Data gaps in Medicine

Representative open questions

Showing 30 of 508 — one per source paper, highest-quality first.

• CUIDADO TRANSICIONAL HOSPITAL-DOMICÍLIO REALIZADO POR ENFERMEIRAS A PESSOAS IDOSAS COM MARCAPASSO ARTIFICIAL: PROTOCOLO DE REVISÃO DE ESCOPO (2026) · doi

  The data extraction table (Quadro 3) lacks specification of standardized instruments or validated assessment scales for measuring outcomes related to transitional nursing care quality, patient safety, and clinical outcomes in elderly pacemaker patients during hospital-to-home transition. No specific outcome measurement tools are defined for systematic comparison across included studies.

• The impact of traumatic injury on the respiratory system; a narrative review of injury-associated and clinically-induced mechanisms of trauma-associated pneumonia (2026) · doi

  The molecular fingerprint of lung inflammation following blunt chest trauma has been partially characterized, but longitudinal profiling of danger-associated molecular patterns (DAMPs), inflammatory mediators, and their kinetics in relation to pneumonia development requires systematic investigation in trauma cohorts.

• FDG-PET/CT based small volume accelerated immuno chemoradiotherapy in locally advanced NSCLC (PACCELIO) – a randomized, open-label, multicenter phase II trial protocol (2026) · doi

  While the PACCELIO trial combines FDG-PET/CT-based target volume reduction with hypofractionated accelerated radiotherapy, the optimal threshold values for FDG-PET/CT uptake-based delineation and the corresponding tumor control probability thresholds specific to accelerated dose delivery schedules in stage III NSCLC remain undefined. Direct comparison of tumor recurrence patterns between volume-reduced and conventional radiotherapy planning is needed.

• Impact of Health Education and Preventive Interventions on Non- Communicable Diseases in Rural Communities: A Community-Based Randomized Controlled Trial (2026) · doi

  The study measured blood glucose levels in the triple-comorbidity group (hypertension + diabetes + obesity) but reported that glucose levels showed improvement with intervention (p=0.0189); however, the paper does not specify the duration of follow-up or long-term sustainability of glycemic control, which is critical for assessing diabetes management in rural non-communicable disease prevention programs.

• From organelles to therapy: rethinking combined hepatocellular-cholangiocarcinoma (2026) · doi

  High-quality prospective or large-sample studies on cHCC-CCA are lacking; most existing research remains retrospective or based on small sample sizes due to the tumor's low incidence and diagnostic complexity, creating a scarcity of high-quality evidence to guide clinical practice.

• Managing Spinal Muscular Atrophy: A Look at the Biology and Treatment Strategies (2025) · doi

  Newborn screening programs for spinal muscular atrophy have been implemented with variations in practice across different regions (as noted in reference 15 regarding United States variations), but comparative outcome data on long-term therapeutic efficacy and timing of intervention across different screening and treatment protocols in diverse populations remains limited.

• Neurosurgery as an immune anchor point: a translational framework for perioperative immunoengineering (2026) · doi

  The translational framework does not address how blood-brain barrier dysfunction varies across different neurosurgical procedures and how this impacts the pharmacokinetics of intratumoral immunotherapeutic administration in glioma resection versus vascular neurosurgery. Comparative pharmacodynamic studies are needed to determine optimal drug delivery strategies for choroid plexus-mediated immune responses in post-operative CNS patients.

• The neuro-immune axis in preeclampsia: from the maternal-fetal interface to systemic dysregulation (2026) · doi

  The prediction that individuals with heightened baseline neuroimmune or autonomic sensitivity show greater neurological vulnerability to placental stressors lacks operationalized criteria for identifying or measuring 'baseline neuroimmune sensitivity' or 'autonomic robustness' in prospective cohorts, and does not specify which cellular or molecular immune markers should define this vulnerability phenotype.

• What is The Effect of Early Enteral Nutrition on Mortality in Critically Ill Patients Receiving Vasopressor Support? : A Systematic Review (2026) · doi

  While the NUTRIREA-3 trial demonstrated that low-calorie enteral nutrition (6 kcal/kg/day) halved bowel ischemia risk compared to standard-calorie feeding (25 kcal/kg/day), no randomized controlled trials have directly compared gradual advancement protocols (3-7 day escalation) versus immediate full-dose feeding in patients with persistent shock receiving high-dose vasopressors (≥0.3 µg/kg/min norepinephrine equivalents) to determine long-term outcome differences.

