TooManyCellsInteractive: A visualization tool for dynamic exploration of single-cell data.

BACKGROUND: As single-cell sequencing technologies continue to advance, the growing volume and complexity of the ensuing data present new analytical challenges. Large cellular populations from single-cell atlases are more difficult to visualize and require extensive processing to identify biologically relevant subpopulations. Managing these workflows is also laborious for technical users and unintuitive for nontechnical users. RESULTS: We present TooManyCellsInteractive (TMCI), a browser-based JavaScript application for interactive exploration of cell populations. TMCI provides an intuitive interface to visualize and manipulate a radial tree representation of hierarchical cell subpopulations and allows users to easily overlay, filter, and compare biological features at multiple resolutions. Here we describe the software architecture and demonstrate how we used TMCI in a pan-cancer analysis to identify unique survival pathways among drug-tolerant persister cells. CONCLUSIONS: TMCI will facilitate exploration and visualization of large-scale sequencing data in a user-friendly way. TMCI is freely available at https://github.com/schwartzlab-methods/too-many-cells-interactive. An example tree from data within this article is available at https://tmci.schwartzlab.ca/.

ONCO-FAIR Project: Improving Data Interoperability in Oncology Chemotherapy Treatments for Data Reuse.

The ONCO-FAIR project's initial experimentation aims to enhance data interoperability in oncology chemotherapy treatments, adhering to the FAIR principles. This study focuses on integrating the HL7 FHIR standard to address interoperability challenges within chemotherapy data exchange. Collaborating with healthcare institutions in Rennes, the research team assessed the limitations of current standards such as PN13, mCODE, and OSIRIS, leading to the customization of twelve FHIR resources complemented by two chemotherapy-specific extensions. The methodological approach follows the Integrating the Healthcare Enterprise (IHE) framework, organizing the process into four key stages to ensure the effectiveness and relevance of health data reuse for research. This framework facilitated the identification of chemotherapy-specific needs, the evaluation of existing standards, and data modeling through a FHIR implementation guide. The article underscores the importance of upstream interoperability for aligning chemotherapy software with clinical data warehouse infrastructure, showcasing the proposed solution's capability to overcome interoperability barriers and promote data reuse in line with FAIR principles. Furthermore, it discusses future directions, including extending this approach to other oncology data categories and enhancing downstream interoperability with health data sharing platforms.

A Hybrid-Approach for Privacy Preserving Record Linkage - A Case Study from Germany.

Over the last decade, the exponential growth in patient data volume and velocity has transformed it into a valuable resource for researchers. Yet, accessing comprehensive, unique patient data sets remains a challenge, particularly when individuals have received treatments across various practices and hospitals. Traditional record linkage methods fall short in adequately protecting patient privacy in these scenarios. Privacy Preserving Record Linkage (PPRL) offers a solution, employing techniques such as data cryptographic methods to identify common patients occurring in multiple datasets, while maintaining the privacy of other patients. This paper proposes an investigation into combined approaches of two common German PPRL tools, namely E-PIX and MainSEL. Each tool, while aiming for 'privacy preservation', employs distinct methods that offer unique advantages and drawbacks. Our research aims to explore these in a combined approach to leverage their respective strengths and mitigate their limitations. We anticipate that this synergistic approach will not only enhance data privacy but also allow for easier synchronisation of research data. This study is particularly pertinent in light of evolving privacy regulations and the increasing complexity of healthcare data management. By advancing PPRL methodologies, we aim to contribute to more robust, privacy-compliant data analysis practices in healthcare research.

Development of a Big Data Platform for the Collection and Utilization of Korea Biobank Network Clinical Information.

Biobanks serve as vital repositories for human biospecimens and clinical data, promoting biomedical and clinical research. The integration of electronic health records particularly enhances research opportunities in the era of genomics and personalized medicine, improving understanding of tumor development and disease progression. Based on the Korea Biobank Network Common Data Model, it is possible to expand data collection across various diseases. We have developed an innovative big data platform designed to efficiently collect large-scale clinical information within the KBN. By implementing the system structure, data quality management processes, and basic statistical preprocessing functionalities, we have collected data from 136,473 individuals from 2021 to 2023, demonstrating the platform's continuous and efficient data collection capabilities. Integration with hospital systems and robust quality management ensure the acquisition of high-quality data.

Harmonization of Data Across Cohorts Using Standard Terminologies.

