived by WebCite at http://www.webcitation.org/6Nch4ldcL); EXDEP study: ClinicalTrials.gov NCT02874833; https://clinicaltrials.gov/ct2/show/NCT02874833 (Archived by WebCite at http://www.webcitation.org/6zJjj7FuA)

scholarly journals A unified platform for outcome measures and exergames with 3D accelerometry

2015 ◽  
Author(s):  
Timur Nuritdinow ◽  
Christian Lederer ◽  
Martin Daumer
Keyword(s):  
Physical Activity ◽  
Heart Rate ◽  
Clinical Trials ◽  
Oxygen Consumption ◽  
Energy Expenditure ◽  
Exercise Therapy ◽  
Moderate Physical Activity ◽  
Large Set ◽  
Controlled Clinical Trials ◽  
Technology Platform

Mobile accelerometry is more and more being used in clinical trials as a tool to measure outcomes related to physical activity. However, it is still difficult to integrate exercise therapy in controlled clinical trials. We want to explore the option to use a unified platform to both measure outcome and prescribe and monitor exercise therapy using the actibelt technology platform. We present a prototype based on the actibelt platform that allows to use the wearable device as a mouse controller for a large set of potentially interesting games. Playing an exergame a person is encouraged to increase its level of daily motion while engaging in an activity that is perceived as interesting and fun, thus, providing an intrinsic motivation. Studies suggest that exergaming can be compared to light or moderate physical activity considering the heart rate, oxygen consumption and energy expenditure.

scholarly journals Interventions promoting physical activity among adults and children in the six Gulf Cooperation Council countries: protocol for a systematic review

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e037122
Author(s):  
Fiona Pearson ◽  
Peijue Huangfu ◽  
Farah M Abu-Hijleh ◽  
Susanne F Awad ◽  
Laith J Abu-Raddad ◽  
...  
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Clinical Trials ◽  
Data Extraction ◽  
Gulf Cooperation Council ◽  
Cochrane Library ◽  
Healthy Children ◽  
Gcc Countries ◽  
Obesity And Diabetes ◽  
Adults And Children

IntroductionPrevalence of overweight, obesity and diabetes are high and rising across the Gulf Cooperation Council (GCC) countries (Oman, Bahrain, Kuwait, Qatar, Saudi Arabia and the United Arab Emirates). In parallel, physical activity (PA) levels are low relative to international standards. PA aids weight control and reduces risk of non-communicable diseases including diabetes and cardiovascular disease. It is likely interventions developed elsewhere will not translate to GCC countries due to unique environmental, social and cultural factors. This protocol is for a systematic review assessing the efficacy of interventions promoting PA within GCC countries among generally healthy adults and children. The primary outcome of interest is change in objectively measured or self-reported PA levels, the secondary outcomes of interest are changes in anthropometry or chronic disease risk factors (eg, blood pressure). Interventions will be compared with no intervention or those of differing PA intensity or duration. The relationships between PA change and the following will be assessed: intervention intensity or duration, season in which intervention occurs, sex, age, nationality and sustainability over time.Methods and analysisA systematic search strategy will identify indexed publications on the efficacy of interventions promoting PA. Randomised controlled trials and quasi-experimental studies recruiting predominantly healthy children and adults will be included. Studies of exercise rehabilitation will be excluded. Medline, Embase, Cinahl, Cochrane Library, SportDiscus, Web of Science, Index Medicus for the Eastern Mediterranean Region and Qscience will be searched. Clinical trial registries including the International Clinical Trials Registry Platform, the Iranian Registry of Clinical Trials and ClinicalTrials.gov will be searched for ongoing and unpublished studies. Searches will be ran from database inception until 1 May 2020 and be supplemented by checking references of key articles. Two reviewers will independently screen identified citations then full texts using prespecified inclusion and exclusion criteria. Piloted data extraction forms will be used in duplicate. Inconsistencies in screening or data extraction will be resolved by a third investigator or study author contact. Risk of bias will be independently assessed by two reviewers using validated tools. A narrative summary of findings will be produced supplemented with meta-analyses and exploration of heterogeneity as appropriate.Ethics and DisseminationThe review aims to strengthen the findings of the primary studies it incorporates and explore the impact of setting. It will synthesise existing published aggregate patient data. If publications or data with ethical concerns are identified, they will be excluded from the review. Results of the systematic review will be published in full and authors will engage directly with research audiences and key stakeholders to share findings.PROSPERO registration number131817.

scholarly journals Comparison of Oropharyngeal Microbiota from Children with Asthma and Cystic Fibrosis

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Sébastien Boutin ◽  
Martin Depner ◽  
Mirjam Stahl ◽  
Simon Y. Graeber ◽  
Susanne A. Dittrich ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bacterial Load ◽  
Amplicon Sequencing ◽  
Healthy Children ◽  
Healthy Controls ◽  
Opportunistic Pathogens ◽  
Core Microbiome ◽  
16S Rrna Amplicon Sequencing ◽  
Children With Asthma ◽  
Host Regulation

