Front. Neurol. Frontiers in Neurology Front. Neurol. 1664-2295 Frontiers Media S.A. 10.3389/fneur.2023.1247698 Neurology Original Research Focus on post-exertional malaise when approaching ME/CFS in specialist healthcare improves satisfaction and reduces deterioration Wormgoor Marjon E. A. 1 * Rodenburg Sanne C. 2 1Vestfold Hospital Trust, Division of Mental Health and Addiction, Tønsberg, Norway 2Neuroscience and Cognition, Graduate School of Life Sciences, Faculty of Medicine, Utrecht University, Utrecht, Netherlands

Edited by: Nuno Sepulveda, Warsaw University of Technology, Poland

Reviewed by: Geoffrey Moore, Cornell University, United States; Nina Muirhead, Buckinghamshire Healthcare NHS Trust, United Kingdom

*Correspondence: Marjon E. A. Wormgoor, rodeworm@online.no; marwor@siv.no
01 12 2023 2023 14 1247698 03 07 2023 31 10 2023 Copyright © 2023 Wormgoor and Rodenburg. 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 this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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 affects 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 be related to the applied explanatory models for ME/CFS and are most likely of relevance to long COVID.

ME/CFS myalgic encephalomyelitis chronic fatigue syndrome post-exertional malaise post-exertional symptom exacerbation patient experience specialist healthcare healthcare quality section-at-acceptance Neurorehabilitation

香京julia种子在线播放

    1. <form id=HxFbUHhlv><nobr id=HxFbUHhlv></nobr></form>
      <address id=HxFbUHhlv><nobr id=HxFbUHhlv><nobr id=HxFbUHhlv></nobr></nobr></address>

      Introduction

      Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term, severe multisystem disease with a distinctive clinical picture, often, 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). This 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.

      This biomedical explanatory model is acknowledged in the diagnostic criteria sets for ME/CFS that have been defined during the last two decades (6, 8–11). These criteria are more specific 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 be an immediate or a delayed, disproportionate response to physical, orthostatic, or cognitive effort, 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. The 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). The PEM phenomenon has been demonstrated in multiple studies, both with patient-reported outcome measures and with objective measures. Objective findings include new or increased structural and functional abnormalities, following controlled exertion situations (23–26). These findings 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 be corrected by increasing physical activity to overcome avoidance behavior and regain physical fitness (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 scientific evidence for effective treatment of ME/CFS and explicitly discourage curative CBT and GET forms (10, 33–37). Instead, pacing strategies are considered to be the most effective 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 differential diagnostic issues, the GP should refer to relevant clinical specialists for further evaluation. The European Network on ME/CFS (EUROMENE) expert consensus (36) recommends referral to specialist service for confirmation of diagnosis, drug treatment, and a range of service offerings, 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 satisfied with the obtained care and specialists’ knowledge about ME/CFS. In another, recent Norwegian study, however, perceived care quality was evaluated related to the specificity of the diagnosis and PEM severity (42). Patients meeting more specific 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 specifically in specialist healthcare practice in Norway. Likewise, it is insufficiently documented what the consequences are of not addressing PEM for the patient-related outcome and the perceived quality of these services regarding clinical effectiveness, patient safety, and patient experiences.

      Awareness and knowledge about PEM seem also of specific 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. Addressing PEM in the approach of long COVID patients is of specific importance as well (54–56).

      The aim of this present study was to assess the significance of acknowledging the PEM phenomenon in the clinical approach of ME/CFS patients in specialist healthcare practice.

      The first objective was to evaluate to what extent ME/CFS patients experienced focus on PEM during clinical consultations, hospital intervention, or rehabilitation.

      The second objective was to estimate to what degree focus on PEM in the received care is related to patient-reported outcomes. The primary outcome is the impact of addressing PEM during an intervention on subsequent changes in health status. The secondary outcome measures are the reported care satisfaction or the perceived general benefit of the obtained care.

      The third objective was to assess whether the acknowledgment of PEM in a clinical situation is associated with patient-reported experiences of perceived healthcare quality.

      Materials and methods

      This study is a non-prespecified secondary analysis, applying data from two patient surveys executed by the Norwegian ME Association (NMEF). The two patient surveys focused on different 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. There were no time restrictions on response during the study period as the questionnaire remained open until submitted.

      The 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. These healthcare services covered two different 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 different departments, the respondents reported that separately, but for each department, only once per consultation and once per intervention.

      The 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. Figure 1 presents the flow chart of the study.

      Study flow chart of survey 1 and survey 2, showing the inclusion of respondents and identification of corresponding evaluated care events for analyzes.

      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. The 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. Then, the respondents reported which diagnosis they regarded as the most appropriate for them. Only the respondents that answered, “ME/CFS or ME,” “sequela after 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.

      Measures

      All measures are presented in Tables 1, 2, including applied methods for dichotomization of variables, if relevant. The complete questionnaires (in Norwegian) can be found in the underlying reports (57, 58).

      Relevant questions describing the respondents’ characteristics and the situational context.

      Domain Survey 1Hospital consultation Survey 1Hospital intervention Survey 2Rehabilitation
      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 benefits (≥75%)/ No education lessons 1. 0%, 2. 25%, 3. 50%, 4. 75%, 5. 100%Sickness benefits (≥75%)/ No education lessons
      Diagnostician Who made the diagnosis? Who made the diagnosis? Who made the diagnosis?
      Disease duration For how long have you had CFS/ME fatigue symptoms?< 6 months, 6–12 months, 1–2 years, 2–5 years, 5–10 years, > 10 years For how long have you had 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 you have?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 you have?What severity degree of ME/CFS did you have 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 flexibility, training to increase activity and fitness, 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.

      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 you asked, directly or indirectly, if you had PEM? 1. No, 3. Unsure, 5. Yes Did you gain 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/Benefit Overall, were you satisfied with the consultation? ** What benefit have you had, overall, from the intervention?1. No benefit, 2. Little benefit, 3. Some benefit, 4. Large benefit, 5. Very large benefit I am satisfied with my stay at the rehabilitation facility *
      Impact on health What severity degree of ME/CFS did you have the first 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 after the stay than beforeI felt better 1 month after the stay than before1. Strongly disagree, 2. Disagree, 3. Neither agree nor disagree, 4. Agree, 5. Strongly agree
      Impact on various domains How did you benefit from the intervention, when it comes to: physical health, cognitive effort, 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 you feel that the intervention was suitable for your situation? * The activity level was adapted to my illness*
      Healthcare provider knowledge? Do you think 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 you think that this therapist/supervisor/institution had good knowledge of ME/CFS?1. Very little, 2. Not much, 3. Both, 4. Good, 5. Very good The healthcare providers had good knowledge on ME/CFS*
      Symptom acknowledgment? Did you feel that your symptoms were taken seriously? * Did you feel that your symptoms were taken seriously? ** The staff at the rehabilitation facility were understanding when I told them about my symptoms *
      Gained beneficial knowledge or skills Did the intervention help you to be able 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 I have benefited from later *
      Incorrect treatment Do you think you obtained incorrect treatment in some way?**
      Intervention completed Did you complete the intervention?1. No I quit because I got worse/ no I quit because I did not think it was helpful, 2. Yes Were you at the rehabilitation facility for the entire period?1. No, I got worse and chose to go home/ no, I got worse and was sent home by the staff, 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.

      Respondent characteristics

      The operationalization of respondents’ characteristics is presented in Table 1. 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.

      Post-exertional malaise-focus as an explanatory variable

      The 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 different wording and different 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 Table 2 as well.

      Patient-reported outcome

      The assessments of the outcome measures are presented in Table 2. The impact of hospital intervention on health status was operationalized by computing changes in the evaluated disease severity before and after the intervention–in the first 2 weeks (post-intervention) and 3 to 6 months (short-term follow-up). Disease severity classification was based on the Norwegian National Guidelines for CFS/ME (41) and ICC (9). More severe disease severity after the intervention was classified as ‘deteriorated’. ‘Not deteriorated’ includes both unchanged and improved health status. In addition, the benefit of the hospital interventions was more specifically evaluated related to various domains: physical health, cognitive effort, mental health, ability to master daily tasks, ability to regulate activity level, and quality of life. The 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 after the stay than before.” Short-term changes reported as “I felt better one month after 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 benefit of the hospital intervention were assessed with 5-point Likert scales and applied as outcome measures.

      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-specific 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.

      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 Table 1).

      In the hospital survey, the type of intervention options was assessed systematically as well: individual treatment, group course, or both. The 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.

      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 different 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 differences 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. The response variables were dichotomized outcome measures of satisfaction or rated general benefit, 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% confidence 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, benefit, health, or function deterioration), whereas OR < 1.0 indicates an association with a lower probability. The results were also presented as bar diagrams with full-scale outcome variables. Mann–Whitney U-test was applied to assess group differences. The 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.

      The care quality variables are presented with Spearman’s rank correlation coefficient (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.

      No power calculation was performed as the primary surveys were considered explorative. Differences 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 first 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. This 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., United States). A p-value of less than 0.05 was considered statistically significant.

