Tag: methodology

Long Covid stigma: estimating burden and validating scale in a UK-based sample

Abstract:

Background: Stigma can be experienced as perceived or actual disqualification from social and institutional acceptance on the basis of one or more physical, behavioural or other attributes deemed to be undesirable. Long Covid is a predominantly multisystem condition that occurs in people with a history of SARSCoV2 infection, often resulting in functional disability.

Aim: To develop and validate a Long Covid Stigma Scale (LCSS); and to quantify the burden of Long Covid stigma.

Design and Setting: Follow-up of a co-produced community-based Long Covid online survey using convenience non-probability sampling.

Method: Thirteen questions on stigma were designed to develop the LCSS capturing three domains – enacted (overt experiences of discrimination), internalised (internalising negative associations with Long Covid and accepting them as self-applicable) and anticipated (expectation of bias/poor treatment by others) stigma. Confirmatory factor analysis tested whether LCSS consisted of the three hypothesised domains. Model fit was assessed and prevalence was calculated.

Results: 966 UK-based participants responded (888 for stigma questions), with mean age 48 years (SD: 10.7) and 85% female. Factor loadings for enacted stigma were 0.70-0.86, internalised 0.75-0.84, anticipated 0.58-0.87, and model fit was good. The prevalence of experiencing stigma at least ‘sometimes’ and ‘often/always’ was 95% and 76% respectively. Anticipated and internalised stigma were more frequently experienced than enacted stigma. Those who reported having a clinical diagnosis of Long Covid had higher stigma prevalence than those without.

Conclusion: This study establishes a scale to measure Long Covid stigma and highlights common experiences of stigma in people living with Long Covid.

Source: Marija Pantelic, Nida Ziauddeen, Mark Boyes, Margaret E O’Hara, Claire Hastie, Nisreen A Alwan. Long Covid stigma: estimating burden and validating scale in a UK-based sample. medRxiv 2022.05.26.22275585; doi: https://doi.org/10.1101/2022.05.26.22275585 (Full text)

Comparing Operationalized Approaches for Substantial Reduction of Functioning in Chronic Fatigue Syndrome and Myalgic Encephalomyelitis

Abstract:

A core criterion for Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME) is a substantial reduction in functioning from pre-illness levels. Despite its ubiquity in diagnostic criteria, there is considerable debate regarding how to measure this domain. The current study assesses five distinct methods for measuring substantial reductions. The analysis used an international, aggregated dataset of patients (N = 2,368) and controls (N=359) to compare the effectiveness of each method.

Four methods involved sophisticated analytic approaches using the Medical Outcomes Survey Short Form-36; the fifth method included a single self-report item on the DePaul Symptom Questionnaire (DSQ). Our main finding was that all methods produced comparable results, though the DSQ item was the most valid in differentiating patients from controls. Having a simple, reliable method to capture a substantial reduction in functioning has considerable advantages for patients and health care workers.

Source: Wiedbusch E, Jason LA. Comparing Operationalized Approaches for Substantial Reduction of Functioning in Chronic Fatigue Syndrome and Myalgic Encephalomyelitis. Arch Community Med. 2022;4(1):59-63. doi: 10.36959/547/653. Epub 2022 Apr 21. PMID: 35673386; PMCID: PMC9168545. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168545/ (Full text)

Comparison of assessment scores for fatigue between multidimensional fatigue inventory (MFI-K) and modified chalder fatigue scale (mKCFQ)

Abstract:

Background: Because of the absence of biological parameters for fatigue, appropriate instruments for assessing the degree of fatigue are important in the diagnosis and management of people complaining of fatigue-like symptoms. This study statistically analyzed the fatigue scores from two typical questionnaire-based instruments: the Korean version of the Multidimensional Fatigue Inventory (MFI-K) and the modified Chalder Fatigue Scale (mKCFQ).

