Reminder, we are an AI patient and wife, not medical scientists, or medical Doctors. This is based on our own observations and experience even though we do discuss legitimate research here.
The origin of the term “Chinese Whispers” isn’t clear according to the wonderful Internet. It has also been called “Russian Scandal” or in the US “Telephone”. We all know what it is and have probably played it. You say a phrase or sentence, whispered into some’s ear. They then, without confirming what was said, repeat that phrase to the next person. This continues until everyone has heard the phrase once.
The challenge is to pass the message through a number of people without it becoming misheard and altered. The enjoyment of the game is that regardless how careful you are, the final message heard invariably is not what was originally said. It is used to show how gossip can affect outcomes, how we feel, what we believe, who we trust. The message being, if it isn’t from the horses mouth, then is it correct.
But were you aware that it can also happen with the written word. Someone writes something, a person looks at it, takes from it what THEY are looking for, and ignores something that although the author thought was relevant, the reader felt was of no significance.
A good recent example would be from a New Zealand Senior School Exam question.
The exam asked pupils to write an essay on the following question: “Julius Caesar once said, ‘Events of importance are the result of trivial causes’. With reference to the causes and consequences of a historical event you have studied this year, analyse the extent to which you agree or disagree with Caesar.”(Otago Daily Times)
The students sitting the exam had a serious issue with the word Trivial. Apparently many of them didn’t actually know what the word meant. I wasn’t so much concerned with the question (or the word Trivial) but with the quote itself. It is a 1980’s rewrite of the original and its context has slightly changed with its reinterpretation.
10 years ago, I would have taken what was written in research as correct, accurate and as it’s peer reviewed, good methodology. But in fact, it’s not always. In reading research for Adrenal Insufficiency, Derek and I have discovered this happens in referencing and “quoting” research as well.
But why is that important?
It doesn’t seem important at all, in fact some could say it’s trivial. But it is those trivial little re wordings’, the leaving out of part of a statement of the not reading the entire document and therefore missing an apparently trivial piece of information, that can have a big impact on how people are treated, and how their Dr’s will, or won’t listen to them.
One example we are looking at currently is dosing. What is better? Twice a day? Thrice a day? Four times a day? Maybe even five?
Derek is currently researching the origins of the belief that 15-25mg HC is all that is required. In doing this, we have come across a number of discussions around how many times a day to dose. What we have found is inconsistencies, misquotes, and lack of acknowledgement of some of the results from an original paper that is quoted.
The Original Paper:
Ekman, Bertil & Bachrach-Lindstrom, Margareta & Lindström, Torbjörn & Wahlberg, Jeanette & Blomgren, Johan & Arnqvist, Hans. (2012). A randomized, double-blind, crossover study comparing two- and four-dose hydrocortisone regimen with regard to quality of life, cortisol and ACTH profiles in patients with primary adrenal insufficiency. Clinical endocrinology. 77. 18-25. 10.1111/j.1365-2265.2012.04352.x.
The four-dose regimen gave a higher serum cortisol before tablet intake in the morning (P = 0·027) and a higher 24-h cortisol (AUC) (P < 0·0001) compared with the two-dose period. In contrast, a lower median plasma ACTH in the morning before tablet intake (P = 0·003) and a lower 24-h ln (ACTH(AUC) ) were found during the four-dose period. The patients preferred the four-dose regimen (P = 0·03), and the HRQoL scores tended to be higher (high score indicates better HRQoL) for the four-dose period. In summary, a four-dose regimen gives increased availability of cortisol and an enhanced effect with a less elevated ACTH in the morning in comparison with a two-dose regimen but the effect on HRQoL remains inconclusive.
The final statement is rather subjective. The patients FELT it improved their QoL, but statistical analysis of the questionnaires could not support how the real life patients perceived it. Is that a fault in the questionnaire rather than the actual results?
Articles (peer reviewed and published) citing the above reference and “quoting” the conclusion:
Amir-Hossein Rahvar, Christian S. Haas, Sven Danneberg, and Birgit Harbeck, “Increased Cardiovascular Risk in Patients with Adrenal Insufficiency: A Short Review,” BioMed Research International, vol. 2017, Article ID 3691913, 5 pages, 2017. https://doi.org/10.1155/2017/3691913.
Nonetheless, all regimens used so far fail to exactly mirror the physiological circadian rhythm, thereby having a negative impact on the metabolic system. However, other approaches like using a four-dose regimen were not able to show significant changes in quality of life, body weight, blood pressure, or glucose levels compared to a two-dose regimen [15*,16].
