Multicentre, interventional, single-arm study protocol of telemonitored circadian rhythms and patient-reported outcomes for improving mFOLFIRINOX safety in patients with pancreatic cancer (MultiDom, NCT04263948).

INTRODUCTION: Circadian clocks regulate cellular proliferation and drug effects. Tolerability and/or efficacy of anticancer therapies have been improved by their administration according to circadian rhythms, while being predicted by circadian robustness. The combination of leucovorin, fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) is a standard treatment for pancreatic ductal adenocarcinoma (PDAC), that generates grades 3-4 adverse events in the majority of patients and an estimated 15%-30% emergency admission rate. The MultiDom study evaluates whether mFOLFIRINOX safety can be improved using a novel circadian-based telemonitoring-telecare platform in patients at home. The detection of early warning signals of clinical toxicities could guide their early management, possibly preventing emergency hospital admissions. METHODS AND ANALYSIS: This multicentre, interventional, prospective, longitudinal, single-arm study hypothesises that the mFOLFIRINOX-related emergency admission rate will be 5% (95% CI 1.7% to 13.7%), among 67 patients with advanced PDAC. Study participation is 7 weeks for each patient, including a reference week before chemotherapy onset and 6 weeks afterwards. Accelerometry and body temperature are measured q1-min using a continuously worn telecommunicating chest surface sensor, daily body weight is self-measured with a telecommunicating balance and 23 electronic patient-reported outcomes (e-PROs) are self-rated using a tablet. Hidden Markov model, spectral analyses and other algorithms automatically compute physical activity, sleep, temperature, body weight change, e-PRO severity and 12 circadian sleep/activity parameters, including the dichotomy index I

Digital circadian and sleep health in individual hospital shift workers: A cross sectional telemonitoring study.

BACKGROUND: Telemonitoring of circadian and sleep cycles could identify shift workers at increased risk of poor health, including cancer and cardiovascular diseases, thus supporting personalized prevention. METHODS: The Circadiem cross-sectional study aimed at determining early warning signals of risk of health alteration in hospital nightshifters (NS) versus dayshifters (DS, alternating morning and afternoon shifts). Circadian rhythmicity in activity, sleep, and temperature was telemonitored on work and free days for one week. Participants wore a bluetooth low energy thoracic accelerometry and temperature sensor that was wirelessly connected to a GPRS gateway and a health data hub server. Hidden Markov modelling of activity quantified Rhythm Index, rest quality (probability, p1-1, of remaining at rest), and rest duration. Spectral analyses determined periods in body surface temperature and accelerometry. Parameters were compared and predictors of circadian and sleep disruption were identified by multivariate analyses using information criteria-based model selection. Clusters of individual shift work response profiles were recognized. FINDINGS: Of 140 per-protocol participants (133 females), there were 63 NS and 77 DS. Both groups had similar median rest amount, yet NS had significantly worse median rest-activity Rhythm Index (0·38 [IQR, 0·29-0·47] vs. 0·69 [0·60-0·77], p<0·0001) and rest quality p1-1 (0·94 [0·94-0·95] vs 0·96 [0·94-0·97], p<0·0001) over the whole study week. Only 48% of the NS displayed a circadian period in temperature, as compared to 70% of the DS (p=0·026). Poor p1-1 was associated with nightshift work on both work (p<0·0001) and free days (p=0·0098). The number of years of past night work exposure predicted poor rest-activity Rhythm Index jointly with shift type, age and chronotype on workdays (p= 0·0074), and singly on free days (p=0·0005). INTERPRETATION: A dedicated analysis toolbox of streamed data from a wearable device identified circadian and sleep rhythm markers, that constitute surrogate candidate endpoints of poor health risk in shift-workers. FUNDING: French Agency for Food, Environmental and Occupational Health & Safety (EST-2014/1/064), University of Warwick, Medical Research Council (United Kingdom, MR/M013170), Cancer Research UK(C53561/A19933).