Methods: Seventy participants (males n = 40, females n = 30, median age 48 years old, range of 25-67) were grouped into three groups (‘mild’ = 20, ‘moderate’ = 42, and ‘severe’ = 8) according to self-reported fatigue levels using a 7-point Likert scale. The similarities and differences between two instrument-derived scores were analyzed using correlations (r) and multidimensional scaling (MDS).

Results: The total scores of the two assessments were significantly correlated (r = 75%, p < 0.001), as were the subscores (‘Total Physical fatigue’: r = 76%, p < 0.001, ‘Total Mental fatigue’: r = 56%, p < 0.001). Relative overestimation of the MFI-K (45.8 ± 11.3) compared to the mKCFQ (36.1 ± 16.2) was observed, which was especially prominent in the ‘mild’ group. The scores of the three groups were more easily distinguished by the mKCFQ than by the MFI-K. In terms of the five dimension scores, we found a higher correlation of the two assessments for ‘general fatigue’ (r = 79%, p < 0.001) and ‘physical fatigue’ (r = 66%, p < 0.001) than for the reductions in ‘motivation’ (r = 41%, p < 0.01) and ‘activity’ (r = 26%, p > 0.05).

Conclusions: Our results may indicate the usefulness of the two instruments, especially for the physical symptoms of fatigue (‘general’ and ‘physical’ fatigue). Furthermore, the MFI-K may be useful for conditions of moderate-to-severe fatigue, such as chronic fatigue syndrome, but the mKCFQ may be useful for all spectra of fatigue, including in subhealthy people.

Source: Lim EJ, Son CG. Comparison of assessment scores for fatigue between multidimensional fatigue inventory (MFI-K) and modified chalder fatigue scale (mKCFQ). J Transl Med. 2022 Jan 3;20(1):8. doi: 10.1186/s12967-021-03219-0. PMID: 34980164. https://pubmed.ncbi.nlm.nih.gov/34980164/

Assessment of systemic joint laxity in the clinical context: Relevance and replicability of the Beighton score in chronic fatigue

Abstract

Background: Persistent symptoms in patients with systemic joint laxity (SJL) are often equivalent with complications. Screening for SJL is an important part of the assessment of musculoskeletal phenotype. The common measuring tool, the Beighton score (BS), still has unclear evidence.

Objective: To assess the Beighton score in a clinical context for (1) ability to classify SJL as absent or present (criterion validity), and (2) interrater reliability (physician-physiotherapist), for a dichotomous cut-off (yes/no), as well as for interpretation in categories (no, some, clear SJL).

Methods: This real-world observational study included 149 consecutive patients seeking secondary care for investigation of possible myalgic encephalomyelitis/chronic fatigue syndrome. Assessment was done during a routine examination. Data were evaluated with Cohen’s kappa and Spearman’s rho.

Results: BS criterion validity showed poor agreement with the assessment of SJL: percentage agreement was 74 % and kappa 0.39 (3-cut level), 73 % and kappa 0.39/0.45 (4-/5-cut level). The best interrater reliability was moderate (rho 0.66) for interpretation in categories.

Conclusions: The BS alone was not a reliable proxy for SJL and should be supplemented with a targeted history. Nevertheless, its interrater reliability was acceptable, and the categorised score appears to have greater clinical relevance than the dichotomous score.

Source: Bernhoff G, Huhmar H, Käll LB. Assessment of systemic joint laxity in the clinical context: Relevance and replicability of the Beighton score in chronic fatigue. J Back Musculoskelet Rehabil. 2021 Dec 13. doi: 10.3233/BMR-210081. Epub ahead of print. PMID: 34957987. https://pubmed.ncbi.nlm.nih.gov/34957987/

Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology

Abstract:

