comparison of Q fever fatigue syndrome and CFS

[msf]

http://www.ncbi.nlm.nih.gov/pubmed/26272528

This seems like bad news, but it may just turn out to be good news, if this trial takes place:

http://www.biomedcentral.com/1471-2334/13/157

In their desperation to prove that Q fever fatigue syndrome is all in the patients´ heads, and can be treated effectively with CBT, they may have made a fatal error - including a biomedical treatment as a comparison. The hope has to be that if they (as they should) find that the biomedical approach is more effective in Q fever fatigue syndrome (which they are likely to find out is just Q fever), they will realise that it may be more effective in CFS too.

 

[A.B.]

I'm not sure what to expect. It's possible that Q fever fatigue syndrome isn't due to an infection with coxiella burnetii.

In this case CBT could prove to be a stronger placebo than a sugar pill (especially if patients have already tried doxycycline and don't expect much from it).

 

[msf]

And here is one of the studies mentioned in the trial abstract: http://www.ncbi.nlm.nih.gov/pubmed/16415546

 

[msf]

Possible, but on the available evidence, unlikely.

Good point about the doxy, they would have already had a short course for the Q fever.

 

[Ecoclimber]

I see no comparison between the two diseases to be alarmed about this trial of course in the Netherlands. The epidemiology is different.

Diagnosis and Management of Q Fever — United States, 2013: Recommendations from CDC and the Q Fever Working Group
The largest known reported Q fever outbreak involved approximately 4,000 human cases and occurred during 2007–2010 in the Netherlands. This outbreak was linked to dairy goat farms near densely populated areas and presumably involved human exposure via a windborne route.
Schimmer B, Dijkstra F, Velllema P, et al. Sustained intensive transmission of Q fever in the south of the Netherlands, 2009. Euro Surveill 2009;14:3.

 

[A.B.]

On the other hand a previous study reported improvement in symptoms and decrease in body temperature in Q fever fatigue syndrome patients treated with an antibiotic for 3 months. It was an open label study but the change in temperature and changes in lab test results suggest there was a real improvement.

http://www.ncbi.nlm.nih.gov/pubmed/14964579

 

[jimells]

I see this is yet another study published in the Journal of Psychosomatic Research. I wonder if they have ever published a study that holds up to close scrutiny.

Results: QFS patients were less often female, had a higher BMI, and had less often received treatment for depression before the onset of symptoms

What does BMI have to do with Q fever or "CFS" or ME? Is it some kind of indirect way of blaming patients for their illness?

 

[alkt]

bmi indicates whether a patient is overweight and thus more prone to fatigue at least if they have a sedentry lifestyle . but the b m i has its own problems with validation as a measurement.

 

[Woolie]

What does BMI have to do with Q fever or "CFS" or ME? Is it some kind of indirect way of blaming patients for their illness?

I have seen it used as an indirect way of claiming a psychological cause for an illness. This is an article about psychogenic nonepileptic seziures (NES):

Psychogenic nonepileptic seizures are associated with an increased risk of obesity. Anna Vinter Marquez, , Sarah T. Farias, Michelle Apperson, Suzanne Koopmans, Julie Jorgensen, Alan Shatzel, Taoufik M. Alsaadi
"What is the relationship between NES, psychiatric disorders, and body weight? It is possible that the psychopathological processes underlying NES also contribute to weight problems. "

I am sure if these patients were too thin, the evidence would be used in a similar way - it would suggest anxiety, compulsivness, whatever.

My guess is that these factors are probably socioeconomic. People with Q fever are more likely to live rurally (and probably work manually) than those with MECFS, which come from all walks. Plus, they may have recently given up a very active lifestyle for a sedentary one. People with psychogenic seizures also tend to come from poorer backgrounds than your average patient.

 

[Dolphin]

I couldn't fit the full title in the title box.

Bleijenberg and Knoop could be described as CBT-obsessed psychologists who have published a lot on CFS.

I don't find this paper that exciting but as I've read it, I'll post some comments.

A comparison of patients with Q fever fatigue syndrome and patients with chronic fatigue syndrome with a focus on inflammatory markers and possible fatigue perpetuating cognitions and behaviour.

Keijmel SP1, Saxe J2, van der Meer JW3, Nikolaus S4, Netea MG5, Bleijenberg G6, Bleeker-Rovers CP7, Knoop H8.

J Psychosom Res. 2015 Jul 17. pii: S0022-3999(15)00492-4. doi: 10.1016/j.jpsychores.2015.07.005. [Epub ahead of print]


Abstract

OBJECTIVE:

Comparison of Q fever fatigue syndrome (QFS) and chronic fatigue syndrome (CFS) patients, with a focus on markers of inflammation and fatigue-related cognitive-behavioural variables.

METHODS:

Data from two independent prospective studies on QFS (n=117) and CFS (n=173), respectively, were pooled and analyzed.

RESULTS:

QFS patients were less often female, had a higher BMI, and had less often received treatment for depression before the onset of symptoms.