      Results Subjects

      Figure 1 shows the study flow chart including both surveys. In the hospital survey, 82 respondents were included in the analyzes. In total, 86 consultations and 89 interventions were evaluated. The 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 different departments. In the rehabilitation survey, 788 respondents who had participated in a rehabilitation program at a rehabilitation facility in Norway were included.

      The non-completers of the hospital survey did not differ in illness duration, age of symptom debut, diagnosis and disease severity, the degree they experienced PEM, and fulfillment of the Canadian Consensus Criteria (8) as evaluated in this survey. The non-completers had less often 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 difference in how long ago the diagnosis was set and by whom, between the respondents that were included or excluded for analyzes (see Figure 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 confirmed 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%). The 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 Table 3.

      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.

      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%).

      The 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. The 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 specifically 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 different 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 Figure 2. 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).

      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+).

      Post-exertional malaise-focus as an explanatory variable for the outcome

      Differences in several outcome measures stratified by PEM-focus (no-PEM or PEM+) are presented in Figures 35. In addition, Table 4 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. The results of the univariate regression analyzes are, therefore, not presented here.

      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 differences.

      Impact of hospital intervention on various domains (n = 88 or 89). Mann–Whitney U-test was applied to assess the group differences.

      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 you satisfied 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 you had, all in all, from the intervention?” answer options: 1. No, 2. Little, 3. Some, 4. Large, 5. Very large. Rehabilitation satisfaction: “I am satisfied 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 differences between no-PEM and PEM+.

      Results of logistic regression analysis for the association between PEM-focus (no-PEM or PEM+) and outcome.

      Setting n Response 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 Benefit PEM-focus 9.74 [1,21–78.57] 0.033
      Disease severitya 0.93 [0.83–1.05] 0.26
      89 Function deteriorationb PEM-focus 0.13 [0.05–0.37] <0.001
      Disease severitya 1.12 [1.01–1.24] 0.034
      88 Worsening disease severity- post, 1–2 wkc PEM-focus 0.37 [0.14–1.04] 0.058
      Disease severitya 0.93 [0.84–1.03] 0.166
      89 Worsening disease severity- 3-6 mosc PEM-focus 0.38 [0.14–1.08] 0.07
      Disease severitya 0.97 [0.88–1.08] 0.57
      Rehabilitation 742 Satisfaction PEM-focus 5.75 [4.14–7.98] <0.001
      Disease severitya 0.63 [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 severitya 1.29 [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 severitya 1.48 [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.

      Figure 3 and Table 4 present the impact of PEM-focus on the health state after finishing the intervention. For the majority, their health state did not change. On average, for respondents in both groups, disease severity was worsened in the first 2 weeks following hospital intervention (p = 0.005 in no-PEM and p = 0.008 in PEM+). From baseline until 3 to 6 months following baseline, differences were only significant in no-PEM (p = 0.042 and p = 0.13 in 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.

      The lack of focus on PEM in the hospital intervention had a significant impact on physical and mental health, cognitive effort, ability to master daily tasks, ability to regulate activity level, and quality of life (see Figure 4; Table 4). The respondents from the no-PEM group experienced over three times more often 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].

      Figure 5 and Table 4 show the treatment outcome assessed as patient satisfaction or benefit following hospital consultations, interventions, or rehabilitation, stratified on PEM-focus. Evaluated satisfaction or benefit was generally significantly 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 benefit 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: 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.

      Care quality related to PEM-focus

      Table 5 presents the correlation between focus on PEM in different 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 sufficiently 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.

      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—hospitalPEM-focus in consultation Survey 1–hospitalPEM-focus in intervention Survey 2–rehabilitationPEM-focus in rehabilitation
      n no-PEM49 (56%) PEM+38 (44%) P-value n no-PEM31 (35%) PEM+58 (65%) P-value n no-PEM414(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 coefficient (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).

      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 benefited from afterward. In hospital intervention, none of 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 specific 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)]. There were, however, no significant differences in dropout ratios: 5.3% in the ME/CFS-specific education and 10.0% in the other courses (p = 0.50).

      Discussion

      The PEM phenomenon is a hallmark feature of ME/CFS and essential to acknowledge in both clinical consultation and intervention. This study was conducted in Norway, generally featuring high-quality care. Nevertheless, according to a significant proportion of the ME/CFS patients, PEM had frequently not been addressed during their contact with specialist healthcare services. This concerned both consultation services at the hospitals as well as the interventions delivered at the hospitals and rehabilitation institutions. This 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 benefit.

      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 effective therapies. Although the Norwegian Guidelines regard PEM as a cardinal symptom, GET and CBT are still suggested as effective treatment approaches in these guidelines (41). This is despite there currently being no research evidence of convincing effects 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 after GET and usually do no benefit 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 Table 6).

      Illustrating citations of the respondents of both underlying surveys (freely translated from Norwegian) (57, 58).

      Psychosomatic approach
      “The doctor said it should not be called ME but rather ‘BE’ because it is Between the Ears.”“We were met by a psychologist who claimed that if you felt exhaustion coming over you, you should think of something pleasant and that ‘feeling’ would go away!.”“There 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 be taken under the same umbrella.”“PEM and exhaustion were seen as complaints and depression, and as an excuse not to exercise.”
      Sustained arousal hypothesis
      “The doctor believed that I could recover completely with their approach; a sustained stress response, which is cured with the right mind-set and individually adapted training.”“They 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, I was never able to become fully comfortable with them. I have a completely different experience of the disease and they focused far too much on the psychological side.”
      Poor disease understanding among healthcare providers
      “The healthcare providers barely knew anything about ME/CFS, but they tried their best. The stay was too much. Just being there. It took many years for me to get back to the same level I was before I left.”
      Ignoring symptoms
      “I told them about all the symptoms, but was then told that we had too much focus on symptoms.”“It was just about not thinking about the symptoms, that you get well as long as you increase your activity and think positively.”“The (rehabilitation) stay is based on CBT and GET, the patient himself must be well 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. I did not get any better, but I brought home some tips on everyday life that make it a little easier.”“The first time I met healthcare providers who believed in me and took my illness into account”“If you could not handle an activity, they said, ‘It’s great that you are taking care of yourself!”
      Failure to acknowledge PEM may cause potential iatrogenic harm
      “Became bedridden for 1 year after rehabilitation because I had to exercise four times a day on weekdays. It was not adapted to ME at all. The basic philosophy at the center was that one could become healthy through exercise.”“Now, 4 months later, I am still worse than when I went to the rehabilitation institution. But the place is very good; one just has to be healthier than I was to benefit from the stay.”
      New knowledge and strategies may take time before potential benefit is recognized
      “It took a long time, approximately 6 months, before there was an effect of the changes I made.”

      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 often 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 benefited from afterward. This 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.

      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 be expected 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 be far 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 be that 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.

      Is addressing PEM related to the explanatory view of me/CFS?

      The PEM phenomenon challenges existing medical assumptions of the health benefits 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 five respondents had noticed that PEM had been addressed in the clinical consultations. The 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. The 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 specific suitability of intervention, is in our opinion an obvious indication of a psychosomatic view. Some of the citations confirm an apparent psychosomatic approach at some of the evaluated healthcare services (see Table 6).

      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 different precipitating factors (interacting with predisposing factors (genetic traits, personality) and learned expectations (classical and operant conditioning)). Although this theory has not been confirmed, the sustained arousal hypothesis has strong support in Norway, including in some of the evaluated departments, as mirrored in some of the comments (see Table 6).

      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.

      The 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 fits 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 ineffective, 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 Table 6). This has also been reported in previous studies (42, 43, 45, 79, 80). The 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 be related 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 identified, such as difficulties in reaching an acceptable diagnosis of ME/CFS and access to medical care and social support.

      Methodological issues, strengths, and limitations

      To our knowledge, this is the first study to evaluate the significance of addressing PEM in the clinical approach to ME/CFS patients in naturalistic settings of specialist healthcare practice. The evaluation of PEM-focus was in fact not the primary outcome of the initial surveys. This may have reduced respondent bias because they were unaware of the aim of the present analyzes of assessing the significance of acknowledging the PEM phenomenon with regard to their health and perceived care quality.

      The 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 effectiveness. This 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 camouflaged 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. Therefore, in the hospital survey, some respondents assessed their experiences from more than one department. These have been analyzed as independent occurrences. We considered 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. The patients’ view concerning PEM-focus and outcome seemed independent of order and number of assessed settings.

      This current study has some limitations, mainly concerning methodological issues. The low sample size of the hospital survey may have reduced the statistical power and the chance of detecting true consequences. This might especially concern the analyzes concerning the impact of the interventions on health. In addition, it limited the opportunity to conduct analysis more specific 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-prespecified analyzes based on an exploration of two retrospective surveys, some applied measures and scales were not optimal and inconsistent. This applied also to the assessment of PEM-focus that was operationalized with different wording and different scales for the three types of healthcare settings. However, we do not expect this to be a major drawback. Additionally, we were 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. This may also have affected the outcome measures that assessed satisfaction and impact on functioning and health status. The 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 benefit is recognized (see Table 6). Psychosomatic approaches may aim at influencing how patients interpret and report their health state and thus may easily bias subjective outcome measures immediately after 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. This could negatively affect the approval of health benefit allowances.

