Patient-centric characterization of multimorbidity trajectories in patients with severe mental illnesses: A temporal bipartite network modeling approach.

Multimorbidity is a major factor contributing to increased mortality among people with severe mental illnesses (SMI). Previous studies either focus on estimating prevalence of a disease in a population without considering relationships between diseases or ignore heterogeneity of individual patients in examining disease progression by looking merely at aggregates across a whole cohort. Here, we present a temporal bipartite network model to jointly represent detailed information on both individual patients and diseases, which allows us to systematically characterize disease trajectories from both patient and disease centric perspectives. We apply this approach to a large set of longitudinal diagnostic records for patients with SMI collected through a data linkage between electronic health records from a large UK mental health hospital and English national hospital administrative database. We find that the resulting diagnosis networks show disassortative mixing by degree, suggesting that patients affected by a small number of diseases tend to suffer from prevalent diseases. Factors that determine the network structures include an individual's age, gender and ethnicity. Our analysis on network evolution further shows that patients and diseases become more interconnected over the illness duration of SMI, which is largely driven by the process that patients with similar attributes tend to suffer from the same conditions. Our analytic approach provides a guide for future patient-centric research on multimorbidity trajectories and contributes to achieving precision medicine.

An implementation framework and a feasibility evaluation of a clinical decision support system for diabetes management in secondary mental healthcare using CogStack.

BACKGROUND: Improvements to the primary prevention of physical health illnesses like diabetes in the general population have not been mirrored to the same extent in people with serious mental illness (SMI). This work evaluates the technical feasibility of implementing an electronic clinical decision support system (eCDSS) for supporting the management of dysglycaemia and diabetes in patients with serious mental illness in a secondary mental healthcare setting. METHODS: A stepwise approach was taken as an overarching and guiding framework for this work. Participatory methods were employed to design and deploy a monitoring and alerting eCDSS. The eCDSS was evaluated for its technical feasibility. The initial part of the feasibility evaluation was conducted in an outpatient community mental health team. Thereafter, the evaluation of the eCDSS progressed to a more in-depth in silico validation. RESULTS: A digital health intervention that enables monitoring and alerting of at-risk patients based on an approved diabetes management guideline was developed. The eCDSS generated alerts according to expected standards and in line with clinical guideline recommendations. CONCLUSIONS: It is feasible to design and deploy a functional monitoring and alerting eCDSS in secondary mental healthcare. Further work is required in order to fully evaluate the integration of the eCDSS into routine clinical workflows. By describing and sharing the steps that were and will be taken from concept to clinical testing, useful insights could be provided to teams that are interested in building similar digital health interventions.

Ferritinophagy and α-Synuclein: Pharmacological Targeting of Autophagy to Restore Iron Regulation in Parkinson's Disease.

A major hallmark of Parkinson's disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated α-synuclein inhibits SNARE protein complexes and destabilizes microtubules to halt vesicular trafficking systems, including that of autophagy effectively. The scope of this review is to describe the physiological and pathological relationship between iron regulation and α-synuclein, providing a detailed understanding of iron metabolism within nigral neurons. The underlying mechanisms of autophagy and ferritinophagy are explored in the context of PD, identifying potential therapeutic targets for future investigation.

Cognitive Trajectories in Comorbid Dementia With Schizophrenia or Bipolar Disorder: The South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Case Register.

