Current LLMs should be regarded as adjunctive tools requiring expert verification for high-risk OMFS pharmacological decisions, as positive correlations among the evaluation criteria within the ChatGPT data indicated convergence among the three scoring dimensions.
Abstract
Background
Pharmacology represents the lowest-performing subcategory in oral and maxillofacial surgery (OMFS) evaluations of large language models (LLMs), yet no study has simultaneously compared the leading commercial LLMs across multiple pharmacological domains and question formats. This study evaluated ChatGPT 5.3, Gemini 3.1 Pro, and Claude 4.6 Sonnet in OMFS pharmacology.
Methods
Thirty-six OMFS pharmacology questions spanning five clinical domains (antibiotic prophylaxis, analgesics, drug-drug interactions, anesthetic pharmacology, special populations) and three formats (open-ended, multiple-choice, true/false; n = 12 each) were submitted to each LLM using a standardized role-conditioning prompt. The 108 responses were independently and blindly evaluated by two oral and maxillofacial surgeons (one specialist and one resident) on three 5-point Likert criteria. Inter-rater reliability was quantified using ICC(2,1) and Cohen's κ_w. Inter-model differences were assessed using Friedman tests; format effects were assessed using Kruskal-Wallis tests with Bonferroni-corrected post-hoc comparisons.
Results
Inter-rater reliability was excellent (ICC = 0.828; κ_w = 0.827; exact agreement 91.0%). A robust hierarchy emerged: Claude > Gemini > ChatGPT (χ²(2) = 47.91, p < 0.001, W = 0.665), with all pairwise comparisons significant. Gemini and Claude did not differ significantly in any format section, indicating clinical equivalence. ChatGPT exhibited a significant decline on open-ended, integrative-reasoning items (H(2) = 17.04, p < 0.001, ε² = 0.456), absent in Gemini and Claude. Significant positive correlations among the evaluation criteria within the ChatGPT data indicated convergence among the three scoring dimensions.
Conclusion
Claude 4.6 Sonnet and Gemini 3.1 Pro achieved near-maximal scores on this structured pharmacology benchmark, while ChatGPT 5.3 showed a significant decline in open-ended reasoning. Current LLMs should be regarded as adjunctive tools requiring expert verification for high-risk OMFS pharmacological decisions.
INTRODUCTION
Methoxyflurane (MOF) is a low-dose inhaled analgesic with rapid onset, patient-controlled titration, and an established safety profile at sub-anesthetic doses. Its potential role in oral and maxillofacial surgery (OMFS) has not been comprehensively mapped.
OBJECTIVE
To map and characterize available evidence on inhaled methoxyflurane in OMFS, including dento-alveolar surgery, acute oral pain emergencies, and outpatient analgesic-sedation.
METHODS
Scoping review conducted following JBI methodology and reported per PRISMA-ScR. Eligibility defined by PCC (Population, Concept, Context) framework. Searched: MEDLINE (PubMed), Embase, Cochrane CENTRAL, Scopus, and Web of Science, with no date restriction. Two independent reviewers screened records; data charted using a standardised form.
RESULTS
Twenty studies were identified: 10 with direct OMFS/dental relevance (2 RCTs, 2 case series, 1 clinical study, 2 narrative reviews, 1 systematic review, 1 feasibility review, 1 ongoing Phase 3 RCT) and 10 with indirect but clinically translatable relevance. MOF demonstrated comparable sedation and greater patient preference versus nitrous oxide in third molar surgery (p<0.05). Systematic reviews in outpatient procedural contexts reported satisfaction rates of 63%->98% and no serious adverse events at analgesic doses. The pivotal METODO trial (NCT06495372), a Phase 3 placebo-controlled RCT in adult dental emergencies, is currently enrolling (expected completion October 2026).
CONCLUSION
Available evidence supports the clinical feasibility of MOF in OMFS, particularly for third molar surgery and acute oral pain. High-quality OMFS-specific RCTs remain lacking. The METODO trial will provide pivotal data to guide practice. Future research should address OMFS-specific protocols and jurisdictions where MOF lacks regulatory approval.
