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Frontiers in Neurology 01 frontiersin.org
Focus on post-exertional malaise
when approaching ME/CFS in
specialist healthcare improves
satisfaction and reduces
deterioration
MarjonE.A.Wormgoor
1
* and SanneC.Rodenburg
2
1 Vestfold Hospital Trust, Division of Mental Health and Addiction, Tønsberg, Norway, 2 Neuroscience and
Cognition, Graduate School of Life Sciences, Faculty of Medicine, Utrecht University, Utrecht,
Netherlands
Background: Post-exertional malaise (PEM) is considered a hallmark characteristic
of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This may also
apply to subgroups of patients with long COVID-induced ME/CFS. However, it is
uncertain to what extent PEM is acknowledged in routine specialist healthcare for
ME/CFS patients, and how this aects patient outcomes.
Objective: This study aims to evaluate to what extent ME/CFS patients experienced
focus on PEM in specialist healthcare practice and its significance for outcome
and care quality.
Methods: Data from two online cross-sectional surveys covering specialist
healthcare services for ME/CFS patients at rehabilitation institutes in Norway
and two regional hospitals, respectively, were analyzed. Evaluations of 788
rehabilitation stays, 86 hospital consultations, and 89 hospital interventions were
included. Logistic regression models and Mann–Whitney U-tests were used to
quantify the impact of addressing PEM on health and functioning, care satisfaction,
or benefit. Spearman’s rank correlation and Cronbach’s alpha of focus on PEM
with the respondents’ perception of healthcare providers’ knowledge, symptom
acknowledgment, and suitability of intervention were assessed as measures for
care quality and their internal consistency, respectively.
Results: PEM was addressed in 48% of the rehabilitation stays, 43% of the
consultations, and 65% of the hospital interventions. Failure to address PEM roughly
doubled the risk of health deterioration, following rehabilitation (OR = 0.39, 95%
CI 0.29–0.52; 40.1% vs. 63.2% P = <0.001) and hospital intervention (OR = 0.34,
95% CI 0.13–0.89; 22.4% vs. 45.2%, p = 0.026). The focus on PEM (PEM-focus)
during the clinical contact was associated with significantly higher scores on
patients’ rated care satisfaction and benefit of both consultation and intervention.
Furthermore, addressing PEM was (inter)related to positive views about healthcare
providers’ level of knowledge of ME/CFS, their acknowledgment of symptoms,
obtained knowledge, and the perceived suitability of intervention (Cronbach’s
alpha ≥0.80).
Discussion: PEM is still frequently not acknowledged in specialist healthcare
practice for ME/CFS patients in Norway. Not addressing PEM substantially
increased the probability of a decline in health and functioning following the
intervention and was strongly associated with reduced perceived care quality,
satisfaction, and benefit. These findings may berelated to the applied explanatory
models for ME/CFS and are most likely of relevance to long COVID.
OPEN ACCESS
EDITED BY
Nuno Sepulveda,
Warsaw University of Technology, Poland
REVIEWED BY
Georey Moore,
Cornell University, UnitedStates
Nina Muirhead,
Buckinghamshire Healthcare NHS Trust,
UnitedKingdom
*CORRESPONDENCE
Marjon E. A. Wormgoor
rodeworm@online.no;
marwor@siv.no
RECEIVED 03 July 2023
ACCEPTED 31 October 2023
PUBLISHED 01 December 2023
CITATION
Wormgoor MEA and Rodenburg SC (2023)
Focus on post-exertional malaise when
approaching ME/CFS in specialist healthcare
improves satisfaction and reduces
deterioration.
Front. Neurol. 14:1247698.
doi: 10.3389/fneur.2023.1247698
COPYRIGHT
© 2023 Wormgoor and Rodenburg. This is an
open-access article distributed under the terms
of the Creative Commons Attribution License
(CC BY). The use, distribution or reproduction
in other forums is permitted, provided the
original author(s) and the copyright owner(s)
are credited and that the original publication in
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accepted academic practice. No use,
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does not comply with these terms.
TYPE Original Research
PUBLISHED 01 December 2023
DOI 10.3389/fneur.2023.1247698
Wormgoor and Rodenburg 10.3389/fneur.2023.1247698
Frontiers in Neurology 02 frontiersin.org
KEYWORDS
ME/CFS, myalgic encephalomyelitis, chronic fatigue syndrome, post-exertional malaise,
post-exertional symptom exacerbation, patient experience, specialist healthcare,
healthcare quality
1 Introduction
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
is a long-term, severe multisystem disease with a distinctive clinical
picture, oen, but not necessarily, preceded by an infection. Its
pathophysiology is still uncertain; therefore, some clinical and
research settings apply a biopsychosocial explanatory model for ME/
CFS. In these settings, ME/CFS is perceived as a fatigue illness,
explained with a psychosomatic understanding as a maladaptive
response to an infection or overload, perpetuated by dysfunctional
personality factors or beliefs, health anxiety, and deconditioning
(1–3). is approach has been criticized for overlooking the evidence
of detectable pathophysiological disturbances explaining the
symptoms of ME/CFS patients (4–7). Others, however, apply a
biomedical approach and consider ME/CFS as a maladaptive
pathophysiological response, following an infection or other trigger
that remains inadequately studied.
is biomedical explanatory model is acknowledged in the
diagnostic criteria sets for ME/CFS that have been dened during the
last two decades (6, 8–11). ese criteria are more specic than earlier
criteria. Core symptoms are fatigue, exertion-induced worsening of
disease and symptoms, cognitive dysfunction, and sleep dysfunction
(11). Furthermore, immune dysfunction, orthostatic intolerance,
neuroendocrine, circulatory, and gastrointestinal dysfunction are
common symptoms, while mental illness as the cause of the symptoms
is explicitly excluded.
Exertion-induced aggravation of symptoms in ME/CFS is generally
called post-exertional malaise (PEM) or post-exertional symptom
exacerbation (PESE). It involves a relatively long-lasting and severe
worsening of symptoms and/or the appearance of new symptoms, with
a further substantial reduction in functioning (9, 12, 13). It may bean
immediate or a delayed, disproportionate response to physical,
orthostatic, or cognitive eort, or sensory stimuli, which previously
were tolerated. It can take days, weeks, or longer to return to baseline
(12, 14, 15). Sometimes, a new, more severe baseline is established. e
delayed onset and the broad constellation of symptom deteriorations
distinguish ME/CFS from other diseases with severe fatigue or
deconditioning (6, 16–21). PEM is widely recognized as the most
debilitating and persistent feature of ME/CFS (22). e PEM
phenomenon has been demonstrated in multiple studies, both with
patient-reported outcome measures and with objective measures.
Objective ndings include new or increased structural and functional
abnormalities, following controlled exertion situations (23–26). ese
ndings indicate disturbances in energy metabolism and a dysfunctional
autonomic nervous system, impairing the body’s ability to recover from
exertion (27, 28). In current practice in Norway, PEM is at best evaluated
by anecdotal described experiences; standardized questionnaires (18)
or clinical objective PEM, e.g., repeated hand grip strength (29) or
cardiopulmonary exercise tests (25), is not routine practice.
If a psychosomatic understanding is applied to approach ME/CFS,
PEM is usually disregarded and rather considered as a dysfunctional
cognition and extreme behavioral response (30). Interventions
typically aim at interrupting the self-perpetuating vicious circle that is
thought to maintain symptoms. Assumed mistaken illness beliefs,
dysfunctional cognitions, and fear of activity are aimed to becorrected
by increasing physical activity to overcome avoidance behavior and
regain physical tness (31, 32). In this view, commonly applied
approaches are cognitive behavioral therapy (CBT) and graded
exercise therapy (GET), respectively, or varieties that share central
conceptual elements.
Current research and clinical recommendations that acknowledge
a biomedical base and the PEM phenomenon, however, recognize that
there is currently no scientic evidence for eective treatment of ME/
CFS and explicitly discourage curative CBT and GET forms (10, 33–
37). Instead, pacing strategies are considered to bethe most eective
approach to reduce the risk of PEM relapse and retain or improve
physical functioning and quality of life (10, 36–40).
In Norway, the main responsibility of the diagnosing process of
adults with ME/CFS symptoms is held by the general practitioner
(GP), preferably a specialist in general medicine (41). In case of
unclear dierential diagnostic issues, the GP should refer to relevant
clinical specialists for further evaluation. e European Network on
ME/CFS (EUROMENE) expert consensus (36) recommends referral
to specialist service for conrmation of diagnosis, drug treatment, and
a range of service oerings, such as multidisciplinary rehabilitation,
supportive counseling, education on self-management, and symptom-
contingent pacing.