A genuine microbiota resides in the lungs which emanates from the colonization by the oropharyngeal microbiota. Changes in the oropharyngeal microbiota might be the source of dysbiosis observed in the lower airways in patients suffering from asthma or cystic fibrosis (CF). To examine this hypothesis, we compared the throat microbiota from healthy children (n=62) and that from children with asthma (n=27) and CF (n=57) aged 6 to 12 years using 16S rRNA amplicon sequencing. Our results show high levels of similarities between healthy controls and children with asthma and CF revealing the existence of a core microbiome represented by Prevotella, Streptococcus, Neisseria, Veillonella, and Haemophilus. However, in CF, the global diversity, the bacterial load, and abundances of 53 OTUs were significantly reduced, whereas abundances of 6 OTUs representing opportunistic pathogens such as Pseudomonas, Staphylococcus, and Streptococcus were increased compared to those in healthy controls controls and asthmatics. Our data reveal a core microbiome in the throat of healthy children that persists in asthma and CF indicating shared host regulation favoring growth of commensals. Furthermore, we provide evidence for dysbiosis with a decrease in diversity and biomass associated with the presence of known pathogens consistent with impaired host defense in children with CF.

scholarly journals Case Report: Ambient Sensor Signals as Digital Biomarkers for Early Signs of Heart Failure Decompensation

2021 ◽  
Vol 8 ◽  
Author(s):  
Hugo Saner ◽  
Narayan Schuetz ◽  
Philipp Buluschek ◽  
Guillaume Du Pasquier ◽  
Giuseppe Ribaudo ◽  
...  
Keyword(s):  
Physical Activity ◽  
Heart Rate ◽  
Respiration Rate ◽  
Health Care Systems ◽  
Clinical Signs ◽  
Home Monitoring ◽  
Sensor System ◽  
Sensor Systems ◽  
Early Signs ◽  
Digital Biomarkers

Home monitoring systems are increasingly used to monitor seniors in their apartments for detection of emergency situations. More recently, multimodal ambient sensor systems are also used to monitor digital biomarkers to detect clinically relevant health problems over longer time periods. Clinical signs of HF decompensation including increase of heart rate and respiration rate, decreased physical activity, reduced gait speed, increasing toilet use at night and deterioration of sleep quality have a great potential to be detected by non-intrusive contactless ambient sensor systems and negative changes of these parameters may be used to prevent further deterioration and hospitalization for HF decompensation. This is to our knowledge the first report about the potential of an affordable, contactless, and unobtrusive ambient sensor system for the detection of early signs of HF decompensation based on data with prospective data acquisition and retrospective correlation of the data with clinical events in a 91 year old senior with a serious heart problem over 1 year. The ambient sensor system detected an increase of respiration rate, heart rate, toilet use at night, toss, and turns in bed and a decrease of physical activity weeks before the decompensation. In view of the rapidly increasing prevalence of HF and the related costs for the health care systems and the societies, the real potential of our approach should be evaluated in larger populations of HF patients.

scholarly journals Heart rate variability, exercise capacity and levels of daily physical activity in children and adolescents with mild-to-moderate cystic fibrosis

2021 ◽  
pp. 1-10
Author(s):  
Pitiguara de Freitas Coelho ◽  
Roberta Ribeiro Batista Barbosa ◽  
Rodrigo dos Santos Lugao ◽  
Fernanda Mayrink Gonçalves Liberato ◽  
Pâmela Reis Vidal ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cystic Fibrosis ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Lung Function ◽  
Children And Adolescents ◽  
Exercise Capacity ◽  
Pancreatic Insufficiency ◽  
Daily Physical Activity ◽  
Rr Intervals

