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Transdiagnostic individualized clinically-based risk calculator for the automatic detection of individuals at-risk and the prediction of psychosis: external replication in 2,430,333 US patients.

ABSTRACT: The real-world impact of psychosis prevention is reliant on effective strategies for identifying individuals at risk. A transdiagnostic, individualized, clinically-based risk calculator to improve this has been developed and externally validated twice in two different UK healthcare trusts with convincing results. The prognostic performance of this risk calculator outside the UK is unknown. All individuals who accessed primary or secondary health care services belonging to the IBM^® MarketScan^® Commercial Database between January 2015 and December 2017, and received a first ICD-10 index diagnosis of nonorganic/nonpsychotic mental disorder, were included. According to the risk calculator, age, gender, ethnicity, age-by-gender, and ICD-10 cluster diagnosis at index date were used to predict development of any ICD-10 nonorganic psychotic disorder. Because patient-level ethnicity data were not available city-level ethnicity proportions were used as proxy. The study included 2,430,333 patients with a mean follow-up of 15.36 months and cumulative incidence of psychosis at two years of 1.43%. There were profound differences compared to the original development UK database in terms of case-mix, psychosis incidence, distribution of baseline predictors (ICD-10 cluster diagnoses), availability of patient-level ethnicity data, follow-up time and availability of specialized clinical services for at-risk individuals. Despite these important differences, the model retained accuracy significantly above chance (Harrell's C?=?0.676, 95% CI: 0.672-0.679). To date, this is the largest international external replication of an individualized prognostic model in the field of psychiatry. This risk calculator is transportable on an international scale to improve the automatic detection of individuals at risk of psychosis.

SUBMITTER: Oliver D

PROVIDER: S-EPMC7596040 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Transdiagnostic individualized clinically-based risk calculator for the automatic detection of individuals at-risk and the prediction of psychosis: external replication in 2,430,333 US patients.

Oliver Dominic D Wong Chiew Meng Johnny CMJ Bøg Martin M Jönsson Linus L Kinon Bruce J BJ Wehnert Allan A Jørgensen Kristian Tore KT Irving Jessica J Stahl Daniel D McGuire Philip P Raket Lars Lau LL Fusar-Poli Paolo P

Translational psychiatry 20201029 1

The real-world impact of psychosis prevention is reliant on effective strategies for identifying individuals at risk. A transdiagnostic, individualized, clinically-based risk calculator to improve this has been developed and externally validated twice in two different UK healthcare trusts with convincing results. The prognostic performance of this risk calculator outside the UK is unknown. All individuals who accessed primary or secondary health care services belonging to the IBM<sup>®</sup> Mar ...[more]

PMID: 33122625

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Project description:ImportanceThe overall effect of At Risk Mental State (ARMS) services for the detection of individuals who will develop psychosis in secondary mental health care is undetermined.ObjectiveTo measure the proportion of individuals with a first episode of psychosis detected by ARMS services in secondary mental health services, and to develop and externally validate a practical web-based individualized risk calculator tool for the transdiagnostic prediction of psychosis in secondary mental health care.Design, setting, and participantsClinical register-based cohort study. Patients were drawn from electronic, real-world, real-time clinical records relating to 2008 to 2015 routine secondary mental health care in the South London and the Maudsley National Health Service Foundation Trust. The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and the Maudsley National Health Service Foundation Trust in the period between January 1, 2008, and December 31, 2015. Data analysis began on September 1, 2016.Main outcomes and measuresRisk of development of nonorganic International Statistical Classification of Diseases and Related Health Problems, Tenth Revision psychotic disorders.ResultsA total of 91 199 patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within South London and the Maudsley National Health Service Foundation Trust were included in the derivation (n = 33 820) or external validation (n = 54 716) data sets. The mean age was 32.97 years, 50.88% were men, and 61.05% were white race/ethnicity. The mean follow-up was 1588 days. The overall 6-year risk of psychosis in secondary mental health care was 3.02 (95% CI, 2.88-3.15), which is higher than the 6-year risk in the local general population (0.62). Compared with the ARMS designation, all of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses showed a lower risk of psychosis, with the exception of bipolar mood disorders (similar risk) and brief psychotic episodes (higher risk). The ARMS designation accounted only for a small proportion of transitions to psychosis (n = 52 of 1001; 5.19% in the derivation data set), indicating the need for transdiagnostic prediction of psychosis in secondary mental health care. A prognostic risk stratification model based on preselected variables, including index diagnosis, age, sex, age by sex, and race/ethnicity, was developed and externally validated, showing good performance and potential clinical usefulness.Conclusions and relevanceThis online individualized risk calculator can be of clinical usefulness for the transdiagnostic prediction of psychosis in secondary mental health care. The risk calculator can help to identify those patients at risk of developing psychosis who require an ARMS assessment and specialized care. The use of this calculator may eventually facilitate the implementation of an individualized provision of preventive focused interventions and improve outcomes of first episode psychosis.

