Tag: SF-36 scales

Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Objectives: In this six-year follow-up study, we used patient-reported outcome measures (PROMs) to compare values at baseline, at 18 months, and at six-year follow up from the CycloME and the RituxME trials.

Methods: Based on the hypothesis that ME/CFS in a subgroup of patients is a variant of an autoimmune disease, we performed two clinical trials between 2014 and 2017. The RituxME trial was a randomized, double-blind and placebo-controlled phase III trial of 151 patients, assessing the B-cell depleting antibody rituximab. The CycloME trial was an open-label phase II trial of 40 patients using intravenous cyclophosphamide. Here we report six-year follow-up from both trials, using the Short Form 36 Physical Function (SF-36 PF) and DePaul short form (DSQ-SF) questionnaires.

Result: Of the patients available after six years, 75.7% of RituxME and 94.4% of CycloME patients participated. In the RituxME rituximab group, the mean SF-36 PF scores were 32.9 at baseline, 42.4 at 18 months and 45.5 at six years. In the placebo group, the mean SF-36 PF scores were 32.3 at baseline, 45.5 at 18 months and 43.1 at six years. In the CycloME trial, mean SF-36 PF increased from 35.4 at baseline to 54.4 at 18 months, and 56.7 at six years. At six-year follow-up, 44.1% of cyclophosphamide-, 27.6% of rituximab- and 20.4% of placebo-treated patients had an SF-36 PF ≥ 70, and further, 17.6%, 8.6% and 7.4% of the corresponding patient groups had an SF-36 PF ≥ 90, which is within normal range. In terms of worsening at six years, 5.9% of cyclophosphamide-treated, 10.3% of rituximab-, and 14.8% of placebo-treated patients had a drop in SF-36 PF of 20 points or more from baseline. There were no serious unexpected adverse reactions.

Conclusions: After six years, 44.1% of the cyclophosphamide group scored an SF-36 PF of at least 70, and 17.6% of at least 90, suggesting that cyclophosphamide in a subgroup may modulate the disease course in a beneficial way. However, cyclophosphamide carries toxicity concerns and should not be used for ME/CFS patients outside clinical trials. Rather, these data should encourage efforts to better understand the disease mechanisms and to search for targeted and less toxic immune modulatory treatment for this patient group.

Source: Rekeland IG, Sørland K, Neteland LL, Fosså A, Alme K, Risa K, Dahl O, Tronstad KJ, Mella O, Fluge Ø. Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. PLoS One. 2024 Jul 23;19(7):e0307484. doi: 10.1371/journal.pone.0307484. PMID: 39042627; PMCID: PMC11265720. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265720/ (Full text)

Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores

Abstract:

Purpose: Myalgic encephalomyelitis, commonly referred to as chronic fatigue syndrome (ME/CFS), is a severe, disabling chronic disease and an objective assessment of prognosis is crucial to evaluate the efficacy of future drugs. Attempts are ongoing to find a biomarker to objectively assess the health status of (ME/CFS), patients. This study therefore aims to demonstrate that oxygen consumption is a biomarker of ME/CFS provides a method to classify patients diagnosed with ME/CFS based on their responses to the Short Form-36 (SF-36) questionnaire, which can predict oxygen consumption using cardiopulmonary exercise testing (CPET).

Methods: Two datasets were used in the study. The first contained SF-36 responses from 2,347 validated records of ME/CFS diagnosed participants, and an unsupervised machine learning model was developed to cluster the data. The second dataset was used as a validation set and included the cardiopulmonary exercise test (CPET) results of 239 participants diagnosed with ME/CFS. Participants from this dataset were grouped by peak oxygen consumption according to Weber’s classification. The SF-36 questionnaire was correctly completed by only 92 patients, who were clustered using the machine learning model. Two categorical variables were then entered into a contingency table: the cluster with values {0,1} and Weber classification {A, B, C, D} were assigned. Finally, the Chi-square test of independence was used to assess the statistical significance of the relationship between the two parameters.

Findings: The results indicate that the Weber classification is directly linked to the score on the SF-36 questionnaire. Furthermore, the 36-response matrix in the machine learning model was shown to give more reliable results than the subscale matrix (p – value < 0.05) for classifying patients with ME/CFS.

Implications: Low oxygen consumption on CPET can be considered a biomarker in patients with ME/CFS. Our analysis showed a close relationship between the cluster based on their SF-36 questionnaire score and the Weber classification, which was based on peak oxygen consumption during CPET. The dataset for the training model comprised raw responses from the SF-36 questionnaire, which is proven to better preserve the original information, thus improving the quality of the model.

