Spousal bereavement severely deteriorates mental health. While palliative care benefits dying patients, its "stress-buffering" effect on survivors' depression remains empirically elusive due to acute small-$N$ constraints in longitudinal dyadic data. This study evaluates the causal impact of palliative care on bereaved spouses while introducing Synthetic Data Generation (SDG) to resolve sample attrition in quasi-experimental designs. Using SHARE panel data, we augment the sparse treated cohort via a Conditional Tabular GAN, anchoring synthetic trajectories to empirical baseline constraints to preserve causal pathways. A Matched Difference-in-Differences estimator applied to the high-fidelity augmented dataset evaluates the treatment effect. Results reveal a non-linear psychological response. Palliative care initially exacerbates acute depressive symptoms at the time of loss ($β_0 = 0.218,\ p < 0.05$), reflecting the intense emotional confrontation of the intervention. However, a sustained stress-buffering effect emerges in subsequent periods ($β_2 = -0.763,\ p < 0.01$), indicating an accelerated long-term recovery compared to standard care. Estimates are highly robust to unob
While palliative care is increasingly commonly delivered to hospitalized patients with serious illnesses, few studies have estimated its causal effects. Courtright et al. (2016) adopted a cluster-randomized stepped-wedge design to assess the effect of palliative care on a patient-centered outcome. The randomized intervention was a nudge to administer palliative care but did not guarantee receipt of palliative care, resulting in noncompliance (compliance rate ~30%). A subsequent analysis using methods suited for standard trial designs produced statistically anomalous results, as an intention-to-treat analysis found no effect while an instrumental variable analysis did (Courtright et al., 2024). This highlights the need for a more principled approach to address noncompliance in stepped-wedge designs. We provide a formal causal inference framework for the stepped-wedge design with noncompliance by introducing a relevant causal estimand and corresponding estimators and inferential procedures. Through simulation, we compare an array of estimators across a range of stepped-wedge designs and provide practical guidance in choosing an analysis method. Finally, we apply our recommended metho
Type 2 diabetes prevention and treatment can benefit from personalized lifestyle prescriptions. However, the delivery of personalized lifestyle medicine prescriptions is limited by the shortage of trained professionals and the variability in physicians' expertise. We propose an offline contextual bandit approach that learns individualized lifestyle prescriptions from the aggregated NHANES profiles of 119,555 participants by minimizing the Magni glucose risk-reward function. The model encodes patient status and generates lifestyle medicine prescriptions, which are trained using a mixed-action Soft Actor-Critic algorithm. The task is treated as a single-step contextual bandit. The model is validated against lifestyle medicine prescriptions issued by three certified physicians from Xiangya Hospital. These results demonstrate that offline mixed-action SAC can generate risk-aware lifestyle medicine prescriptions from cross-sectional NHANES data, warranting prospective clinical validation.
Model Medicine is the science of understanding, diagnosing, treating, and preventing disorders in AI models, grounded in the principle that AI models -- like biological organisms -- have internal structures, dynamic processes, heritable traits, observable symptoms, classifiable conditions, and treatable states. This paper introduces Model Medicine as a research program, bridging the gap between current AI interpretability research (anatomical observation) and the systematic clinical practice that complex AI systems increasingly require. We present five contributions: (1) a discipline taxonomy organizing 15 subdisciplines across four divisions -- Basic Model Sciences, Clinical Model Sciences, Model Public Health, and Model Architectural Medicine; (2) the Four Shell Model (v3.3), a behavioral genetics framework empirically grounded in 720 agents and 24,923 decisions from the Agora-12 program, explaining how model behavior emerges from Core--Shell interaction; (3) Neural MRI (Model Resonance Imaging), a working open-source diagnostic tool mapping five medical neuroimaging modalities to AI interpretability techniques, validated through four clinical cases demonstrating imaging, compari
The transition of end-of-life care to palliative care (PC) sparks intense debate: does it provide economic relief or shift unremunerated labor costs onto families? Evaluating this is hindered by causal inference challenges and skewed healthcare costs. To overcome these limitations, we introduce a Synthetic Data Generation framework. Using pan-European SHARE data (2016-2021), we deploy Tabular Denoising Diffusion Probabilistic Models within a Two-Learner architecture to synthesize high-fidelity digital twins. By including the 2020-2021 lockdowns, we leverage the COVID-19 pandemic to isolate structural inequalities from transient market shocks. Our findings challenge the strict cost-shifting hypothesis: on average, PC acts as a "double shield", truncating out-of-pocket expenditures (financial toxicity) and informal caregiving shadow values (time poverty). However, quantile treatment models expose a "broken shield" for vulnerable households and severe tail events. Non-cancer trajectories drive massive structural penalties that escalate at the distribution's tail, mechanically compounded by physical dependency. Socio-demographics heavily modulate this exposure: lacking a spousal net in