Korean National Institute of Health initiated data harmonization across cohorts with the aim to ensure semantic interoperability of data and to create a common database of standardized data elements for future collaborative research. With this aim, we reviewed code books of cohorts and identified common data items and values which can be combined for data analyses. We then mapped data items and values to standard health terminologies such as SNOMED CT. Preliminary results of this ongoing data harmonization work will be presented.

Greek Tweets on Long COVID: Topic Modelling Following Sentiment Analysis and ChatGPT Interpretation.

Long COVID is a disease that makes it hard for patients to get an official diagnosis while it impacts their quality of life. Many people are turning to social networks such as Facebook, WhatsApp, Twitter (now X) to express their opinions and feelings regarding Long COVID. In this paper, positive (or neutral) and negative text messages in the Greek language, posted on the Twitter platform in 2022, regarding Long COVID are analyzed and popular discussion topics are extracted. Analysis revealed that when topic modelling follows sentiment analysis more coherent topics are created. Furthermore, ChatGPT is used to assign a label to each topic that, in turn, is assessed by a human expert.

Predicting Asthma Exacerbation Risk in the Adult South Korean Population Using Integrated Health Data and Machine Learning Models.

Asthma is a chronic inflammatory airway disease with significant burden; exacerbations can severely affect quality of life and healthcare costs. Advances in big data analysis and artificial intelligence have made it easier to predict future exacerbations more accurately. This study used an integrated dataset of Korean National Health Insurance, meteorological, air pollution, and viral data from national public databases to develop a model to predict asthma exacerbations on a daily basis in South Korea. We merged these sources and applied random forest, AdaBoost, XGBoost, and LightGBM machine learning models to compare their performances at predicting future exacerbations. Of the models, XGBoost (AUROC of 0.68 and accuracy of 0.96) and LightGBM (AUROC of 0.67 and accuracy of 0.96) were the most promising. Common important variables were the number of visits and exacerbations per year, and medical resource utilization, including the prescription of asthma medications. Comorbid diabetes, hypertension, gastroesophageal reflux, arthritis, metabolic syndrome, osteoporosis, and ischemic heart disease were also associated with elevated exacerbation risk. The models examined in this study highlight the importance of previous exacerbations, use of medical resources, and comorbidities in the prediction of future exacerbations in patients with asthma.

End-tidal carbon dioxide and arterial to end-tidal carbon dioxide gradient are associated with mortality in patients with neurological injuries.

Pre-hospital end-tidal carbon dioxide (EtCO2) monitoring and arterial to end-tidal carbon dioxide gradient (Pa-EtCO2) have been associated with mortality in patients with traumatic brain injury. Our study aimed to analyze the association between alveolar EtCO2 or Pa-EtCO2 and mortality in patients admitted in intensive care unit (ICU) with neurological injuries. In our retrospective analysis from using large de-identified ICU databases (MIMIC-III and -IV and eICU databases), we included 2872 ICU patients with neurological injuries, identified according to the International Classification of Diseases (ICD-9 and -10), who underwent EtCO2 monitoring. We performed logistic regression and extended Cox regression to assess the association between mortality and candidate covariates, including EtCO2 and Pa-EtCO2. In-hospital mortality was 26% (n = 747). In univariate analysis, both the Pa-EtCO2 gradient and EtCO2 levels during the first 24 h were significantly associated with mortality (for a 1 mmHg increase: OR = 1.03 [CI95 1.016-1.035] and OR = 0.94 [CI95 0.923-0.953]; p < 0.001). The association remained significant in multivariate analysis. The time-varying evolution of EtCO2 was independently associated with mortality (for a 1 mmHg increase: HR = 0.976 [CI95 0.966-0.985]; p < 0.001). The time-varying Pa-EtCO2 gradient was associated with mortality only in univariate analysis. In neurocritical patients, lower EtCO2 levels at admission and throughout the ICU stay were independently associated with mortality and should be avoided.

Role of big data and technological advancements in monitoring and development of smart cities.

