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Francesca Ieva

Publications and source records attributed to Francesca Ieva.

At least 37 records · Page 2Linked to original sources
arXiv2025

Interpretable phenotyping of Heart Failure patients with Dutch discharge letters

Objective: Heart failure (HF) patients present with diverse phenotypes affecting treatment and prognosis. This study evaluates models for phenotyping HF patients based on left ventricular ejection fraction (LVEF) classes, using structured and unstructured data, assessing performance and interpretability. Materials and Methods: The study analyzes all HF hospitalizations at both Amsterdam UMC hospitals (AMC and VUmc) from 2015 to 2023 (33,105 hospitalizations, 16,334 patients). Data from AMC were used for model training, and from VUmc for external validation. The dataset was unlabelled and included tabular clinical measurements and discharge letters. Silver labels for LVEF classes were generated by combining diagnosis codes, echocardiography results, and textual mentions. Gold labels were manually annotated for 300 patients for testing. Multiple Transformer-based (black-box) and Aug-Linear (white-box) models were trained and compared with baselines on structured and unstructured data. To evaluate interpretability, two clinicians annotated 20 discharge letters by highlighting information they considered relevant for LVEF classification. These were compared to SHAP and LIME explanations from black-box models and the inherent explanations of Aug-Linear models. Results: BERT-based and Aug-Linear models, using discharge letters alone, achieved the highest classification results (AUC=0.84 for BERT, 0.81 for Aug-Linear on external validation), outperforming baselines. Aug-Linear explanations aligned more closely with clinicians' explanations than post-hoc explanations on black-box models. Conclusions: Discharge letters emerged as the most informative source for phenotyping HF patients. Aug-Linear models matched black-box performance while providing clinician-aligned interpretability, supporting their use in transparent clinical decision-making.

cs.CL↗
arXiv2025

DISARM++: Beyond scanner-free harmonization

Harmonization of T1-weighted MR images across different scanners is crucial for ensuring consistency in neuroimaging studies. This study introduces a novel approach to direct image harmonization, moving beyond feature standardization to ensure that extracted features remain inherently reliable for downstream analysis. Our method enables image transfer in two ways: (1) mapping images to a scanner-free space for uniform appearance across all scanners, and (2) transforming images into the domain of a specific scanner used in model training, embedding its unique characteristics. Our approach presents strong generalization capability, even for unseen scanners not included in the training phase. We validated our method using MR images from diverse cohorts, including healthy controls, traveling subjects, and individuals with Alzheimer's disease (AD). The model's effectiveness is tested in multiple applications, such as brain age prediction (R2 = 0.60 \pm 0.05), biomarker extraction, AD classification (Test Accuracy = 0.86 \pm 0.03), and diagnosis prediction (AUC = 0.95). In all cases, our harmonization technique outperforms state-of-the-art methods, showing improvements in both reliability and predictive accuracy. Moreover, our approach eliminates the need for extensive preprocessing steps, such as skull-stripping, which can introduce errors by misclassifying brain and non-brain structures. This makes our method particularly suitable for applications that require full-head analysis, including research on head trauma and cranial deformities. Additionally, our harmonization model does not require retraining for new datasets, allowing smooth integration into various neuroimaging workflows. By ensuring scanner-invariant image quality, our approach provides a robust and efficient solution for improving neuroimaging studies across diverse settings. The code is available at this link.

cs.CV↗
arXiv2024

Uncover mortality patterns and hospital effects in COVID-19 heart failure patients: a novel Multilevel logistic cluster-weighted modeling approach

