Long Term Follow up of Young People With Chronic Fatigue Syndrome Attending a Pediatric Outpatient Service, 2019, Rowe

I think normalisation is a major consideration; I think it is part of how humans adapt to prevailing conditions. After some time it becomes hard to remember what the original normality was.

 

The last day of a flu feels amazing compared to the worst of it, but it's still pretty bad and doesn't mean much until you can get back to normal activity levels. Most of us just adjust to a normal that a healthy person would be horrified to imagine having to suffer when we are in remission, something a questionnaire is simply unable to differentiate.

Until there is a way to get an absolute measure, rather than a relative one, any claim of recovery needs to take this into account. It would be better described as remission, but that won't happen until the psychosocial zombie is dead and gone, as they obsess over the belief that pretending that it's harmless is key to spiritual enlightenment, I'm sorry, I meant "achieving recovery".

Genuine researchers would really do well to adopt the concept of remission, as opposed to recovery, however. No matter how many angry letters they get from the ideologues. Recovery implies being cured, that is how people understand the word and physicians do the same.

 

I agree.

It is hard to have an "absolute measure" of recovery though, as there is no true basis for a clear demarcation

 

I think it is dangerous to talk about recovery. Forums have lots of people who thought they were recovered, adopted an active lifestyle then became much worse than they had been before.

If you have well controlled diabetes you can lead a normal life. If you have your thyroid destroyed by radiation you need thyroxine for the rest of your life but you cam lead a fairly normal life.

If you have ever had ME (as opposed to a post viral syndrome) you need to be aware of it for the rest of your life. Everyone else in the office may be training for a marathon but you should not feel pressured. What we can achieve is good control. It might lead to a life with little restriction or you may need to factor in more rest than normal but we are not cured.

It sounds as if people in this survey and in Dr Bell's have managed this sort of coping and that is great and may be achievable by many more people if ME is managed properly from the start.

 

I don't see it either. At one point the paper claims:

But that seems unlikely since they followed up from 1991 (The Fukuda criteria weren't published three years later). Also the paper claims that the mean duration of illness prior to being diagnosed ranges from 4 months to 7 years. But the Fukuda-criteria require 6 months of symptoms before the diagnosis can be made - so how can patients received a Fukuda-diagnosis if they were only ill for 4 months...

I don't know either. The fact that they give functional scores of those who have and have not recovered and that these show substantial overlap, suggests that this did not form the basis of reporting recovery.

There's some supplementary material available for this study (https://www.frontiersin.org/articles/10.3389/fped.2019.00021/full#supplementary-material), including a questionnaire that was used at follow-up and that asks:

So I think that's where the recovery figure comes from. This doesn't seem reliable to me. If you look at the functional scores of patients who reported recovery, about 30% scores an 8 or lower. A score of 8 corresponds with "Has periods with some symptoms and rarely feels ‘refreshed’" and "Needs occasional day to ‘recover’. Even a score of 9 corresponds to "Gets more tired than would expect" and "Manages well but needs to ‘pace". To me, it seems that these patients improved a lot and are quite functional (most were able to study or work), but that doesn't mean they were recovered. They seem to have lingering symptoms and less stamina.

 

Sometimes I wonder how things would have turned out if there was none of this wishful optimism.

So... no hope that some trivial thing like B vitamins or exercise would cure us.
No illusions that patients can figure this out on their own.
No illusions that it will just go away on its own, or isn't serious, or can be controlled through willpower and so on.

This would be a very negative view for some, but it could be the approach that yields real results faster than anything else. Nobody would waste time but instead begin right away to set up a research program and ask politicians for funding.

 

Interestingly on a parent's group someone asked if kids had had growth issues ( growth pains, skin stretch marks, hip/ knee/ feet - usually when tendons/ bones grow at different rates). A large number had

Puberty itself could be a stressor as the hormone factory ramps up a gear or two and emotions start that rollercoaster ride.

If you have genetic glitches for cofactors or processes that are expressed during this time, that may add a vulnerability too.

 

Commentary ​

[Relatively good] long term outcomes for young people with ME/CFS
Katherine S Rowe, 2019

apologies that I haven't taken part in this thread - awful migrainesmeans screens are deadly (I read the paper in print, dictated wtih Dragon and a friend cleaned it up for me).​

This is a large study providing solid evidence for good outcomes, including recovery, for young people with ME/CFS. Although the figure of 68% for recovery at 10 years may overstate the situation, the outcomes are much better than for adults.

About the study

The study covers 784 young people with ME/CFS treated at a specialist outpatient clinic in Melbourne, Australia.