Driven by rapid advancements in technology and data science, a revolutionary transformation is sweeping across environmentally friendly cities worldwide. This surge stems from a pressing need to tackle the intricate complexities of urban sustainability, encompassing everything from infrastructure and governance to fragmented design and technological solutions. To effectively manage these complexities and accurately measure, assess, and optimize their sustainability performance, sustainable communities are increasingly tapping into the potential of smart city technologies, particularly big data and its fictionalized applications. This trend culminates in the emergence of smart cities. This article delves into the current state of research surrounding data-driven, environmentally conscious smart cities, aiming to assess the extent to which these two concepts are currently being integrated and identify potential gaps in this field. Through a strong emphasis on evidence-based research, the study underscores the potential of big data technologies to offer innovative approaches for monitoring, comprehending, evaluating, and ultimately managing sustainable urban development. It further highlights the crucial role of data-driven advancements in formulating strategic development policies and operational management procedures, ensuring that environmentally conscious cities can continue to contribute to sustainability goals even amidst rapid urbanization.

Youth mental health care use during the COVID-19 pandemic in Alberta, Canada: an interrupted time series, population-based study.

BACKGROUND: During the COVID-19 pandemic, youth had rising mental health needs and changes in service accessibility. Our study investigated changes in use of mental health care services for Canadian youth in Alberta before and during the COVID-19 pandemic. We also investigated how youth utilization patterns differed for subgroups based on social factors (i.e., age, gender, socioeconomic status, and geography) previously associated with health care access. METHODS: We used cross-sectional population-based data from Alberta, Canada to understand youth (15-24 year) mental health care use from 2018/19 to 2021/22. We performed interrupted time series design, segmented regression modeling on type of mental health care use (i.e., general physician, psychiatrist, emergency room, and hospitalization) and diagnosis-related use. We also investigated the characteristics of youth who utilized mental health care services and stratified diagnosis-related use patterns by youth subgroups. RESULTS: The proportion of youth using mental health care significantly increased from 15.6% in 2018/19 to 18.8% in 2021/22. Mental health care use showed an immediate drop in April 2020 when the COVID-19 pandemic was declared and public health protections were instituted, followed by a steady rise during the next 2 years. An increase was significant for general physician and psychiatrist visits. Most individual diagnoses included in this study showed significant increasing trends during the pandemic (i.e., anxiety, adjustment, ADHD, schizophrenia, and self-harm), with substance use showing an overall decrease. Mortality rates greatly increased for youth being seen for mental health reasons from 71 per 100,000 youth in 2018/19 to 163 per 100,000 in 2021/22. In addition, there were clear shifts over time in the characteristics of youth using mental health care services. Specifically, there was increased utilization for women/girls compared to men/boys and for youth from wealthier neighborhoods. Increases over time in the utilization of services for self-harm were limited to younger youth (15-16 year). CONCLUSIONS: The study provides evidence of shifts in mental health care use during the COVID-19 pandemic. Findings can be used to plan for ongoing mental health needs of youth, future pandemic responses, and other public health emergencies.

A computational study of gene expression patterns in head and neck squamous cell carcinoma using TCGA data.

Aim: Head and Neck squamous cell carcinoma (HNSCC) is the second most prevalent cancer in Pakistan. Methods: Gene expression data from TCGA and GETx for normal genes to analyze Differentially Expressed Genes (DEGs). Data was further investigated using the Enrichr tool to perform Gene Ontology (GO). Results: Our analysis identified most significantly differentially expressed genes and explored their established cellular functions as well as their potential involvement in tumor development. We found that the highly expressed Keratin family and S100A9 genes. The under-expressed genes KRT4 and KRT13 provide instructions for the production of keratin proteins. Conclusion: Our study suggests that factors such as poor oral hygiene and smokeless tobacco can result in oral stress and cellular damage and cause cancer.

The Cancer Genome Atlas (TCGA) holds vast cancer data processed with powerful computers and cloud tech. This sparks new bioinformatics for better cancer diagnosis, treatment, and prevention. In Southeast Asia, Head and Neck Squamous Cell Carcinoma (HNSCC) is prevalent. We used TCGA and GETx data to study gene expression. High-expression Keratin and S100A9 genes fight cellular damage under stress, while under-expressed KRT4 and KRT13 genes shape cell structure. Poor oral care and smokeless tobacco could induce cell damage, sparking cancer mutations. Unveiling HNSCC mechanisms may guide targeted treatments and preventive strategies.

Understanding the Use of Mobility Data in Disasters: Exploratory Qualitative Study of COVID-19 User Feedback.

