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      Predicting one-year outcome in first episode psychosis using machine learning

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          Abstract

          Background

          Early illness course correlates with long-term outcome in psychosis. Accurate prediction could allow more focused intervention. Earlier intervention corresponds to significantly better symptomatic and functional outcomes. Our study objective is to use routinely collected baseline demographic and clinical characteristics to predict employment, education or training (EET) status, and symptom remission in patients with first episode psychosis (FEP) at one-year.

          Methods and findings

          83 FEP patients were recruited from National Health Service (NHS) Glasgow between 2011 and 2014 to a 24-month prospective cohort study with regular assessment of demographic and psychometric measures. An external independent cohort of 79 FEP patients were recruited from NHS Glasgow and Edinburgh during a 12-month study between 2006 and 2009. Elastic net regularised logistic regression models were built to predict binary EET status, period and point remission outcomes at one-year on 83 Glasgow patients (training dataset). Models were externally validated on an independent dataset of 79 patients from Glasgow and Edinburgh (validation dataset). Only baseline predictors shared across both cohorts were made available for model training and validation. After excluding participants with missing outcomes, models were built on the training dataset for EET status, period and point remission outcomes and externally validated on the validation dataset. Models predicted EET status, period and point remission with receiver operating curve (ROC) area under the curve (AUC) performances of 0.876 (95%CI: 0.864, 0.887), 0.630 (95%CI: 0.612, 0.647) and 0.652 (95%CI: 0.635, 0.670) respectively. Positive predictors of EET included baseline EET and living with spouse/children. Negative predictors included higher PANSS suspiciousness, hostility and delusions scores. Positive predictors for symptom remission included living with spouse/children, and affective symptoms on the Positive and Negative Syndrome Scale (PANSS). Negative predictors of remission included passive social withdrawal symptoms on PANSS. A key limitation of this study is the small sample size (n) relative to the number of predictors (p), whereby p approaches n. The use of elastic net regularised regression rather than ordinary least squares regression helped circumvent this difficulty. Further, we did not have information for biological and additional social variables, such as nicotine dependence, which observational studies have linked to outcomes in psychosis.

          Conclusions and relevance

          Using advanced statistical machine learning techniques, we provide the first externally validated evidence, in a temporally and geographically independent cohort, for the ability to predict one-year EET status and symptom remission in individual FEP patients.

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          Most cited references40

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          The positive and negative syndrome scale (PANSS) for schizophrenia.

          The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
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            Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review.

            Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.
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              Assessing the generalizability of prognostic information.

              Physicians are often asked to make prognostic assessments but often worry that their assessments will prove inaccurate. Prognostic systems were developed to enhance the accuracy of such assessments. This paper describes an approach for evaluating prognostic systems based on the accuracy (calibration and discrimination) and generalizability (reproducibility and transportability) of the system's predictions. Reproducibility is the ability to produce accurate predictions among patients not included in the development of the system but from the same population. Transportability is the ability to produce accurate predictions among patients drawn from a different but plausibly related population. On the basis of the observation that the generalizability of a prognostic system is commonly limited to a single historical period, geographic location, methodologic approach, disease spectrum, or follow-up interval, we describe a working hierarchy of the cumulative generalizability of prognostic systems. This approach is illustrated in a structured review of the Dukes and Jass staging systems for colon and rectal cancer and applied to a young man with colon cancer. Because it treats the development of the system as a "black box" and evaluates only the performance of the predictions, the approach can be applied to any system that generates predicted probabilities. Although the Dukes and Jass staging systems are discrete, the approach can also be applied to systems that generate continuous predictions and, with some modification, to systems that predict over multiple time periods. Like any scientific hypothesis, the generalizability of a prognostic system is established by being tested and being found accurate across increasingly diverse settings. The more numerous and diverse the settings in which the system is tested and found accurate, the more likely it will generalize to an untested setting.
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                Author and article information

                Contributors
                Role: Formal analysisRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – original draft
                Role: Data curationRole: Project administration
                Role: Data curationRole: Funding acquisition
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Funding acquisitionRole: MethodologyRole: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 March 2019
                2019
                : 14
                : 3
                : e0212846
                Affiliations
                [1 ] Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom
                [2 ] Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom
                [3 ] ESTEEM First Episode Psychosis Service, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom
                [4 ] Department of Clinical & Health Psychology, University of Edinburgh, Edinburgh, United Kingdom
                Universita degli Studi di Napoli Federico II, ITALY
                Author notes

                Competing Interests: Andrew Gumley has been commissioned by NHS Education for Scotland to provide training for NHS staff in early intervention for psychosis, psychosocial interventions for psychosis and CBT. Jonathan Cavanagh is part of the Wellcome Trust-funded consortium on the Neuroimmunology of Mood and Alzheimer’s. In addition to the academic partners, this consortium includes industrial collaborators: GSK, Lundbeck, Pfizer and Janssen. GSK, Lundbeck, Pfizer and Janssen are commercial funders; this does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors declare no conflict of interest involving the work under consideration for publication.

                ‡ These authors are joint senior authors on this work.

                Author information
                http://orcid.org/0000-0002-3999-4204
                http://orcid.org/0000-0001-6845-5894
                http://orcid.org/0000-0002-8888-938X
                Article
                PONE-D-18-14368
                10.1371/journal.pone.0212846
                6405084
                30845268
                027abf63-c5a0-484a-b4d8-78951438765c
                © 2019 Leighton et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 May 2018
                : 11 February 2019
                Page count
                Figures: 4, Tables: 2, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000589, Chief Scientist Office;
                Award Recipient :
                The authors acknowledge funding and financial support from NHS Research Scotland (NRS), the Chief Scientist Office, the Wellcome Trust and of the Scottish Mental Health Research Network for various parts of the study.
                Categories
                Research Article
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Psychoses
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Forecasting
                Physical Sciences
                Mathematics
                Statistics
                Statistical Methods
                Forecasting
                Computer and Information Sciences
                Artificial Intelligence
                Machine Learning
                Social Sciences
                Economics
                Labor Economics
                Employment
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Biology and Life Sciences
                Psychology
                Psychometrics
                Social Sciences
                Psychology
                Psychometrics
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Mood Disorders
                Depression
                Medicine and Health Sciences
                Health Care
                Patients
                Custom metadata
                Data files are submitted within the Supporting Information files. In addition, the code is available from https://github.com/samleighton87/PONE-D-18-14368.

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