Evaluating hospitals' performance and its relation to patients' characteristics is of utmost importance to ensure timely, effective, and optimal treatment. Such a matter is particularly relevant in areas and situations where the healthcare system must contend with an unexpected surge in hospitalizations, such as for heart failure patients in the Lombardy region of Italy during the COVID-19 pandemic. Motivated by this issue, the paper introduces a novel Multilevel Logistic Cluster-Weighted Model (ML-CWMd) for predicting 45-day mortality following hospitalization due to COVID-19. The methodology flexibly accommodates dependence patterns among continuous, categorical, and dichotomous variables; effectively accounting for hospital-specific effects in distinct patient subgroups showing different attributes. A tailored Expectation-Maximization algorithm is developed for parameter estimation, and extensive simulation studies are conducted to evaluate its performance against competing models. The novel approach is applied to administrative data from the Lombardy Region, aiming to profile heart failure patients hospitalized for COVID-19 and investigate the hospital-level impact on their overall mortality. A scenario analysis demonstrates the model's efficacy in managing multiple sources of heterogeneity, thereby yielding promising results in aiding healthcare providers and policy-makers in the identification of patient-specific treatment pathways.

stat.AP↗
arXiv2023

Integrating state-sequence analysis to uncover dynamic drug-utilization patterns to profile heart failure patients

Globally, the incidence of heart failure is increasing, and its principal treatment involves drug therapy. However, widespread non-adherence to therapies is prevalent among heart failure patients and often results in worsening health conditions and an increase in hospital admissions. This study aims to develop an innovative approach, the State-Sequence analysis, to profile heart failure patients based on different drug-utilization patterns. These patterns aim to capture both the multidimensional and dynamic effects of therapies. Subsequently, the study explores how combining clustering algorithms with this technique influences overall patient survival. Findings highlight the importance of continued drug therapy after the first hospitalization in improving heart failure prognosis, irrespective of its severity. The proposed approach can assist healthcare specialists in evaluating the pathways provided to patients, allowing for a change in analysis from a transversal and syntactical approach to a holistic one that leverages statistical tools that are slightly more complex than traditional methods. Moreover, because of the many options available for defining states, temporal granularity, and spacing metrics, SSA is a flexible method applicable to various epidemiological scenarios.

stat.AP↗
arXiv2023

Estimation of Dynamic Origin-Destination Matrices in a Railway Transportation Network integrating Ticket Sales and Passenger Count Data

Accurately estimating Origin-Destination (OD) matrices is a topic of increasing interest for efficient transportation network management and sustainable urban planning. Traditionally, travel surveys have supported this process; however, their availability and comprehensiveness can be limited. Moreover, the recent COVID-19 pandemic has triggered unprecedented shifts in mobility patterns, underscoring the urgency of accurate and dynamic mobility data supporting policies and decisions with data-driven evidence. In this study, we tackle these challenges by introducing an innovative pipeline for estimating dynamic OD matrices. The real motivating problem behind this is based on the Trenord railway transportation network in Lombardy, Italy. We apply a novel approach that integrates ticket and subscription sales data with passenger counts obtained from Automated Passenger Counting (APC) systems, making use of the Iterative Proportional Fitting (IPF) algorithm. Our work effectively addresses the complexities posed by incomplete and diverse data sources, showcasing the adaptability of our pipeline across various transportation contexts. Ultimately, this research bridges the gap between available data sources and the escalating need for precise OD matrices. The proposed pipeline fosters a comprehensive grasp of transportation network dynamics, providing a valuable tool for transportation operators, policymakers, and researchers. Indeed, to highlight the potentiality of dynamic OD matrices, we showcase some methods to perform anomaly detection of mobility trends in the network through such matrices and interpret them in light of events that happened in the last months of 2022.

stat.AP↗
arXiv2023

Causal effect of chemotherapy received dose intensity on survival outcome: a retrospective study in osteosarcoma