This report presents a small language model (SLM) for Japanese clinical and medicine, named NCVC-slm-1. This 1B parameters model was trained using Japanese text classified to be of high-quality. Moreover, NCVC-slm-1 was augmented with respect to clinical and medicine content that includes the variety of diseases, drugs, and examinations. Using a carefully designed pre-processing, a specialized morphological analyzer and tokenizer, this small and light-weight model performed not only to generate text but also indicated the feasibility of understanding clinical and medicine text. In comparison to other large language models, a fine-tuning NCVC-slm-1 demonstrated the highest scores on 6 tasks of total 8 on JMED-LLM. According to this result, SLM indicated the feasibility of performing several downstream tasks in the field of clinical and medicine. Hopefully, NCVC-slm-1 will be contributed to develop and accelerate the field of clinical and medicine for a bright future.
Bias and inequity in palliative care disproportionately affect marginalised groups. Large language models (LLMs), such as GPT-4o, hold potential to enhance care but risk perpetuating biases present in their training data. This study aimed to systematically evaluate whether GPT-4o propagates biases in palliative care responses using adversarially designed datasets. In July 2024, GPT-4o was probed using the Palliative Care Adversarial Dataset (PCAD), and responses were evaluated by three palliative care experts in Canada and the United Kingdom using validated bias rubrics. The PCAD comprised PCAD-Direct (100 adversarial questions) and PCAD-Counterfactual (84 paired scenarios). These datasets targeted four care dimensions (access to care, pain management, advance care planning, and place of death preferences) and three identity axes (ethnicity, age, and diagnosis). Bias was detected in a substantial proportion of responses. For adversarial questions, the pooled bias rate was 0.33 (95% confidence interval [CI]: 0.28, 0.38); "allows biased premise" was the most frequently identified source of bias (0.47; 95% CI: 0.39, 0.55), such as failing to challenge stereotypes. For counterfactual s
The revolutionary progress in development of next-generation sequencing (NGS) technologies has made it possible to deliver accurate genomic information in a timely manner. Over the past several years, NGS has transformed biomedical and clinical research and found its application in the field of personalized medicine. Here we discuss the rise of personalized medicine and the history of NGS. We discuss current applications and uses of NGS in medicine, including infectious diseases, oncology, genomic medicine, and dermatology. We provide a brief discussion of selected studies where NGS was used to respond to wide variety of questions in biomedical research and clinical medicine. Finally, we discuss the challenges of implementing NGS into routine clinical use.
Effective communication in serious illness and palliative care is essential but often under-taught due to limited access to training resources like standardized patients. We present PAL (Palliative Assisted Learning-bot), a conversational system that simulates emotionally nuanced patient interactions and delivers structured feedback grounded in an existing empathy-based framework. PAL supports text and voice modalities and is designed to scaffold clinical skill-building through repeated, low-cost practice. Through a mixed-methods study with 17 U.S. medical trainees and clinicians, we explore user engagement with PAL, evaluate usability, and examine design tensions around modalities, emotional realism, and feedback delivery. Participants found PAL helpful for reflection and skill refinement, though some noted limitations in emotional authenticity and the adaptability of feedback. We contribute: (1) empirical evidence that large language models can support palliative communication training; (2) design insights for modality-aware, emotionally sensitive simulation tools; and (3) implications for systems that support emotional labor, cooperative learning, and AI-augmented training in hi
With the increasing interest in deploying Artificial Intelligence in medicine, we previously introduced HAIM (Holistic AI in Medicine), a framework that fuses multimodal data to solve downstream clinical tasks. However, HAIM uses data in a task-agnostic manner and lacks explainability. To address these limitations, we introduce xHAIM (Explainable HAIM), a novel framework leveraging Generative AI to enhance both prediction and explainability through four structured steps: (1) automatically identifying task-relevant patient data across modalities, (2) generating comprehensive patient summaries, (3) using these summaries for improved predictive modeling, and (4) providing clinical explanations by linking predictions to patient-specific medical knowledge. Evaluated on the HAIM-MIMIC-MM dataset, xHAIM improves average AUC from 79.9% to 90.3% across chest pathology and operative tasks. Importantly, xHAIM transforms AI from a black-box predictor into an explainable decision support system, enabling clinicians to interactively trace predictions back to relevant patient data, bridging AI advancements with clinical utility.