In several studies (42–45), various aspects of perceived care
quality in specialist healthcare for ME/CFS patients have been
evaluated, but they did not focus on the attention to PEM. In general,
only a minority was satised with the obtained care and specialists’
knowledge about ME/CFS. In another, recent Norwegian study,
however, perceived care quality was evaluated related to the specicity
of the diagnosis and PEM severity (42). Patients meeting more specic
criteria and patients with higher PEM scores reported more negative
experiences with specialist care.
It appears essential to acknowledge PEM in the diagnostic
process and therapeutic approach of ME/CFS. To our knowledge, it
is inadequately documented to what degree PEM generally is
addressed in ordinary healthcare practice or more specically in
specialist healthcare practice in Norway. Likewise, it is insuciently
documented what the consequences are of not addressing PEM for
the patient-related outcome and the perceived quality of these
services regarding clinical eectiveness, patient safety, and
patient experiences.
Awareness and knowledge about PEM seem also of specic
relevance for a new growing subgroup of patients facing similar
symptoms and biological abnormalities, and PEM (46–52). In the
patients with persistent, debilitating symptoms following acute
COVID-19 (long COVID), approximately up to half of the patients
will meet the diagnostic criteria for ME/CFS (46, 51, 53).
Consequently, ME/CFS prevalence is increasing dramatically.
Wormgoor and Rodenburg 10.3389/fneur.2023.1247698
Frontiers in Neurology 03 frontiersin.org
Addressing PEM in the approach of long COVID patients is of specic
importance as well (54–56).
e aim of this present study was to assess the signicance of
acknowledging the PEM phenomenon in the clinical approach of ME/
CFS patients in specialist healthcare practice.
e rst objective was to evaluate to what extent ME/CFS patients
experienced focus on PEM during clinical consultations, hospital
intervention, or rehabilitation.
e second objective was to estimate to what degree focus on
PEM in the received care is related to patient-reported outcomes. e
primary outcome is the impact of addressing PEM during an
intervention on subsequent changes in health status. e secondary
outcome measures are the reported care satisfaction or the perceived
general benet of the obtained care.
e third objective was to assess whether the acknowledgment of
PEM in a clinical situation is associated with patient-reported
experiences of perceived healthcare quality.
2 Materials and methods
is study is a non-prespecied secondary analysis, applying data
from two patient surveys executed by the Norwegian ME Association
(NMEF). e two patient surveys focused on dierent healthcare
settings, but objectives, methods, and questionnaires are partly similar
and described below.
Both surveys were retrospective, anonymous, Internet-based on
the platform SurveyMonkey and limited to one response per IP
address. ere were no time restrictions on response during the study
period as the questionnaire remained open until submitted.
e objective of the hospital survey (57) was to evaluate the
experiences of ME/CFS patients with specialist healthcare services at
two regional hospitals in Southeast Norway. ese healthcare services
covered two dierent types of clinical settings: consultations and
interventions. Experiences with these settings were evaluated
separately in the analyzes. Data collection was performed in the
period 5–31 March 2022 and aimed at covering the period since 2017.
If they in that period had received care at dierent departments, the
respondents reported that separately, but for each department, only
once per consultation and once per intervention.
e rehabilitation survey (58) aimed at retrospectively mapping
the experiences of ME/CFS patients with Norwegian rehabilitation
services. Data collection was carried out from 4 September 2017 until
15 October 2017 with no restrictions on region and date of stay at one
of the rehabilitation facilities.
For the current study, analyzes were restricted to adult respondents
included in the surveys. Respondents should have obtained hospital
care at one of the two concerning hospitals or rehabilitation at an
institute in Norway. Furthermore, they should have an ME/CFS
diagnosis or long COVID with PEM and have answered the question
concerning PEM-focus in the obtained healthcare setting. Figure1
presents the ow chart of the study.
2.1 Subjects
For both surveys, invitations were shared on various relevant open
and closed Norwegian Facebook groups for ME/CFS patients, their
relatives, and other interested parties, both within and outside the ME
Association’s auspices. Relatives could answer on behalf of patients
who were too ill to answer themselves.
In the hospital survey, members of Vestfold and Telemark
Regional ME Association were also directly approached by email. e
survey was open for respondents who had been referred to the
relevant hospitals during the last 5 years and had an ME/CFS or long
COVID diagnosis, were in a diagnosing process for this, or considered
themselves as having ME/CFS, post-viral syndrome, or long COVID
with PEM. Before evaluating the occurrence of PEM, as well as other
typical ME/CFS symptoms, PEM was explained in the survey. en,
the respondents reported which diagnosis they regarded as the most
appropriate for them. Only the respondents that answered, “ME/CFS
or ME,” “sequela aer COVID-19 infection with PEM” or “Post-viral
syndrome” and had PEM could progress further in the survey.
Respondents not being adults (here below 20) were excluded from the
analyzes in the analysis.
In the rehabilitation survey, respondents residing in Norway who
previously had obtained an ME/CFS diagnosis G93.3 (59) from the
specialist health service or A04 (60) from a GP specialist in general
medicine were invited to participate.
2.2 Measures
All measures are presented in Tables 1, 2, including applied
methods for dichotomization of variables, if relevant. e complete
questionnaires (in Norwegian) can befound in the underlying reports
(57, 58).
2.2.1 Respondent characteristics
e operationalization of respondents’ characteristics is presented
in Table1. Sociodemographic characteristics covering gender, age, and
participation degree in work and school were only evaluated in the
hospital survey. Both surveys evaluated some disease characteristics
such as diagnosis, disease duration, and severity grading.
2.2.2 Post-exertional malaise-focus as an
explanatory variable
e primary variable of interest was the focus on PEM
(PEM-focus) in specialist healthcare settings and its impact.
PEM-focus in the three types of healthcare settings was operationalized
with closed questions, but with dierent wording and dierent scales
for each type of healthcare setting (see Table 2). In the analyzes,
PEM-focus was dichotomized as PEM+ (PEM was addressed) or
no-PEM (PEM was not addressed); this is described in Table2 as well.
2.2.3 Patient-reported outcome
e assessments of the outcome measures are presented in
Table2. e impact of hospital intervention on health status was
operationalized by computing changes in the evaluated disease
severity before and aer the intervention–in the rst 2 weeks (post-
intervention) and 3 to 6 months (short-term follow-up). Disease
severity classication was based on the Norwegian National
Guidelines for CFS/ME (41) and ICC (9). More severe disease severity
aer the intervention was classied as ‘deteriorated’. ‘Not deteriorated’
includes both unchanged and improved health status. In addition, the
benet of the hospital interventions was more specically evaluated
Wormgoor and Rodenburg 10.3389/fneur.2023.1247698
Frontiers in Neurology 04 frontiersin.org
related to various domains: physical health, cognitive eort, mental
health, ability to master daily tasks, ability to regulate activity level,
and quality of life. e answer options “much worse” and “somewhat
worse” were rated as “deteriorated.”
Post-intervention changes in health status following rehabilitation
were operationalized as ‘deteriorated’ if the respondents strongly
disagreed with the statement “I felt healthier just aer the stay than
before.” Short-term changes reported as “I felt better one month aer
the stay than before” were considered as “deteriorated” if the
respondent strongly disagreed. Other replies were valued as
‘not deteriorated’.
In addition, satisfaction with the consultation or the rehabilitation
program and perceived general benet of the hospital intervention
were assessed with 5-point Likert scales and applied as
outcome measures.
2.2.4 Patient-reported experiences of perceived
healthcare quality
Relevant items are presented in Table 2. In addition to
treatment completion, all care quality variables were assessed with
5-point Likert scales. Operationalization varies by care setting.
Appraisal of the quality of the clinical consultations (the hospital
survey) was assessed by evaluating the patients’ view on the ME/
CFS-specic knowledge and experienced symptom with respect to
the healthcare professionals. Rated suitability of the intervention
to the respondents’ condition and the proportion who completed
treatment were considered as additional indicators for care quality
of intervention and rehabilitation. An item of the rehabilitation
survey that evaluated whether the respondents felt they had
obtained useful knowledge was included. For hospital intervention,
respondents’ opinion of the extent to which they had acquired
PEM coping skills and whether they had obtained incorrect
treatment was included as well.
