Search Results (198)

Background: Childhood cancer survivors commonly experience long-term treatment effects that impair physical function. Access to in-person physical fitness assessments is often limited by geographic, logistical, and resource constraints. Virtually supervised physical fitness assessments may offer a feasible alternative; however, evidence in this population remains limited. Methods: This study evaluated the feasibility of delivering virtually supervised physical fitness assessments via videoconference for children and adolescents aged 5–18 years following completion of cancer treatment. Assessments evaluated lower-body strength (30 s sit-to-stand), upper-body strength (30 s push-up), mobility (timed up-and-go), balance (single-leg balance), aerobic endurance (two-minute step), and flexibility (sit-and-reach). Pre-defined feasibility benchmarks included recruitment (≥15 participants within three months), assessment completion (≥85% of participants completing all six assessments), individual assessment completion (≥90% of planned assessments completed), technique fidelity (≥85% of assessments performed with correct technique), session duration (≥90% of sessions completed in ≤30 min), safety (no adverse events), and participant satisfaction (qualitative feedback). Results: Twenty-nine participants were enrolled, with 28 completing the virtual assessments. The sample (61% male) had a mean age of 9.8 ± 3.7 years (range 5–16), with acute lymphoblastic leukaemia the most common diagnosis (46%). Recruitment exceeded benchmarks (23 participants within three months). Assessment completion was 92.9% (26/28), individual assessment completion was 98.8% (166/168), and technique fidelity was 90.9%, with the lowest fidelity for push-ups (73.1%). Most sessions were completed within 30 min (92.9%; median 19.5 min, range 15–33). No adverse events occurred. Feedback indicated high satisfaction, highlighting convenience, engagement, and practicality. Conclusions: Virtually supervised physical fitness assessments were feasible, safe, and acceptable for childhood cancer survivors. These findings provide initial feasibility evidence to support further validation and implementation research before broader clinical application. Full article

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, debilitating condition that significantly impairs patient quality of life and often necessitates dose modification or discontinuation of chemotherapy, which can adversely impact patient outcomes and overall survival. This study aims to explore the experiences of cancer patients affected by CIPN and identify the challenges encountered in managing this condition. Methods: Data were collected through qualitative semi-structured interviews with 20 cancer patients with confirmed CIPN. The semi-structured interviews were held between April and June 2025 at a cancer center in the Qassim Region, Saudi Arabia, and were audio-recorded, transcribed, and analyzed using thematic analysis following Braun and Clarke. Results: Patients reported experiencing a considerable burden of CIPN symptoms, particularly during the early phases of chemotherapy, with some reporting gradual changes over time. Symptom unpredictability was reported across different types of cancer and regimens, regardless of age or gender. Sensory disruptions and functional impairments were prominent among many participants. Patients with higher levels of education, including those with family members in healthcare, demonstrated a stronger understanding of their condition and treatment explanations. Across cancer groups, patients expressed dissatisfaction with the prescribed therapies’ side effects. A subset of patients expressed a strong willingness to participate in clinical trials. Conclusions: The findings highlight the need for improved patient education, early symptom recognition, and comprehensive supportive care strategies. Healthcare providers should proactively address CIPN in treatment discussions and offer tailored interventions that go beyond physical symptoms. Additionally, further research is needed to identify and prevent CIPN across diverse populations. Full article

The safety of titanium dioxide (TiO₂), widely used in foods and personal care products, has been of on-going concern. Adverse effects of TiO₂ have been reported, suggesting risk to human health. To evaluate its potential epigenotoxicity, the effect of exposure to a TiO₂ product, to which humans could be exposed, on microRNA (miRNA) expression (a primary epigenetic mechanism) was investigated using human cell lines (Caco-2, HCT116 (colorectal) and HepG2, SNU387 (liver)) relevant to human exposure. The effect of TiO₂ nanomaterial exposure on expression levels of miRNA was determined using the TaqMan Array Human microRNA A+B Card Set v3.0 platform. Differentially expressed miRNAs were identified (SNU387 (n = 112), HepG2 (n = 97), Caco-2 (n = 94), and HCT116 (n = 53)). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analysis of target genes provided insights into the roles of modulating pathways, which can be associated with diseases. Top 10 KEGG pathways in each cell line included MAPK signaling pathway, Axon guidance, cell cycle, Hippo signaling pathway, and Endocytosis. Findings from the study clearly demonstrate the impact of TiO₂ exposure on miRNA expression, supporting the potential involvement of this epigenetic mechanism in its biological responses. Hence, epigenetic studies are important for the complete assessment of the potential risk from exposure. Full article