Bernardo Correia Lima, Pedro Américo Felizardo dos Santos, Michelle Alonso Coutinho et al.· Journal of Stomatology Oral...· 0 citations
Background Head and facial pain caused by local invasion in nasopharyngeal carcinoma (NPC) is notoriously severe and traditionally managed with opioids, which carry substantial dependence and tolerability risks. Because this tumor-related pain intrinsically involves both neuropathic and inflammatory pathways, we retrospectively evaluated a novel opioid-sparing analgesic strategy combining celecoxib and gabapentin. Methods This exploratory retrospective cohort analysis included 60 newly diagnosed NPC patients experiencing severe head and facial pain secondary to cranial nerve or skull base invasion. Patients received either opioid monotherapy (extended-release oxycodone, n=30) or a combined regimen of celecoxib and gabapentin (n=30). The primary endpoint was the absolute reduction in Numeric Rating Scale (NRS) scores at 48 hours. Secondary endpoints included sleep quality improvement, assessed via the Insomnia Severity Index (ISI), and adverse events. Longitudinal data were rigorously analyzed using Generalized Estimating Equations (GEE) to account for repeated measures and adjust for baseline clinical covariates. Results Baseline clinical characteristics were broadly comparable between the cohorts, with no statistically significant differences in premedication NRS scores (6.5 in both groups) or ISI scores (16.5 vs 19.5, P = 0.118); however, the combined group had a numerically higher baseline ISI score, and all ISI comparisons were therefore based on change-from-baseline scores. The GEE longitudinal analysis revealed a significant treatment-by-time interaction for pain relief. At the 48-hour primary endpoint, the combined regimen demonstrated a significantly greater absolute reduction in NRS scores compared to the opioid group (Estimated Mean Difference [MD], 2.15; 95% CI, 1.45 to 2.85; P < 0.001). Furthermore, the combined therapy yielded a profoundly larger improvement in sleep architecture (ISI reduction MD, 9.85; 95% CI, 7.50 to 12.20; P < 0.001). Safety profiles analyzed via Fisher’s exact test confirmed the combined group had a significantly lower incidence of nausea and vomiting (0.0% vs 20.0%, P = 0.024); no significant between-group differences were observed for other adverse events including constipation, dizziness, and somnolence. Conclusion Combining celecoxib and gabapentin appears to offer an effective, opioid-sparing alternative for managing complex tumor-related pain in NPC, and was associated with greater pain reduction over the 48-hour observation period, accelerated sleep recovery, and significantly better gastrointestinal tolerability compared to conventional opioid therapy in this retrospective cohort. These findings are hypothesis-generating and warrant prospective validation.
Xiang-Rong Cao, Lin Xu, Wei-Wei Ta· Journal of Pain Research· 0 citations
Methotrexate (MTX) is a cornerstone therapy for rheumatoid arthritis and graft-versus-host disease prophylaxis but is frequently complicated by oral mucositis. This systematic review and network meta-analysis, registered in PROSPERO (CRD420251048475) and conducted in accordance with PRISMA 2020 and PRISMA-NMA guidelines, evaluated the comparative effectiveness of preventive interventions for MTX-associated mucositis. PubMed, Embase, Cochrane CENTRAL, Scopus, and Web of Science were searched from 2000 to July 2025 without language restrictions. Randomised controlled trials involving adults or children receiving MTX were included if they assessed cryotherapy, low-level laser therapy (LLLT), palifermin, folinic acid rescue, or high-dose leucovorin versus standard care or placebo. Two reviewers independently extracted data and assessed risk of bias. Random-effects pairwise meta-analyses and a frequentist network meta-analysis were performed. Of 1,432 records screened, six trials including 321 participants met the inclusion criteria. LLLT (OR 0.30; 95% CI 0.17–0.54) and palifermin (OR 0.39; 95% CI 0.22–0.68) substantially reduced the risk of severe mucositis compared with standard care. Cryotherapy and high-dose leucovorin demonstrated modest benefit, while folinic acid rescue showed no protective effect. Indirect comparisons between active interventions were imprecise. Overall, LLLT and palifermin appear to be the most effective preventive strategies for MTX-associated oral mucositis, although larger, well-designed head-to-head trials are required to strengthen the evidence base.
BACKGROUND
Acetaminophen is widely used in multimodal analgesia after total joint arthroplasty (TJA), but the comparative effects of different regimens remain uncertain.
METHODS
PubMed, Embase, Cochrane Library, and Web of Science were searched through September 22, 2025 for randomized controlled trials evaluating acetaminophen or propacetamol regimens after total hip or knee arthroplasty. A Bayesian network meta-analysis was performed using R 4.4.0 and JAGS 4.3.1. Outcomes included pain scores at 6, 12, and 24 h and 24 h supplemental analgesic consumption, expressed as standardized mean differences (SMDs) with 95% credible intervals (CrIs).