BACKGROUND: Human mobility data have been used as a potential novel data source to guide policies and response planning during the COVID-19 global pandemic. The COVID-19 Mobility Data Network (CMDN) facilitated the use of human mobility data around the world. Both researchers and policy makers assumed that mobility data would provide insights to help policy makers and response planners. However, evidence that human mobility data were operationally useful and provided added value for public health response planners remains largely unknown. OBJECTIVE: This exploratory study focuses on advancing the understanding of the use of human mobility data during the early phase of the COVID-19 pandemic. The study explored how researchers and practitioners around the world used these data in response planning and policy making, focusing on processing data and human factors enabling or hindering use of the data. METHODS: Our project was based on phenomenology and used an inductive approach to thematic analysis. Transcripts were open-coded to create the codebook that was then applied by 2 team members who blind-coded all transcripts. Consensus coding was used for coding discrepancies. RESULTS: Interviews were conducted with 45 individuals during the early period of the COVID-19 pandemic. Although some teams used mobility data for response planning, few were able to describe their uses in policy making, and there were no standardized ways that teams used mobility data. Mobility data played a larger role in providing situational awareness for government partners, helping to understand where people were moving in relation to the spread of COVID-19 variants and reactions to stay-at-home orders. Interviewees who felt they were more successful using mobility data often cited an individual who was able to answer general questions about mobility data; provide interactive feedback on results; and enable a 2-way communication exchange about data, meaning, value, and potential use. CONCLUSIONS: Human mobility data were used as a novel data source in the COVID-19 pandemic by a network of academic researchers and practitioners using privacy-preserving and anonymized mobility data. This study reflects the processes in analyzing and communicating human mobility data, as well as how these data were used in response planning and how the data were intended for use in policy making. The study reveals several valuable use cases. Ultimately, the role of a data translator was crucial in understanding the complexities of this novel data source. With this role, teams were able to adapt workflows, visualizations, and reports to align with end users and decision makers while communicating this information meaningfully to address the goals of responders and policy makers.

Patent data-driven analysis of literature associations with changing innovation trends.

Patents are essential for transferring scientific discoveries to meaningful products that benefit societies. While the academic community focuses on the number of citations to rank scholarly works according to their "scientific merit," the number of citations is unrelated to the relevance for patentable innovation. To explore associations between patents and scholarly works in publicly available patent data, we propose to utilize statistical methods that are commonly used in biology to determine gene-disease associations. We illustrate their usage on patents related to biotechnological trends of high relevance for food safety and ecology, namely the CRISPR-based gene editing technology (>60,000 patents) and cyanobacterial biotechnology (>33,000 patents). Innovation trends are found through their unexpected large changes of patent numbers in a time-series analysis. From the total set of scholarly works referenced by all investigated patents (~254,000 publications), we identified ~1,000 scholarly works that are statistical significantly over-represented in the references of patents from changing innovation trends that concern immunology, agricultural plant genomics, and biotechnological engineering methods. The detected associations are consistent with the technical requirements of the respective innovations. In summary, the presented data-driven analysis workflow can identify scholarly works that were required for changes in innovation trends, and, therefore, is of interest for researches that would like to evaluate the relevance of publications beyond the number of citations.

Public Involvement and Engagement in Big Data Research: Scoping Review.

BACKGROUND: The success of big data initiatives depends on public support. Public involvement and engagement could be a way of establishing public support for big data research. OBJECTIVE: This review aims to synthesize the evidence on public involvement and engagement in big data research. METHODS: This scoping review mapped the current evidence on public involvement and engagement activities in big data research. We searched 5 electronic databases, followed by additional manual searches of Google Scholar and gray literature. In total, 2 public contributors were involved at all stages of the review. RESULTS: A total of 53 papers were included in the scoping review. The review showed the ways in which the public could be involved and engaged in big data research. The papers discussed a broad range of involvement activities, who could be involved or engaged, and the importance of the context in which public involvement and engagement occur. The findings show how public involvement, engagement, and consultation could be delivered in big data research. Furthermore, the review provides examples of potential outcomes that were produced by involving and engaging the public in big data research. CONCLUSIONS: This review provides an overview of the current evidence on public involvement and engagement in big data research. While the evidence is mostly derived from discussion papers, it is still valuable in illustrating how public involvement and engagement in big data research can be implemented and what outcomes they may yield. Further research and evaluation of public involvement and engagement in big data research are needed to better understand how to effectively involve and engage the public in big data research. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-https://doi.org/10.1136/bmjopen-2021-050167.

How digital transformation enhances corporate innovation performance: The mediating roles of big data capabilities and organizational agility.