2.2.5 Situational context
In both surveys, the intervention duration and the involved
hospital, department, or rehabilitation institution were assessed with
closed questions and an ‘other’ option (see Table1).
In the hospital survey, the type of intervention options was
assessed systematically as well: individual treatment, group course,
or both. e types of treatment options were exercises to increase
mobility, aerobic condition, or relaxation, cognitive behavioral
therapy (CBT) aimed at reducing symptom focus and
increasing activity, CBT focused on support and illness coping,
or medication.
Apart from which particular rehabilitation institution was
evaluated, no context variables were assessed systematically in the
rehabilitation survey.
FIGURE1
Study flow chart of survey 1 and survey 2, showing the inclusion of respondents and identification of corresponding evaluated care events for analyzes.
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Frontiers in Neurology 05 frontiersin.org
2.3 Analysis
Analyzes are based on available data from two surveys: a hospital
survey (57) and a rehabilitation survey (58).
Perceived PEM-focus (PEM+ or no-PEM) in provided specialist
healthcare is the main object of interest. For the dierent healthcare
settings, PEM-focus, as evaluated by the respondents, is mainly
analyzed as dichotomized variables.
Situational context variables, such as which hospital, department,
or rehabilitation institution, as well as type of intervention, are not
presented in detail. General context dierences in PEM-focus were
evaluated with chi-square tests.
To determine the impact of PEM-focus on the outcome, binary
univariate and multivariate logistic regression were used with
PEM-focus as the explanatory variable and disease duration and
severity (14, 61, 62) included as covariates if available. e response
variables were dichotomized outcome measures of satisfaction or
rated general benet, impact on health status following the
intervention, and additionally for the hospital interventions, the
impact on various ME/CFS-related domains. Because of the limited
expected improvement in health status and the real possibility of
deterioration following the intervention, health impact was evaluated
as ‘no-deterioration’ versus ‘deterioration’.
Satisfaction with clinical consults was only evaluated with
univariate analyzes; crude odds ratios (ORs) with corresponding 95%
condence intervals (95% CI) are presented. For both intervention
settings, both crude and adjusted OR were calculated. Hence, OR > 1.0
indicates that the variable is associated with a higher probability of the
response variable (satisfaction, benet, health, or function
deterioration), whereas OR < 1.0 indicates an association with a lower
probability. e results were also presented as bar diagrams with full-
scale outcome variables. Mann–Whitney U-test was applied to assess
group dierences. e impact of PEM-focus on changes in health
status following hospital intervention was evaluated with paired-
sample Wilcoxon signed rank-sum tests for PEM+ and no-PEM.
e care quality variables are presented with Spearman’s rank
correlation coecient (Spearman’s rho: ρ) as a measure of association
with PEM-focus. In addition, Cronbach’s alpha was calculated as a
measure of internal consistency of the care quality variables and the
full scale of PEM-focus answers.
TABLE1 Relevant questions describing the respondents’ characteristics and the situational context.
Domain Survey 1
Hospital consultation
Survey 1
Hospital intervention
Survey 2
Rehabilitation
Respondents’ characteristics
Gender Female/male 1. Female, 2. male -
Age < 10, 10–19, 20–29, 30–39, 40–49,
50–59, 60–69, ≥ 70
< 10, 10–19, 20–29, 30–39, 40–49, 50–59, 60–
69, ≥ 70
… over 18
Participation work/education 1. 0%, 2. 25%, 3. 50%, 4. 75%, 5. 100%
Sickness benets (≥75%)/ No education
lessons
1. 0%, 2. 25%, 3. 50%, 4. 75%, 5. 100%
Sickness benets (≥75%)/ No education lessons
Diagnostician Who made the diagnosis? Who made the diagnosis? Who made the diagnosis?
Disease duration For how long have youhad CFS/ME
fatigue symptoms?
< 6 months, 6–12 months, 1–2 years,
2–5 years, 5–10 years, > 10 years
For how long have youhad CFS/ME fatigue
symptoms?
< 6 months, 6–12 months, 1–2 years, 2–5 years,
5–10 years, > 10 years
When was the ME/CFS diagnosis set?
(year)—was recalculated to the categories
< 1 year, 1–2 years, 2–5 years, 5–10 years, >
10 years
Disease severity What severity degree of ME/CFS do
youhave?
1. Below mild, 2. Mild, 3, mild–
moderate, 4. Moderate, 5. Moderate–
severe, 6. Severe, 7. Sever-very severe, 8.
Very severe
What severity degree of ME/CFS do youhave?
What severity degree of ME/CFS did youhave
at start of the intervention?
1. Below mild, 2. Mild, 3, mild–moderate, 4.
Moderate, 5. Moderate–severe, 6. Severe, 7.
Sever-very severe, 8. Very severe
What was the severity degree at start of the
rehabilitation stay?
2. Mild, 4. Moderate, 6. Severe, 8. Very severe
Situational context
Medical specialty Which department or clinic? Which department or clinic? What sort of
intervention?
Which rehabilitation facility?
Intervention duration How many days? (open answer) How many weeks? 1 /2/3/4/other
Type of treatment Counseling, group course, training to increase
exibility, training to increase activity and
tness, relaxation, CBT aimed at coping of
severe illness, CBT aimed at symptom
reduction and activity increase, medications or
supplements, or other
Group course-target patient
group
ME/CFS, fatigue, or various health complaints
Answer alternatives are italicized.
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TABLE2 Relevant questions that were applied in the analyzes: PEM-focus in the clinical contacts, variables assessing patient-reported outcome, and
patient-reported experiences of perceived healthcare quality.
Domain Survey 1 Hospital
consultation
Survey 1 Hospital
intervention
Survey 2 Rehabilitation
Post-exertional malaise (PEM)
PEM-focus Were youasked, directly or indirectly, if
youhad PEM? 1. No, 3. Unsure, 5. Yes
Did yougain any new knowledge or
understanding about PEM?
Was PEM explained during the stay?
1. No, 5. Yes
1. PEM was not seen as typical or
relevant, 2. No information, 3. Nothing
new, 4. Some, 5. A lot
Patient-reported outcome
Care satisfaction/Benet Overall, were yousatised with the
consultation? **
What benet have youhad, overall,
from the intervention?
1. No benet, 2. Little benet, 3. Some
benet, 4. Large benet, 5. Very large
benet
I amsatised with my stay at the
rehabilitation facility *
Impact on health What severity degree of ME/CFS did
youhave the rst following 2 weeks/the
following 3 to 6 months? 1. below mild,
2. Mild, 3. Mild–moderate, 4. Moderate,
5. Moderate–severe, 6. Severe, 7. Sever-
very severe, 8. Very severe
I felt better just aer the stay than before
I felt better 1 month aer the stay than
before
1. Strongly disagree, 2. Disagree, 3. Neither
agree nor disagree, 4. Agree, 5. Strongly
agree
Impact on various domains How did youbenet from the
intervention, when it comes to: physical
health, cognitive eort, mental health,
and ability to master daily tasks, ability
to regulate activity level, quality of life?
1. Much worse, 2. Somewhat worse, 3.
No, change, 4. Somewhat improved, 5.
Strongly improved
Patient-reported experiences of perceived healthcare quality
Suitability of the intervention Did youfeel that the intervention was
suitable for your situation? *
e activity level was adapted to my
illness*
Healthcare provider knowledge?Do youthink that the doctor or possibly
other healthcare provider had a good
knowledge of M//CFS?
1. Very little, 2. Not much, 3. Both, 4.
Good, 5. Very good
Do youthink that this therapist/
supervisor/institution had good
knowledge of ME/CFS?
1. Very little, 2. Not much, 3. Both, 4.
Good, 5. Very good
e healthcare providers had good
knowledge on ME/CFS*
Symptom acknowledgment?Did youfeel that your symptoms were
taken seriously? *
Did youfeel that your symptoms were
taken seriously? **
e sta at the rehabilitation facility were
understanding when Itold them about my
symptoms *
Gained benecial knowledge or skills Did the intervention help youto beable
to prevent and manage PEM?
1. PEM was not seen as typical or
relevant, 2. No information, 3. Nothing,
4. Somewhat, 5. A lot
I learned a lot that Ihave beneted from
later *
Incorrect treatment Do youthink youobtained incorrect
treatment in some way?**
–
Intervention completed Did youcomplete the intervention?
1. No Iquit because Igot worse/ no Iquit
because Idid not think it was helpful, 2.
