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A novel approach to estimate the minimally important difference for the Fatigue Impact Scale in multiple sclerosis patients
Abstract
The Fatigue Impact Scale (FIS) has been used extensively to assess the impact of fatigue on health-related quality of life (HRQOL) in multiple sclerosis (MS). The objective of this study was to estimate the minimally important difference (MID) of the FIS to facilitate the interpretation of the scale in patients with MS.
Data came from a cross-sectional study of 184 patients with MS. Anchor-based estimates of the MID were evaluated using patients' ratings of their own health and a clinical rating of MS severity. Using the proportional odds model, estimates of the MID were evaluated by finding FIS score differences that corresponded to a 50% increase in the odds of poorer health. Convergence between distribution- and anchor-based estimates was assessed.
Nineteen items met the selection criteria for anchors. Triangulation of the anchor- and distribution-based approaches indicated that the MID of the FIS ranged between 10 and 20 points, approximately.
A common metric of meaningful difference of FIS was defined across anchors measuring a broad range of HRQOL domains. The MID estimates in the current study can be used for sample size calculation in the planning of future studies and to aid researchers and clinicians in interpreting FIS score differences in patients with MS.
... 57-62 Moreover, for most above-mentioned pharmacological agents adverse effects have been reported. 58,63,64 In addition, several non-pharmacological treatment interventions, such as aerobic training, [65][66][67][68][69] cognitive behaviour therapy 61, 70 and energy management strategies 71,72 aim to reduce the impact of fatigue on patients with MS and are not associated with adverse effects. There is some evidence from RCTs 61,65,67-72 that these interventions might be beneficial to MS patients. ...
... No multidimensional questionnaires were identified that were adequately validated in patients with PD or stroke. Interpretability is considered an important characteristic of a measurement scale, 16 Self-report fatigue questionnaires: a review of measurement properties 3 69 Although it is believed that measurement properties are sample dependent, 80 versions, so it is not likely that this resulted in selection bias. Second, the COSMIN checklist has some items that require subjective judgment, which may lead to disagreement between raters. ...
... Chapter_3_Marc.indd69 29-7-2015 10:42:11 ...
... Seven studies [39, 40, 54, 59, 61, 70, 75] that translated a questionnaire scored poor methodological quality because the translated questionnaires were not pre-tested in a small sample to check interpretation, cultural relevance and ease of comprehension of the translation. All studies [53, 56, 69, 71, 74] that reported on responsiveness scored poor methodological quality.Table 5 presents the overall quality of the measurement properties per self-report questionnaire, accompanied by the level of evidence. ...
... Five studies [53, 56, 69, 71, 74] reported on responsiveness . None of these studies presented details about the correlation coefficient between change scores in the investigated questionnaires with change in an external anchor. ...
... showed a floor effect in patients with MS (on 12 of the 20 items, more than 25% of patients achieved the lowest possible score) [51]. The D-FIS [61], FACIT-F [50], FSS [50] , PFS-16 (5) and PFS- 16 (2) [57] showed no floor or ceiling effects in patients with PD. Values for the MIC were reported for the D-FIS (MIC = 3.65) [41], FIS (MIC = 9.0–24.0) [69] and U-FIS (MIC = 2.4–7.0) [74] in patients with MS. ...
To critically appraise, compare and summarize the measurement properties of self-report fatigue questionnaires validated in patients with multiple sclerosis (MS), Parkinson's disease (PD) or stroke.
MEDLINE, EMBASE, PsycINFO, CINAHL and SPORTdiscus were searched. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the methodological quality of studies. A qualitative data synthesis was performed to rate the measurement properties for each questionnaire.
Thirty-eight studies out of 5,336 records met the inclusion criteria, evaluating 31 questionnaires. Moderate evidence was found for adequate internal consistency and structural validity of the Fatigue Scale for Motor and Cognitive functions (FSMC) and for adequate reliability and structural validity of the Unidimensional Fatigue Impact Scale (U-FIS) in MS.
We recommend the FSMC and U-FIS in MS. The Functional Assessment of Chronic Illness Therapy Fatigue subscale (FACIT-F) and Fatigue Severity Scale (FSS) show promise in PD, and the Profile of Mood States Fatigue subscale (POMS-F) for stroke. Future studies should focus on measurement error, responsiveness and interpretability. Studies should also put emphasis on providing input for the theoretical construct of fatigue, allowing the development of questionnaires that reflect generic and disease-specific symptoms of fatigue.
... The measures were chosen as being well-validated scales that were evaluated in both TEMSO and TOWER. FIS scores range from 0 to 160, with higher scores reflecting increased fatigue, and a minimally important difference (MID) ranging from 10 to 20 points (Rendas-Baum et al., 2010). Physical health component summary (PCS) and MCS scores were derived from the SF-36 survey with scores (1-100) standardized to 50 for the general population (lower scores reflecting poorer HRQoL), and with a MID in patients with MS of 2.5-5.0 (Ware and Sherbourne, 1992; Rudick et al., 2007). ...
... Differences in FIS score changes from baseline to Week 108 between Group 3 and Group 1 for each definition of severe relapse ranged from 9.993 (relapse requiring IV corticosteroids; Fig. 3) to 14.785 (relapse leading to hospitalization; Fig. 2). Since the MID for the FIS in patients with MS has been estimated at 10-20 points (Rendas-Baum et al., 2010), the increase in fatigue in patients experiencing severe relapses is likely to be clinically meaningful. ...
Background:
Two pivotal phase 3 teriflunomide studies provided data on relapses, fatigue, and health-related quality of life (HRQoL) in patients with relapsing forms of multiple sclerosis (MS).
Objectives:
Using pooled data from the TEMSO (NCT00134563) and TOWER (NCT00751881) studies, we investigated the association between relapse severity, and changes from baseline to Week 108 in fatigue and HRQoL outcomes.
Methods:
Four definitions of relapse severity were applied in this analysis: sequelae post-relapse; relapse leading to hospitalization; relapse requiring intravenous corticosteroids; and intense relapse. We assessed the association between relapse severity and changes in Fatigue Impact Scale score (n=959), physical and mental health component summary scores from the Short Form (SF)-36 questionnaire (n=904), and SF-6D utility index scores (n=820).
Results:
Irrespective of the definition of relapse severity applied, in patients experiencing severe relapse(s), fatigue was increased and HRQoL was decreased; these changes were statistically significant (p<0.0001), and were also clinically significant in many cases. The greatest worsening in fatigue and HRQoL was observed in patients with relapses leading to hospitalization.
Conclusions:
Given that severe relapses adversely affect patient-reported fatigue and HRQoL, prevention of severe relapses should be an important therapeutic aim in the treatment of patients with MS.
... 57-62 Moreover, for most above-mentioned pharmacological agents adverse effects have been reported. 58,63,64 In addition, several non-pharmacological treatment interventions, such as aerobic training, [65][66][67][68][69] cognitive behaviour therapy 61, 70 and energy management strategies 71,72 aim to reduce the impact of fatigue on patients with MS and are not associated with adverse effects. There is some evidence from RCTs 61,65,67-72 that these interventions might be beneficial to MS patients. ...
... Clinically relevant differences in scores between subgroups were reported for the FIS, 48 Interpretability is considered an important characteristic of a measurement scale, 16 Self-report fatigue questionnaires: a review of measurement properties 3 69 Although it is believed that measurement properties are sample dependent, 80 versions, so it is not likely that this resulted in selection bias. Second, the COSMIN checklist has some items that require subjective judgment, which may lead to disagreement between raters. ...
Both fatigue and reduced physical activity are important consequences of multiple sclerosis (MS). However, their mutual association is poorly understood.
The objective of the study was to determine the relation between perceived fatigue and home-based recording of motor activity in patients with MS.
Found associations were checked for confounding by age, Expanded Disability Status Scales (EDSS), disease duration, sub-type of MS, anxiety, and depression. Forty-three ambulatory patients with MS were recruited. Ambulatory physical activity was recorded for 24 hours. Fatigue was assessed with the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale (MFIS) and the Checklist Individual Strength (CIS20R). Linear regression was applied after which potential confounding factors were introduced in a multivariate regression model.
No significant associations between physical activity and fatigue scores were found, except for the MFIS sub-scale 'physical activity' (ß(physical_activity) [ß(pa)] = -0.044; SE = 0.020). The association between physical activity and the FSS score was distorted by age, MS-type, anxiety and depression and the association between physical activity and the MFIS score by age and depression. The inverse association between MFIS sub-scale 'physical activity' and physical activity was significantly strengthened by adjusting for age (ß(pa) = - 0.052; SE = 0.019), sub-type of MS (ß(pa) = - 0.048; SE = 0.020), anxiety (ß(pa) = - 0.070; SE = 0.023) and depression (ß(pa) = - 0.083; SE = 0.023).
In MS, there is no, or at best a weak association between severity of perceived fatigue and physical activity. Depending on the fatigue questionnaire used, patient characteristics such as age, type of MS, depression and anxiety are factors that may affect this relationship.
... Some standard measurement tools can provide specific and robust information on the severity of fatigue and assess the effective intervention [96,97]. Fatigue assessment scale [98,99], modified fatigue impact scale [100,101] are used to measure the frequency of fatigue randomly or daily also in patients with multiple sclerosis [102] fatigue impact scales [103,104] for daily use [105,106] are constructed to the measurement of the severity of fatigue impact, sometimes on daily life. One of the subscales for measurement is the profile of mood states [107] that can provide information on the feeling of patients based on some specific questionnaires. ...
Considerable evidence supports that cytokines are important mediators of pathophysiologic processes within the central nervous system (CNS). Numerous studies have documented the increased production of various cytokines in the human CNS in various neurological and neuropsychiatric disorders. Deciphering cytokine actions in the intact CNS has important implications for our understanding of the pathogenesis and treatment of these disorders.
The purpose of this study is to discuss the recent research on treating cytokine storm and amyloids, including stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's condition, Multi-sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). Neuroinflammation observed in neurological disorders has a pivotal role in exacerbating Aβ burden and tau hyperphosphorylation, suggesting that stimulating cytokines in response to an undesirable external response could be a checkpoint for treating neurological disorders. Furthermore, the pro-inflammatory cytokines help our immune system through a neuroprotective mechanism in clearing viral infection by recruiting mononuclear cells. This study reveals that cytokine applications may play a vital role in providing novel regulation and methods for the therapeutic approach to neurological disorders and the causes of the deregulation, which is responsible for neuroinflammation and viral infection. However, it needs to be further investigated to clarify better the mechanisms of cytokine release in response to various stimuli, which could be the central point for treating neurological disorders.
... We measured stable total FIS scores and cognitive and psychosocial components, along with a small but statistically significant improvement in the physical component. To place this in context, Rendas-Baum et al., (2010) [27] calculated that the minimum improvement in FIS total score to achieve a clinically meaningful change was 10-20 points. Likewise, depression scores in our study were stable or underwent small yet significant improvements, but these were well short of the almost 20% improvement from baseline BDI scores needed to be considered clinically meaningful [28]. ...
