*3.5. Comparison*

Participants assigned to the control group were either placed on the waiting list [28–30,40,41] or received standard medical care [39]. They were advised to keep their usual lifestyle activities including seeking general medical care but not to participate in any activities similar to the intervention of interest.

## *3.6. Outcomes*

Many different outcomes and outcome measures were reported in the included studies. Four studies clearly stated their primary and secondary outcomes/objectives [30,39–41]. Fatigue severity was measured by seven studies using Chalder fatigue scale [10,28–30,40,41,43].One study (published as two reports), listed Chalder fatigue scale in one of the reports as the administered questionnaire [51]. In the other report, however, they measured fatigue using patient-rated Likert-type scales [39]. Other studies used either profile of mood state (POMS) [42,45] or multidimensional fatigue inventory (MFI-20) [44].

Eight studies measured anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) [29,30,40,41,43,44,51,91]. Six studies measured quality of life or physical and/or mental functioning using different quality of life outcome measures [28–30,41,45,51]. Seven studies measured objective outcomes including ventilatory parameters [38], performance testing by computer programs [51], telomerase activity [70], autonomic nervous system functions, blood biomarkers [42,91], adiponectin levels [83], and microRNA changes [10]. Table 2 describes the details of these outcome measures and the other outcomes measured in the included studies.

#### *3.7. Effects of Interventions*

Due to heterogeneous interventions and outcome measures used in the included studies, a meta-analysis was not performed. The statistically significant outcomes reported by these studies are presented in Tables 3 and 4. Tables A3 and A4 show the statistically insignificant outcomes.


**Table 3.** Significant outcomes in the included studies using CDC, Canadian and international consensus criteria for diagnosing CFS.

*Medicina* **2021**, *57*, 652




*Medicina* **2021**, *57*, 652




Multidimensional fatigue inventory-20, ACT: Acceptance and commitment therapy, MBCT: Mindfulness-based cognitive therapy, CBSM: Cognitive-based stress management. \* measure

of stress-related damage at a cellular level. \*\* to test the interaction effect of time and group.


195



Short-Form Health Survey.

In comparison to the control group, both mental and physical fatigue scores improved significantly in four included studies using MBCT [30], isometric yoga [28], Qigong exercise [41] and Baduanjin Qigong [40]. Two studies showed within-group fatigue improvement in participants receiving an 8-week mindfulness therapy [29] and in participants receiving a 10-week relaxation program [39] (Tables 3 and 4)

Anxiety and depression were improved in participants receiving Baduanjin Qigong compared to the controls after 16 sessions (9 weeks) of therapy [40]. Depression was improved in participants after 4 months of Qigong exercise [41] and 8 weeks of MBCT [30] compared to the control groups. Surawy et al. [29] also showed improvement of anxiety after 8 weeks of MBSR/MBCT intervention compared to the control group.

In comparison to the control group, quality of life improved in participants receiving Qigong exercise [41,70,71] and cognitive-behavioral stress managemen<sup>t</sup> [45].

Tables 3 and 4 show the details of all the significant outcomes of the included studies according to the diagnosis of ME/CFS (Oxford or CDC criteria).

#### *3.8. Adverse Events*

Seven studies assessed adverse events: Four did not identify any adverse events [30,39,41,43]; and three studies recorded adverse events such as deterioration of their symptoms, muscle ache, palpitation, dizziness, knee pain, backache, fatigue, and nervousness [28,40,44]. Five studies did not report if they assessed adverse events [10,29,38,42,45]

#### *3.9. Risk of Bias in the Included Studies*

All the included RCT studies were assessed at a high risk of bias in relation to the lack of blinding of participants and personnel. We were not able to assess the risk of bias in many areas as most of the studies were poorly reported (Figure 2). The risk of bias assessment for the single-arm experimental studies using the ROBINS-I assessment tool is shown in Table A5.

**Figure 2.** Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