OBJECTIVES: We aimed to compare trajectories of cognitive performance in individuals diagnosed with dementia with and without severe mental illness (SMI). DESIGN: Retrospective cohort study. SETTING: We used data from a large longitudinal mental healthcare case register, the Clinical Record Interactive Search (CRIS), at the South London and Maudsley NHS Foundation Trust (SLaM) which provides mental health services to four south London boroughs. PARTICIPANTS: Our sample (N = 4718) consisted of any individual who had a primary or secondary diagnosis of dementia from 2007 to 2018, was 50 years old or over at first diagnosis of dementia and had at least 3 recorded Mini-Mental State Examination (MMSE) scores. MEASUREMENTS: Cognitive performance was measured using MMSE. Linear mixed models were fitted to explore whether MMSE trajectories differed between individuals with or without prior/current SMI diagnoses. Models were adjusted by socio-demographics, cardiovascular risk, smoking, and medication. RESULTS AND CONCLUSIONS: Our results showed differences in the rate of change, where individuals with comorbid SMI had a faster decline when compared with those that have dementia without comorbid SMI. However, this association was partially attenuated when adjusted by socio-demographics, smoking and cardiovascular risk factors; and more substantially attenuated when medication was included in models. Additional analyses showed that this accelerated decline might be more evident in individuals with bipolar disorders. Future research to detangle the potential biological underlying mechanisms of these associations is needed.

Using clinical Natural Language Processing for health outcomes research: Overview and actionable suggestions for future advances.

The importance of incorporating Natural Language Processing (NLP) methods in clinical informatics research has been increasingly recognized over the past years, and has led to transformative advances. Typically, clinical NLP systems are developed and evaluated on word, sentence, or document level annotations that model specific attributes and features, such as document content (e.g., patient status, or report type), document section types (e.g., current medications, past medical history, or discharge summary), named entities and concepts (e.g., diagnoses, symptoms, or treatments) or semantic attributes (e.g., negation, severity, or temporality). From a clinical perspective, on the other hand, research studies are typically modelled and evaluated on a patient- or population-level, such as predicting how a patient group might respond to specific treatments or patient monitoring over time. While some NLP tasks consider predictions at the individual or group user level, these tasks still constitute a minority. Owing to the discrepancy between scientific objectives of each field, and because of differences in methodological evaluation priorities, there is no clear alignment between these evaluation approaches. Here we provide a broad summary and outline of the challenging issues involved in defining appropriate intrinsic and extrinsic evaluation methods for NLP research that is to be used for clinical outcomes research, and vice versa. A particular focus is placed on mental health research, an area still relatively understudied by the clinical NLP research community, but where NLP methods are of notable relevance. Recent advances in clinical NLP method development have been significant, but we propose more emphasis needs to be placed on rigorous evaluation for the field to advance further. To enable this, we provide actionable suggestions, including a minimal protocol that could be used when reporting clinical NLP method development and its evaluation.

Inpatient use and area-level socio-environmental factors in people with psychosis.

PURPOSE: There is consistent evidence that socio-environmental factors measured at an area-level, such as ethnic density, urban environment and deprivation are associated with psychosis risk. However, whether area-level socio-environmental factors are associated with outcomes following psychosis onset is less clear. This study aimed to examine whether the number of inpatient days used by people presenting to mental health services for psychosis was associated with five key area-level socio-environmental factors: deprivation, ethnic density, social capital, population density and social fragmentation. METHODS: Using a historical cohort design based on electronic health records from the South London and Maudsley NHS Trust Foundation electronic Patient Journey System, people who presented for the first time to SLAM between 2007 and 2010 with psychosis were included. Structured data were extracted on age at presentation, gender, ethnicity, residential area at first presentation and number of inpatient days over 5 years of follow-up. Data on area-level socio-environmental factors taken from published sources were linked to participants' residential addresses. The relationship between the number of inpatient days and each socio-environmental factor was investigated in univariate negative binomial regression models with time in contact with services treated as an offset variable. RESULTS: A total of 2147 people had full data on area level outcomes and baseline demographics, thus, could be included in the full analysis. No area-level socio-environmental factors were associated with inpatient days. CONCLUSION: Although a robust association exists between socio-environmental factors and psychosis risk, in this study we found no evidence that neighbourhood deprivation was linked to future inpatient admissions following the onset of psychosis. Future work on the influence of area-level socio-environmental factors on outcome should examine more nuanced outcomes, e.g. recovery, symptom trajectory, and should account for key methodological challenges, e.g. accounting for changes in address.