Relapsing-remitting multiple sclerosis (RRMS) is a degenerative, inflammatory disease of the central nervous system in which symptoms and disability progression vary significantly among patients. Teri-REAL was a prospective, real-world observational study that examined quality-of-life (QoL) and treatment outcomes in a Hungarian cohort of RRMS patients treated with once-daily oral teriflunomide. QoL was assessed at baseline, 12, and 24 months with the Multiple Sclerosis Quality of Life-54 (MSQoL-54) questionnaire. Other measurements included disease progression (Patient Determined Disease Steps [PDDS]), clinical efficacy (relapses), fatigue (Fatigue Impact Scale [FIS]), depression (Beck Depression Inventory [BDI]), cognition (Brief International Cognitive Assessment in MS [BICAMS]), persistence and safety. 212 patients were enrolled (69.1% female, 50.5% treatment naïve), with 146 (69%) completing the study. Statistically significant improvements in subscales of the MSQoL-54 versus baseline were found at Month 12 and Month 24. Significant improvements were also observed for individual components of the BICAMS score at 24 months, while PDDS, FIS and BDI scores remained stable. The mean annualised relapse rate was 0.08 ± 0.32. There were 93 safety events, most of which were mild to moderate. Improved QoL and cognitive outcomes in teriflunomide-treated patients over 2 years offer a unique perspective to this real-world study.
... But an important point in using the assessment tools is the meaning of their scores. 49 By qualifying the amount of change in the score of an assessment tool using concepts such as MCID and RCID, changes in the individual's condition may be better interpreted and therapists -and patients' views on recovery may be brought closer together. 46 Also, in the research setting, the effectiveness of interventions is mainly assessed by statistical comparison methods and significance level, which depends on the sample size and does not examine the significance of interventions from a clinical perspective. ...
Background:
Fatigue assessment scale (FAS), fatigue subscale of the Profile of Mood States (POMS-F), and vitality subscale of the Short Form Health Survey (SF-36-VT) are among the first and most widely used adapted tools for assessing post-stroke fatigue.
Objective:
To identify the minimal clinically important difference (MCID) and robust clinically important difference (RCID) of FAS, POMS-F, and SF-36-VT in stroke survivors.
Methods:
Participants completed the FAS, POMS-F, and SF-36-VT before and after receiving 6-week intervention including graded activity training and pacing therapy. MCID was calculated using the distribution-based and anchor-based methods. Further, accuracy, sensitivity, and specificity of calculated values using the distribution-based method were used for determining RCID.
Result:
A total of 124 stroke survivors participated in this study. MCID for FAS, POMS-F, and SF-36-VT was found to be 4.86, 3.32, and -10.10 (using score change) and 3.5, 2.5, and -10.5 (using ROC analysis), respectively. Using the distribution-based method, the MCID value obtained for the FAS was in the range of 3.16 to 8.76, for the POMS-F was in the range of 1.49 to 5.63, and for the SF-36-VT was in the range of -15.43 to -5.58. ½SD for FAS, ½ SD and 1.96 SEM for POMS-F, and 1.96 SEM and SD for SF-36-VT showed the best discriminative ability to use as the RCID.
Conclusions:
The MCID and RCID were calculated for FAS, POMS-F, and SF-36-VT using different methods. The results can be used by researchers and clinicians for interpreting their findings in subjects similar to those who participated in this study.
... The reported levels of fatigue were independent of the age, comorbidity, and sex of the study participants. Moreover, IgGsd scores were even poorer in the cognitive and social dimensions than in Multiple Sclerosis (36). The poorest FIS scores were among those IgGsd individuals who needed to reintroduce the IgRT, suggesting that observed fatigue is associated with increased susceptibility to bacterial infections. ...
Purpose
Individuals with immunoglobulin G deficiency (IgGsd) often complain of fatigue. The correlation between systemic inflammation and fatigue is unknown. In this study perceived quality of life (QoL) and fatigue in individuals with IgGsd, on and off immunoglobulin replacement therapy (IgRT) were correlated to inflammatory markers in plasma to identify the subgroup that benefits from IgRT.
Method
Thirty-five IgGsd-patients were sampled on three occasions: at baseline, after being on IgRT for at least 18 months, and 18 months after discontinuation of IgRT. Short form 36, EQ-5D-5L visual analogue scale and fatigue impact scale questionnaires were used for evaluation of QoL and fatigue. Furthermore, a panel of 92 inflammatory markers were analysed in plasma. Thirty-two gender- and age-matched healthy individuals were included as controls and sampled on one occasion.
Results
QoL was lower and perceived fatigue higher in IgGsd compared to the controls. Severe fatigue and low QoL were associated with the need to restart IgRT (which is considered in IgGsd-individuals with a high burden of infections in Sweden). Twenty-five inflammatory factors were dysregulated in IgGsd and the plasma protein patterns were similar regardless of whether IgRT was ongoing or not. Enrichment analysis indicated IL-10 signalling as the most affected pathway. Severe fatigue was associated with decreased levels of the neurotrophic factors VEGFA and CSF-1.
Conclusion
Fatigue is a major contributory factor to impaired health-related QoL in IgGsd and is related to the need for IgRT. Low-grade systemic inflammation is a potential driver of fatigue. In addition to the burden of infections, we suggest the degree of fatigue should be considered when the decision to introduce IgRT is made.
... 2). (Guidelines MSCfCP 1998) While there have been several reports pertaining to the psychometrics (Amtmann et al., 2012, Learmonth et al., 2013, Larson, 2013 and meaningful change scores on the MFIS (Kluger et al., 2017, Rendas-Baum et al., 2010, Rooney et al., 2019 since then, normative data on the MFIS remains sparse even over 20 years later. Normative data is crucial because it allows for more precise clinical cut-points that account for common confounding variables. ...
Background
: The Modified Fatigue Impact Scale (MFIS) is one of the most common self-report measures used to assess fatigue in multiple sclerosis (MS). Despite its widespread use, there are no existing normative data for the MFIS.
Objective
The present investigation aimed to develop normative data for the MFIS in a large community sample, stratified by age, gender, and education and to compare the derived new cutoffs to an existing cutoff.
Methods
A total of 675 healthy individuals, stratified by age, gender, and education completed the MFIS. After the removal of 19 outliers, the final sample consisted of 656 individuals. Archival data of 540 individuals with MS who completed the MFIS were also included to analyze the utility of the new cutoffs.
Results
There were no main effects on the MFIS for gender. However, there were main effects for age and education. Specifically, younger cohorts (25-34 and 35-44) reported less physical fatigue compared to the two oldest cohorts (55-64 and 65-74). Similar effects were found for total MFIS fatigue with individuals aged 55-64 reporting greater overall fatigue than 35-44 year olds. Finally, 18-24 year olds reported significantly higher levels of cognitive fatigue compared to 35-44 and 65-74 aged cohorts. No other effects were observed for age. Individuals with higher education consistently reported less fatigue. Subsequent analyses also revealed an interaction effect for age x gender. When examining the age x gender interaction, women age 18-24 reported significantly greater levels of physical, cognitive, psychosocial, and total fatigue than their male counterparts. In contrast, men aged 65-74 reported greater physical, cognitive, and total fatigue than women their age. Comparisons of the existing cutoff of the MFIS to the new age, gender, and education specific cutoffs found either comparable or slightly higher rates of fatigue with the latter.
Conclusion
Based on these findings, updated normative data and age, gender, and education specific cutoffs are provided. Utilization of these updated norms will result in a more accurate assessment of fatigue and will be valuable for those conducting research and/or clinical practice with individual with MS.
... 46 The prespecified inferiority margin is 10 points, which is based on triangulating anchor-based and distribution-based methods to calculate the minimally important difference (MID) on the Fatigue Impact Scale (FIS), and is consistent with a standardised mean difference of 0.3. [47][48][49] Recruitment and eligibility The primary recruitment method is community outreach in the Midwestern and Northeastern United States, involving four approaches: (1) advertising with non-profit organisations (eg, visiting support groups and going to events), (2) using social media (eg, Facebook), (3) asking neurologists and rehabilitation professionals to provide flyers to their patients, and (4) engaging community stakeholders (eg, snowballing recruitment). Inclusion criteria are a self-reported diagnosis of MS, at least 18 years of age, moderate-to-severe fatigue (ie, Fatigue Severity scale score ≥4), 50 and ability to speak and read English (ie, confirmed via phone conversation and selfreport). ...
Introduction:
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. It is considered a major cause of non-traumatic disability in young adults. One of the most common and disabling symptoms of MS is fatigue. MS fatigue can impact all aspects of quality of life, including physical, mental and social function. Fortunately, fatigue self-management interventions, such as 'Managing Fatigue: A 6 week energy conservation course', can decrease the impact of fatigue and improve health-related quality of life. The purpose of this study is to compare three modes of delivering the Managing Fatigue intervention-two remote delivery formats (teleconference and internet) and one in-person format-on perceptions of fatigue and its impact on physical, mental and social function.
Methods and analysis:
A non-inferiority randomised clinical trial is being conducted to compare the three delivery formats (1:1:1 allocation ratio) among 582 participants with MS living in the Midwestern and Northeastern United States. The hypothesis is that teleconference and internet versions of the intervention are non-inferior to the traditional mode of clinical service delivery (ie, one to one, in person) in terms of the primary outcome of self-reported fatigue impact (ie, Fatigue Impact Scale) and the secondary outcome of health-related quality of life (ie, Multiple Sclerosis Impact Scale). Outcomes are being measured at baseline, 2 months, 3 months and 6 months. The primary analysis tool will be linear mixed effects model. The prespecified inferiority margin for the primary outcome is 10 points. We will also examine whether baseline characteristics (eg, sociodemographic) moderate outcomes of the Managing Fatigue intervention and whether changes in self-efficacy and fatigue self-management behaviours mediate changes in outcomes.
Ethics and dissemination:
The protocol is approved centrally by the institutional review board at Case Western Reserve University. Eligible participants give consent before being enrolled and randomised into the study. The study results will be disseminated through relevant advocacy organisations, newsletters to participants, publication in peer-reviewed journals and presentations at scientific conferences.
Trial registration number:
NCT03550170; Pre-results.
... In the self-administered questionnaire consisting of 40 questions, scored 1-4 (minimal to severe), higher scores imply more fatigue [31]. The MCID is 10-20 points for FIS [32]. ...
Abstract
PURPOSE:
Respiratory muscles are known to be weakened and are a cause of reduced exercise capacity in both recipients and candidates of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Effects of inspiratory muscle training (IMT) in this patient population have not been comprehensively investigated so far. The current study was planned to investigate the effects of IMT during allo-HSCT on early transplantation-related outcomes.
METHODS:
This is a prospective, randomized controlled, double-blinded study. Thirty-eight allo-HSCT recipients, 20 of whom were allocated to the treatment group (40 % of maximal inspiratory pressure (MIP)) and 18 to the control group (5 % of MIP), received IMT for 6 weeks. Pulmonary functions, dyspnea, respiratory (MIP, maximal expiratory pressure (MEP)) and peripheral muscle strength, maximal exercise capacity using modified incremental shuttle walking test (MISWT) and submaximal exercise capacity using 6-min walking test (6-MWT), fatigue, depression, and quality of life were evaluated before and after IMT.
RESULTS:
The distance covered during MISWT (61.94 m) and 6-MWT (29.30 m), respiratory muscle strength (MIP 34.99 cmH2O, MEP 12.69 cmH2O), depression (-0.95), and modified Borg dyspnea scores (-0.11) showed a significant improvement in the treatment group compared to controls (p ≤ 0.05).
