Prediction models using artificial intelligence and longitudinal data from electronic health records: a systematic methodological review

Objective: To describe and appraise the use of artificial intelligence (AI) techniques that can cope with longitudinal data from electronic health records (EHRs) to predict health-related outcomes. Methods: This review included studies in any language that: EHR was at least one of the data sources, collected longitudinal data, used an AI technique capable of handling longitudinal data, and predicted any health-related outcomes. We searched MEDLINE, Scopus, Web of Science, and IEEE Xplorer from inception to January 3, 2022. Information on the dataset, prediction task, data preprocessing, feature selection, method, validation, performance, and implementation was extracted and summarized using descriptive statistics. Risk of bias and completeness of reporting were assessed using a short form of PROBAST and TRIPOD, respectively. Results: Eighty-one studies were included. Follow-up time and number of registers per patient varied greatly, and most predicted disease development or next event based on diagnoses and drug treatments. Architectures generally were based on Recurrent Neural Networks-like layers, though in recent years combining different layers or transformers has become more popular. About half of the included studies performed hyperparameter tuning and used attention mechanisms. Most performed a single train-test partition and could not correctly assess the variability of the model’s performance. Reporting quality was poor, and a third of the studies were at high risk of bias. Conclusions: AI models are increasingly using longitudinal data. However, the heterogeneity in reporting methodology and results, and the lack of public EHR datasets and code sharing, complicate the possibility of replication.The project received a research grant from the Carlos III Institute of Health, Ministry of Economy and Competitiveness (Spain), awarded on the 2019 call under the Health Strategy Action 2013-2016, within the National Research Programme oriented to Societal Challenges, within the Technical, Scientific and Innovation Research National Plan 2013-2016 (reference PI19/00535), and the PFIS Grant FI20/00040, cofunded with European Union ERDF (European Regional Development Fund) funds. The project has also been partially funded by Generalitat de Catalunya through the AGAUR (grant numbers 2021-SGR-01033, 2021-SGR-01537).Peer ReviewedPostprint (published version

Polypharmacy Patterns in Multimorbid Older People with Cardiovascular Disease : Longitudinal Study

(1) Introduction: Cardiovascular disease is associated with high mortality, especially in older people. This study aimed to characterize the evolution of combined multimorbidity and polypharmacy patterns in older people with different cardiovascular disease profiles. (2) Material and methods: This longitudinal study drew data from the Information System for Research in Primary Care in people aged 65 to 99 years with profiles of cardiovascular multimorbidity. Combined patterns of multimorbidity and polypharmacy were analysed using fuzzy c-means clustering techniques and hidden Markov models. The prevalence, observed/expected ratio, and exclusivity of chronic diseases and/or groups of these with the corresponding medication were described. (3) Results: The study included 114,516 people, mostly men (59.6%) with a mean age of 78.8 years and a high prevalence of polypharmacy (83.5%). The following patterns were identified: Mental, behavioural, digestive and cerebrovascular ; Neuropathy, autoimmune and musculoskeletal ; Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological ; Non-specific ; Multisystemic ; Respiratory, cardiovascular, behavioural and genitourinary ; Diabetes and ischemic cardiopathy ; and Cardiac. The prevalence of overrepresented health problems and drugs remained stable over the years, although by study end, cohort survivors had more polypharmacy and multimorbidity. Most people followed the same pattern over time; the most frequent transitions were from Non-specific to Mental, behavioural, digestive and cerebrovascular and from Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological to Non-specific. (4) Conclusions: Eight combined multimorbidity and polypharmacy patterns, differentiated by sex, remained stable over follow-up. Understanding the behaviour of different diseases and drugs can help design individualised interventions in populations with clinical complexity

Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses

Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance and ample phenotypic expressivity in CVID suggest the participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for CVID are uniquely valuable for studying the contribution of epigenetics to the disease. Here, we generate a single-cell epigenomics and transcriptomics census of naïve-to-memory B cell differentiation in a CVID-discordant MZ twin pair. Our analysis identifies DNA methylation, chromatin accessibility and transcriptional defects in memory B-cells mirroring defective cell-cell communication upon activation. These findings are validated in a cohort of CVID patients and healthy donors. Our findings provide a comprehensive multi-omics map of alterations in naïve-to-memory B-cell transition in CVID and indicate links between the epigenome and immune cell cross-talk. Our resource, publicly available at the Human Cell Atlas, gives insight into future diagnosis and treatments of CVID patients

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Análisis de la evolución del nivel de precios de las viviendas en las Islas Baleares

[spa] Este trabajo analiza la evolución del índice de los precios de las viviendas (IPV) en las Islas Baleares durante el período 2007-2018. Se cuestiona si hay estacionalidad en el IPV y si ésta es estadísticamente significativa. También se repasarán algunos estudios para conocer los factores que influyen en los precios de las viviendas en las Islas Baleares. Se utilizará la serie del IPV trimestral para conocer con más detalle la variación inter-trimestral y se estimará esta serie por medio de distintos modelos como Holt, Holt-Winters aditivo y Holt-Winters multiplicativo. Por último, se compararán los modelos estimados donde se comprobará que las variaciones estacionales varían proporcionalmente al nivel de la serie. Estos descubrimientos pueden ser útiles tanto para compañías inmobiliarias, empresas turísticas e individuos particulares. También para organismos públicos con el fin de corregir desequilibrios y que su evolución no dañe ni se propague a otros sectores. Gracias a este análisis los agentes pueden definir una estrategia donde optimicen sus recursos y decidan mejor el precio a negociar y el momento adecuado para comprar o vender una vivienda en las Islas Baleares.[eng] This paper analyzes the evolution of the housing price index (IPV) in the Balearic Islands during the 2007-2018 period. We verify whether there is seasonality the IPV, and if it is statistically significant. Besides, we review some studies that to know the factors that influence the IPV in the Balearic Islands. We apply the quarterly IPV series to examine the quarterly variation in more detail, and we model the IPV by different methods such as Holt, additive Holt-Winters, and multiplicative Holt-Winters. Finally, we compare the estimated models, and we find that seasonal variations fluctuate proportionally to the level of the IPV. These findings are useful for real estate companies, tourism companies, and private individuals. They are also relevant for public organizations to correct imbalances so that the evolution of the IPV does not spread to other sectors of the economy. Our analysis allows economic agents to define an optimal allocation of their resources, to decide the best negotiable price, and to define the best time to sell or to buy a house in the Balearic Islands

Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses.

Funder: Wellcome TrustCommon variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance and ample phenotypic expressivity in CVID suggest the participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for CVID are uniquely valuable for studying the contribution of epigenetics to the disease. Here, we generate a single-cell epigenomics and transcriptomics census of naïve-to-memory B cell differentiation in a CVID-discordant MZ twin pair. Our analysis identifies DNA methylation, chromatin accessibility and transcriptional defects in memory B-cells mirroring defective cell-cell communication upon activation. These findings are validated in a cohort of CVID patients and healthy donors. Our findings provide a comprehensive multi-omics map of alterations in naïve-to-memory B-cell transition in CVID and indicate links between the epigenome and immune cell cross-talk. Our resource, publicly available at the Human Cell Atlas, gives insight into future diagnosis and treatments of CVID patients