CogStack - experiences of deploying integrated information retrieval and extraction services in a large National Health Service Foundation Trust hospital.

BACKGROUND: Traditional health information systems are generally devised to support clinical data collection at the point of care. However, as the significance of the modern information economy expands in scope and permeates the healthcare domain, there is an increasing urgency for healthcare organisations to offer information systems that address the expectations of clinicians, researchers and the business intelligence community alike. Amongst other emergent requirements, the principal unmet need might be defined as the 3R principle (right data, right place, right time) to address deficiencies in organisational data flow while retaining the strict information governance policies that apply within the UK National Health Service (NHS). Here, we describe our work on creating and deploying a low cost structured and unstructured information retrieval and extraction architecture within King's College Hospital, the management of governance concerns and the associated use cases and cost saving opportunities that such components present. RESULTS: To date, our CogStack architecture has processed over 300 million lines of clinical data, making it available for internal service improvement projects at King's College London. On generated data designed to simulate real world clinical text, our de-identification algorithm achieved up to 94% precision and up to 96% recall. CONCLUSION: We describe a toolkit which we feel is of huge value to the UK (and beyond) healthcare community. It is the only open source, easily deployable solution designed for the UK healthcare environment, in a landscape populated by expensive proprietary systems. Solutions such as these provide a crucial foundation for the genomic revolution in medicine.

Extracting antipsychotic polypharmacy data from electronic health records: developing and evaluating a novel process.

BACKGROUND: Antipsychotic prescription information is commonly derived from structured fields in clinical health records. However, utilising diverse and comprehensive sources of information is especially important when investigating less frequent patterns of medication prescribing such as antipsychotic polypharmacy (APP). This study describes and evaluates a novel method of extracting APP data from both structured and free-text fields in electronic health records (EHRs), and its use for research purposes. METHODS: Using anonymised EHRs, we identified a cohort of patients with serious mental illness (SMI) who were treated in South London and Maudsley NHS Foundation Trust mental health care services between 1 January and 30 June 2012. Information about antipsychotic co-prescribing was extracted using a combination of natural language processing and a bespoke algorithm. The validity of the data derived through this process was assessed against a manually coded gold standard to establish precision and recall. Lastly, we estimated the prevalence and patterns of antipsychotic polypharmacy. RESULTS: Individual instances of antipsychotic prescribing were detected with high precision (0.94 to 0.97) and moderate recall (0.57-0.77). We detected baseline APP (two or more antipsychotics prescribed in any 6-week window) with 0.92 precision and 0.74 recall and long-term APP (antipsychotic co-prescribing for 6 months) with 0.94 precision and 0.60 recall. Of the 7,201 SMI patients receiving active care during the observation period, 338 (4.7 %; 95 % CI 4.2-5.2) were identified as receiving long-term APP. Two second generation antipsychotics (64.8 %); and first -second generation antipsychotics were most commonly co-prescribed (32.5 %). CONCLUSIONS: These results suggest that this is a potentially practical tool for identifying polypharmacy from mental health EHRs on a large scale. Furthermore, extracted data can be used to allow researchers to characterize patterns of polypharmacy over time including different drug combinations, trends in polypharmacy prescribing, predictors of polypharmacy prescribing and the impact of polypharmacy on patient outcomes.

Getting more out of biomedical documents with GATE's full lifecycle open source text analytics.

