INTERNATIONAL JOURNAL OF QUALITATIVE STUDIES ON HEALTH AND WELL-BEING 2020, VOL. 15, 1764830 https://doi.org/10.1080/17482631.2020.1764830 Patients’ experiences and effects of non-pharmacological treatment for myalgic encephalomyelitis/chronic fatigue syndrome – a scoping mixed methods review Anne Marit Mengshoel a, Ingrid Bergliot Hellandb, Mira Meeus c,d,e, Jesus Castro-Marrero f, Derek Phebyg and Elin Bolle StrandOn behalf of the European Network on Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (EUROMENE) h a Department of Interdisciplinary Health Sciences, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway; b Norwegian National Advisory Unit on CFS/ME, Division of Pediatrics and Adolescents, Rikshospitalet, Oslo University Hospital, Oslo, Norway; cResearch Group MOVANT, Department of Rehabilitation Sciences and Physiotherapy, University of Antwerp, Wilrijk, Belgium; d Department of Rehabilitation Sciences and Physiotherapy, Ghent University, Ghent, Belgium; ePain in Motion, International Research Group; fCFS/ME Unit, Vall d’Hebron University Hospital Research Institute, Universitat Autònoma De Barcelona, Barcelona, Spain; g Society and Health, Buckinghamshire New University, High Wycombe, UK; hFaculty of Health Studies, VID Specialized University, Oslo, Norway ABSTRACT ARTICLE HISTORY Purpose: The EU COST Action 15111 collaboration on myalgic encephalomyelitis/chronic Accepted 30 April 2020 fatigue syndrome (ME/CFS) aims to assess current research and identify knowledge gaps in KEYWORDS Europe. Presently, our purpose is to map the effects of non-pharmacological therapies (NPTs) Myalgic encephalomyelitis; for ME/CFS, and what patients find important in the treatment process. chronic fatigue syndrome; Methods: A scoping mixed methods literature review of European studies identified 16 systematic literature review; papers fulfiling our inclusion criteria. The quantitative and qualitative studies were synthe- cognitive behavioural sized separately in tables. Additionally, extracts from the qualitative studies were subjected to therapy; activity pacing; translational analysis. exercise; rehabilitation; Results: Effect studies addressed cognitive behavioural therapy (CBT, n = 4), multimodal effect; patient experiences; rehabilitation (n = 2) and activity-pacing (n = 2). CBT reduced fatigue scores more than usual non-pharmacological care or waiting list controls. The effects of rehabilitation and activity-pacing were inconsistent. treatments The contents, assessment methods and effects of rehabilitation and activity pacing studies varied. For patients, health professionals’ recognition of ME/CFS and support were crucial, but they expressed ambiguous experiences of what the NPTs entail. Conclusions: Methodological differences make comparisons across NPTs impossible, and from a patient perspective the relevance of the specific contents of NPTs are unclear. Future well-designed studies should focus on developing NPTs tailored to patients’ concerns and evaluation tools reflecting what is essential for patients. Introduction The diagnosis is based on reported symptoms and exclusion of other diseases and fatiguing conditions The EUROMENE collaboration (COST Action 15111) on (Fukuda et al., 1994), and diagnostic activities may myalgic encephalomyelitis/chronic fatigue syndrome take time (Hannon et al., 2012). The main symptom (ME/CFS) aims to assess current knowledge, identify of ME/CFS is excessive new onset fatigue and post- knowledge gaps, and deliver information on the disease exertional malaise (Institute of Medicine, 2015), fre- burden, potential biomarkers, clinical diagnosis and quently accompanied by unrefreshing sleep, cognitive potential treatment in Europe (http://www.euromene. dysfunction, and muscle and joint pain (Larun & eu/). On behalf of EUROMENE, we conducted a scoping Malterud, 2007; Strand et al., 2019a). ME/CFS seriously mixed methods review on the evidence of effectiveness restricts daily living and social participation (Njølstad (quantitative studies) and patients’ experiences of treat- et al., 2019) which creates burdens for patients and ment processes (qualitative studies) of non- their families (Nacul et al., 2011). Given the lack of pharmacological therapies (NPTs) in Europe to identify curative pharmacological therapy, many patients are knowledge gaps for future research in ME/CFS. frequently referred to NPTs that, in various ways, aim ME/CFS is a contested diagnosis because it cannot to help patients living with ME/CFS. Studies of NPTs be explained by any definite pathology, and there is include cognitive behaviour therapy (CBT), which is no known cure (Sharpe, 2011). Patients feel ill, but based on principles of classical and operant learning objective clinical tests cannot verify or explain this. theories (Davidson, 2008), and aims to modify CONTACT Anne Marit Mengshoel a.m.mengshoel@medisin.uio.no Department of Interdisciplinary Health Sciences, University of Oslo, 1089 Blindern, 0317 Oslo, Norway © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 2 A. M. MENGSHOEL ET AL. dysfunctional beliefs and improve patients’ coping a personal engagement in a process of coming to skills and behaviour (Price et al., 2008). Another terms with or overcoming an illness condition. With approach, activity pacing, is based on the envelope respect to NPTs, the patient’s efforts and engagement theory that claims, if expended energy levels are kept during a treatment process is essential to arrive at relatively constant, patients will slowly recover (Jason, successful outcome of treatment. A dominant under- 2008). Thus, the aims are to reduce avoidance beha- standing of health is absence or reduction of disease viour, overexertion and symptom fluctuations that can be assessed in terms of fewer disease-related through activity-rest cycling, energy conservation, biological abnormalities and symptoms (Cassell, 2004). and graded activity (Antcliff et al., 2016). Also offered Accordingly, recovery is based on a causal logic where is graded exercise therapy (GET) that presupposes an effective treatment should lead to outcomes of that exercise avoidance perpetuates symptoms reduced disease. Whereas disease relates to objectivity, through deconditioning (Clark & White, 2005), and illness is communicating the subjective, personal therefore aims to increase the activity level and experiences of patients of how a disease afflicts and improve functional capacity via a low-level exercise disrupts a self and life (Kleinman, 1988). Thus, recovery programme, gradually increasing in intensity. can be understood as a personal process of acting Rehabilitation programmes can be provided, includ- upon own illness experiences to bring more wellness ing a mixture of, for example, CBT, GET, activity into life (Cassell, 2004). This process claims a person’s pacing, mindfulness, relaxation strategies, body resources, efforts and engagement (Mattingly, 1998). In awareness therapy, sleep hygiene, stress manage- different ways, though, the purpose of NPTs is to facil- ment, and gradual physical and social reactivation itate such a process. The progress becomes “visible” (Thomas et al., 2008). through people’s story-telling about small and big Over the last decades, systematic literature reviews events (turning points) that make a difference and have reported some effects of NPTs, but the inclusion enable a patient to proceed (Frank, 1995; Mattingly, of patients is based on various diagnostic criteria 1998). Presently, this interpretation informed our ana- (Castro-Marrero et al., 2017; Chambers et al., 2006; lysis of qualitative data. Edmonds et al., 2004; Kim et al., 2020; Larun et al., 2015; Nijs et al., 2011; Price et al., 2008; Van Cauwenbergh et al., 2012). Studies have not necessa- Methods rily excluded patients with mental illnesses, for which the results have been widely criticized. As CBT and Design GET are used for