Background: Incidence of adverse outcome events rises as patients with advanced illness approach end-of-life. Exposures that tend to occur near end-of-life, e.g., use of wheelchair, oxygen therapy and palliative care, may therefore be found associated with the incidence of the adverse outcomes. We propose a strategy for time-to-event analysis to mitigate the time-varying confounding. Methods: We propose a concept of reverse time-to-death (rTTD) and its use for the time-scale in time-to-event analysis. We used data on community-based palliative care uptake (exposure) and emergency department visits (outcome) among patients with advanced cancer in Singapore to illustrate. We compare the results against that of the common practice of using time-on-study (TOS) as time-scale. Results: Graphical analysis demonstrated that cancer patients receiving palliative care had higher rate of emergency department visits than non-recipients mainly because they were closer to end-of-life, and that rTTD analysis made comparison between patients at the same time-to-death. Analysis of emergency department visits in relation to palliative care using TOS time-scale showed significant increase in hazard ra
Artificial intelligence (AI) has become increasingly central to precision medicine by enabling the integration and interpretation of multimodal data, yet implementation in clinical settings remains limited. This paper provides a scoping review of literature from 2019-2024 on the implementation of AI in precision medicine, identifying key barriers and enablers across data quality, clinical reliability, workflow integration, and governance. Through an ecosystem-based framework, we highlight the interdependent relationships shaping real-world translation and propose future directions to support trustworthy and sustainable implementation.
Objectives: Prior event rate ratio (PERR) is a method shown to perform well in mitigating confounding in real-world evidence research but it depends on several model assumptions. We propose an analytic strategy to correct biases arising from violation of two model assumptions, namely, population homogeneity and event-independent treatment. Study Design and Setting: We reformulate PERR estimation by embedding a treatment-by-period interaction term in an analytic model for recurrent event data, which is robust to bias arising from unobserved heterogeneity. Based on this model, we propose a set of methods to examine the presence of event-dependent treatment and to correct the resultant bias. We evaluate the proposed methods by simulation and apply it to a de-identified dataset on palliative care and emergency department visits in patients with advanced cancer. Results: Simulation results showed that the proposed method could mitigate the two sources of bias in PERR. In the palliative care study, analysis by the Cox model showed that patients who had started receiving palliative care had higher incidence of emergency department visits than their match controls (hazard ratio 3.31; 95% c
As digital health solutions continue to reshape healthcare delivery, telehealth software applications have become vital for improving accessibility, continuity of care, and patient outcomes. This paper presents an analysis of designing a software application focused on Enhanced Telehealth Capabilities (ETHC) for palliative care, integrating across three socio-technical dimensions: quality, human values, and real-world. Designing for quality attributes -- such as performance, maintainability, safety, and security -- ensured that the system is technically robust and compliant with clinical standards. Designing for human values -- empathy, inclusivity, accessibility, and transparency -- helped enhance patient experience, trust, and ethical alignment. Designing for real-world -- through a multidisciplinary, experience-based co-design approach involving clinicians, patients, and carers that guided iterative cycles of prototyping, usability testing, and real-world evaluation -- ensured continuous refinement of features and alignment with clinical practice. The resulting telehealth software solution demonstrated that our socio-technical design framework was successful in producing a secur
What does Artificial Intelligence (AI) have to contribute to health care? And what should we be looking out for if we are worried about its risks? In this paper we offer a survey, and initial evaluation, of hopes and fears about the applications of artificial intelligence in medicine. AI clearly has enormous potential as a research tool, in genomics and public health especially, as well as a diagnostic aid. It's also highly likely to impact on the organisational and business practices of healthcare systems in ways that are perhaps under-appreciated. Enthusiasts for AI have held out the prospect that it will free physicians up to spend more time attending to what really matters to them and their patients. We will argue that this claim depends upon implausible assumptions about the institutional and economic imperatives operating in contemporary healthcare settings. We will also highlight important concerns about privacy, surveillance, and bias in big data, as well as the risks of over trust in machines, the challenges of transparency, the deskilling of healthcare practitioners, the way AI reframes healthcare, and the implications of AI for the distribution of power in healthcare ins
This article explores the critical role of statistical analysis in precision medicine. It discusses how personalized healthcare is enhanced by statistical methods that interpret complex, multidimensional datasets, focusing on predictive modeling, machine learning algorithms, and data visualization techniques. The paper addresses challenges in data integration and interpretation, particularly with diverse data sources like electronic health records (EHRs) and genomic data. It also delves into ethical considerations such as patient privacy and data security. In addition, the paper highlights the evolution of statistical analysis in medicine, core statistical methodologies in precision medicine, and future directions in the field, emphasizing the integration of artificial intelligence (AI) and machine learning (ML).