The average age at onset was 14.6 and at follow-up it was 22.5 years. Ideally, each patient would have been followed up for the same length of time, but this was a retrospective study and all cases were followed up between January 2008 and June 2011, and the average follow-up time was eight years but with a wide range — from 1 to 21 years. This makes interpretation of the findings a bit more complicated.

Impressively, the study managed to follow up 82% of patients (641).

The study used fairly strict diagnostic criteria. Most patients were diagnosed with Fukuda with the additional requirement for PEM, unrefreshing sleep and cognitive difficulties. Some of the very early cases were diagnosed using the Holmes criteria, which are generally seen as stricter them Fukuda.

75% of patients were female and 80% of all patients had a definite onset following an infection, most commonly EBV. This might be an unusually high proportion of sudden-onset illness for young people.


Recovery rates

Overall, 46% of patients reported that they had recovered. However, recovery rates by total length of follow up is more revealing:

• up to 5 years: 30%
  
  
• 5 to 10 years: 54%
  
  
• 10 years or more: 68%
  

The figures indicate that recovery rates steadily increase over time. Patients followed up for more than 5 years had eventual recovery rates of 54% to 68%, but 29% of this group said they recovered within the first 5 years.

These recovery rates and generally good outcomes were supported by the proportion of all patients reporting working or studying full- or part-time:

• 63% full-time
  
  
• 24% part-time, more than half of the time
  
  
• 8% part-time, less than half of the time
  
  
• 5% not working or studying at all
  

66% had continued education after school, of whom 20% had worked or were working part-time while studying.

29% received disability support. The majority of these were studying (the government had a special scheme to help people with chronic illnesses continue their education) or working part-time.


Looking more closely at "recovery"

The study appears to have defined recovery as those people who answer the question "Duration of illness if recovered" (though another question asked, "Are you no longer suffering from CFS?").

Patients also scored themselves between 1 and 10 on an ME/CFS global functional scale created by the clinical team, where each score is defined by five factors: work/study, social life, recovery from physical exertion, stamina and symptoms (I like the scale).

A score of 10/10 means that the patient is working/studying full-time, able to have an active social life and has no problems at all. A score of 9/10 is similar but stamina is qualified by "more tired than would expect" and "manage well but need to pace".

However, a score of 8/10 is qualified by "needs occasional day to recover" and "with some symptoms and rarely feel refreshed".

While 10/10 sounds like a full recovery to me, and 9/10 might be described as a "good recovery", 8/10 sounds more like a good situation but not really "recovered". The average score for recovered patients was 9 , which breaks down as:

• 34% 10
  
  
• 36% 9
  
  
• 20% 8
  
  
• 10% 7 or less
  

See the graph



Figures 5 & 6 from the paper, with the horizontal axes aligned for clarity.

Patients reported that the functional score wasn't simply due to ME/CFS; some had illnesses they differentiated from ME/CFS, including depression and IBS, and others reported that they had small children and were sleep-deprived. The paper doesn’t say what proportion of scores below 9 could be explained by these non-ME/CFS reasons.

On the other hand, patients also commented that they weren't quite sure what normal function was any more, and parents "often scored [young people's functioning] one point lower", all of which suggests that some functional scores, and "recovery" rates, might not be quite as good as reported.

So there is some uncertainty about the true rate of recovery in this study, and, overall, it seems likely the true rate is below the recorded one. Is there a way to get a feel for how much lower? Perhaps only counting as recovered patients who also scored themselves 9 or 10 would give an estimate of the lower bound for recovery rates. Does this sound reasonable? The numbers below are for patients who say they recovered and scored themselves 9 or 10 on the mecfs functional scale (numbers in brackets are the full recovery rates, regardless of functional score).

• 21% (30%) up to 5 years follow-up
  
  
• 38% (54%) 5 to 10 years
  
  
• 48% (68%) 10 years and more
  

• whole group: 33% (46%)
  

Overlap between "recovered" and "not recovered"

As the paper points out, there was considerable overlap between the functional scores of those who reported that they were recovered, and those who did not report recovery (see the figure). That overlap reinforces the idea that there is some "fuzziness" around the concept of recovery. However, while 70% of patients reporting recovery scored themselves at 9 or 10, only 1% of non-recovered patients reported such high scores.

The most common score amongst those not reporting recovery was 6/10, which corresponds to working or studying part-time, with limited social life, mild physical activity such as walking, continuous symptoms and the need to pace carefully.

Around 10% of all patients had a functional score of 4 or less. 4 equates to a “major impact on life”.

The relatively good outcomes in this study reflect those of an earlier and smaller study by David Bell. This followed 35 patients for an average of 13 years. 37% of them reported recovery while 43% reported that that they were not completely recovered, but felt pretty well. 10% remained very ill.