      The recruitment method with open online surveys may, however, have affected the representativeness of the study population. Because of the anonymity, diagnoses could not be verified. ME/CFS status was self-reported by the respondents, therefore is misclassification possible (53). We have limited descriptive data on the respondents, and we have 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 be overrepresented. 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 be less active on social media and has limited energy to answer a questionnaire. They 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 confirmed 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.

      The 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 identified themselves as an ME/CFS patient.

      Implications for research and clinical practice

      Quality of healthcare is typically described in terms of clinical effectiveness, patient safety, and patient experience. This study evaluated ‘real-life’ experiences of ME/CFS with routine specialist healthcare service in a country with generally high-quality healthcare. The 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.

      The findings 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. In patients with (suspected) ME/CFS or long COVID, early identification and management of PEM may be a cost-effective and the most important method for stabilizing symptoms and improving prognosis and patients’ quality of life (10, 35, 87–89).

      In general, ME/CFS-specific knowledge seems limited in many healthcare providers (80, 81, 90–93) and usually ignored in their education (93). The reported iatrogenesis may be traced back to this but also to the fact that at present, ME/CFS is not covered by a defined 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, often proceeded by an infection, neither the disciplines of infectious diseases, immunology, nor neurology has claimed ‘ownership’ over the diagnosis. This ‘orphaned’ position may have significant implications for whether medical specialists feel an interest or obligation to keep up to date in the field. This might be a reason that still, among many healthcare providers, skepticism is established about whether the disease is primarily ‘physical’ (80, 81, 90, 91). This affects 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. This 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. The significance 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. The analyzes and findings presented here can be considered exploratory. Further well-designed research is needed to validate these findings and investigate the value of acknowledging PEM in the approach of ME/CFS and long COVID.

      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 benefit. 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.

      This study confirmed the significance 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 be described as ineffective, 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

      The 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. The 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 first draft of the manuscript. SR conducted the analyzes related to the rehabilitation survey and contributed to the final draft of the manuscript. All authors contributed to the article and approved the submitted version.

      The authors are grateful to all respondents who volunteered their time and energy to answer the surveys so that we might learn more about their experiences which we hope can contribute to better care for ME/CFS patients. The authors want to thank Trude Schei and Arild Angelsen (Norwegian ME Association) for providing them data from the rehabilitation survey (58). The 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.

      The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict 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 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

      The views and opinions expressed in this paper are ours and do not necessarily reflect those of our institutions.