CONCLUSIONS:
Inspiratory muscle training is a safe and effective intervention which improves respiratory muscle strength and exercise capacity and decreases depression and dyspnea in allo-HSCT recipients. These positive changes might be further enhanced by prolonging the duration of training or inclusion of more recipients with inspiratory muscle weakness.
CLINICAL TRIAL REGISTRATION NUMBER:
NCT02270346.
... When anchored to measures of health-related quality of life, FIS demonstrates an MCID of 10 to 20 points. 42 Of the two included studies that used the FIS, both reported significant improvements in fatigue after the intervention (mean ± SD differences of 18.8 ± 14.3 [P < .001] 31 and 15.7 ± 25 [P < .01] ...
Background: Rehabilitation interventions are recommended to manage Multiple Sclerosis (MS) related fatigue. However, existing research has largely been generalised to those with relapsing-remitting MS, making it difficult to determine the effectiveness of these interventions amongst people with progressive MS. Therefore, this study aimed to systematically review the evidence related to the effectiveness of fatigue management interventions in reducing the severity and/or impact of fatigue in people with progressive MS.
Methods: Six electronic databases (CINAHL, Cochrane Library, MEDLINE, PEDro, ProQuest, and Web of Science Core Collections) were searched for relevant articles up until November 2017. Randomised controlled trials and quasi-experimental studies that examined the effects of exercise, behavioural interventions, and rehabilitation on fatigue in people with progressive MS using self-reported fatigue outcome measures were included in this review.
Results: Eight exercise, two rehabilitation and two behavioural interventions were investigated by the 13 articles included in this review. Heterogeneous effects were reported between studies with only two exercise, one behavioural, and two rehabilitation interventions recording significant improvements in fatigue severity or impact post-intervention. However, most studies were underpowered, only two studies used fatigue as the primary outcome, and only one specifically recruited participants with pre-defined levels of fatigue.
Conclusion: Evidence from this review is inconclusive regarding the effectiveness of non-pharmacological interventions in reducing the impact and severity of fatigue in progressive MS populations. Adequately powered randomised controlled trials are required to evaluate fatigue management interventions in people with progressive MS experiencing high levels of fatigue and using fatigue as the primary outcome.
... Nevertheless, the interpretation of what constitutes a clinically meaningful difference has been challenging. Mixed qualitative and quantitative methods, including clinical standards setting [26], combined anchor and distribution approaches [11,27,28], and search for convergence across anchors [29,30], have emerged to address this. The present study used multiple anchor-based models to estimate the ID for the FKSI-DRS instrument in patients undergoing treatment in the first-or second-line treatment of mRCC. ...
Background:
The Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) is important to gauge clinical benefit in metastatic renal cell carcinoma (mRCC).
Objectives:
To estimate important difference (ID) in FKSI-DRS scores that is considered to be meaningful when comparing treatment effect between groups, using mRCC trial data.
Methods:
Data were derived from two pivotal phase III mRCC trials comparing sunitinib versus interferon alfa (N = 750) in first-line mRCC, and axitinib versus sorafenib (N = 723) in second-line mRCC. The change from baseline in FKSI-DRS score was examined as a function of a set of anchors using the repeated-measures model. Several anchors were evaluated: FKSI item "I am bothered by side effects of treatment," EuroQol five-dimensional questionnaire utility score, and adverse events.
Results:
When the "I am bothered by side effects of treatment" score was used as an anchor, the ID ranged between 1.2 and 1.3 points. When change in the EuroQol five-dimensional questionnaire utility score was used as an anchor, the FKSI-DRS ID ranged between 0.62 and 0.63 points. Selecting the adverse events that corresponded to a maximum worsening in the FKSI-DRS score in either trial, the ID ranged between 0.62 and 0.74 points.
Conclusions:
Among patients undergoing treatment for mRCC, between-group differences in FKSI-DRS scores as low as 1 point might be meaningful.
... One cross-sectional study with MS patients [49] reported MIDs for the FIS ranging from 9-24 points for the different patient and clinician rating anchors, with a mean of 15.5 and SD 4.9. Distribution-based methods yielded MIDs ranging between 4.8-17.3 ...
Background:
Fatigue is the most frequent symptom reported by patients with chronic illnesses. As a subjective experience, fatigue is commonly assessed with patient-reported outcome measures (PROMs). Currently, there are more than 40 generic and disease-specific PROMs for assessing fatigue in use today. The interpretation of changes in PROM scores may be enhanced by estimates of the so-called minimal important difference (MID). MIDs are not fixed attributes of PROMs but rather vary in relation to estimation method, clinical and demographic characteristics of the study group, etc. The purpose of this paper is to compile published MIDs for fatigue PROMs, spanning diagnostic/patient groups and estimation methods, and to provide information relevant for appraising their appropriateness for use in specific clinical trials and in monitoring fatigue in defined patient groups in routine clinical practice.
Methods:
A systematic search of three databases (Scopus, CINAHL and Cochrane) for studies published between January 2000 to April 2015 using fatigue and variations of the term MID, e.g. MCID, MIC, etc. Two authors screened search hits and extracted data independently. Data regarding MIDs, anchors used and study designs were compiled in tables.
Results:
Included studies (n = 41) reported 60 studies or substudies estimating MID for 28 fatigue scales, subscales or single item measures in a variety of diagnostic groups and study designs. All studies used anchor-based methods, 21/60 measures also included distribution-based methods and 17/60 used triangulation of methods. Both similarities and dissimilarities were seen within the MIDs.
Conclusions:
Magnitudes of published MIDs for fatigue PROMs vary considerably. Information about the derivation of fatigue MIDs is needed to evaluate their applicability and suitability for use in clinical practice and research.
... In the self-administered questionnaire consisting of 40 questions, scored 1-4 (minimal to severe), higher scores imply more fatigue [31]. The MCID is 10-20 points for FIS [32]. ...
Background: During hematopoetic stem cell transplantation (HSCT) patients exposed to considerable physical and physcological stress. In addition to infections and graft versus host disease, decline in exercise capacity and muscle strength have negative effects on patients. There are few studies that investigates the effects of pulmonary rehabilitation (PR) during HSCT. The aim of this study was to investigate the effects of PR during HSCT.
Method: Twenty six HSCT recipients randomized into treatment group (TG) (6M/5F; 37.27±15.44) and control group (CG) (10M/5F; 45.00±15.10). Inspiratory muscle training, aerobic exercise training and resistance training were applied to TG. Mobilization and breathing exercises were applied to CG. Functional exercise capacity was evaluated using 6-minute walk test (6MWT), respiratory muscle strength (MIP, MEP) using a mouth pressure device, pulmonary function test using spirometry before and after transplantation.
Results: Baseline characteristics were similar in groups (p>0.05). No significant differences were present in pulmonary function test (p>0.05), 6MWT distance (p=0.199) and MEP (p=0.922). There was significant difference in MIP (p=0.003) after PR. In TG there was no significant difference in 6MWT distance (-20.06m, p=0.348) and MIP (p=0.233). There was significant decline in 6MWT distance (-50.13m, p=0.004) and MIP (p=0.001) in CG.
Discussion: Pulmonary rehabilitation during transplantation preserves functional capacity and inspiratory muscle strength. After HSCT considerable decline in exercise capacity and muscle strength is seen. To prevent from negative effects of HSCT, patients should be conducted to PR as soon as possible.
... In the self-administered questionnaire consisting of 40 questions, scored 1-4 (minimal to severe), higher scores imply more fatigue [31]. The MCID is 10-20 points for FIS [32]. ...
Purpose
Respiratory muscles are known to be weakened and are a cause of reduced exercise capacity in both recipients and candidates of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Effects of inspiratory muscle training (IMT) in this patient population have not been comprehensively investigated so far. The current study was planned to investigate the effects of IMT during allo-HSCT on early transplantation-related outcomes.
Methods
This is a prospective, randomized controlled, double-blinded study. Thirty-eight allo-HSCT recipients, 20 of whom were allocated to the treatment group (40 % of maximal inspiratory pressure (MIP)) and 18 to the control group (5 % of MIP), received IMT for 6 weeks. Pulmonary functions, dyspnea, respiratory (MIP, maximal expiratory pressure (MEP)) and peripheral muscle strength, maximal exercise capacity using modified incremental shuttle walking test (MISWT) and submaximal exercise capacity using 6-min walking test (6-MWT), fatigue, depression, and quality of life were evaluated before and after IMT.
Results
The distance covered during MISWT (61.94 m) and 6-MWT (29.30 m), respiratory muscle strength (MIP 34.99 cmH2O, MEP 12.69 cmH2O), depression (−0.95), and modified Borg dyspnea scores (−0.11) showed a significant improvement in the treatment group compared to controls (p ≤ 0.05).
Conclusions
Inspiratory muscle training is a safe and effective intervention which improves respiratory muscle strength and exercise capacity and decreases depression and dyspnea in allo-HSCT recipients. These positive changes might be further enhanced by prolonging the duration of training or inclusion of more recipients with inspiratory muscle weakness.
Clinical trial registration number: NCT02270346
... 9,10 Patient-reported fatigue and mental health-related quality of life (HRQoL) remained stable over the course of the long-term extension study, and the physical decrease in HRQoL paralleled the benefits observed on EDSS scores. 13 Although findings are limited by the relatively small number of patients who remained on treatment at the interim cut-off date (85/179 patients), this study provides useful data which will help clinicians understand the safety profile of teriflunomide over the long-term. To the best of our knowledge, this study of teriflunomide in RMS provides the longest exposure data of any oral DMT to date. ...
Teriflunomide, an oral disease-modifying therapy in development for patients with relapsing forms of multiple sclerosis (RMS), was well tolerated and effective in reducing magnetic resonance imaging (MRI) lesions in 179 RMS patients in a phase 2 36-week, placebo-controlled study.
A total of 147 patients who completed the core study entered an open-label extension. Teriflunomide patients continued their assigned dose, and placebo patients were re-allocated to teriflunomide, 7 mg/day or 14 mg/day. An interim analysis was performed at a cut-off on January 8 2010.
The mean and median duration of study treatment, including both the core and extension phase, from baseline to the interim cut-off, was 5.6 years (standard deviation: 2.7 years) and 7.1 years (range: 0.05-8.5 years), respectively. Of 147 patients, 62 (42.2%) discontinued (19% due to treatment-emergent adverse events (TEAEs)). The most common TEAEs were mild infections, fatigue, sensory disturbances and diarrhoea. No serious opportunistic infections occurred, with no discontinuations due to infection. Asymptomatic alanine aminotransferase increases (≤3× upper limit of normal (ULN)) were common (7 mg, 64.2%; 14 mg, 62.1%); increases >3×ULN were similar across groups (7 mg, 12.3%; 14 mg, 12.1%). Mild decreases in neutrophil counts occurred; none led to discontinuation. The incidence of malignancies was comparable to that of the general population, and cases were not reminiscent of those observed in immunocompromised patients. Annualised relapse rates remained low, minimal disability progression was observed, with a dose-dependent benefit with teriflunomide 14 mg for several MRI parameters.
Teriflunomide had a favourable safety profile for up to 8.5 years.
Introduction
Telerehabilitation may be effective on average but is not equally effective among all people with multiple sclerosis (MS). Thus, the purpose of this secondary analysis of a randomized controlled trial was to explore whether baseline characteristics of participants with MS influence fatigue and physical activity outcomes of three telerehabilitation interventions.