Source: Lacasa M, Launois P, Prados F, Alegre J, Casas-Roma J. Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores. Clin Ther. 2023 Oct 4:S0149-2918(23)00352-1. doi: 10.1016/j.clinthera.2023.09.007. Epub ahead of print. PMID: 37802746. https://www.clinicaltherapeutics.com/article/S0149-2918(23)00352-1/fulltext (Full text)

Altered Effective Connectivity of Resting-State Networks by Tai Chi Chuan in Chronic Fatigue Syndrome Patients: A Multivariate Granger Causality Study

Abstract:

Numerous evidence has shown that patients with chronic fatigue syndrome (CFS) have changes in resting brain functional connectivity, but there is no study on the brain network effect of Tai Chi Chuan intervention in CFS. To explore the influence of Tai Chi Chuan exercise on the causal relationship between brain functional networks in patients with CFS, 21 patients with CFS and 19 healthy controls were recruited for resting-state functional magnetic resonance imaging (rs-fMRI) scanning and 36-item Short-Form Health Survey (SF-36) scale assessment before and after 1month-long training in Tai Chi Chuan.

We extracted the resting brain networks using the independent component analysis (ICA) method, analyzed the changes of FC in these networks, conducted Granger causality analysis (GCA) on it, and analyzed the correlation between the difference causality value and the SF-36 scale. Compared to the healthy control group, the SF-36 scale scores of patients with CFS were lower at baseline. Meanwhile, the causal relationship between sensorimotor network (SMN) and default mode network (DMN) was weakened. ‘

The above abnormalities could be improved by Tai Chi Chuan training for 1 month. In addition, the correlation analyses showed that the causal relationship between SMN and DMN was positively correlated with the scores of Role Physical (RP) and Bodily Pain (BP) in CFS patients, and the change of causal relationship between SMN and DMN before and after training was positively correlated with the change of BP score.

The findings suggest that Tai Chi Chuan is helpful to improve the quality of life for patients with CFS. The change of Granger causality between SMN and DMN may be a readout parameter of CFS. Tai Chi Chuan may promote the functional plasticity of brain networks in patients with CFS by regulating the information transmission between them.

Source: Li Y, Wu K, Hu X, Xu T, Li Z, Zhang Y, Li K. Altered Effective Connectivity of Resting-State Networks by Tai Chi Chuan in Chronic Fatigue Syndrome Patients: A Multivariate Granger Causality Study. Front Neurol. 2022 Jun 3;13:858833. doi: 10.3389/fneur.2022.858833. PMID: 35720086; PMCID: PMC9203735. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203735/ (Full text)

Investigating the factors associated with meaningful improvement on the SF-36-PFS and exploring the appropriateness of this measure for young people with ME/CFS accessing an NHS specialist service: a prospective cohort study

Abstract:

Objectives: Paediatric myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is relatively common and disabling, but little is known about the factors associated with outcome. We aimed to describe the number and characteristics of young people reaching the 10-point minimal clinically important difference (MCID) of SF-36-Physical Function Subscale (SF-36-PFS), and to investigate factors associated with reaching the MCID.

Design: Prospective observational cohort.

Setting: A specialist UK National Health Service (NHS) ME/CFS service, Southwest England. Recruitment between March 2014 and August 2015.

Participants: 193 eligible patients with ME/CFS aged 8 to 17 years reported baseline data. 124 (65%) and 121 (63%) with outcome data at six- and 12-months, respectively.

Outcome measures: SF-36-PFS (primary outcome). Chalder Fatigue Questionnaire, school attendance, visual analogue pain scale, Hospital Anxiety and Depression Scale, Spence Young people Anxiety Scale, Clinical Global Impression scale, and EQ-5D-Y (secondary)

Results: At six-months 48/120 (40%) had reached the MCID for SF-36-PFS. This had increased to 63/117 (54%) at 12-months. On the CGI, 77% and 79% reported feeling either a little better, much better, or very much better. Those with worse SF-36-PFS at baseline assessment were more likely to achieve the MCID for SF-36-PFS at six-months (OR 0.97, 95% CI 0.96 to 0.99, p-value 0.003), but there was no evidence of effect at 12-months (OR 0.98, 95% CI 0.97 to 1.00, p-value 0.038). No other factors at baseline were associated with the odds of reaching the MCID at six-months. However, at 12-months there was strong evidence of an effect of pain on MCID (OR 0.97, 95% CI 0.95 to 0.99, p-value 0.001), and SF-36-PFS on MCID (OR 0.96, 95% CI 0.94 to 0.98, p-value 0.001).