Yes
Were youat the rehabilitation facility for
the entire period?
1. No, Igot worse and chose to go home/ no,
Igot worse and was sent home by the sta,
2. Yes
Answer alternatives are italicized, and in the case of dichotomized response options, the desirable responses are underlined. *1. Strongly disagree, 2. Disagree, 3. Neither agree nor disagree,
4. Agree, 5. Strongly agree; **1. Not at all, 2. To a small degree, 3. To some degree, 4. To a great degree, 5. To a very great degree.
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No power calculation was performed as the primary surveys were
considered explorative. Dierences between respondents that were
included and excluded in the analyzes of this study are compared in the
available disease characteristics within both surveys with chi-square tests.
In the hospital survey, screening for ME/CFS diagnosis and possible
exclusion if ME/CFS was not considered as their main diagnosis was done
in the rst part of the survey. Sociodemographics were questioned at the
end of the survey and thus were not answered by most of the excluded
respondents. In the rehabilitation survey, no sociodemographic
characteristics were collected. is made it impossible to compare the
sociodemographics of respondents who completed vs. not completed
the surveys.
Data analyzes were performed using IBM SPSS Statistics for
Windows, version 28 (IBM Corp., Armonk, N.Y., UnitedStates). A
p-value of less than 0.05 was considered statistically signicant.
3 Results
3.1 Subjects
Figure1 shows the study ow chart including both surveys. In the
hospital survey, 82 respondents were included in the analyzes. In total,
86 consultations and 89 interventions were evaluated. e majority
had evaluated only one consultation (71%) or intervention (69%), 21
and 23%, respectively, had evaluated two, and 8% had evaluated
consultations and interventions with three dierent departments. In
the rehabilitation survey, 788 respondents who had participated in a
rehabilitation program at a rehabilitation facility in Norway
were included.
e non-completers of the hospital survey did not dier in illness
duration, age of symptom debut, diagnosis and disease severity, the
degree they experienced PEM, and fulllment of the Canadian
Consensus Criteria (8) as evaluated in this survey. e non-completers
had less oen obtained an ME/CFS or long COVID with PEM
diagnosis (80.5% vs. 97.5%, p = 0.002). In the rehabilitation survey,
there was no dierence in how long ago the diagnosis was set and by
whom, between the respondents that were included or excluded for
analyzes (see Figure1).
3.1.1 Sociodemographic and disease
characteristics
In the hospital survey, 84.5% was female and the age
distribution at the time of the survey was 26.4% 20–29 yr., 18.1%
30–39 yr., 27.8% 40–49 yr., 26.4% 50–59 yr., and one respondent
older than 60. The majority (88.7%) was not working or studying
at all, 5.6% worked or studied 1–5 h weekly, 4.2% 6–20 h, and only
one respondent worked or studied more than 20 h weekly. There
were no sociodemographic data available from the respondents
of the rehabilitation survey.
ME/CFS was self-reported as the main diagnosis by 80 of the 82
respondents of the hospital survey; for 79, a physician had set this
diagnosis as well. One respondent had obtained a ‘burnout or chronic
fatigue’ diagnosis. Two respondents had long COVID; this was conrmed
for one respondent. In total, 24% of the respondents were diagnosed by a
GP only, 39% by a specialist of one of the hospitals only, or by other
specialists in private practice only (7%). e remaining respondents were
diagnosed by both a GP and a specialist (24%) or by both a hospital and
a private specialist (5%). No respondents had reported that they ‘had a
fatigue illness (including ME/CFS) before but not now’.
All patients in the rehabilitation survey self-reported that they had
been diagnosed with ME/CFS. Twenty patients (0.9%) of the subjects that
had started the survey reported they were neither a ME/CFS patient nor
a relative and had been excluded. 20% of the respondents had received the
diagnosis from their GP, 23% had consulted a specialist in private practice,
and 49% had received the diagnosis from the local or regional hospital.
8% had received the diagnosis from the national CFS/ME center, a third-
line service for advanced interdisciplinary assessment and guidance for
adult patients.
Disease duration and severity are reported in Table3.
TABLE3 Disease duration and severity.
Hospital survey Rehabilitation survey
n(%) n(%)
ME disease duration*82 770
< 1 yr. 0 0.0% 21 2.7%
1–2 yr. 5 6.1% 182 23.7%
2–5 yr. 19 23.2% 247 32.2%
5–10 yr. 33 40.2% 217 28.3%
> 10 yr. 25 30.5% 100 13.0%
Disease severity at intervention start 52 788
Mild 2 3.7% 162 20.6%
Mild to moderate 20 37.0%
Moderate 17 31.5% 519 65.9%
Moderate to severe 12 22.2%
Severe 3 5.6% 106 13.5%
Severe to very severe 0 0.0%
Very Severe 0 0.0% 1 0.1%
*Hospital survey: duration of ME/CFS symptoms at the date of survey response. Rehabilitation survey: time from year of diagnosis until intervention start.
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3.2 Situational context and PEM-focus
The clinical consultations with a health provider at the two
relevant hospitals (n = 86) were received at mainly six different
types of departments. The majority had been at an ME/CFS
Medicine Clinic (30.2%), a department of Physical Medicine
(23.3%), or Neurology (20.9%). The others had been at a
department of Infectious Diseases (8.1%), Mental Health (8.1%),
or an ME/CFS Outpatient Clinic (5.8%), Gastroenterology
(2.3%), or Pulmonary (1.2%). The hospital interventions (n = 89)
were mainly received at a department of Physical Medicine
(38.2%) or a department for Therapeutic Patient Education
(38.2%). The remaining interventions were received at an ME/
CFS Medicine Clinic (6.7%), departments of Mental Health
(6.7%), Health and Work (5.6%), or Neurology (4.5%).
e type and duration of the hospital interventions varied.
Intervention could include educational group courses (70.8%),
individual consultation/one-to-one counseling (57.3%), or both. In
addition to education in the group courses, the interventions
comprised CBT aimed at reducing symptom focus and increasing
activity (14.6%), CBT focused on support and illness coping (11.2%),
exercises to increase mobility (4.5%), aerobic condition (3.4%), or
relaxation (4.5%), as well as medication or dietary supplements
(2.2%). Most hospital interventions were delivered on an outpatient
basis, generally once or a few times. e educational courses were
either intensive (3 days within 1 week) or spread over a longer period
(6–8 times, once every 1 or 2 weeks). Only 67.2% of the respondents
attended educational courses aimed specically at ME/CFS, and the
rest of the courses were aimed at patients with either general fatigue
(21.8%) or other health complaints (10.9%).
Experiences of obtained rehabilitation services (n = 788) were
evaluated for over 20 rehabilitation facilities in Norway. Two
rehabilitation facilities were each evaluated by over 100 respondents
(32.1% of respondents), four by over 50 respondents (35.3%), and four
by at least 20 respondents. In the rehabilitation survey, applied
intervention methods were not evaluated systematically. However,
according to the open-ended comments in the survey, the
rehabilitation institutions had dierent approaches to the
rehabilitation of ME/CFS patients. Some encouraged CBT aimed at
reducing symptom focus combined with a graded activity increase.
Other rehabilitation facilities provided explanations about exertion-
induced symptom exacerbation (PEM) and focused on the importance
of managing and adjusting activity levels according to the patient’s
capacity (“energy envelope theory”) to prevent PEM (58).
Overall, respondents reported that PEM was addressed in
43.0% of the consultations, 65.2% of the hospital interventions,
and 47.5% of the rehabilitation stays. A more detailed distribution
is presented in Figure2. Whether PEM was addressed (PEM+) or
not (no-PEM) varied significantly across the different settings
from zero to 81% for clinical consultations (p < 0.001) and from
29 to 100% for hospital intervention (p < 0.001). Among the
respondents who had participated in an educational group course
or had received counseling, 71.4 and 45.1%, respectively, reported
that PEM had been addressed. In the group courses specifically
aimed at ME/CFS patients, 97.7% perceived PEM+, while PEM+
was 14.3% in the groups for fatigue and other health complaints.
Among the rehabilitation facilities, reported PEM+ varied
significantly as well, from 2.2 to 68.8% (p < 0.001).
3.3 Post-exertional malaise-focus as an
explanatory variable for the outcome
Dierences in several outcome measures stratied by PEM-focus
(no-PEM or PEM+) are presented in Figures3–5. In addition, Table4
summarizes the results of logistic regression analyzes for the
association between PEM-focus and binary outcome measures.
