**4. Discussion**

#### *4.1. Prior Teaching, Experience and Confidence Level*

A minority of respondents had had formal teaching on ME, though most had had some experience of ME patients. Despite this, few knew how to diagnose ME, and nearly all lacked confidence in dealing with ME patients.

The majority of participants (82%) believed that ME is at least in part psychological, and it is a matter of concern that 91% of respondents who had had teaching or experience of ME thought this, when only 50% of those without such experience thought so. This places a considerable question mark over the content of such teaching and experience, since those who had received it more frequently expressed erroneous views about ME than those who had not.

It is also of particular note that doctors who expressed confidence in diagnosing ME or in dealing with ME patients were universally wrong in their understanding of the nature of ME, its diagnostic criteria, and its treatment. All six of them (100%) thought ME was at least in part psychological/psychosomatic, failed to select the right combination of diagnostic features, and thought ME could be treated with extremely hazardous graded exercise therapy.

#### *4.2. Making the Diagnosis*

Myalgic encephalomyelitis is mainly diagnosed with a careful and thorough history. Physical examination and appropriate investigations are performed to rule out other pathology, but the diagnosis is made on the presence of post exertional malaise (PEM) and other symptoms, as identified in the history. While certain physical signs can be present, such as orthostatic changes in blood pressure or heart rate, pallor, and a multitude of neurological signs including tremor, incoordination, ataxia, photophobia, muscle weakness, fatiguability, fasciculations and myopathic facies, they are, like everything else in ME, variable and fluctuating.

On diagnostic criteria, 38 participants (86.3%; 95% confidence interval: 73.3–93.6%) believed six months of fatigue is necessary for diagnosis. This is contrary to the MYAL-GIC ENCEPHALOMYELITIS—Adult and Paediatric: International Consensus Primer for Medical Practitioners, which allows one to make a positive diagnosis based on symptom constellation, without having to wait six months [16]. This is important as it allows timely diagnosis and management. Diagnostic delay and lack of crucial medical advice in the early part of the illness frequently results in significant harm and increased severity of illness.

A total of 39% of respondents incorrectly believed that psychiatric symptoms, or signs of anxiety or depression, were necessary for a diagnosis of ME, in line with the misconception that ME is a psychological or psychosomatic problem. None of the respondents were in fact psychiatrists, psychologists or psychotherapists. These doctors could misdiagnose depression or other mental health problems as ME, depriving patients of necessary treatment. They could also miss the diagnosis of ME, depriving patients of crucial recognition, medical advice and support. Of course, where ME and depression coexist, both need to be recognised and appropriately managed. It should be noted that comorbid depression is as common in other chronic diseases such as multiple sclerosis as it is in ME [17].

The same proportion did not realise that an essential requirement for diagnosis is post exertional malaise, which is an exacerbation of the symptoms of ME/CFS after exertion, which may be physical or cognitive [16,18]. It is recognised as the defining characteristic of ME/CFS [19], can persist for prolonged periods [20], and is unrelieved by sleep or rest [21]. These doctors could erroneously diagnose ME while missing other pathologies. Only 13.6% of participants chose the correct combination of post exertional malaise and

symptoms from multiple systems, without psychiatric features, as being necessary to make the diagnosis.

#### *4.3. Clinical Understanding*

Most participants responded correctly to a series of propositions on the general epidemiology of ME, and nearly all respondents recognised that children with ME can miss long periods of school. However, it is a matter of concern that around a third of respondents considered the statement "children with ME miss school because their parents support their sick role and this should be discouraged" to be correct. ME/CFS is the single most common cause of long-term school absence for medical reasons in England [22], and this has been shown to be due to physical incapacity rather than anxiety [23]. Given the high incidence of unjustified child protection and safeguarding proceedings instigated against families of children with ME, often with disastrous consequences to the health of these children, this misconception is of grave concern [24].

On the overall categorization of ME, most respondents thought that ME belonged in the class of illness called medically unexplained symptoms. This is an umbrella term that encompasses many conditions once thought to be "functional", or without a pathological basis, and for which psychological treatments were advised [25]. However, the underlying pathology is steadily being elucidated, so the condition can no longer be regarded as being medically unexplained [26].

There were also considerable misapprehensions among the participants regarding the level of disability suffered by ME patients, with approximately two-thirds of all respondents under-estimating the level of disability among people with ME, compared to other common or serious illnesses. Only just over a third of participants correctly recognised that ME patients can be as disabled as patients with all seven of the other conditions named. These are multiple sclerosis, cancer, advanced HIV, chronic respiratory disease, end stage renal failure, heart failure and a broken leg. All these conditions have previously been identified in the literature or described by expert clinicians as having comparable levels of disability to ME, both in adults [18,27–29] and in children [30–32].