Background/Objectives: Walking impairment and fatigue are common in multiple sclerosis (MS) and contribute to reduced physical function and quality of life (QoL). This study evaluated the feasibility, safety, and pre–post changes associated with a 12-week treadmill walking training (TWT) programme on walking performance, physical function, fatigue, and QoL in people with MS. Methods: Single-arm pilot study with pre–post assessments (T1–T2). Eleven adults with MS (Expanded Disability Status Scale [EDSS] ≤ 6) completed supervised TWT for 12 weeks (two 25 min sessions/week) at the Complejo Asistencial Universitario de Soria (Spain). Outcomes included SF-36, Timed Up and Go (TUG), 4 m gait speed, Short Physical Performance Battery (SPPB), and Modified Fatigue Impact Scale (MFIS). Within-participant changes were analysed using paired t-tests or Wilcoxon signed-rank tests as appropriate; effect sizes were reported as appropriate for the statistical test. Results: SF-36 total score did not change significantly (p = 0.160), while general health (p = 0.039) and vitality (p = 0.043) improved. Walking performance improved (TUG, p = 0.007; 4 m gait speed, p < 0.001), and physical function increased (SPPB, p = 0.003). Fatigue impact decreased (MFIS total, p = 0.015; physical, p = 0.007; psychosocial, p = 0.026), whereas the cognitive subscale did not change significantly (p = 0.094). Adherence was 91.7%, and no adverse events were reported. Conclusions: In this pilot sample, a 12-week TWT programme was feasible and safe and was associated with improvements in walking performance, physical function, and fatigue, with QoL changes limited to specific SF-36 domains. These findings support proceeding to a randomised controlled trial to establish efficacy. These findings should be interpreted as preliminary and exploratory, given the single-arm pre–post study design. Full article

Background: β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors demonstrated amyloid-lowering efficacy but failed in phase II/III clinical trials due to adverse effects and limited disease-modifying outcomes. This study employed an integrated network pharmacology and molecular docking approach to quantitatively elucidate the multitarget mechanisms of 4 (phase II/III) discontinued BACE1 inhibitors (Verubecestat, Lanabecestat, Elenbecestat, and Umibecestat) and the preclinical compound AM-6494 in Alzheimer’s disease (AD). Methods: Drug-associated targets were intersected with AD-related genes to construct a protein–protein interaction (PPI) network, followed by topological analysis to identify hub proteins. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using statistically significant thresholds (p < 0.05, FDR-adjusted). Molecular docking was conducted using AutoDock Vina to quantify binding affinities and interaction modes between the selected compounds and the identified hub proteins. Results: Network analysis identified 10 hub proteins (CASP3, STAT3, BCL2, AKT1, MTOR, BCL2L1, HSP90AA1, HSP90AB1, TNF, and MDM2). GO enrichment highlighted key biological processes, including the negative regulation of autophagy, regulation of apoptotic signalling, protein folding, and inflammatory responses. KEGG pathway analysis revealed significant enrichment in the PI3K–AKT–MTOR signalling, apoptosis, and TNF signalling pathways. Molecular docking demonstrated strong multitarget binding, with binding affinities ranging from approximately −6.6 to −11.4 kcal/mol across the hub proteins. Umibecestat exhibited the strongest binding toward AKT1 (−11.4 kcal/mol), HSP90AB1 (−9.5 kcal/mol), STAT3 (−8.9 kcal/mol), HSP90AA1 (−8.5 kcal/mol), and MTOR (−8.3 kcal/mol), while Lanabecestat showed high affinity for AKT1 (−10.6 kcal/mol), HSP90AA1 (−9.9 kcal/mol), BCL2L1 (−9.2 kcal/mol), and CASP3 (−8.5 kcal/mol), respectively. These interactions were stabilized by conserved hydrogen bonding, hydrophobic contacts, and π–alkyl interactions within key regulatory domains of the target proteins, supporting their multitarget engagement beyond BACE1 inhibition. Conclusions: This study demonstrates that clinically failed BACE1 inhibitors engage multiple non-structural regulatory proteins that are central to AD pathogenesis, particularly those governing autophagy, apoptosis, proteostasis, and neuroinflammation. The identified ligand–hub protein complexes provide a mechanistic rationale for repurposing and optimization strategies targeting network-level dysregulation in Alzheimer’s disease, warranting further in silico refinement and experimental validation. Full article