patients with mental illnesses, for Three researchers (AMM, EBS, and IBH) planned the example, those with severe depression, it was impor- present study. A scoping mixed methods review design tant for us to find out whether such therapies are was considered appropriate for mapping research evi- found efficient when patients suffering from mental dence and identifying knowledge gaps (Munn et al., illnesses were explicitly excluded. Therefore, we have 2018). The literature search and inclusion/exclusion reviewed papers based on case definitions in line with process followed the procedures of a systematic litera- the EUROMENE recommendations (Strand et al., ture search, but according to a scoping review design, 2019b); which explicitly exclude mental illnesses. We the included papers were not subjected to any meth- also sought to record what were defined as primary odological quality appraisal (Munn et al., 2018). outcome variables and which instruments were used for assessments. Furthermore, with a view that effects of NPTs relate to what patients’ find meaningful and Information sources and search do during a treatment process, we also included stu- dies referring interviews with patients about their With the help of a research librarian, a systematic views about participating in NPTs. Thus, our review literature search was conducted on the following aimed to map the effects of NPTs in patients with ME/ e-data bases: Medline, Cinahl, PsychInfo, Embase, CFS and to examine what patients find important in Cochrane Database, Cochrane Library, Web of the treatment process. Science and Epistemonikos. Separate search strategies for quantitative and qualitative studies were created for Ovid Medline (Table I) and adapted to the other Recovery as treatment effects and personal databases. We decided to examine the research trend healing work in Europe over a period of the last 10 years (from Recovery is an umbrella term with various interpreta- January 2009 to January 2019). The reason to include tions related to different understandings of health only the last 10 years was that we wanted to examine (Jacobson, 2004). For example, recovery can be seen if there were any new trends in focus for research as an outcome or evidence of a particular therapy’s compared with what described in prior systematic effect of improving a disease, or alternately, as literature reviews. Later, an updated search following INTERNATIONAL JOURNAL OF QUALITATIVE STUDIES ON HEALTH AND WELL-BEING 3 Table I. The search profile applied in Medline being adapted for the other databases. Outcome studies: 1 (Fatigue Syndrome, Chronic/or ((CFS adj3 (ME or SEID)) or myalgic encephalo* or chronic fatigue* or fatigue syndrom* or systemic exertion intolerance or PVFS or royal free disease* or akureyri disease or Iceland disease).tw,kf.) and ((randomis* or randomiz* or randomly or trial or intervention? or effect? or impact? or multicenter or multi centre or multicentre or multi centre or controlled or control group? or (before adj5 after) or (pre adj5 post) or ((pre-test or pre test) and (post-test or post test)) or quasiexperiment* or quasi experiment* or evaluat* or time series or time point? or repeated measur*).ti,ab. or ((treatment outcome/and follow up study/) or ((followup or follow up or longitud* or cohort*) and (treatment* or therap* or intervention* or management)).tw,kf. or (treatment* or therap* or intervention* or management).ti.)) 2 Fatigue Syndrome, Chronic/or ((CFS adj3 (ME or SEID)) or myalgic encephalo* or chronic fatigue* or fatigue syndrom* or systemic exertion intolerance or PVFS or royal free disease* or akureyri disease or Iceland disease).tw,kf. 3 limit 2 to (clinical study or clinical trial, all or clinical trial, phase i or clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or clinical trial or controlled clinical trial or randomized controlled trial) 4 limit 2 to “therapy (best balance of sensitivity and specificity)” 5 1 or 3 or 4 6 limit 5 to (english language and yr = “2009 -Current”) Qualitative studies about patients’ experiences: (Fatigue Syndrome, Chronic/or ((CFS adj3 (ME or SEID)) or myalgic encephalo* or chronic fatigue* or fatigue syndrom* or systemic exertion intolerance or PVFS or royal free disease* or akureyri disease or Iceland disease).tw,kf.) and ((((“semi-structured” or semistructured or unstructured or informal or “in-depth” or indepth or “face-to-face” or structured or guide) adj3 (interview* or discussion* or questionnaire*)) or (focus group* or qualitative or ethnograph* or ethnological or fieldwork or field work or field stud* or key informant or focus group* or narrat* or phenomenolog* or hermeneutical or ethonurs* or grounded theory)).tw,kf. or interviews as topic/or focus groups/or narration/or qualitative research/) Limited to English language and from January 2009 up till March 2020 prior procedures was performed up till 18 March 2020 references were retrieved and reviewed by the without identifying any additional studies. researchers in full-text. After the independent reading, the papers were discussed, and more papers were excluded. Eligibility criteria We included studies of patients ≥12 years old. For quantitative studies addressing our first aim, ME/CFS Research team was determined by the Canadian Consensus Criteria The authors have various backgrounds from physiother- (CCC) (Carruthers et al., 2003), the International apy, psychology, medicine, biology and economy, and Consensus Criteria (ICC) (Carruthers et al., 2011), or we are representing a European collaborative group of the Centre for Disease Control and Prevention (CDC- researchers from about 20 countries. 94) criteria definitions (Fukuda et al., 1994), consis- tent with EUROMENE recommendations (Strand et al., 2019b). The qualitative studies for the second Synthesis and analysis of qualitative data aim, however, often failed to report diagnostic cri- teria, so they were included irrespective of case defi- The synthesis of the studies includes case definition, nitions. For the first study aim, only randomized recruitment methods, type of NPT, primary outcome controlled trials (RCTs), and for the second aim, indi- measures (quantitative methods), data collection, vidual or focus group interviews, and in both cases outcomes of primary outcome variable and effect only European patients, were included, to describe size whenever reported in the papers (quantitative the European landscape. Excluded were studies with- studies) and analytical themes developed by the out full text, case reports, pilot studies, protocols for authors of primary papers (qualitative studies), see effect studies, non-English language papers, second- Table II for quantitative and Table III for qualitative ary analysis of RCTs, other designs than RCTs includ- studies. Additionally, text from the qualitative ing experimental studies of exercise or mental papers’ result sections addressing patients’ experi- mechanisms, duplicates and non-European studies. ences of NPT was identified and extracted. All text, In planning the study, we decided to exclude con- including what patients experienced as unimportant ference reports, proceedings, Master’s and PhD the- or meaningful by participating in NPTs, was ses as such literature can be difficult to search and extracted and imported into the software pro- retrieve (Peters et al., 2015). gramme NVivo for further analysis. The extracts of each paper were coded and compared across papers for similarities or dissimilarities, in accordance with Study selection reciprocal and refutational translational analysis The search strategy identified titles and abstracts. Two (Britten et al., 2002; Noblit & Hare, 1988). During authors (EBS, AMM) independently screened the this process, new categories were developed to cap- papers for potential eligibility by reading titles and ture what was described in the papers as a whole. As abstracts. Each reference for which initial agreement our analysis emerged, three overarching themes was not reached were discussed before a final set of were developed. 