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Curious to read what you wrote in the letter @Jonathan Edwards

Do I understand their view correctly that Rituximab might work if applied long enough so that new plasma cells cannot be formed. If it is applied too briefly like in the phase III trial, the B-cells are targeted but the long-lived plasma cells might still be producing antibodies?

It also seems that they are p-hacking the database for all possible connections and then publish these in separate papers, which can be quite misleading.

Yes quite disappointing. This paper goes against all basic statistical principles. Hard to take the authors seriously after this.

I meant the true scientists, the people who really want to figure things out, discover truth etc, rather than academics making a career. The people who will win future Nobel prizes. I suspect that they simply ignore most of what gets published.

Seems like the sample size increased from 16 HC, 15 ME/CFS, and 15 LC to 25, 27 and 20 respectively.

It still find it weird that standards are so low in (medical) science. So how do real scientists deal with this: do they simply ignore 90% of the literature and only focus on results from labs/teams they know and trust?

The effects appear to be driven by sex and contraception use which were not properly matched between ME/CFS patients and healthy controls.

If we could get hold of the data, we could do this analysis ourselves and see if the result can be explained by sex and contraception. The paper states:

There was a massive sex difference between groups: 47% of controls were males compared to only 17% in the Canadian ME cohort. So what does frequency-matching mean in this context? Pretty much all of their measures were affected by sex, suggesting that the difference between ME and HC could be...

The emails are interesting. Garner and Flottorp appear very assertive and activitst-like. They try to get themselves on the committee and are very dismissive if guideline text doesn't mention psychological treatments and recovery, often suggesting that this will cause harm. They use COFFI and...

From the paper:

Don't quite understand why figure 32 (below) shows decreases in % change in zeta-potential in ME/CFS patients while on Figure 21 that Murph posted above, it seems that zeta-potential increased after 1.5 hours in the ME/CFS patients. Figure 32| Normalised ζ-potential data for PBMCs incubated...

Another questionnaire, The Revised Fibromyalgia Impact Questionnaire (FIQR, range 0-100), did show a significant difference between groups. The RLZ has a score of 62.3 (57.32 to 67.28) compared to 70.70 (64.90 to 76.50) in the control group, with lower scores being better. The p-value of the...

Using the CI of the means, I've tried to calculate the mean difference and its confidence interval and p-value. I got: 0.54 (-0.42, 1.50), p-value = 0.26. So it seems like the difference was not statistically significant and might be due to random variation.

The primary outcome was the Brief Pain Inventory Short Form (BPI-SF). The results show 41 participants analyzed in both groups with the following means: Placebo: 6.30 (5.59 to 7.01) RLZ: 5.76 (5.11 to 6.41)

This was a bit surprising: One might suspect that patients try more medications early after getting a diagnosis but then reduce them because most don't work. Perhaps those patients fall in the 1/3 group that doesn't take medication for ME/CFS symptoms anymore.

Not sure what you mean but if there are multiple trials on the same intervention/outcome then they are pooled using meta-analysis. They are added together so that there is one estimate and then the GRADE approach is only applied after that on that pooled estimate. If these are estimates of the...

I don't see an issue with the Vortioxetine rating but other estimates (from non-behavioral interventions such as hyperbaric oxygen or transcranial stimulation) were downgraded with two levels for imprecision. There seems to be an inconsistency where non-behavioral interventions were downgraded...

The conclusion would be: 'We are uncertain that treatment X improves symptoms' and 'Treatment Y probably has little or no effect on symptoms.' Agree. GRADE allows it (probably because it was the standard in the past) but it makes little or no sense. As a reviewer you want to determine if there...