This study aims to analyse the effects of reducing Received Dose Intensity (RDI) in chemotherapy treatment for osteosarcoma patients on their survival by using a novel approach. In this scenario, toxic side effects are risk factors for mortality and predictors of future exposure levels, introducing post-assignment confounding. Chemotherapy administration data from BO03 and BO06 Randomized Clinical Trials (RCTs) in ostosarcoma are employed to emulate a target trial with three RDI-based exposure strategies: 1) standard, 2) reduced, and 3) highly-reduced RDI. Investigations are conducted between subgroups of patients characterised by poor or good Histological Responses (HRe). Inverse Probability of Treatment Weighting (IPTW) is first used to transform the original population into a pseudo-population which mimics the target randomized cohort. Then, a Marginal Structural Cox Model with effect modification is employed. Conditional Average Treatment Effects (CATEs) are ultimately measured as the difference between the Restricted Mean Survival Time of reduced/highly-reduced RDI strategy and the standard one. Confidence Intervals for CATEs are obtained using a novel IPTW-based bootstrap procedure. Significant effect modifications based on HRe were found. Increasing RDI-reductions led to contrasting trends for poor and good responders: the higher the reduction, the better (worsen) was the survival in poor (good) reponders. This study introduces a novel approach to (i) comprehensively address the challenges related to the analysis of chemotherapy data, (ii) mitigate the toxicity-treatment-adjustment bias, and (iii) repurpose existing RCT data for retrospective analyses extending beyond the original trials' intended scopes.

stat.AP↗
arXiv2023

Joint modelling of recurrent and terminal events with discretely-distributed non-parametric frailty: application on re-hospitalizations and death in heart failure patients

In the context of clinical and biomedical studies, joint frailty models have been developed to study the joint temporal evolution of recurrent and terminal events, capturing both the heterogeneous susceptibility to experiencing a new episode and the dependence between the two processes. While discretely-distributed frailty is usually more exploitable by clinicians and healthcare providers, existing literature on joint frailty models predominantly assumes continuous distributions for the random effects. In this article, we present a novel joint frailty model that assumes bivariate discretely-distributed non-parametric frailties, with an unknown finite number of mass points. This approach facilitates the identification of latent structures among subjects, grouping them into sub-populations defined by a shared frailty value. We propose an estimation routine via Expectation-Maximization algorithm, which not only estimates the number of subgroups but also serves as an unsupervised classification tool. This work is motivated by a study of patients with Heart Failure (HF) receiving ACE inhibitors treatment in the Lombardia region of Italy. Recurrent events of interest are hospitalizations due to HF and terminal event is death for any cause.

stat.ME↗
arXiv2023

How much of the past matters? Using dynamic survival models for the monitoring of potassium in heart failure patients using electronic health records

Statistical methods to study the association between a longitudinal biomarker and the risk of death are very relevant for the long-term care of subjects affected by chronic illnesses, such as potassium in heart failure patients. Particularly in the presence of comorbidities or pharmacological treatments, sudden crises can cause potassium to undergo very abrupt yet transient changes. In the context of the monitoring of potassium, there is a need for a dynamic model that can be used in clinical practice to assess the risk of death related to an observed patient's potassium trajectory. We considered different dynamic survival approaches, starting from the simple approach considering the most recent measurement, to the joint model. We then propose a novel method based on wavelet filtering and landmarking to retrieve the prognostic role of past short-term potassium shifts. We argue that while taking into account past information is important, not all past information is equally informative. State-of-the-art dynamic survival models are prone to give more importance to the mean long-term value of potassium. However, our findings suggest that it is essential to take into account also recent potassium instability to capture all the relevant prognostic information. The data used comes from over 2000 subjects, with a total of over 80 000 repeated potassium measurements collected through Administrative Health Records and Outpatient and Inpatient Clinic E-charts. A novel dynamic survival approach is proposed in this work for the monitoring of potassium in heart failure. The proposed wavelet landmark method shows promising results revealing the prognostic role of past short-term changes, according to their different duration, and achieving higher performances in predicting the survival probability of individuals.

