Cytokine Study in Moderate and Severe ME Patients

[SOC]

Moderate CFS/ME patients were those who were mobile, initially identified as those who were able to regularly leave the house unassisted and who had the potential to maintain a job, even with reduced hours.

Ah, that clears it up! There's a big difference between "able to leave the house" and "able to regularly leave the house unassisted and has the potential to maintain a job". I'd say homebound vs able to work part-time or more is a reasonable severity level difference.

These guys are good. Unlike the entire BPS "research" contingent. I'm thrilled that these Griffith U folks are on our side. They're producing some very impressive work.

 

[Sea]

The CFS/ME patients were classified as either mobile or housebound and these severities were translated to 'moderate' and 'severe' subgroups respectively. Moderate CFS/ME patients were those who were mobile, initially identified as those who were able to regularly leave the house unassisted and who had the potential to maintain a job, even with reduced hours. Severe CFS/ME patients were those who were initially identified as housebound, unable to sustain a job due to the constraints of their symptoms and those who were not able to leave the house unassisted. These severity subgroups were then confirmed through the use of an extensive questionnaire containing routinely used severity scales in CFS/ME: the Fatigue Severity Scale (FSS), Dr Bell's Disability Scale, the FibroFatigue Scale and the Karnofsky Performance Scale (KPS) 9.

Ah, that clears it up! There's a big difference between "able to leave the house" and "able to regularly leave the house unassisted and has the potential to maintain a job". I'd say homebound vs able to work part-time or more is a reasonable severity level difference.

These guys are good. Unlike the entire BPS "research" contingent. I'm thrilled that these Griffith U folks are on our side. They're producing some very impressive work.

Not sure what to say to that. I have answered all their questions honestly and am classified in their study as moderate. I am able to drive to the blood draw. I have zero potential to work at all.

 

[SOC]

Not sure what to say to that. I have answered all their questions honestly and am classified in their study as moderate. I am able to drive to the blood draw. I have zero potential to work at all.

Oh dear. So it wasn't, in fact, as clear as it seemed. Sigh... what a roller coaster I've been on with this paper. I guess the bottom line is that we all, including decent researchers, would like to have objective measures that could be used to judge severity.

I am frequently annoyed by how severity or functionality are judged. At one point I was dragging myself out of bed twice a day for an hour to tutor at home. I was miserable the whole time and crawled back into bed to sleep afterwards. I tutored instead of showering or cooking a meal because I was desperate for the small amount of money it brought in. My specialist's nurse rated me as "mild-able to work" because of that. It's all about the checkboxes on the questionnaires.

Questionnaires asking things like how often you get out of the house can be very misleading, too. When you have to go out to buy groceries or you don't eat, you go out no matter how much pain you're in, how nauseated you are, how dizzy you feel, or how utterly exhausted you are. You can feel like death warmed over the whole time and know you'll be in bed feeling even worse for the rest of the week, but if you're going to eat, you have no choice. Until you get to the point where you pass out any time you stand up, you go out because you have to or starve. So you get rated moderate. Meanwhile, someone who may be very sick, but not a sick as you, but has a spouse or parent or other helper is able to do what you should be doing -- stay in bed. They get rated severe. I've been on both sides of that one, so I know. Severity rates are much, much too subjective. Too much depends on personality traits and personal social circumstances unrelated to the level of illness.

 

[Sea]

@SOC yes yes yes! Exactly my thinking too. I don't think questionnaires will ever truly be able to capture illness severity, but I guess it's all we've got for now. I suppose with large enough numbers there will be enough of a difference in answers to split 2 groups, but there will be a significant overlap in each one

 

[Effi]

Questionnaires asking things like how often you get out of the house can be very misleading

I don't think questionnaires will ever truly be able to capture illness severity

How many of us get the: 'but you did it, so you CAN do it, so you're fine'? And that's why we need a biomarker. But we can't get to the biomarker without the stupid questionaires. *frustration*

 

[Scarecrow]

The investigators measured 26 cytokines and they were looking for differences between three groups - moderate, severe and control (i.e. 3 comparisons; severe-moderate, severe-control and moderate-control).

26 * 3 = 78 comparisons.

The p value for significance was less than 0.05

On average you would expect four significant differences from 78 comparisons purely by chance. The investigators calculated eight significant differences. It's beyond me to calculate how likely or unlikely it is that eight would have happened by chance but I think it's safe to say that although there may have been eight statistically significant differences, an unknown proportion of those differences may or may not be biologically significant. And because of the small samples sizes, some of the other cytokines measured may be biologically significant but still failed the level of statistical significance.

 

[sdmcvicar]

26 * 3 = 78 comparisons.

The p value for significance was less than 0.05

Beat me to it Scarecrow. It's easy to hit p<0.05 if you do 20+ comparisons. The high IFN-gamma in severe patients could be real, the RANTES difference between moderate and severe groups is most likely by chance. For biological significance of cytokine differences, you'd need a database of pooled "normal" values from the controls of many studies, so you could get an idea of their distribution across a population. Then one could determine whether, for example, all of the patients in group "X" have values at the upper/lower ends of the normal range.

Honestly, pretty much all cytokine profiling from human serum is terrible, as there are far too many conditional modifiers contributing to the noise (age, sex, diet, supplements, medication, time of day, co-morbidities, .... ad nauseam), only a few of which can be controlled.

I keep on rolling the possibility of a "good day/bad day" sequential sampling series over in my head, in order to look at what changes occur per patient, and if the trends form subgroups. Incredibly difficult to initiate in practice.

Who knows, maybe some brilliant administrator will figure out how to crowdsource sampling by trained volunteers and patient advocates, using something akin to chain of evidence tracking to ensure sample validity. It's the only way I can think of to capture those times where you go from partially functional to bed-ridden. It'd be a great start to a drug development program for symptom relief, though.

 

[anciendaze]

As long as medical data ignores dynamic variation as random there will be few solid results concerning sub-lethal chronic diseases. Immune response is about as complicated a dynamical system as you are likely to find. You don't get far by treating dynamical systems as something else, (read Aristotle's "Physics" to see how thoroughly his teleological approach muddled the discussion of ordinary physical changes). A great deal has changed since Aristotle's time, but this still hasn't penetrated substantial parts of medicine. I've said this before.

We have variations in response to upright posture and exercise a day previous. We have variations in response to various immune challenges. We have variations in response to a wide range of other conditions. Ignore all these and the disease disappears.