Methods
Participants were randomized to contact-control intervention (CC), physical activity-only intervention (PA-only), and physical activity plus fatigue self-management intervention (FM+). The 12-week interventions were delivered over the phone. Sociodemographic (age and income), clinical (comorbidities, mental function and physical function), psychosocial (self-efficacy, outcome expectations and goal-setting), and behavioural baseline characteristics (step count and fatigue self-management behaviors) were used in a moderated regression analysis and a responder analysis to examine their influence on the Fatigue Impact Scale (FIS) and Godin Leisure-Time Exercise Questionnaire (GLTEQ) at post-test (i.e. immediately post-interventions).
Results
No interactions terms were statistically significant in the moderation analysis. However, the responder analysis showed that baseline psychosocial characteristics and mental function were significantly different ( p < 0.05) between responders and non-responders. Specifically, non-responders on the FIS at post-test in the PA-only intervention had significantly lower baseline scores in goal setting for engaging in fatigue self-management behaviours. Also, non-responders on the GLTEQ at post-test in the FM+ intervention had significantly worse baseline scores in mental function.
Discussion
Further research is needed to understand the complex relationship among baseline characteristics, telerehabilitation and response heterogeneity. We discuss how research on examining response heterogeneity may be advanced by conducting mega-clinical trials, secondary analyses of big data, meta-analyses and employing non-traditional research designs.
Trial registration
Clinicaltrials.gov (NCT01572714).
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the effect of patient education programmes on fatigue in people with MS compared to standard care or alternative approaches. To assess whether the effects of patient education programmes on fatigue differ according to different intervention approaches or type of comparator intervention. © Copyright 2019 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.
Aim and objectives:
This study was conducted to determine the effects of cooling suit on fatigue and activities of daily living of individuals with multiple sclerosis (MS).
Background:
Fatigue is one of the most common symptoms in people with MS and adversely affects their activities of daily living. Studies evaluating fatigue associated with MS have reported that most of the fatigue cases are related to the increase in body temperature and that cooling therapy is effective in coping with fatigue.
Design:
This study used a two sample, control group design.
Methods:
The study sample comprised 75 individuals who met the inclusion criteria. Data were collected with study forms. After the study data were collected, cooling suit treatment was administered to the experimental group. During home visits paid at the fourth and eighth weeks after the intervention, the aforementioned scales were re-administered to the participants in the experimental and control groups.
Results:
The analyses performed demonstrated that the severity levels of fatigue experienced by the participants in the experimental group wearing cooling suit decreased. The experimental group also exhibited a significant improvement in the participants' levels of independence in activities of daily living.
Conclusions:
The cooling suit worn by individuals with MS was determined to significantly improve the participants' levels of fatigue and independence in activities of daily living.
Relevance to clinical practice:
The cooling suit therapy was found to be an effective intervention for the debilitating fatigue suffered by many MS patients, thus significantly improving their level of independence in activities of daily living. This article is protected by copyright. All rights reserved.
Objectives:
To analyze the impact of fatigue on individuals' global, cognitive, physical, and psychosocial functioning in the long term after hepatitis C virus (HCV) treatment and its relationship with HCV clearance among patients coinfected with HIV and HCV exposed to peg-interferon/ribavirin-containing regimens.
Patients and methods:
The study sample included 107 coinfected patients treated for HCV during follow-up in the French ANRS CO13-HEPAVIH cohort. Analyses used scores from the Fatigue Impact Scale (FIS), assessed before treatment initiation and at last available measure after the end of treatment (2 years in median). Patient proportions with a clinically significant improvement in fatigue impact, defined as a decrease higher than 10 points in the 160-point global FIS score, were compared between HCV clearers and chronic HCV patients (Fisher's exact test). Relationships between HCV clearance and FIS scores were analyzed in linear regression models adjusted for sex, time since end of HCV treatment, and pretreatment scores.
Results:
Twenty-nine percent of patients showed a clinically significant improvement in fatigue (15/57 in HCV clearers vs. 16/50 in chronic HCV patients, P=0.52). HCV clearance was not significantly associated with FIS scores in multivariate models.
Conclusion:
The role of HCV clearance in coinfected patients' functional recovery in the long term after peg-interferon/ribavirin treatment may be lesser than expected. Additional studies are needed in patients treated with direct-acting antiviral agents. In the meantime, the effectiveness of palliative care and targeted psychological treatments such as cognitive-behavioral therapy in reducing fatigue impact needs to be assessed in the many HCV-cured patients with HIV exposed to suboptimal interferon-based first-generation therapies.
Objectives:
Fatigue is an important problem in inflammatory diseases and affects the quality of life (QoL). We aimed to evaluate the severity and impact of fatigue in Behçet's syndrome (BS) and to determine its association with type of organ involvement and gender.
Methods:
One hundred and fifty-two BS, 51 rheumatoid arthritis (RA), 51 systemic lupus erythematosus (SLE), 51 ankylosing spondylitis (AS) patients and 65 healthy controls were evaluated by the fatigue severity scale, fatigue impact scale, fibromyalgia impact questionnaire (FIQ), RAPID3, SF-36 and Behçet's syndrome activity scale (the latter only in BS patients). We also analysed subgroups of BS patients with predominantly eye, vascular, joint and mucocutaneous involvement and did an additional gender analysis.
Results:
Fatigue severity and fatigue impact scores were similar among BS, RA, SLE and AS patients and significantly higher than that in healthy controls (F4df =8.51; p<0.001 and F4df = 8.67; p<0.001, respectively). The fatigue severity and fatigue impact scores were similarly high in BS subgroups with different types of organ involvement, and in both genders.
Conclusions:
Fatigue is an important problem in BS, as it is in other inflammatory conditions. It is similarly severe in subgroups of patients with eye, vascular, joint and mucocutaneous involvement and in either gender. Fatigue is a candidate outcome measure for clinical trials, to assess the life impact of Behçet's syndrome.
Background:
Factors contributing to subjective fatigue in people with idiopathic Parkinson's disease (PD) are not well known. This makes it difficult to manage fatigue effectively in PD.
Objectives:
To evaluate the effects of pharmacological and non-pharmacological interventions, compared to an inactive control intervention, on subjective fatigue in people with PD.
Search methods:
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE (via PubMed); Ovid EMBASE; EBSCO CINAHL; Ovid PsycINFO; PEDro; and the WHO International Clinical Trials Registry Platform Search Portal up to April 2015. References of included studies and identified review articles were screened for additional studies. There were no restrictions based on language, date of publication or study setting.
Selection criteria:
Randomised controlled trials (RCTs) that report on subjective fatigue in people with PD.
Data collection and analysis:
Two review authors independently performed study selection, data collection and risk of bias assessments.
Main results:
Eleven studies were eligible for this systematic review, with a total of 1817 people. Three studies included only people who experienced clinically relevant fatigue (Fatigue Severity Scale score ≥ 4 out of 7 or Multidimensional Fatigue Inventory total score > 48 out of 100), whereas all other studies did not select participants on the basis of experienced fatigue. Nine studies investigated the effects of medication (i.e. levodopa-carbidopa, memantine, rasagiline, caffeine, methylphenidate, modafinil or doxepin) on subjective fatigue. All studies were placebo controlled. There was insufficient evidence to determine the effect of doxepin on the impact of fatigue on activities in daily life (ADL) or fatigue severity (one study, N = 12, standardised mean difference (SMD) = -1.50, 95% confidence interval (CI) -2.84 to -0.15; low quality evidence). We found high quality evidence that rasagiline reduced or slowed down the progression of physical aspects of fatigue (one study, N = 1176, SMD = -0.27, 95% CI -0.39 to -0.16, I(2) = 0%). None of the other pharmacological interventions affected subjective fatigue in PD. With regard to adverse effects, only levodopa-carbidopa showed an increase for the risk of nausea (one study, N = 361, risk ratio (RR) = 1.85, 95% CI 1.05 to 3.27; high quality evidence). Two studies investigated the effect of exercise on fatigue compared with usual care. We found low quality evidence for the effect of exercise on reducing the impact of fatigue on ADL or fatigue severity (two studies, N = 57, SMD = -0.45, 95% CI -1.21 to 0.32, I(2) = 44%).
Authors' conclusions:
Based on the current evidence, no clear recommendations for the treatment of subjective fatigue in PD can be provided. Doxepin may reduce the impact of fatigue on ADL and fatigue severity; however, this finding has to be confirmed in high quality studies. Rasagiline may be effective in reducing levels of physical fatigue in PD. No evidence was found for the effectiveness of levodopa-carbidopa, memantine, caffeine, methylphenidate, modafinil or exercise. Studies are needed to investigate the effect of exercise intensity on exercise capacity and subjective fatigue. Future studies should focus on interventions that address the maladaptive behavioural or cognitive aspects of fatigue in people with PD. Characteristics, such as severity and nature of perceived fatigue and underlying mood disorders should be considered to identify responders and non-responders when studying interventions for fatigue. The development of a core-set of self-report fatigue questionnaires with established responsiveness and known minimal important difference values will facilitate the interpretation of change in fatigue scores.
To assess the efficacy of physiotherapy interventions, including exercise therapy, for the rehabilitation of people with progressive Multiple Sclerosis.
Five databases (Cochrane Library, Physiotherapy Evidence Database (PEDro), Web of Science Core Collections, Medline, EMBASE) and reference lists of relevant articles were searched.
Randomised experimental trials which included participants with progressive multiple sclerosis and investigated a physiotherapy intervention or an intervention containing a physiotherapy element were included.
Data were independently extracted using a standardised form and methodological quality was assessed using the PEDro scale.
Thirteen studies (described by 15 articles) were identified; scoring between 5 and 9 out of 10 on the PEDro scale. Eight interventions were assessed: exercise therapy, multi-disciplinary rehabilitation, functional electrical stimulation, botulinum toxin type A injections and manual stretches, inspiratory muscle training, therapeutic standing, acupuncture and body weight supported treadmill training. All studies, apart from one, produced positive results in at least one outcome measure, however, only one article used a power calculation to determine their sample size and due to 'drop outs' the results were subsequently underpowered.
This review suggests that physiotherapy may be effective for the rehabilitation of people with progressive Multiple Sclerosis. However, further appropriately powered studies are required.
Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
The randomised controlled trial (RCT) is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to the design and validity of a RCT is a calculation of the number of participants needed (the sample size). The value used to determine the sample size can be considered the 'target difference'. From both a scientific and an ethical standpoint, selecting an appropriate target difference is of crucial importance. Determination of the target difference, as opposed to statistical approaches to calculating the sample size, has been greatly neglected though a variety of approaches have been proposed the current state of the evidence is unclear.
The aim was to provide an overview of the current evidence regarding specifying the target difference in a RCT sample size calculation. The specific objectives were to conduct a systematic review of methods for specifying a target difference; to evaluate current practice by surveying triallists; to develop guidance on specifying the target difference in a RCT; and to identify future research needs.
