The effectiveness of activity pacing interventions for people with chronic fatigue syndrome: a systematic review and meta-analysis

Purpose: To investigate whether activity pacing interventions (alone or in conjunction with other evidence-based interventions) improve fatigue, physical function, psychological distress, depression, and anxiety in people with chronic fatigue syndrome (CFS). Materials and methods: Seven databases were searched until 13 August 2022 for randomised controlled trials that included activity pacing interventions for CFS and a validated measure of fatigue. Secondary outcomes were physical function, psychological distress, depression, and anxiety. Two reviewers independently screened studies by title, abstract and full text. Methodological quality was evaluated using the PEDro scale. Random-effects meta-analyses were performed in R. Results: 6390 articles were screened, with 14 included. Good overall study quality was supported by PEDro scale ratings. Activity pacing interventions were effective (Hedges’ g (95% CI)) at reducing fatigue (–0.52 (–0.73 to −0.32)), psychological distress (–0.37 (–0.51 to −0.24)) and depression (–0.29 (–0.49 to −0.09)) and improving physical function (mean difference 7.18 (3.17–11.18)) when compared to no treatment/usual care. The extent of improvement was greater for interventions that encouraged graded escalation of physical activities and cognitive activities. Conclusion: Activity pacing interventions are effective in reducing fatigue and psychological distress and improving physical function in CFS, particularly when people are encouraged to gradually increase activities. Registration: PROSPERO CRD42016036087. IMPLICATIONS FOR REHABILITATION A key feature of chronic fatigue syndrome (CFS) is a prolonged post-exertional exacerbation of symptoms following physical activities or cognitive activities. Activity pacing is a common strategy often embedded in multi-component management programs for CFS. Activity pacing interventions are effective in reducing fatigue and psychological distress and improving physical function in CFS, particularly when patients are encouraged to gradually increase their activities. Healthcare professionals embedding activity pacing as part of treatment should work collaboratively with patients to ensure successful, individualised self-management strategies

eLearning improves allied health professionals' knowledge and confidence to manage medically unexplained chronic fatigue states: A randomized controlled trial

Objectives: To evaluate the impact of eLearning by allied health professionals on improving the knowledge and confidence to manage people with medically unexplained chronic fatigue states (FS). Methods: Using a parallel randomized controlled trial design, participants were randomized 1:1 to a 4-week eLearning or wait-list control group. Knowledge and self-reported confidence in clinical skills to implement a therapeutic intervention for patients with FS were assessed at baseline, post-intervention and follow-up. Secondary outcomes (adherence and satisfaction with online education, knowledge retention) were also assessed. Data was analyzed using intention-to-treat. Results: There were 239 participants were randomized (eLearning n = 119, control n = 120), of whom 101 (85%) eLearning and 107 (89%) control participants completed baseline assessments and were included in the analysis. Knowledge (out of 100) improved significantly more in the eLearning group compared to the control group [mean difference (95% CI) 8.6 (5.9 to 11.4), p < 0.001]. Knowledge was reduced in the eLearning group at follow-up but was still significantly higher than baseline [6.0 (3.7 to 8.3), p < 0.001]. Median change (out of 5) in confidence in clinical skills to implement the FS intervention was also significantly greater in the eLearning group compared to the control group [knowledge: eLearning (1.2), control (0); clinical skills: eLearning (1), control (0.1); both p < 0.001)]. Average time spent on the eLearning program was 8.8 h. Most participants (80%) rated the lesson difficulty as at the “right level”, and 91% would recommend it to others. Conclusions: eLearning increased knowledge and confidence to manage FS amongst allied health professionals and was well-accepted. Registration: ACTRN12616000296437 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370222&isReview=true

Prevalence and Characteristics Associated With Post-COVID-19 Condition Among Nonhospitalized Adolescents and Young Adults