4 Table II. An overview of included papers referring effects of non-pharmacological programmes. Setting for Statistically significant group intervention, Length of follow- differences in primary outcome Aim/research question Diagnostic criteria Interventions and control up Sample characteristics Primary outcome measures variable, and effect size if reported Cognitive behavioural therapy (CBT) for adults: Janse et al., To test the efficacy of Outpatient Protocol-driven- feedback iCBT At end of therapy 80 patients in each three Checklist Individual Strength No difference between the two iCBT 2018 internet-based CBT specialized clinic vs. at 6 months groups, 145 women. Mean fatigue severity subscale formats, but both groups better A. M. MENGSHOEL ET AL. Netherlands (iCBT) CDC-94 criteria † feedback-on-demand iCBT age in groups from 37 to fatigue than controls. vs. 40 yrs 43% in iCBT groups reached normal waiting list fatigue and 15% in waiting list control group No serious adverse events Tummers To test whether a minimal Community-based Self-instruction booklet based on CBT At time of Guided CBT, n=62, 46 Checklist Individual Strength Decreased fatigue was found in guided et al., 2012 intervention was mental health and email-contacts once every 2 completing women, mean age 36 yrs, fatigue severity subscale CBT group compared with waiting Netherlands effective when delivered centre weeks intervention and illness duration 6 to 464 list controls. Controlled effect size in a community-based CDC-94 criteria † vs. waiting list after months was 0.70. mental health centre waiting list 6 months Waiting list, n=61, 50 women, 33% showed clinical reduced fatigue mean age 36 years, illness compared to 9% in waiting list duration 6 to 625 months control group Tummers To examine effectiveness of Expert centre of Stepped care: Minimal self-instruction At completion self- Self-instruction and CBT, Checklist Individual Strength No statistically significant difference et al., 2010 a stepped care guided ME/CFS booklet followed by 6 months instruction/ n=84, 69 women, mean fatigue severity subscale between two groups in fatigue, Netherlands self-instruction and CBT CDC-94 criteria † individual face to face CBT vs. waiting period. age 37 yrs effect size 1.37 compared to usual care waiting list followed by CBT After Waiting list and regular CBT, Number of patients reaching clinical completing n=85, characteristics not significant improvement higher in additional CBT reported the stepped care group than the or regular CBT other group CBT for adolescents: Nijhof et al., To compare short-term Outpatient CBT delivered as 21 modules over At 6 months CBT group, n=68, usual care School attendance in % of School attendance in CBT group 2012 effectiveness of the specialist care internet, with interactions between n= 67, CBT group, 54 girls, normal increased to 84% vs 51% in usual Netherlands FITNET programme with CDC-94 criteria † trained CBT therapists and children mean age 16 yrs and care group, and 75% reached full usual care in reduction and their parents separately first duration of symptoms 16 school attendance at 6 months vs of fatigue, school once a week and then each other yrs 16% in usual care group. absence, and physical week vs. usual care controls Usual care group, 57 girls, dysfunction mean age 16 yrs and duration of disease 19 yrs. Rehabilita- tion: Nunez et al., To compare quality of life Outpatient Multidisciplinary rehabilitation with 3 months therapy Rehabilitation, n=60, 53 Medical Outcomes Study- No group differences in quality of 2011 of those receiving specialist clinic CBT, supervised GET and assessed 1 year women, mean age 43 yrs Short Form-36 health, worse bodily pain scores in Spain conventional drugs, CDC-94 criteria † conventional drugs after end of the and illness duration 32 rehabilitation group than control group CBT and GET with vs. GET counselling and conventional programme months Controls, n=60, 48 group drug and exercise drugs women mean age 44 years, counselling illness duration 33 months (Continued ) Table II. (Continued). Setting for Statistically significant group intervention, Length of follow- differences in primary outcome Aim/research question Diagnostic criteria Interventions and control up Sample characteristics Primary outcome measures variable, and effect size if reported Vos-Vromans To evaluate the difference Rehabilitation CBT alone (tailored to active or passive 26 and 52 weeks CBT, n=60, 47 women, mean Checklist Individual Strength Fatigue improved more in MR than in et al., 2016 in treatment effect centres patients) after treatment age 41 yrs and illness fatigue severity subscale CBT group Netherlands between CBT and CDC-94 criteria † vs. initiation duration mostly ≥ 5 yrs After one year the improvement in multidisciplinary Rehabilitation (including CBT and a MR, n=62, 50 women, mean fatigue score was sustained in MR rehabilitation (MR) mix of strategies) age 40, illness duration group, but not in the CBT group. mostly ≥5 yrs Activity pacing: Kos et al., To evaluate effectiveness of Outpatient Three individual sessions with either At end of therapy APS, n= 16 women, mean Canadian Occupational COPM performance and COPM 2015 activity pacing self- rehabilitation activity-pacing self-management at 3 weeks age 39 yrs Performance Measure satisfaction scores changed Belgium management clinic (APS) or relaxation therapy (RT) RT, n= 17 women, mean age (COPM) significantly in both group with CDC-94 criteria † 41 yrs moderate to high effect size in favour of APS group with 33% and 42% in APS group vs. 14% and none in the RT group. Pinxsterhuis To evaluate the Primary health Self-management educational At 6 months and Self-management, n=71, 67 SF-36 physical functioning No group difference in physical et al., 2017 effectiveness of a group- care setting program after 1 year women, mean age 44 yrs, subscale functioning after 6 or 12 months Norway based self-management CDC-94 criteria † vs. diagnose for 1-21 yrs programme CCD criteria ‡ treatment as usual (controls) Controls n=66, 54 women and diagnosis for 0-17 yrs † the Centres for Disease Control and Prevention diagnosis criteria ‡ the Canadian Consensus Criteria for diagnosis INTERNATIONAL JOURNAL OF QUALITATIVE STUDIES ON HEALTH AND WELL-BEING 5 6 Table III. An overview of included papers of patients’ treatment experiences. Sample Findings expressed in the References Aim/research question Recruitment methods Setting Diagnostic criteria Research design and analysis Intervention characteristics authors’ themes Broughton et al., 2017 To explore experiences of Convenience sampling Specialist clinics Diagnosed- criteria not Semi-structured, individual Comprehensive 14 women. 