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      A Nation-Wide, Multi-Center Study on the Quality of Life of ALS Patients in Germany

      research-article
      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 16 , 17 , 18 , 19 , 1 , 1 , 1 , 18 , 20 , 21 , 19 , 19 , 22 , 23 , 24 , 5 , 2 , 2 , 1 , 1 , *
      Brain Sciences
      MDPI
      Amyotrophic Lateral Sclerosis (ALS), Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5), ALS treatment, “bulbar-onset” ALS (bALS), “limb-onset” ALS (lALS), EuroQol Five Dimension Five Level Scale (EQ-5D-5L), health-related quality of life (HRQoL), quality of life (QoL), symptom-specific treatment, assistive devices

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          Abstract

          Improving quality of life (QoL) is central to amyotrophic lateral sclerosis (ALS) treatment. This Germany-wide, multicenter cross-sectional study analyses the impact of different symptom-specific treatments and ALS variants on QoL. Health-related QoL (HRQoL) in 325 ALS patients was assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) and EuroQol Five Dimension Five Level Scale (EQ-5D-5L), together with disease severity (captured by the revised ALS Functional Rating Scale (ALSFRS-R)) and the current care and therapies used by our cohort. At inclusion, the mean ALSAQ-5 total score was 56.93 (max. 100, best = 0) with a better QoL associated with a less severe disease status (β = −1.96 per increase of one point in the ALSFRS-R score, p < 0.001). “Limb-onset” ALS ( lALS) was associated with a better QoL than “bulbar-onset” ALS ( bALS) (mean ALSAQ-5 total score 55.46 versus 60.99, p = 0.040). Moreover, with the ALSFRS-R as a covariate, using a mobility aid (β = −7.60, p = 0.001), being tracheostomized (β = −14.80, p = 0.004) and using non-invasive ventilation (β = −5.71, p = 0.030) were associated with an improved QoL, compared to those at the same disease stage who did not use these aids. In contrast, antidepressant intake (β = 5.95, p = 0.007), and increasing age (β = 0.18, p = 0.023) were predictors of worse QoL. Our results showed that the ALSAQ-5 was better-suited for ALS patients than the EQ-5D-5L. Further, the early and symptom-specific clinical management and supply of assistive devices can significantly improve the individual HRQoL of ALS patients. Appropriate QoL questionnaires are needed to monitor the impact of treatment to provide the best possible and individualized care.

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          The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies.

          Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. 18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available on the Web sites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.
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            Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L)

            Purpose This article introduces the new 5-level EQ-5D (EQ-5D-5L) health status measure. Methods EQ-5D currently measures health using three levels of severity in five dimensions. A EuroQol Group task force was established to find ways of improving the instrument’s sensitivity and reducing ceiling effects by increasing the number of severity levels. The study was performed in the United Kingdom and Spain. Severity labels for 5 levels in each dimension were identified using response scaling. Focus groups were used to investigate the face and content validity of the new versions, including hypothetical health states generated from those versions. Results Selecting labels at approximately the 25th, 50th, and 75th centiles produced two alternative 5-level versions. Focus group work showed a slight preference for the wording ‘slight-moderate-severe’ problems, with anchors of ‘no problems’ and ‘unable to do’ in the EQ-5D functional dimensions. Similar wording was used in the Pain/Discomfort and Anxiety/Depression dimensions. Hypothetical health states were well understood though participants stressed the need for the internal coherence of health states. Conclusions A 5-level version of the EQ-5D has been developed by the EuroQol Group. Further testing is required to determine whether the new version improves sensitivity and reduces ceiling effects.
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              Making sense of Cronbach's alpha