Osteoarthritis (OA) is a prevalent chronic pain syndrome and a leading cause of disability worldwide, characterized by progressive deterioration of articular cartilage. This degradation leads to pain, swelling, inflammation, and eventual stiffness as the cartilage wears down, causing bone-on-bone friction. Current medical treatments primarily aim at pain relief; however, many interventions, especially invasive or surgical ones, carry risks of adverse outcomes. Consequently, intra-articular (IA) therapy, particularly hyaluronic acid (HA) injections, is widely adopted as a conservative treatment option. HA plays a crucial role in maintaining joint homeostasis by supporting proteoglycan synthesis and scaffolding, restoring optimal HA concentrations in synovial fluid, and providing chondroprotective and anti-inflammatory effects. In recent years, hydrogels composed of natural and synthetic materials have emerged as promising candidates for OA treatment. Our research focuses on the biosynthesis and characterization of novel hydrogel composites combining short peptide hydrogelators with aminated graphene oxide (a-GO) nanosheets functionalized with HA (a-GO-HA@Hgel). These a-GO-HA@Hgel nanocomposites are designed to facilitate the controlled release of HA into the extracellular matrix, aiming to promote cartilage regeneration and mitigate inflammation. The strategy is to exploit the oxygen-containing functional groups of GO nanosheets to enable covalent coupling or physical adsorption of HA molecules through various chemical approaches. The resulting a-GO-HA are incorporated within hydrogel matrices to achieve sustained and controlled HA release. We study the influence of a-GO-HA on the native hydrogel structure and its viscoelastic properties, which are critical for mimicking the mechanical environment of native cartilage tissue. Through this multidisciplinary approach combining advanced materials science and cellular biology, this work aims to develop innovative nanocomposite hydrogels capable of delivering HA in a controlled manner, enhancing cartilage repair and providing a potential therapeutic strategy for OA management. Full article

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder that causes progressive renal failure, nephrolithiasis, and nephrocalcinosis in children. It is characterized by hepatic overproduction of oxalate. Conventional management, which involves combined liver–kidney transplantation, vitamin B6 supplementation, and intense hydration, does not address the underlying metabolic defect for most patients and it generally provides only supportive care. The first approved disease-modifying treatment for pediatric PH1 is Lumasiran, a small interfering RNA (siRNA) therapeutic. By specifically inhibiting the hepatic glycolate oxidase mRNA, Lumasiran lowers the production of oxalate at its origin. Along with fewer kidney stone events and stabilization of nephrocalcinosis, clinical trials (ILLUMINATE-A/B/C) showed significant decreases in urinary oxalate excretion. The most frequently reported adverse event is mild injection-site reactions, which are generally well tolerated. The molecular mechanism, pharmacokinetics, and clinical effectiveness of Lumasiran in children with PH1 are compiled in this review. We go over possible long-term safety concerns, the impact of early intervention on renal outcomes, and the function of siRNA therapies in pediatric precision medicine. Furthermore, we highlight Lumasiran’s importance as a model for targeted treatment in uncommon pediatric kidney diseases by considering it in the larger context of RNAi-based therapies. A paradigm shift in pediatric nephrology is signaled by Lumasiran, which changes the therapeutic approach from supportive care to precision, targeted medicine. Further research and empirical data will clarify its long-term advantages, the best ways to treat it, and the possible use of siRNA technologies for other genetic renal disorders. Full article