2 Journey to specialist care, Things UK patients who were reported interviews Thematic treatment men Age 24 that hinder treatment Support completing a treatment at analysis including CBT to 62 yrs systems specialist clinics and GET Illness duration 1 to 17 yrs A. M. MENGSHOEL ET AL. Cheshire et al., 2020 UK What are the differences and Strategic sampling according Specialist clinic Diagnosed—criteria not Semi-structured, individual Guided graded 17 women, 3 Getting started and false starts similarities in treatment to responses to reported interviews Thematic exercise self- men Age 21 Indeterminate phase of GES perceptions and questionnaires showing analysis help (GES) to 66 yrs Competing commitments experiences of guided much improvements/much Interfering symptoms and graded exercise among deterioration comorbid conditions those reporting Maintaining motivation improvements compared with those deteriorated? Chew-Graham et al., What factors are important for Purposive sampling from an Primary health care Diagnosed by Oxford criteria Semi-structured individual Nurse-led 13 women, 6 Feeling accepted by therapist 2011 UK patients to engage in RCT trial interviews Inductive rehabilitation men Age 23 Own acceptance of diagnosis a new intervention? thematic analysis based on program to 61 yrs Accept of (treatment) model data from those in trial arm Illness duration 9 months to 16 yrs Dennison et al., 2010 UK To examine participants’ views All participants in an RCT Outpatient clinic at a hospital Diagnosed—criteria not Semi-structured individual Either cognitive 16 out of 46 Pre-therapy ideas and and experiences of taking around three years earlier reported interviews Inductive behavioural invited were expectations Therapy part in family-focused were invited thematic analysis therapy or interviewed experiences Perspectives on cognitive behavioural psycho- 10 women, effectiveness therapy education 6 men Age 16 to 24 yrs McDermott et al., 2011 To explore hopes and All referred to the service last Specialist clinic Diagnosed—criteria not Semi-structured individual Self-help advice to 20 out of 56 Needing a diagnosis In search of UK expectations of patients five months were invited reported interviews Constant improve invited guidance and support newly referred to a ME/CFS comparative analysis symptoms were Engaging with complexity to centre informed by interviewed understand the illness In Lifestyle 17 women, search of hope for the future Management 3 men Group Program Age 22 to 60 yrs Picariello et al., 2017 UK To explore the reasons for Consecutively recruited if Specialist clinic Diagnosed—criteria not Semi-structured individual Cognitive 13 out of 32 Hopes and expectations Real, not why some patients engage finished or in follow-up reported interviews Inductive behavioural invited were imagined Collaborative in treatment more than after treatment thematic analysis therapy (CBT) interviewed therapeutic alliance others, and to assess 11 women, 2 Motivation and engagement whether CBT meets men Age 18 Gain and loss Change patients’ needs to 64 yrs (Continued ) INTERNATIONAL JOURNAL OF QUALITATIVE STUDIES ON HEALTH AND WELL-BEING 7 Results Experiences of understanding, expectations Experiences with and coping Mediating factors First aim: effects of non-pharmacological Findings expressed in the treatment Perspectives on Pretreatment thoughts and treatments (NPTs) Experiences of chaos and authors’ themes Study selection effectiveness acceptance The search strategies on effect studies retrieved 2697 insecurity quantitative studies, but records screened by titles and abstracts showed that 2651 papers did not meet the inclusion criteria. Thematically, the latter papers duration 2 to 57 yrs Illness male Age 14 2.5 to 20 yrs invited were characteristics interviewed 2 men Age reported about non-ME/CFS illnesses, effects of phar- 8 women, A self-management 10 out of 33 Lightening Process 8 females, 1 to 26 yrs Sample duration 12 yrs Illness macological interventions or traditional Chinese med- 32 to icine, and studies of disease or treatment mechanisms. Forty-six eligible papers were read in envelope and full-text. This reading resulted in further exclusion of Intervention programme self-efficacy based on papers, for reasons shown in Figure 1. theories Study characteristics after the program Thematic immediately and 9 months Research design and analysis Eight RCT studies were included in the review (Table Semi-structured individual II). One study fulfiling the inclusion criteria examined Focus group interviews interviews Inductive thematic analysis 135 children/adolescents with ME/CFS (Nijhof et al., 2012), while the others included 772 adult patients analysis with ME/CFS. Five studies were from the Netherlands (Janse et al., 2018; Nijhof et al., 2012; Tummers et al., 2010, 2012; Vos-Vromans et al., 2016), and one each from Belgium (Kos et al., 2015), Norway (Pinxsterhuis Centres for Disease Control and Prevention—1994 criteria and Canadian Diagnostic criteria et al., 2017), and Spain (Nunez et al., 2011). The effects Consensus Criteria of CBT (n = 4), activity pacing (n = 2), and multi- disciplinary rehabilitation, including CBT and GET Oxford criteria (n = 2) were examined. In all but one study (Tummers et al., 2010), the sample sizes were deter- mined by statistical power calculations based on esti- Outpatient clinic at a hospital mated given clinical relevant changes in the primary Members of website forum outcome variable. Mostly, effects were assessed Setting immediately after completing NPT, except for one study, which assessed outcomes after 1 year (Nunez et al., 2011). Two studies assessed both immediate and long-term effects, either multiple times during 1 year (Vos-Vromans et al., 2016) or after 1 year for young people with ME Recruited through a website management programme (Pinxsterhuis et al., 2017). A registry number of All participants in a patient Recruitment methods Clinical Trial Gov. was not included in any papers, but one study was registered in a Dutch trial registry education, self- were invited (Janse et al., 2018). Outcome measures applied in the studies The primary outcome variables from which power education programme and young people after having experiences with a patient Reme et al., 2013 US/UK To explore the experienes of Aim/research question calculations were estimated included; fatigue, physical undergone Lightening functioning, dimensions of health-related quality of To elicit participants’ life and school attendance. The Checklist Individual its usefulness Strength (CIS) fatigue severity subscale assessed fati- process gue (Janse et al., 2018; Tummers et al., 2010, 2012; Vos-Vromans et al., 2016). Physical functioning was Table III. (Continued). assessed by the Canadian Occupational Performance Pinxsterhuis et al., 2015 Measure (Kos et al., 2015) or the Medical Outcomes Study-Short Form-36 (SF-36) physical functioning sub- References scale (Pinxsterhuis et al., 2017; Tummers et al., 2010). Norway The SF-36 assessed various dimensions of health- related quality of life (Nunez et al., 2011; Vos- 8 A. M. MENGSHOEL ET AL. Figure 1. PRISMA flow chart: the selection of scientific papers for the systematic scoping review. Vromans et al., 2016), and school attendance was Cognitive behavioural therapy compared with assessed as a proportion of the normal school-time waiting list and usual care controls schedule (Nijhof et al., 2012). Three RCTs, all from the Netherlands, addressed self- instructed CBT programmes either delivered by inter- net or by self-instruction booklet sent by mail for Patient characteristics adult patients. In the study of Janse et al. (2018), no Seven studies included 772 adult patients with ME/CFS, detailed information of the content was provided, but while the one involving children/adolescents had 135 Tummers et al. (2010, 2012) describe the CBT booklet participants. One study of adults did not report sex for as informing about triggering and maintaining fac- a control group, but among the others, there were 583 tors, reducing focus on fatigue, establishing sleep women and 111 men. The children/adolescent study routines, managing either an overactive or sedentary included 111 girls and 24 boys (Nijhof et al., 2012). The physical activity pattern, and the planning of work study participants were recruited from tertiary care (Janse resumption. Janse et al. (2018) provided the CBT et al., 2018; Kos et al., 2015; Nijhof et al., 2012; Pinxsterhuis booklet over the internet to a group, with or without et al., 2017; Tummers et al., 2010), primary health care guidance from a psychologist, and the groups were (Nunez et al., 2011; Tummers et al., 2012) or from multiple compared with waiting list controls. After the inter- sources (Pinxsterhuis et al., 2017). The participants’ mean vention period, there was no difference in CIS fatigue ages varied from 36 to 52 years in the adult samples, and severity subscale score between the two CBT