In a previous study using mobile-health technology (mHealth), we reported a robust association between chronic fatigue symptoms and heart rate variability (HRV) in female patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study explores HRV analysis as an objective, non-invasive and easy-to-apply marker of ME/CFS using mHealth technology, and evaluates differential gender effects on HRV and ME/CFS core symptoms. In our methodology, participants included 77 ME/CFS patients (32 men and 45 women) and 44 age-matched healthy controls (19 men and 25 women), all self-reporting subjective scores for fatigue, sleep quality, anxiety, and depression, and neurovegetative symptoms of autonomic dysfunction. The inter-beat cardiac intervals are continuously monitored/recorded over three 5-min periods, and HRV is analyzed using a custom-made application (iOS) on a mobile device connected via Bluetooth to a wearable cardiac chest band.

Male ME/CFS patients show increased scores compared with control men in all symptoms and scores of fatigue, and autonomic dysfunction, as with women in the first study. No differences in any HRV parameter appear between male ME/CFS patients and controls, in contrast to our findings in women. However, we have found negative correlations of ME/CFS symptomatology with cardiac variability (SDNN, RMSSD, pNN50, LF) in men. We have also found a significant relationship between fatigue symptomatology and HRV parameters in ME/CFS patients, but not in healthy control men.

Gender effects appear in HF, LF/HF, and HFnu HRV parameters. A MANOVA analysis shows differential gender effects depending on the experimental condition in autonomic dysfunction symptoms and HF and HFnu HRV parameters. A decreased HRV pattern in ME/CFS women compared to ME/CFS men may reflect a sex-related cardiac autonomic dysfunction in ME/CFS illness that could be used as a predictive marker of disease progression. In conclusion, we show that HRV analysis using mHealth technology is an objective, non-invasive tool that can be useful for clinical prediction of fatigue severity, especially in women with ME/CFS.

Source: Capdevila L, Castro-Marrero J, Alegre J, Ramos-Castro J, Escorihuela RM. Analysis of Gender Differences in HRV of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Mobile-Health Technology. Sensors (Basel). 2021 May 28;21(11):3746. doi: 10.3390/s21113746. PMID: 34071326. https://pubmed.ncbi.nlm.nih.gov/34071326/

Assessing functioning in adolescents with chronic fatigue syndrome: psychometric properties and factor structure of the School and Social Adjustment Scale and the Physical Functioning Subscale of the SF36

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) has a major impact on functioning. However, no validated measures of functioning for this population exist.

AIMS: We aimed to establish the psychometric properties of the 5-item School and Social Adjustment Scale (SSAS) and the 10-item Physical Functioning Subscale of the SF-36 in adolescents with CFS.

METHOD: Measures were completed by adolescents with CFS (n = 121).

RESULTS: For the Physical Functioning Subscale, a 2-factor solution provided a close fit to the data. Internal consistency was satisfactory. For the SSAS, a 1-factor solution provided an adequate fit to the data. The internal consistency was satisfactory. Inter-item and item-total correlations did not indicate any problematic items and functioning scores were moderately correlated with other measures of disability, providing evidence of construct validity.

CONCLUSION: Both measures were found to be reliable and valid and provide brief measures for assessing these important outcomes. The Physical Functioning Subscale can be used as two subscales in adolescents with CFS.

Source: Loades ME, Vitoratou S, Rimes KA, Chalder T. Assessing functioning in adolescents with chronic fatigue syndrome: psychometric properties and factor structure of the School and Social Adjustment Scale and the Physical Functioning Subscale of the SF36. Behav Cogn Psychother. 2020 Apr 1:1-11. doi: 10.1017/S1352465820000193. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/32234097

Pitfalls in cytokine measurements – Plasma TGF-β1 in chronic fatigue syndrome

Abstract:

BACKGROUND: Serum TGF-β1 concentrations are reported to be elevated in chronic fatigue syndrome (CFS). However, measurement of circulating cytokines is a complex procedure and control of pre-analytical procedures is essential. The objective of the current study was to measure circulating TGF-β1 concentrations in CFS patients compared to healthy controls, taking into account differences in pre-analytical procedures.