      References MarksDF. The rise and fall of the psychosomatic approach to medically unexplained symptoms, Myalgic encephalomyelitis and chronic fatigue syndrome. Arch Epidemiol Pub Health Res. (2022) 1:97143. doi: 10.33140/AEPHR.01.02.06 WrightA FisherPL BakerN O’RourkeL CherryMG. Perfectionism, depression and anxiety in chronic fatigue syndrome: a systematic review. J Psychosom Res. (2021) 140:110322. doi: 10.1016/j.jpsychores.2020.110322, PMID: 33278659 AlmeTN AndreassonA AsprustenTT BakkenAK BeadsworthMB BoyeB . Chronic fatigue syndromes: real illnesses that people can recover from. Scand J Prim Health Care. (2023) 2023:15. doi: 10.1080/02813432.2023.2235609, PMID: 37740918 SweetmanE NobleA EdgarC MackayA HelliwellA VallingsR . Current research provides insight into the biological basis and diagnostic potential for Myalgic encephalomyelitis/chronic fatigue syndrome (me/Cfs). Diagnostics. (2019) 9:73. doi: 10.3390/diagnostics9030073, PMID: 31295930 HoldenS MaksoudR Eaton-FitchN CabanasH StainesD Marshall-GradisnikS. A systematic review of mitochondrial abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease. J Transl Med. (2020) 18:290. doi: 10.1186/s12967-020-02452-3 IOM. Beyond Myalgic encephalomyelitis/chronic fatigue syndrome: Redefining an illness. Washington DC: US Institute of Medicine (2015). MaksoudR MagawaC Eaton-FitchN ThapaliyaK Marshall-GradisnikS. Biomarkers for Myalgic encephalomyelitis/chronic fatigue syndrome (me/Cfs): a systematic review. BMC Med. (2023) 21:118. doi: 10.1186/s12916-023-02893-9 CarruthersBM JainAK de MeirleirKL PetersonDL KlimasNG LernerAM . Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. J Chronic Fatigue Syndr. (2003) 11:2. doi: 10.1300/J092v11n01_02 CarruthersBM van de SandeMI De MeirleirKL KlimasNG BroderickG MitchellT . Myalgic encephalomyelitis: international consensus criteria. J Intern Med. (2011) 270:32738. doi: 10.1111/j.1365-2796.2011.02428.x, PMID: 21777306 NICE. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: Diagnosis and management. Nice Guideline [Ng206]. National Institute for Health and Care Excellence. (2021). Available at: https://www.nice.org.uk/guidance/ng206. ConroyKE IslamMF JasonLA. Evaluating case diagnostic criteria for Myalgic encephalomyelitis/chronic fatigue syndrome (me/Cfs): toward an empirical case definition. Disabil Rehabil. (2022) 45:8407. doi: 10.1080/09638288.2022.2043462, PMID: 35236205 ChuL ValenciaIJ GarvertDW MontoyaJG. Deconstructing post-exertional malaise in Myalgic encephalomyelitis/ chronic fatigue syndrome: a patient-centered, cross-sectional survey. PLoS One. (2018) 13:e0197811. doi: 10.1371/journal.pone.0197811, PMID: 29856774 MayM MilradSF PerdomoDM CzajaSJ FletcherMA JutagirDR . Post-exertional malaise is associated with greater symptom burden and psychological distress in patients diagnosed with chronic fatigue syndrome. J Psychosom Res. (2020) 129:109893. doi: 10.1016/j.jpsychores.2019.109893, PMID: 31884303 HartleM BatemanL VernonSD. Dissecting the nature of post-exertional malaise. Fatigue. (2021) 9:3344. doi: 10.1080/21641846.2021.1905415 StussmanB WilliamsA SnowJ GavinA ScottR NathA . Characterization of post–exertional malaise in patients with Myalgic encephalomyelitis/chronic fatigue syndrome. Front Neurol. (2020) 11:1025. doi: 10.3389/fneur.2020.01025, PMID: 33071931 JasonLA DamrongvachiraphanD HunnellJ BartgisL BrownA EvansM . Myalgic encephalomyelitis: case definitions. Auton Control Physiol State Funct. (2012) 1:114. doi: 10.4303/acpsf/K110601 MateoLJ ChuL StevensS StevensJ SnellCR DavenportT . Post-exertional symptoms distinguish Myalgic encephalomyelitis/chronic fatigue syndrome subjects from healthy controls. Work. (2020) 66:26575. doi: 10.3233/WOR-203168, PMID: 32568143 CotlerJ HoltzmanC DudunC JasonLA. A brief questionnaire to assess post-exertional malaise. Diagnostics (Basel). (2018) 8:66. doi: 10.3390/diagnostics8030066, PMID: 30208578 HodgesLD NielsenT BakenD. Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study. Clin Physiol Funct Imaging. (2018) 38:63944. doi: 10.1111/cpf.12460, PMID: 28782878 KlebekL SunnquistM JasonLA. Differentiating post-polio syndrome from Myalgic encephalomyelitis and chronic fatigue syndrome. Fatigue. (2019) 7:196206. doi: 10.1080/21641846.2019.1687117, PMID: 33014628 van CampenC VisserFC. Comparing idiopathic chronic fatigue and Myalgic encephalomyelitis/chronic fatigue syndrome (me/Cfs) in males: response to two-day cardiopulmonary exercise testing protocol. Healthcare (Basel). (2021) 9:683. doi: 10.3390/healthcare9060683 BrownA JasonLA. Meta-analysis investigating post-exertional malaise between patients and controls. J Health Psychol. (2018) 25:205371. doi: 10.1177/1359105318784161, PMID: 29974812 LimEJ KangEB JangES SonCG. The prospects of the two-day cardiopulmonary exercise test (Cpet) in me/Cfs patients: a Meta-analysis. J Clin Med. (2020) 9:40. doi: 10.3390/jcm9124040 NijsJ NeesA PaulL De KooningM IckmansK MeeusM . Altered immune response to exercise in patients with chronic fatigue syndrome/Myalgic encephalomyelitis: a systematic literature review. Exerc Immunol Rev. (2014) 20:94116. PMID: 24974723 StevensS SnellC StevensJ KellerB VanNessJM. Cardiopulmonary exercise test methodology for assessing exertion intolerance in Myalgic encephalomyelitis/chronic fatigue syndrome. Front Pediatr. (2018) 6:242. doi: 10.3389/fped.2018.00242, PMID: 30234078 CookDB LightAR LightKC BroderickG ShieldsMR DoughertyRJ . Neural consequences of post-exertion malaise in Myalgic encephalomyelitis/chronic fatigue syndrome. Brain Behav Immun. (2017) 62:8799. doi: 10.1016/j.bbi.2017.02.009, PMID: 28216087 JosephP ArevaloC OliveiraRKF Faria-UrbinaM FelsensteinD OaklanderAL . Insights from invasive cardiopulmonary exercise testing of patients with Myalgic encephalomyelitis/chronic fatigue syndrome. Chest. (2021) 160:64251. doi: 10.1016/j.chest.2021.01.082, PMID: 33577778 FlugeO TronstadKJ MellaO. Pathomechanisms and possible interventions in Myalgic encephalomyelitis/chronic fatigue syndrome (me/Cfs). J Clin Invest. (2021) 131:377. doi: 10.1172/JCI150377, PMID: 34263741 JäkelB KedorC GrabowskiP WittkeK ThielS ScherbakovN . Hand grip strength and fatigability: correlation with clinical parameters and diagnostic suitability in me/Cfs. J Transl Med. (2021) 