ClinCirc identifies alterations of the circadian peripheral oscillator in critical care patients.

BackgroundAssessing circadian rhythmicity from infrequently sampled data is challenging; however, these types of data are often encountered when measuring circadian transcripts in hospitalized patients.MethodsWe present ClinCirc. This method combines 2 existing mathematical methods (Lomb-Scargle periodogram and cosinor) sequentially and is designed to measure circadian oscillations from infrequently sampled clinical data. The accuracy of this method was compared against 9 other methods using simulated and frequently sampled biological data. ClinCirc was then evaluated in 13 intensive care unit (ICU) patients as well as in a separate cohort of 29 kidney-transplant recipients. Finally, the consequences of circadian alterations were investigated in a retrospective cohort of 726 kidney-transplant recipients.ResultsClinCirc had comparable performance to existing methods for analyzing simulated data or clock transcript expression of healthy volunteers. It had improved accuracy compared with the cosinor method in evaluating circadian parameters in PER2:luc cell lines. In ICU patients, it was the only method investigated to suggest that loss of circadian oscillations in the peripheral oscillator was associated with inflammation, a feature widely reported in animal models. Additionally, ClinCirc was able to detect other circadian alterations, including a phase shift following kidney transplantation that was associated with the administration of glucocorticoids. This phase shift could explain why a significant complication of kidney transplantation (delayed graft dysfunction) oscillates according to the time of day kidney transplantation is performed.ConclusionClinCirc analysis of the peripheral oscillator reveals important clinical associations in hospitalized patients.FundingUK Research and Innovation (UKRI), National Institute of Health Research (NIHR), Engineering and Physical Sciences Research Council (EPSRC), National Institute on Academic Anaesthesia (NIAA), Asthma+Lung UK, Kidneys for Life.

The Relationship of the COVID-19 pandemic with the Incidence and Management of Upper Limb Fractures: Double-Centre Study.

Background: The COVID-19 pandemic brought about the placement of severe social restrictions in the United Kingdom, limiting activity and impacting public behavior. Limited studies have been published on the relationship of the coronavirus pandemic with the presentation and management of upper limb fractures. The aims of this study were first to assess the change in the incidence of upper limb fractures at key points during the COVID-19 pandemic such as the enactment and lifting of lockdowns, and second to evaluate the relationship between local COVID-19 burden and measures of service efficiency across our trust. Methods: We undertook a retrospective analysis of all upper limb fracture referrals, admissions, and surgical procedures from the 1st of March 2020 to the 28th of February 2021. Changes in upper limb fracture incidence were mapped to significant changes in social restrictions. Measurements of service efficiency including time from admission to theatre and length of stay for admitted upper limb fracture patients were mapped to local COVID-19 burden. Subgroup analysis was undertaken to compare across age groups, including the pediatric population, all adults, and the elderly. Results: The study involved 1251, 659, and 641 patients with upper limb fracture referrals, admissions, and procedures across the trust, respectively. Referrals (n=128) and procedures (n=72) both peaked in August 2020. Admissions peaked in both May and December 2020 (63 for both). Admissions and procedures both demonstrated a decrease in March and April 2020 compared to the rest of the study period (40 and 38 admissions, as well as 48 and 29 procedures respectively). Across the cohort, referrals and admissions did not demonstrate a statistically significant relationship with the relaxing of social restrictions (P=0.504). There were statistically significant differences among referrals, admissions, and procedures when stratifying patients by age (p =<0.001). Length of stay demonstrated an inverse relationship with COVID-19 burden throughout the study period, with the shortest average length of stay recorded in months with the highest number of local COVID-19 cases. The average time from injury occurrence to theatre increased during the winter months (P=0.001). Conclusion: There is a relationship between changes in social restrictions and the incidence of upper limb fractures. These changes also had differing impacts on upper limb fracture rates when stratifying by patient age groups. The orthopedic service demonstrated adaptability in response to the local COVID-19 burden, and further research is needed to determine what effect this had on clinical outcomes.