Digital transformation has emerged as a key driver of high-quality enterprise development and an essential tool in forging an innovation-driven paradigm.Existing studies fail to delve into the specific mechanisms of their impact on firms' innovation performance, and views on their impact are divergent. Some studies suggest that digital transformation can enhance innovation performance, while others point out that it may have negative impacts, and cannot clearly answer how big data capabilities and organisational agility play a role in the digital transformation process. Therefore, based on dynamic capability theory and systems engineering theory, this study adopts the logical framework of "strategy-behaviour-performance" to systematically explore the process of digital transformation that enhances firms' innovation performance through the enhancement of big data capability and organisational agility. By empirically analysing the survey data of 476 manufacturing enterprises in China, the study reveals the chain-mediated effects of big data capability and organisational agility, and confirms the key roles of both in the transformation process. The findings suggest that digital transformation significantly improves firms' innovation performance, and that the dual mediating effects of big data capability and organisational agility are important links in its influencing mechanism. These findings not only provide empirical support for the theoretical model of digital transformation, but also provide practical guidance for enterprises to formulate strategies and optimise resource allocation in the digital era. We suggest that enterprises should strengthen the cultivation of big data capabilities and organisational agility while promoting digital transformation to better adapt to and lead market changes.

Synergies between the circular economy and carbon emission reduction.

Climate change and sustainable development drive transformation in economic development models. Carbon emission reduction and the circular economy propel climate change and sustainable development, yet it's unclear if they synergize or counteract each other. This study examines the question from theoretical and practical perspectives. Using a theory-practice framework, bibliometric and big data analyses were conducted on the Web of Science and Chinese case data, totaling 2.29GB, to explore synergies between carbon emission reduction and the circular economy. The study finds predominantly synergistic interactions between the circular economy and carbon emission reduction, with minimal offsetting effects. That is, the circular economy markedly enhances carbon emissions reduction. At the theoretical level, the two fields are gradually evolving towards in-depth research, while at the practical level, collaboration is coalescing around four areas: hot fields, potential fields, auxiliary fields and common goals. A noteworthy contribution of this study is the development of a framework that synergizes theory and practice, providing a structured approach for future research in this domain. By quantifying the synergistic and offsetting relationship between the circular economy and carbon emissions reduction through systematic big data analysis, this research offers insights essential for achieving the UN's Sustainable Development Goals. We also stress the need for diverse case studies and multi-dimensional analyses in ongoing research.

The Use of Deep Learning and Machine Learning on Longitudinal Electronic Health Records for the Early Detection and Prevention of Diseases: Scoping Review.

BACKGROUND: Electronic health records (EHRs) contain patients' health information over time, including possible early indicators of disease. However, the increasing amount of data hinders clinicians from using them. There is accumulating evidence suggesting that machine learning (ML) and deep learning (DL) can assist clinicians in analyzing these large-scale EHRs, as algorithms thrive on high volumes of data. Although ML has become well developed, studies mainly focus on engineering but lack medical outcomes. OBJECTIVE: This study aims for a scoping review of the evidence on how the use of ML on longitudinal EHRs can support the early detection and prevention of disease. The medical insights and clinical benefits that have been generated were investigated by reviewing applications in a variety of diseases. METHODS: This study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search was performed in 2022 in collaboration with a medical information specialist in the following databases: PubMed, Embase, Web of Science Core Collection (Clarivate Analytics), and IEEE Xplore Digital Library and computer science bibliography. Studies were eligible when longitudinal EHRs were used that aimed for the early detection of disease via ML in a prevention context. Studies with a technical focus or using imaging or hospital admission data were beyond the scope of this review. Study screening and selection and data extraction were performed independently by 2 researchers. RESULTS: In total, 20 studies were included, mainly published between 2018 and 2022. They showed that a variety of diseases could be detected or predicted, particularly diabetes; kidney diseases; diseases of the circulatory system; and mental, behavioral, and neurodevelopmental disorders. Demographics, symptoms, procedures, laboratory test results, diagnoses, medications, and BMI were frequently used EHR data in basic recurrent neural network or long short-term memory techniques. By developing and comparing ML and DL models, medical insights such as a high diagnostic performance, an earlier detection, the most important predictors, and additional health indicators were obtained. A clinical benefit that has been evaluated positively was preliminary screening. If these models are applied in practice, patients might also benefit from personalized health care and prevention, with practical benefits such as workload reduction and policy insights. CONCLUSIONS: Longitudinal EHRs proved to be helpful for support in health care. Current ML models on EHRs can support the detection of diseases in terms of accuracy and offer preliminary screening benefits. Regarding the prevention of diseases, ML and specifically DL models can accurately predict or detect diseases earlier than current clinical diagnoses. Adding personally responsible factors allows targeted prevention interventions. While ML models based on textual EHRs are still in the developmental stage, they have high potential to support clinicians and the health care system and improve patient outcomes.