stat.ME↗
arXiv2023

Dynamic treatment effect phenotyping through functional survival analysis

In recent years, research interest in personalised treatments has been growing. However, treatment effect heterogeneity and possibly time-varying treatment effects are still often overlooked in clinical studies. Statistical tools are needed for the identification of treatment response patterns, taking into account that treatment response is not constant over time. We aim to provide an innovative method to obtain dynamic treatment effect phenotypes on a time-to-event outcome, conditioned on a set of relevant effect modifiers. The proposed method does not require the assumption of proportional hazards for the treatment effect, which is rarely realistic. We propose a spline-based survival neural network, inspired by the Royston-Parmar survival model, to estimate time-varying conditional treatment effects. We then exploit the functional nature of the resulting estimates to apply a functional clustering of the treatment effect curves in order to identify different patterns of treatment effects. The application that motivated this work is the discontinuation of treatment with Mineralocorticoid receptor Antagonists (MRAs) in patients with heart failure, where there is no clear evidence as to which patients it is the safest choice to discontinue treatment and, conversely, when it leads to a higher risk of adverse events. The data come from an electronic health record database. A simulation study was performed to assess the performance of the spline-based neural network and the stability of the treatment response phenotyping procedure. In light of the results, the suggested approach has the potential to support personalized medical choices by assessing unique treatment responses in various medical contexts over a period of time.

stat.ME↗
arXiv2023

Scaling Survival Analysis in Healthcare with Federated Survival Forests: A Comparative Study on Heart Failure and Breast Cancer Genomics

Survival analysis is a fundamental tool in medicine, modeling the time until an event of interest occurs in a population. However, in real-world applications, survival data are often incomplete, censored, distributed, and confidential, especially in healthcare settings where privacy is critical. The scarcity of data can severely limit the scalability of survival models to distributed applications that rely on large data pools. Federated learning is a promising technique that enables machine learning models to be trained on multiple datasets without compromising user privacy, making it particularly well-suited for addressing the challenges of survival data and large-scale survival applications. Despite significant developments in federated learning for classification and regression, many directions remain unexplored in the context of survival analysis. In this work, we propose an extension of the Federated Survival Forest algorithm, called FedSurF++. This federated ensemble method constructs random survival forests in heterogeneous federations. Specifically, we investigate several new tree sampling methods from client forests and compare the results with state-of-the-art survival models based on neural networks. The key advantage of FedSurF++ is its ability to achieve comparable performance to existing methods while requiring only a single communication round to complete. The extensive empirical investigation results in a significant improvement from the algorithmic and privacy preservation perspectives, making the original FedSurF algorithm more efficient, robust, and private. We also present results on two real-world datasets demonstrating the success of FedSurF++ in real-world healthcare studies. Our results underscore the potential of FedSurF++ to improve the scalability and effectiveness of survival analysis in distributed settings while preserving user privacy.

cs.LG↗
arXiv2023

Longitudinal Latent Overall Toxicity (LOTox) profiles in osteosarcoma: a new taxonomy based on latent Markov models

Due to the presence of multiple types of adverse events with different levels of severity, the analysis of longitudinal toxicity data is a difficult task in cancer studies. In this work, a novel approach based on latent Markov models and compositional data techniques is proposed. The latent status of interest is the Latent Overall Toxicity (LOTox) condition of each patient. The main objectives consist in identifying different latent states of overall toxicity burden and investigating the evolution of individual toxicity risk during cancer treatment. This methodology is applied to osteosarcoma treatment data to provide novel techniques that may support medical decisions in childhood cancer therapy.

stat.AP↗
arXiv2023

A general framework for penalized mixed-effects multitask learning with applications on DNA methylation surrogate biomarkers creation