Similarly, nearly half of the respondents over-estimated the ability of ME patients to stay in work, even though research indicates that loss of employment among people with ME/CFS is widespread. A Spanish community-based study found that 63% of ME/CFS patients were unable to work [33], while the comparable percentage in a large UK study, using data from the UK CFS/ME National Outcomes Database, was 50.1% [34]. This British study found that 998 (50.1%) of 1991 patients had lost employment because of illness. Extrapolation suggested the impact of ME/CFS on employment was responsible for UK annual productivity costs of £102.2 million (range £75.5–£128.9 million) [23]. Another Spanish report from the same research group found that 636 of 1116 people with ME/CFS were unemployed (58.6%) [35], while a Norwegian study of hospital patients [36] found that 43 (45%) of 92 were unemployed. Vink and Vink-Niese in a wide-ranging review of the literature on employment in ME/CFS reported both these studies. They also reported a series of studies by national patient organisations that came to similar conclusions, and additionally demonstrated that where patients were able to continue to work, most had to make adjustments to the nature and duration of the work that they undertook [37].

Most participants appreciated that ME is painful. However, only 25% knew that ME can kill, though research indicates increased mortality from cardiovascular disease, cancer and suicide [38,39], the latter being particularly tragic [40,41]. A recent paper has pointed out that there is a considerable risk to life from malnutrition among patients with very severe ME [42]. About two-thirds of participants did not appreciate the wide range of symptoms occurring in ME patients (Tables 5 and 9). Seven body systems very commonly affected in ME were listed, and only 30% of respondents indicated that ME can affect all seven body systems (see Table 9). These are the nervous system, the cardiovascular system, the endocrine system, the musculoskeletal system, the gastrointestinal system, the immune system and cellular metabolism [20]. The International Consensus Panel made clear the

multi-system nature of the condition in 2012 [16], and this was reiterated in the IACFS/ME (International Association for CFS/ME) Primer for Clinical Practitioners in 2014 [19] and the Institute of Medicine case definition of 2015 [18]. This is applicable to children and adolescents [21] as well as adults.

#### *4.4. Hazardous Treatments*

The responses regarding treatment were a matter of grea<sup>t</sup> concern, with nearly all participants (98%) believing that graded exercise therapy (GET) is a suitable treatment for ME (Table 10), while 61% believed that cognitive behavioural therapy (CBT), designed to help patients ge<sup>t</sup> out of the sick role and to rethink their illness beliefs, is also an appropriate treatment. It is salutary to reflect on why such misconceptions have become so widespread. Much of this may have been shaped by previous research on ME, particularly that promoting the cognitive-behavioural model of ME/CFS. Thus, one study concluded that behavioural, cognitive and affective factors had a role in prolonging fatigue and that therefore these factors should be the focus of treatment [43], but later work concluded that this model lacked credibility as it had inadequate supporting evidence and did not address the increasing evidence of pathophysiological changes in ME/CFS [44].

As outlined above, ME is a serious and debilitating multi-system neuro-immune condition. As such, CBT, attempting to convince patients that they are not actually sick, is no more a useful treatment than it is for cancer [45,46]. Instead, by convincing patients that they are not ill, it is likely to cause harm, for patients who over-exert themselves may suffer a deterioration in their illness. Even without the behavioural effects, just travelling to and sitting through unhelpful CBT sessions can be harmful to ME patients, whose energy is in short supply and who already struggle to manage minimum essential daily activities. Patient evidence sugges<sup>t</sup> adverse outcomes occur in 20% of cases treated with CBT [47].

Many of the participants (98%) believed that graded exercise therapy (GET) was a suitable treatment for ME, perhaps not a surprise given that NICE UK included it as a recommended treatment in 2007. However, many doctors may not be aware of how unpopular this treatment is among ME patients [48], or that it can lead to worsening of symptoms for some patients with ME, and there is in any event increasing evidence that such treatment is ineffective and can be damaging in patients of all levels of severity [19]. The evidence base for GET use has revealed that exercise therapy is not an effective treatment for ME. Reanalysis of the largest GET trial, the PACE trial, revealed recovery rates close to just 10% (little above natural recovery rates), rather than the 22% recovery rate reported by the PACE trial authors [49]. Adverse effects in the trial were dismissed as a consequence of inappropriate implementation by inexperienced practitioners [45]. A 2019 Cochrane review considered eight reports on the use of exercise therapy on ME in adults and concluded that such treatment probably had a positive effect on fatigue [50]. However, a subsequent reanalysis found that this analysis was flawed due to the non-reporting of harms in the reports initially studied, and that in fact GET appeared to not only be ineffective but also unsafe [47].

Similarly, a 2011 review of eight surveys found that 51% of survey respondents had reported that GET had made their health worse [51]. An analysis of primary and secondary surveys found that 54–74% of patients responded negatively to GET [52]. The UK ME Association reported this finding, and advised that GET should play no part in activity managemen<sup>t</sup> advice in ME. They also recommended that CBT, which also impacted negatively on outcomes, should be avoided in ME/CFS [53]. An American report by experienced clinicians concluded that not only did GET fail to improve function, but that it could provoke the hallmark ME symptom of post exertional malaise (PEM) [48]. CBT, similarly, was found to be of benefit to only 8–35% of patients [48], which supports the earlier view of the authors of the IACFS/ME *Primer for Clinical Practitioners* that the belief that CBT and GET can cure ME "is not supported by post-intervention outcome data" [19].