Multivariate logistic regression analyzes produced nearly identical
results as univariate logistic regression for the impact of PEM. e
results of the univariate regression analyzes are, therefore, not
presented here.
Figure3 and Table4 present the impact of PEM-focus on the
health state aer nishing the intervention. For the majority, their
health state did not change. On average, for respondents in both
groups, disease severity was worsened in the rst 2 weeks following
hospital intervention (p = 0.005in no-PEM and p = 0.008 in PEM+).
From baseline until 3 to 6 months following baseline, dierences were
only signicant in no-PEM (p = 0.042 and p = 0.13in PEM+).
However, there was a tendency that at both time points,
around twice as many respondents from the no-PEM group
experienced a deterioration of health status, following the
intervention compared to the PEM+ group. Overall, if PEM had
not been addressed in the intervention, logistic regression
showed that the odds of experiencing health deterioration on at
least one of the two time points increased significantly following
both hospital intervention (proportion 22.4% in PEM+ vs. 45.2%
in no-PEM, p = 0.026) and rehabilitation (40.1% vs. 63.2%
P = <0.001) [adjusted OR: 0.34 (95% CI 0.13–0.89; p = 0.027) and
0.39 (95% CI 0.29–0.52; P = <0.001), respectively]. At the time of
data collection (up to 5 years after hospital intervention), 35.5%
of no-PEM respondents and 17.2% of PEM+ respondents had a
more severe disease degree (OR 0.38, 95% CI 0.14–1.03, p = 0.058)
compared to the start of the intervention. In the rehabilitation
survey, changes in disease severity were not assessed.
e lack of focus on PEM in the hospital intervention had a
signicant impact on physical and mental health, cognitive eort, ability
to master daily tasks, ability to regulate activity level, and quality of life
(see Figure 4; Table 4). e respondents from the no-PEM group
experienced over three times more oen any physical, cognitive, or
mental function worsening following hospital intervention [61.3% vs.
19.0%, p < 0.001, adjusted OR = 0.13 (95% CI 0.05–0.37), p < 0.001].
Figure5 and Table4 show the treatment outcome assessed as
patient satisfaction or benet following hospital consultations,
interventions, or rehabilitation, stratied on PEM-focus. Evaluated
satisfaction or benet was generally signicantly higher (all p < 0.001)
in all three clinical settings when PEM was addressed. Satisfaction
with consultation and rehabilitation was twice as high and over 4-fold
as many respondents reported to have perceived at least some benet
of the hospital intervention.
In the educational group courses at the hospitals, outcome
measures were strongly related to the specificity of the
intervention. Deterioration of health and functioning and
perceived benefit was significantly less frequently reported after
the ME/CFS-specific courses, compared to the courses for general
fatigue or health complaints. Worsening of health was
experienced by 25.6% vs. 52.4% (p = 0.034), and deterioration of
physical, cognitive, or mental function was reported by 18.6% vs.
71.4% (p < 0.001). Perceived benefit was low in both groups:
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23.3% of the respondents that had participated in ME/
CFS-specific courses and 9.5% of the participants of less specific
courses (p = 0.19) had reported large or very large benefits of
the education.
3.4 Care quality related to PEM-focus
Table 5 presents the correlation between focus on PEM in
dierent clinical situations and care quality as perceived by the
respondents. In all three types of healthcare settings, respondents’
perceptions of the healthcare provider’s level of ME/CFS knowledge
and symptom acknowledgment were strongly associated with
whether or not there had been attention to PEM. PEM-focus in
hospital intervention and rehabilitation was also strongly correlated
with respondents’ opinion on whether the intervention was suitable
and suciently adjusted to their situation. Cronbach’s alpha of
respective 0.89, 0.89, and 0.80 of the care quality variables and
PEM-focus indicates high internal consistency.
During rehabilitation, 28.4% of the no-PEM respondents vs.
73.5% of the PEM+ respondents (p < 0.001) had learned a lot which
they had beneted from aerward. In hospital intervention, none of
FIGURE2
PEM-focus in the healthcare settings. Answer options of Assessment of PEM, in consultation (n = 86): 1. No (no-PEM), 3. Unsure (no-PEM), 5. Yes
(PEM+). Knowledge gain following hospital intervention (n = 89): 1. PEM was not seen as typical or relevant (no-PEM), 2. No information (no-PEM) n,
3. Yes, but nothing new (PEM+), 4. Some (PEM+), 5. A lot (PEM+). PEM explained in rehabilitation setting (n = 788): 1. No (no-PEM), 5. Yes (PEM+).
TABLE4 Results of logistic regression analysis for the association between PEM-focus (no-PEM or PEM+) and outcome.
Setting nResponse variables
(Outcome)
Explanatory
variables
OR [95% CI] p
Hospital consultation 79 Satisfaction PEM-focus 11.57 [3.72–35.96] <0.001
Hospital intervention 89 Benet PEM-focus 9.74 [1,21–78.57] 0.033
Disease severitya0.93 [0.83–1.05] 0.26
89 Function deteriorationbPEM-focus 0.13 [0.05–0.37] <0.001
Disease severitya1.12 [1.01–1.24] 0.034
88 Worsening disease severity- post, 1–2 wkcPEM-focus 0.37 [0.14–1.04] 0.058
Disease severitya0.93 [0.84–1.03] 0.166
89 Worsening disease severity- 3-6 moscPEM-focus 0.38 [0.14–1.08] 0.07
Disease severitya0.97 [0.88–1.08] 0.57
Rehabilitation 742 Satisfaction PEM-focus 5.75 [4.14–7.98] <0.001
Disease severitya0.63 [0.48–0.84] 0.002
Disease duration 0.99 [0.94–1,05] 0.77
768 Worsening health–post PEM-focus 0.46 [0.34–0.63] <0.001
Disease severitya1.29 [1.00–1.67] 0.052
Disease duration 0.98 [0.93–1.03] 0.44
769 Worsening health–1 mo. PEM-focus 0.35 [0.26–0.48] <0.001
Disease severitya1.48 [1.13–1,94] 0.005
Disease duration 0.99 [0.94–1.05] 0.83
Relevant disease variables were included as covariates, if available. ‘No-PEM’ is the reference category for PEM focus. aDisease severity at intervention start; bWorsening physical, cognitive, or
mental functioning; cchanges in disease severity compared to baseline.
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the no-PEM respondents versus 58.6% (p < 0.001) of PEM+ had
obtained new knowledge or understanding about PEM, and 3.3% of
no-PEM vs. 46.5% of PEM+ (p < 0.001) had obtained new PEM coping
skills. Almost half (48.4%) of the no-PEM group vs. 5.2% (p < 0.001)
of the PEM+ group felt that they had been treated incorrectly in the
intervention obtained at the hospital.
For the educational group courses, most care quality measures
were also strongly correlated with whether the target group was
specic for ME/CFS patients or not [healthcare providers’ ME/CFS
knowledge, ρ = 0.64 (p < 0.001); symptom acknowledgment, p = 0.59
(p < 0.001); and suitability of intervention, ρ = 0.63 (p < 0.001)].
ere were, however, no signicant dierences in dropout ratios:
5.3% in the ME/CFS-specic education and 10.0% in the other
courses (p = 0.50).
4 Discussion
e PEM phenomenon is a hallmark feature of ME/CFS and
essential to acknowledge in both clinical consultation and
intervention. is study was conducted in Norway, generally featuring
high-quality care. Nevertheless, according to a signicant proportion
of the ME/CFS patients, PEM had frequently not been addressed
during their contact with specialist healthcare services. is concerned
both consultation services at the hospitals as well as the interventions
delivered at the hospitals and rehabilitation institutions. is lack of
focus on PEM increased the probability of experiencing deterioration,
following hospital intervention and rehabilitation care. On the other
hand, addressing PEM was related to increased rated care satisfaction,
healthcare quality, and benet.
FIGURE3
Impact of hospital intervention and rehabilitation on the state of health stratified by PEM-focus in the therapeutic approach. Changes from intervention
start. Hospital intervention: self-reported severity degree at baseline, 2 weeks (n = 88), and 3 to 6 months (n = 89) following the intervention. Change in
clinical severity degree: 1. Higher disease degree, 2. Unchanged, 3. Lower disease degree. Rehabilitation: reply to the statements “I felt better just after
the stay than before” and “I felt better 1 month after the stay than before,” answer options: 1. Strongly disagree, 2. Disagree/neither agree nor disagree,
3. Strongly agree. Mann–Whitney U-test was applied to assess group dierences.
FIGURE4
Impact of hospital intervention on various domains (n = 88 or 89). Mann–Whitney U-test was applied to assess the group dierences.