groups, the children/adolescents were aged from 12 to 18 years. but they both improved compared with waiting list Illness duration was not always reported but varied con- controls, and 43% of those receiving CBT achieved siderably within studies from months to several years, normal fatigue scores versus 15% of waiting list con- and in one study, time since diagnosis was reported to trols. In two studies, Tummers and co-workers exam- vary from 1 year to 21 years (Pinxsterhuis et al., 2017). ined the effects of a self-instruction CBT booklet sent INTERNATIONAL JOURNAL OF QUALITATIVE STUDIES ON HEALTH AND WELL-BEING 9 by mail followed by email and face to face consulta- drug therapy and counselling about GET, whereas the tions with a psychologist in tertiary care (Tummers rehabilitation group showed worse SF-36 pain scores et al., 2010), and later the same treatment procedure after 1 year. was tried out with mental nurse consultations in a community mental health setting (Tummers et al., Activity-pacing alone or integrated in 2012). In these studies, no differences in CIS fatigue self-management education severity subscale scores were found compared to the A Belgian study compared the effects of activity- control groups of usual care or waiting list controls pacing with relaxation therapy (Kos et al., 2015). (participants in both control groups could also receive Three individual therapy sessions of 60 to 90 min CBT), but more patients reached clinically relevant a week for three consecutive weeks were provided. changes in fatigue score in the experimental group Activity pacing, but not relaxation therapy, brought than those receiving usual care (Tummers et al., 2010) about improvements in self-determined daily activ- or waiting list controls (Tummers et al., 2012). ities assessed by the patient-specific assessment Also, a CBT programme provided to children/adoles- method the Canadian Occupational Performance cents and their parents was examined. CBT was deliv- Measure. A Norwegian study based on envelop and ered as 21 modules on the internet to patients and their self-efficacy theories examined effects of a group- parents separately. Trained psychologists provided sup- based self-management education programme (goal- port by regular email contacts with each individual setting, modelling self-management skills, guided every other week (Nijhof et al., 2012). The results were mastery practice, relaxation exercise). The interven- compared with usual care, including either group-based tion was delivered in eight sessions of 2.5 h’ duration multimodal rehabilitation, CBT, GET or a combination of every other week. The self-management programme CBT and GET. Both the internet CBT and usual care were did not improve SF-36 physical functioning scores delivered over a period of 6 months, and after 6 months compared with usual care controls either at 6 months 84% improvement in school attendance occurred in the or 1 year (Pinxsterhuis et al., 2017). CBT group, versus 52% in the usual care control group. Second aim: patients’ treatment experiences Rehabilitation including cognitive behavioural therapy and graded exercise therapy Study selection Rehabilitation comprised several modalities, among them The search strategies about patients’ treatment CBT and GET. In a Dutch study, a multidisciplinary rehabi- experiences retrieved 521 studies, but 505 were litation programme (gradual activity reactivation, body excluded, mostly because they did not apply qualita- awareness therapy, sleep routines following principles of tive interviews or described patients’ experiences CBT and mindfulness) was compared with a CBT alone unrelated to NPTs. After reading 16 papers in full programme, with a focus on perpetuating cognitions and text, eight papers were excluded because they did behaviour (Vos-Vromans et al., 2016). The rehabilitation not refer to treatment experiences or lacked qualita- programme was provided in the form of weekly indivi- tive data analysis (Figure 1). Thus, eight papers were dual visits to a physiotherapist and an occupational thera- included in the analysis. pist, and biweekly visits to a psychologist and social Seven studies concerned UK patients (Broughton worker over a period of 10 weeks, in total 33 h for each et al., 2017; Cheshire et al., 2020; Chew-Graham et al., individual. In the control group, CBT was provided in 16 2011; Dennison et al., 2010; McDermott et al., 2011; sessions of 45–60 min over a period of 6 months. Picariello et al., 2017; Reme et al., 2013) and one Compared to the rehabilitation programme, CBT was Norwegians (Pinxsterhuis et al., 2015). The studies less effective in reducing the CIS fatigue severity subscale explored experiences of psychological treatment pro- score after 4, 14 and 52 weeks. A Spanish study combined grammes as CBT (Dennison et al., 2010; Picariello conventional symptom-relieving pharmacological ther- et al., 2017) or the Lightning Process programme apy with CBT (90 min sessions twice a week for 2.5 months (Reme et al., 2013). Other studies related treatment including education about the multifactorial character of experiences to education in self-management based ME/CFS, progressive relaxation technique, sleep hygiene, on envelop and self-efficacy theories (Chew-Graham modifying non-adaptive and catastrophic thought pat- et al., 2011; Pinxsterhuis et al., 2015), self-help GET terns) and supervised GET (1 h exercise thrice a week for (Cheshire et al., 2020) and multimodal specialist care 3 months, starting with 10 min exercise and adding 5 min (Broughton et al., 2017; McDermott et al., 2011). for each session until reaching 40 min) compared with conventional drug therapy in combination with counsel- Patient characteristics ling about GET (advice to exercise 10 min aerobically and Interviews were performed with 162 patients (133 stretching exercises three times a day) (Nunez et al., 2011). females and 29 males) varying in age from 14 to Pain reduction assessed by the SF-36 pain subscale was 66 years, and four studies reported that the partici- demonstrated in the control group with conventional pants had been ill from 9 months to 20 years. One 10 A. M. MENGSHOEL ET AL. study recruited participants from websites for young 2017). Their services were called a “security blanket” people with ME/CFS (Reme et al., 2013), one study or “lifeboat” (Broughton et al., 2017), a place where from primary health care (Chew-Graham et al., 2011), patients could talk openly without being judged. and the other six studies recruited from specialist Initially, patients could express a preference for clinics or outpatient clinics at hospitals. face-to-face consultations with health professionals (Broughton et al., 2017; Picariello et al., 2017), but Recognition and support a crucial part of the NPTs often NPTs were delivered in group formats. Despite Patients mentioned protracted, distressing history of patients’ doubts about group sessions, they often medical consultations and numerous tests, before turned out better than expected. Patients found it being diagnosed as ME/CFS (Broughton et al., 2017; supportive to share experiences with others, affirming McDermott et al., 2011; Picariello et al., 2017). They their challenges, and enabling learning from others had expected that diagnosis would provide authoriza- about illness management (Broughton et al., 2017; tion for guilt-free downregulation of daily life (Chew- Pinxsterhuis et al., 2015; Reme et al., 2013). This sup- Graham et al., 2011), which was an important step of port system could collapse after discharge, though, regaining self-respect and control (Dennison et al., leaving patients uncertain about ability to manage 2010; McDermott et al., 2011). However, it was unclear alone (Broughton et al., 2017; Picariello et al., 2017; for them what the diagnosis meant, compounded by Pinxsterhuis et al., 2015). They were losing their lack of knowledge of