              Medical educators attempt to create reliable and valid tests and questionnaires in order to enhance the accuracy of their assessment and evaluations. Validity and reliability are two fundamental elements in the evaluation of a measurement instrument. Instruments can be conventional knowledge, skill or attitude tests, clinical simulations or survey questionnaires. Instruments can measure concepts, psychomotor skills or affective values. Validity is concerned with the extent to which an instrument measures what it is intended to measure. Reliability is concerned with the ability of an instrument to measure consistently. 1 It should be noted that the reliability of an instrument is closely associated with its validity. An instrument cannot be valid unless it is reliable. However, the reliability of an instrument does not depend on its validity. 2 It is possible to objectively measure the reliability of an instrument and in this paper we explain the meaning of Cronbach’s alpha, the most widely used objective measure of reliability. Calculating alpha has become common practice in medical education research when multiple-item measures of a concept or construct are employed. This is because it is easier to use in comparison to other estimates (e.g. test-retest reliability estimates) 3 as it only requires one test administration. However, in spite of the widespread use of alpha in the literature the meaning, proper use and interpretation of alpha is not clearly understood. 2 , 4 , 5 We feel it is important, therefore, to further explain the underlying assumptions behind alpha in order to promote its more effective use. It should be emphasised that the purpose of this brief overview is just to focus on Cronbach’s alpha as an index of reliability. Alternative methods of measuring reliability based on other psychometric methods, such as generalisability theory or item-response theory, can be used for monitoring and improving the quality of OSCE examinations 6 - 10 , but will not be discussed here. What is Cronbach alpha? Alpha was developed by Lee Cronbach in 1951 11 to provide a measure of the internal consistency of a test or scale; it is expressed as a number between 0 and 1. Internal consistency describes the extent to which all the items in a test measure the same concept or construct and hence it is connected to the inter-relatedness of the items within the test. Internal consistency should be determined before a test can be employed for research or examination purposes to ensure validity. In addition, reliability estimates show the amount of measurement error in a test. Put simply, this interpretation of reliability is the correlation of test with itself. Squaring this correlation and subtracting from 1.00 produces the index of measurement error. For example, if a test has a reliability of 0.80, there is 0.36 error variance (random error) in the scores (0.80×0.80 = 0.64; 1.00 – 0.64 = 0.36). 12 As the estimate of reliability increases, the fraction of a test score that is attributable to error will decrease. 2 It is of note that the reliability of a test reveals the effect of measurement error on the observed score of a student cohort rather than on an individual student. To calculate the effect of measurement error on the observed score of an individual student, the standard error of measurement must be calculated (SEM). 13 If the items in a test are correlated to each other, the value of alpha is increased. However, a high coefficient alpha does not always mean a high degree of internal consistency. This is because alpha is also affected by the length of the test. If the test length is too short, the value of alpha is reduced. 2 , 14 Thus, to increase alpha, more related items testing the same concept should be added to the test. It is also important to note that alpha is a property of the scores on a test from a specific sample of testees. Therefore investigators should not rely on published alpha estimates and should measure alpha each time the test is administered. 14 Use of Cronbach’s alpha Improper use of alpha can lead to situations in which either a test or scale is wrongly discarded or the test is criticised for not generating trustworthy results. To avoid this situation an understanding of the associated concepts of internal consistency, homogeneity or unidimensionality can help to improve the use of alpha. Internal consistency is concerned with the interrelatedness of a sample of test items, whereas homogeneity refers to unidimensionality. A measure is said to be unidimensional if its items measure a single latent trait or construct. Internal consistency is a necessary but not sufficient condition for measuring homogeneity or unidimensionality in a sample of test items. 