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4.1 Addressing PEM in the intervention
Over one-third of the respondents of the hospital
interventions and half of the individuals who had stayed at a
rehabilitation institute reported that PEM had not been
addressed. This doubled the number of respondents that acquired
a more severe disease degree for a long time; for the hospital
respondents, the data demonstrated that these differences were
still present at the time of data collection (i.e., up to 5 years after
the intervention).
From a psychosomatic point of view (3, 63, 64), PEM is ignored
as a direct physiological response to physical or mental exertion. From
this perspective, GET and CBT are considered as eective therapies.
Although the Norwegian Guidelines regard PEM as a cardinal
symptom, GET and CBT are still suggested as eective treatment
approaches in these guidelines (41). is is despite there currently
being no research evidence of convincing eects of these approaches
for ME/CFS patients with PEM (10, 33, 34, 65, 66) and despite the fact
that several surveys actually reported that over half of the ME/CFS
patients experience substantial deterioration aer GET and usually do
no benet from CBT (67–69).
GET and curative CBT were seldom explicitly mentioned as
applied method in both our hospital and rehabilitation surveys.
Yet, many patients reported that they encountered elements of
CBT and GET, such as being encouraged to believe their disease
is not serious or physical, encouragement to increase activity
levels, and disregarding symptoms. This usually happened in
settings where PEM was not addressed. Some of the citations that
the respondents had added in comments text fields in both
surveys testify to this (see Table6).
When evidence for curative treatments for ME/CFS is
lacking, intervention should at least aim at educating the patient
to optimize their ability to maintain function in everyday
activities and reduce PEM. This may help to alleviate symptoms
and increase quality of life (35, 36). Therefore, in updated clinical
recommendations for ME/CFS, educational approaches are
included. They typically aim at empowering the patient for self-
management with a focus on pacing strategies to conserve energy
and focus on coping with a disease with substantial function loss
and symptom burden.
In the rehabilitation survey, applied intervention methods were
not evaluated systematically, but the programs are usually
multidisciplinary and patient education is oen part of a
rehabilitation program. In the case PEM was addressed in the
rehabilitation, nearly three-quarters of respondents reported that
they had learned a lot which they had beneted from aerward.
is applied to less than a third of the patients if PEM had not
been discussed.
In the hospital survey, a considerable portion of the
respondents had received educational group courses as well.
Some patients received educational courses that were aimed
exclusively at ME/CFS patients, while others were included in
courses aimed at patients with more general fatigue or health
problems. Nearly all participants of ME/CFS-specific courses
reported to have obtained information about PEM, but only one
of seven participants of the less specific courses reported the
same. Apparently, the focus on education, and counseling had
been delivered from clinical settings with different explanatory
approaches to ME/CFS. Not informing ME/CFS patients about
their main disabling symptoms is both worrying and unacceptable
and may lead to severe consequences for the patients. In our
study, functional deterioration was reported by over seven out of
10 participants of the non-specific courses, but only by less than
two out of 10 of the participants of the ME/CFS-specific
education. Understandably, the perceived impact on health and
functioning and rated care quality was associated with this. Half
of the patients who had not received information about PEM
during their hospital intervention, versus only one in each 20
patients who had received this, felt that they had been
treated incorrectly.
FIGURE5
Impact of hospital consultation (n = 85), intervention (n = 89), and rehabilitation (n = 783) on rated satisfaction or benefit, stratified by PEM-focus during
clinical contact. Consultation satisfaction: “All in all, were yousatisfied with the consultation?,” answer options: 1. not at all, 2. to a small degree, 3. to
some degree, 4. to a great degree, 5. to a very great degree. Intervention benefit, hospital intervention: “What benefit have youhad, all in all, from the
intervention?” answer options: 1. No, 2. Little, 3. Some, 4. Large, 5. Very large. Rehabilitation satisfaction: “I amsatisfied with my stay at the rehabilitation
facility,” answer options: 1. Strongly disagree, 2. Disagree, 3. Neither agree nor disagree, 4. Agree, 5. Strongly agree. Mann–Whitney U-test was applied
to assess the dierences between no-PEM and PEM+.
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Generally, in intervention effect studies, clinical effectiveness
is evaluated. Unfortunately, as reported in our study, even when
PEM was addressed in the therapeutic approach, clinical
improvements were generally absent. Due to the nature of the
disease, some deterioration can beexpected after out-of-home
interventions, particularly among patients with higher disease
degrees. The combined burden of travel, social interaction,
coping with time schedules, etc. will often befar beyond the
patients’ day-to-day activity level.
Compared to our study, higher improvement rates were
reported following specialist ME/CFS services in England (70).
At 1-year follow-up, 28% reported overall improvement, and only
8% worsened health. One reason might bethat the specialist
services are indeed better tailored to this specific patient
group. Other reasons might be that the evaluated patients
had a shorter duration of ME/CFS and were only mildly affected
(70). Our data did not cover treatment at a specialist ME/
CFS service.
4.2 Is addressing PEM related to the
explanatory view of me/CFS?
e PEM phenomenon challenges existing medical
assumptions of the health benets of exercise and other physical
and mental activity and sensory stimuli (71). As knowledge and
understanding of PEM are crucial for diagnosis and maintaining
optimal functioning in ME/CFS, early screening and explaining
explicitly about PEM are essential in clinical consultations where
ME/CFS is suspected (14, 35). Failure to recognize ME/CFS and
PEM may result in poor management in daily life and in the
clinical approach, which may hamper recovery potential and
aggravate the disease (62, 72).
Only two out of ve respondents had noticed that PEM had been
addressed in the clinical consultations. e main reason for not
discussing PEM in a clinical consultation is probably that the clinician
does not acknowledge PEM as an essential feature in ME/CFS. e
TABLE5 Distribution of degree of perceived care quality on several factors as reported by the respondents in the three types of care settings, stratified
and tested by PEM-focus. Measures for internal consistencies calculated of all variables, including PEM-focus, are presented as well.
Survey 1—hospital
PEM-focus in consultation
Survey 1–hospital
PEM-focus in intervention
Survey 2–rehabilitation
PEM-focus in rehabilitation
nno-
PEM
49
(56%)
PEM+
38
(44%)
P-
value
nno-
PEM
31
(35%)
PEM+
58
(65%)
P-
value
nno-
PEM
414
(53%)
PEM+
374
(48%)
P-
value
Test statistics Test statistics Test statistics
Healthcare provider ME/
CFS knowledge
86 ρ= 0.62 <0.001 89 ρ= 0.74 <0.001 786 ρ= 0.56 <0.001
Very little 11 22.4% 0.0% 18 51.6% 3.4% 125 28.4% 2.1%
Not much 10 18.4% 2.7% 9 25.8% 1.7% 115 23.3% 5.1%
Both 17 28.6% 8.1% 17 19.4% 19.0% 125 19.2% 12.3%
Good 16 16.3% 21.6% 23 3.2% 37.9% 228 21.1% 37.6%
Very good 32 14.3% 67.6% 22 0.0% 37.9% 193 8.0% 42.8%
Symptom acknowledgment 86 ρ= 0.60 <0.001 88 ρ= 0.55 <0.001 784 ρ= 0.48 <0.001
Not at all 10 20.4% 0.0% 12 30.0% 5.2% 73 16.8% 1.1%
To a small degree 9 18.4% 0.0% 9 23.3% 3.4% 72 14.1% 3.8%
To some degree 13 22.4% 5.4% 17 23.3% 17.2% 84 16.1% 4.8%
To a great degree 17 18.4% 21.6% 26 20.0% 34.5% 275 36.0% 34.0%
To a very great degree 37 20.4% 73.0% 24 3.3% 39.7% 280 17.0% 56.3%
Suitability of intervention 89 ρ= 0.61 <0.001 785 ρ= 0.46 <0.001
Not at all 17 45.2% 5.2% 161 34.2% 5.4%
To a small degree 10 22.6% 5.2% 127 18.9% 13.1%
To some degree 22 22.6% 25.9% 113 17.7% 10.7%
To a great degree 24 6.5% 37.9% 243 22.3% 40.5%
To a very great degree 16 3.2% 25.9% 141 6.8% 30.3%
Completed intervention 78 ρ= 0.26 0.021 784 ρ= 0.06 0.12
No 12 27.6% 8.2% 104 15.0% 11.3%
Yes 66 72.4% 91.8% 680 85.0% 88.7%
Cronbach’s alpha 0.89 0.89 0.80
Spearman’s rank correlation coecient (Spearman’s rho: ρ) as a measure of association with PEM-focus. Cronbach’s alpha as a measure of internal consistency (with the full scale of
PEM-focus).
