**4. Discussion**

The quantitative surveys of GPs were carried out over a fourteen-year period, and are consistent in demonstrating that a substantial proportion of GPs, which changed little over that time, did not accept ME/CFS as a genuine clinical entity. In addition, it is clear that many GPs, even when they accept that ME/CFS is real, lack confidence in diagnosing or managing it. There is a similar degree of consistency in the surveys of patients with clinically confirmed ME/CFS. Despite differences in geographical location, they again report degrees of criticism of aspects of GP care which are similar in magnitude. Other reviewed quantitative studies suggested that diagnostic fashion played a part in GP diagnosis, that there were substantial delays in diagnosing ME/CFS in primary care in children, and that the problem of lack of recognition of ME/CFS was geographically widespread despite cultural differences between different countries.

Similarly, the qualitative studies of GPs, despite differences in geographical location and methodology, were consistent in demonstrating marked gaps in GPs' knowledge and the understanding of ME/CFS. The extremely heterogeneous studies of patients all came to similar conclusions: that there were problems for patients over legitimation of the illness, and over lack of sympathy and knowledge among GPs. The reviewed overview papers acknowledged that ME/CFS was poorly understood in primary care, but that ME/CFS was best managed by GPs, who needed to show respect for patients and humility.

The strengths of the study are firstly that we were able to perform a wide-ranging review of the literature, including qualitative, quantitative and mix-methods research, from both the GP and the patient perspectives. Secondly, we were able to take a methodologically rigorous approach, following the SWiM methodology. The weakness of the study was that, because of the heterogeneity of the literature identified, we were not able to perform a systematic review, and we were unable to carry out a meta-synthesis of the qualitative papers, or a meta-analysis of the quantitative papers. It is also possible that some papers may have been missed by our search.

The studies of both GPs and patients all point in the same direction. Many doctors display uncertainty about whether ME/CFS is a real illness, either not having been trained in it or refusing to recognise ME/CFS as a genuine clinical entity, with consequent delays in diagnosis and treatment for patients. Patients with ME/CFS, for their part, often experience suspicion from healthcare professionals and resultant marginalisation, which represents professional failure, with ethical and practical consequences for care and treatment [46]. There are other pointers in the research literature, in addition to those papers identified in our MEDLINE search, which lead to the same conclusions. For example, a Dutch study of the prevalence of ME/CFS-like illness in the working population concluded that such illness may be under-detected in the working population and perhaps in other populations as well [47]. An English study assessing the feasibility of a randomised controlled trial of an early intervention for ME/CFS in primary care concluded that this was not feasible, partly because of evidence of GPs' difficulties in diagnosing ME/CFS and managing the condition [48].

The factors underlying under-ascertainment of ME/CFS are complex and multiple. The mistaken conclusion [49,50] that an early recorded manifestation of epidemic ME/CFS, Royal Free disease, was epidemic hysteria [51] has coloured thinking for half a century, with its insistence on the biopsychosocial hypothesis that ME/CFS can be totally explained away as being due to faulty illness beliefs combined with deconditioning. This has been important in creating disbelief and uncertainty among healthcare professionals in respect of diagnosis, living with ME/CFS, treatment and management, professional values, and support for people with ME/CFS, with insufficient importance attached to listening skills and to establishing a therapeutic relationship [52]. Such controversies surrounding the diagnosis have led to tension between patients and healthcare professionals [53], and the helplessness many GPs feel because of their lack of knowledge of ME/CFS leads to avoidance and neglect [54].

The consequences of under-ascertainment, and the lack of services to treat ME/CFS, contributes to patient stress and depression, which is frequently associated with fatigue [55]. Diagnostic delay is a risk factor for severe disease (i.e., rendering the patient housebound or bedbound) [56], and such patients may lie at home without having seen a doctor for many years. Furthermore, diagnostic failures in primary care affect outcomes adversely; for example, it has been shown that failure to diagnose primary sleep disorders in individuals with ME/CFS may be implicated in the development of psychological disturbances [57].

Many of the papers in this review were published some years ago, but there is evidence in the grey literature that very little has changed. A survey of members of the Oxfordshire ME supporters' group in England (OMEGA) in 2012 reported that, of the 56 who responded, all had been diagnosed with ME/CFS, half of them (28) by a GP. However, only 10 had seen their GP in the month prior to completing the questionnaire. Only 27% of OMEGA members surveyed found their GP to be either helpful or most helpful. The report's author commented that "listening to the patient, believing what they say and coming to an accurate diagnosis would seem to be the most basic starting point for any effective treatment or help. However, this is not the case for many ME/CFS patients. 39% mentioned lack of diagnosis and belief as the most unhelpful thing". Uninformed, negative or hostile attitudes from healthcare professionals are very stressful and detrimental to the health and well-being of people with ME/CFS, and could deter them from seeking treatment. Patients had low expectations of their GPs, and frequently failed to receive good advice or effective symptom control because of a lack of information on the part of GPs. They themselves have identified this as a problem, although most GPs (93%) recognised ME/CFS as a genuine clinical entity. Three-quarters (74%) of GPs recognised the need for better information and training about diagnosis and treatment, and the availability of local services. Uninformed, negative, or hostile attitudes to people with ME/CFS from healthcare professionals were very stressful and detrimental to health and well-being, and could deter them from seeking treatment [58].

An unpublished survey was conducted in 2018 in the U.K. of 44 hospital doctors attending a regional training event. They completed a questionnaire, the responses to which showed that 72% did not know how to diagnose ME, while 76% lacked confidence in dealing with ME patients. Eighty-two percent of respondents believed ME to be at least in part a psychological or psychosomatic problem, while 39% did not realise that post exertional malaise is an essential requirement for the diagnosis of ME [59].

Other evidence has been provided in a report from the European Federation of Neurological Associations (EFNA), which published a survey on stigma and neurological disorder. There were 1373 responses to the survey; 402 of these were received from people with ME/CFS, many of whom felt stigmatised in their interactions with medical professionals. A total of 74% felt that a medical professional did not believe the extent or severity of their symptoms, and the same percentage felt that they did not receive adequate or appropriate treatment because a medical professional did not take them seriously. Stigma was also widespread within families and in social situations. Forty-nine percent said that their families sometimes make them feel that they exaggerate their condition and, sadly, 32% of respondents with children have been made to feel that they are inadequate parents. Almost half of respondents who lived with a neurological disorder during childhood found it difficult to make friends or maintain friendships at school, and a similar number were excluded from school events on account of their condition [60].

Finally, in an Australian survey of 1055 people with ME, 70% expressed a wish for better-informed GPs, and 48% of respondents said their GPs were poorly or very poorly informed, compared with 44% in 2015. Only 29% of respondents stated that their GPs were well or very well informed, and only 31% regarded health professionals as a key source of information about ME/CFS [61].

The quantitative studies of GP attitudes in the U.K., which demonstrated a considerable degree of scepticism about ME/CFS, were undertaken in the aftermath of the publication of the report of the U.K. Chief Medical Officer's working party on ME/CFS,

which had confirmed its existence as a genuine clinical entity [62]. This suggests that the impact of that report on a substantial body of medical opinion was minimal, which is disappointing. The qualitative studies, and studies involving patients, from a wider time scale and range of geographical locations, sugges<sup>t</sup> that such attitudes are by no means confined to the U.K., and remain widespread. The lack of undergraduate and postgraduate teaching on ME/CFS for medical students and doctors may account in large measure for the persistence of such attitudes, and, in a parallel study, we have investigated the current status of medical education on ME/CFS across Europe, as well as possible solutions to the problem.