The biomedical and social science databases searched were MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register, PsycINFO, Science Citation Index, EconLit, Education Resources Information Center (ERIC) and Scopus for in-press publications. All were searched from 1966 or the earliest date of the database coverage and searches were undertaken between November 2010 and January 2011. There were three interlinked components: (1) systematic review of methods for specifying a target difference for RCTs - a comprehensive search strategy involving an electronic literature search of biomedical and some non-biomedical databases and clinical trials textbooks was carried out; (2) identification of current trial practice using two surveys of triallists - members of the Society for Clinical Trials (SCT) were invited to complete an online survey and respondents were asked about their awareness and use of, and willingness to recommend, methods; one individual per triallist group [UK Clinical Research Collaboration (UKCRC)-registered Clinical Trials Units (CTUs), Medical Research Council (MRC) UK Hubs for Trials Methodology Research and National Institute for Health Research (NIHR) UK Research Design Services (RDS)] was invited to complete a survey; (3) production of a structured guidance document to aid the design of future trials - the draft guidance was developed utilising the results of the systematic review and surveys by the project steering and advisory groups.
Methodological review incorporating electronic searches, review of books and guidelines, two surveys of experts (membership of an international society and UK- and Ireland-based triallists) and development of guidance.
The two surveys were sent out to membership of the SCT and UK- and Ireland-based triallists.
The review focused on methods for specifying the target difference in a RCT. It was not restricted to any type of intervention or condition.
Methods for specifying the target difference for a RCT were considered.
The search identified 11,485 potentially relevant studies. In total, 1434 were selected for full-text assessment and 777 were included in the review. Seven methods to specify the target difference for a RCT were identified - anchor, distribution, health economic, opinion-seeking, pilot study, review of evidence base (RoEB) and standardised effect size (SES) - each having important variations in implementation. A total of 216 of the included studies used more than one method. A total of 180 (15%) responses to the SCT survey were received, representing 13 countries. Awareness of methods ranged from 38% (n =69) for the health economic method to 90% (n =162) for the pilot study. Of the 61 surveys sent out to UK triallist groups, 34 (56%) responses were received. Awareness ranged from 97% (n =33) for the RoEB and pilot study methods to only 41% (n =14) for the distribution method. Based on the most recent trial, all bar three groups (91%, n =30) used a formal method. Guidance was developed on the use of each method and the reporting of the sample size calculation in a trial protocol and results paper.
There is a clear need for greater use of formal methods to determine the target difference and better reporting of its specification. Raising the standard of RCT sample size calculations and the corresponding reporting of them would aid health professionals, patients, researchers and funders in judging the strength of the evidence and ensuring better use of scarce resources.
The Medical Research Council UK and the National Institute for Health Research Joint Methodology Research programme.
Objective:
To systemically review the psychometric properties and clinical utility (feasibility) of tools to measure fatigue in neurological conditions.
Data sources:
AMED, CINAHL, MEDLINE, Science Direct and Web of Knowledge were searched for studies of the psychometric properties of fatigue measures in adults with central nervous system disorders. Search terms were: Fatigue AND assess* OR measure* OR tool OR outcome OR index OR test OR scale AND stroke OR cerebrovascular* OR hemi* OR parkinson* OR sclerosis OR head injury OR brain injury OR motor neurone disease OR neuro* REVIEW METHODS: Articles that addressed validity; reliability and ability to detect change were selected. Two authors independently selected articles and extracted data. Strength of the psychometric properties and clinical utility were assessed against predetermined thresholds.
Results:
A total of 25 articles were selected and 17 measurement tools identified including six versions of the Fatigue Severity Scale and five versions of the Fatigue Impact Scale. All were clinically feasible but none met all the criteria. Most were valid. Reliability and ability to detect change were infrequently evaluated, but were adequate when reported. The most thoroughly developed and psychometrically robust measures were the Neurological Fatigue Indices.
Conclusion:
Although many measures of fatigue in neurological conditions have published, none met all of the criteria for psychometric robustness and clinical utility but the Neurological Fatigue Indices are the best and can be used with caution.
One can classify ways to establish the interpretability of quality-of-life measures as anchor based or distribution based. Anchor-based measures require an independent standard or anchor that is itself interpretable and at least moderately correlated with the instrument being explored. One can further classify anchor-based approaches into population-focused and individual-focused measures. Population-focused approaches are analogous to construct validation and rely on multiple anchors that frame an individual's response in terms of the entire population (eg, a group of patients with a score of 40 has a mortality of 20%). Anchors for population-based approaches include status on a single item, diagnosis, symptoms, disease sever- ity, and response to treatment. Individual-focused ap- proaches are analogous to criterion validation. These methods, which rely on a single anchor and establish a minimum important difference in change in score, require 2 steps. The first step establishes the smallest change in score that patients consider, on average, to be important (the minimum important difference). The second step esti- mates the proportion of patients who have achieved that minimum important difference. Anchors for the indi- vidual-focused approach include global ratings of change within patients and global ratings of differences between patients. Distribution-based methods rely on expressing an effect in terms of the underlying distribution of results. Investigators may express effects in terms of between- person standard deviation units, within-person standard deviation units, and the standard error of measurement. No single approach to interpretability is perfect. Use of multiple strategies is likely to enhance the interpretability of any particular instrument. Mayo Clin Proc. 2002;77:371-383
A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form.
One possible reason for the continued neglect of statistical power analysis in research in the behavioral sciences is the inaccessibility of or difficulty with the standard material. A convenient, although not comprehensive, presentation of required sample sizes is provided. Effect-size indexes and conventional values for these are given for operationally defined small, medium, and large effects. The sample sizes necessary for .80 power to detect effects at these levels are tabled for 8 standard statistical tests: (1) the difference between independent means, (2) the significance of a product-moment correlation, (3) the difference between independent rs, (4) the sign test, (5) the difference between independent proportions, (6) chi-square tests for goodness of fit and contingency tables, (7) 1-way analysis of variance (ANOVA), and (8) the significance of a multiple or multiple partial correlation.
A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form.
We conducted a cross-sectional, geographically based study of functional status in an incident cohort of 124 multiple sclerosis (MS) patients with onset of disease from 1 January 1976 to 31 December 1986 in Møre and Romsdal County, Norway. The cohort comprised 58 men (46.8%) and 66 women (53.2%). One hundred and thirteen patients (91.1%) had a primary remitting course of disease and 11 (8.9%) had primary progressive MS. The mean age of onset was 33.3 years (range 14-64), and the mean duration of disease 7.8 years (range 1-23). The Minimal Record of Disability (MRD) of multiple sclerosis was applied to measure the degree of impairment, disability and handicap. The mean Kurtzke Expanded Disability Status Scale (EDSS) score was 3.76 (0-10), and the frequency distribution of the EDSS scores in the cohort was bimodal. Twenty-eight (22.6%) patients in the cohort had marked paraparesis, paraplegia of quadriplegia. Nineteen patients (15.3%) had frequent urinary incontinence, need for almost constant catheterization, or need for constant use of measures to evacuate stools. Five patients (4%) had a severe decrease in mentation or dementia. Forty-eight patients (38.7%) reported frequent problems with fatigue or fatigability preventing sustained physical function. Less than half of the cohort (42.7%) was working full-time, and 49.2% of the patients reported that they received external support to maintain their usual financial standard. Lack of ability to work full-time and accordingly the dependence upon external financial support were significantly associated with the primary progressive course of disease. Fatigue was statistically significantly related to lack of working ability. The estimated cost of MS in the county in 1991 was 48.2 million NOK (approximately 7.531.250 US $) based on the cost-of-illness methodology.
To evaluate the cost-effectiveness of interferon beta-1b (IFbeta-1b) for relapsing-remitting multiple sclerosis (RRMS).
Construction of a cost-effectiveness model using published data on IFbeta-1b effectiveness and the natural history of RRMS, and new data on costs and quality of life (QoL) from a sample of 102 patients with RRMS and resident in northern England.
Poorer QoL was found for patients with multiple sclerosis compared with the general population; those who had had a relapse; those with worse states identified by a clinical measure (expanded disability status scale (EDSS)). Relapses have effects over several months. Health state valuations were higher than in the general population. Costs were higher in relapse than remission and for worse EDSS states. IFbeta-1b costs were larger than cost savings. The best cost-effectiveness estimate was pound28 700 per relapse avoided, which is pound809 900 per QALY gained; or pound328 300 per QALY gained allowing for effects of progression over 5 years. Estimates were robust to changes in assumptions.
The impact of multiple sclerosis on QoL is substantial. Future trials should base outcomes measurement on QoL and be better linked to natural history and cost data. IFbeta-1b produces important occasional short term QoL gains, but small gains in QALYs overall and large additional costs.
To assess the efficacy and safety of modafinil for the treatment of fatigue in multiple sclerosis (MS).
Patients aged 18-65 years with a diagnosis of MS, a stable disability level < or =6 on the Kurtzke extended disability status scale (EDSS), and a mean score >4 on the fatigue severity scale (FSS) were eligible for the 9 week, single blind, phase 2, two centre study. Exclusion criteria included a diagnosis of narcolepsy, sleep apnoea, or clinically significant major systemic disease and recent use of medications affecting fatigue. All patients, who remained blinded for the treatment regimen, received placebo during weeks 1-2, 200 mg/day modafinil during weeks 3-4, 400 mg/day modafinil during weeks 5-6, and placebo during weeks 7-9. Safety was evaluated by unblinded investigators. Efficacy was evaluated by self rating scales, using the FSS, the modified fatigue impact scale (MFIS), a visual analogue scale for fatigue (VAS-F), and the Epworth sleepiness scale (ESS). Adverse events were recorded.
Seventy two patients (MS type: 74% relapsing-remitting; 7% primary progressive; 19% secondary progressive) received treatment. After treatment with 200 mg/day modafinil for 2 weeks, a significant improvement in fatigue versus placebo run in was demonstrated. Mean scores after treatment with 200 mg/day modafinil were: FSS, 4.7 versus 5.5 for placebo (p<0.001); MFIS, 37.7 versus 44.7 (p<0.001); and VAS-F, 5.4 versus 4.5 (p=0.003). Fatigue scores for 400 mg/day modafinil were not significantly improved versus placebo run in. Mean ESS scores were significantly improved (p<0.001) with 200 mg/day modafinil (7.2) and 400 mg/day (7.0) versus the score at baseline (9.5). Serious adverse events were not found at either dose. The most common adverse events were headache, nausea, and aesthenia. Sixty five patients (90%) completed the study.
These data suggest that 200 mg/day modafinil significantly improves fatigue and is well tolerated in patients with MS.
The test-retest reliability and the convergent validity of the Fatigue Impact Scale (FIS) were evaluated using secondary data from 54 persons with multiple sclerosis (MS).
This reliability and validity study used FIS data from before and after two control periods to evaluate test-retest reliability. Convergent validity of the FIS with the Fatigue Severity Scale and with subscales of the SF-36 Health Survey was evaluated using data collected before the first control period.
No significant differences between before and after FIS measurements and intraclass correlation coefficients ranging from .68 to .85 indicate that the FIS has good test-retest reliability except for the physical subscale. The expected moderate correlations between the FIS and several subscales of the SF-36 support its convergent validity. In contrast, the unexpected low correlation between the FIS and Fatigue Severity Scale does not support convergent validity.
The FIS has adequate reliability and validity and is recommended to evaluate the effectiveness of fatigue management interventions such as energy conservation education for persons with MS.