Conclusions: 40% and 54% of young people reached the MCID at 6 and 12 months respectively. No factors at assessment (other than SF-36-PFS at six-months, and pain and SF-36-PFS at 12-months) are associated with MCID of SF-36-PFS at either six-, or 12- months. Further work is needed to explore the most appropriate outcome measure for capturing clinical meaningful improvement for young people with ME/CFS.

Source: Gaunt, D. M., Brigden, A. L. C., Metcalfe, C., Loades, M., & Crawley, E. M. (Accepted/In press). Investigating the factors associated with meaningful improvement on the SF-36-PFS and exploring the appropriateness of this measure for young people with ME/CFS accessing an NHS specialist service: a prospective cohort study. BMJ Open. https://research-information.bris.ac.uk/en/publications/investigating-the-factors-associated-with-meaningful-improvement- 

Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19

Abstract:

A growing number of patients with SARS-CoV-2 infections experience long-lasting symptoms. Even patients who suffered from a mild acute infection show a variety of persisting and debilitating neurocognitive, respiratory, or cardiac symptoms (Long-Covid syndrome), consequently leading to limitations in everyday life. Because data on health-related quality of life (HRQoL) is scarce, we aimed to characterize the impact of Long-Covid symptoms after a mild or moderate acute infection on HRQoL.

In this observational study, outpatients seeking counseling in the interdisciplinary Post-Covid consultation of the University Hospital Zurich with symptoms persisting for more than 4 weeks were included. Patients who received an alternative diagnosis or suffered from a severe acute Covid-19 infection were excluded. St. George’s Respiratory Questionnaire (SGRQ), Euroquol-5D-5L (EQ-5D-5L), and the Short form 36 (SF-36) were distributed to assess HRQoL. 112 patients were included, 86 (76.8%) were female, median (IQR) age was 43 (32.0, 52.5) years with 126 (91, 180) days of symptoms.

Patients suffered frequently from fatigue (81%), concentration difficulties (60%), and dyspnea (60%). Patients mostly stated impairment in performing usual activities and having pain/discomfort or anxiety out of the EQ-5D-5L. EQ index value and SGRQ activity score component were significantly lower in females. SF-36 scores showed remarkably lower scores in the physical health domain compared to the Swiss general population before and during the COVID-19 pandemic.

Long-Covid syndrome has a substantial impact on HRQoL. Long-term surveillance of patients must provide clarity on the duration of impairments in physical and mental health.

Trial registration: The study is registered on www.ClinicalTrials.gov , NCT04793269.

Source: Malesevic S, Sievi NA, Baumgartner P, Roser K, Sommer G, Schmidt D, Vallelian F, Jelcic I, Clarenbach CF, Kohler M. Impaired health-related quality of life in long-COVID syndrome after mild to moderate COVID-19. Sci Rep. 2023 May 12;13(1):7717. doi: 10.1038/s41598-023-34678-8. PMID: 37173355; PMCID: PMC10175927. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175927/ (Full text)

Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogenous disease characterized by unexplained persistent fatigue and other features including cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Cytokines are present in plasma and encapsulated in extracellular vesicles (EVs), but there have been only a few reports of EV characteristics and cargo in ME/CFS. Several small studies have previously described plasma proteins or protein pathways that are associated with ME/CFS.

Methods: We prepared extracellular vesicles (EVs) from frozen plasma samples from a cohort of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) cases and controls with prior published plasma cytokine and plasma proteomics data. The cytokine content of the plasma-derived extracellular vesicles was determined by a multiplex assay and differences between patients and controls were assessed. We then performed multi-omic statistical analyses that considered not only this new data, but extensive clinical data describing the health of the subjects.

Results: ME/CFS cases exhibited greater size and concentration of EVs in plasma. Assays of cytokine content in EVs revealed IL2 was significantly higher in cases. We observed numerous correlations among EV cytokines, among plasma cytokines, and among plasma proteins from mass spectrometry proteomics. Significant correlations between clinical data and protein levels suggest roles of particular proteins and pathways in the disease. For example, higher levels of the pro-inflammatory cytokines Granulocyte-Monocyte Colony-Stimulating Factor (CSF2) and Tumor Necrosis Factor (TNFα) were correlated with greater physical and fatigue symptoms in ME/CFS cases. Higher serine protease SERPINA5, which is involved in hemostasis, was correlated with higher SF-36 general health scores in ME/CFS. Machine learning classifiers were able to identify a list of 20 proteins that could discriminate between cases and controls, with XGBoost providing the best classification with 86.1% accuracy and a cross-validated AUROC value of 0.947. Random Forest distinguished cases from controls with 79.1% accuracy and an AUROC value of 0.891 using only 7 proteins.