After controlling for symptom duration and correcting for differences in diagnostic criteria for QFS and CFS with respect to the level of impairment and the presence of additional symptoms, differences in the proportion of females and BMI remained significant.

After correction, QFS patients were also significantly older. In all analyses QFS patients were as fatigued and distressed as CFS patients, but reported less additional symptoms.

QFS patients had stronger somatic attributions, and higher levels of physical activity.

No differences were found with regard to inflammatory markers and in other fatigue-related cognitive-behavioural variables.

The relationship between cognitive-behavioural variables and fatigue, previously established in CFS, could not be confirmed in QFS patients with the exception of the negative relationship between physical activity and fatigue.

CONCLUSION:

Differences and similarities between QFS and CFS patients were found.

Although the relationship between perpetuating factors and fatigue previously established in CFS could not be confirmed in QFS patients, the considerable overlap in fatigue-related cognitive-behavioural variables and the relationship found between physical activity and fatigue may suggest that behavioural interventions could reduce fatigue severity in QFS patients.

Copyright © 2015 Elsevier Inc. All rights reserved.

KEYWORDS:
CFS; Chronic fatigue syndrome; Coxiella burnetii; Q fever; Q fever fatigue syndrome; QFS

PMID: 26272528
[PubMed - as supplied by publisher]

 

[Dolphin]

From Introduction:

This consensus guideline was partly based on the diagnosis and treatment of chronic fatigue syndrome (CFS), as QFS and CFS at least partly overlap in symptoms[11]. In this guideline QFS is defined as a severe fatigue causing significant disabilities in daily life with a duration of at least six months, with a reference to an acute Q fever infection, and not being caused by somatic or psychiatric co-morbidity. In addition, the fatigue should be absent before the acute Q fever infection or significantly increased since the acute Q fever infection. No study has been published so far comparing the clinical characteristics of QFS and CFS patients. One study determined the prevalence of CFS in patients with Q fever compared to a healthy control group. In both groups only one patient met these criteria, although a substantial proportion of the patients with Q fever was chronically fatigued[12].

[12] B Strauss, M Loschau, T Seidel, A Stallmach, A Thomas, Are fatigue symptoms and chronic fatigue syndrome following Q fever infection related to psychosocial variables? J. Psychosom. Res. 72 (2012) 300–304.

One might think from that that not many have CFS after Q fever.
But in this study they found:

After excluding all QFS patients with <4 additional symptoms (n = 14) and a SIP8 total scoreb700 (n = 18), a total of 88/117 (75.2%) QFS patients met the criteria as applied for CFS.

Admittedly these are Q fever fatigue syndrome patients so one can't make a direct comparison. But the introduction says around 1/5 of those with Q fever have QFS:

In addition, around 20% of the known symptomatic acute Q fever patients remain chronically fatigued, and this condition has been named Q fever fatigue syndrome (QFS)

 

[Dolphin]

Can't say I'm a fan of this paper but they do seem to do this right to help ensure that one isn't comparing QFS patients with QFS patients:

The cohort of CFS patients was referred to the Expert Centre for Chronic Fatigue of the Radboudumc for cognitive-behavioural therapy (CBT) between 2008 and 2010. All CFS patients met the Centers for Disease Control and Prevention (CDC) criteria for CFS[26,27], and were functionally impaired, operationalized as scoring≥700 on the SIP8 and reporting≥4 additional symptoms. These criteria were met by 183 patients; however, it was unclear whether Q fever was considered as a possible origin of complaints. Therefore, as QFS is characterized by a sudden onset of fatigue, all CFS patients with a sudden or unknown onset of fatigue after 2007 (the start of the Q fever outbreak) were excluded (n = 10). Both studies were approved by the medical ethical board of the Radboudumc, and all patients gave written informed consent.

 

[Dolphin]

Ferritin and haemochromatosis

Little is known about the aetiology of QFS. It has been hypothesized that persistence of C. burnetii or its antigens could result in inflammation[13]. Ferritin, a cellular storage protein for iron that is important in iron absorption control, orchestrates cellular defence against oxidative stress and inflammation and is an acute phase reactant. It is induced by cytokines such as interleukin (IL)-6 and IL-18, and has been found to be significantly higher in acute Q fever patients than in controls[14]. Furthermore, elevated ferritin concentrations were observed in QFS patients, whereas in medically unexplained fatigue, such inflammatory markers are normally not present. To explore the presence of an inflammatory component in the pathogenesis of QFS, inflammatory markers of QFS patients were compared with those of CFS patients.

Nine out of 117 QFS and none of the CFS patients had an elevated ferritin serum concentration (<190 ng/mL in women and <280 ng/mL in men). The illness haemochromatosis, a condition of accumulation of iron resulting in systemic iron overload and end-organ damage, which could be a possible explanation for both fatigue and elevated ferritin concentrations, was excluded in these QFS patients. After excluding patients with an elevated serum concentration, the serum ferritin concentrations still differed significantly (mean 95 ± 65 vs. 61 ± 45, p = 0.001). However, correcting ferritin concentrations for gender resulted in no significant differences between both men (mean 180 ± 140 vs. 133 ± 55, p = 0.387) and women (mean 62 ± 43 vs. 50 ± 33, p = 0.118;Table 3, Fig. 1).