Project description:BackgroundYoung people with psychosis are at high risk of developing cardiometabolic disorders; however, there is no suitable cardiometabolic risk prediction algorithm for this group. We aimed to develop and externally validate a cardiometabolic risk prediction algorithm for young people with psychosis.MethodsWe developed the Psychosis Metabolic Risk Calculator (PsyMetRiC) to predict up to 6-year risk of incident metabolic syndrome in young people (aged 16-35 years) with psychosis from commonly recorded information at baseline. We developed two PsyMetRiC versions using the forced entry method: a full model (including age, sex, ethnicity, body-mass index, smoking status, prescription of a metabolically active antipsychotic medication, HDL concentration, and triglyceride concentration) and a partial model excluding biochemical results. PsyMetRiC was developed using data from two UK psychosis early intervention services (Jan 1, 2013, to Nov 4, 2020) and externally validated in another UK early intervention service (Jan 1, 2012, to June 3, 2020). A sensitivity analysis was done in UK birth cohort participants (aged 18 years) who were at risk of developing psychosis. Algorithm performance was assessed primarily via discrimination (C statistic) and calibration (calibration plots). We did a decision curve analysis and produced an online data-visualisation app.Findings651 patients were included in the development samples, 510 in the validation sample, and 505 in the sensitivity analysis sample. PsyMetRiC performed well at internal (full model: C 0·80, 95% CI 0·74-0·86; partial model: 0·79, 0·73-0·84) and external validation (full model: 0·75, 0·69-0·80; and partial model: 0·74, 0·67-0·79). Calibration of the full model was good, but there was evidence of slight miscalibration of the partial model. At a cutoff score of 0·18, in the full model PsyMetRiC improved net benefit by 7·95% (sensitivity 75%, 95% CI 66-82; specificity 74%, 71-78), equivalent to detecting an additional 47% of metabolic syndrome cases.InterpretationWe have developed an age-appropriate algorithm to predict the risk of incident metabolic syndrome, a precursor of cardiometabolic morbidity and mortality, in young people with psychosis. PsyMetRiC has the potential to become a valuable resource for early intervention service clinicians and could enable personalised, informed health-care decisions regarding choice of antipsychotic medication and lifestyle interventions.FundingNational Institute for Health Research and Wellcome Trust.

Project description:BackgroundCardiometabolic dysfunction is common in young people with psychosis. Recently, the Psychosis Metabolic Risk Calculator (PsyMetRiC) was developed and externally validated in the UK, predicting up-to six-year risk of metabolic syndrome (MetS) from routinely collected data. The full-model includes age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations; the partial-model excludes biochemical predictors.MethodsTo move toward a future internationally-useful tool, we externally validated PsyMetRiC in two independent European samples. We used data from the PsyMetab (Lausanne, Switzerland) and PAFIP (Cantabria, Spain) cohorts, including participants aged 16-35y without MetS at baseline who had 1-6y follow-up. Predictive performance was assessed primarily via discrimination (C-statistic), calibration (calibration plots), and decision curve analysis. Site-specific recalibration was considered.FindingsWe included 1024 participants (PsyMetab n=558, male=62%, outcome prevalence=19%, mean follow-up=2.48y; PAFIP n=466, male=65%, outcome prevalence=14%, mean follow-up=2.59y). Discrimination was better in the full- compared with partial-model (PsyMetab=full-model C=0.73, 95% C.I., 0.68-0.79, partial-model C=0.68, 95% C.I., 0.62-0.74; PAFIP=full-model C=0.72, 95% C.I., 0.66-0.78; partial-model C=0.66, 95% C.I., 0.60-0.71). As expected, calibration plots revealed varying degrees of miscalibration, which recovered following site-specific recalibration. PsyMetRiC showed net benefit in both new cohorts, more so after recalibration.InterpretationThe study provides evidence of PsyMetRiC's generalizability in Western Europe, although further local and international validation studies are required. In future, PsyMetRiC could help clinicians internationally to identify young people with psychosis who are at higher cardiometabolic risk, so interventions can be directed effectively to reduce long-term morbidity and mortality.FundingNIHR Cambridge Biomedical Research Centre (BRC-1215-20014); The Wellcome Trust (201486/Z/16/Z); Swiss National Research Foundation (320030-120686, 324730- 144064, and 320030-173211); The Carlos III Health Institute (CM20/00015, FIS00/3095, PI020499, PI050427, and PI060507); IDIVAL (INT/A21/10 and INT/A20/04); The Andalusian Regional Government (A1-0055-2020 and A1-0005-2021); SENY Fundacion Research (2005-0308007); Fundacion Marques de Valdecilla (A/02/07, API07/011); Ministry of Economy and Competitiveness and the European Fund for Regional Development (SAF2016-76046-R and SAF2013-46292-R).For the Spanish and French translation of the abstract see Supplementary Materials section.

