On 2013 Oct 24, Tom Kindlon commented:

(contd.)

5 Van Houdenhove B, Onghena P, Neerinckx E, Hellin J: Does high "action-proneness" make people more vulnerable to chronic fatigue syndrome? A controlled psychometric study. J Psychosom Res 1995, 39:633-40.

6 MacDonald KL, Osterholm MT, LeDell KH, White KE, Schenck CH, Chao CC, Persing DH, Johnson RC, Barker JM, Peterson PK: A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome. Am J Med 1996, 100:548-54.

7 Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006 Sep 16;333(7568):575. Epub 2006 Sep 1.

8 White PD. "Overview of post-viral fatigue: CFS or what?". International Symposium on Viruses in CFS & Post-viral Fatigue - A satellite meeting of the 6th International Conference on HHV-6 & 7 in Baltimore (2008). http://scivee.tv/node/6895

On 2013 Oct 24, Tom Kindlon commented:

This study did not have information on the physical fitness of the patients before becoming ill. The authors suggest that the patients may have been more inactive before becoming ill. However the evidence is stacking up that this is not generally the case and indeed that patients who develop CFS may, on average, be a little more active or fitter than the general population.

A recent prospective population study¹ on the illness 4779 people from birth for the first 53 years of their lives. At age 53, 34 reported a diagnosis of CFS. Amongst other things, it found that "increased levels of exercise throughout childhood and early adult life and a lower body mass index were associated with an increased risk of later CFS." As it was a prospective study, there was no issue of recall bias. It also wasn't simply self-rated, as it also involved reporting by a teacher at age 13. Also they used the subject's BMI index - patients who went on to have CFS at age 53 had a (statistically significant) lower BMI than those who did not go on to develop CFS at ages 36 and 43 (before they had CFS). The authors say this "this may provide some indirect but objective evidence of increased levels of activity at these ages, especially as this difference had resolved by the age of 53 years" (when the people with CFS were no longer more active).

A study involving the corresponding author² found that, compared to healthy controls, patients with chronic, unexplained fatigue rated themselves as more active before their illness. In this study, they also reported that "the high levels of physical activity reported by patients have been corroborated by their spouses, partners, or parents" (in another study³ ). At least three other retrospective studies reporting that CFS patients perceived themselves as more active before their illness began than healthy controls.^4-6

In 2006, a CDC-funded prospective cohort study following patients from the time of acute infection with Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis) was published.⁷ 253 patients were enrolled and followed at regular intervals over 12 months by self report, structured interview, and clinical assessment. It found that prolonged illness was "characterised by disabling fatigue, musculoskeletal pain, neurocognitive difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue syndrome phenotype was stereotyped and occurred at a similar incidence after each infection. The syndrome was predicted largely by the severity of the acute illness".

Given only a correlation was found and that no intervention was tested in the current study, along with the preceeding information, I believe the authors' suggestion that "prevention of postinfectious fatigue by an early return to physical activity may be possible" is highly speculative (this claim was recently re-iterated by the corresponding author at a conference on CFS when presenting data from this study⁸ ).

1 Harvey SB, Wadsworth M, Wessely S, Hotopf M: Etiology of Chronic Fatigue Syndrome: Testing Popular Hypotheses Using a National Birth Cohort Study. Psychosom Med. 2008 Mar 31

2 Smith WR, White PD, Buchwald D. A case control study of premorbid and currently reported physical activity levels in chronic fatigue syndrome. BMC Psychiatry. 2006 Nov 13;6:53.

3 Van Houdenhove B, Neerinckx E, Onghena P, Lysens R, Vertommnen H: Premorbid "overactive" lifestyle in chronic fatigue syndrome and fibromyalgia: an etiological relationship or proof of good citizenship? J Psychosom Res 2001, 51:571-6.

4 Riley MS, O'Brien CJ, McCluskey DR, Bell NP, Nicholls DP: Aerobic work capacity in patients with chronic fatigue syndrome. BMJ 1990, 301:953-6.

(contd.)

On 2013 Oct 24, Tom Kindlon commented:

Test of "physical fitness" used seems far from ideal for this cohort

The authors state in the abstract that "an empirically defined fatigue syndrome 6 months after onset" was associated with "lower physical fitness". "Lower physical fitness" is a term that is regularly used throughout this paper. However, has it been properly defined especially for this post-viral group? And what can be inferred from the correlation?

Firstly it should be remembered that the study used two measures of physical fitness from the exercise test: What they called "exercise power" was calculated as "the number of stairs climbed, multiplied by the height of each stair, and the participant's weight." A measure of "physical fitness" was calculated by "dividing the number of stairs climbed by the exercise pulse-rate difference". It seems rather arbitrary to ignore the first when mentioning "physical fitness" in the study and abstract.

It also needs to be pointed out that this is an unusual way to define fitness and may not be suitable for people with CFS and related post-viral syndromes. For example, Postural Orthostatic Tachycardia Syndrome (POTS) has found to be more common in this sort of population than in other populations. A recent study¹ using a standing test of 2 minutes duration found a prevalence rate of POTS of 27% compared to 9% in a control group (p=0.006). A previous case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome had found a significant higher rate (p=0.01) POTS without hypotension in the patients with CFS compared to the controls (but no difference of the rate of POTS with hypotension).² Other researchers in the field feel POTS is an important issue in the area of CFS, ME and related syndromes.³ So in the light of these findings it seems questionable that this is a suitable test to test for "physical fitness".

It should also be remembered that it is not easy to test somebody's fitness when they have an infection - a "fit" person such as (say) a sportsperson can seem unfit if one tests them when they are ill but within a short period of time could be playing sport competitively and generally showing better physical fitness than could be explained by any physical training in the interim.