Recent evidence highlights the usefulness of DNA methylation (DNAm) biomarkers as surrogates for exposure to risk factors for non-communicable diseases in epidemiological studies and randomized trials. DNAm variability has been demonstrated to be tightly related to lifestyle behavior and exposure to environmental risk factors, ultimately providing an unbiased proxy of an individual state of health. At present, the creation of DNAm surrogates relies on univariate penalized regression models, with elastic-net regularizer being the gold standard when accomplishing the task. Nonetheless, more advanced modeling procedures are required in the presence of multivariate outcomes with a structured dependence pattern among the study samples. In this work we propose a general framework for mixed-effects multitask learning in presence of high-dimensional predictors to develop a multivariate DNAm biomarker from a multi-center study. A penalized estimation scheme based on an expectation-maximization algorithm is devised, in which any penalty criteria for fixed-effects models can be conveniently incorporated in the fitting process. We apply the proposed methodology to create novel DNAm surrogate biomarkers for multiple correlated risk factors for cardiovascular diseases and comorbidities. We show that the proposed approach, modeling multiple outcomes together, outperforms state-of-the-art alternatives, both in predictive power and bio-molecular interpretation of the results.

stat.AP↗
arXiv2023

Clustering Hierarchies via a Semi-Parametric Generalized Linear Mixed Model: a statistical significance-based approach

We introduce a novel statistical significance-based approach for clustering hierarchical data using semi-parametric linear mixed-effects models designed for responses with laws in the exponential family (e.g., Poisson and Bernoulli). Within the family of semi-parametric mixed-effects models, a latent clustering structure of the highest-level units can be identified by assuming the random effects to follow a discrete distribution with an unknown number of support points. We achieve this by computing α-level confidence regions of the estimated support point and identifying statistically different clusters. At each iteration of a tailored Expectation Maximization algorithm, the two closest estimated support points for which the confidence regions overlap collapse. Unlike the related state-of-the-art methods that rely on arbitrary thresholds to determine the merging of close discrete masses, the proposed approach relies on conventional statistical confidence levels, thereby avoiding the use of discretionary tuning parameters. To demonstrate the effectiveness of our approach, we apply it to data from the Programme for International Student Assessment (PISA - OECD) to cluster countries based on the rate of innumeracy levels in schools. Additionally, a simulation study and comparison with classical parametric and state-of-the-art models are provided and discussed.

stat.ME↗
arXiv2023

An Evaluation of Researchers' Migration Patterns in Europe using Digital Trace Data

The comprehension of the mechanisms behind the mobility of skilled workers is of paramount importance for policy making. The lacking nature of official measurements motivates the use of digital trace data extracted from ORCID public records. We use such data to investigate European regions, studied at NUTS2 level, over the time horizon of 2009 to 2020. We present a novel perspective where regions roles are dictated by the overall activity of the research community, contradicting the common brain drain interpretation of the phenomenon. We find that a high mobility is usually correlated with strong university prestige, high magnitude of investments and an overall good schooling level in a region.

stat.AP↗
arXiv2023

Imaging-based representation and stratification of intra-tumor Heterogeneity via tree-edit distance

Personalized medicine is the future of medical practice. In oncology, tumor heterogeneity assessment represents a pivotal step for effective treatment planning and prognosis prediction. Despite new procedures for DNA sequencing and analysis, non-invasive methods for tumor characterization are needed to impact on daily routine. On purpose, imaging texture analysis is rapidly scaling, holding the promise to surrogate histopathological assessment of tumor lesions. In this work, we propose a tree-based representation strategy for describing intra-tumor heterogeneity of patients affected by metastatic cancer. We leverage radiomics information extracted from PET/CT imaging and we provide an exhaustive and easily readable summary of the disease spreading. We exploit this novel patient representation to perform cancer subtyping according to hierarchical clustering technique. To this purpose, a new heterogeneity-based distance between trees is defined and applied to a case study of prostate cancer. Clusters interpretation is explored in terms of concordance with severity status, tumor burden and biological characteristics. Results are promising, as the proposed method outperforms current literature approaches. Ultimately, the proposed method draws a general analysis framework that would allow to extract knowledge from daily acquired imaging data of patients and provide insights for effective treatment planning.

stat.ME↗
arXiv2022

Mining and evaluation of patients' diagnostic therapeutic paths through state sequences analysis