Purpose:
There is increasing recognition that the global wellbeing of patients with chronic neurological disease is an important outcome in research and clinical practice alike. Many studies involving individuals with multiple sclerosis have demonstrated that the overall wellbeing is not a simple manifestation of impairment or disability. The strongest correlations with health-related quality of life appear to be patient rated emotional adjustment to illness and patient rated handicap. In recent years, health-related quality of life questionnaires that measure the physical, social, emotional, and occupational impact of illness have been developed and validated in populations with MS. Most questionnaires are now available in a range of languages. This development is likely to lead to increasing recognition of neuropsychiatric complications of MS in clinical practice and better quantification of treatment responses in clinical trials.
Conclusion:
Further work is required to decide which scale is most suited to which purpose. Assessment of multiple sclerosis-specific health-related quality of life should be included in future clinical trials to provide a complete picture of patients' health status.
To evaluate the effect of the oral synthetic delta-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis.
Randomised double blind placebo controlled crossover trial.
Outpatient clinic, University Hospital of Aarhus, Denmark.
24 patients aged between 23 and 55 years with multiple sclerosis and central pain.
Orally administered dronabinol at a maximum dose of 10 mg daily or corresponding placebo for three weeks (15-21 days), separated by a three week washout period.
Median spontaneous pain intensity (numerical rating scale) in the last week of treatment.
Median spontaneous pain intensity was significantly lower during dronabinol treatment than during placebo treatment (4.0 (25th to 75th centiles 2.3 to 6.0) v 5.0 (4.0 to 6.4), P = 0.02), and median pain relief score (numerical rating scale) was higher (3.0 (0 to 6.7) v> 0 (0 to 2.3), P = 0.035). The number needed to treat for 50% pain relief was 3.5 (95% confidence interval 1.9 to 24.8). On the SF-36 quality of life scale, the two items bodily pain and mental health indicated benefits from active treatment compared with placebo. The number of patients with adverse events was higher during active treatment, especially in the first week of treatment. The functional ability of the multiple sclerosis patients did not change.
Dronabinol has a modest but clinically relevant analgesic effect on central pain in patients with multiple sclerosis. Adverse events, including dizziness, were more frequent with dronabinol than with placebo during the first week of treatment.
Sixty relapsing remitting multiple sclerosis (MS) patients were selected on the basis of their score on the Fatigue Severity Scale (FSS) and formed two groups: 40 patients (fatigued MS; MSf) scored above the 75th percentile of a previously assessed representative MS sample (100 patients), and 20 age- and sex-matched patients (nonfatigued MS patients; MSnf) scored below the 25th percentile. The patients underwent clinical evaluation (Expanded Disability Status Scale (EDSS)), further assessment of fatigue (Fatigue Impact Scale), scales evaluating depression (Hamilton Depression Rating Scale (HDRS) and Beck's Depression Inventory (BDI)) and neuropsychological tests. All patients were evaluated for muscle fatigability and central activation by means of a biomechanical test of sustained contraction; they also underwent somatosensory evoked potentials (SSEPs) and transcranial magnetic stimulation (TMS). The patients of the MSf subgroup were then randomized to one of the following two treatments: 4-aminopyridine (4-AP) 24 mg/day and fluoxetine (FLX) 20 mg/day. After a one-week titration this treatment proceeded for 8 weeks. At the end of the treatment, EDSS, fatigue and depression scores were further evaluated. At baseline, fatigue test scores consistently correlated with depression and cognitive test scores, but not with the fatigability test. Fatigue scores decreased in both treatment groups in a similar way. Due to the design of the study, this cannot be disjoined from a placebo effect. The changes of fatigue scores could not be predicted in the FLX group, whereas in the 4-AP group higher basal fatigability test scores were associated with greater reduction in fatigue scores.
One can classify ways to establish the interpretability of quality-of-life measures as anchor based or distribution based. Anchor-based measures require an independent standard or anchor that is itself interpretable and at least moderately correlated with the instrument being explored. One can further classify anchor-based approaches into population-focused and individual-focused measures. Population-focused approaches are analogous to construct validation and rely on multiple anchors that frame an individual's response in terms of the entire population (eg, a group of patients with a score of 40 has a mortality of 20%). Anchors for population-based approaches include status on a single item, diagnosis, symptoms, disease severity, and response to treatment. Individual-focused approaches are analogous to criterion validation. These methods, which rely on a single anchor and establish a minimum important difference in change in score, require 2 steps. The first step establishes the smallest change in score that patients consider, on average, to be important (the minimum important difference). The second step estimates the proportion of patients who have achieved that minimum important difference. Anchors for the individual-focused approach include global ratings of change within patients and global ratings of differences between patients. Distribution-based methods rely on expressing an effect in terms of the underlying distribution of results. Investigators may express effects in terms of between-person standard deviation units, within-person standard deviation units, and the standard error of measurement. No single approach to interpretability is perfect. Use of multiple strategies is likely to enhance the interpretability of any particular instrument.
In representing a realationship between a response and a number of independent variables, it is preferable when possible to work with a simple functional form in transformed variables rather than with a more complicated form in the original variables. This paper describes and illustrates a procedure to estimate appropriate transformations in this context.
In the course of developing a standardised, non-disease-specific instrument for describing and valuing health states (based on the items in Table 1), the EuroQol Group (whose members are listed In the Appendix) conducted postal surveys in England, The Netherlands and Sweden which indicate a striking similarity in the relative valuations attached to 14 different health states (see Table 3). The data were collected using a visual analogue scale similar to a thermometer (see Table 2). The EuroQol Instrument Is Intended to complement other quality-of-life measures and to facilitate the collection of a common data set for reference purposes. Others interested in participating in the extension of this work are invited to contact the EuroQol Group.
Objectives:
Because published utility estimates in multiple sclerosis (MS) are concentrated in people with moderate to severe disease severity and focus on specific types of MS, we conducted a cross-sectional study of people with MS to estimate the utility associated with disease, functional status as measured by the Adapted Patient Determined Disease Steps (APDDS) Scale, and relapse to enhance knowledge of the association of these factors and utility.
Methods:
The study was conducted by a postal questionnaire sent to 12,968 people in a database managed by a UK charity (the MS Trust). Utility was assessed using the EQ-5D multiattribute utility scale. The APDDS is closely related to the more commonly reported Expanded Disability Status Scale (EDSS).
Results:
A total of 2708 (20.9%) questionnaires were returned and 2048 (15.8%) respondents provided data suitable for analysis. The mean age of the sample was 51 years, and 22.5% of people were aged 60 years or more. Disease severity was concentrated in people with moderately severe MS (EDSS 4-6.5), with 21%, 60%, and 19% of people reporting mild, moderate, and severe disease, respectively. Results show that disease severity has an inverse relationship with utility. The mean utility is 0.491. Utility varies between 0.870 and -0.195 for EDSS states 0 and 9. Number of years since diagnosis, type of disease, and recent relapse status are also all significantly associated with utility.
Conclusions:
The results are comparable with previous published utility estimates. We have demonstrated a clear relationship between functional status, disease type, relapse status, duration of illness, and utility. As a set of coefficients, the utility estimates we have calculated may be used to compare the quality of life of people with MS with other illnesses and to inform future economic evaluations in MS.
A general class of regression models for ordinal data is developed and discussed. These models utilize the ordinal nature of the data by describing various modes of stochastic ordering and this eliminates the need for assigning scores or otherwise assuming cardinality instead of ordinality. Two models in particular, the proportional odds and the proportional hazards models are likely to be most useful in practice because of the simplicity of their interpretation. These linear models are shown to be multivariate extensions of generalized linear models. Extensions to non‐linear models are discussed and it is shown that even here the method of iteratively reweighted least squares converges to the maximum likelihood estimate, a property which greatly simplifies the necessary computation. Applications are discussed with the aid of examples.
One possible reason for the continued neglect of statistical power analysis in research in the behavioral sciences is the inaccessibility of or difficulty with the standard material. A convenient, although not comprehensive, presentation of required sample sizes is provided here. Effect-size indexes and conventional values for these are given for operationally defined small, medium, and large effects. The sample sizes necessary for .80 power to detect effects at these levels are tabled for eight standard statistical tests: (a) the difference between independent means, (b) the significance of a product-moment correlation, (c) the difference between independent rs, (d) the sign test, (e) the difference between independent proportions, (f) chi-square tests for goodness of fit and contingency tables, (g) one-way analysis of variance, and (h) the significance of a multiple or multiple partial correlation.
Fatigue is a common symptom associated with a wide range of chronic diseases. A large number of instruments have been developed to measure fatigue. An assessment regarding the reliability, validity, and utility of fatigue measures is time-consuming for the clinician and researcher, and few reviews exist on which to draw such information. The aim of this article is to present a critical review of fatigue measures, the populations in which the scales have been used, and the extent to which the psychometric properties of each instrument have been evaluated to provide clinicians and researchers with information on which to base decisions. Seven databases were searched for all articles that measured fatigue and offered an insight into the psychometric properties of the scales used over the period 1980-2007. Criteria for judging the "ideal" measure were developed to encompass scale usability, clinical/research utility, and the robustness of psychometric properties. Twenty-two fatigue measures met the inclusion criteria and were evaluated. A further 17 measures met some of the criteria, but have not been tested beyond initial development, and are reviewed briefly at the end of the article. The review did not identify any instrument that met all the criteria of an ideal instrument. However, a small number of short instruments demonstrated good psychometric properties (Fatigue Severity Scale [FSS], Fatigue Impact Scale [FIS], and Brief Fatigue Inventory [BFI]), and three comprehensive instruments demonstrated the same (Fatigue Symptom Inventory [FSI], Multidimensional Assessment of Fatigue [MAF], and Multidimensional Fatigue Symptom Inventory [MFSI]). Only four measures (BFI, FSS, FSI, and MAF) demonstrated the ability to detect change over time. The clinician and researcher also should consider the populations in which the scale has been used previously to assess its validity with their own patient group, and assess the content of a scale to ensure that the key qualitative aspects of fatigue of the population of interest are covered.
The proportional odds model for ordinal logistic regression provides a useful extension of the binary logistic model to situations where the response variable takes on values in a set of ordered categories. The model may be represented by a series of logistic regressions for dependent binary variables, with common regression parameters reflecting the proportional odds assumption. Key to the valid application of the model is the assessment of the proportionality assumption. An approach is described arising from comparisons of the separate (correlated) fits to the binary logistic models underlying the overall model. Based on asymptotic distributional results, formal goodness-of-fit measures are constructed to supplement informal comparisons of the different fits. A number of proposals, including application of bootstrap simulation, are discussed and illustrated with a data example.
Fatigue is a frequent symptom in multiple sclerosis (MS) that can interfere with a patient's daily functioning. The cause of MS fatigue, its clinical characteristics, and its relationship to other symptoms remain poorly understood. Structured interviews were conducted with 32 patients with MS and 33 normal healthy adults. Fatigue proved to be both more frequent and more severe among the patients with MS. Multiple sclerosis fatigue was unrelated to either depression or global impairment. Multiple sclerosis fatigue appears to be a distinct clinical entity, often disabling, that can be distinguished from normal fatigue, affective disturbance, and neurologic impairment.
One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional Systems (FS) and an overall Disability Status Scale (DSS) that had steps from 0 (normal) to 10 (death due to MS). A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 . . . 9) now divided into two (1.0, 1.5, 2.0 . . . 9.5). The lower portion is obligatorily defined by Functional System grades. The FS are Pyramidal, Cerebellar, Brain Stem, Sensory, Bowel & Bladder, Visual, Cerebral, and Other; the Sensory and Bowel & Bladder Systems have been revised. Patterns of FS and relations of FS by type and grade to the DSS are demonstrated.