This report focused on the results of a small group over 8 weeks with 2 different dosing regimes. What they didn’t mention was the significant variation + of the: Free urine cortisol nmol/24-h 2 doses (337 ± 173) vs 4 doses (330 ± 93). Although the mean was close, the variation was very wide and over time, could this have a higher impact on other health outcomes. Also the preference to four doses a day was significantly higher than twice a day dosing preference for quality of life. Without the full document, and the figures, we could believe the above statement in it’s entirety.
Stefan R. Bornstein Bruno Allolio Wiebke Arlt Andreas Barthel Andrew Don-Wauchope Gary D. Hammer Eystein S. Husebye Deborah P. Merke M. Hassan Murad Constantine A. Stratakis David J. Torpy. (2016). Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, Volume 101, Issue 2, 1 February 2016, Pages 364–389, https://doi.org/10.1210/jc.2015-1710
One double-blind, randomized, crossover study evaluating two-dose vs four-dose hydrocortisone treatments (98) concluded that cortisol pharmacokinetics were more physiological on the four-dose regimen; surprisingly, participating patients preferred this regimen.
The preference was a statistically valid conclusion, yet this group were surprised at the result.
They appear to have got the information right yet although the document notes that HRQoL scores tended to be higher indicating a better HRQoL with four doses a day they still only recommend 2-3 doses a day, with a rider that “high frequency regimes and size-based dosing may be beneficial in individual cases”. They do recommend 3-4 doses a day for children.
Derek and I use this paper a lot the good work in it. You just have to know if using it for your Dr, the parts to point highlight. If you are in the US and you see a lot of non US researchers listed don’t worry as NADF do approve and reproduce this document for use within America so it is valid there as well.
Jitske Tiemensma, Cornelie D Andela, Ad A Kaptein, Johannes A Romijn, Roos C van der Mast, Nienke R Biermasz, Alberto M Pereira. (2014). Psychological morbidity and impaired quality of life in patients with stable treatment for primary adrenal insufficiency: cross-sectional study and review of the literature
in European Journal of Endocrinology. https://doi.org/10.1530/EJE-14-0023
QoL did not differ between patients on a four-dose regimen and patients on a two-dose regimen, but patients on a four-dose regimen tended to report better QoL .
This one has me a little confused. One sentence which states QoL did not differ, AND reported better QoL?
Frédéric Castinetti, Laurence Guignat, Claire Bouvattier, Dinane Samara-Boustani, Yves Reznik. (2017). Group 4: Replacement therapy for adrenal insufficiency. Annales d’Endocrinologie. 78. 525-534. 10.1016/j.ando.2017.10.007
Quote (invalid cite?)
Hydrocortisone must be delivered in 2 or 3 doses per day, the first and highest dose on waking and the last (in the case of a 3 dose regimen) 4 to 6 hours before going to bed. An international cohort study of 1245 patients with primary adrenal insufficiency (84%) or secondary adrenal insufficiency (16%) underlined that the majority of patients were on a 2 or 3 dose regimen (42% and 32%) while other regimens were less common (one dose, 10%, other regimens, 17%) . Neither of the two most common therapeutic regimens were shown to be better, but the number of comparative studies is quite small [21, 32, 33]
One paper references the original research to justify 2 or 3 doses a day, yet the original document had no mention of 3 doses a day.
Forss M, Batcheller G, Skrtic S, Johannsson G. (2012). Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency – a worldwide patient survey. BMC Endocrine Disorders 2012 12:8. https://doi.org/10.1186/1472-6823-12-8
The results from this survey are in line with a recently published clinical study  which showed that a majority of the patients preferred the four-daily dosing regimen to twice daily when comparing equal doses of hydrocortisone given either twice daily or four times daily. The reasons reported were less fatigue, more alertness during the day, less headache and a feeling that the treatment effect was less varying during the day. The patients had complaints after the study that a four-dose regimen may be difficult to manage in the long run .
This final document quotes things correctly and picked up on the information buried within the report. It looks like they may have actually read the document properly.
My take on this.
If your Dr had only read the original document, he would have no problem if you wanted to move to 4 doses a day, especially when you aren’t increasing your dose, but spreading it out. It was also noted that on 4 doses a day, there was the potential to reduce your overall daily dose. Yet if they read some of the other more recent documents they would say there is no difference, so why change?
Chinese Whispers? Or just misinterpretation? This is just ONE example Derek and I have looked at. There are many more out there. And these changes in wording, or missing wording, can actually have an impact on a persons’ health and quality of life.
Next time a Dr tells you that “according to X research, Y is the case” ask them if that is the original research, or someone’s interpretation right or wrong, of that research. Then check that he has read the original research or just the abstract? The answer to the latter question will probably be no, because in a busy practice, Doctors don’t have time to read all the research. It is up to the well-educated/informed patient to politely assist them by highlighting the significant parts. That is, if the Doctor is happy to work as part of a team, with your best health outcomes in mind.