19:112. doi: 10.1186/s12967-021-02774-w GrandeT GrandeB GernerP HammerS StinglM VinkM . The role of psychotherapy in the Care of Patients with Myalgic encephalomyelitis/chronic fatigue syndrome. Medicina. (2023) 59:719. doi: 10.3390/medicina59040719, PMID: 37109676 SurawyC HackmannA HawtonK SharpeM. Chronic fatigue syndrome: a cognitive approach. Behav Res Ther. (1995) 33:53544. doi: 10.1016/0005-7967(94)00077-w GeraghtyKJ BleaseC. Myalgic encephalomyelitis/chronic fatigue syndrome and the biopsychosocial model: a review of patient harm and distress in the medical encounter. Disabil Rehabil. (2019) 41:3092102. doi: 10.1080/09638288.2018.1481149, PMID: 29929450 WormgoorMEA RodenburgSC. The evidence base for physiotherapy in Myalgic encephalomyelitis/chronic fatigue syndrome when considering post-exertional malaise: a systematic review and narrative synthesis. J Transl Med. (2021) 19:1. doi: 10.1186/s12967-020-02683-4, PMID: 33397399 AhmedSA MewesJC VrijhoefH. Assessment of the scientific rigour of randomized controlled trials on the effectiveness of cognitive Behavioural therapy and graded exercise therapy for patients with Myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review. J Health Psychol. (2020) 25:24055. doi: 10.1177/1359105319847261, PMID: 31072121 BatemanL BestedAC BonillaHF ChhedaBV ChuL CurtinJM . Myalgic encephalomyelitis/chronic fatigue syndrome: essentials of diagnosis and management. Mayo Clin Proc. (2021) 96:286178. doi: 10.1016/j.mayocp.2021.07.004, PMID: 34454716 NaculL AuthierFJ ScheibenbogenC LorussoL HellandIB MartinJA . European network on Myalgic encephalomyelitis/chronic fatigue syndrome (Euromene): Expert consensus on the diagnosis, service provision, and Care of People with me/Cfs in Europe. Medicina (Kaunas). (2021) 57:510. doi: 10.3390/medicina57050510, PMID: 34069603 GrachSL SeltzerJ ChonTY GaneshR. Diagnosis and Management of Myalgic Encephalomyelitis/chronic fatigue syndrome. Mayo Clin Proc. (2023) 96:286178. doi: 10.1016/j.mayocp.2023.07.032 GeraghtyK HannM KurtevS. Myalgic encephalomyelitis/chronic fatigue syndrome Patients' reports of symptom changes following cognitive Behavioural therapy, graded exercise therapy and pacing treatments: analysis of a primary survey compared with secondary surveys. J Health Psychol. (2019) 24:131833. doi: 10.1177/1359105317726152 BrownM KhoranaN JasonLA. The role of changes in activity as a function of perceived available and expended energy in nonpharmacological treatment outcomes for me/Cfs. J Clin Psychol. (2011) 67:25360. doi: 10.1002/jclp.20744, PMID: 21254053 Sanal-HayesNE MclaughlinM HayesLD MairJL OrmerodJ CarlessD . A scoping review of ‘Pacing’for Management of Myalgic Encephalomyelitis/chronic fatigue syndrome (me/Cfs): lessons learned for the long Covid pandemic. J Transl Med. (2023) 21:122. doi: 10.1186/s12967-023-04587-5 Helsedirektoratet. Nasjonal Veileder. Pasienter Med Cfs/Me: Utredning, Diagnostikk, Behandling, Rehabilitering, Pleie Og Omsorg. Oslo: Helsedirektoratet (2015). KiellandA LiuJ JasonLA. Do diagnostic criteria for me matter to patient experience with services and interventions? Key results from an online Rds survey targeting fatigue patients in Norway. J Health Psychol. (2023) 28:1189203. doi: 10.1177/13591053231169191, PMID: 37114822 TschoppR KönigRS RejmerP ParisDH. Health system support among patients with me/Cfs in Switzerland. J Taibah Univ Med Sci. (2023) 18:87685. doi: 10.1016/j.jtumed.2022.12.019, PMID: 36852237 SunnquistM NicholsonL JasonLA FriedmanKJ. Access to medical Care for Individuals with Myalgic encephalomyelitis and chronic fatigue syndrome: a call for centers of excellence. Mod Clin Med Res. (2017) 1:2835. doi: 10.22606/mcmr.2017.11005, PMID: 28713878 FroehlichL HattesohlDB JasonLA ScheibenbogenC BehrendsU ThomaM. Medical care situation of people with Myalgic encephalomyelitis/chronic fatigue syndrome in Germany. Medicina. (2021) 57:646. doi: 10.3390/medicina57070646, PMID: 34201825 DavisHE McCorkellL VogelJM TopolEJ. Long Covid: major findings, mechanisms and recommendations. Nat Rev Microbiol. (2023) 21:13346. doi: 10.1038/s41579-022-00846-2, PMID: 36639608 WongTL WeitzerDJ. Long Covid and Myalgic encephalomyelitis/chronic fatigue syndrome (me/Cfs)-a systemic review and comparison of clinical presentation and symptomatology. Medicina (Kaunas). (2021) 57:418. doi: 10.3390/medicina57050418, PMID: 33925784 MarksDF. Converging evidence of similar symptomatology of me/Cfs and Pasc indicating multisystemic Dyshomeostasis. Biomedicine. (2023) 11:180. doi: 10.3390/biomedicines11010180, PMID: 36672687 JosephP SinghI OliveiraR CaponeCA MullenMP CookDB . Exercise pathophysiology in Myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of Sars-Cov-2: more in common than not? Chest. (2023) 164:71726. doi: 10.1016/j.chest.2023.03.049, PMID: 37054777 VernonSD HartleM SullivanK BellJ AbbaszadehS UnutmazD . Post-exertional malaise among people with long Covid compared to Myalgic encephalomyelitis/chronic fatigue syndrome (me/Cfs). Work. (2023) 74:117986. doi: 10.3233/wor-220581, PMID: 36911963 KomaroffAL LipkinWI. Me/Cfs and long Covid share similar symptoms and biological abnormalities. Front Med. (2023) 10:1059. doi: 10.3389/fmed.2023.1187163 SinghI JosephP HeerdtPM CullinanM LutchmansinghDD GulatiM . Persistent exertional intolerance after Covid-19: insights from invasive cardiopulmonary exercise testing. Chest. (2022) 161:5463. doi: 10.1016/j.chest.2021.08.010, PMID: 34389297 JasonLA DorriJA. Me/Cfs and post-exertional malaise among patients with long Covid. Neurol Int. (2022) 15:111. doi: 10.3390/neurolint15010001, PMID: 36648965 World Health Organisation. Clinical Management of Covid-19: Living Guideline. Geneva: World Health Organization (2022). GhaliA LacombeV RavaiauC DelattreE GhaliM UrbanskiG . The relevance of pacing strategies in managing symptoms of post-Covid-19 syndrome. J Transl Med. (2023) 21:375. doi: 10.1186/s12967-023-04229-w, PMID: 37291581 ScheibenbogenC Bellmann-StroblJT HeindrichC WittkeK SteinE FrankeC . Fighting post-Covid and me/Cfs–development of curative therapies. Front Med. (2023) 10:1194754. doi: 10.3389/fmed.2023.1194754, PMID: 37396922 WormgoorMEA. Pasienterfaringer med Utredning Og Behandling Av me Ved Sykehuset I Vestfold Og Telemark Sykehus [patient experiences with clinical evaluations and treatment of me at Vestfold hospital and Telemark hospital]. (2023). ScheiT AngelsenA. Me-Pasienters Erfaring med Rehabiliteringsopphold [me Patients' experience with rehabilitation stays]. Norges Myalgisk Encefalopati Forening, (2018). WHO. Icidh-2: International classification of function and disability, Prefinal draft. Geneva, Switzerland: World Health Organization (2000). WHO. International Classification of Primary Care, -Icpc-2. Geneva: WHO (2009). VinkM Vink-NieseF. Work rehabilitation and medical retirement for Myalgic encephalomyelitis/chronic fatigue syndrome patients. A review and appraisal of diagnostic strategies. Diagnostics (Basel). (2019) 9:124. doi: 10.3390/diagnostics9040124, PMID: 31547009 GhaliA LacoutC FortratJ-O DepresK GhaliM LavigneC. Factors influencing the prognosis of patients with Myalgic encephalomyelitis/chronic fatigue syndrome. Diagnostics. (2022) 12:2540. doi: 10.3390/diagnostics12102540, PMID: 36292229 WesselyS DavidA ButlerS ChalderT. Management of Chronic (post-viral) fatigue syndrome. J R Coll Gen Pract. (1989) 39:269. PMID: 2553945 KnoopH PrinsJB Moss-MorrisR BleijenbergG. The central role of cognitive processes in the perpetuation of chronic fatigue syndrome. J Psychosom Res. (2010) 68:48994. doi: 10.1016/j.jpsychores.2010.01.022, PMID: 20403509 VinkM Vink-NieseA. Cognitive Behavioural therapy for Myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-Analysis of a Cochrane Review. Health Psychol Open. (2019) 6:84061. doi: 10.1177/2055102919840614 McPheeG BaldwinA KindlonT HughesBM. Monitoring treatment harm in Myalgic encephalomyelitis/chronic fatigue syndrome: a freedom-of-information study of National Health Service Specialist Centres in England. J Health Psychol. (2021) 26:97584. doi: 10.1177/1359105319854532 ShepherdC. Pacing and exercise in chronic fatigue syndrome. Physiotherapy. (2001) 87:3956. doi: 10.1016/S0031-9406(05)65457-0 GladwellPW PhebyD RodriguezT PolandF. Use of an online survey to explore positive and negative outcomes of rehabilitation for people with Cfs/me. Disabil Rehabil. (2014) 36:38794. doi: 10.3109/09638288.2013.797508, PMID: 23735013 DawesH. Results of the forward me survey for Cbt and get. Oxford: Oxford Brookes University (2019). CollinSM CrawleyE. Specialist treatment of chronic fatigue syndrome/me: a cohort study among adult patients in England. BMC Health Serv Res. (2017) 17:488. doi: 10.1186/s12913-017-2437-3, PMID: 28709432 ReidH RidoutAJ TomazSA KellyP JonesN. Benefits outweigh the risks: a consensus statement on the risks of physical activity for people living with long-term conditions. Br J Sports Med. (2022) 56:42738. doi: 10.1136/bjsports-2021-104281, PMID: 34649919 NaculL O'BoyleS PallaL NaculFE MudieK KingdonCC . How Myalgic encephalomyelitis/chronic fatigue syndrome (me/Cfs) progresses: the natural history of me/Cfs. Front Neurol. (2020) 11:826. doi: 10.3389/fneur.2020.00826 WyllerVB EriksenHR MalterudK. Can sustained arousal explain the chronic fatigue syndrome? Behav Brain Funct. (2009) 5:10. doi: 10.1186/1744-9081-5-10, PMID: 19236717 UrsinH EriksenHR. The cognitive activation theory of stress. Psychoneuroendocrinology. (2004) 29:56792. doi: 10.1016/S0306-4530(03)00091-X LarunL MalterudK. Identity and coping experiences in chronic fatigue syndrome: a synthesis of qualitative studies. Patient Educ Couns. (2007) 69:208. doi: 10.1016/j.pec.2007.06.008, PMID: 17698311 De BoerML. Epistemic in/Justice in Patient Participation. A discourse analysis of the Dutch me/Cfs health council advisory process. Sociol Health Illn. (2021) 43:133554. doi: 10.1111/1467-9566.13301, PMID: 34137042 ÅsbringP NärvänenA-L. Women’s experiences of stigma in relation to chronic fatigue syndrome and fibromyalgia. Qual Health Res. (2002) 12:14860. doi: 10.1177/104973230201200202, PMID: 11837367 MengshoelAM HellandIB MeeusM Castro-MarreroJ PhebyD BolleSE. Patients' experiences and effects of non-pharmacological treatment for Myalgic encephalomyelitis/chronic fatigue syndrome - a scoping mixed methods review. Int J Qual Stud Health Wellbeing. (2020) 15:1764830. doi: 10.1080/17482631.2020.1764830, PMID: 32432991 GiljeAM SöderlundA MalterudK. Obstructions for quality care experienced by patients with chronic fatigue syndrome (Cfs)—a case study. Patient Educ Couns. (2008) 73:3641. doi: 10.1016/j.pec.2008.04.001 HngKN GeraghtyK PhebyDFH. An audit of Uk hospital Doctors' knowledge and experience of Myalgic encephalomyelitis. Medicina (Kaunas). (2021) 57:885. doi: 10.3390/medicina57090885, PMID: 34577808 KomaroffAL. Myalgic encephalomyelitis/chronic fatigue syndrome: a real illness. Ann Intern Med. (2015) 162:8712. doi: 10.7326/M15-0647 BellmanV ZolnikovTR. Understanding patient-provider interaction, treatment acceptance, and outcomes in medically unexplained symptoms. Cureus. (2022) 14:e32915. doi: 10.7759/cureus.32915 CairnsR HotopfM. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med (Lond). (2005) 55:2031. doi: 10.1093/occmed/kqi013, PMID: 15699087 SommerfeltK ScheiT AngelsenA. Severe and very severe Myalgic encephalopathy/chronic fatigue syndrome me/Cfs in Norway: symptom burden and access to care. J Clin Med. (2023) 12:1487. doi: 10.3390/jcm12041487, PMID: 36836022 KomaroffAL BatemanL. Will Covid-19 Lead to Myalgic encephalomyelitis/chronic fatigue syndrome? Front Med (Lausanne). (2020) 7:606824. doi: 10.3389/fmed.2020.606824, PMID: 33537329 TwomeyR DeMarsJ FranklinK Culos-ReedSN WeatheraldJ WrightsonJG. Chronic fatigue and Postexertional malaise in people living with long Covid: an observational study. Phys Ther. (2022) 102:5. doi: 10.1093/ptj/pzac005, PMID: 35079817 DecaryS GabouryI PoirierS GarciaC SimpsonS BullM . Humility and acceptance: working within our limits with long Covid and Myalgic encephalomyelitis/chronic fatigue syndrome. J Orthop Sports Phys Ther. (2021) 51:197200. doi: 10.2519/jospt.2021.0106, PMID: 33930983 PhebyDFH ArajaD BerkisU BrennaE CullinanJ de KorwinJD . The role of prevention in reducing the economic impact of me/Cfs in Europe: A report from the socioeconomics working Group of the European Network on me/Cfs (Euromene). Medicina (Kaunas). (2021) 57:388. doi: 10.3390/medicina57040388, PMID: 33923830 OliveiraCR JasonLA UnutmazD BatemanL VernonSD. Improvement of long Covid symptoms over one year. Front Med. (2023) 9:1065620. doi: 10.3389/fmed.2022.1065620, PMID: 36698810 HolgateST KomaroffAL ManganD WesselyS. Chronic fatigue syndrome: understanding a complex illness. Nat Rev Neurosci. (2011) 12:53944. doi: 10.1038/nrn3087 WojcikW ArmstrongD KanaanR. Is chronic fatigue syndrome a neurological condition? A survey of Uk neurologists. J Psychosom Res. (2011) 70:5734. doi: 10.1016/j.jpsychores.2011.02.007 PhebyDF ArajaD BerkisU BrennaE CullinanJ de KorwinJ-D . A literature review of Gp knowledge and understanding of me/Cfs: a report from the socioeconomic working Group of the European Network on me/Cfs (Euromene). Medicina. (2020) 57:7. doi: 10.3390/medicina57010007, PMID: 33374291 MuirheadN MuirheadJ LaveryG MarshB. Medical school education on Myalgic encephalomyelitis. Medicina. (2021) 57:542. doi: 10.3390/medicina57060542