This software article describes the GATE family of open source text analysis tools and processes. GATE is one of the most widely used systems of its type with yearly download rates of tens of thousands and many active users in both academic and industrial contexts. In this paper we report three examples of GATE-based systems operating in the life sciences and in medicine. First, in genome-wide association studies which have contributed to discovery of a head and neck cancer mutation association. Second, medical records analysis which has significantly increased the statistical power of treatment/outcome models in the UK's largest psychiatric patient cohort. Third, richer constructs in drug-related searching. We also explore the ways in which the GATE family supports the various stages of the lifecycle present in our examples. We conclude that the deployment of text mining for document abstraction or rich search and navigation is best thought of as a process, and that with the right computational tools and data collection strategies this process can be made defined and repeatable. The GATE research programme is now 20 years old and has grown from its roots as a specialist development tool for text processing to become a rather comprehensive ecosystem, bringing together software developers, language engineers and research staff from diverse fields. GATE now has a strong claim to cover a uniquely wide range of the lifecycle of text analysis systems. It forms a focal point for the integration and reuse of advances that have been made by many people (the majority outside of the authors' own group) who work in text processing for biomedicine and other areas. GATE is available online <1> under GNU open source licences and runs on all major operating systems. Support is available from an active user and developer community and also on a commercial basis.

Identifying Mentions of Pain in Mental Health Records Text: A Natural Language Processing Approach.

Pain is a common reason for accessing healthcare resources and is a growing area of research, especially in its overlap with mental health. Mental health electronic health records are a good data source to study this overlap. However, much information on pain is held in the free text of these records, where mentions of pain present a unique natural language processing problem due to its ambiguous nature. This project uses data from an anonymised mental health electronic health records database. A machine learning based classification algorithm is trained to classify sentences as discussing patient pain or not. This will facilitate the extraction of relevant pain information from large databases. 1,985 documents were manually triple-annotated for creation of gold standard training data, which was used to train four classification algorithms. The best performing model achieved an F1-score of 0.98 (95% CI 0.98-0.99).

Distributions of recorded pain in mental health records: a natural language processing based study.

OBJECTIVE: The objective of this study is to determine demographic and diagnostic distributions of physical pain recorded in clinical notes of a mental health electronic health records database by using natural language processing and examine the overlap in recorded physical pain between primary and secondary care. DESIGN, SETTING AND PARTICIPANTS: The data were extracted from an anonymised version of the electronic health records of a large secondary mental healthcare provider serving a catchment of 1.3 million residents in south London. These included patients under active referral, aged 18+ at the index date of 1 July 2018 and having at least one clinical document (≥30 characters) between 1 July 2017 and 1 July 2019. This cohort was compared with linked primary care records from one of the four local government areas. OUTCOME: The primary outcome of interest was the presence of recorded physical pain within the clinical notes of the patients, not including psychological or metaphorical pain. RESULTS: A total of 27 211 patients were retrieved. Of these, 52% (14,202) had narrative text containing relevant mentions of physical pain. Older patients (OR 1.17, 95% CI 1.15 to 1.19), females (OR 1.42, 95% CI 1.35 to 1.49), Asians (OR 1.30, 95% CI 1.16 to 1.45) or black (OR 1.49, 95% CI 1.40 to 1.59) ethnicities, living in deprived neighbourhoods (OR 1.64, 95% CI 1.55 to 1.73) showed higher odds of recorded pain. Patients with severe mental illnesses were found to be less likely to report pain (OR 0.43, 95% CI 0.41 to 0.46, p<0.001). 17% of the cohort from secondary care also had records from primary care. CONCLUSION: The findings of this study show sociodemographic and diagnostic differences in recorded pain. Specifically, lower documentation across certain groups indicates the need for better screening protocols and training on recognising varied pain presentations. Additionally, targeting improved detection of pain for minority and disadvantaged groups by care providers can promote health equity.

Social media users' attitudes toward cyberbullying during the COVID-19 pandemic: associations with gender and verification status.

