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AI-Driven Pharmacovigilance and Molecular Profiling of Fluoroquinolone-Associated Cardiotoxicity in the UAE: A Geospatial and Machine Learning Analysis with Structural Modification Strategies (2018-2023)

Iftikhar, H.

2025-05-13 health informatics
10.1101/2025.05.10.25327319 medRxiv
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BackgroundFluoroquinolones, while clinically indispensable, carry underappreciated cardiovascular risks, particularly QT prolongation and life-threatening arrhythmias. Emerging evidence suggests geographic and genetic variations in susceptibility, yet Middle Eastern populations remain underrepresented in global pharmacovigilance datasets. ObjectiveThis study investigates the prescribing trends and awareness of fluoroquinolone-related adverse effects among healthcare providers in the UAE using a multimodal combination of artificial intelligence (AI) integrating pharmacovigilance data, environmental exposure mapping, predictive ECG analytics and natural language (NLP) of electronic health records (EHRs) MethodsWe conducted a retrospective cohort study (2018-2023) combining structured ADR reports from UAE MOHAP, WHO-VigiAccess, FAERS, and EMA with unstructured clinical narratives. A hybrid NLP pipeline (BioBERT-based NER, sentiment analysis, and relationship extraction) identified unreported risk patterns. Machine learning (Random Forest, SVM, BioBERT-NLP) stratified high-risk cases, validated against MIMIC-IV ECG waveforms. Geospatial modeling correlated wastewater fluoroquinolone levels with regional arrhythmia incidence. ResultsAmong 1,522 adjudicated ADRs, moxifloxacin demonstrated the strongest cardiotoxicity signal (OR=1.45, 95% CI 1.2-1.8, *p*<0.001), with AI-ECG models detecting subclinical torsades de pointes at 96% sensitivity (AUC 0.97). NLP revealed significant ECG monitoring disparities in Northern Emirates (under documentation rate: 43%). Environmental analyses identified a dose-dependent relationship between moxifloxacin water contamination and arrhythmia hospitalizations (+22% in high-exposure regions, *p*=0.01). Molecular dynamics simulations implicated C7 substituent modification as a viable strategy to reduce hERG channel binding. ConclusionWe integrated multi-omics analysis with pharmacovigilance mining to stratify cardiotoxic risk among fluoroquinolone users in the UAE bridging pharmacovigilance, environmental epidemiology, and structural pharmacology. Our framework enables precision monitoring through AI-ECG integration, policy interventions targeting high-risk prescribing, and drug redesigning to mitigate hERG liability.

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