Loss to Follow Up Among Glaucoma Patients: An IRIS® Registry (Intelligent Research in Sight) Retrospective Cohort Analysis.

PURPOSE: To identify prevalence of and risk factors for loss to follow up (LTFU) among a national cohort of patients with primary open-angle glaucoma (POAG). METHODS: This retrospective cohort study analyzed data from the IRIS® Registry (Intelligent Research in Sight) database from 2014 through 2019 to assess LTFU among adult patients with POAG. POAG patients with at least one clinical encounter in 2014 were included. LTFU was defined as exceeding one year without a clinical encounter during the study period. RESULTS: Among 553,663 glaucoma patients, 277,019 (50%) became LTFU, of whom 184,548 (67%) never returned to care and 92,471 (33%) re-established follow-up after a lapse. Risk of LTFU was greatest among those younger than 60 years (RR = 1.38; 95% CI: 1.36-1.39) or older than 80 years (RR = 1.39; 95% CI: 1.38-1.40) compared to those in their 60s. Compared to White race, risk for LTFU was highest among Native Hawaiian/Pacific Islander (RR = 1.24; 95% CI: 1.17-1.31), Hispanic ethnicity (RR = 1.19; 95% CI: 1.18-1.20), and Black race (RR = 1.10; 95% CI: 1.09-1.11). Medicare insurance was associated with lower risk of LTFU (RR = 0.79; 95% CI: 0.78-0.79), whereas unknown/missing/no insurance was associated with greater risk (RR = 1.33; 95% CI: 1.32-1.34), compared to private insurance. Compared to mild-stage POAG, risk of LTFU was higher for moderate-stage (RR = 1.10; 95% CI: 1.08-1.13) and severe-stage disease (RR = 1.35; 95% CI: 1.32-1.38). CONCLUSION: We found a 50% prevalence of LTFU among POAG patients in the IRIS Registry over a 6-year study period, with greater risk among minority groups and those with more advanced disease.

From bed to bench and back again: Challenges facing deployment of intracranial pressure data analysis in clinical environments.

Introduction: Numerous complex physiological models derived from intracranial pressure (ICP) monitoring data have been developed. More recently, techniques such as machine learning are being used to develop increasingly sophisticated models to aid in clinical decision-making tasks such as diagnosis and prediction. Whilst their potential clinical impact may be significant, few models based on ICP data are routinely available at a patient's bedside. Further, the ability to refine models using ongoing patient data collection is rare. In this paper we identify and discuss the challenges faced when converting insight from ICP data analysis into deployable tools at the patient bedside. Research question: To provide an overview of challenges facing implementation of sophisticated ICP models and analyses at the patient bedside. Material and methods: A narrative review of the barriers facing implementation of sophisticated ICP models and analyses at the patient bedside in a neurocritical care unit combined with a descriptive case study (the CHART-ADAPT project) on the topic. Results: Key barriers found were technical, analytical, and integrity related. Examples included: lack of interoperability of medical devices for data collection and/or model deployment; inadequate infrastructure, hindering analysis of large volumes of high frequency patient data; a lack of clinical confidence in a model; and ethical, trust, security and patient confidentiality considerations governing the secondary use of patient data. Discussion and conclusion: To realise the benefits of ICP data analysis, the results need to be promptly delivered and meaningfully communicated. Multiple barriers to implementation remain and solutions which address real-world challenges are required.

Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial.

BACKGROUND: The serotonin 4 receptor (5-HT4R) is a promising target for the treatment of depression. Highly selective 5-HT4R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established. AIMS: To determine whether prucalopride (a 5-HT4R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system. METHOD: Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders. RESULTS: Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76-0.99; P = 0.038; n = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69-0.91; P < 0.001; n = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses. CONCLUSIONS: These findings support preclinical data and suggest a role for 5-HT4R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.