Introduction: Social media platforms such as Twitter and Weibo facilitate both positive and negative communication, including cyberbullying. Empirical evidence has revealed that cyberbullying increases when public crises occur, that such behavior is gendered, and that social media user account verification may deter it. However, the association of gender and verification status with cyberbullying is underexplored. This study aims to address this gap by examining how Weibo users' gender, verification status, and expression of affect and anger in posts influence cyberbullying attitudes. Specifically, it investigates how these factors differ between posts pro- and anti-cyberbullying of COVID-19 cases during the pandemic. Methods: This study utilized social role theory, the Barlett and Gentile Cyberbullying Model, and general strain theory as theoretical frameworks. We applied text classification techniques to identify pro-cyberbullying and anti-cyberbullying posts on Weibo. Subsequently, we used a standardized mean difference method to compare the emotional content of these posts. Our analysis focused on the prevalence of affective and anger-related expressions, particularly examining variations across gender and verification status of the users. Results: Our text classification identified distinct pro-cyberbullying and anti-cyberbullying posts. The standardized mean difference analysis revealed that pro-cyberbullying posts contained significantly more emotional content compared to anti-cyberbullying posts. Further, within the pro-cyberbullying category, posts by verified female users exhibited a higher frequency of anger-related words than those by other users. Discussion: The findings from this study can enhance researchers' algorithms for identifying cyberbullying attitudes, refine the characterization of cyberbullying behavior using real-world social media data through the integration of the mentioned theories, and help government bodies improve their cyberbullying monitoring especially in the context of public health crises.

Question answering systems for health professionals at the point of care-a systematic review.

OBJECTIVES: Question answering (QA) systems have the potential to improve the quality of clinical care by providing health professionals with the latest and most relevant evidence. However, QA systems have not been widely adopted. This systematic review aims to characterize current medical QA systems, assess their suitability for healthcare, and identify areas of improvement. MATERIALS AND METHODS: We searched PubMed, IEEE Xplore, ACM Digital Library, ACL Anthology, and forward and backward citations on February 7, 2023. We included peer-reviewed journal and conference papers describing the design and evaluation of biomedical QA systems. Two reviewers screened titles, abstracts, and full-text articles. We conducted a narrative synthesis and risk of bias assessment for each study. We assessed the utility of biomedical QA systems. RESULTS: We included 79 studies and identified themes, including question realism, answer reliability, answer utility, clinical specialism, systems, usability, and evaluation methods. Clinicians' questions used to train and evaluate QA systems were restricted to certain sources, types and complexity levels. No system communicated confidence levels in the answers or sources. Many studies suffered from high risks of bias and applicability concerns. Only 8 studies completely satisfied any criterion for clinical utility, and only 7 reported user evaluations. Most systems were built with limited input from clinicians. DISCUSSION: While machine learning methods have led to increased accuracy, most studies imperfectly reflected real-world healthcare information needs. Key research priorities include developing more realistic healthcare QA datasets and considering the reliability of answer sources, rather than merely focusing on accuracy.

Implementation of an Electronic Clinical Decision Support System for the Early Recognition and Management of Dysglycemia in an Inpatient Mental Health Setting Using CogStack: Protocol for a Pilot Hybrid Type 3 Effectiveness-Implementation Randomized Controlled Cluster Trial.

