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Antipyretics

Diurnal Variations in Temperature and work potential

This image comes to us from Souissi  (2007).  These authors wished to test the hypothesis that the time of day affects the performance a short, all out test of anerobic capacity of skeletal muscles.  This YouTube video gives an idea of how this test works.

DiurnalTemp
From (2007). Diurnal temperature variation for 11 male subjects. The authors used temperature data to choose the time of day to perform the Total work as measured in kJ was one of many parameters that was significantly greater at 18 hour.  These values are inserted in the valley and the peak of the temperature curve.

In infections like Covid-19 in which blood oxygen can become compromised, do slight increases in temperature improve the ability of cells of the immune system operate on glycolysis?

Real time temperature recording or by hand?

For a while we consideredOnio.com  We were advised not to use expensive real time temperature monitoring devices.

Fevers2
The “area under the curve” for fevers is calculated by the “trapezoid” rule. The AUC is pretty easy to calculate with a spreadsheet.

 

 

Unfortunately Onio just isn’t telling us what the time scale is on these graphs but we can hypothesize that the dual peaks occur on top of normal diurnal variations over perhaps two days.

Measuring oral temperatures every hour, is it difficult?

I measured my own oral temperature approximately every waking hour for 48 hours staring at about 4:30 PM, or 16:30 on a Friday afternoon. Measuring temperatures right on the hour is rather difficult at times.  As long as the minutes are recorded, it is pretty easy to compensate for being off  with a spread sheet.

My Saturday and Sunday mornings are filled with bicycling, running, and swimming.  Sunrise is usually around 4:30 AM this time of year in AZ….

Or about 29  and 53 hours in this graph.  Oddly enough, my lowest temperatures were recorded when I was out exercising.

With manual data recording every hour it is hard to tell which data points belong to natural down spikes or up spikes.

Fevers1

We will be instructing our participants not to take NSAIDS or Tylenol for their fevers.  They might get dehydrated and drink a large amount of ice cold water. They might use the trick of sticking a wet towel in the freezer and then place it around their neck to cool off.  As long as they record their “rescue interventions” we should be able to compensate.

Things for Mitosynergy to consider that others have not

  • How curprous niacin affects the natural diurnal variations in body temperature? Does it increase the peaks and valleys?  Does it change how fast these peaks or valleys are reached?
  • If cuprous niacin decreases Covid-19 temperatures, does it do so in natural times of decreasing temperature?  This is one thing that will complicate time to maximum temperature decrease that has been used in previous studies.
  • Correlate temperature with blood oxygen saturation.

Anti-Pyretic Methods on ClinicalTrials.gov

Viral Fevers

Primary Outcome Measures :

Area under the curve (AUC) of the orally measured change of body temperature from baseline over a period of 0 – 4 hours post dose. [ Time Frame: Up to 4 hours post dose ]

Secondary Outcome Measures :

Maximum temperature difference between baseline and the lowest measured temperature [ Time Frame: Up to 4 hours post dose ]
Time to reach the maximum temperature difference [ Time Frame: Up to 4 hours post dose ]
Intensity of Upper Respiratory Tract Infection symptoms [ Time Frame: 0, 2, 4, and 6 hours post dose ]
Safety – assessment of adverse events [ Time Frame: Up to 7 hours post dose ]

Anti-pyretics in CNS malaria

Primary Outcome Measures :

Mean Maximum temperature [ Time Frame: 72 hours ]

Mean maximum temperature (TMAX). TMAX will be defined as the highest temperature during the study duration (72 hours) in degrees Celsius recorded by a continuous temperature monitor.

Secondary Outcome Measures :

Seizures [ Time Frame: 72 hours ]
Seizures detected clinically or on daily EEG

Parasite burden [ Time Frame: 72 hours ]
based upon HRP2 levels and quantitative blood film Q6 hourly until aparasitemic on thick blood smear

Area-under-the-curve of fever [ Time Frame: 72 hours ]
AUC fever for temperatures above 37.5 degrees Celsius based upon continuous temperature monitoring

 

Pediatric fevers

Primary Outcome Measures :

The primary endpoint will be the Area under the curve for fever in the 4 hours after administration of each study arm relative to Area under the curve for fever of Ibuprofen [ Time Frame: 4 hours ]
Area under the curve for fever will be calculated as the difference between measured temperature at a given time and 38°C.

Secondary Outcome Measures :

A febrile period/time to first fever recurrence [ Time Frame: 6 hours ]
Afebrile period as calculated to be the time from first temperature measurement less than 38°C occurring after fever until the first temperature greater than or equal to 38.3°C occurring after fever.

 

References

 

Souissi N, Bessot N, Chamari K, Gauthier A, Sesboüé B, Davenne D. (2007) Effect of time of day on aerobic contribution to the 30-s Wingate test performance. Chronobiol Int. 2007;24(4):739-48.

 

Area under the curve in spreadsheets

 

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