treatment options and prognosis “safety net”, and would have felt better if offered (McDermott et al., 2011). In the beginning, patients review appointments after discharge as a “backup” if hoped to recover fully and return to how life used to needed (Broughton et al., 2017; Picariello et al., 2017). be (Broughton et al., 2017). But over time, few patients expected a miraculous cure, and they rather Importance of overcoming own scepticism to expressed hopes for more modest symptom relief engage in non-pharmacological therapies (Dennison et al., 2010; McDermott et al., 2011), recog- If symptoms were not explained in physical terms, nition and legitimacy (McDermott et al., 2011). In any patients concluded that health professionals consid- case, diagnosis was essential for NPT referral (Chew- ered symptoms to be psychological (Chew-Graham Graham et al., 2011), where patients hoped for appro- et al., 2011). They disliked it when psychological priate advice about how to do the right things to live aspects were presented as facts (Chew-Graham et al., a life without aggravating symptoms, and thereby 2011; McDermott et al., 2011), and their engagement balance illness and practical pressures in work and and compliance diminished (Chew-Graham et al., family contexts (Dennison et al., 2010). 2011). In particular, those reporting lack of improve- Several patients had received advice and treat- ment and attributing their ME/CFS exclusively to ments that had made them worse (Pinxsterhuis organic causes refused psychological explanations et al., 2015; Reme et al., 2013). Prior negative experi- (Picariello et al., 2017). This hindered their attempts ences made patients sceptical about other treatments to balance life in relation to illness and meant that (Dennison et al., 2010; McDermott et al., 2011; they were told to push themselves more than their Picariello et al., 2017; Reme et al., 2013), but they body tolerated (McDermott et al., 2011). By contrast, if were willing to be open and take whatever it cost. health professionals presented physiological explana- This was better than doing nothing, even if health tions that matched patients’ own illness models, it professionals’ advice seemed counterintuitive and helped them to formulate their understandings more caused them to end up in bed for days (Broughton clearly, and to form alliances with health professionals et al., 2017). Often referral to a specialist centre was (Chew-Graham et al., 2011; Picariello et al., 2017). a last resort (Broughton et al., 2017; Dennison et al., Grief over loss of prior life and disruption of plans 2010), even sometimes experienced as healing in itself for future was expressed (Broughton et al., 2017). The (Picariello et al., 2017). At specialist centres, the valid- need to accept the here-and-now, and willingness to ity of ME/CFS was not questioned, and there was say good-bye to one’s former life and to make acceptance that symptoms were real and serious changes, were important in engaging fully in treat- (Broughton et al., 2017). Health professionals who ment (Broughton et al., 2017). Patients could be acknowledged their illness were highly valued by uncertain that ME/CFS was a correct diagnosis, but the patients (Broughton et al., 2017; Chew-Graham participation in NPTs increased their confidence et al., 2011; Picariello et al., 2017; Pinxsterhuis et al., (Pinxsterhuis et al., 2015). Explanation and under- 2015), who then felt safe (Pinxsterhuis et al., 2015). standing of symptoms was fundamental to illness A key feature was that the staff listened and under- acceptance and beginning recovery work (Chew- stood (Chew-Graham et al., 2011; Dennison et al., Graham et al., 2011; Pinxsterhuis et al., 2015). 2010). Patients developed alliances with these thera- Patients needed to accept that treatment was not pists, who they found knowledgeable, inspiring, curative, that improved coping would help friendly, supportive and helpful (Picariello et al., (Pinxsterhuis et al., 2015), and that life henceforth INTERNATIONAL JOURNAL OF QUALITATIVE STUDIES ON HEALTH AND WELL-BEING 11 should be lived in a “slow lane” (Broughton et al., hard work, without immediate benefits. They often 2017). NPTs could make patients more realistic, aban- felt too unwell to start exercising, and in particular, don the search for miracle cures (Pinxsterhuis et al., in the early phases, setbacks were experienced that 2015), and help them to focus on day-to-day goals for restricted motivation to continue (Cheshire et al., their lives (Broughton et al., 2017). 2020). Usually, improvements due to NPTs were small and Ambiguous experiences of non-pharmacological hardly noticeable (Picariello et al., 2017), and patients therapies felt disheartened by recovering with “baby steps” It appeared important for patients to build awareness (Broughton et al., 2017). Nevertheless, patients noted of their condition (Picariello et al., 2017), by learning that because of their new skills, the end of the treat- to plan and manage activity to avoid fatigue triggers ment marked a new beginning (Dennison et al., 2010). and illness fluctuations (Picariello et al., 2017; They felt more in control (Picariello et al., 2017) and Pinxsterhuis et al., 2015). Balancing ME/CFS and daily able to balance activities and avoid exacerbations life required adjustment and changes to daily routines (Pinxsterhuis et al., 2015), but had to persevere as (Pinxsterhuis et al., 2015). Patients needed help to progress was slow, particularly for GET. Thus, even achieve this (McDermott et al., 2011). Help in finding starting with light, regular activities, some felt worse the right activity level and implement sleep routines with GET, and it could take weeks or months to was an important early step (Cheshire et al., 2020; tolerate even a 10-min walk (Cheshire et al., 2020). In Dennison et al., 2010). Learning pacing, energy con- contrast, for some the Lightning Process led to servation, relaxation exercises and coping with nega- immediate changes, including absence of symptoms tive feelings helped to balance everyday life and ability to resume former activities (Reme et al., (Pinxsterhuis et al., 2015). 2013). When participants in NPTs described their Acceptance of the psychological explanations on expectations for the future, tension between hope which CBT is founded (Chew-Graham et al., 2011; and fear was evident (McDermott et al., 2011). They Pinxsterhuis et al., 2015), was an essential prerequisite hoped to recover fully (McDermott et al., 2011; to investing effort in CBT (Picariello et al., 2017). The Pinxsterhuis et al., 2015) but also feared deterioration Lightning Process programme also applies mental (Dennison et al., 2010; McDermott et al., 2011) or techniques, but the biological model explaining how recurrence (Picariello et al., 2017). the body is affected by thoughts and emotions was mostly accepted (Reme et al., 2013). Although both Discussion CBT and the Lightning Process focus on changing patterns of thought and behaviour, for those experi- CBT caused reduced fatigue among adults and led to encing both it was confusing that, whereas CBT higher school attendance among adolescents. The focuses on accepting illness, coping with its restric- results of activity pacing and multimodal rehabilita- tions and adjusting to the new situation, the tion programmes, including CBT and GET, were incon- Lightning Process emphasizes the importance of clusive. Patients highlighted the importance of refusing to allow the illness to take control (Reme recognition and support by health professionals, of et al., 2013). CBT provided a better understanding of making sense of symptoms, and of accepting the the activity patterns that trigger fatigue, and provided situation, enduring slow improvement, and finding skills to manage and plan ahead to prevent overdoing the right activity level for everyday life. Nevertheless, things (Dennison et al., 