A report from the Centers for Disease Control and Prevention concluded that patients with ME cannot tolerate vigorous aerobic exercise regimes [54], and the evidence on GET continues to accumulate. A recent survey of the experience of ME patients in Italy, Latvia and the UK found that, while none of the Italian or Latvian participants reported having experienced GET, in the UK out of 70 respondents who had had GET, only 1 (1.4%) reported that it had been effective [55]. For these reasons, of ineffectiveness, distress to patients, and risk of harmful sequelae, the National Academy of Medicine in the US no longer recommends GET for ME [18], and it is noteworthy that the draft guideline from NICE in the UK on ME/CFS recommends that GET, or indeed any therapy based on fixed incremental increases in physical activity or exercise, or any programme founded on the supposition that deconditioning is the cause of ME, should no longer be offered to patients [56].

#### *4.5. The Urgent Need and Appetite for Medical Education*

The results of this study make a strong case for putting Myalgic Encephalomyelitis into formal medical education in the UK. We would argue that with ME being more than twice as common as multiple sclerosis [4] and as debilitating or worse than most other chronic illnesses such as heart failure or end stage renal disease [18,27–29] and being the single greatest cause of long term school absence in children [22], the medical profession cannot afford to be so ignorant, and so misinformed, about ME. This becomes even more evident when considering the hazards of currently favoured therapies, as outlined above, in conjunction with the rising costs of clinical negligence [52]. The costs to the UK economy are also considerable, with direct costs estimated at £3.3 billion per annum to the country [57] and productivity costs at £102.2 million per annum [34].

Doctors need to be able to recognise ME regardless of their specialty, as it has such a wide range of symptoms and presentations. Not only does this audit demonstrate the grea<sup>t</sup> and urgen<sup>t</sup> need for medical education on ME, which must be scientifically accurate and up-to-date, responses also demonstrate the appetite for it. More than half the respondents (56%) who answered this question wished to have more in-depth teaching on ME, and a total of 92% were amenable to it. Medical royal colleges and medical schools should take heed.

#### *4.6. Strengths and Weaknesses*

The main strength of this study is that it is one of the few studies in the United Kingdom to make a formal appraisal of doctors' knowledge and understanding of myalgic encephalomyelitis. It also conducted an investigation into the beliefs regarding ME of a group of hospital doctors. The weakness of the study is that it was relatively small-scale, ad hoc and may not be representative of all doctors' views. Furthermore, the small size of the study meant that only relatively large effects could be detected. However, our findings do appear to be consistent with other studies [58,59], and such findings of poor knowledge and negative attitudes appear persistent over decades. These may be linked to how doctors are taught and trained in UK medical schools [59], with both doctors and medical students developing their ideas about ME from lay and informal sources rather than scientific knowledge and evidence on the disease. Although attendance at the training event was mandatory, the participants were self-selected, since returning the survey was not obligatory and participants opted to take part in the survey, which may reflect a selfselection bias. Clearly, future research is needed, with larger samples, the involvement of doctors from different specialties, and the use of a pre-post design in any future training event in order to assess the impact of the event on participants' knowledge of ME.

#### **5. Conclusions and Recommendations**

ME suffers from being a Cinderella topic within the medical profession, largely ignored by the research community, as is evidenced by very low levels of institutional research funding over many years [60], as well as by high levels of ignorance and disbelief among doctors. This clinical audit has sought to investigate the beliefs about ME of a group of hospital doctors attending a training event and their knowledge and understanding of the condition. It has demonstrated areas of ignorance so considerable that patients treated on the basis of this would be put very much at risk. Nevertheless, it was encouraging that participants recognised a need for further training and indicated a wish to participate in this. It is strongly recommended that scientifically accurate and up-to-date medical education on ME be made a priority at undergraduate and postgraduate levels. It is also recommended that this audit be repeated following a period of medical education.

**Author Contributions:** Conceptualisation, K.N.H.; methodology, K.N.H.; validation, K.N.H.; formal analysis, K.N.H. and D.F.H.P.; investigation, K.N.H. and D.F.H.P.; resources, K.N.H.; writing— original draft preparation, K.N.H.; writing—review and editing, K.N.H., K.G. and D.F.H.P.; visualization, K.N.H. and D.F.H.P.; project administration, K.N.H. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Respondents took part in this audit voluntarily on the basis of informed consent. All responses were completely anonymous.

**Data Availability Statement:** Tabulations of the original data are available from the corresponding author.

**Conflicts of Interest:** The authors declare no conflict of interest. Geraghty has no financial conflicts of interest to declare but declares that he has previously received research grants from ME charities, UK non-governmental bodies, and crowdfunding. All of this funding has supported research on ME/CFS.

#### **Appendix A. Doctors' Knowledge and Understanding of ME, UK 2018**

Myalgic Encephalomyelitis-please base answers on your knowledge before today's lecture.