Note that most patients in this earlier study had a gradual onset, unlike the sudden onset of most patients in the new study.



Other findings

Although the clinic had baseline data for around 60% of patients, no baseline factors, including depression, predicted the eventual outcome of the illness.

My comments here have focused on overall outcomes. However, the clinic describes treatment for young people that is multidisciplinary, pragmatic, flexible and patient-centred. It seems plausible that this approach is contributing to the good outcomes, but there was no control group for comparison.

Overall, this study strikes me as an important one. It is very large, used fairly strict diagnostic criteria, and had a very high follow-up rate (particularly considering the young and mobile age-group studied). The recovery figures were backed up by high functional scores, and the overall good outcomes were supported by the high levels of people working or studying full-time and also managing a social life alongside that.

There is some uncertainty over the actual rate of recovery but it could be as high as two-thirds (68%) - at least for those with a post-infectious onset. Many of the remainder have reasonable levels of functioning, able to work part time. However a minority of around 10% remain severely affected.

We desperately need similar large and well-done studies of long-term outcomes for adults with ME/CFS.

*Check the study paper supplementary materials for details of the questionnaires used.

 

I haven’t followed the thread except to read Simon’s post but just to add that some of the recoveries might be better described as remissions if people later relapse.

 

Thank you for providing a bit more info on this @Simon M . It is much appreciated. Parents' problems are that children and adolescents " recover", the most postulated recovery period being two years.

Our paediatrician did impart that not all recover but "most do". The fact that most don't, and many of those who do later relapse, should therefore form part of medical and clinical information.

Perhaps the Rowe and Bell studies could be used to better inform both children and parents re what to expect re " recovery" and timescales , and perhaps charities can update their advice. tagging @Action for M.E. as they have yet to address the 2 year period in their info to professionals. As their website info is being revised, this would provide a good opportunity to revisit this particular section, with an interpretation such as Simon's and not simply quoting the top line.
Given other threads re FII, this needs some urgency.

 

Thanks @Simon M

 

The Brown, Bell and Jason paper from 2012 is important in relation to the new study as it aims to see if patients who said they were recovered really were or not. They did this by checking if symptoms and function scores were consistent with recovery, and found "that over time many individuals will not maintain a CFS diagnosis but will not return to their premorbid level of functioning."

This is a very significant finding. However, there is some ambiguity in the findings as the study asked participants if they currently had a diagnosis of ME/CFS. As the paper notes, patients may not have had access to medical healthcare to get the diagnosis, or there may have been uncertainty over the diagnosis [patients need a certain level of disability and number of symptoms to meet diagnostic criteria]. So some patients could have been (and were) better but not fully recovered.

A quick recap: in 1985, there was a cluster of ME/CFS cases centred on Lyndonville in rural New York State, including 60 children or adolescents. Bell and colleagues published a 13-year follow-up study on 35 cases (58% of the 60) in 2001. This 2012 paper was a 25-year follow-up on 25 (42%) of these cases.

The cases were split by asking patients to self-report whether they currently had a diagnosis of CFS/ME. The five patients who said they did were classed as being in the "Persist" group. The 20 that did not have a current diagnosis were classed as being in the "Remit" group. Unfortunately, this 2012 study did not use the 13-year follow-up categories of:

• "I have recovered completely and feel entirely well" and
• "I have never recovered completely but feel pretty well".

I think that's the critical missing information because we have a mix of people who say they are fully well and those who say they are not fully recovered. The latter group would not be expected to match healthy people on functioning and symptoms. So what we have is data from two different types of person in one group - the Remit group.

So here is the key data for functioning and symptoms.

Results are in the order: Persist, Remit, Control.

Functioning (work, physical and social)

Full-time employment rate: 20%, 75%, 90%

SF-36 (median scores):

• Physical functioning: 30, 87.5, 100
• Social functioning: 42, 87, 100
• General health: 22, 65, 88

In all these cases, the Remit group functioning is much closer to the healthy controls then to the Persist group that still reported an ME/CFS diagnosis.


Symptoms

Fatigue (0-160): 106, 26, 2.5 (Fatigue Impact Scale)

Other symptoms, examples (visual analogue scale, 0-10):

• PEM: 7, 4, 0.5
• Sleep disturbances: 9, 4.5, 0
• Memory/concentration: 6, 3, 1
• Muscle pain: 7, 3, 0

Total symptom score (0-90): 64, 30, 5

Although fatigue is much lower in the Remit group, the other symptoms are roughly halfway between those in the Persist and the Control group.