• Decision-ready evidence for vital pulp therapy: a network meta-analysis of bioactive materials in mature permanent teeth (2026) · doi

  Follow-up attrition and uneven time windows limited certainty of evidence beyond 24 months for several bioactive material comparisons in mature permanent teeth undergoing vital pulp therapy. Prospective cohort studies with standardized follow-up intervals at 3, 5, and 10 years post-pulpotomy or pulp capping are needed to establish durability of modern calcium-silicate cements and assess long-term success decay patterns.

• Exercise benefits in metabolism on cardiovascular disease (2026) · doi

  While SIRT1 and SIRT6 signaling pathways have been identified as protective mechanisms in cardiovascular disease, the specific role of SIRT1 gene single-nucleotide polymorphisms on exercise-induced metabolic adaptations and cardiovascular outcomes in diverse ethnic populations remains unexplored beyond the Han Chinese population study cited.

• Deep learning-based multimodal prediction of chronic kidney disease stage (2026) · doi

  The multimodal model fuses numerical clinical indicators (creatinine, BUN) with symptom and complication information, but the paper does not specify which particular symptom features or complication variables were included, nor does it analyze the relative contribution or importance of each symptom modality to the overall CKD stage prediction performance.

• A systematic review of sample size determination in Bayesian randomized clinical trials: full Bayesian methods are rarely used (2026) · doi

  Many trials in the review are coded as 'No Justification' for their sample size methodology (e.g., Bolinski, Banooni, Bardia), indicating that a substantial proportion of clinical trials lack explicit documentation of their sample size determination approach. There is a need to investigate whether these trials employed Bayesian, frequentist, or hybrid methods but failed to report them, versus genuinely lacking formal sample size justification.

• A behaviour and disease model of testing and isolation (2026) · doi

  Real-time compliance estimates from community surveys on testing and isolation uptake across fine-scale geographical levels and sociodemographic groups require improved integration into behaviour and disease (BaD) models. Specific work is needed to develop methods for onboarding survey-based compliance data to enhance the model's ability to predict impactful testing interventions.

• Treatment options for long head of biceps tendon tenodesis (2026) · doi

  While high-quality long-term comparative clinical studies are identified as necessary, the paper does not specify which specific patient populations (age groups, overhead athletes, rotator cuff tear severity) require investigation to define optimal indications for each of the nine non-subpectoral tenodesis techniques presented. Comparative outcome data stratified by these clinical parameters is absent.

• Artificial intelligence approaches to predicting treatment non-adherence in chronic diseases: a narrative review (2026) · doi

  AI-based adherence prediction models predominantly rely on retrospective electronic health record and administrative datasets that contain incomplete or missing data and may not capture routine real-world medication-taking behaviors. There is a critical need for adherence prediction studies utilizing prospective data collection methods and real-time monitoring technologies to validate model performance against actual adherence patterns.

• Evidence-based approaches for Empty Nose Syndrome management: a systematic review highlighting current treatments and future directions (2026) · doi

  Sex representation is uneven across Empty Nose Syndrome treatment studies, limiting the generalizability of findings regarding how biological sex influences surgical outcomes, implant integration, or response to pharmacological-cognitive interventions in this patient population.

• Human-centered Perspectives on a Clinical Decision Support System for Intensive Outpatient Veteran PTSD Care (2026) · doi

  The study examined only clinicians and former patients in the PTSD treatment sociotechnical system, but did not investigate how integrating perspectives from trusted others (family and friends) affects patient experience tracking and therapy progress monitoring in intensive outpatient PE therapy. Evans et al. examined this integration conceptually, but the situated objectivity of patient experience when social networks are incorporated into CDSS design remains unexplored.

• Multimodal artificial intelligence in urologic precision oncology: from algorithm to translational medicine (a systemized narrative review) (2026) · doi

  Biomarkers in localized high-risk prostate cancer have limitations toward precision oncology (reference 35), but integration of novel omics-derived biomarkers (genomic, proteomic, metabolomic) with multimodal imaging and AI for stratifying castration-resistant prostate cancer treatment responses remains inadequately characterized.