Physical inactivity in older adults is associated with decreased mobility, functional decline, and reduced quality of life. Music may enhance exercise engagement and adherence. This pilot randomized controlled trial evaluated the feasibility of a music-enhanced calisthenic exercise program in residential care homes and explored its preliminary effects on functional and psychosocial outcomes. Thirty-one healthy, sedentary older adults (mean age = 74.4 ± 5.9 years) were randomly assigned to a Calisthenic Exercise Group (CEG), a Music-Enhanced Calisthenic Exercise Group (MCEG), or a Control Group (CG). Intervention groups completed 16 supervised sessions over 8 weeks. The MCEG performed exercises with rhythmic music. Feasibility outcomes included recruitment, retention, adherence, and adverse events. Functional outcomes were assessed using the Timed Up and Go (TUG), 30-Second Sit-to-Stand test, and Joint Position Sense test; health-related quality of life was measured using the Nottingham Health Profile (NHP). Recruitment was 96.9%, retention 100%, and adherence 87.5%. No adverse events occurred. Both intervention groups improved significantly compared with the CG (p = 0.001), with larger effects in the MCEG, particularly in proprioception (p = 0.002, d = 1.46). TUG scores improved by 17% (p = 0.004, d = 0.26). Music-enhanced calisthenic exercise was feasible, safe, and well tolerated. Preliminary findings indicate benefits for physical function and health-related quality of life, supporting the need for larger trials. Trial Registration. ClinicalTrials.gov Identifier: NCT06973538 (retrospectively registered) Full article

Objectives: This study investigated whether CoQ10 supplementation enhances physical adaptations to high-intensity interval training (HIIT) in muscular strength, power, and physical function in older adults. Method: In a double-blind, randomized controlled trial, 38 adults aged 65–75 were assigned to either a CoQ10 (Females: 8; Males: 11) or placebo (Females: 8; Males: 11) group and completed an 8-week supervised HIIT program. Lower- and upper-body strength (30s 5-repetition chair stand [5XSST], chair standing [30CST], handgrip strength [HGR/L]), balance (single-leg stand [SLS], timed up and go [TUG]), mobility (25-foot walk [25FW]), and aerobic endurance (6-minute walk [6MWT]) were assessed pre- and post-intervention. Results: The CoQ10 group demonstrated significantly greater improvements in 5XSST and 30CST compared to the placebo group (p < 0.05). Both groups showed significant within-group improvements in right and left handgrip strength, SLS, 6MWT, and TUG (all p < 0.001), with no significant between-group differences observed for these outcomes (p > 0.05). No adverse events were reported. Conclusion: While CoQ10 supplementation enhanced improvements in lower-body strength and power, as indicated by the greater gains in 5XSST and 30CST performance compared to the placebo, no between-group differences were observed in TUG, grip strength, or other functional outcomes. This suggests that the performance-related effects of CoQ10 may be more specific to muscular power output and fatigue resistance, rather than general mobility or balance-related tasks. These findings highlight the potential of CoQ10 as a targeted adjunct in exercise for supporting lower-body function and physical performance in older adults. Full article

Canine epilepsy often resists conventional antiepileptic drugs (AEDs), which affects their quality of life. Cannabidiol (CBD) has anticonvulsant properties; however, evidence of its use in canine epilepsy is limited and contradictory. This prospective pilot study aimed to investigate the potential advantages, safety profile, and effects of CBD on quality of life when used as an adjunctive therapy in cases of drug-resistant epilepsy in canines. Thirteen dogs with refractory epilepsy, all on 2–6 concurrent AEDs, were enrolled. A single-arm pretest–post-test design was used. CBD was titrated from 0.5 mg/kg BID 2.5 mg/kg q12h. The primary outcome was the change in seizure frequency. Secondary outcomes included changes in seizure severity, seizure cluster, hematological and biochemical parameters, and owner-reported quality of life (QoL). Significant overall seizure frequency reduction (p = 0.02) with the median decreased from 11 (IQR 9–22) during the pre-intervention period to 5 (IQR 2–13) at the post-intervention follow-up. Notably, 61.5% of the dogs achieved a ≥50% reduction in seizure frequency. The number of seizure clusters was significantly decreased (p = 0.001). Most hematological/renal parameters remained stable; however, Alkaline Phosphatase (ALP) levels significantly increased (p < 0.001). The owners reported positive CBD perceptions and an improved quality of life. CBD shows the potential for refractory canine epilepsy, especially in clusters. Increased hepatic enzyme levels necessitate rigorous monitoring, particularly with the concurrent use of AEDs. This groundbreaking study explored the application of CBD in managing canine epilepsy, utilizing a “start-low, go-slow” strategy to minimize adverse effects while effectively controlling seizures. Our findings underscore the necessity of customizing CBD dosages for individual needs and highlight the critical importance of monitoring liver function. This study challenged the traditional one-size-fits-all dosing approach. It provides the first evidence and practical framework for the use of CBD to treat canine epilepsy in Asia, detailing the pioneering approach and the initial findings from this cohort. Full article