References:

[1] Hoad A, Spickett G, Elliott J, Newton J. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome. QJM. 2008 Sep 19.

[2] Galland BC, Jackson PM, Sayers RM, Taylor BJ. A matched case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome. Pediatr Res. 2008 Feb;63(2):196-202.

[3] Spence V & Stewart J (2004) Standing up for ME, Biologist 51(2): 65-70.

On 2013 Oct 24, Tom Kindlon commented:

Test of "physical fitness" used seems far from ideal for this cohort

The authors state in the abstract that "an empirically defined fatigue syndrome 6 months after onset" was associated with "lower physical fitness". "Lower physical fitness" is a term that is regularly used throughout this paper. However, has it been properly defined especially for this post-viral group? And what can be inferred from the correlation?

Firstly it should be remembered that the study used two measures of physical fitness from the exercise test: What they called "exercise power" was calculated as "the number of stairs climbed, multiplied by the height of each stair, and the participant's weight." A measure of "physical fitness" was calculated by "dividing the number of stairs climbed by the exercise pulse-rate difference". It seems rather arbitrary to ignore the first when mentioning "physical fitness" in the study and abstract.

It also needs to be pointed out that this is an unusual way to define fitness and may not be suitable for people with CFS and related post-viral syndromes. For example, Postural Orthostatic Tachycardia Syndrome (POTS) has found to be more common in this sort of population than in other populations. A recent study¹ using a standing test of 2 minutes duration found a prevalence rate of POTS of 27% compared to 9% in a control group (p=0.006). A previous case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome had found a significant higher rate (p=0.01) POTS without hypotension in the patients with CFS compared to the controls (but no difference of the rate of POTS with hypotension).² Other researchers in the field feel POTS is an important issue in the area of CFS, ME and related syndromes.³ So in the light of these findings it seems questionable that this is a suitable test to test for "physical fitness".

It should also be remembered that it is not easy to test somebody's fitness when they have an infection - a "fit" person such as (say) a sportsperson can seem unfit if one tests them when they are ill but within a short period of time could be playing sport competitively and generally showing better physical fitness than could be explained by any physical training in the interim.

References:

[1] Hoad A, Spickett G, Elliott J, Newton J. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome. QJM. 2008 Sep 19.

[2] Galland BC, Jackson PM, Sayers RM, Taylor BJ. A matched case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome. Pediatr Res. 2008 Feb;63(2):196-202.

[3] Spence V & Stewart J (2004) Standing up for ME, Biologist 51(2): 65-70.

On 2013 Oct 24, Tom Kindlon commented:

This study did not have information on the physical fitness of the patients before becoming ill. The authors suggest that the patients may have been more inactive before becoming ill. However the evidence is stacking up that this is not generally the case and indeed that patients who develop CFS may, on average, be a little more active or fitter than the general population.

A recent prospective population study¹ on the illness 4779 people from birth for the first 53 years of their lives. At age 53, 34 reported a diagnosis of CFS. Amongst other things, it found that "increased levels of exercise throughout childhood and early adult life and a lower body mass index were associated with an increased risk of later CFS." As it was a prospective study, there was no issue of recall bias. It also wasn't simply self-rated, as it also involved reporting by a teacher at age 13. Also they used the subject's BMI index - patients who went on to have CFS at age 53 had a (statistically significant) lower BMI than those who did not go on to develop CFS at ages 36 and 43 (before they had CFS). The authors say this "this may provide some indirect but objective evidence of increased levels of activity at these ages, especially as this difference had resolved by the age of 53 years" (when the people with CFS were no longer more active).

A study involving the corresponding author² found that, compared to healthy controls, patients with chronic, unexplained fatigue rated themselves as more active before their illness. In this study, they also reported that "the high levels of physical activity reported by patients have been corroborated by their spouses, partners, or parents" (in another study³ ). At least three other retrospective studies reporting that CFS patients perceived themselves as more active before their illness began than healthy controls.^4-6

In 2006, a CDC-funded prospective cohort study following patients from the time of acute infection with Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis) was published.⁷ 253 patients were enrolled and followed at regular intervals over 12 months by self report, structured interview, and clinical assessment. It found that prolonged illness was "characterised by disabling fatigue, musculoskeletal pain, neurocognitive difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue syndrome phenotype was stereotyped and occurred at a similar incidence after each infection. The syndrome was predicted largely by the severity of the acute illness".

Given only a correlation was found and that no intervention was tested in the current study, along with the preceeding information, I believe the authors' suggestion that "prevention of postinfectious fatigue by an early return to physical activity may be possible" is highly speculative (this claim was recently re-iterated by the corresponding author at a conference on CFS when presenting data from this study⁸ ).

1 Harvey SB, Wadsworth M, Wessely S, Hotopf M: Etiology of Chronic Fatigue Syndrome: Testing Popular Hypotheses Using a National Birth Cohort Study. Psychosom Med. 2008 Mar 31

2 Smith WR, White PD, Buchwald D. A case control study of premorbid and currently reported physical activity levels in chronic fatigue syndrome. BMC Psychiatry. 2006 Nov 13;6:53.

3 Van Houdenhove B, Neerinckx E, Onghena P, Lysens R, Vertommnen H: Premorbid "overactive" lifestyle in chronic fatigue syndrome and fibromyalgia: an etiological relationship or proof of good citizenship? J Psychosom Res 2001, 51:571-6.

4 Riley MS, O'Brien CJ, McCluskey DR, Bell NP, Nicholls DP: Aerobic work capacity in patients with chronic fatigue syndrome. BMJ 1990, 301:953-6.

(contd.)