5 , 15 Fundamentally, the concept of reliability assumes that unidimensionality exists in a sample of test items 16 and if this assumption is violated it does cause a major underestimate of reliability. It has been well documented that a multidimensional test does not necessary have a lower alpha than a unidimensional test. Thus a more rigorous view of alpha is that it cannot simply be interpreted as an index for the internal consistency of a test. 5 , 15 , 17 Factor Analysis can be used to identify the dimensions of a test. 18 Other reliable techniques have been used and we encourage the reader to consult the paper “Applied Dimensionality and Test Structure Assessment with the START-M Mathematics Test” and to compare methods for assessing the dimensionality and underlying structure of a test. 19 Alpha, therefore, does not simply measure the unidimensionality of a set of items, but can be used to confirm whether or not a sample of items is actually unidimensional. 5 On the other hand if a test has more than one concept or construct, it may not make sense to report alpha for the test as a whole as the larger number of questions will inevitable inflate the value of alpha. In principle therefore, alpha should be calculated for each of the concepts rather than for the entire test or scale. 2 , 3 The implication for a summative examination containing heterogeneous, case-based questions is that alpha should be calculated for each case. More importantly, alpha is grounded in the ‘tau equivalent model’ which assumes that each test item measures the same latent trait on the same scale. Therefore, if multiple factors/traits underlie the items on a scale, as revealed by Factor Analysis, this assumption is violated and alpha underestimates the reliability of the test. 17 If the number of test items is too small it will also violate the assumption of tau-equivalence and will underestimate reliability. 20 When test items meet the assumptions of the tau-equivalent model, alpha approaches a better estimate of reliability. In practice, Cronbach’s alpha is a lower-bound estimate of reliability because heterogeneous test items would violate the assumptions of the tau-equivalent model. 5 If the calculation of “standardised item alpha” in SPSS is higher than “Cronbach’s alpha”, a further examination of the tau-equivalent measurement in the data may be essential. Numerical values of alpha As pointed out earlier, the number of test items, item inter-relatedness and dimensionality affect the value of alpha. 5 There are different reports about the acceptable values of alpha, ranging from 0.70 to 0.95. 2 , 21 , 22 A low value of alpha could be due to a low number of questions, poor inter-relatedness between items or heterogeneous constructs. For example if a low alpha is due to poor correlation between items then some should be revised or discarded. The easiest method to find them is to compute the correlation of each test item with the total score test; items with low correlations (approaching zero) are deleted. If alpha is too high it may suggest that some items are redundant as they are testing the same question but in a different guise. A maximum alpha value of 0.90 has been recommended. 14 Summary High quality tests are important to evaluate the reliability of data supplied in an examination or a research study. Alpha is a commonly employed index of test reliability. Alpha is affected by the test length and dimensionality. Alpha as an index of reliability should follow the assumptions of the essentially tau-equivalent approach. A low alpha appears if these assumptions are not meet. Alpha does not simply measure test homogeneity or unidimensionality as test reliability is a function of test length. A longer test increases the reliability of a test regardless of whether the test is homogenous or not. A high value of alpha (> 0.90) may suggest redundancies and show that the test length should be shortened. Conclusions Alpha is an important concept in the evaluation of assessments and questionnaires. It is mandatory that assessors and researchers should estimate this quantity to add validity and accuracy to the interpretation of their data. Nevertheless alpha has frequently been reported in an uncritical way and without adequate understanding and interpretation. In this editorial we have attempted to explain the assumptions underlying the calculation of alpha, the factors influencing its magnitude and the ways in which its value can be interpreted. We hope that investigators in future will be more critical when reporting values of alpha in their studies.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Brain Sci
                Brain Sci
                brainsci
                Brain Sciences
                MDPI
                2076-3425
                14 March 2021
                March 2021
                : 11
                : 3
                : 372
                Affiliations
