Measuring fatigue in people with multiple sclerosis - which questionnaire should be used? A Plain Language Summary of Publication.

WHAT IS THIS SUMMARY ABOUT?: This summary explains the findings of a recent study that compared different questionnaires used by doctors to measure levels of fatigue in people with multiple sclerosis (MS). The aim of the study was to find out which questionnaire doctors should use to measure fatigue in people with MS in the future. Fatigue, which can be described as the overwhelming feeling of tiredness or exhaustion, is a very common symptom of MS. For the majority of people with MS, fatigue is one of the worst symptoms of MS, so it is essential that doctors can measure it accurately. Currently, people with MS are asked to complete questionnaires so that their care team can see the effect of fatigue on their day-to-day lives. There are many questionnaires that are used to measure fatigue in people with MS. It would be valuable to come to an agreement, based on evidence from research like this study, on which questionnaire is the most appropriate for measuring fatigue in both research and healthcare settings. This study compared a questionnaire called the PROMIS® Fatigue (MS) 8a, referred to throughout this summary as the PROMIS® MS Fatigue Short Form, with two of the most commonly used questionnaires: the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). The questionnaires were compared to see which one should be recommended to doctors for measuring fatigue in people with MS. WHAT ARE THE KEY TAKEAWAYS?: It was found that while all three questionnaires were good, the PROMIS® MS Fatigue Short Form questionnaire was better than the other two questionnaires at showing differences in levels of fatigue between people with MS. The PROMIS® MS Fatigue Short Form was also found to be better than the Fatigue Severity Scale (FSS) at showing changes in the person with MS's level of fatigue. The PROMIS® MS Fatigue Short Form questionnaire may help people with MS to better communicate challenges with their fatigue to their doctors. WHAT WAS THE MAIN CONCLUSION REPORTED BY THE RESEARCHERS?: The study suggests that the PROMIS® MS Fatigue Short Form questionnaire is a helpful tool for doctors and people with MS to measure fatigue.

Appearance of ghost bands in gel electrophoresis depending on agarose concentration.

Standard agarose gel electrophoresis is a widely used method to analyse diversity of nucleic acids. Certain conditions, however, may give rise to artefactual bands. We report on artefactual bands frequently occurring, especially when partially homologous nucleic acids, such as splicing variants of DNA transcripts, are analysed simultaneously. Interestingly, to some extent agarose concentration may influence the occurrence of artefactual bands.

Mixotrophic chain elongation with syngas and lactate as electron donors.

Feeding microbial communities with both organic and inorganic substrates can improve sustainability and feasibility of chain elongation processes. Sustainably produced H2 , CO2 , and CO can be co-fed to microorganisms as a source for acetyl-CoA, while a small amount of an ATP-generating organic substrate helps overcome the kinetic hindrances associated with autotrophic carboxylate production. Here, we operated two semi-continuous bioreactor systems with continuous recirculation of H2 , CO2 , and CO while co-feeding an organic model feedstock (lactate and acetate) to understand how a mixotrophic community is shaped during carboxylate production. Contrary to the assumption that H2 , CO2 , and CO support chain elongation via ethanol production in open cultures, significant correlations (p < 0.01) indicated that relatives of Clostridium luticellarii and Eubacterium aggregans produced carboxylates (acetate to n-caproate) while consuming H2 , CO2 , CO, and lactate themselves. After 100 days, the enriched community was dominated by these two bacteria coexisting in cyclic dynamics shaped by the CO partial pressure. Homoacetogenesis was strongest when the acetate concentration was low (3.2 g L-1 ), while heterotrophs had the following roles: Pseudoramibacter, Oscillibacter, and Colidextribacter contributed to n-caproate production and Clostridium tyrobutyricum and Acidipropionibacterium spp. grew opportunistically producing n-butyrate and propionate, respectively. The mixotrophic chain elongation community was more efficient in carboxylate production compared with the heterotrophic one and maintained average carbon fixation rates between 0.088 and 1.4 g CO2 equivalents L-1  days-1 . The extra H2 and CO consumed routed 82% more electrons to carboxylates and 50% more electrons to carboxylates longer than acetate. This study shows for the first time long-term, stable production of short- and medium-chain carboxylates with a mixotrophic community.