With the growing use of transformer-based language models in medicine, it is unclear how well these models generalize to nuclear medicine which has domain-specific vocabulary and unique reporting styles. In this study, we evaluated the value of domain adaptation in nuclear medicine by adapting language models for the purpose of 5-point Deauville score prediction based on clinical 18F-fluorodeoxyglucose (FDG) PET/CT reports. We retrospectively retrieved 4542 text reports and 1664 images for FDG PET/CT lymphoma exams from 2008-2018 in our clinical imaging database. Deauville scores were removed from the reports and then the remaining text in the reports was used as the model input. Multiple general-purpose transformer language models were used to classify the reports into Deauville scores 1-5. We then adapted the models to the nuclear medicine domain using masked language modeling and assessed its impact on classification performance. The language models were compared against vision models, a multimodal vision language model, and a nuclear medicine physician with seven-fold Monte Carlo cross validation, reported are the mean and standard deviations. Domain adaption improved all langu
The last few years have seen rapid progress in transitioning quantum computing from lab to industry. In healthcare and life sciences, more than 40 proof-of-concept experiments and studies have been conducted; an increasing number of these are even run on real quantum hardware. Major investments have been made with hundreds of millions of dollars already allocated towards quantum applications and hardware in medicine. In addition to pharmaceutical and life sciences uses, clinical and medical applications are now increasingly coming into the picture. This chapter focuses on three key use case areas associated with (precision) medicine, including genomics and clinical research, diagnostics, and treatments and interventions. Examples of organizations and the use cases they have been researching are given; ideas how the development of practical quantum computing applications can be further accelerated are described.
The success of precision medicine requires computational models that can effectively process and interpret diverse physiological signals across heterogeneous patient populations. While foundation models have demonstrated remarkable transfer capabilities across various domains, their effectiveness in handling individual-specific physiological signals - crucial for precision medicine - remains largely unexplored. This work introduces a systematic pipeline for rapidly and efficiently evaluating foundation models' transfer capabilities in medical contexts. Our pipeline employs a three-stage approach. First, it leverages physiological simulation software to generate diverse, clinically relevant scenarios, particularly focusing on data-scarce medical conditions. This simulation-based approach enables both targeted capability assessment and subsequent model fine-tuning. Second, the pipeline projects these simulated signals through the foundation model to obtain embeddings, which are then evaluated using linear methods. This evaluation quantifies the model's ability to capture three critical aspects: physiological feature independence, temporal dynamics preservation, and medical scenario d
This paper explores the potential opportunities, risks, and challenges associated with the use of large language models (LLMs) in sports science and medicine. LLMs are large neural networks with transformer style architectures trained on vast amounts of textual data, and typically refined with human feedback. LLMs can perform a large range of natural language processing tasks. In sports science and medicine, LLMs have the potential to support and augment the knowledge of sports medicine practitioners, make recommendations for personalised training programs, and potentially distribute high-quality information to practitioners in developing countries. However, there are also potential risks associated with the use and development of LLMs, including biases in the dataset used to create the model, the risk of exposing confidential data, the risk of generating harmful output, and the need to align these models with human preferences through feedback. Further research is needed to fully understand the potential applications of LLMs in sports science and medicine and to ensure that their use is ethical and beneficial to athletes, clients, patients, practitioners, and the general public.