Much ado about nothing? Discrepancy between the available data on the antiviral effect of hydroxychloroquine in March 2020 and its inclusion in COVID-19 clinical trials and outpatient prescriptions.

OBJECTIVES: Many of the 2020 COVID-19 clinical trials included an (hydroxy)chloroquine ((H)CQ) arm. We aimed to juxtapose the state of science before April 2020 regarding the benefits of (H)CQ for viral infections with the number and size of the clinical trials studying (H)CQ and the volume of (H)CQ dispensed in France. STUDY DESIGN: We identified and analysed published scientific material regarding the antiviral activity of (H)CQ and publicly available data regarding clinical trials and drug dispensation in France. METHODS: We conducted a review of scientific publications available before April 2020 and a systematic analysis of COVID-19 clinical trials featuring (H)CQ registered on clinicaltrials.gov. RESULTS: Before April 2020, 894 scientific publications mentioning (H)CQ for viruses other than coronaviruses were available, including 35 in vitro studies (reporting an inconstant inhibition of viral replication), 11 preclinical studies (reporting no or disputable positive effects), and 32 clinical trials (reporting no or disputable positive effects). Moreover, 67 publications on (H)CQ and coronavirus infections were available, including 12 in vitro studies (reporting an inconstant inhibition of viral replication), two preclinical studies (reporting contradictory results), and no clinical trials. Meanwhile, 253 therapeutic clinical trials featuring an HCQ arm were registered in 2020, intending to enrol 246,623 patients. CONCLUSIONS: The number and size of (H)CQ clinical trials for COVID-19 launched in 2020 were not supported by the literature published before April 2020.

Desynchronization of the oral temperature circadian rhythm and intolerance to shift work.

The present study tested the hypothesis that subjects with a good tolerance to shift work maintain the circadian period tau of their temperature rhythm equal to 24 h, while tau may differ from 24 h when subjects exhibit one or several clinical signs of intolerance. These latter are mainly: persisting sleep disturbance, persisting fatigue, changes in mood and behaviour, and digestive troubles, from gastritis to overt peptic ulcer. These symptoms were used here to classify the subjects studied. Medications, including all types of sleeping pills, are ineffective. As was the case in the present study, some subjects may tolerate shift work for 35 yr, reaching 57 yr of age without complaint, while others, after several months or many years, quite rapidly (within 6 months) develop symptoms of intolerance.

Circadian and ultradian rhythms in the feeding behaviour and nutrient intakes of oil refinery operators with shift-work every 3--4 days.

Seven healthy adult men, five shift-workers and two non-shift-workers (from 21 to 36 years; mean = 26.4) volunteered to record what and when they ate, both at work and at home, every day, during eight consecutive weeks (Oct. - Dec. 1974). 1) All the subjects maintained the timing of main-meal (lunch and supper) during all shifts. 2) The major intake of protein and lipid was concentrated on the two main meals during all shifts. 3) Only the pattern of carbohydrate intake was modified by the shift-work: e.g. night-shift is associated with nibbling behaviour. 4) However, shift-work and in particular the occurence of nibbling behaviour did not result in change either in the mean 24 h caloric intake, or in the percentage of protein calories. 5) The comparison between the constancy of the timing of major meals and the shift of the timing of circadian rhythm acrophases of the 5 shift-workers leads to conclude that meal timing had a poor synchronizing effect, if any.

Is the rhythm amplitude related to the ability to phase-shift circadian rhythms of shift-workers?

The magnitude of the circadian acrophase adjustment deltaphi to a phase shift of socio-ecologic synchronizers (as in shift-work) varies from subject to subject. According to J. Aschoff, the ability to adjust rapidly to a phase-shift could be associated with having a small amplitude for certain circadian rhythms. To test this hypothesis, the correlation coefficient (r) between the mean circadian rhythm amplitude A and the acrophase shift deltaphi (measured after the first night-shift) were calculated from estimates of chronobiological time series analyses (Halberg's single cosinor method). Data were obtained from two groups of selected shift-workers (20 and 5 subjects, respectively). A negative correlation between A and deltaphi (the smaller the amplitude, the greater the delpaphi) was observed in the circadian rhythms of the following variables: oral temperature (r = .63;P less than .01), peak expiratory flow (r = . 53: P less than . 01), and urinary 17-OHCS (r = . 60; P less than . 01), but not for other variables such as : grip strength, urinary K+ and Na+. The small amplitude of certain circadian rhythms could be considered as an index of an individual's ability to phase-shift easily. However, chronobiological characteristics, other than the small circadian rhythm ampliture, remain to be identified, for both a better detection of one's ability to do shift-work and a better knowledge for practical applications.