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applied explanatory model in the various clinical settings was not
explicitly evaluated in the surveys. However, not acknowledging PEM
as a key phenomenon, which in this study was associated with little
focus on the patients’ symptoms and poor specic suitability of
intervention, is in our opinion an obvious indication of a psychosomatic
view. Some of the citations conrm an apparent psychosomatic
approach at some of the evaluated healthcare services (see Table6).
One of the assumptions derived from a biopsychosocial
perspective is the sustained arousal hypothesis (73), based on ‘the
cognitive activation theory of stress’ (CATS) (74). According to CATS,
the sustained stress responses may originate from dierent
precipitating factors (interacting with predisposing factors (genetic
traits, personality) and learned expectations (classical and operant
conditioning)). Although this theory has not been conrmed, the
sustained arousal hypothesis has strong support in Norway, including
in some of the evaluated departments, as mirrored in some of the
comments (see Table6).
Because of the presence of a strong psychosomatic network in
Norway (3), and the equivocal explanatory view and recommendations
for approaching ME/CFS of both the National Advisory Unit on CFS/
ME and the Norwegian CFS/ME guidelines (41), it was not surprising
to meet a psychosomatic view in several of the specialist healthcare
services evaluated in our study.
e respondents’ own underlying assumptions explaining their
symptoms had not been assessed. However, for majority of the ME/
CFS patients, a predominantly biomedical explanation of their disease
usually ts their experiences better than a psychosomatic approach
(32, 75, 76). Generally, many ME/CFS patients feel that the doctors
psychologize too much, trivialize the symptoms, or tell them that their
symptoms are psychosomatic (43, 77–79). If patients meet an
opposing explanatory model in healthcare practice, negative patient
experiences and dissatisfaction with received care may arise (75, 79).
In our study, failure to address PEM led to ineective, harmful
healthcare and respondents reported poor disease understanding of
ME/CFS among healthcare providers and a lack of validation of their
illness experiences (see also Table6). is has also been reported in
previous studies (42, 43, 45, 79, 80). e high internal consistency of
not addressing PEM and a reported approach that was poorly
customized to ME/CFS suggests that these elements may measure a
similar notion of viewing ME/CFS (58).
Illnesses that lack clear pathophysiology, that has inconsistent
diagnostic criteria, inadequate research focus, and lack of proper
training, seem frequently to berelated to negative consequences or
iatrogenesis for the patient (80–82). As in our study, Geraghty and
Blease (32) recognized several modalities of iatrogenesis in ME/CFS
such as high levels of patient dissatisfaction, challenges to the patients’
narratives and experiences, and negative responses to therapy. In
addition, other modalities were identied, such as diculties in
reaching an acceptable diagnosis of ME/CFS and access to medical
care and social support.
TABLE6 Illustrating citations of the respondents of both underlying surveys (freely translated from Norwegian) (57, 58).
Psychosomatic approach
“e doctor said it should not becalled ME but rather ‘BE’ because it is Between the Ears.”
“We were met by a psychologist who claimed that if youfelt exhaustion coming over you, youshould think of something pleasant and that ‘feeling’ would go away!.”
“ere was a great deal of focus on stress management and stuck-thought- patterns.”
“I felt that ME was not taken very seriously; all forms of exhaustion seemed to betaken under the same umbrella.”
“PEM and exhaustion were seen as complaints and depression, and as an excuse not to exercise.”
Sustained arousal hypothesis
“e doctor believed that Icould recover completely with their approach; a sustained stress response, which is cured with the right mind-set and individually adapted training.”
“ey were only concerned with the body’s stress response.”
Consequences of opposing explanatory models of ME/CFS
“Because of their perception that ME comes from a biopsychosocial model of explanation, Iwas never able to become fully comfortable with them. Ihave a completely dierent
experience of the disease and they focused far too much on the psychological side.”
Poor disease understanding among healthcare providers
“e healthcare providers barely knew anything about ME/CFS, but they tried their best. e stay was too much. Just being there. It took many years for me to get back to the same
level Iwas before Ile.”
Ignoring symptoms
“I told them about all the symptoms, but was then told that wehad too much focus on symptoms.”
“It was just about not thinking about the symptoms, that youget well as long as youincrease your activity and think positively.”
“e (rehabilitation) stay is based on CBT and GET, the patient himself must bewell aware of his own limits, otherwise it can become too much.”
Addressing PEM perceived as more positively
“It was a very nice stay and it was nice to meet more people like me. Idid not get any better, but Ibrought home some tips on everyday life that make it a little easier.”
“e rst time Imet healthcare providers who believed in me and took my illness into account”
“If youcould not handle an activity, they said, ‘It’s great that youare taking care of yourself!”
Failure to acknowledge PEM may cause potential iatrogenic harm
“Became bedridden for 1 year aer rehabilitation because Ihad to exercise four times a day on weekdays. It was not adapted to ME at all. e basic philosophy at the center was
that one could become healthy through exercise.”
“Now, 4 months later, Iamstill worse than when Iwent to the rehabilitation institution. But the place is very good; one just has to behealthier than Iwas to benet from the stay.”
New knowledge and strategies may take time before potential benet is recognized
“It took a long time, approximately 6 months, before there was an eect of the changes Imade.”
Wormgoor and Rodenburg 10.3389/fneur.2023.1247698
Frontiers in Neurology 14 frontiersin.org
4.3 Methodological issues, strengths, and
limitations
To our knowledge, this is the rst study to evaluate the signicance of
addressing PEM in the clinical approach to ME/CFS patients in naturalistic
settings of specialist healthcare practice. e evaluation of PEM-focus was
in fact not the primary outcome of the initial surveys. is may have
reduced respondent bias because they were unaware of the aim of the
present analyzes of assessing the signicance of acknowledging the PEM
phenomenon with regard to their health and perceived care quality.
e inclusion of two comparable surveys, together covering specialist
healthcare for ME/CFS patients in Norway, and the large sample size from
a large geographical area in the rehabilitation survey were also strengths
of this study. Another key feature of this study is the focus on intervention-
induced ‘deterioration’ versus ‘no-deterioration’ instead of evaluating
clinical eectiveness. is seems especially relevant in the evaluation of
‘real-life’ interventions for ME/CFS because of general limited
improvement in health status. Instead, exacerbations are frequently
described in patient surveys but usually ignored or camouaged in the
presentation of average scores.
In the analyzes of our study, the occurrences of provided healthcare
are in fact the main study focus and not the individual respondents.
erefore, in the hospital survey, some respondents assessed their
experiences from more than one department. ese have been analyzed
as independent occurrences. Weconsidered this as acceptable since ME/
CFS is a chronic disease with very limited recovery potential (35, 72, 83),
the provided healthcare could cover a time frame of 5 years and the order
in which the setting was evaluated was random. Notably, each respondent
could evaluate each department only once. e patients’ view concerning
PEM-focus and outcome seemed independent of order and number of
assessed settings.
is current study has some limitations, mainly concerning
methodological issues. e low sample size of the hospital survey may
have reduced the statistical power and the chance of detecting true
consequences. is might especially concern the analyzes concerning
the impact of the interventions on health. In addition, it limited the
opportunity to conduct analysis more specic per clinical specialty.
Furthermore, the limited diversity of potential covariates in the
available data reduced the number of possible factors of interest to
adjust for in the regression analyzes.
As a consequence of performing non-prespecied analyzes based
on an exploration of two retrospective surveys, some applied measures
and scales were not optimal and inconsistent. is applied also to the
assessment of PEM-focus that was operationalized with dierent
wording and dierent scales for the three types of healthcare settings.
However, wedo not expect this to bea major drawback. Additionally,
wewere not able to assess the actual focus on PEM in the clinical
settings. We were dependent on patients’ perception of its
acknowledgment and recall bias may have occurred. is may also
have aected the outcome measures that assessed satisfaction and
impact on functioning and health status. e retrospective design,
however, might have been a methodological plus as the participants
gained the opportunity to put their experiences into a longer-term
perspective. It may take time to implement new knowledge and
learned strategies in daily life before the potential benet is recognized
(see Table6). Psychosomatic approaches may aim at inuencing how
patients interpret and report their health state and thus may easily bias
subjective outcome measures immediately aer the intervention.
