Technical validity and usability of a novel smartphone-connected spirometry device for pediatric patients with asthma and cystic fibrosis

Background: Diagnosis and follow-up of respiratory diseases traditionally rely on pulmonary function tests (PFTs), which are currently performed in hospitals and require trained personnel. Smartphone-

Public Preferences in Priority Setting when Admitting Patients to the ICU During the COVID-19 Crisis: A Pilot Study

Introduction: One of the challenges faced by hospitals during the coronavirus disease 2019 (COVID-19) pandemic is resource shortages in intensive care units (ICUs). In times of scarcity, patient prioritization based on non-medical considerations might be necessary. Objective: The aim of this study was to pilot test a survey to elicit public opinions on the relative importance of non-medical considerations in priority setting when admitting patients to the ICU in times of crisis. Methods: A discrete-choice experiment was used to collect social preferences for priority setting when admitting patients to the ICU during the COVID-19 pandemic. The six attributes were patient age, profession, guardianship, risk-conscious behavior on a societal level, health-conscious behavior, and expected ICU length of stay. The data were analyzed using a mixed multinomial logit model. Interactions between the age and profession of the respondents and the age and profession of the patient profiles were considered. Results: The mean (± standard deviation) age of respondents was 35.9 ± 14.5 years. In all, 70% of respondents indicated that medical and/or non-medical considerations should play a role in prioritizing patients for the ICU, whereas 15% agreed with a “first come, first served” strategy and the remaining 15% had no opinion. Respondents deemed risk-conscious behavior on a societal level to be the most important non-medical factor that should be used to prioritize patients in phase three of the framework, garnering an attribute importance (AI) of 31.2%, followed by patient age (AI 16.3%) and health-conscious behavior (AI 16.0%). ICU length of stay had the lowest impact on patient prioritization for ICU admittance (AI 10.9%). Younger and older respondents attached more importance to age than respondents in the middle age group and indicated a stronger preference to prioritize patients in their own age group (p = 0.042). Conclusion: The results of our study demonstrate the relative importance members of the public attach to responsible societal behavior during the COVID-19 pandemic. In the next phase of the study, we will elicit the perspectives of a representative sample of the Dutch population. Changes to the task design and attribute operationalization could improve the external validity of the study findings, and optimization of the experimental design will improve the internal validity of the study

Clinical validation of digital biomarkers for paediatric patients with asthma and cystic fibrosis:potential for clinical trials and clinical care

BACKGROUND: Digital 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 forced expiratory volume in 1 s (FEV1) as digital biomarkers measured by a smartwatch and portable spirometer in children with asthma and cystic fibrosis (CF). METHODS: This was a prospective cohort study including 60 children with asthma and 30 children with CF (aged 6-16 years). 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 end-points. Data from 128 healthy children were 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 effects models. RESULTS: Median compliance was 88%. On average, patients exhibited lower physical activity and FEV1 compared with healthy children, whereas the heart rate of children with asthma was higher compared with 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 appeared able to describe a pulmonary exacerbation. CONCLUSIONS: Portable spirometer- and smartwatch-derived digital biomarkers show promise as candidate end-points for use in clinical trials or clinical care in paediatric lung disease

Olfactomedin-4 Regulation by Estrogen in the Human Endometrium Requires Epidermal Growth Factor Signaling

Olfactomedin-4 (OLFM-4) is an extracellular matrix protein that is highly expressed in human endometrium. We have examined the regulation and function of OLFM-4 in normal endometrium and in cases of endometriosis and endometrial cancer. OLFM-4 expression levels are highest in proliferative-phase endometrium, and 17β-estradiol up-regulates OLFM-4 mRNA in endometrial explant cultures. Using the luciferase reporter under control of the OLFM-4 promoter, it was shown that both 17β-estradiol and OH-tamoxifen induce luciferase activity, and epidermal growth factor receptor-1 is required for this estrogenic response. In turn, EGF activates the OLFM-4 promoter, and estrogen receptor-α is needed for the complete EGF response. The cellular functions of OLFM-4 were examined by its expression in OLFM-4-negative HEK-293 cells, which resulted in decreased vimentin expression and cell adherence as well as increased apoptosis resistance. In cases of endometriosis and endometrial cancer, OLFM-4 expression correlated with the presence of epidermal growth factor receptor-1 and estrogen receptor-α (or estrogen signaling). An increase of OLFM-4 mRNA was observed in the endometrium of endometriosis patients. No change in OLFM-4 expression levels were observed in patients with endometrial cancer relative with controls. In conclusion, cross-talk between estrogen and EGF signaling regulates OLFM-4 expression. The role of OLFM-4 in endometrial tissue remodeling before the secretory phase and during the predisposition and early events in endometriosis can be postulated but requires additional investigation