Conclusions: These findings add to the substantial number of objective differences in biomolecules that have been identified in individuals with ME/CFS. The observed correlations of proteins important in immune responses and hemostasis with clinical data further implicates a disturbance of these functions in ME/CFS.

Source: Giloteaux L, Li J, Hornig M, Lipkin WI, Ruppert D, Hanson MR. Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls. J Transl Med. 2023 May 13;21(1):322. doi: 10.1186/s12967-023-04179-3. PMID: 37179299. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04179-3 (Full text)

What is the impact of post-COVID-19 syndrome on health-related quality of life and associated factors: a cross-sectional analysis

Abstract:

Background: After the acute phase, symptoms or sequelae related to post-COVID-19 syndrome may persist for months. In a population of patients, previously hospitalized and not, followed up to 12 months after the acute infection, we aim to assess whether and to what extent post-COVID-19 syndrome may have an impact on health-related quality of life (HRQoL) and to investigate influencing factors.

Methods: We present the cross-sectional analysis of a prospective study, including patients referred to the post-COVID-19 service. Questionnaires and scales administered at 3, 6, 12 months were: Short-Form 36-item questionnaire (SF-36); Visual Analogue Scale of the EQ5D (EQ-VAS); in a subgroup, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II) and Pittsburgh Sleep Quality Index (PSQI). Linear regression models were fitted to identify factors associated with HRQoL.

Results: We considered the first assessment of each participant (n = 572). The mean scores in SF-36 and in EQ-VAS were significantly lower than the Italian normative values and remained stable over time, except the mental components score (MCS) of the SF-36 and EQ-VAS which resulted in lower ratings at the last observations. Female gender, presence of comorbidities, and corticosteroids treatment during acute COVID-19, were associated with lower scores in SF-36 and EQ-VAS; patients previously hospitalized (54%) reported higher MCS. Alterations in BAI, BDI-II, and PSQI (n = 265)were associated with lower ratings in SF-36 and EQ-VAS.

Conclusions: This study provides evidence of a significantly bad perception of health status among persons with post-COVID-19 syndrome, associated with female gender and, indirectly, with disease severity. In case of anxious-depressive symptoms and sleep disorders, a worse HRQoL was also reported. A systematic monitoring of these aspects is recommended to properly manage the post-COVID-19 period.

Source: Mastrorosa I, Del Duca G, Pinnetti C, Lorenzini P, Vergori A, Brita AC, Camici M, Mazzotta V, Baldini F, Chinello P, Mencarini P, Giancola ML, Abdeddaim A, Girardi E, Vaia F, Antinori A. What is the impact of post-COVID-19 syndrome on health-related quality of life and associated factors: a cross-sectional analysis. Health Qual Life Outcomes. 2023 Mar 22;21(1):28. doi: 10.1186/s12955-023-02107-z. PMID: 36949439; PMCID: PMC10031164. https://hqlo.biomedcentral.com/articles/10.1186/s12955-023-02107-z (Full text)

Health outcomes of sensory hypersensitivities in myalgic encephalomyelitis/chronic fatigue syndrome and multiple sclerosis

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood chronic illness with many case definitions that disagree on key symptoms, including hypersensitivities to noise and lights. The aim of the current study was to understand the prevalence rates and characteristics of these symptoms amongst people with ME/CFS and to compare them to people with another chronic illness, multiple sclerosis (MS).

International datasets consisting of 2,240 people with either ME/CFS or MS have completed the DePaul Symptom Questionnaire (DSQ) and the Short Form Health Survey Questionnaire (SF-36). Hypersensitivities to noise and lights were indicated from items on the DSQ, and participants were analyzed against DSQ and SF-36 subscales through a multivariate analysis of covariance.

There were significantly higher percentages of people with hypersensitivities in the ME/CFS sample compared to the MS sample. Regardless of illness, participants that exhibited both hypersensitivities reported greater symptomology than those without hypersensitivities. Healthcare providers and researchers should consider these symptoms when developing treatment plans and evaluating ME/CFS case diagnostic criteria.