      ‘Oh, my dear Thomas, you haven’t heard the terrible news then?’ she said. ‘I thought you would be sure to have seen it placarded somewhere. Alice went straight to her room, and I haven’t seen her since, though I repeatedly knocked at the door, which she has locked on the inside, and I’m sure it’s most unnatural of her not to let her own mother comfort her. It all happened in a moment: I have always said those great motor-cars shouldn’t be allowed to career about the streets, especially when they are all paved with cobbles as they are at Easton Haven, which are{331} so slippery when it’s wet. He slipped, and it went over him in a moment.’ My thanks were few and awkward, for there still hung to the missive a basting thread, and it was as warm as a nestling bird. I bent low--everybody was emotional in those days--kissed the fragrant thing, thrust it into my bosom, and blushed worse than Camille. "What, the Corner House victim? Is that really a fact?" "My dear child, I don't look upon it in that light at all. The child gave our picturesque friend a certain distinction--'My husband is dead, and this is my only child,' and all that sort of thing. It pays in society." leave them on the steps of a foundling asylum in order to insure [See larger version] Interoffice guff says you're planning definite moves on your own, J. O., and against some opposition. Is the Colonel so poor or so grasping—or what? Albert could not speak, for he felt as if his brains and teeth were rattling about inside his head. The rest of[Pg 188] the family hunched together by the door, the boys gaping idiotically, the girls in tears. "Now you're married." The host was called in, and unlocked a drawer in which they were deposited. The galleyman, with visible reluctance, arrayed himself in the garments, and he was observed to shudder more than once during the investiture of the dead man's apparel. HoME香京julia种子在线播放 ENTER NUMBET 0016mgchain.com.cn
      eyzwnl.com.cn
      www.huntingx.com.cn
      udaway.com.cn
      www.wangcio.com.cn
      www.uspybf.com.cn
      www.sxsilin.com.cn
      www.shuimozi.com.cn
      nabakem.com.cn
      www.wqhibi.com.cn
      处女被大鸡巴操 强奸乱伦小说图片 俄罗斯美女爱爱图 调教强奸学生 亚洲女的穴 夜来香图片大全 美女性强奸电影 手机版色中阁 男性人体艺术素描图 16p成人 欧美性爱360 电影区 亚洲电影 欧美电影 经典三级 偷拍自拍 动漫电影 乱伦电影 变态另类 全部电 类似狠狠鲁的网站 黑吊操白逼图片 韩国黄片种子下载 操逼逼逼逼逼 人妻 小说 p 偷拍10幼女自慰 极品淫水很多 黄色做i爱 日本女人人体电影快播看 大福国小 我爱肏屄美女 mmcrwcom 欧美多人性交图片 肥臀乱伦老头舔阴帝 d09a4343000019c5 西欧人体艺术b xxoo激情短片 未成年人的 插泰国人夭图片 第770弾み1 24p 日本美女性 交动态 eee色播 yantasythunder 操无毛少女屄 亚洲图片你懂的女人 鸡巴插姨娘 特级黄 色大片播 左耳影音先锋 冢本友希全集 日本人体艺术绿色 我爱被舔逼 内射 幼 美阴图 喷水妹子高潮迭起 和后妈 操逼 美女吞鸡巴 鸭个自慰 中国女裸名单 操逼肥臀出水换妻 色站裸体义术 中国行上的漏毛美女叫什么 亚洲妹性交图 欧美美女人裸体人艺照 成人色妹妹直播 WWW_JXCT_COM r日本女人性淫乱 大胆人艺体艺图片 女同接吻av 碰碰哥免费自拍打炮 艳舞写真duppid1 88电影街拍视频 日本自拍做爱qvod 实拍美女性爱组图 少女高清av 浙江真实乱伦迅雷 台湾luanlunxiaoshuo 洛克王国宠物排行榜 皇瑟电影yy频道大全 红孩儿连连看 阴毛摄影 大胆美女写真人体艺术摄影 和风骚三个媳妇在家做爱 性爱办公室高清 18p2p木耳 大波撸影音 大鸡巴插嫩穴小说 一剧不超两个黑人 阿姨诱惑我快播 幼香阁千叶县小学生 少女妇女被狗强奸 曰人体妹妹 十二岁性感幼女 超级乱伦qvod 97爱蜜桃ccc336 日本淫妇阴液 av海量资源999 凤凰影视成仁 辰溪四中艳照门照片 先锋模特裸体展示影片 成人片免费看 自拍百度云 肥白老妇女 女爱人体图片 妈妈一女穴 星野美夏 日本少女dachidu 妹子私处人体图片 yinmindahuitang 舔无毛逼影片快播 田莹疑的裸体照片 三级电影影音先锋02222 妻子被外国老头操 观月雏乃泥鳅 韩国成人偷拍自拍图片 强奸5一9岁幼女小说 汤姆影院av图片 妹妹人艺体图 美女大驱 和女友做爱图片自拍p 绫川まどか在线先锋 那么嫩的逼很少见了 小女孩做爱 处女好逼连连看图图 性感美女在家做爱 近距离抽插骚逼逼 黑屌肏金毛屄 日韩av美少女 看喝尿尿小姐日逼色色色网图片 欧美肛交新视频 美女吃逼逼 av30线上免费 伊人在线三级经典 新视觉影院t6090影院 最新淫色电影网址 天龙影院远古手机版 搞老太影院 插进美女的大屁股里 私人影院加盟费用 www258dd 求一部电影里面有一个二猛哥 深肛交 日本萌妹子人体艺术写真图片 插入屄眼 美女的木奶 中文字幕黄色网址影视先锋 九号女神裸 和骚人妻偷情 和潘晓婷做爱 国模大尺度蜜桃 欧美大逼50p 西西人体成人 李宗瑞继母做爱原图物处理 nianhuawang 男鸡巴的视屏 � 97免费色伦电影 好色网成人 大姨子先锋 淫荡巨乳美女教师妈妈 性nuexiaoshuo WWW36YYYCOM 长春继续给力进屋就操小女儿套干破内射对白淫荡 农夫激情社区 日韩无码bt 欧美美女手掰嫩穴图片 日本援交偷拍自拍 入侵者日本在线播放 亚洲白虎偷拍自拍 常州高见泽日屄 寂寞少妇自卫视频 人体露逼图片 多毛外国老太 变态乱轮手机在线 淫荡妈妈和儿子操逼 伦理片大奶少女 看片神器最新登入地址sqvheqi345com账号群 麻美学姐无头 圣诞老人射小妞和强奸小妞动话片 亚洲AV女老师 先锋影音欧美成人资源 33344iucoom zV天堂电影网 宾馆美女打炮视频 色五月丁香五月magnet 嫂子淫乱小说 张歆艺的老公 吃奶男人视频在线播放 欧美色图男女乱伦 avtt2014ccvom 性插色欲香影院 青青草撸死你青青草 99热久久第一时间 激情套图卡通动漫 幼女裸聊做爱口交 日本女人被强奸乱伦 草榴社区快播 2kkk正在播放兽骑 啊不要人家小穴都湿了 www猎奇影视 A片www245vvcomwwwchnrwhmhzcn 搜索宜春院av wwwsee78co 逼奶鸡巴插 好吊日AV在线视频19gancom 熟女伦乱图片小说 日本免费av无码片在线开苞 鲁大妈撸到爆 裸聊官网 德国熟女xxx 新不夜城论坛首页手机 女虐男网址 男女做爱视频华为网盘 激情午夜天亚洲色图 内裤哥mangent 吉沢明歩制服丝袜WWWHHH710COM 屌逼在线试看 人体艺体阿娇艳照 推荐一个可以免费看片的网站如果被QQ拦截请复制链接在其它浏览器打开xxxyyy5comintr2a2cb551573a2b2e 欧美360精品粉红鲍鱼 教师调教第一页 聚美屋精品图 中韩淫乱群交 俄罗斯撸撸片 把鸡巴插进小姨子的阴道 干干AV成人网 aolasoohpnbcn www84ytom 高清大量潮喷www27dyycom 宝贝开心成人 freefronvideos人母 嫩穴成人网gggg29com 逼着舅妈给我口交肛交彩漫画 欧美色色aV88wwwgangguanscom 老太太操逼自拍视频 777亚洲手机在线播放 有没有夫妻3p小说 色列漫画淫女 午间色站导航 欧美成人处女色大图 童颜巨乳亚洲综合 桃色性欲草 色眯眯射逼 无码中文字幕塞外青楼这是一个 狂日美女老师人妻 爱碰网官网 亚洲图片雅蠛蝶 快播35怎么搜片 2000XXXX电影 新谷露性家庭影院 深深候dvd播放 幼齿用英语怎么说 不雅伦理无需播放器 国外淫荡图片 国外网站幼幼嫩网址 成年人就去色色视频快播 我鲁日日鲁老老老我爱 caoshaonvbi 人体艺术avav 性感性色导航 韩国黄色哥来嫖网站 成人网站美逼 淫荡熟妇自拍 欧美色惰图片 北京空姐透明照 狼堡免费av视频 www776eom 亚洲无码av欧美天堂网男人天堂 欧美激情爆操 a片kk266co 色尼姑成人极速在线视频 国语家庭系列 蒋雯雯 越南伦理 色CC伦理影院手机版 99jbbcom 大鸡巴舅妈 国产偷拍自拍淫荡对话视频 少妇春梦射精 开心激动网 自拍偷牌成人 色桃隐 撸狗网性交视频 淫荡的三位老师 伦理电影wwwqiuxia6commqiuxia6com 怡春院分站 丝袜超短裙露脸迅雷下载 色制服电影院 97超碰好吊色男人 yy6080理论在线宅男日韩福利大全 大嫂丝袜 500人群交手机在线 5sav 偷拍熟女吧 口述我和妹妹的欲望 50p电脑版 wwwavtttcon 3p3com 伦理无码片在线看 欧美成人电影图片岛国性爱伦理电影 先锋影音AV成人欧美 我爱好色 淫电影网 WWW19MMCOM 玛丽罗斯3d同人动画h在线看 动漫女孩裸体 超级丝袜美腿乱伦 1919gogo欣赏 大色逼淫色 www就是撸 激情文学网好骚 A级黄片免费 xedd5com 国内的b是黑的 快播美国成年人片黄 av高跟丝袜视频 上原保奈美巨乳女教师在线观看 校园春色都市激情fefegancom 偷窥自拍XXOO 搜索看马操美女 人本女优视频 日日吧淫淫 人妻巨乳影院 美国女子性爱学校 大肥屁股重口味 啪啪啪啊啊啊不要 操碰 japanfreevideoshome国产 亚州淫荡老熟女人体 伦奸毛片免费在线看 天天影视se 樱桃做爱视频 亚卅av在线视频 x奸小说下载 亚洲色图图片在线 217av天堂网 东方在线撸撸-百度 幼幼丝袜集 灰姑娘的姐姐 青青草在线视频观看对华 86papa路con 亚洲1AV 综合图片2区亚洲 美国美女大逼电影 010插插av成人网站 www色comwww821kxwcom 播乐子成人网免费视频在线观看 