2010; Picariello et al., 2017), patients could find NPTs ambiguous and incomplete. but developing a more consistent daily routine could mean abandoning favoured activities (Picariello et al., A need for more systematic development and 2017). Nevertheless, CBT was considered incomplete, testing of non-pharmacological therapies and not addressing all aspects of illness (Dennison et al., 2010). Patients’ experiences suggested the Many effect studies were excluded because they used Lightning Process programme was helpful, but they diagnostic criteria found inappropriate by EUROMENE, felt it was not specific for ME/CFS and could benefit for example, the Oxford criteria (Sharpe et al., 1991), anyone. Negatively, there was a normative pressure to and in particular, this excluded studies examining the be positive and not express scepticism embedded in effects of GET. In a review of papers until 2004, the Lightning Process programme, as the therapists Friedberg et al. (2007) showed a trend that the effect claimed a 100% recovery rate, so patients who did not studies were mostly conducted in the US and improve felt blamed for failing to recover (Reme et al., England, and then to less extent in the Netherlands 2013). By practicing energy conservation and relaxa- and Australia. This trend seems to continue; we tion techniques patients felt more in control, but they excluded many studies from England (not fulfiling did not experience better health (Pinxsterhuis et al., the diagnostic criteria set for the present study), the 2015). All patients receiving GET found exercising US and Australia. However, we also excluded studies 12 A. M. MENGSHOEL ET AL. from Asia mainly addressing effects of acupuncture, Reviewing patients’ treatment experiences, patients herbal treatment and meditative exercises. Also prior found acknowledgement, reassurance and support by reviews included mostly European studies, and our health professionals to be important, and they felt safer reported effects are consistent with those reported if they had a follow-up after completing NPTs. Previous in prior reviews across the world and including papers reviews of adolescent (Parslow et al., 2017) and adult irrespective of case definition. As in our study, pre- studies (Drachler et al., 2009) have, consistent with our vious systematic reviews concluded that CBT reduces findings, reported that patients are frustrated about the fatigue (Chambers et al., 2006; Malouff et al., 2008; disputes over the nature of ME/CFS, find recognition by Price et al., 2008). Our study suggests that the results health professionals valuable, resist psychological expla- may be even better, as the control groups also often nations, and strive to find effective self-management received CBT. Unfortunately, the present effect studies strategies. The interviews highlight that health profes- of CBT do not include long-time follow-up assess- sionals meet the patients’ needs for recognition, but ments, so whether the effects are sustained should they also have negative experiences. Health profes- be addressed. The multimodal rehabilitation pro- sionals are “instruments” in delivering NPTs, and what grammes included both CBT and GET (Nunez et al., is delivered appears inseparable from how it is delivered 2011; Vos-Vromans et al., 2016). These rehabilitation and by whom. Therefore, attitudes and behaviours of programmes vary with respect to content, duration, health professionals matter. It may be very challenging control groups, and findings. Therefore, like the to meet patients when they have had negative experi- authors of a recent systematic review who included ences of former consultations with health professionals, two studies of rehabilitation in addition to ours as demonstrated by accounts of patients with chronic (Galeoto et al., 2018), we cannot draw conclusions musculoskeletal pain (Mengshoel et al., 2019). In the about effects of rehabilitation. Vos-Vromans’s study words of Hurwitz et al (2004, p. 90), “personal healing (Vos-Vromans et al., 2016) compared rehabilitation does not merely depend on what happens during ther- (including CBT) with CBT alone, but CBT differed in apy, but how therapy becomes an episode in a larger the two groups. Similarly, Nunez et al. (2011) com- narrative of illness and recovery experiences.” In addi- pared rehabilitation (including supervised GET) with tion, patients conclude that NPTs are incomplete. They GET counselling without any control of compliance. tend to feel uncertain about the meaning of illness and Therefore, it is also impossible to draw any conclu- express a need to find effective self-management stra- sions about how the CBT and GET components con- tegies, and this has to be given priority when designing tributed to the effects of the rehabilitation new NPTs. It seems that patients search to understand programmes. In fact, a recent meta-analysis concludes how to connect themselves and their lives to a non- that GET has minor positive effects (Larun et al., 2019). comprehensible illness and its fluctuating course. Nunez et al. (2011) found a positive effect on pain in Therefore, more knowledge about these issues has to counselled GET and worse pain in supervised GET. It be pursued by future research. seems plausible that those following supervised GET performed more exercise than those getting counsel- ling in GET. This indicates that more exercise can Methodological issues worsen pain. Activity pacing was found efficient in The content and delivery of NPTs varied considerably improving physical functioning in one study (Kos in the studies, and any theoretical reasons for includ- et al., 2015), but such improvement was not found ing the various components are not given. As NPTs after a self-management education programme fol- are based on various theoretical assumptions, each lowing principles of activity pacing (Pinxsterhuis NPT should first be tested to see if it is successful in et al., 2017). To our knowledge, there has not been achieving what it theoretically is supposed to do, and any previous published systematic review on the whether the changes are relevant in helping patients effects of activity pacing for patients with ME/CFS. with ME/CFS. If successful in both respects, other Taken together, the effects of NPTs, except for CBT, components could be added step by step and tested are inconclusive. We carefully compared our findings in accordance with the framework of developing com- with other systematic reviews applying broader diag- plex interventions (Craig et al., 2013; Richards & nostic criteria for inclusion of patients with ME/CFS Hallberg, 2015). Future RCTs should also include long- (Chambers et al., 2006; Drachler et al., 2009; Galeoto time follow-up and cost-benefit analysis, and in parti- et al., 2018; Kim et al., 2020; Larun et al., 2019; Malouff cular, more studies on the role of NPTs for children et al., 2008; Parslow et al., 2017; Price et al., 2008). The and adolescents are needed. conclusions of these systematic reviews are in line The studies of CBT showed rather consistent results with ours, so our assumption that diagnosis criteria in having an effect on modifying fatigue, while the could explain the positive effects reported in some effects of activity pacing and multimodal rehabilitation prior studies, for example, from CBT, is not supported. were inconsistent. However, a timely question is INTERNATIONAL JOURNAL OF QUALITATIVE STUDIES ON HEALTH AND WELL-BEING 13 whether the outcome measures were appropriate in we lost monographs of qualitative studies. However, the evaluating whether the intentions of the NPTs, and limited time for conducting the review made it impos- what was found relevant for patients, were reached. sible to analyse data from such theses. A strength of our At present, generic instruments, such as SF-36 and the scoping review is that the authors have various back- CIS fatigue subscale, mostly