Respiratory diseases represent one of the most significant economic burdens on healthcare systems worldwide. The variation in the increasing number of cases depends greatly on climatic seasonal effects, socioeconomic factors, and pollution. Therefore, understanding these variations and obtaining precise forecasts allows health authorities to make correct decisions regarding the allocation of limited economic and human resources. This study aims to model and forecast weekly hospitalizations due to respiratory conditions in seven regional hospitals in Costa Rica using four statistical learning techniques (Random Forest, XGboost, Facebook's Prophet forecasting model, and an ensemble method combining the above methods), along with 22 climate change indices and aerosol optical depth as an indicator of pollution. Models are trained using data from 2000 to 2018 and are evaluated using data from 2019 as testing data. Reliable predictions are obtained for each of the seven regional hospitals
New biological assays like Perturb-seq link highly parallel CRISPR interventions to a high-dimensional transcriptomic readout, providing insight into gene regulatory networks. Causal gene regulatory networks can be represented by directed acyclic graph (DAGs), but learning DAGs from observational data is complicated by lack of identifiability and a combinatorial solution space. Score-based structure learning improves practical scalability of inferring DAGs. Previous score-based methods are sensitive to error variance structure; on the other hand, estimation of error variance is difficult without prior knowledge of structure. Accordingly, we present $\texttt{dotears}$ [doo-tairs], a continuous optimization framework which leverages observational and interventional data to infer a single causal structure, assuming a linear Structural Equation Model (SEM). $\texttt{dotears}$ exploits structural consequences of hard interventions to give a marginal estimate of exogenous error structure, bypassing the circular estimation problem. We show that $\texttt{dotears}$ is a provably consistent estimator of the true DAG under mild assumptions. $\texttt{dotears}$ outperforms other methods in varied simulations, and in real data infers edges that validate with higher precision and recall than state-of-the-art methods through differential expression tests and high-confidence protein-protein interactions.
Covariate adjustment is a ubiquitous method used to estimate the average treatment effect (ATE) from observational data. Assuming a known graphical structure of the data generating model, recent results give graphical criteria for optimal adjustment, which enables efficient estimation of the ATE. However, graphical approaches are challenging for high-dimensional and complex data, and it is not straightforward to specify a meaningful graphical model of non-Euclidean data such as texts. We propose an general framework that accommodates adjustment for any subset of information expressed by the covariates. We generalize prior works and leverage these results to identify the optimal covariate information for efficient adjustment. This information is minimally sufficient for prediction of the outcome conditionally on treatment. Based on our theoretical results, we propose the Debiased Outcome-adapted Propensity Estimator (DOPE) for efficient estimation of the ATE, and we provide asymptotic results for the DOPE under general conditions. Compared to the augmented inverse propensity weighted (AIPW) estimator, the DOPE can retain its efficiency even when the covariates are highly predictive of treatment. We illustrate this with a single-index model, and with an implementation of the DOPE based on neural networks, we demonstrate its performance on simulated and real data. Our results show that the DOPE provides an efficient and robust methodology for ATE estimation in various observational settings.
Estimands using the treatment policy strategy for addressing intercurrent events are common in Phase III clinical trials. One estimation approach for this strategy is retrieved dropout whereby observed data following an intercurrent event are used to multiply impute missing data. However, such methods have had issues with variance inflation and model fitting due to data sparsity. This paper introduces likelihood-based versions of these approaches, investigating and comparing their statistical properties to the existing retrieved dropout approaches, simpler analysis models and reference-based multiple imputation. We use a simulation based upon the data from the PIONEER 1 Phase III clinical trial in Type II diabetics to present complex and relevant estimation challenges. The likelihood-based methods display similar statistical properties to their multiple imputation equivalents, but all retrieved dropout approaches suffer from high variance. Retrieved dropout approaches appear less biased than reference-based approaches, resulting in a bias-variance trade-off, but we conclude that the large degree of variance inflation is often more problematic than the bias. Therefore, only the simpler retrieved dropout models appear appropriate as a primary analysis in a clinical trial, and only where it is believed most data following intercurrent events will be observed. The jump-to-reference approach may represent a more promising estimation approach for symptomatic treatments due to its relatively high power and ability to fit in the presence of much missing data, despite its strong assumptions and tendency towards conservative bias. More research is needed to further develop how to estimate the treatment effect for a treatment policy strategy.
Functional Connectivity between brain regions is known to be altered in Alzheimer's disease, and promises to be a biomarker for early diagnosis of the disease. While several approaches for functional connectivity obtain an un-directed network representing stochastic associations (correlations) between brain regions, association does not necessarily imply causation. In contrast, Causal Functional Connectivity is more informative, providing a directed network representing causal relationships between brain regions. In this paper, we obtained the causal functional connectome for the whole brain from recordings of resting-state functional magnetic resonance imaging (rs-fMRI) for subjects from three clinical groups: cognitively normal, mild cognitive impairment, and Alzheimer's disease. We applied the recently developed Time-aware PC (TPC) algorithm to infer the causal functional connectome for the whole brain. TPC supports model-free estimation of whole brain causal functional connectivity based on directed graphical modeling in a time series setting. We then perform an exploratory analysis to identify the causal brain connections between brain regions which have altered strengths between pairs of subject groups, and over the three subject groups, based on edge-wise p-values from statistical tests. We used the altered causal brain connections thus obtained to compile a comprehensive list of brain regions impacted by Alzheimer's disease according to the current data set. The brain regions thus identified are found to be in agreement with literature on brain regions impacted by Alzheimer's disease, published by researchers from clinical/medical institutions.