Background: There is a critical need for feasible, non-equipment based, safe, and cost-effective exercise interventions to promote muscle strength, dynamic postural balance, and independent mobility in adolescents with cerebral palsy (CP) or spina bifida (SB). Objectives: This study aimed to examine the feasibility and preliminary response of a novel exercise program: Functionally Loaded High-Intensity Circuit Training (FUNHIT) and conventional High-Intensity Circuit Training (HIT) in adolescents with CP/SB. Methods: Enrolled participants were allocated to FUNHIT or HIT or Controls in our randomized control trial. The interventions were delivered 2×/week × 4 weeks. Feasibility was assessed through process, operational, and scientific metrics. Outcome measures included maximum walking speed, Four Square Step Test (FSST), Timed Up and Go (TUG) and its dual-task variants, Lateral Step-Up Test (LSUT), Fear of Falling (FoF) and physical activity (PA) questionnaires. Results: We tested 5 participants (1 CP, 4 SB) in our study. Recruitment and retention rates were acceptable (63% enrollment, 100% retention and adherence). FUNHIT (n = 2) participants showed improvements in maximum walking speed (8–12%), FSST (15–29%), LSUT (22–33%), and TUG (4%). The HIT participant (n = 1) demonstrated improved TUG dual-task performance (40%) and FSST (30%) only. Control participants (n = 2) had varied changes (from 0–24%) in mobility, strength, balance. No adverse events were reported. Participants successfully followed (100%) the prescribed exercise dosage over the four-week period. Conclusions: FUNHIT and HIT are feasible and safe interventions for adolescents with ambulatory CP and SB who retain motor function, showing promising preliminary improvements in muscle strength, dynamic balance, and independent mobility. Our findings need to be validated in larger samples. Full article

Dexmedetomidine is a commonly used sedative because it has minimal adverse effects on respiratory function. Nevertheless, its cardiovascular safety profile, particularly bradycardia risk and drug–drug interactions (DDIs), remains incompletely understood. Additionally, current studies, including our previous analysis using the FDA adverse event reporting system (FAERS), hold several limitations. In this study, the electronic health record (EHR) platform TriNetX was utilized for pharmacovigilance analyses of dexmedetomidine. The significantly elevated incidence of bradycardia in dexmedetomidine-treated patients was demonstrated compared to other prevalent anesthetics. Age-stratified analyses revealed pronounced susceptibility in geriatric patients, while a slightly increased susceptibility in male patients was observed. In addition, elevated DDIs of dexmedetomidine with risperidone and albuterol were identified using disproportionality analysis with propensity score matching. Finally, to investigate molecular mechanisms of dexmedetomidine-associated bradycardia, analyses were conducted on a public microarray dataset, and nine differentially expressed miRNAs were identified following dexmedetomidine administration. Gene Ontology (GO) analysis of target genes of all five up-regulated miRNAs revealed rhythmic process and muscle tissue development as potential explanations. Notably, the target genes of the up-regulated miRNAs miR-26a-5p and miR-30c-5p were significantly enriched in GO terms associated with bradycardia. Together, this study identified bradycardia as a significant adverse drug event (ADE) of dexmedetomidine administration, observed possible clinically meaningful DDIs with dexmedetomidine, demonstrated a greater risk in elderly patients, and provided transcriptomic evidence that miRNA-mediated pathway dysregulation may contribute to dexmedetomidine-associated bradycardia. Full article

