Abstract
The dichotomy index (I < O), a quantitative estimate of the circadian regulation of daytime activity and sleep, predicted overall cancer survival and emergency hospitalization, supporting its integration in a mHealth platform. Modifiable causes of I < O deterioration below 97.5%—(I < O)low—were sought in 25 gastrointestinal cancer patients and 33 age- and sex-stratified controls. Rest-activity and temperature were tele-monitored with a wireless chest sensor, while daily activities, meals, and sleep were self-reported for one week. Salivary cortisol rhythm and dim light melatonin onset (DLMO) were determined. Circadian parameters were estimated using Hidden Markov modelling, and spectral analysis. Actionable predictors of (I < O)low were identified through correlation and regression analyses. Median compliance with protocol exceeded 95%. Circadian disruption—(I < O)low—was identified in 13 (52%) patients and four (12%) controls (p = 0.002). Cancer patients with (I < O)low had lower median activity counts, worse fragmented sleep, and an abnormal or no circadian temperature rhythm compared to patients with I < O exceeding 97.5%—(I < O)high—(p < 0.012). Six (I < O)low patients had newly-diagnosed sleep conditions. Altered circadian coordination of rest-activity and chest surface temperature, physical inactivity, and irregular sleep were identified as modifiable determinants of (I < O)low. Circadian rhythm and sleep tele-monitoring results support the design of specific interventions to improve outcomes within a patient-centered systems approach to health care.
Highlights
Chronic disease patients represent the largest burden for our health care system, and are at highest risk of acute complications, as currently seen in the COVID-19 pandemic [1,2]
Twenty-two cancer patients (88%) were taking at least one concurrent medication, which were mostly related to the treatment of associated cardiovascular (N = 11, 44%), endocrine/metabolic (N = 10, 40%), and/or respiratory (N = 6, 24%) pathologies
While salivary cortisol data were of high quality for almost all participants, melatonin secretion mechanisms might be impaired in cancer patients and in controls older than 40 y.o., for whom dim light melatonin onset (DLMO) could hardly be precisely computed in real life conditions [31]
Summary
Chronic disease patients represent the largest burden for our health care system, and are at highest risk of acute complications, as currently seen in the COVID-19 pandemic [1,2]. Data during daily life, and provides them and their families and hospital physicians with information enabling shared decision-making procedures [3,4]. Such a “domomedicine” system will anticipate and prevent emergency hospitalizations through proactive interventions, based on early warning signals extracted from critical health functions dynamics tele-monitoring. This presents an immense opportunity for progress through circadian medicine to integrate our rapidly increased understanding of how molecular circadian clocks work and control cellular and organismic physiologies over the course of 24 h [5]. Circadian oscillations are generated in each mammalian cell by a molecular oscillator involving some 15 specific genes regulating each other through transcriptional and post transcriptional feedback loops [8,9]
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