A comparison of the measurement properties of the PROMIS Fatigue (MS) 8a against legacy fatigue questionnaires.

BACKGROUND: Amidst the growing number of patient-reported outcome (PRO) measures of fatigue being used in multiple sclerosis (MS) clinical trials and clinics, evidence-based consensus on the most appropriate and generalizable measures across different settings would be beneficial for clinical research and patient care. The objective of this research was to compare the validity and responsiveness of scores from the PROMIS Fatigue (MS) 8a with those of the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS), across US and UK MS populations. METHODS: Two observational studies were performed in MS populations as part of a PRO measure development project, including a cross-sectional study in two tertiary US MS centers (n = 340) and a 96-week longitudinal study in the UK MS Register cohort (n = 352). In post-hoc analyses, we examined  relative validity, based on ability to discriminate across patient groups with different fatigue levels or functional status at baseline (i.e., ANOVA-F PROX ÷ ANOVA-F PROMIS (MS) 8a), and relative responsiveness, based on baseline-to-Week-52 score change (effect sizes) across fatigue or functional status response groups . RESULTS: Mean ± standard deviation (SD) age was 44.6 ± 11.3/50.0 ± 9.7; and 72.9%/77.3% were female (US/UK samples). The mean PROMIS Fatigue (MS) 8a T-score ± SD at baseline was 57.7 ± 10.5/58.9 ± 9.3 (US/UK samples). Compared with the PROMIS Fatigue (MS) 8a, relative validity (anchor: Global Health Score [GHS] fatigue global question) was 85% for MFIS symptom score, 48% for MFIS total score, and 44% for the FSS. Relative to the FSS, PROMIS Fatigue (MS) 8a scores were more sensitive to worsening (effect size = -0.43 versus -0.18) as well as improvement (effect size = 0.5 versus 0.2) in fatigue (≥1-point increase/decrease in GHS fatigue global question) over 52 weeks of follow-up. A similar pattern of score changes was observed based on a second anchor. CONCLUSION: The PROMIS Fatigue (MS) 8a scores showed higher responsiveness to fatigue changes than those of the FSS. The PROMIS measure also had higher precision in differentiating levels of fatigue compared to the FSS, the MFIS physical, and MFIS total scores. These differences have practical implications for the application of these questionnaires in both clinical practice and research settings (e.g., sample size estimation in clinical trials).

The validity, responsiveness, and score interpretation of the PROMISnq Physical Function - Multiple Sclerosis 15a short form in multiple sclerosis.

BACKGROUND: A valid, sensitive patient-reported outcome (PRO) measure of physical function (PF) for people with multiple sclerosis (MS) would have substantial value in routine care and clinical research. We now describe development of the PROMISnq Short Form v2.0 PF - Multiple Sclerosis 15a [PROMISnq PF(MS)15a] for assessing PF in relapsing and progressive MS. Also, the validity, reliability, and responsiveness of the PROMISnq PF(MS)15a is evaluated, minimal important difference (MID) thresholds for score change estimated and a score interpretation guide developed. METHODS: A mixed-methods sequential design was employed. Relevant PF concepts were elicited through semi-structured interviews with people with relapsing MS, and then mapped to the PROMIS PF item bank. Measurement experts integrated results from interviews with people with MS and input from a panel of neurologists to generate a draft short form. Relevance and comprehensiveness of the draft short form were assessed in cognitive debriefing interviews with people with relapsing or progressive MS. Subsequently, item reduction and evaluation of psychometric properties were performed in two observational studies: a cross-sectional study in the US (n = 296), and a 96-week longitudinal study in the UK MS Register cohort (n = 558). The main outcomes and measures are estimates of: known-groups validity, convergent validity, reliability, responsiveness; MID for worsening. RESULTS: Factor analyses supported the unidimensionality of the newly derived 15-item short form. Cronbach's alpha (≥ 0.97) and intraclass correlation coefficient (≥ 0.97) of test-retest scores (5-27 days) indicated strong reliability. Convergent validity was demonstrated by moderate-to-strong correlations with scores on related PRO measures. Scores discriminated among patient groups classified by levels of physical health and other criteria. Score changes of 2.3-2.7 points are proposed as MID criteria for minimal worsening in PF. CONCLUSION: PROMISnq PF(MS)15a demonstrated reliability, validity and sensitivity to change. Input from patients and clinicians ensured the content is comprehensive and relevant for people with MS.

