BMC Medical Research Methodology

Hybrid controlled trials (HCTs) incorporate real-world data into randomized controlled trials (RCTs) by augmenting the internal control arm with patients receiving the same treatment in routine care. Beyond increasing power, HCTs may improve recruitment by supporting unequal randomization ratios that increase patient access to experimental treatments. However, HCT validity is threatened by bias from unmeasured confounding due to lack of randomization of external controls, leading to outcome non-...

PurposeLarge language models (LLMs) are used for biomedical text processing, but individual decisions are often hard to audit. We evaluated whether enforcing a mechanically checkable "show your work" quote affects accuracy, stability, and verifiability for trial eligibility-scope classification from abstracts. MethodsWe used 200 oncology randomized controlled trials (2005 - 2023) and provided models with only the title and abstract. Trials were labeled with whether they allowed for the inclusio...

BackgroundSystematic reviews (SRs) are essential for evidence-based medicine but require extensive time and resources for abstract screening. Large language models (LLMs) offer potential for automating this process, yet concerns about data privacy, intellectual property protection, and reproducibility limit the use of cloud-based solutions in research settings. ObjectiveTo evaluate the performance of a locally deployed 20-billion parameter LLM for automated abstract screening in systematic revi...

BackgroundPersonalized medicine promises to tailor treatments to the individual, but it carries a hidden risk: mistaking statistical noise for actionable clinical insight. Current machine learning approaches often provide predictions, but fail to inform clinicians when those predictions are unreliable. ObjectiveDevelop a deployment-readiness framework that integrates causal inference, interpretable effect-trees, and calibration assessment to distinguish actionable signal from unreliable variati...

ObjectiveTo systematically identify and characterize methodological heterogeneity in sepsis case detection methods using the MIMIC-III database or the eICU-CRD, and to quantify the resulting variability in sepsis detection rates. Materials and MethodsWe conducted a PRISMA-guided systematic review of PubMed and Web of Science (2016-2024), and stratified studies by cohort definition to obtain comparable subsets. We extracted information on sepsis case detection methodology across six domains: par...

BackgroundArtificial intelligence chatbots (AICs) are increasingly being integrated into scholarly publishing, with the potential to automate routine editorial tasks and streamline workflows. In traditional, complementary, and integrative medicine (TCIM) publishing, editorial and peer review processes can be particularly complex due to diverse methodologies and culturally embedded knowledge systems, presenting unique opportunities and challenges for AIC adoption. MethodsAn anonymous, online cro...

BackgroundPredictive models employing machine learning algorithms are increasingly being used in clinical decision making, and improperly calibrated models can result in systematic harm. We sought to investigate the impact of class imbalance correction, a commonly applied preprocessing step in machine learning model development, on calibration and modelled clinical decision making in a large real-world context. MethodsA histogram boosted gradient classifier was trained on a highly imbalanced na...

Objective: Evaluating and monitoring patients with cervical spondylotic myelopathy (CSM) remains a challenge due to limited tools for assessing objective neurological disability longitudinally and in the home environment. Given their prevalence and low cost, mobile health (mHealth), and specifically smartphone technologies offer a promising approach to fill this gap. This study explored stakeholder perspectives on the role of mHealth in CSM monitoring to inform development of a smartphone-based ...

BackgroundClinical research coordinators play a crucial role in ensuring the scientific rigor, regulatory compliance, and operational integrity of clinical trials. However, in Africa, they often lack access to structured, competency-based training, especially in operational, regulatory, and trial management domains. This study evaluated the effectiveness of a comprehensive training intervention designed to standardize and enhance core competencies of clinical trial coordinators. MethodsWe condu...

Thyroid carcinoma is one of the most prevalent endocrine malignancies worldwide, and accurate preoperative differentiation between benign and malignant thyroid nodules remains clinically challenging. Diagnostic methods that medical practitioners use at present depend on their personal judgment to evaluate both imaging results and separate clinical tests, which creates inconsistency that leads to incorrect medical evaluations. The combination of radiological imaging with clinical information syst...