assessed effects. grounds, come from various European countries, and A systematic literature review by Haywood et al. are active researchers within this field. Our strategies (2012) examined whether patient-reported measures, follow a well-defined structure, and hopefully, our find- including those used in our review, had undergone ings are presented in a transparent way, so the trust- rigorous, scientific evaluations in patients with ME/ worthiness should be appropriate. The majority of the CFS. No evidence was found that patients had been included studies were from North-Western Europe. The involved in evaluating the relevance of any question- strict inclusion criteria might have excluded papers from naire, the content validities of which are therefore other European regions. However, with respect to the questionable. Likewise, measures showed little or mod- excluded effect studies, they were mostly conducted in erate responsiveness to NPTs, which is essential in the UK. The qualitative studies were not selected on the detecting effects. Another issue to be considered is basis of diagnostic criteria, and all except one were UK how to interpret statistically significant differences in studies, and thus all were conducted in the North- relation to clinical importance. It is questionable how Western Europe. We may have overlooked some stu- much change is needed in an instrument’s scale to dies, but also prior systematic reviews include papers make it both clinically relevant and meaningful for mostly from North-Western Europe, and studies from patients (Angst et al., 2017). For future research, we Eastern Europe and the South would be welcomed. recommend developing robust patient-reported dis- In conclusion; this scoping review underlines the ease-specific measures in collaboration with patients, importance of more positive social attitudes towards and international consensus should be reached about ME/CFS in general, and by health professionals in the use of such instruments in making findings com- particular. But the patients express ambiguity towards parable across studies. the contents of the programmes and consider them Patients with ME/CFS are not homogenous. Severely to be incomplete. CBT was found to relieve fatigue, affected patients are house- or bedbound, while others, but its long-term effects need more investigation. well represented in the effect studies we identified, Studies on activity-pacing and rehabilitation are struggle to maintain their living patterns. We did not scarce, and the effects are inconsistent. Patients, clin- find any studies on NPTs for severely affected patients. icians and researchers should collaborate in critically One reason for this may be that RCT designs are not scrutinizing existing patient reported outcome mea- appropriate in evaluating effects of such therapies for sures, and in systematically developing disease- severely affected patients. To attempt to close this specific measures and NPTs that are tailored to the knowledge gap, case studies are high priority. particular needs of patients with ME/CFS. Interviews with severely afflicted patients about their illness experiences, and interviews with patients that have become better after being bed- or house bond Acknowledgments about what mattered for their progress, are needed to We like to thank Hilde I. Flaatten, the librarian at the develop meaningful NPTs in the future. An alternative University Library of the Medical Faculty, University of Oslo means of testing such new NPTs could be to apply for performing the literature search. single subject experimental designs in which a subject serves as his/her own control (Bates, 1996; Zhan & Disclosure statement Ottenbacher, 2001). Patient-specific measures, such as Canadian Occupational Performance Measure as used No potential conflict of interest was reported by the authors. by Kos et al. (Kos et al., 2015) can be appropriate to examine eventual progress but are less easy to use because of the semi-structured format. In terms of clin- Notes on contributors ical practice, the semi-structured format has the advan- tage of being already a first step in the communication Anne Marit Mengshoel, RPT, PhD is professor at the with the patients, but in research, reliability can be an Department of Interdisciplinary Health Sciences, the Medical Faculty, University of Oslo, Norway. She founded issue when the assessors are not well trained. and chaired the research group Self-Management until last year. Her main research interests are patients’ illness and recovery experiences, rehabilitation outcomes and practices. Methodological considerations of the scoping review Ingrid Bergliot Helland, MD, PhD is a pediatrician working at Oslo University Hospital, Department of Clinical A limitation of our study is that we excluded grey Neurosciences for Children, Rikshospitalet. She is also the papers. By excluding doctorial theses, we noticed that head of the Norwegian National Advisory Unit on CFS/ME 14 A. M. MENGSHOEL ET AL. and the National Advisory Unit on Feeding Disorders in Bates, B. T. (1996). Single-subject methodology: An alterna- Children, and has a special interest in the neurodegenera- tive approach. Medical Science of Sports and Exercise, 28, tive disease Neuronal Ceroid Lipofuscinosis. Her main 631–638. research interests are related to these fields. Britten, N., Campbell, R., Pope, C., Donovan, J., Myfanwy, M., & Pill, R. (2002). Using meta ethnography to synthesise Mira Meeus holds a PhD in Rehabilitation Sciences and qualitative research: A worked example. Journal of Health Physiotherapy. She is full-time appointed as professor at Services Research and Policy, 7(4), 209–215. https://doi. the Departments of Rehabilitation Sciences and org/10.1258/135581902320432732 Physiotherapy at the University of Antwerp and Ghent Broughton, J., Harris, S., Beasant, L., Crawley, E., & University (Belgium). She is co-founder of the International Collin, S. M. (2017). Adult patients’ experiences of NHS research group Pain in Motion and is internationally recog- specialist services for chronic fatigue syndrome (CFS/ME): nized for her expertise in chronic pain and central A qualitative study in England. BMC Health Services sensitization. Research, 17(1), 384. https://doi.org/10.1186/s12913-017- Jesús Castro-Marrero PhD is currently Senior Researcher in 2337-6 the Division of Rheumatology, ME/CFS Research Unit at the Carruthers, B. M., Jain, A. K., De Meirleir, K. L., Peterson, D. L., Vall d'Hebron University Hospital, Barcelona, Spain. His Klimas, N. G., Lerner, A. M., Bested, A. C., Flor-Henry, P., research is focusing on the neurobiological basis of ME/ Joshi, P., Powles, A. C. P., Sherkey, J., & van de Sande, M. I. CFS, with special interest in neuroinflammation and micro- (2003). Myalgic Encephalomyelitis/Chronic Fatigue biota-gut-brain axis and the autonomic nervous system, Syndrome. Journal of Chronic Fatigue Syndrome, 11(1), including the enteric nervous system and the vagus nerve 7–115. https://doi.org/10.1300/J092v11n01_02 stimulation in ME/CFS. Carruthers, B. M., van de Sande, M. I., De Meirleir, K. L., Klimas, N. G., Broderick, G., Mitchell, T., Staines, D., Derek Pheby has recently retired. His most recent appoint- Powles, A. C., Speight, N., Vallings, R., Bateman, L., ment was as Visiting Professor of Epidemiology at Baumgarten-Austrheim, B., Bell, D. S., Carlo-Stella, N., Buckinghamshire New University, High Wycombe, England. Chia, J., Darragh, A., Jo, D., Lewis, D., Light, A. R., Marshall- He has been involved in ME/CFS research for many years in Gradisnik, S., … Stevens, S. (2011). Myalgic encephalo- the UK, and was a member successively of the National Task myelitis: International Consensus Criteria. Journal of Force, the Chief Medical Officer's Working Group, and the Internal Medicine, 270(4), 327–338. https://doi.org/10. 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