Importance: The prevalence and baseline risk factors of post-COVID-19 condition (PCC) remain unresolved among the large number of young people who experienced mild COVID-19. Objectives: To determine the point prevalence of PCC 6 months after the acute infection, to determine the risk of development of PCC adjusted for possible confounders, and to explore a broad range of potential risk factors. Design, Setting, and Participants: This cohort study included nonhospitalized individuals from 2 counties in Norway between ages 12 and 25 years who underwent reverse transcription-polymerase chain reaction (RT-PCR) testing. At the early convalescent stage and at 6-month follow-up, participants underwent a clinical examination; pulmonary, cardiac, and cognitive functional testing; immunological and organ injury biomarker analyses; and completion of a questionnaire. Participants were classified according to the World Health Organization case definition of PCC at follow-up. Association analyses of 78 potential risk factors were performed. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The point prevalence of PCC 6 months after RT-PCR testing in the SARS-CoV-2-positive and SARS-CoV-2-negative groups, and the risk difference with corresponding 95% CIs. Results: A total of 404 individuals testing positive for SARS-CoV-2 and 105 individuals testing negative were enrolled (194 male [38.1%]; 102 non-European [20.0%] ethnicity). A total of 22 of the SARS-CoV-2-positive and 4 of the SARS-CoV-2-negative individuals were lost to follow-up, and 16 SARS-CoV-2-negative individuals were excluded due to SARS-CoV-2 infection in the observational period. Hence, 382 SARS-CoV-2-positive participants (mean [SD] age, 18.0 [3.7] years; 152 male [39.8%]) and 85 SARS-CoV-2-negative participants (mean [SD] age, 17.7 [3.2] years; 31 male [36.5%]) could be evaluated. The point prevalence of PCC at 6 months was 48.5% in the SARS-CoV-2-positive group and 47.1% in the control group (risk difference, 1.5%; 95% CI, -10.2% to 13.1%). SARS-CoV-2 positivity was not associated with the development of PCC (relative risk [RR], 1.06; 95% CI, 0.83 to 1.37; final multivariable model utilizing modified Poisson regression). The main risk factor for PCC was symptom severity at baseline (RR, 1.41; 95% CI, 1.27-1.56). Low physical activity (RR, 0.96; 95% CI, 0.92-1.00) and loneliness (RR, 1.01; 95% CI, 1.00-1.02) were also associated, while biological markers were not. Symptom severity correlated with personality traits. Conclusions and Relevance: The persistent symptoms and disability that characterize PCC are associated with factors other than SARS-CoV-2 infection, including psychosocial factors. This finding raises questions about the utility of the World Health Organization case definition and has implications for the planning of health care services as well as for further research on PCC

Multi-Level Targeting of the Phosphatidylinositol-3-Kinase Pathway in Non-Small Cell Lung Cancer Cells

Introduction: We assessed expression of p85 and p110a PI3K subunits in non-small cell lung cancer (NSCLC) specimens and the association with mTOR expression, and studied effects of targeting the PI3K/AKT/mTOR pathway in NSCLC cell lines. Methods: Using Automated Quantitative Analysis we quantified expression of PI3K subunits in two cohorts of 190 and 168 NSCLC specimens and correlated it with mTOR expression. We studied effects of two PI3K inhibitors, LY294002 and NVP-BKM120, alone and in combination with rapamycin in 6 NSCLC cell lines. We assessed activity of a dual PI3K/mTOR inhibitor

Cognitive remediation training improves performance in patients with chronic fatigue syndrome

Neurocognitive disturbance with subjectively-impaired concentration and memory is a common, disabling symptom reported by patients with chronic fatigue syndrome (CFS). We recently reported preliminary evidence for benefits of cognitive remediation as part of an integrated cognitive-behavioral therapy (CBT)/ graded exercise therapy (GET) program. Here, we describe a contemporaneous, case-control trial evaluating the effectiveness of an online cognitive remediation training program (cognitive exercise therapy; CET) in addition to CBT/GET (n=36), compared to CBT/GET alone (n=36). The study was conducted in an academic, tertiary referral outpatient setting over 12 weeks (11 visits) with structured, home-based activities between visits. Participants self-reported standardized measures of symptom severity and functional status before and after the intervention. Those in the CET arm also completed standardized neurocognitive assessment before, and following, treatment. The addition of formal CET led to significantly greater improvements in self-reported neurocognitive symptoms compared to CBT/GET alone. Subjective improvement was predicted by CET group and lower baseline mood disturbance. In the CET group, significant improvements in objectively-measured executive function, processing speed, and working memory were observed. These subjective and objective performance improvements suggest that a computerized, home-based cognitive training program may be an effective intervention for patients with CFS, warranting randomized controlled trials