BACKGROUND: Severe mental illnesses (SMIs), including schizophrenia, bipolar affective disorder, and major depressive disorder, are associated with an increased risk of physical health comorbidities and premature mortality from conditions including cardiovascular disease and diabetes. Digital technologies such as electronic clinical decision support systems (eCDSSs) could play a crucial role in improving the clinician-led management of conditions such as dysglycemia (deranged blood sugar levels) and associated conditions such as diabetes in people with a diagnosis of SMI in mental health settings. OBJECTIVE: We have developed a real-time eCDSS using CogStack, an information retrieval and extraction platform, to automatically alert clinicians with National Health Service Trust-approved, guideline-based recommendations for dysglycemia monitoring and management in secondary mental health care. This novel system aims to improve the management of dysglycemia and associated conditions, such as diabetes, in SMI. This protocol describes a pilot study to explore the acceptability, feasibility, and evaluation of its implementation in a mental health inpatient setting. METHODS: This will be a pilot hybrid type 3 effectiveness-implementation randomized controlled cluster trial in inpatient mental health wards. A ward will be the unit of recruitment, where it will be randomly allocated to receive either access to the eCDSS plus usual care or usual care alone over a 4-month period. We will measure implementation outcomes, including the feasibility and acceptability of the eCDSS to clinicians, as primary outcomes, alongside secondary outcomes relating to the process of care measures such as dysglycemia screening rates. An evaluation of other implementation outcomes relating to the eCDSS will be conducted, identifying facilitators and barriers based on established implementation science frameworks. RESULTS: Enrollment of wards began in April 2022, after which clinical staff were recruited to take part in surveys and interviews. The intervention period of the trial began in February 2023, and subsequent data collection was completed in August 2023. Data are currently being analyzed, and results are expected to be available in June 2024. CONCLUSIONS: An eCDSS can have the potential to improve clinician-led management of dysglycemia in inpatient mental health settings. If found to be feasible and acceptable, then, in combination with the results of the implementation evaluation, the system can be refined and improved to support future successful implementation. A larger and more definitive effectiveness trial should then be conducted to assess its impact on clinical outcomes and to inform scalability and application to other conditions in wider mental health care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04792268; https://clinicaltrials.gov/study/NCT04792268. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49548.

Development and evaluation of a de-identification procedure for a case register sourced from mental health electronic records.

BACKGROUND: Electronic health records (EHRs) provide enormous potential for health research but also present data governance challenges. Ensuring de-identification is a pre-requisite for use of EHR data without prior consent. The South London and Maudsley NHS Trust (SLaM), one of the largest secondary mental healthcare providers in Europe, has developed, from its EHRs, a de-identified psychiatric case register, the Clinical Record Interactive Search (CRIS), for secondary research. METHODS: We describe development, implementation and evaluation of a bespoke de-identification algorithm used to create the register. It is designed to create dictionaries using patient identifiers (PIs) entered into dedicated source fields and then identify, match and mask them (with ZZZZZ) when they appear in medical texts. We deemed this approach would be effective, given high coverage of PI in the dedicated fields and the effectiveness of the masking combined with elements of a security model. We conducted two separate performance tests i) to test performance of the algorithm in masking individual true PIs entered in dedicated fields and then found in text (using 500 patient notes) and ii) to compare the performance of the CRIS pattern matching algorithm with a machine learning algorithm, called the MITRE Identification Scrubber Toolkit - MIST (using 70 patient notes - 50 notes to train, 20 notes to test on). We also report any incidences of potential breaches, defined by occurrences of 3 or more true or apparent PIs in the same patient's notes (and in an additional set of longitudinal notes for 50 patients); and we consider the possibility of inferring information despite de-identification. RESULTS: True PIs were masked with 98.8% precision and 97.6% recall. As anticipated, potential PIs did appear, owing to misspellings entered within the EHRs. We found one potential breach. In a separate performance test, with a different set of notes, CRIS yielded 100% precision and 88.5% recall, while MIST yielded a 95.1% and 78.1%, respectively. We discuss how we overcome the realistic possibility - albeit of low probability - of potential breaches through implementation of the security model. CONCLUSION: CRIS is a de-identified psychiatric database sourced from EHRs, which protects patient anonymity and maximises data available for research. CRIS demonstrates the advantage of combining an effective de-identification algorithm with a carefully designed security model. The paper advances much needed discussion of EHR de-identification - particularly in relation to criteria to assess de-identification, and considering the contexts of de-identified research databases when assessing the risk of breaches of confidential patient information.

Characterizing the Differences in Descriptions of Violence on Reddit During the COVID-19 Pandemic.