Project description:BackgroundTransition to psychosis is among the most adverse outcomes of clinical high-risk (CHR) syndromes encompassing ultra-high risk (UHR) and basic symptom states. Clinical risk calculators may facilitate an early and individualized interception of psychosis, but their real-world implementation requires thorough validation across diverse risk populations, including young patients with depressive syndromes.MethodsWe validated the previously described NAPLS-2 (North American Prodrome Longitudinal Study 2) calculator in 334 patients (26 with transition to psychosis) with CHR or recent-onset depression (ROD) drawn from the multisite European PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Patients were categorized into three risk enrichment levels, ranging from UHR, over CHR, to a broad-risk population comprising patients with CHR or ROD (CHR|ROD). We assessed how risk enrichment and different predictive algorithms influenced prognostic performance using reciprocal external validation.ResultsAfter calibration, the NAPLS-2 model predicted psychosis with a balanced accuracy (BAC) (sensitivity, specificity) of 68% (73%, 63%) in the PRONIA-UHR cohort, 67% (74%, 60%) in the CHR cohort, and 70% (73%, 66%) in patients with CHR|ROD. Multiple model derivation in PRONIA-CHR|ROD and validation in NAPLS-2-UHR patients confirmed that broader risk definitions produced more accurate risk calculators (CHR|ROD-based vs. UHR-based performance: 67% [68%, 66%] vs. 58% [61%, 56%]). Support vector machines were superior in CHR|ROD (BAC = 71%), while ridge logistic regression and support vector machines performed similarly in CHR (BAC = 67%) and UHR cohorts (BAC = 65%). Attenuated psychotic symptoms predicted psychosis across risk levels, while younger age and reduced processing speed became increasingly relevant for broader risk cohorts.ConclusionsClinical-neurocognitive machine learning models operating in young patients with affective and CHR syndromes facilitate a more precise and generalizable prediction of psychosis. Future studies should investigate their therapeutic utility in large-scale clinical trials.

Project description:Comorbid mental disorders in subjects at clinical high risk for psychosis (CHR-P) may impact preventive care. We conducted a PRISMA/MOOSE-compliant systematic meta-analysis, searching PubMed/PsycInfo up to June 21st, 2021 for observational studies/randomized controlled trials reporting on comorbid DSM/ICD-mental disorders in CHR-P subjects ( protocol ). The primary and secondary outcomes were baseline and follow-up prevalence of comorbid mental disorders. We also explored the association of comorbid mental disorders compared with CHR-P versus psychotic/non-psychotic control groups, their impact on baseline functioning and transition to psychosis. We conducted random-effects meta-analyses, meta-regression, and assessed heterogeneity/publication bias/quality (Newcastle Ottawa Scale, NOS). We included 312 studies (largest meta-analyzed sample = 7834, any anxiety disorder, mean age = 19.98 (3.40), females = 43.88%, overall NOS > 6 in 77.6% of studies). The prevalence was 0.78 (95% CI = 0.73-0.82, k = 29) for any comorbid non-psychotic mental disorder, 0.60 (95% CI = 0.36-0.84, k = 3) for anxiety/mood disorders, 0.44 (95% CI = 0.39-0.49, k = 48) for any mood disorders, 0.38 (95% CI = 0.33-0.42, k = 50) for any depressive disorder/episode, 0.34 (95% CI = 0.30-0.38, k = 69) for any anxiety disorder, 0.30 (95% CI 0.25-0.35, k = 35) for major depressive disorders, 0.29 (95% CI, 0.08-0.51, k = 3) for any trauma-related disorder, 0.23 (95% CI = 0.17-0.28, k = 24) for any personality disorder, and <0.23 in other mental disorders (I2 > 50% in 71.01% estimates). The prevalence of any comorbid mental disorder decreased over time (0.51, 95% CI = 0.25-0.77 over 96 months), except any substance use which increased (0.19, 95% CI = 0.00-0.39, k = 2, >96 months). Compared with controls, the CHR-P status was associated with a higher prevalence of anxiety, schizotypal personality, panic, and alcohol use disorders (OR from 2.90 to 1.54 versus without psychosis), a higher prevalence of anxiety/mood disorders (OR = 9.30 to 2.02) and lower prevalence of any substance use disorder (OR = 0.41, versus psychosis). Higher baseline prevalence of alcohol use disorder/schizotypal personality disorder was negatively associated with baseline functioning (beta from -0.40 to -0.15), while dysthymic disorder/generalized anxiety disorder with higher functioning (beta 0.59 to 1.49). Higher baseline prevalence of any mood disorder/generalized anxiety disorder/agoraphobia (beta from -2.39 to -0.27) was negatively associated with transition to psychosis. In conclusion, over three-quarters of CHR-P subjects have comorbid mental disorders, which modulate baseline functionig and transition to psychosis. Transdiagnostic mental health assessment should be warranted in subjects at CHR-P.

Dataset Information

Transdiagnostic individualized clinically-based risk calculator for the automatic detection of individuals at-risk and the prediction of psychosis: external replication in 2,430,333 US patients.

Publications

Transdiagnostic individualized clinically-based risk calculator for the automatic detection of individuals at-risk and the prediction of psychosis: external replication in 2,430,333 US patients.

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