BackgroundNo randomized clinical trial comparing the most established new modalities of treatment for patients with localized prostate cancer has been published, and there is scarce comparative effectiveness research assessing Patient-Reported Outcome Measures (PROMs). Objectiveto compare the impact of active surveillance, robot-assisted radical prostatectomy (RARP), Intensity-modulated radiotherapy (IMRT), and real-time brachytherapy on patients, through PROMs, from pre-treatment to five years...

Large language models (LLMs) perform strongly across a wide range of medical applications, yet it remains unclear whether such success reflects genuine understanding of medical concepts. We present an ontology-grounded, concept-centered evaluation of medical concept understanding in LLMs. Using 6,252 phenotype concepts from Human Phenotype Ontology, we decompose concept understanding into three core dimensions--concept identity, concept hierarchy, and concept meaning--and design corresponding be...

BackgroundLarge language models (LLMs) are increasingly deployed in medical contexts as patient-facing assistants, providing medication information, symptom triage, and health guidance. Understanding their robustness to adversarial inputs is critical for patient safety, as even a single safety failure can lead to adverse outcomes including severe harm or death. ObjectiveTo systematically evaluate the safety guardrails of state-of-the-art LLMs through adversarial red-teaming specifically designe...

UK-based quantitative research on the health and education outcomes of Unaccompanied Asylum-Seeking Children (UASC) remains limited, especially at national level. Linked administrative data provide an unprecedented opportunity to study these outcomes among UASC. This paper lays a foundation for further research, particularly examining the influence of socio-demographic, legal and environmental factors on UASCs health and educational outcomes. We described the UASC population with a first record...

Wearable devices present transformative opportunities for personalized healthcare through continuous monitoring of digital biomarkers; however, individual variations in device wear time could mask or otherwise impact signal identification. Despite the widespread adoption of wearable devices in research, no comprehensive framework exists for understanding how wear time varies across populations or for addressing wear time-related biases in analysis. Using Fitbit data from 11,901 participants in t...

We present results from the second season of Influcast, a multi-model collaborative forecasting hub focused on influenza in Italy. During the 2024/25 winter season, Influcast collected one-to four-week-ahead probabilistic forecasts of influenza-like illness (ILI) incidence alongside influenza A and B ILI+ incidence signals. New ILI+ targets were constructed integrating syndromic surveillance data with virological detections collected weekly by the Italian National Institute of Health. Forecasts ...

Health behaviors such as physical activity and sleep affect mental health, but the effect of each health behavior varies substantially across individuals, limiting the usefulness of generic behavioral recommendations. We collected one year of continuous wearable and ecological momentary assessment data from 3,139 participants in the Intern Health Study (2018-2023), and examined individual-level associations between wearable-derived features and mood across the internship year. The behaviors asso...

As of early 2026, over 115 million US adults (more than 1 in 3) have prediabetes, a condition with an annual conversion rate of 5%-10% to type 2 diabetes. Total diabetes (diagnosed and undiagnosed) affects approximately 40.1 million Americans, or 12% of the population, with roughly 1.5 million new cases diagnosed annually. Continuous Glucose Monitoring (CGM) provides real-time, 24/7 insights into glycemic variability, detecting dangerous highs, lows, and trends that HbA1c (a 3-month average) mis...

With significant population fractions in many societies who refuse vaccines, it is important to reconsider how vaccination is incorporated into compartmental epidemiology models. It is still most common to apply the vaccination rate to the entire class of susceptibles, rather than to use the more realistic assumption that the vaccination rate function should depend only on the population of susceptibles who are willing and able to receive a vaccination. This study uses a simple generic disease m...

Wastewater is increasingly being recognized as an important data stream that can contribute to infectious disease surveillance and forecasting. With this recognition, a growing number of statistical inference approaches are being developed to use wastewater data to provide quantitative insights into epidemiological dynamics. However, few existing approaches have allowed for systematic integration of data streams for inference, for example by combining case incidence data and/or serological data ...