Concerns have been raised over the experiences of violence such as domestic violence (DV) and intimate partner violence (IPV) during the COVID-19 pandemic. Social media such as Reddit represent an alternative outlet for reporting experiences of violence where healthcare access has been limited. This study analyzed seven violence-related subreddits to investigate the trends of different violence patterns from January 2018 to February 2022 to enhance the health-service providers' existing service or provide some new perspective for existing violence research. Specifically, we collected violence-related texts from Reddit using keyword searching and identified six major types with supervised machine learning classifiers: DV, IPV, physical violence, sexual violence, emotional violence, and nonspecific violence or others. The increase rate (IR) of each violence type was calculated and temporally compared in five phases of the pandemic. The phases include one pre-pandemic phase (Phase 0, the date before February 26, 2020) and four pandemic phases (Phases 1-4) with separation dates of June 17, 2020, September 7, 2020, and June 4, 2021. We found that the number of IPV-related posts increased most in the earliest phase; however, that for COVID-citing IPV was highest in the mid-pandemic phase. IRs for DV, IPV, and emotional violence also showed increases across all pandemic phases, with IRs of 26.9%, 58.8%, and 28.8%, respectively, from the pre-pandemic to the first pandemic phase. In the other three pandemic phases, all the IRs for these three types of violence were positive, though lower than the IRs in the first pandemic phase. The findings highlight the importance of identifying and providing help to those who suffer from such violent experiences and support the role of social media site monitoring as a means of informative surveillance for help-providing authorities and violence research groups.

Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.

OBJECTIVES: An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors. In contrast, we controlled such factors by utilizing a general population sample of individuals undiagnosed with schizophrenia. We hypothesized that if schizophrenia genetics impact T2DM development and such impact is not fully mediated by schizophrenia-related environment, people with high polygenic schizophrenia risk would exhibit elevated T2DM incidence. METHODS: Using a population-representative sample of adults aged ≥50 from English Longitudinal Study of Ageing ( n  = 5968, 493 T2DM cases, average follow-up 8.7 years), we investigated if schizophrenia polygenic risk score (PGS-SZ) is associated with T2DM onset. A proportional hazards model with interval censoring was adjusted for age and sex (Model 1), and age, sex, BMI, hypertension, cardiovascular diseases, exercise, smoking, depressive symptoms and T2DM polygenic risk score (Model 2). According to the power calculations, hazard rates > 1.14 per standard deviation in PGS-SZ could be detected. RESULTS: We did not observe a significant association between PGS-SZ and T2DM incidence (hazard ratio 1.04; 95% CI 0.93-1.15; and 1.01, 95% CI 0.94-1.09). CONCLUSION: Our results suggest low contribution of the intrinsic biological mechanisms driven by the polygenic risk of schizophrenia on future T2DM onset. Further research is needed.

Identifying encephalopathy in patients admitted to an intensive care unit: Going beyond structured information using natural language processing.

Background: Encephalopathy is a severe co-morbid condition in critically ill patients that includes different clinical constellation of neurological symptoms. However, even for the most recognised form, delirium, this medical condition is rarely recorded in structured fields of electronic health records precluding large and unbiased retrospective studies. We aimed to identify patients with encephalopathy using a machine learning-based approach over clinical notes in electronic health records. Methods: We used a list of ICD-9 codes and clinical concepts related to encephalopathy to define a cohort of patients from the MIMIC-III dataset. Clinical notes were annotated with MedCAT and vectorized with a bag-of-word approach or word embedding using clinical concepts normalised to standard nomenclatures as features. Machine learning algorithms (support vector machines and random forest) trained with clinical notes from patients who had a diagnosis of encephalopathy (defined by ICD-9 codes) were used to classify patients with clinical concepts related to encephalopathy in their clinical notes but without any ICD-9 relevant code. A random selection of 50 patients were reviewed by a clinical expert for model validation. Results: Among 46,520 different patients, 7.5% had encephalopathy related ICD-9 codes in all their admissions (group 1, definite encephalopathy), 45% clinical concepts related to encephalopathy only in their clinical notes (group 2, possible encephalopathy) and 38% did not have encephalopathy related concepts neither in structured nor in clinical notes (group 3, non-encephalopathy). Length of stay, mortality rate or number of co-morbid conditions were higher in groups 1 and 2 compared to group 3. The best model to classify patients from group 2 as patients with encephalopathy (SVM using embeddings) had F1 of 85% and predicted 31% patients from group 2 as having encephalopathy with a probability >90%. Validation on new cases found a precision ranging from 92% to 98% depending on the criteria considered. Conclusions: Natural language processing techniques can leverage relevant clinical information that might help to identify patients with under-recognised clinical disorders such as encephalopathy. In the MIMIC dataset, this approach identifies with high probability thousands of patients that did not have a formal diagnosis in the structured information of the EHR.

