(2017) Predictors of survival in progressive supranuclear palsy and multiple system atrophy: a systematic review and meta-analysis. Journal of Neurology, Neurosurgery and Psychiatry, 88 (16). This version is available from Sussex Research Online: http://sro.sussex.ac.uk/67644/ This document is made available in accordance with publisher policies and may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the URL above for details on accessing the published version. Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. ABSTRACTObjective: To undertake a systematic review and meta-analysis of studies that investigated prognostic factors and survival in patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA).Methods: Publications of at least 10 patients with a likely or confirmed diagnosis of PSP or MSA were eligible for inclusion. Methodological quality was rated using a modified version of the Quality in Prognostic Studies tool. For frequently examined prognostic factors, hazard ratios (HR) derived by univariate and multivariate analysis were pooled in separate subgroups; other results were synthesised narratively and HRs could not be reported here. Results:Thirty-seven studies presenting findings on 6193 patients (1911 PSP, 4282 MSA) fulfilled the inclusion criteria. We identified the following variables as unfavourable predictors of survival: In PSP: PSP-Richardson's phenotype (univariate HR: 2.53; 95%CIs: 1.69, 3.78), early dysphagia and early cognitive symptoms. In MSA: severe dysautonomia and early development of combined autonomic and motor features but not MSA phenotype (multivariate HR: 1.22; 95%CIs: 0.83, 1.80).In PSP and MSA survival was predicted by early falls (multivariate HR: 2.32; 95%CIs: 1.94, 2.77), the NNIPPS Parkinson plus score and the Clinical Global Impression disease severity score but not sex (multivariate HR: 0.93; 95%CIs: 0.67, 1.28). There was conflicting evidence regarding the prognostic effect of age at onset and stridor. Conclusion:Several clinical variables were strongly associated with shorter survival in PSP and MSA. Results on most prognostic factors were consistent across methodologically diverse studies;...

The natural history of relapsing remitting multiple sclerosis (RRMS) is variable and prediction of individual prognosis challenging. The inability to reliably predict prognosis at diagnosis has important implications for informed decision making especially in relation to disease modifying therapies. We conducted a systematic review in order to collate, describe and assess the methodological quality of published prediction models in RRMS. We searched Medline, Embase and Web of Science. Two reviewers independently screened abstracts and full text for eligibility and assessed risk of bias. Studies reporting development or validation of prediction models for RRMS in adults were included. Data collection was guided by the checklist for critical appraisal and data extraction for systematic reviews (CHARMS) and applicability and methodological quality assessment by the prediction model risk of bias assessment tool (PROBAST). 30 studies were included in the review. Applicability was assessed as high risk of concern in 27 studies. Risk of bias was assessed as high for all studies. The single most frequently included predictor was baseline EDSS (n = 11). T2 Lesion volume or number and brain atrophy were each retained in seven studies. Five studies included external validation and none included impact analysis. Although a number of prediction models for RRMS have been reported, most are at high risk of bias and lack external validation and impact analysis, restricting their application to routine clinical practice.

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of phase II, phase II/III and phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15000 people with amyotrophic lateral sclerosis. 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis.

BackgroundLactate concentration is a robust predictor of mortality but in many low resource settings facilities for its analysis are not available. Anion gap (AG), calculated from clinical chemistry results, is a marker of metabolic acidosis and may be more easily obtained in such settings. In this systematic review and meta-analysis we investigated whether the AG predicts mortality in adult patients admitted to critical care settings.MethodsWe searched Medline, Embase, Web of Science, Scopus, The Cochrane Library and regional electronic databases from inception until May 2016. Studies conducted in any clinical setting that related AG to in-hospital mortality, in-intensive care unit mortality, 31-day mortality or comparable outcome measures were eligible for inclusion. Methodological quality of included studies was assessed using the Quality in Prognostic Studies tool. Descriptive meta-analysis was performed and the I2 test was used to quantify heterogeneity. Subgroup analysis was undertaken to identify potential sources of heterogeneity between studies.ResultsNineteen studies reporting findings in 12,497 patients were included. Overall, quality of studies was poor and most studies were rated as being at moderate or high risk of attrition bias and confounding. There was substantial diversity between studies with regards to clinical setting, age and mortality rates of patient cohorts. High statistical heterogeneity was found in the meta-analyses of area under the ROC curve (I2 = 99 %) and mean difference (I2 = 97 %) for the observed AG. Three studies reported good discriminatory power of the AG to predict mortality and were responsible for a large proportion of statistical heterogeneity. The remaining 16 studies reported poor to moderate ability of the AG to predict mortality. Subgroup analysis suggested that intravenous fluids affect the ability of the AG to predict mortality.ConclusionBased on the limited quality of available evidence, a single AG measurement cannot be recommended for risk stratification in critically ill patients. The probable influence of intravenous fluids on AG levels renders the AG an impractical tool in clinical practice. Future research should focus on increasing the availability of lactate monitoring in low resource settings.PROSPERO registration number CRD42015015249. Registered on 4th February 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s12871-016-0241-y) contains supplementary material, which is available to authorized users.