RESULTS
Fifteen RCTs including 1986 patients and six interventions were analyzed. For 24 h supplemental analgesic consumption, multiple-dose intravenous propacetamol and multiple-dose intravenous acetaminophen ranked highest (SUCRA 90.37% and 86.94%) and were superior to control (SMD 0.49 [0.18, 0.81] and 0.45 [0.27, 0.63], respectively). For 24 h pain, multiple oral and multiple intravenous acetaminophen reduced scores versus control (SMD 0.25 [0.05, 0.45] and 0.18 [0.005, 0.35], respectively). No significant differences were found at 12 h. At 6 h, multiple-dose intravenous propacetamol showed the largest effect (SMD 0.96 [0.49, 1.42]).
CONCLUSIONS
Acetaminophen-based regimens may provide modest postoperative analgesic and opioid-sparing benefits after TJA, particularly with selected multiple-dose intravenous protocols. However, no single regimen was consistently superior across outcomes and time points, and SUCRA rankings should be interpreted alongside effect estimates and clinical feasibility.
Yinghua Liao, Baiyun Wang· Journal of Orthopaedic Scien...· 0 citations
BACKGROUND
Multimodal anesthesia (MMA) is widely used to reduce opioid use and improve postoperative recovery. However, evidence for bundled MMA regimens-defined as opioids plus ≥2 adjunct analgesic modalities-has not been systematically synthesized across patient-centered outcomes.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials comparing MMA (opioids plus ≥2 adjuncts, including regional techniques and/or systemic agents such as dexmedetomidine, ketamine, intravenous lidocaine, clonidine, or magnesium) with opioid-based general anesthesia in adults undergoing elective surgery. MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Library were searched to 28 October 2025. Primary outcomes were postoperative pain, PONV, QoR-15, and pulmonary complications. Secondary outcomes included opioid consumption in Morphine Milligram Equivalent (MME) and PACU length of stay. Risk of bias was assessed with RoB 2 and certainty with GRADE. Registered in PROSPERO (CRD42024470056).
RESULTS
Twenty-one RCTs (n = 1828) were included. At 24 h, no clear effect of MMA on pain intensity was observed (10 trials, n = 785; MD -0.6, 95% CI -1.5 to 0.2; very low certainty). MMA reduced PONV incidence (4 trials, n = 352; RR 0.59, 95% CI 0.44 to 0.77; low certainty). For secondary outcomes, MMA reduced opioid consumption (10 trials, n = 915; MD -7.0 mg MME, 95% CI -12.8 to -1.3; moderate certainty), with the opioid-sparing effect persisting at 48 h (MD -14.0 mg MME) and study end (MD -16.0 mg). Data for QoR-15, PACU stay, and pulmonary complications were insufficient for pooling.
CONCLUSIONS
MMA shows no clear effect on postoperative pain at 24 h but reduces PONV incidence and opioid consumption. Evidence certainty ranges from moderate to very low. Larger, standardized trials are needed to define optimal MMA regimens and patient selection.
Stefano M Arigoni, Adina B Heitmann-Frei, Marc S. von Gernler et al.· Journal of clinical anesthes...· 0 citations
Intrathecal baclofen (ITB) acts as a selective GABA
B
receptor agonist to modulate spinal inhibitory pathways. While effective for severe spasticity, the pharmacotherapeutic efficacy and safety profile across distinct neurological etiologies—cerebral palsy (CP), spinal cord injury (SCI), and brain injury (BI)—remain poorly characterized from a comparative pharmacological perspective.
We systematically searched five global databases (up to August 2025) for trials evaluating ITB therapy. Random-effects models were employed to synthesize efficacy data, focusing on dose-response relationships and clinical outcomes. 15 studies (6 RCTs, 9 observational) were analyzed. Our results demonstrate that ITB significantly reduced Ashworth Scale scores across all subgroups, but with marked etiology-specific variations in effective dosage requirements. Specifically, SCI patients exhibited the most significant reduction in spasm frequency. Safety pharmacology analysis revealed that pharmacological adverse events (AEs), such as somnolence and respiratory depression, were dose-dependent and more prevalent in BI populations. In contrast, hardware-related complications (e.g., catheter malfunction) were idiosyncratic but clinically severe.
ITB therapy provides robust anti-spasticity effects mediated through its targeted action on spinal inhibitory circuits. However, the heterogeneity in dosage efficacy suggests etiology-driven differences in GABA
B
receptor sensitivity or drug distribution. These findings underscore the necessity for precision titration strategies based on patient-specific pathophysiology and highlight the importance of differentiating between pharmacodynamic side effects and mechanical complications to optimize the therapeutic index of ITB.
https://www.crd.york.ac.uk/PROSPERO/view/CRD420251112388
, identifier CRD420251112388.
Haoyuan Chen, Hong-Hui Lei, Yang Yu et al.· Frontiers in Pharmacology· 0 citations