Predicting type 2 diabetes prevalence for people with severe mental illness in a multi-ethnic East London population.

BACKGROUND AND AIMS: Prevalence of type two diabetes mellitus (T2DM) in people with severe mental illness (SMI) is 2-3 times higher than in general population. Predictive modelling has advanced greatly in the past decade, and it is important to apply cutting-edge methods to vulnerable groups. However, few T2DM prediction models account for the presence of mental illness, and none seemed to have been developed specifically for people with SMI. Therefore, we aimed to develop and internally validate a T2DM prevalence model for people with SMI. METHODS: We utilised a large cross-sectional sample representative of a multi-ethnic population from London (674,000 adults); 10,159 people with SMI formed our analytical sample (1,513 T2DM cases). We fitted a linear logistic regression and XGBoost as stand-alone models and as a stacked ensemble. Age, sex, body mass index, ethnicity, area-based deprivation, past hypertension, cardiovascular diseases, prescribed antipsychotics, and SMI illness were the predictors. RESULTS: Logistic regression performed well while detecting T2DM presence for people with SMI: area under the receiver operator curve (ROC-AUC) was 0.83 (95 % CI 0.79-0.87). XGBoost and LR-XGBoost ensemble performed equally well, ROC-AUC 0.83 (95 % CI 0.79-0.87), indicating a negligible contribution of non-linear terms to predictive power. Ethnicity was the most important predictor after age. We demonstrated how the derived models can be utilised and estimated a 2.14 % (95 %CI 2.03 %-2.24 %) increase in T2DM prevalence in East London SMI population in 20 years' time, driven by the projected demographic changes. CONCLUSIONS: Primary care data, the setting where prediction models could be most fruitfully used, provide enough information for well-performing T2DM prevalence models for people with SMI. We demonstrated how thorough internal cross-validation of an ensemble of a linear and machine-learning model can quantify the predictive value of non-linearity in the data.

Development of a Knowledge Graph Embeddings Model for Pain.

Pain is a complex concept that can interconnect with other concepts such as a disorder that might cause pain, a medication that might relieve pain, and so on. To fully understand the context of pain experienced by either an individual or across a population, we may need to examine all concepts related to pain and the relationships between them. This is especially useful when modeling pain that has been recorded in electronic health records. Knowledge graphs represent concepts and their relations by an interlinked network, enabling semantic and context-based reasoning in a computationally tractable form. These graphs can, however, be too large for efficient computation. Knowledge graph embeddings help to resolve this by representing the graphs in a low-dimensional vector space. These embeddings can then be used in various downstream tasks such as classification and link prediction. The various relations associated with pain which are required to construct such a knowledge graph can be obtained from external medical knowledge bases such as SNOMED CT, a hierarchical systematic nomenclature of medical terms. A knowledge graph built in this way could be further enriched with real-world examples of pain and its relations extracted from electronic health records. This paper describes the construction of such knowledge graph embedding models of pain concepts, extracted from the unstructured text of mental health electronic health records, combined with external knowledge created from relations described in SNOMED CT, and their evaluation on a subject-object link prediction task. The performance of the models was compared with other baseline models.