• Quercetin in metabolic diseases: mechanisms, therapeutics, and multidimensional frontiers (2026) · doi

  Quercetin's protective effects against diabetic complications (cataract, nephropathy, encephalopathy) have been demonstrated via aldose reductase inhibition and TGF-β2/PI3K/Akt pathway modulation in individual rodent disease models, but cross-organ penetration studies assessing whether quercetin nanoformulations achieve therapeutic concentrations simultaneously in the lens, kidney glomeruli, and brain in multi-organ diabetic complications models have not been conducted.

• Lipidomics and machine learning revealing dysregulation of specific triacylglycerol and phosphatidylglycerol as hub lipids associated with fetal growth in gestational diabetes mellitus (2026) · doi

  The identified 12 serum lipid metabolites associated with GDM risk require confirmation using self-built external databases and comparable lipidomic datasets from other research teams to validate the TG and PG metabolic pathway findings across different populations and analytical platforms.

• Deep learning-based differential diagnosis of major depression and bipolar disorder using microglia-cellular sensors and patient-derived small extracellular vesicles (2026) · doi

  The current study uses only 45 subjects for training and validation; the impact of sex, age, medication status, other demographic variables, and childhood trauma on microglial-cellular sensor performance and patient stratification in mood disorder classification has not been systematically investigated.

• Psychiatric conditions in palliative medicine (2020) · doi

  The paper identifies multiple contributing factors for anxiety in palliative patients (breathlessness, sepsis, refractory pain, medication effects, drug withdrawal, delirium), but does not specify the relative prevalence or impact of each factor. Empirical studies quantifying the contribution of each anxiety precipitant in different palliative populations are needed to guide targeted intervention strategies.

• Echocardiographic Assessment of Left Ventricular Mass Regression and Functional Changes after Bariatric Surgery (2026) · doi

  The study notes that follow-up duration was restricted, limiting analysis of long-term cardiac remodeling patterns after bariatric surgery. Research with extended follow-up periods (≥2-5 years post-surgery) is needed to characterize the temporal dynamics of diastolic performance improvement and LV mass regression sustained over time.

• Principles and ethics in medicine (2020) · doi

  The paper identifies that happiness and well-being in consequentialist medical ethics mean different things to different people, and the relationship between happiness and measurable health outcomes (health, wealth, intelligence, mobility) is far from straightforward. However, there is no empirical investigation into how to operationalize and measure happiness across diverse patient populations in clinical settings, particularly in terminal illness contexts where the paper notes cancer patients' happiness does not decline predictably as death approaches.

• The portability paradox of foundation models for clinical decision support (2026) · doi

  The paper references generative models for disease prediction using multimodal data (sleep foundation model, reference 17) and medical image analysis (reference 15), but does not specify which combinations of modalities (structured EHR, imaging, sensor data, genomics) maintain prediction performance when foundation models are transferred across institutions with different data collection protocols and equipment specifications.

• Reflections on Medicine in Japan (2015) · doi

  Rural-urban discrepancies in healthcare access and quality are identified as an international problem, but no quantified metrics are provided comparing service availability, provider density, patient outcomes, or resource allocation between rural and urban medical facilities in Japan and the US.

• Antipsychotics (2020) · doi

  The interaction between clozapine and multiple CYP450 enzyme inhibitors (fluvoxamine, ciprofloxacin, fluoxetine, paroxetine) is documented, but quantitative pharmacokinetic data on the magnitude and clinical significance of concentration increases for each inhibitor combination are not provided, limiting precision dosing in polypharmacy scenarios.

• Evidence-based Medicine: Alternative Medicine [Non-drug Medicine, CAM] versus Pharmacological Medicine (2015) · doi

  While the paper references meta-analyses of positive effects and adverse events of holistic mind-body medicine across Denmark, Sweden, United Kingdom, and Germany, it does not specify standardized outcome measurement instruments or quality-of-life assessment scales needed for cross-national comparative analysis of non-pharmaceutical holistic interventions.

• Evasive Eragrostis: A Unique Case of Intralingual Plant Implantation with Persistent Viability (2026) · doi

  The material properties of radiolucent plant species (including Eragrostis intermedia) that affect imaging detectability have not been characterized; density, calcification patterns, and radiographic appearance across different plant taxa implanted in oral mucosa require systematic comparison to establish species-specific detection parameters.