The discharge summary is a one of critical documents in the patient journey, encompassing all events experienced during hospitalization, including multiple visits, medications, tests, surgery/procedures, and admissions/discharge. Providing a summary of the patient's progress is crucial, as it significantly influences future care and planning. Consequently, clinicians face the laborious and resource-intensive task of manually collecting, organizing, and combining all the necessary data for a discharge summary. Therefore, we propose "NOTE", which stands for "Notable generation Of patient Text summaries through an Efficient approach based on direct preference optimization". NOTE is based on Medical Information Mart for Intensive Care- III dataset and summarizes a single hospitalization of a patient. Patient events are sequentially combined and used to generate a discharge summary for each hospitalization. In the present circumstances, large language models' application programming interfaces (LLMs' APIs) are widely available, but importing and exporting medical data presents significant challenges due to privacy protection policies in healthcare institutions. Moreover, to ensure optimal performance, it is essential to implement a lightweight model for internal server or program within the hospital. Therefore, we utilized DPO and parameter efficient fine tuning (PEFT) techniques to apply a fine-tuning method that guarantees superior performance. To demonstrate the practical application of the developed NOTE, we provide a webpage-based demonstration software. In the future, we will aim to deploy the software available for actual use by clinicians in hospital. NOTE can be utilized to generate various summaries not only discharge summaries but also throughout a patient's journey, thereby alleviating the labor-intensive workload of clinicians and aiming for increased efficiency.
Stroke is one of the leading causes of disability worldwide. The efficacy of recovery is determined by a variety of factors, including patient adherence to rehabilitation programs. One way to increase patient adherence to their rehabilitation program is to show patients their progress that is visualized in a simple and intuitive way. We begin to gather preliminary information on Functional Capacity, Motor Function, and Mood/cognition from occupational Therapists at the Bruyere Hospital to gain a better understanding of how stroke recovery data is collected within in-patient stroke rehabilitation centers. The future aim is to design, develop, and evaluate a data visualization tool representing progress made by patients recovering from stroke.
Intracranial aneurysms are the leading cause of stroke. One of the established treatment approaches is the embolization induced by coil insertion. However, the prediction of treatment and subsequent changed flow characteristics in the aneurysm, is still an open problem. In this work, we present an approach based on patient specific geometry and parameters including a coil representation as inhomogeneous porous medium. The model consists of the volume-averaged Navier-Stokes equations including the non-Newtonian blood rheology. We solve these equations using a problem-adapted lattice Boltzmann method and present a comparison between fully-resolved and volume-averaged simulations. The results indicate the validity of the model. Overall, this workflow allows for patient specific assessment of the flow due to potential treatment.
For training registration networks, weak supervision from segmented corresponding regions-of-interest (ROIs) have been proven effective for (a) supplementing unsupervised methods, and (b) being used independently in registration tasks in which unsupervised losses are unavailable or ineffective. This correspondence-informing supervision entails cost in annotation that requires significant specialised effort. This paper describes a semi-weakly-supervised registration pipeline that improves the model performance, when only a small corresponding-ROI-labelled dataset is available, by exploiting unlabelled image pairs. We examine two types of augmentation methods by perturbation on network weights and image resampling, such that consistency-based unsupervised losses can be applied on unlabelled data. The novel WarpDDF and RegCut approaches are proposed to allow commutative perturbation between an image pair and the predicted spatial transformation (i.e. respective input and output of registration networks), distinct from existing perturbation methods for classification or segmentation. Experiments using 589 male pelvic MR images, labelled with eight anatomical ROIs, show the improvement in registration performance and the ablated contributions from the individual strategies. Furthermore, this study attempts to construct one of the first computational atlases for pelvic structures, enabled by registering inter-subject MRs, and quantifies the significant differences due to the proposed semi-weak supervision with a discussion on the potential clinical use of example atlas-derived statistics.
Analyzing longitudinal data in health studies is challenging due to sparse and error-prone measurements, strong within-individual correlation, missing data and various trajectory shapes. While mixed-effect models (MM) effectively address these challenges, they remain parametric models and may incur computational costs. In contrast, Functional Principal Component Analysis (FPCA) is a non-parametric approach developed for regular and dense functional data that flexibly describes temporal trajectories at a lower computational cost. This paper presents an empirical simulation study evaluating the behaviour of FPCA with sparse and error-prone repeated measures and its robustness under different missing data schemes in comparison with MM. The results show that FPCA is well-suited in the presence of missing at random data caused by dropout, except in scenarios involving most frequent and systematic dropout. Like MM, FPCA fails under missing not at random mechanism. The FPCA was applied to describe the trajectories of four cognitive functions before clinical dementia and contrast them with those of matched controls in a case-control study nested in a population-based aging cohort. The average cognitive declines of future dementia cases showed a sudden divergence from those of their matched controls with a sharp acceleration 5 to 2.5 years prior to diagnosis.
Breast cancer remains a global challenge, causing over 1 million deaths globally in 2018. To achieve earlier breast cancer detection, screening x-ray mammography is recommended by health organizations worldwide and has been estimated to decrease breast cancer mortality by 20-40%. Nevertheless, significant false positive and false negative rates, as well as high interpretation costs, leave opportunities for improving quality and access. To address these limitations, there has been much recent interest in applying deep learning to mammography; however, obtaining large amounts of annotated data poses a challenge for training deep learning models for this purpose, as does ensuring generalization beyond the populations represented in the training dataset. Here, we present an annotation-efficient deep learning approach that 1) achieves state-of-the-art performance in mammogram classification, 2) successfully extends to digital breast tomosynthesis (DBT; "3D mammography"), 3) detects cancers in clinically-negative prior mammograms of cancer patients, 4) generalizes well to a population with low screening rates, and 5) outperforms five-out-of-five full-time breast imaging specialists by improving absolute sensitivity by an average of 14%. Our results demonstrate promise towards software that can improve the accuracy of and access to screening mammography worldwide.