An interpretation of the standardized difference is given which assists in judging the importance of such a difference. This is useful for designing two sample studies when information on mean difference or standard deviation is unavailable.
Current clinical scales in multiple sclerosis (MS) are often complicated to administer, suffer from interrater variability and lack of uniform representation across grades, and are insensitive to progression at certain stages. Furthermore, they are not easily applied by neurologists and do not clearly differentiate among functional stages of MS. For these reasons, we developed Disease Steps to assess disability in MS. A total of 1,323 patients were classified using both Disease Steps and the Expanded Disability Status Scale (EDSS) for a total of 2,755 assessments. The Disease Steps scale consists of 0 = Normal; 1 = Mild disability, mild symptoms or signs; 2 = Moderate disability, visible abnormality of gait; 3 = Early cane, intermittent use of cane; 4 = Late cane, cane-dependent; 5 = Bilateral support; 6 = Confined to wheelchair; and U = Unclassifiable. Results demonstrate that raters could simply and quickly categorize patients using Disease Steps. Patients were uniformly distributed with Disease Steps, whereas a bimodal distribution occurred with the EDSS. On the EDSS, 40.3% of patients scored between 1.0 and 3.5 and 36.0% scored from 6.0 to 6.5, with only 6.9% of patients scoring between 4.0 and 5.5. For 60 patients seen by two neurologists, concordance between raters was excellent for Disease Steps (kappa = 0.8) but only moderate for the EDSS (kappa = 0.54). As a simple and reproducible measure of different functional steps of MS, Disease Steps can be used as a guide in therapeutic decision-making, following response to therapy, and in assessing disease progression.
Multiple sclerosis (MS) clinical rating scales are used to classify the degree of neurological dysfunction and to plan treatment measures. In clinical trials, rating scales are used to monitor clinical course and response to experimental therapies. Selection of the appropriate clinical rating scale is determined by the nature of the research question (e.g., disability, impairment, handicap). The Expanded Disability Status Scale (EDSS, an impairment scale) has been the most widely used clinical rating method in natural history studies and clinical trials. The EDSS has the advantage of familiarity, yet is difficult to use consistently between evaluators. In the mid and higher ranges, the EDSS is relatively insensitive to clinical changes that do not impair gait. Evaluator unblinding may invalidate the clinical assessment of response to treatment. Additional work is needed to develop clinical and laboratory (imaging) measures of MS disease activity that will be objective, reliable, sensitive, responsive, and valid. Recent comparative studies have demonstrated that serial magnetic resonance imaging (MRI) studies are 7- to 10-fold more sensitive than clinical methods in detecting subclinical evidence of apparent MS disease activity. Widespread acceptance of MRI as a primary trial outcome measure awaits the results of studies designed to determine whether MRI findings accurately reflect irreversible pathological changes and predict future disability.
The fatigue impact scale (FIS) was developed to improve our understanding of the effects of fatigue on quality of life. The
FIS examines patients' perceptions of the functional limitations that fatigue has caused over the past month. FIS items reflect
perceived impact on cognitive, physical, and psychosocial functioning. This study compared 145 patients referred for investigation
of chronic fatigue (ChF) with 105 patients with multiple sclerosis (MS) and 34 patients with mild hypertension (HT). Internal
consistency for the FIS and its three subscales was >.87 for all analyses. Fatigue impact was highest for the ChF group although
the MS group's reported fatigue also exceeded that of the HT group. Discriminant function analysis correctly classified 80.0%
of the ChF group and 78.1% of the MS group when these groups were compared. This initial validation study indicates that the
FIS has considerable merit as a measure of patients' attribution of functional limitations to symptoms of fatigue.
Although fatigue is recognized as a symptom of MS, there have been insufficient methods for evaluating this symptom. We administered the Fatigue Impact Scale to 85 MS patients and 20 hypertensive patients. Neurologic impairment, mental health, and general health status were also assessed. MS patients reported significantly higher fatigue impact than hypertensive patients. Most MS patients reported fatigue as either their worst (14%), or one of their worst (55%) symptoms. Disease classification and neurologic impairment had little bearing on Fatigue Impact Scale scores in the MS sample. The best predictive models for mental health and general health status in the MS sample both included the Fatigue Impact Scale as a significant factor. This study demonstrates that: 1) fatigue is a very prevalent and severe problem in MS, 2) fatigue impact cannot be predicted by clinical measures of neurologic impairment, 3) fatigue has a significant effect on the mental health and general health status of MS patients.
Fatigue is probably the most common symptom of illness affecting sufferers of both acute and chronic conditions. However, confusion surrounds the definition and use of the term fatigue. As with many other nursing concepts, it is a word that is commonly used in colloquial language. This concept analysis aims to identify the attributes that are essential to the concept of fatigue, and to distinguish between its colloquial and its nursing usage by following the strategy suggested by Walker and Avant (1995, Strategies for Theory Construction in Nursing, Appleton Lange, London). A review of the literature identifies nursing uses of the term fatigue which reflect and conflict with colloquial uses. Defining attributes, demonstration cases, antecedents, consequences and empirical referents are identified before a definition of fatigue is developed and proposed for nursing. This clarification of the phenomenon has particular relevance for clinical nursing, future research and the development of fatigue theories.
Three self-report scales and an objective measure were examined for their value in assessing fatigue in patients with brain injury. Patients with brain injury and healthy controls completed the Fatigue Impact Scale (FIS), Visual Analogue Scale for Fatigue (VAS-F) and Fatigue Severity Scale (FSS). Fatigue was objectively measured via a continuous thumb pressing task. Patients scored higher on all fatigue measures than did participants without brain injury. Significant group differences were found on the FIS, the vigour subscale of the VAS-F, and the FSS. The FIS provided a comprehensive assessment of patients' fatigue experience. The FSS, although differentiating between groups, did not provide as comprehensive an examination of fatigue as the FIS and the scale's internal consistency requires review. No significant group differences in fatigue ratings were found on the VAS-F, possibly due to the scale's failure to differentiate between fatigue and sleepiness. The objective measure of fatigue found patients with brain injury fatigued more quickly than participants without brain injury. Although group differences were not significant, this trend suggest that further examination of this fatigue measure is warranted. Overall, patients with brain injury were found to experience significant levels of fatigue and the FIS provided the most comprehensive examination of fatigue.
Multiple sclerosis is a chronic neurological disease which can cause a variety of symptoms (motor and sensory impairment, visual problems, bladder and bowel problems, sexual dysfunction, and decline in cognitive function). Both the Medical Outcome Study Short Form-36, a generic questionnaire regarding health-related quality of life, and the Disability and Impact Profile, a similar questionnaire developed for people with chronic diseases, are used regularly to assess patients with multiple sclerosis. Over a 6-mo. interval 187 patients with multiple sclerosis completed these questionnaires twice. Internal consistency of both questionnaires at Times 1 and 2 was .60 or above for all eight scales of the Medical Outcome Study Short Form-36 and five scales of the Disability and Impact Profile. Estimates of test-retest reliability for three scales of the Medical Outcome Study Short Form-36 were below .60, but for all scales of the Disability and Impact Profile were .60 or higher. The two questionnaires appeared to be reliable for our sample of patients with multiple sclerosis.
To determine the frequency and outcome of fatigue, its impact on functioning, and its relationship with depression in patients 3 to 13 months poststroke.
Survey.
Community.
Eighty-eight individuals from a pool of 181 consecutive patients previously admitted to an acute stroke service who were willing and able to complete the self-report questionnaires, and 56 elderly controls living independently in the community.
Fatigue Impact Scale (a self-report measure of the presence and severity of fatigue and its impact on cognitive, physical, and psychosocial functions) and the Geriatric Depression Scale.
The frequency of self-reported fatigue problems was greater in the stroke group (68%) than in the control group (36%, p < .001) and was not related to time poststroke, stroke severity, or lesion location. Forty percent of the stroke group reported that fatigue was either their worst or one of their worst symptoms. Patients attributed more functional limitations to their fatigue than did control subjects with fatigue. Although the presence of fatigue was independent of depression, the impact of fatigue on functional abilities was strongly influenced by depression.
Fatigue can contribute to functional impairment up to 13 months after stroke, and its recognition and treatment are important for maximizing recovery.
OullII;l y Many clinical rating scales have been proposed to assess the impact of multiple sclerosis on patients, but only few have been evaluated formally for reliability, validity and responsiveness. We assessed the psychometric properties of five commonly used scales in multiple sclerosis, the Expanded Disability Status Scale (EDSS), the Scripps Neurological Rating Scale (SNRS), the Functional Independence Measure (FIM), the Ambulation Index (AI) and the Cambridge Multiple Sclerosis Basic Score (CAMBS). The score frequency distributions of all five scales were either bimodal (EDSS and AI) or severely skewed (SNRS, FIM and CAMBS). The reliability of each scale depended on the definition of 'agreement'. Inter-and intra-rater reliabilities were high when 'agreement' was considered to exist despite a difference of up to 1.0 EDSS point (two 0.5 steps), 13 SNRS points, 9 FIM points, 1 AI point and 1 point on the various CAMBS domains. The FIM, AI, and the relapse and progression domains of the CAMBS were sensitive to clinical change, but the EDSS and the SNRS were unresponsive. The validity of these scales as impairment (SNRS and EDSS) and disability (EDSS, FIM, AI and the disability domain of the CAMBS) measures was established. All scales correlated closely with other measures of handicap and quality of life. None of these scales satisfied the psychometric requirements of outcome measures completely, but each had some desirable properties. The SNRS and the EDSS were reliable and valid measures of impairment and disability, but they were unresponsive. The FIM was a reliable, valid and responsive measure of disability, but it is cumbersome to administer and has a limited content validity. The AI was a reliable and valid ambulation-related disability scale, but it was weakly responsive. The CAMBS was a reliable (all four domains) and responsive (relapse and progression domains) outcome measure, but had a limited validity (handicap domain). These psychometric properties should be considered when designing further clinical trials in multiple sclerosis.
Health-related quality of life (HRQoL) questionnaires finding increasing use in medicine, but still only few publications have reported on HRQoL in patients with multiple sclerosis (MS). Because of its progressive and disabling nature, the disease has a considerable effect on HRQoL. To facilitate the interpretation of scores for the heterogeneous MS population, we explored differences between subgroups of MS out-patients (n = 90) on two HRQoL instruments: the Medical Outcome Study Short Form-36 and the Disability and Impact Profile. Three disease-related characteristics were studied: severity of MS, time since diagnosis, and MS progression in the past 6 months. The results show that each of these have an effect on one or more aspects of HRQoL. Thus, the longer the disease duration and the more severe and progressive the MS, the lower is the patient's experienced HRQoL.