Background: Knee osteoarthritis (OA) is a leading cause of disability globally. Conventional physiotherapy, while effective, faces barriers including accessibility and adherence. Telerehabilitation augmented by wearable sensor technology and AI-driven feedback offers a scalable alternative. Objective: This pilot randomized controlled trial compared the feasibility, safety, and preliminary clinical effectiveness of a sensor-based telerehabilitation protocol using the KneE-PAD patient monitoring approach which was also combined with an avatar-guided visual feedback add-on tool. Although this approach is capable of AI-driven postural error detection, this feature was not enabled during the current study, and feedback was provided solely through visual cues. Methods: Twenty adults with radiographically confirmed Kellgren–Lawrence grade 1 to 3 knee OA were randomized into two groups (Control/Intervention groups, n = 10 in each). The control group received in-person physiotherapy, while the intervention group engaged in remote rehabilitation supported by wearable sEMG and IMU sensors. The 8-week program included supervised and home-based sessions. Primary outcomes were WOMAC scores (Functionality/Pain), quadriceps strength, and sEMG-derived neuromuscular activation. Secondary outcomes included Timed Up and Go test (TUG), psychological measures (HADS, TSK), and self-efficacy measure (ASES). Analyses employed both parametric and non-parametric statistics including an effect size estimation. Results: Both groups demonstrated significant improvements in WOMAC total scores (Intervention: −11.8 points; Control: −6.4 points), exceeding the minimal clinically important difference (MCID) for knee OA. Strength and mobility also improved significantly in both groups, with the Intervention group showing superior gains in sEMG measures (RMS: p = 0.0077; Peak-to-Peak: p < 0.005), indicating enhanced neuromuscular adaptation. TUG performance improved more in the intervention group (–3.17 s vs. –2.57 s, p = 0.037). Psychological outcomes favored the control group, particularly in depression scores (HADS-D, t(18) = 2.37, p = 0.03). Adherence was high (94.8%), with zero attrition and no adverse events. Conclusions: The KneE-PAD monitoring approach offers a feasible and clinically effective alternative to conventional physiotherapy, enhancing neuromuscular outcomes through real-time sensor feedback. These findings support the viability of intelligent telerehabilitation for scalable OA care and inform the design of future large-scale trials. Full article

Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular event with high mortality and long-term morbidity. While clinical grading scales such as Hunt and Hess or the World Federation of Neurological Surgeons (WFNS) score aid in prognosis, their accuracy implies a neurological assessment that can be confounded in sedated patients, highlighting the need for objective biomarkers. Biomarkers offer an alternative approach for risk stratification. This review examines the prognostic value of the glucose/potassium ratio (GPR) in patients with aneurysmal SAH and its potential integration into future predictive models. A literature review of retrospective studies assessing the association between GPR and clinical outcomes in SAH was conducted. Evidence on the pathophysiological basis of stress-induced hyperglycemia and hypokalemia in SAH is presented, along with findings from five key clinical studies evaluating GPR in relation to mortality, vasospasm, delayed cerebral ischemia, and functional outcomes. Elevated GPR levels were consistently associated with poor short- and long-term outcomes in SAH patients. Studies reported significant correlations between GPR and 30-day mortality, poor Glasgow Outcome Scale (GOS) scores, increased incidence of cerebral vasospasm, and higher rates of rebleeding. The optimal GPR cutoff for predicting adverse outcomes was greater than 37 mg/dL, with multivariate analyses confirming GPR as an independent prognostic factor. GPR is a promising, cost-effective biomarker that integrates two stress-response parameters (glucose and potassium), both of which are independently associated with SAH prognosis. Its incorporation into future predictive models may enhance early risk stratification and guide clinical decision-making. Further prospective studies are warranted to validate its utility and standardize its clinical application. Full article

Pharmacovigilance approaches have conventionally focused on the use of epidemiological data to detect emergent adverse drug reactions (ADRs). Recent advances in the use and availability of real-world data have expanded opportunities to detect ADR signals in medical records. We provide a limited review of pharmacovigilance practices and tools we have specifically considered implementing into our comprehensive medication management clinic and associated research programs. Use of pharmacogenomic variants has proven useful only on a limited scale as such data are reliant on low-dimensional approaches matching variants to drugs, often with small effect sizes. As such, most ADRs go unrecognized, undocumented, and unactionable. We posit that an idealized pharmacovigilance framework that relies on artificial-intelligence-assisted reporting with adjudication by pharmacovigilance experts and new models of ambulatory pharmaceutical practice would establish the following attributes: (1) all metadata relating to medication use would be available in the medical record in computable and interoperable data models, (2) digital surveillance tools would detect most ADR events with attributed pharmacological contributions, (3) all events would be characterized using standard adjudication rubrics, and (4) all events would iteratively inform an ADR knowledgebase and improve models to advance detection and prediction of ADR during the course of patient care with a focus on having the necessary tools for clinicians to prevent ADRs. This review provides a limited and focused framework for more systematic documentation of ADRs and tactics to mitigate the idiopathic nature of most ADRs. Full article