The concept of care pathways is increasingly being used to enhance the quality of care and to optimize the use of resources for health care. Nevertheless, recommendations regarding the sequence of care are mostly based on consensus-based decisions as there is a lack of evidence on effective treatment sequences. In a real-world setting, classical statistical tools resulted to be insufficient to adequately consider a phenomenon with such high variability and has to be integrated with novel data mining techniques suitable of identifying patterns in complex data structures. Data-driven techniques can potentially support the empirical identification of effective care sequences by extracting them from data collected routinely. The purpose of this study is to perform sequence analysis to identify different patterns of treatment and to assess the most efficient in preventing adverse events. The clinical application that motivated the study of this method concerns the several problems frequently encountered in the quality of care provided in the mental health field. In particular, we analyzed administrative data provided by Regione Lombardia related to all the beneficiaries of the National Health Service with a diagnosis of schizophrenia from 2015 to 2018 resident in Lombardy, a region of northern Italy. This methodology considers the patient's therapeutic path as a conceptual unit, i.e., a sequence, composed of a succession of different states that can describe longitudinal patient's status. This kind of information, such as common patterns of care that allowed us to risk profile patients, can provide health policymakers an opportunity to plan optimum and individualized patient care by allocating appropriate resources, analyzing trends in the health status of a population, and finding the risk factors that can be leveraged to prevent the decline of mental health status at the population level.

stat.ME↗
arXiv2021

Learning Signal Representations for EEG Cross-Subject Channel Selection and Trial Classification

EEG technology finds applications in several domains. Currently, most EEG systems require subjects to wear several electrodes on the scalp to be effective. However, several channels might include noisy information, redundant signals, induce longer preparation times and increase computational times of any automated system for EEG decoding. One way to reduce the signal-to-noise ratio and improve classification accuracy is to combine channel selection with feature extraction, but EEG signals are known to present high inter-subject variability. In this work we introduce a novel algorithm for subject-independent channel selection of EEG recordings. Considering multi-channel trial recordings as statistical units and the EEG decoding task as the class of reference, the algorithm (i) exploits channel-specific 1D-Convolutional Neural Networks (1D-CNNs) as feature extractors in a supervised fashion to maximize class separability; (ii) it reduces a high dimensional multi-channel trial representation into a unique trial vector by concatenating the channels' embeddings and (iii) recovers the complex inter-channel relationships during channel selection, by exploiting an ensemble of AutoEncoders (AE) to identify from these vectors the most relevant channels to perform classification. After training, the algorithm can be exploited by transferring only the parametrized subgroup of selected channel-specific 1D-CNNs to new signals from new subjects and obtain low-dimensional and highly informative trial vectors to be fed to any classifier.

eess.SP↗
arXiv2021

Feature Selection for Imbalanced Data with Deep Sparse Autoencoders Ensemble

Class imbalance is a common issue in many domain applications of learning algorithms. Oftentimes, in the same domains it is much more relevant to correctly classify and profile minority class observations. This need can be addressed by Feature Selection (FS), that offers several further advantages, s.a. decreasing computational costs, aiding inference and interpretability. However, traditional FS techniques may become sub-optimal in the presence of strongly imbalanced data. To achieve FS advantages in this setting, we propose a filtering FS algorithm ranking feature importance on the basis of the Reconstruction Error of a Deep Sparse AutoEncoders Ensemble (DSAEE). We use each DSAE trained only on majority class to reconstruct both classes. From the analysis of the aggregated Reconstruction Error, we determine the features where the minority class presents a different distribution of values w.r.t. the overrepresented one, thus identifying the most relevant features to discriminate between the two. We empirically demonstrate the efficacy of our algorithm in several experiments on high-dimensional datasets of varying sample size, showcasing its capability to select relevant and generalizable features to profile and classify minority class, outperforming other benchmark FS methods. We also briefly present a real application in radiogenomics, where the methodology was applied successfully.

stat.ML↗