Standardizing fatigue measurement in multiple sclerosis: the validity, responsiveness and score interpretation of the PROMIS SF v1.0 - Fatigue (MS) 8a.

BACKGROUND: Fatigue is one of the most common and the single most disabling symptom of multiple sclerosis (MS). However, there is a lack of consensus on the most appropriate fatigue measures in clinical practice and research, based upon rigorously validated, generalizable, and publicly available instruments. The objective of this research was to generate additional evidence regarding the validity and applicability of the PROMIS SF v1.0 - Fatigue (MS) 8a, including content validity, reliability, construct validity and responsiveness, as well as to assess minimal important difference (MID) estimates and a score interpretation tool to aide meaningful individual level score interpretation. METHODS: A mixed-methods, sequential design was followed. Cognitive debriefing (CD) interviews (n=29) were performed with MS patients, to assess the relevance and comprehensiveness of the PROMIS Fatigue (MS) 8a scores. To evaluate the psychometric properties of the PROMIS Fatigue (MS) 8a, two observational studies were conducted: a cross-sectional study at two US MS centers (n=296), and a 96-week longitudinal study in a UK MS Register cohort (n=384). Main outcomes and measures were estimates of known-groups validity, convergence validity, reliability, and responsiveness, a guide for interpreting PROMIS Fatigue (MS) 8a T-scores, and anchor-based MID estimates. RESULTS: The CD interviews confirmed the comprehensiveness and relevance of the PROMIS Fatigue (MS) 8a in assessing MS fatigue. Cronbach's alpha (>0.9) and intra-class correlation coefficient (≥0.9) for test-retest scores at 5-7 days follow-up, supported strong internal consistency and test-retest reliability. Hypothesized differences were found across patient groups in patient reported fatigue and related concepts (analysis of variance [ANOVA], P <0.001). PROMIS Fatigue (MS) 8a scores were sensitive to bi-directional changes in fatigue (GHS fatigue global question) and physical health (PROMIS GHS GPH), over a 52-week follow-up. Score changes of 3.4-4 points are proposed as MID criteria for minimal improvement or worsening in fatigue. CONCLUSION: This research extends the evidence supporting the content validity and the robust psychometric performance of the PROMIS Fatigue (MS) 8a across US and UK MS populations. Importantly, data supporting the measure's integration in clinical practice and research, including meaningful score interpretation, are now available.

Long-term data of gait characteristics and moment-knee angle relations in female total knee arthroplasty patients.

BACKGROUND: Despite the clinical success of total knee arthroplasty, impaired gait patterns and quadriceps and hamstring maximal voluntary force production might persist years post-surgery. Long-term data of gait patterns and quadriceps and hamstring maximal force production are rarely published with total knee arthroplasty patients. This work examined gait characteristics and the moment-knee angle relations of the knee extensors and flexors about 10 years post-total knee arthroplasty. METHODS: About a decade post-surgery, 10 female total knee arthroplasty patients (64 years, mobile-bearing inlay) and 10 age-matched female controls were examined. Sagittal plane kinematics in the hip and knee joint during treadmill walking at 2 kilometres per hour were recorded using motion analysis. Spatiotemporal gait parameters were analyzed at self-selected walking speeds with a pressure-platform. The unilateral isometric moment-knee angle relations of the knee extensors and flexors and the electromyographic knee angle relation of the quadriceps were studied using dynamometry. Due to group differences for body mass index values, univariate analysis of variance (main effect: group, secondary effect: body mass index) was used for statistical analysis. FINDINGS: Total knee arthroplasty patients demonstrated significant (P<0.05) gait deficits during constant and self-selected walking speeds and lower average absolute values in the moment-knee angle relations of the knee extensors and flexors. Significant (P<0.05) lower body-mass-normalized knee extension moments were detected at all knee joint positions for the patients. INTERPRETATION: Long-term impairments of gait characteristics and maximal voluntary force production, especially for the knee extensors, might persist after total knee arthroplasty.