Background: Autonomic nervous system balance is altered in cystic fibrosis (CF), although its influence on physical fitness has been poorly explored. Objective: This study aimed to evaluate the association of heart rate variability (HRV) with exercise capacity and levels of daily physical activity in children and adolescents with mild-to-moderate CF. Methods: A cross-sectional study including individuals with CF aged 6–18 years, not under CFTR modulator therapy, was performed. Sociodemographic (age, sex) and clinical information (airway colonization, pancreatic insufficiency, and genotyping) were collected. In addition, exercise capacity (modified shuttle test — MST), lung function (spirometry), body composition (bioimpedance), levels of daily physical activity (5-day accelerometer), and HRV (both at rest and during the MST) were evaluated. Results: 30 individuals (20 females) aged [Formula: see text] years, mean FEV[Formula: see text]%, were included. A sympathovagal balance (LF/HF) increase ([Formula: see text]) during the MST was shown, indicating a predominance of sympathetic modulation. The standard deviation of all RR intervals (SDNN) and the high frequency (HF) index during exercise correlated significantly with FEV1 ([Formula: see text], [Formula: see text] and [Formula: see text], [Formula: see text]; respectively). MST distance also correlated positively and significantly with SDNN ([Formula: see text], [Formula: see text]), square root of the mean of the sums of squares of frequencies between RR intervals greater than 50[Formula: see text]ms — RMSSD ([Formula: see text], [Formula: see text]), low frequency — LF ([Formula: see text], [Formula: see text]), HF ([Formula: see text], [Formula: see text]), dispersion of points perpendicular to the short-term identity line — SD1 ([Formula: see text], [Formula: see text]) and negatively with LF/HF ([Formula: see text], [Formula: see text]). Regarding daily physical activity, SDNN at rest ([Formula: see text], [Formula: see text]) and exercise ([Formula: see text], [Formula: see text]) showed positive correlations with time in moderate-to-vigorous activities. When normalizing the SDNN and classifying individuals as normal or altered, those presenting altered SDNN showed poorest FEV1 ([Formula: see text]) and lower exercise capacity ([Formula: see text]). Conclusion: HRV correlates with lung function, exercise capacity and levels of daily physical activity in children and adolescents with CF. The study highlights the influence of CF on autonomic function and suggests HRV measurement as an easy tool to be used in clinical settings as an alternative marker to monitor CF individuals.

scholarly journals Evaluation of Clinical Outcomes and Simultaneous Digital Tracking of Daily Physical Activity, Heart Rate, and Inhalation Behavior in Patients With Pulmonary Arterial Hypertension Treated With Inhaled Iloprost: Protocol for the Observational VENTASTEP Study (Preprint)

2018 ◽  
Author(s):  
Christian Mueller ◽  
Barbara Stollfuss ◽  
Alexander Roitenberg ◽  
Jonas Harder ◽  
Manuel J Richter
Keyword(s):  
Physical Activity ◽  
Heart Rate ◽  
Clinical Trials ◽  
Sleep Quality ◽  
Daily Physical Activity ◽  
Inhaled Iloprost ◽  
Digital Monitoring ◽  
Activity Measures ◽  
Pulmonary Arterial ◽  
Digital Tracking

BACKGROUND Pulmonary arterial hypertension (PAH)—a progressive, ultimately fatal disease—patients often experience dyspnea, which can limit their daily physical activities. Iloprost is an inhaled therapy for PAH that has shown efficacy in clinical trials. However, clinical trials in PAH have provided only limited data on daily physical activity. Digital monitoring of daily physical activity in PAH is therefore attracting growing interest. To fully understand a patient’s response to treatment, monitoring of treatment adherence is also required. The Breelib nebulizer for administration of iloprost saves inhalation data, thus allowing digital monitoring of adherence. OBJECTIVE This study aims to perform parallel digital tracking of daily physical activity parameters, heart rate, and iloprost inhalation data in patients with PAH, before and after starting inhaled iloprost treatment. The primary objective is to investigate correlations between changes in digital measures of daily physical activity and traditional clinical measures. Secondary objectives are to assess iloprost inhalation behavior, the association between daily physical activity measures and time since last inhalation, changes in sleep quality and heart rate, the association of heart rate with daily physical activity measures and iloprost inhalation, and adverse events. METHODS VENTASTEP is a digital, prospective, observational, multicenter, single-arm cohort study of adults with PAH in Germany, starting inhaled iloprost treatment via the Breelib nebulizer, in addition to existing PAH therapy. The study comprises a baseline period without iloprost treatment (≤2 weeks) and an observation period with iloprost treatment (3 months±2 weeks). The Apple Watch Series 2 and iPhone 6s are used with a dedicated study app to continuously measure digital daily physical activity parameters and heart rate during the baseline and observation periods; the watch is also used with a 6-min walk distance (6MWD) app to measure digital 6MWD at baseline and the end-of-observation visit. Inhalation frequency, completeness, and duration are monitored digitally via the nebulizer and the BreeConnect app. Sleep quality is assessed using the Pittsburgh Sleep Quality Index at baseline and the end-of-observation visit. Changes in traditional outcome measures (6MWD, Borg dyspnea scale, EuroQol 5-dimensions questionnaire, functional class, and brain natriuretic peptide [BNP] or N-terminal proBNP) between baseline and the end-of-observation visit will be correlated with changes in digital daily physical activity parameters and digital 6MWD as the primary analysis. RESULTS The first participant was enrolled in February 2018 (estimated study completion by July 2019; planned sample size: 80 patients). CONCLUSIONS The VENTASTEP study will inform future research on the utility of digital parameters as outcome assessment tools for disease monitoring in PAH. The study will also provide insight into clinical outcomes, daily physical activity, and quality of life in patients adding inhaled iloprost, to existing PAH therapy. CLINICALTRIAL ClinicalTrials.gov NCT03293407; https://clinicaltrials.gov/ct2/show/NCT03293407 (Archived by WebCite at http://www.webcitation.org/6ywPGcn4I) INTERNATIONAL REGISTERED REPOR DERR1-10.2196/12144

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