大炮撸在线影院 ,www4KkKcom 野花鲁最近30部 wwwCC213wapwww2233ww2download 三客优最新地址 母亲让儿子爽的无码视频 全国黄色片子 欧美色图美国十次 超碰在线直播 性感妖娆操 亚洲肉感熟女色图 a片A毛片管看视频 8vaa褋芯屑 333kk 川岛和津实视频 在线母子乱伦对白 妹妹肥逼五月 亚洲美女自拍 老婆在我面前小说 韩国空姐堪比情趣内衣 干小姐综合 淫妻色五月 添骚穴 WM62COM 23456影视播放器 成人午夜剧场 尼姑福利网 AV区亚洲AV欧美AV512qucomwwwc5508com 经典欧美骚妇 震动棒露出 日韩丝袜美臀巨乳在线 av无限吧看 就去干少妇 色艺无间正面是哪集 校园春色我和老师做爱 漫画夜色 天海丽白色吊带 黄色淫荡性虐小说 午夜高清播放器 文20岁女性荫道口图片 热国产热无码热有码 2015小明发布看看算你色 百度云播影视 美女肏屄屄乱轮小说 家族舔阴AV影片 邪恶在线av有码 父女之交 关于处女破处的三级片 极品护士91在线 欧美虐待女人视频的网站 享受老太太的丝袜 aaazhibuo 8dfvodcom成人 真实自拍足交 群交男女猛插逼 妓女爱爱动态 lin35com是什么网站 abp159 亚洲色图偷拍自拍乱伦熟女抠逼自慰 朝国三级篇 淫三国幻想 免费的av小电影网站 日本阿v视频免费按摩师 av750c0m 黄色片操一下 巨乳少女车震在线观看 操逼 免费 囗述情感一乱伦岳母和女婿 WWW_FAMITSU_COM 偷拍中国少妇在公车被操视频 花也真衣论理电影 大鸡鸡插p洞 新片欧美十八岁美少 进击的巨人神thunderftp 西方美女15p 深圳哪里易找到老女人玩视频 在线成人有声小说 365rrr 女尿图片 我和淫荡的小姨做爱 � 做爱技术体照 淫妇性爱 大学生私拍b 第四射狠狠射小说 色中色成人av社区 和小姨子乱伦肛交 wwwppp62com 俄罗斯巨乳人体艺术 骚逼阿娇 汤芳人体图片大胆 大胆人体艺术bb私处 性感大胸骚货 哪个网站幼女的片多 日本美女本子把 色 五月天 婷婷 快播 美女 美穴艺术 色百合电影导航 大鸡巴用力 孙悟空操美少女战士 狠狠撸美女手掰穴图片 古代女子与兽类交 沙耶香套图 激情成人网区 暴风影音av播放 动漫女孩怎么插第3个 mmmpp44 黑木麻衣无码ed2k 淫荡学姐少妇 乱伦操少女屄 高中性爱故事 骚妹妹爱爱图网 韩国模特剪长发 大鸡巴把我逼日了 中国张柏芝做爱片中国张柏芝做爱片中国张柏芝做爱片中国张柏芝做爱片中国张柏芝做爱片 大胆女人下体艺术图片 789sss 影音先锋在线国内情侣野外性事自拍普通话对白 群撸图库 闪现君打阿乐 ady 小说 插入表妹嫩穴小说 推荐成人资源 网络播放器 成人台 149大胆人体艺术 大屌图片 骚美女成人av 春暖花开春色性吧 女亭婷五月 我上了同桌的姐姐 恋夜秀场主播自慰视频 yzppp 屄茎 操屄女图 美女鲍鱼大特写 淫乱的日本人妻山口玲子 偷拍射精图 性感美女人体艺木图片 种马小说完本 免费电影院 骑士福利导航导航网站 骚老婆足交 国产性爱一级电影 欧美免费成人花花性都 欧美大肥妞性爱视频 家庭乱伦网站快播 偷拍自拍国产毛片 金发美女也用大吊来开包 缔D杏那 yentiyishu人体艺术ytys WWWUUKKMCOM 女人露奶 � 苍井空露逼 老荡妇高跟丝袜足交 偷偷和女友的朋友做爱迅雷 做爱七十二尺 朱丹人体合成 麻腾由纪妃 帅哥撸播种子图 鸡巴插逼动态图片 羙国十次啦中文 WWW137AVCOM 神斗片欧美版华语 有气质女人人休艺术 由美老师放屁电影 欧美女人肉肏图片 白虎种子快播 国产自拍90后女孩 美女在床上疯狂嫩b 饭岛爱最后之作 幼幼强奸摸奶 色97成人动漫 两性性爱打鸡巴插逼 新视觉影院4080青苹果影院 嗯好爽插死我了 阴口艺术照 李宗瑞电影qvod38 爆操舅母 亚洲色图七七影院 被大鸡巴操菊花 怡红院肿么了 成人极品影院删除 欧美性爱大图色图强奸乱 欧美女子与狗随便性交 苍井空的bt种子无码 熟女乱伦长篇小说 大色虫 兽交幼女影音先锋播放 44aad be0ca93900121f9b 先锋天耗ばさ无码 欧毛毛女三级黄色片图 干女人黑木耳照 日本美女少妇嫩逼人体艺术 sesechangchang 色屄屄网 久久撸app下载 色图色噜 美女鸡巴大奶 好吊日在线视频在线观看 透明丝袜脚偷拍自拍 中山怡红院菜单 wcwwwcom下载 骑嫂子 亚洲大色妣 成人故事365ahnet 丝袜家庭教mp4 幼交肛交 妹妹撸撸大妈 日本毛爽 caoprom超碰在email 关于中国古代偷窥的黄片 第一会所老熟女下载 wwwhuangsecome 狼人干综合新地址HD播放 变态儿子强奸乱伦图 强奸电影名字 2wwwer37com 日本毛片基地一亚洲AVmzddcxcn 暗黑圣经仙桃影院 37tpcocn 持月真由xfplay 好吊日在线视频三级网 我爱背入李丽珍 电影师傅床戏在线观看 96插妹妹sexsex88com 豪放家庭在线播放 桃花宝典极夜著豆瓜网 安卓系统播放神器 美美网丝袜诱惑 人人干全免费视频xulawyercn av无插件一本道 全国色五月 操逼电影小说网 good在线wwwyuyuelvcom www18avmmd 撸波波影视无插件 伊人幼女成人电影 会看射的图片 小明插看看 全裸美女扒开粉嫩b 国人自拍性交网站 萝莉白丝足交本子 七草ちとせ巨乳视频 摇摇晃晃的成人电影 兰桂坊成社人区小说www68kqcom 舔阴论坛 久撸客一撸客色国内外成人激情在线 明星门 欧美大胆嫩肉穴爽大片 www牛逼插 性吧星云 少妇性奴的屁眼 人体艺术大胆mscbaidu1imgcn 最新久久色色成人版 l女同在线 小泽玛利亚高潮图片搜索 女性裸b图 肛交bt种子 最热门有声小说 人间添春色 春色猜谜字 樱井莉亚钢管舞视频 小泽玛利亚直美6p 能用的h网 还能看的h网 bl动漫h网 开心五月激 东京热401 男色女色第四色酒色网 怎么下载黄色小说 黄色小说小栽 和谐图城 乐乐影院 色哥导航 特色导航 依依社区 爱窝窝在线 色狼谷成人 91porn 包要你射电影 色色3A丝袜 丝袜妹妹淫网 爱色导航(荐) 好男人激情影院 坏哥哥 第七色 色久久 人格分裂 急先锋 撸撸射中文网 第一会所综合社区 91影院老师机 东方成人激情 怼莪影院吹潮 老鸭窝伊人无码不卡无码一本道 av女柳晶电影 91天生爱风流作品 深爱激情小说私房婷婷网 擼奶av 567pao 里番3d一家人野外 上原在线电影 水岛津实透明丝袜 1314酒色 网旧网俺也去 0855影院 在线无码私人影院 搜索 国产自拍 神马dy888午夜伦理达达兔 农民工黄晓婷 日韩裸体黑丝御姐 屈臣氏的燕窝面膜怎么样つぼみ晶エリーの早漏チ○ポ强化合宿 老熟女人性视频 影音先锋 三上悠亚ol 妹妹影院福利片 hhhhhhhhsxo 午夜天堂热的国产 强奸剧场 全裸香蕉视频无码 亚欧伦理视频 秋霞为什么给封了 日本在线视频空天使 日韩成人aⅴ在线 日本日屌日屄导航视频 在线福利视频 日本推油无码av magnet 在线免费视频 樱井梨吮东 日本一本道在线无码DVD 日本性感诱惑美女做爱阴道流水视频 日本一级av 汤姆avtom在线视频 台湾佬中文娱乐线20 阿v播播下载 橙色影院 奴隶少女护士cg视频 汤姆在线影院无码 偷拍宾馆 业面紧急生级访问 色和尚有线 厕所偷拍一族 av女l 公交色狼优酷视频 裸体视频AV 人与兽肉肉网 董美香ol 花井美纱链接 magnet 西瓜影音 亚洲 自拍 日韩女优欧美激情偷拍自拍 亚洲成年人免费视频 荷兰免费成人电影 深喉呕吐XXⅩX 操石榴在线视频 天天色成人免费视频 314hu四虎 涩久免费视频在线观看 成人电影迅雷下载 能看见整个奶子的香蕉影院 水菜丽百度影音 gwaz079百度云 噜死你们资源站 主播走光视频合集迅雷下载 thumbzilla jappen 精品Av 古川伊织star598在线 假面女皇vip在线视频播放 国产自拍迷情校园 啪啪啪公寓漫画 日本阿AV 黄色手机电影 欧美在线Av影院 华裔电击女神91在线 亚洲欧美专区 1日本1000部免费视频 开放90后 波多野结衣 东方 影院av 页面升级紧急访问每天正常更新 4438Xchengeren 老炮色 a k福利电影 色欲影视色天天视频 高老庄aV 259LUXU-683 magnet 手机在线电影 国产区 欧美激情人人操网 国产 偷拍 直播 日韩 国内外激情在线视频网给 站长统计一本道人妻 光棍影院被封 紫竹铃取汁 ftp 狂插空姐嫩 xfplay 丈夫面前 穿靴子伪街 XXOO视频在线免费 大香蕉道久在线播放 电棒漏电嗨过头 充气娃能看下毛和洞吗 夫妻牲交 福利云点墦 yukun瑟妃 疯狂交换女友 国产自拍26页 腐女资源 百度云 日本DVD高清无码视频 偷拍,自拍AV伦理电影 A片小视频福利站。 大奶肥婆自拍偷拍图片 交配伊甸园 超碰在线视频自拍偷拍国产 小热巴91大神 rctd 045 类似于A片 超美大奶大学生美女直播被男友操 男友问 你的衣服怎么脱掉的 亚洲女与黑人群交视频一 在线黄涩 木内美保步兵番号 鸡巴插入欧美美女的b舒服 激情在线国产自拍日韩欧美 国语福利小视频在线观看 作爱小视颍 潮喷合集丝袜无码mp4 做爱的无码高清视频 牛牛精品 伊aⅤ在线观看 savk12 哥哥搞在线播放 在线电一本道影 一级谍片 250pp亚洲情艺中心,88 欧美一本道九色在线一 wwwseavbacom色av吧 cos美女在线 欧美17,18ⅹⅹⅹ视频 自拍嫩逼 小电影在线观看网站 筱田优 贼 水电工 5358x视频 日本69式视频有码 b雪福利导航 韩国女主播19tvclub在线 操逼清晰视频 丝袜美女国产视频网址导航 水菜丽颜射房间 台湾妹中文娱乐网 风吟岛视频 口交 伦理 日本熟妇色五十路免费视频 A级片互舔 川村真矢Av在线观看 亚洲日韩av 色和尚国产自拍 sea8 mp4 aV天堂2018手机在线 免费版国产偷拍a在线播放 狠狠 婷婷 丁香 小视频福利在线观看平台 思妍白衣小仙女被邻居强上 萝莉自拍有水 4484新视觉 永久发布页 977成人影视在线观看 小清新影院在线观 小鸟酱后丝后入百度云 旋风魅影四级 香蕉影院小黄片免费看 性爱直播磁力链接 小骚逼第一色影院 性交流的视频 小雪小视频bd 小视频TV禁看视频 迷奸AV在线看 nba直播 任你在干线 汤姆影院在线视频国产 624u在线播放 成人 一级a做爰片就在线看狐狸视频 小香蕉AV视频 www182、com 腿模简小育 学生做爱视频 秘密搜查官 快播 成人福利网午夜 一级黄色夫妻录像片 直接看的gav久久播放器 国产自拍400首页 sm老爹影院 谁知道隔壁老王网址在线 综合网 123西瓜影音 米奇丁香 人人澡人人漠大学生 色久悠 夜色视频你今天寂寞了吗? 菲菲影视城美国 被抄的影院 变态另类 欧美 成人 国产偷拍自拍在线小说 不用下载安装就能看的吃男人鸡巴视频 插屄视频 大贯杏里播放 wwwhhh50 233若菜奈央 伦理片天海翼秘密搜查官 大香蕉在线万色屋视频 那种漫画小说你懂的 祥仔电影合集一区 那里可以看澳门皇冠酒店a片 色自啪 亚洲aV电影天堂 谷露影院ar toupaizaixian sexbj。com 毕业生 zaixian mianfei 朝桐光视频 成人短视频在线直接观看 陈美霖 沈阳音乐学院 导航女 www26yjjcom 1大尺度视频 开平虐女视频 菅野雪松协和影视在线视频 华人play在线视频bbb 鸡吧操屄视频 多啪啪免费视频 悠草影院 金兰策划网 (969) 橘佑金短视频 国内一极刺激自拍片 日本制服番号大全magnet 成人动漫母系 电脑怎么清理内存 黄色福利1000 dy88午夜 偷拍中学生洗澡磁力链接 花椒相机福利美女视频 站长推荐磁力下载 mp4 三洞轮流插视频 玉兔miki热舞视频 夜生活小视频 爆乳人妖小视频 国内网红主播自拍福利迅雷下载 不用app的裸裸体美女操逼视频 变态SM影片在线观看 草溜影院元气吧 - 百度 - 百度 波推全套视频 国产双飞集合ftp 日本在线AV网 笔国毛片 神马影院女主播是我的邻居 影音资源 激情乱伦电影 799pao 亚洲第一色第一影院 av视频大香蕉 老梁故事汇希斯莱杰 水中人体磁力链接 下载 大香蕉黄片免费看 济南谭崔 避开屏蔽的岛a片 草破福利 要看大鸡巴操小骚逼的人的视频 黑丝少妇影音先锋 欧美巨乳熟女磁力链接 美国黄网站色大全 伦蕉在线久播 极品女厕沟 激情五月bd韩国电影 混血美女自摸和男友激情啪啪自拍诱人呻吟福利视频 人人摸人人妻做人人看 44kknn 娸娸原网 伊人欧美 恋夜影院视频列表安卓青青 57k影院 如果电话亭 avi 插爆骚女精品自拍 青青草在线免费视频1769TV 令人惹火的邻家美眉 影音先锋 真人妹子被捅动态图 男人女人做完爱视频15 表姐合租两人共处一室晚上她竟爬上了我的床 性爱教学视频 北条麻妃bd在线播放版 国产老师和师生 magnet wwwcctv1024 女神自慰 ftp 女同性恋做激情视频 欧美大胆露阴视频 欧美无码影视 好女色在线观看 后入肥臀18p 百度影视屏福利 厕所超碰视频 强奸mp magnet 欧美妹aⅴ免费线上看 2016年妞干网视频 5手机在线福利 超在线最视频 800av:cOm magnet 欧美性爱免播放器在线播放 91大款肥汤的性感美乳90后邻家美眉趴着窗台后入啪啪 秋霞日本毛片网站 cheng ren 在线视频 上原亚衣肛门无码解禁影音先锋 美脚家庭教师在线播放 尤酷伦理片 熟女性生活视频在线观看 欧美av在线播放喷潮 194avav 凤凰AV成人 - 百度 kbb9999 AV片AV在线AV无码 爱爱视频高清免费观看 黄色男女操b视频 观看 18AV清纯视频在线播放平台 成人性爱视频久久操 女性真人生殖系统双性人视频 下身插入b射精视频 明星潜规测视频 mp4 免賛a片直播绪 国内 自己 偷拍 在线 国内真实偷拍 手机在线 国产主播户外勾在线 三桥杏奈高清无码迅雷下载 2五福电影院凸凹频频 男主拿鱼打女主,高宝宝 色哥午夜影院 川村まや痴汉 草溜影院费全过程免费 淫小弟影院在线视频 laohantuiche 啪啪啪喷潮XXOO视频 青娱乐成人国产 蓝沢润 一本道 亚洲青涩中文欧美 神马影院线理论 米娅卡莉法的av 在线福利65535 欧美粉色在线 欧美性受群交视频1在线播放 极品喷奶熟妇在线播放 变态另类无码福利影院92 天津小姐被偷拍 磁力下载 台湾三级电髟全部 丝袜美腿偷拍自拍 偷拍女生性行为图 妻子的乱伦 白虎少妇 肏婶骚屄 外国大妈会阴照片 美少女操屄图片 妹妹自慰11p 操老熟女的b 361美女人体 360电影院樱桃 爱色妹妹亚洲色图 性交卖淫姿势高清图片一级 欧美一黑对二白 大色网无毛一线天 射小妹网站 寂寞穴 西西人体模特苍井空 操的大白逼吧 骚穴让我操 拉好友干女朋友3p