 

[Dolphin]

They divided physical activity into two types both of which are seen as abnormal i.e. everyone by definition was going to have an abnormal activity pattern:

Physical activity

The level of physical activity was objectified using an actometer, a motion sensing device that registers and quantifies physical activity[38], worn during a period of 12 days around the ankle. A mean activity level was calculated and two activity patterns were discerned; a persistent low-active pattern and a fluctuating active pattern[38].A fluctuating active pattern is characterized by fluctuating bursts of activity followed by a period of inactivity. Low active patients are characterized by consistent low levels of physical activity. The actometer is a reliable and valid instrument for the assessment of physical activity in CFS[38]. Self-reported activity was measured by the SIP8 mobility subscale.

 

[Dolphin]

Cognitive-behavioural variables Results of the actometer showed that QFS patients were physically more active than CFS patients (75 ± 18 vs. 67 ± 19, p = 0.001), with more fluctuating active patients (93% vs. 79%, p = 0.001,Table 4).

67 is around pretty standard for CFS patients in these Dutch studies.

I think a control group had 93 or so by comparison.

 

[Dolphin]

Demographics and premorbid psychiatric treatment

The total group of QFS patients were less often female (52% vs. 75%, p<0.001), had a higher BMI (mean 26 vs. 24, p<0.001), and were less often treated for depression (17% vs. 35%, p = 0.001) (Table 1). The number of patients who had received treatment for other psychiatric disorders than depression did not differ between CFS and QFS.

(they don't seem to control for gender)

But there was no statistical difference in terms of BDI scores >= 4 (26% vs 31%).

They say the following on this which is a little conciliatory/similar

However, there was no difference in current psychological distress or depressive symptoms, indicating that premorbid psychiatric illness in CFS might not be related to current complaints, but only plays a predisposing role, and that current psychological problems are secondary to the chronic fatigue itself and its consequences.

 

[Dolphin]

Perhaps not surprising with people like Bleijenberg and Knoop writing it: they push for CBT for QFS even though the evidence they produced doesn't point in that direction:

The relationship previously found between perpetuating factors and fatigue in CFS could not be confirmed in QFS patients. As expected, the model significantly predicted fatigue in CFS patients, with CIS fatigue being significantly related to both self-efficacy and self-reported physical activity. The relationship between CIS fatigue and focusing on bodily symptoms was nearly significant, which perhaps can be explained by the relatively small sample size. In QFS patients, a significant negative correlation was found between objectively assessed physical activity and CIS fatigue. Also, self-reported limitations in physical activity were related to fatigue severity. Both may suggest that higher activity levels are associated with reduced fatigue. This has also been found in CFS and other conditions like rheumatoid arthritis[49]. The fact that other cognitive-behavioural variables were not related to fatigue in QFS may indicate that the processes involved in the perpetuation of fatigue in QFS are different from the processes related to fatigue in CFS. On the other hand, the small sample size might be an alternative explanation of badfit of the model of perpetuating cognitions and behaviour. As the pathophysiological mechanism of QFS still needs to be clarified, treatment based on aetiological insight is hampered. However, CBT aimed at fatigue-related beliefs and behaviour, has already proved to be effective in other forms of chronic fatigue[50,51]. CBT is a complex intervention in which several fatigue-related beliefs and therefore several (potential) perpetuating factors are influenced. Because factors related to cognition and behaviour overlap substantially between QFS and CFS patients, and gradually increasing physical activity is a key component of CBT, QFS patients might benefit from treatment directed at these factors. Furthermore, the inverse relation between physical activity and fatigue severity suggests that aside from CBT, graded exercise therapy might also be beneficial[52].

 

[alex3619]

What does BMI have to do with Q fever or "CFS" or ME? Is it some kind of indirect way of blaming patients for their illness?

Its not really a blame thing at this point, I think. Its more they are fishing for associations. They will then create a story that uses those associations in its explanation ... that is the next step.

We already know that some biomedical treatments give results much better than CBT/GET, yet they are not claimed as cures. Antivirals do this for subsets with measurable viral titres. Ampligen does this in responders. Ditto Rituximab, though this particular one might turn out to be a cure for a subset. This does not stop the march of babble. They know this.

One thing to watch out for are inappropriate comparison arms in a trial. They did this in PACE with adaptive pacing, a therapy nobody has used except for them in that one trial. It relies on the confusion with regular pacing to have an impact on people reading the paper or articles about the paper.

 

[jimm]

kejimel conveniently cherry picks evidence to back up his views, check out his preliminary data it using now outdated data on CBT used in fatigue illness and conveniently ignoring the body of work from the Q fever research group done by the now sadly deceased Prof Marmion. Marmion et al had already done lots of preliminary studies finding underlying problems
one such paper is here:
http://qjmed.oxfordjournals.org/content/103/11/847