A strength of recruiting respondents outside the healthcare
settings and collecting anonymous feedback is a better chance of
obtaining objective opinions. Patients may hesitate to share negative
experiences with healthcare providers because they fear they will
appear unmotivated and non-cooperative. is could negatively aect
the approval of health benet allowances.
e recruitment method with open online surveys may, however,
have aected the representativeness of the study population. Because
of the anonymity, diagnoses could not beveried. ME/CFS status was
self-reported by the respondents, therefore is misclassication possible
(53). We have limited descriptive data on the respondents, and
wehave no insight into the population of eligible patients who have
visited the hospitals or rehabilitation institutions in the studied period.
Invitation of participation to the surveys was shared online among
groups that are interested in ME/CFS. However, subjects who are
active on social media or are members of the Norwegian ME
Association may beoverrepresented. Former ME/CFS patients had
the possibility to participate in the hospital survey as well. However,
none had selected the diagnostic alternative ‘had a fatigue illness
before but not now’. In the rehabilitation survey, 20 respondents
(0.9%) were excluded because they were neither a patient nor a
relative. Some might have been former patients.
Notably, patients with a severe or very severe degree of the disease
are poorly represented. An obvious reason is that this group of patients
might beless active on social media and has limited energy to answer
a questionnaire. ey are also less likely to have obtained secondary
healthcare because their severe disease status might hamper access to
specialist healthcare. In the region of the hospital survey, ambulant
healthcare services are not available for this patient group. Challenges
in obtaining adequate healthcare have been conrmed in a recent
Norwegian study where this was the case for around seven out of ten
ME/CFS patients with a severe or very severe sickness degree (84).
Some respondents reported that they no longer dared to have contact
with healthcare providers due to frequent negative experiences with
various healthcare providers.
e hospital survey had aimed at including long COVID patients
as well but did not succeed in this. Only two long COVID patients
with PEM are part of the study population. Although a relatively high
proportion of long COVID patients are expected to develop ME/CFS
(47, 85–87), this was not common knowledge at the beginning of
2022, and many long COVID patients with ME/CFS symptoms may
not have identied themselves as an ME/CFS patient.
4.4 Implications for research and clinical
practice
Quality of healthcare is typically described in terms of clinical
eectiveness, patient safety, and patient experience. is study
evaluated ‘real-life’ experiences of ME/CFS with routine specialist
healthcare service in a country with generally high-quality healthcare.
e quality of care services delivered to ME/CFS patients seemed
strongly related to the acknowledgment of the disease and its cardinal
symptom PEM in particular. Ignoring PEM in the approach of ME/
CFS appears as a reckless maltreatment of patients.
e ndings seem relevant for long COVID as well. Alertness to
the possibility of the development of COVID-induced PEM and ME/
CFS is, therefore, essential in patients with post-COVID symptoms.
Wormgoor and Rodenburg 10.3389/fneur.2023.1247698
Frontiers in Neurology 15 frontiersin.org
In patients with (suspected) ME/CFS or long COVID, early
identication and management of PEM may bea cost-eective and
the most important method for stabilizing symptoms and improving
prognosis and patients’ quality of life (10, 35, 87–89).
In general, ME/CFS-specic knowledge seems limited in many
healthcare providers (80, 81, 90–93) and usually ignored in their
education (93). e reported iatrogenesis may betraced back to this
but also to the fact that at present, ME/CFS is not covered by a
dened clinical specialty. As seen from our study, patients had been
referred to several medical specialties, both for clinical consultations
and intervention. Although ME/CFS is regarded as a multisystem
disease, with a neuroimmunological base, oen proceeded by an
infection, neither the disciplines of infectious diseases, immunology,
nor neurology has claimed ‘ownership’ over the diagnosis. is
‘orphaned’ position may have signicant implications for whether
medical specialists feel an interest or obligation to keep up to date in
the eld. is might bea reason that still, among many healthcare
providers, skepticism is established about whether the disease is
primarily ‘physical’ (80, 81, 90, 91). is aects care quality. It has
been demonstrated that health providers’ view of ME/CFS being a
psychosomatic disorder is associated with worse outcomes than
views of ME/CFS as a physical illness (38). Immediate large-scale
investment in updated education of (future) healthcare providers
about the management of ME/CFS, long COVID, and PEM is
essential. In our study, the inter-variability between the departments
of how patients rated PEM-focus and related care quality was
substantial. is provides opportunities to learn from each other’s
clinical practice if interested and open-minded about alternative
approaches to ME/CFS.
In healthcare, there is a growing need and recognition of patient
experiences as an important aspect of evidence-based practice. Patient
experiences as described in our study may contribute to the
improvement of the quality of specialist healthcare practice for ME/
CFS. e signicance of acknowledging the PEM phenomenon for
outcome and healthcare quality in ME/CFS or long COVID has not
been studied systematically before. It seems unethical to study this in
an experimental design, therefore evaluating this in pragmatic settings
seems most appropriate. e analyzes and ndings presented here can
beconsidered exploratory. Further well-designed research is needed
to validate these ndings and investigate the value of acknowledging
PEM in the approach of ME/CFS and long COVID.
5 Conclusion
Despite the inclusion of PEM as a core symptom of ME/CFS in
updated diagnostic criteria sets, and the biomedical evidence of the
existence of the phenomenon, PEM is still not always accepted and
taken into consideration in specialist healthcare practice in Norway.
PEM was not addressed in more than half of the evaluated
consultations and rehabilitation stays, and one-third of the hospital
interventions. Not addressing PEM doubled the probability of a
decline in health and functioning following the intervention and was
strongly associated with reduced perceived care quality, satisfaction,
and benet. Acknowledgment of PEM by the healthcare provider was
correlated with a more positive rating by the patients of the healthcare
providers’ recognition of patient’s symptoms, level of ME/CFS
knowledge, and suitability of the intervention to their condition.
is study conrmed the signicance of acknowledging the PEM
phenomenon in the clinical approach of ME/CFS patients in specialist
healthcare practice. When disregarding the PEM phenomenon, healthcare
for ME/CFS patients can bedescribed as ineective, harmful, and of poor
quality. In this respect, it seems essential to raise awareness among
healthcare providers in specialist healthcare about ME/CFS and PEM.
Data availability statement
e raw data supporting the conclusions of this article will be
made available by the authors, without undue reservation.
Ethics statement
Ethical approval was not required for the studies involving
humans because the study was based on the anonymous replies on two
online surveys. e studies were conducted in accordance with the
local legislation and institutional requirements. Written informed
consent for participation was not required from the participants or the
participants’ legal guardians/next of kin in accordance with the
national legislation and institutional requirements because the study
was based on anonymous replies.
Author contributions
MW conceptualized and designed the study, conducted the hospital
survey and the analyzes related to the hospital survey, and wrote the rst
dra of the manuscript. SR conducted the analyzes related to the
rehabilitation survey and contributed to the nal dra of the manuscript.
All authors contributed to the article and approved the submitted version.
Acknowledgments
e authors are grateful to all respondents who volunteered their
time and energy to answer the surveys so that wemight learn more
about their experiences which wehope can contribute to better care
for ME/CFS patients. e authors want to thank Trude Schei and
Arild Angelsen (Norwegian ME Association) for providing them data
from the rehabilitation survey (58). e authors also thank Jens
Egeland (Oslo University and Vestfold Hospital Trust) and Trude
Schei for their comments on the manuscript.
Conflict of interest
MW was employed by one of the evaluated hospitals.
e remaining author declares that the research was conducted in
the absence of any commercial or nancial relationships that could
beconstrued as a potential conict of interest.
Publisher’s note
All claims expressed in this article are solely those of the
authors and do not necessarily represent those of their affiliated
Wormgoor and Rodenburg 10.3389/fneur.2023.1247698
Frontiers in Neurology 16 frontiersin.org
organizations, or those of the publisher, the editors and the
reviewers. Any product that may be evaluated in this article, or
claim that may be made by its manufacturer, is not guaranteed or
endorsed by the publisher.
Author disclaimer
e views and opinions expressed in this paper are ours and do
not necessarily reect those of our institutions.
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