So the problem in interpreting this is that we don't know what proportion of these "better" patients describe themselves as fully recovered and we don't know their separate scores. It is certainly possible that, say, 40% of the patients are recovered and they have credible recovery scores. Looking at the scores shown above, there could be a group functioning very well indeed, though they are likely to have low levels of symptoms.

Note that while fatigue levels were statistically significantly different between Persist and Remit patients, as were the total symptom scores, none of their other individual symptom scores were significantly different.

Stats-geek alert! This finding of non-significance is tricky to interpret. The Persist group is tiny (five patients) and is there is a lot of variation in the Remit group (and only 20 patients). These issues make it hard for results to achieve statistical significance. The high level of variation in the Remit group could indicate that it contains two quite different types of patient: those who have fully recovered and have very low levels of symptoms and those who still have substantial problems with symptoms. We don't know. ​

One other question is whether or not the findings from this study generalise to most patients. The study is small and of patients froma cluster so may be unrepresentative. The follow-up rate is under 50%; it is quite possible that young people who recovered moved away and lost touch, as young people do, so the remaining patients might be biased towards those who did less well - we simply don't know, but a low follow-up rate always carries substantial risk of bias of some form.

By contrast, the Australian clinic study is very large, has a wide range of patients, and achieved a high follow-up rate of 82%. However, the majority of its cases were post-infectious, and so the recovery figures from the study might not apply to gradual-onset cases.

What would have been very helpful would have been similar approach to the Brown study for the large new Australian clinic study, to further probe the health of those who said they were recovered. Unfortunately, the Aussie data were collected in 2010/11 so I am not sure that would be feasible.

The Brown study is important. It looked more carefully at what happens when patients recover, partially or fully and the results cast some doubt on the degree to which patients really recover. But there is some ambiguity, both because there were not separate results for fully vs partially recovered patients, and because it is not clear how well its findings would hold up in other patient populations.

What patients and carers need is clear information on the chances of full (or even partial) recovery. Both the Australian and the Brown study throw some light on that but we don't yet have solid answers on true level of recovery rates.

 

Unfortunately, my migraines are getting ever worse and I probably won't be able to return to this thread after this post.

Yes, the distinction between remission and recovery is very important. In this case, though, I think most of the results will cover recovery. If you look at the group with more than 10 years of follow-up they have the highest recovery rate (68%) and will have had plenty of time to realise what was remission as opposed to lasting recovery. The group most likely to have confused the two were those followed up for less than five years (30% recovery). Interestingly, those who were followed up for more than 10 years reported recovery rate of 29% within the first five years.

On top of that, the high rates of studying/working full time, particularly working, are likely to indicate recovery over remission.

Thanks. There's lot there that I will try to unpick.


I would love to know the evidence for the claim that "most children and adolescents recover, typically in two years" advice. Parents and young people need advice based on the best available evidence.


On the face of it, the Australian study says that most do recover (and the average time to recovery is five years, though there is a lot of variation). As I said, I suspect the true rate is lower than this but it still be substantial, quite possibly over 50%.


The Bell (Brown) study casts some doubt on the true rate of recovery but doesn't give a clear cut answer for the reasons I outlined outlined in my previous post. We need more research here.


Also, the high recovery rates for those followed up for more than 10 years doesn't support the idea of most people later relapsing.


One final point: certainly for post infectious cases, recovery rates are much better earlier on. So if the diagnosis is given three months after the original infection there may be a very high rate of recovery and a likely short illness. If you haven't been diagnosed for over two years, the prospects would be considerably worse. I hope that clinical advice would take that into account.

Anyway, maybe somene could direct Action for ME to this thread, so they can see the views and research.

 

Thanks for delving into this. Figures are not my strong point, although, thanks to this forum, I am improving.
It's AfME who quote the two year period in their GP info, probably based on EC research where the 80% recovery in 2 years seems to be an oft quoted soundbite. ( as well as 80% recovering naturally - figures seem to be a weak point and in tandem with the conflation with chronic fatigue this serves no one well)
This is particularly important as FII implications can swing in if your child has not " recovered" within the timescale.

It would be helpful for studies if there were clear agreed definitions of what constitutes recovery, remission etc, together with less leading questions - I think that there is a tendency to " acclimatise" to a new normal - this is alluded to in the international paediatric primer too, so using scores on function etc is important and helps to differentiate a bit more clearly. If recovery was a generally defined criteria then studies would be more directly comparable.

Given that recovery seems to be a set of goalposts that are continually moving, a consensus as to what it actually is and how to measure it seems a key aspect that should be buttoned down sooner rather than later.

thank you again @Simon M . I hope you get some respite from migraines soon.