Source: Maeda KI, Islam MF, Conroy KE, Jason L. Health outcomes of sensory hypersensitivities in myalgic encephalomyelitis/chronic fatigue syndrome and multiple sclerosis. Psychol Health Med. 2023 Mar 28:1-12. doi: 10.1080/13548506.2023.2195670. Epub ahead of print. PMID: 36977713. https://pubmed.ncbi.nlm.nih.gov/36977713/

Assessment of short- and long-term functionality and quality of life in patients with post-acute COVID-19 syndrome

Abstract:

Background: Although the number of new cases of coronavirus 2019 (COVID-19) has been drastically reduced worldwide, patients who demonstrate long-term symptoms need more attention from health systems, as these symptoms can negatively affect functionality and quality of life.

Objective: To evaluate muscle function and quality of life at 3, 6, 9 and 12 months in patients with post-acute COVID-19 syndrome and to assess their associations with general fatigue and lung function.

Methods: This observational and longitudinal study evaluated patients with post-acute COVID-19 syndrome. Participants were subjected to the following evaluations: Short Form-36; handgrip strength; Functional Assessment of Chronic Illness Therapy-Fatigue scale; and spirometry.

Results: Among the 350 participants who were evaluated in the third month, 74.6%, 61.4% and 45.4% reported general fatigue, dyspnoea and cough, respectively. In the comparisons between the third month and the sixth month, there were significant increases in Functional Assessment of Chronic Illness Therapy-Fatigue scale, pulmonary function and several Short Form-36 domains. In the comparisons between the sixth month and the ninth month, there was a significant increase only in the social functioning domain of the Short Form-36. In the comparisons between the ninth month and the twelfth month, there was an increase only in some Short Form-36 domains. Significant correlations were observed between the Short Form-36 domains with Functional Assessment of Chronic Illness Therapy-Fatigue scale, handgrip strength and pulmonary function.

Conclusion: In patients with post-acute COVID-19 syndrome, there was a progressive improvement in quality of life, general fatigue and pulmonary function during the 12 months of follow-up, with this improvement being more pronounced in the first 6 months. There was a relationship between functionality and quality of life in these patients.

Source: de Azevedo Vieira JE, Mafort TT, Monnerat LB, da Cal MS, Ghetti ATA, Lopes AJ. Assessment of short- and long-term functionality and quality of life in patients with post-acute COVID-19 syndrome. J Back Musculoskelet Rehabil. 2023 Feb 2. doi: 10.3233/BMR-220308. Epub ahead of print. PMID: 36776041. https://content.iospress.com/articles/journal-of-back-and-musculoskeletal-rehabilitation/bmr220308 (Full text)

Activity monitoring and patient-reported outcome measures in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients

Abstract:

Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease with no validated specific and sensitive biomarker, and no standard approved treatment. In this observational study with no intervention, participants used a Fitbit activity tracker. The aims were to explore natural symptom variation, feasibility of continuous activity monitoring, and to compare activity data with patient reported outcome measures (PROMs).

Materials and methods: In this pilot study, 27 patients with mild to severe ME/CFS, of mean age 42.3 years, used the Fitbit Charge 3 continuously for six months. Patients wore a SenseWear activity bracelet for 7 days at baseline, at 3 and 6 months. At baseline and follow-up they completed the Short Form 36 Health Survey (SF-36) and the DePaul Symptom Questionnaire-Short Form (DSQ-SF).

Results: The mean number of steps per day decreased with increasing ME/CFS severity; mild 5566, moderate 4991 and severe 1998. The day-by-day variation was mean 47% (range 25%-79%). Mean steps per day increased from the first to the second three-month period, 4341 vs 4781 steps, p = 0.022. The maximum differences in outcome measures between 4-week periods (highest vs lowest), were more evident in a group of eight patients with milder disease (baseline SF-36 PF > 50 or DSQ-SF < 55) as compared to 19 patients with higher symptom burden (SF-36 PF < 50 and DSQ-SF > 55), for SF-36 PF raw scores: 16.9 vs 3.4 points, and for steps per day: 958 versus 479 steps. The correlations between steps per day and self-reported SF-36 Physical function, SF-36 Social function, and DSQ-SF were significant. Fitbit recorded significantly higher number of steps than SenseWear. Resting heart rates were stable during six months.

Conclusion: Continuous activity registration with Fitbit Charge 3 trackers is feasible and useful in studies with ME/CFS patients to monitor steps and resting heart rate, in addition to self-reported outcome measures.

Source: Rekeland IG, Sørland K, Bruland O, Risa K, Alme K, Dahl O, Tronstad KJ, Mella O, Fluge Ø. Activity monitoring and patient-reported outcome measures in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. PLoS One. 2022 Sep 19;17(9):e0274472. doi: 10.1371/journal.pone.0274472. PMID: 36121803. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0274472 (Full text)