                [1 ]Department of Neurology, Hannover Medical School, 30625 Hannover, Germany; Peseschkian.Tara@ 123456mh-hannover.de (T.P.); Erik.Schoenfelder@ 123456stud.mh-hannover.de (E.S.); Felix.Heinrich@ 123456stud.mh-hannover.de (F.H.); dr.almaosmanovic@ 123456gmail.com (A.O.); Petri.Susanne@ 123456mh-hannover.de (S.P.)
                [2 ]Department of Neurology, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany; isabell.cordts@ 123456tum.de (I.C.); marcus.deschauer@ 123456mri.tum.de (M.D.); paul.lingor@ 123456tum.de (P.L.)
                [3 ]Department of Neurology, University Hospital Carl Gustav Carus, 01307 Dresden, Germany; Rene.Guenther@ 123456uniklinikum-dresden.de
                [4 ]German Center for Neurodegenerative Diseases (DZNE), 01307 Dresden, Germany
                [5 ]Department of Neurology, University Medicine Essen, 45147 Essen, Germany; benjamin.stolte@ 123456uk-essen.de (B.S.); tim.hagenacker@ 123456uk-essen.de (T.H.)
                [6 ]Department of Neurology, University of Würzburg, 97080 Würzburg, Germany; Zeller_D@ 123456ukw.de
                [7 ]Hoher Meißner Clinic, Neurology, 37242 Bad Sooden-Allendorf, Germany; Schroeter@ 123456reha-klinik.de
                [8 ]Department of Neurology, Ruhr-University Bochum, BG-Kliniken Bergmannsheil, 44789 Bochum, Germany; ute.weyen@ 123456bergmannsheil.de
                [9 ]Department of Molecular Neurology, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany; Martin.Regensburger@ 123456uk-erlangen.de
                [10 ]Department of Neurology, Diakonissen Hospital Mannheim, 68163 Mannheim, Germany; j.wolf@ 123456diako-mannheim.de
                [11 ]Department of Neurology, Martin-Luther University Halle/Saale, 06120 Halle, Germany; Ilka.Schneider@ 123456sanktgeorg.de
                [12 ]Department of Neurology, Klinikum Sankt Georg, 04129 Leipzig, Germany
                [13 ]Translational Neurodegeneration Section “Albrecht-Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany; Andreas.Hermann@ 123456med.uni-rostock.de
                [14 ]German Center for Neurodegenerative Diseases Rostock/Greifswald, 18147 Rostock, Germany
                [15 ]Department of Neurology, University Hospital Leipzig, 04103 Leipzig, Germany; Moritz.Metelmann@ 123456medizin.uni-leipzig.de
                [16 ]Department of Neurology, University of Regensburg, 93053 Regensburg, Germany; zacharias.kohl@ 123456klinik.uni-regensburg.de (Z.K.); Ralf.Linker@ 123456klinik.uni-regensburg.de (R.A.L.)
                [17 ]Department of Neurology, University Medicine Göttingen, 37075 Göttingen, Germany; jkoch@ 123456med.uni-goettingen.de
                [18 ]Friedrich-Baur Institute, Department of Neurology, University Hospital, Ludwig Maximilian University of Munich, 80336 Munich, Germany; Boriana.Buechner@ 123456med.uni-muenchen.de (B.B.); Thomas.Klopstock@ 123456med.uni-muenchen.de (T.K.)
                [19 ]Department of Neurology, University of Ulm, 89081 Ulm, Germany; Ulrike.Weiland@ 123456uniklinik-ulm.de (U.W.); johannes.dorst@ 123456rku.de (J.D.); albert.ludolph@ 123456rku.de (A.C.L.)
                [20 ]Munich Cluster for Systems Neurology (SyNergy), 80336 Munich, Germany
                [21 ]German Center for Neurodegenerative Diseases (DZNE), 80336 Munich, Germany
                [22 ]German Center for Neurodegenerative Diseases (DZNE), 89081 Ulm, Germany
                [23 ]Department of Neurology with the Institute of Translational Neurology, University Hospital Münster, 48149 Münster, Germany; Matthias.Boentert@ 123456ukmuenster.de
                [24 ]Department of Medicine, UKM Marienhospital, 48565 Steinfurt, Germany
                Author notes
                Author information
                https://orcid.org/0000-0003-0329-5644
                https://orcid.org/0000-0002-2774-067X
                https://orcid.org/0000-0002-2172-7386
                https://orcid.org/0000-0002-7364-7791
                https://orcid.org/0000-0002-4147-8866
                https://orcid.org/0000-0002-1241-3684
                https://orcid.org/0000-0002-6012-8423
                https://orcid.org/0000-0001-6133-1397
                https://orcid.org/0000-0002-3631-3450
                https://orcid.org/0000-0001-9362-7096
                https://orcid.org/0000-0001-5621-4487
                Article
                brainsci-11-00372
                10.3390/brainsci11030372
                7998410
                33799476
                0cea7485-416a-450e-9844-8fabcae7bf00
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 February 2021
                : 10 March 2021
                Categories
                Article

                amyotrophic lateral sclerosis (als),amyotrophic lateral sclerosis assessment questionnaire 5 (alsaq-5),als treatment,“bulbar-onset” als (bals),“limb-onset” als (lals),euroqol five dimension five level scale (eq-5d-5l),health-related quality of life (hrqol),quality of life (qol),symptom-specific treatment,assistive devices

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