METHODS: Two cohorts of female CFS patients were included. In both studies patients were asked to bring a healthy, age-matched control. At baseline, TGF-β1 levels were measured in plasma and additionally P-selectin, a marker of platelet activity, was determined in a subgroup of participants.

RESULTS: 50 patients and 48 controls were included in cohort I, and 90 patients and 29 controls in cohort II. Within the cohorts there were no differences in TGF-β1 concentrations. However, between the cohorts there was a large discrepancy, which appeared to be caused by differences in g-force of the centrifuges used. The lower g-force used in cohort II (1361 g) caused more platelet activation, reflected by higher p-selectin concentrations, compared to cohort I (p < 0.0001), which was confirmed in a second independent experiment. There was a correlation between TGF-β1 and p-selectin concentrations (r 0.79, p < 0.0001).

CONCLUSION: These results demonstrate that control of pre-analytical procedures is an essential aspect when measuring circulating cytokines. No evidence for enhanced TGF-β1 in patients with CFS was found.

Source: Roerink ME, van der Schaaf ME, Hawinkels LJAC, Raijmakers RPH, Knoop H, Joosten LAB, van der Meer JWM. Pitfalls in cytokine measurements – Plasma TGF-β1 in chronic fatigue syndrome. Neth J Med. 2018 Sep;76(7):310-313. https://www.ncbi.nlm.nih.gov/pubmed/30220655

Distribution of xenotropic murine leukemia virus-related virus (XMRV) infection in chronic fatigue syndrome and prostate cancer

Abstract:

In 2006, sequences described as xenotropic murine leukemia virus-related virus (XMRV) were discovered in prostate cancer patients. In October 2009, we published the first direct isolation of infectious XMRV from humans and the detection of infectious XMRV in patients with chronic fatigue syndrome. In that study, a combination of classic retroviral methods were used including: DNA polymerase chain reaction and reverse transcriptase polymerase chain reaction for gag and env, full length genomic sequencing, immunoblotting for viral protein expression in activated peripheral blood mononuclear cells, passage of infectious virus in both plasma and peripheral blood mononuclear cells to indicator cell lines, and detection of antibodies to XMRV in plasma. A combination of these methods has since allowed us to confirm infection by XMRV in 85% of the 101 patients that were originally studied.

Since 2009, seven studies, predominantly using DNA polymerase chain reaction of blood products or tumor tissue, have reported failures to detect XMRV infection in patients with either prostate cancer or chronic fatigue syndrome. A review of the current literature on XMRV supports the importance of applying multiple independent techniques in order to determine the presence of this virus. Detection methods based upon the biological and molecular amplification of XMRV, which is usually present at low levels in unstimulated blood cells and plasma, are more sensitive than assays for the virus by DNA polymerase chain reaction of unstimulated peripheral blood mononuclear cells.

When we examined patient blood samples that had originally tested negative by DNA polymerase chain reaction by more sensitive methods, we observed that they were infected with XMRV; thus, the DNA polymerase chain reaction tests provided false negative results.

Therefore, we conclude that molecular analyses using DNA from unstimulated peripheral blood mononuclear cells or from whole blood are not yet sufficient as stand-alone assays for the identification of XMRV-infected individuals. Complementary methods are reviewed, that if rigorously followed, will likely show a more accurate snapshot of the actual distribution of XMRV infection in humans.

 

Source: Mikovits JA, Huang Y, Pfost MA, Lombardi VC, Bertolette DC, Hagen KS, Ruscetti FW. Distribution of xenotropic murine leukemia virus-related virus (XMRV) infection in chronic fatigue syndrome and prostate cancer. AIDS Rev. 2010 Jul-Sep;12(3):149-52. https://www.ncbi.nlm.nih.gov/pubmed/20842203

 

Sensitive, qualitative detection of human herpesvirus-6 and simultaneous differentiation of variants A and B

Abstract:

BACKGROUND: The current limitations of laboratory testing for the detection of human herpesvirus virus 6 (HHV-6) in clinical specimens with low HHV-6 viral loads make this area a priority for further research and development.