Objective: To explore relations of fatigue, physical disabilities, and depression in patients with multiple sclerosis (MS) cross-sectionally and over time. Methods: Ninety-eight MS patients were interviewed twice at an interval of a year. Relationships of physical and mental fatigue, and reduced activity and motivation with depression and physical disabilities were established cross-sectionally by regression analyses and longitudinally by structural equation modelling. Results: Cross-sectionally, physical fatigue was related with physical disabilities, and mental fatigue was associated with depression. Prospectively, physical fatigue was a predictor of the physical disabilities of a year later. The reverse relationship of physical disabilities predicting the physical fatigue of one year later was, however, not significant, while depression predicted this physical fatigue and reduced activity of a year later. Depression did not predict the later mental fatigue nor was depression predicted by preceding fatigue experiences. Conclusions: Fatigue in MS should be studied over time as relationships of fatigue with physical and mental health change during the course of a year. Moreover, differentiating in fatigue experiences sheds light on the relationship of fatigue with physical and mental health.
To evaluate the efficacy of an energy conservation course on fatigue impact, self-efficacy, and quality of life (QOL) for persons with multiple sclerosis (MS).
Repeated measures with control and experimental interventions conducted during a 19-week study.
Community-based treatment center.
A convenience sample of 54 individuals from 79 community-dwelling volunteers with fatigue secondary to MS.
A 6-session, 2-hr/wk energy conservation course taught by occupational therapists for groups of 8 to 10 participants.
Fatigue Impact Scale (self-report measure of fatigue impact on cognitive, physical, social functions), Self-Efficacy Gauge (self-report measure of confidence in ability to perform specific behaviors), and Medical Outcomes Study Short-Form Health Survey (QOL measure).
Participants reported, as predicted, significantly less fatigue impact, increased self-efficacy, and improved QOL (ie, 3 of 4 subscales expected to improve). There were no significant differences, as predicted, in any of the dependent variables after the control (ie, support group) and no intervention periods.
Results provide strong evidence for the efficacy of this energy conservation course for persons with MS.
The quality of life of multiple sclerosis (MS) patients was assessed using two MS specific quality of life measures (FAMS and SF-54) and a short generic measure (EuroQol) in order to make recommendations for routine assessment. Factors contributing to quality of life within this population were also considered.
Questionnaires were either sent by post or completed at interview. Ninety-six MS patients known to a consultant in rehabilitation medicine completed the questionnaires.
Patients scored very low on subscales related to physical health. Correlations were high between the FAMS and SF-54 but low with the EuroQoL. Stepwise multiple linear regressions showed mood measures to account for the most variance on all quality of life composite scores. The MS patients within the study had much lower SF-36 quality of life scores than the general population and other illness groups.
The EuroQol did not measure the same aspects of quality of life as the FAMS and SF-54 and was not found to be a sensitive measure within this sample. The SF-54 suffered from floor effects on physical health subscales and therefore the FAMS was recommended.
To study if the use of a cooling-suit by individuals with multiple sclerosis (MS) influenced their experience of fatigue and consequent restrictions in daily life.
The majority of MS patients consider fatigue as one of their most disabling symptoms and as having a significant impact on their daily lives. Fatigue often increases in a warm environment. A cooling-suit has been reported as a practical method of cooling, but the effect on fatigue has not yet been studied.
Eight individuals used a cooling-suit in their own homes during a test-period. In a single case-control design, their experience of fatigue was studied before and after. Quantitative and qualitative methods were used: self-assessments using the Fatigue Impact Scale (FIS), open-ended interviews and semi-structured diaries.
All study participants reported a reduction in fatigue during the test period. On the FIS, they scored reductions in the physical, cognitive and psycho-social dimensions of daily life. They experienced fatigue less often and for shorter periods. In their diaries and interviews they described decreased muscular strain, less sense of fatigue in relation to intake of food and positive effects on cognitive, social or affective problems related to fatigue.
The cooling-suit is a practical method for cooling. It gives freedom and flexibility and can be used regardless of setting. Nurses who meet heat-sensitive individuals with MS have the opportunity to give information on cooling methods, including how to use a cooling-suit. In this pilot study we found that individuals with MS who suffered from fatigue reported a number of improvements in quality of daily life.
The result indicates that use of a cooling-suit by individuals with MS may decrease their sense of fatigue. In this sample positive outcomes on daily life situations were reported. Further studies are needed to support these results.
To investigate the quantitative impact of fatigue on health-related quality of life (HRQoL) in multiple sclerosis (MS) and to determine whether fatigue was related to HRQoL independently from bodily disability, data on HRQoL were ascertained for 87 patients with definite MS by using the SF-36. HRQoL scores and subscores were related to the basic MS disability score (EDSS) and further MS parameters, and to fatigue, which was assessed by using different fatigue scales. Factors related to predominantly physical but not mental HRQoL aspects were identified as related to EDSS, duration of disease, and age. Different fatigue scores did impact significantly on both physical and especially mental HRQoL. The influence of fatigue on physical HRQoL was independent from EDSS. Fatigue experience reduces HRQoL markedly and independently from EDSS. Therefore, fatigue assessment provides additional information to disability-derived scales such as the EDSS with relevant implications for therapeutic decisions.
It is well accepted that rehabilitative treatment can be effective in reducing disability and optimizing quality of life (QoL) of people with multiple sclerosis (MS). The aim of this study was to evaluate the effects of a comprehensive outpatient rehabilitative treatment on QoL in patients suffering from MS. We selected 111 patients from a sample of 407 patients who had consecutively entered the MS Center of Catania (which is located in southern Italy) in 1998. Fifty-eight were randomly assigned to the study treatment and 53 to a waiting list (control treatment). Kurtzke's EDSS and quality of Life (QoL)were the primary endpoints. QoL was measured with the generic multi-item SF-36 scales. We also used: the Beck Depression Inventory (BDI) for depression, the Tempelaar Social Experience Check-list (SET) for social activities and the Fatigue Impact Scale (FIS). The study treatment group was treated for 6 consecutive weeks, 6 days a week with a comprehensive rehabilitative outpatient model. The control treatment group was in a waiting list and was trained to self-exercises at home. EDSS remained unchanged in both groups. All health related QoL domains significantly improved in the study treatment (p < 0.001 in physical functioning, role physical, bodily pain, general health, and social functioning; p < 0.05 in vitality, role emotional and mental health). FIS, SET and BDI also improved significantly after the rehabilitative treatment in the study group (p < 0.001). The results of this study confirm the effectiveness of a short comprehensive outpatient model of rehabilitative treatment in people with MS and in particular in their QoL.
Quality of Life (QOL) is impaired in multiple sclerosis (MS) in part due to physical disability. MS-associated fatigue (MSF) and depression (MSD) are common and treatable features of MS, which could also impact on QOL, independent of physical disability. We prospectively studied 60 consecutive patients with MS. QOL was assessed using Multiple Sclerosis Quality of Life (MSQOL)-54. Group differences in QOL scores were assessed after adjusting for Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS) and Hamilton Depression Inventory scores. MS patients were grouped into relapsing-remitting (RR) or secondary-progressive (SP), MSF (FSS> or =5) or MS-nonfatigue (MSNF) (FSS< or =4), and MSD or MS-nondepression (MSND). After accounting for disability and depression, fatigue was associated with impaired QOL with respect to health perception (p=0.03) and limitations due to physical dysfunction (p=0.008). After accounting for disability and fatigue, depression was associated with lower QOL with respect to health perception (p=0.02), sexual dysfunction (p=0.03), health distress (p=0.03), mental health (p=0.006), overall QOL (p=0.006), emotional dysfunction (p=0.04), and limitations due to emotional dysfunction (p=0.03). This study demonstrates that fatigue and depression are independently associated with impaired QOL in MS, after accounting for physical disability, suggesting that their recognition and treatment can potentially improve QOL.
Introduction and method:
In recent years the need to create scales for measuring the dysfunction or impairment suffered by patients with multiple sclerosis has increased. The aim of the scales that measure neurological impairment is two fold: to homogenise the data from different series so that studies into the prognosis and natural history of the disease can be compared, and to measure the changes in the progress of the disease when a therapy has been established. Over the past few years a large number of scales have appeared that attempt to redress the shortcomings of the EDSS (Expanded Disability Status Scale). The latest of these, the MSF Composite, manages to overcome the statistical problems of the EDSS and enables significant differences between two groups to be detected when studying the effect of a treatment.
Conclusions:
In the coming years we will possibly witness a joint use of several of the scales described, and both the EDSS and the Composite will be employed together in the evaluation of patients in therapeutic protocols, perhaps together with a quality of life scale.
Magnitude differences in scores on a measure of quality of life that correspond to differences in function or clinical course are called clinically important differences (CIDs). Anchor-based and distribution-based methods were used to provide ranges of CIDs for five targeted scale scores of the Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire. Three samples of cancer patients were used: Sample 1 included 50 patients participating in a validation study of the FACT-An; Sample 2 included 131 patients participating in a longitudinal study of chemotherapy-induced fatigue; sample 3 included 2,402 patients enrolled in a community-based clinical trial evaluating the effectiveness and safety of a treatment for anemia. Three clinical indicators (hemoglobin level; performance status; response to treatment) were used to determine anchor-based differences. One-half of the standard deviation and 1 standard error of measurement were used as distribution-based criteria. Analyses supported the following whole number estimates of a minimal CID for these five targeted scores: Fatigue Scale = 3.0; FACT-G total score = 4.0; FACT-An total score = 7.0; Trial Outcome Index-Fatigue = 5.0; and Trial Outcome Index-Anemia = 6.0. These estimates provide a basis for sample size estimation when planning for a clinical trial or other longitudinal study, when the purpose is to ensure detection of meaningful change over time. They can also be used in conjunction with more traditional clinical markers to assist investigators in determining treatment efficacy.
To compare methods of assessing fatigue.
Cross sectional.
Community.
Forty Multile Sclerosis (MS) patients and 20 healthy controls.
Fatigue questionnaires, SDSA dot cancellation test, finger tapping test, TEA Lottery.
The MS patients had significantly higher levels of fatigue than the controls on the Task Induced Fatigue Scale, Fatigue Severity Scale and Fatigue Impact Scale. The Task Induced Fatigue Scale completed whilst imagining oneself driving and the Fatigue Assessment Instrument did not differentiate between MS patients and controls. Finger tapping differentiated between MS patients and controls but there was no significant difference between MS patients and controls on visual and auditory concentration tests. A factor analysis indicated that questionnaire measures of fatigue were interrelated but independent of objective test performance.
Questionnaire measures can be used to assess fatigue in people with MS. The FSS differentiated MS patients from controls and is relatively short. It was therefore recommended for clinical use.
To determine distribution- and anchor-based minimal important difference (MID) estimates for four scores from the Functional Assessment of Cancer Therapy-Breast (FACT-B): the breast cancer subscale (BCS), Trial Outcome Index (TOI), FACT-G (the general version), and FACT-B.
We used data from a Phase III clinical trial in metastatic breast cancer (ECOG study 1193; n=739) and a prospective observational study of pain in metastatic breast cancer (n=129). One third and one half of the standard deviation and 1 standard error of measurement were used as distribution-based criteria. Clinical indicators used to determine anchor-based differences included ECOG performance status, current pain, and response to treatment.
FACT-B scores were responsive to performance status and pain anchors, but not to treatment response. By combining the results of distribution- and anchor-based methods, MID estimates were obtained: BCS=2-3 points, TOI=5-6 points, FACT-G=5-6 points, and FACT-B=7-8 points.
Distribution- and anchor-based estimates of the MID do show convergence. These estimates can be used in combination with other measures of efficacy to determine meaningful benefit and provide a basis for sample size estimation in clinical trials.