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      Neurocognitive and functional impairment in adult and paediatric tuberculous meningitis

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          Abstract

          In those who survive tuberculous meningitis (TBM), the long-term outcome is uncertain; individuals may suffer neurocognitive, functional and psychiatric impairment, which may significantly affect their ability to lead their lives as they did prior to their diagnosis of TBM. In children who survive, severe illness has occurred at a crucial timepoint in their development, which can lead to behavioural and cognitive delay. The extent and nature of this impairment is poorly understood, particularly in adults. This is in part due to a lack of observational studies in this area but also inconsistent inclusion of outcome measures which can quantify these deficits in clinical studies. This leads to a paucity of appropriate rehabilitative therapies available for these individuals and their caregivers, as well as burden at a socioeconomic level. In this review, we discuss what is known about neurocognitive impairment in TBM, draw on lessons learnt from other neurological infections and discuss currently available and emerging tools to evaluate function and cognition and their value in TBM. We make recommendations on which measures should be used at what timepoints to assess for impairment, with a view to optimising and standardising assessment of neurocognitive and functional impairment in TBM research.

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          The Barthel ADL Index: a reliability study.

          The Barthel Index is a valid measure of disability. In this study we investigated the reliability of four different methods of obtaining the score in 25 patients: self-report, asking a trained nurse who had worked with the patient for at least one shift, and separate testing by two skilled observers within 72 hours of admission. Analysis of total (summed) scores revealed a close correlation between all four methods: a difference of 4/20 points was likely to reflect a genuine difference. In individual items, most disagreement was minor and involved the definition of middle grades. Asking an informed nurse or relative was as reliable as testing, and is quicker.
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            Barthel index for stroke trials: development, properties, and application.

            Robust measures of functional outcome are required to determine treatment effects in stroke trials. Of the various measures available, the Barthel index (BI) is one of the more prevalent. We aimed to describe validity, reliability, and responsiveness (clinimetric properties) of the BI in stroke trials. Narrative review of published articles describing clinimetric properties or use of the BI as a stroke trial end point. Definitive statements on properties of BI are limited by heterogeneity in methodology of assessment and in the content of "BI" scales. Accepting these caveats, evidence suggests that BI is a valid measure of activities of daily living; sensitivity to change is limited at extremes of disability (floor and ceiling effects), and reliability of standard BI assessment is acceptable. However, these data may not be applicable to contemporary multicenter stroke trials. Substantial literature describing BI clinimetrics in stroke is available; however, questions remain regarding certain properties. The "BI" label is used for a number of instruments and we urge greater consistency in methods, content, and scoring. A 10-item scale, scoring 0 to 100 with 5-point increments, has been used in several multicenter stroke trials and it seems reasonable that this should become the uniform stroke trial BI.
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              Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin Scale.

              The modified Rankin Scale is widely used to assess changes in activity and lifestyle after stroke, but it has been criticized for its subjectivity. The purpose of the present study was to compare conventional assessment on the modified Rankin Scale with assessment through a structured interview. Sixty-three patients with stroke 6 to 24 months previously were interviewed and graded independently on the modified Rankin Scale by 2 observers. These observers then underwent training in use of a structured interview for the scale that covered 5 areas of everyday function. Eight weeks after the first assessment, the same observers reassessed 58 of these patients using the structured interview. Interrater reliability was measured with the kappa statistic (weighted with quadratic weights). For the scale applied conventionally, overall agreement between the 2 raters was 57% (kappa(w)=0.78); 1 rater assigned significantly lower grades than the other (P=0.048). On the structured interview, the overall agreement between raters was 78% (kappa(w)=0.93), and there was no overall difference between raters in grades assigned (P=0.17). Rankin grades from the conventional assessment and the structured interview were highly correlated, but there was significantly less disagreement between raters when the structured interview was used (P=0.004). Variability and bias between raters in assigning patients to Rankin grades may be reduced by use of a structured interview. Use of a structured interview for the scale could potentially improve the quality of results from clinical studies in stroke.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Review & Editing
                Role: ConceptualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Journal
                Wellcome Open Res
                Wellcome Open Res
                Wellcome Open Res
                Wellcome Open Research
                F1000 Research Limited (London, UK )
                2398-502X
                13 November 2019
                2019
                : 4
                : 178
                Affiliations
                [1 ]University College London, Gower Street, London, WC1E 6BT, UK
                [2 ]Francis Crick Institute, Midland Road, London, NW1 1AT, UK
                [3 ]Institute of Infectious Diseases and Molecular Medicine. Department of Medicine, University of Cape Town, Observatory, 7925, South Africa
                [4 ]HIV Mental Health Research Unit, University of Cape Town,, Observatory, 7925, South Africa
                [5 ]Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
                [6 ]The Institute for Rehabilitation and Research Memorial Hermann, Department of Rehabilitation Psychology and Neuropsychology,, Houston, Texas, USA
                [7 ]Baylor College of Medicine, Department of Physical Medicine and Rehabilitation, Houston, Texas, USA
                [8 ]Department of Infectious Diseases, Imperial College London, London, W2 1PG, UK
                [9 ]Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Diseases and Molecular Medicine at Department of Medicine, University of Cape Town, Observatory, 7925, South Africa
                [10 ]MRC Clinical Trials Unit at UCL, University College London, London, WC1E 6BT, UK
                [11 ]Evelina Community, Guys and St Thomas’ NHS Trust, 5 Dugard Way, London, SE11 4TH, UK
                [12 ]Weill Institute of Neurosciences, Department of Neurology and Division of Infectious Diseases, University of California, San Francisco, California, USA
                [1 ]Blizard Institute, Queen Mary University of London, London, UK
                [2 ]Barts Health NHS Trust, London, UK
                [1 ]HIV Center for Clinical and Behavioral Studies, New York State Psychiatric Institute, New York City, NY, USA
                Author notes

                No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0001-8914-5094
                https://orcid.org/0000-0001-8882-5688
                https://orcid.org/0000-0002-5607-8443
                https://orcid.org/0000-0002-2753-1800
                https://orcid.org/0000-0001-9440-9349
                Article
                10.12688/wellcomeopenres.15516.1
                6971841
                31984243
                22cbd52f-57cf-45df-9049-92b032b1623e
                Copyright: © 2019 Davis AG et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 November 2019
                Funding
                Funded by: Cancer Research UK
                Award ID: FCOO10208
                Funded by: Meningitis Now
                Funded by: National Institutes of Health
                Award ID: R21TW011035
                Funded by: Newton Fund
                Funded by: National Research Foundation of South Africa
                Award ID: 109437
                Funded by: Wellcome Trust
                Award ID: 104803
                Funded by: Wellcome Trust
                Award ID: 203135
                Funded by: Wellcome Trust
                Award ID: 175479
                Funded by: Wellcome Trust
                Award ID: FCOO10218
                AGD is supported through a UCL Wellcome Trust PhD Programme for Clinicians Fellowship (award number 175479). SN is supported by the Newton Fund Grant for the CONNECT study. RS is supported by the National Research Foundation of South Africa, Grant Number 109437. RJW is supported by Wellcome (104803, 203135); Francis Crick Institute which receives support from Wellcome (FCOO10218), CRUK (FCOO10208); Meningitis Now; and EDCTP. FCC is supported by the National Institutes of Health/Fogarty International Center (R21TW011035). This work was supported by the Wellcome Trust through funding to the Tuberculous Meningitis International Research Consortium.
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Articles

                tuberculous meningitis,neurocognitive,functional,neurobehavioural,neurodevelopmental,psychiatric

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