OBJECTIVES: To develop and validate a sensitive qualitative assay for simultaneous HHV-6 detection and variant differentiation.

METHODS: We developed a diagnostic procedure, which combines a magnetic bead-based nucleic acid extraction, PCR amplification, and colorimetric microtiter plate identification (MAG-PCR-EIA), for the sensitive detection of HHV-6 and the simultaneous differentiation of HHV-6A and HHV-6B.

RESULTS: Analytic sensitivities of the MAG-PCR-EIA assay were 10 copies per reaction for both HHV-6A and HHV-6B variants, which is equivalent to 20 copies/ml when 1ml of clinical specimen was processed. A proficiency panel containing 11 blinded specimens covering HHV-6A viral loads from 0 to 100,000 copies was tested, and the MAG-PCR-EIA was able to detect the lowest concentration at one copy in 200microl. A panel of 27 urine specimens, which were collected from patients with and without chronic fatigue syndrome, was tested by the MAG-PCR-EIA. HHV-6 was detected in two (HHV-6A) patients who have chromosomally integrated HHV-6A and in one (HHV-6B) patient who was a healthy control and diagnosed as cervical cancer later on. The HHV-6 results did not correlate with results previously determined by HHV-6 antigenemia in urine.

CONCLUSION: With large specimen volumes processed and an additional signal amplification incorporated, the MAG-PCR-EIA provides a sensitive and qualitative system for HHV-6 detection and simultaneous variant differentiation. Clinical relevance of the assay awaits further investigation.

 

Source: Li H, Meng S, Levine SM, Stratton CW, Tang YW. Sensitive, qualitative detection of human herpesvirus-6 and simultaneous differentiation of variants A and B. J Clin Virol. 2009 Sep;46(1):20-3. doi: 10.1016/j.jcv.2009.05.016. Epub 2009 Jun 21. https://www.ncbi.nlm.nih.gov/pubmed/19540801

 

Generation of classification criteria for chronic fatigue syndrome using an artificial neural network and traditional criteria set

Abstract:

OBJECTIVE: The definition of chronic fatigue syndrome (CFS) is still disputed and no validated classification criteria have been published. Artificial neural networks (ANN) are computer-based models that can help to evaluate complex correlations. We examined the utility of ANN and other conventional methods in generating classification criteria for CFS compared to other diseases with prominent fatigue, systemic lupus erythematosus (SLE) and fibromyalgia syndrome (FMA).

PATIENTS AND METHODS: Ninety-nine case patients with CFS, 41 patients with SLE and 58 with FMA were recruited from a generalist outpatient population. Clinical symptoms were documented with help of a predefined questionnaire. The patients were randomly divided into two groups. One group (n = 158) served to derive classification criteria sets by two-fold cross-validation, using a) unweighted application of criteria, b) regression coefficients, c) regression tree analysis, and d) artificial neural networks in parallel. These criteria were validated with the second group (n = 40).

RESULTS: Classification criteria developed by ANN were found to have a sensitivity of 95% and a specificity of 85%. ANN achieved a higher accuracy than any of the other methods.

CONCLUSION: We present validated criteria for the classification of CFS versus SLE and FMA, comparing different classification approaches. The most accurate criteria were derived with the help of ANN. We therefore recommend the use of ANN for the classification of syndromes with complex interrelated symptoms like CFS.

 

Sour ce: Linder R, Dinser R, Wagner M, Krueger GR, Hoffmann A. Generation of classification criteria for chronic fatigue syndrome using an artificial neural network and traditional criteria set. In Vivo. 2002 Jan-Feb;16(1):37-43. http://www.ncbi.nlm.nih.gov/pubmed/11980359