British Journal of Anaesthesia

Background Postoperative nausea and vomiting (PONV) remains a frequent and distressing complication after gynecologic laparoscopic surgery, with residual incidence approaching 30-40% despite contemporary multimodal antiemetic prophylaxis. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique that activates auricular vagal afferents projecting to brainstem nuclei implicated in emetic reflexes. We present the protocol of a randomized trial to evaluate taVNS as an adjunctive, nonpharmacologic strategy to reduce PONV in this high-risk population. Methods This single-center, prospective, randomized, double-blind, sham-controlled, parallel-group superiority trial will enroll 146 adult women undergoing elective gynecologic laparoscopy under general anesthesia. Participants will be randomized 1:1 to active taVNS or sham stimulation, with stratification by Apfel risk score ([≤]2 vs. [≥]3). Two 30-minute sessions will be delivered: one beginning 30 minutes before anesthesia induction and another 30 minutes after arrival in the post-anesthesia care unit. The primary outcome is the incidence of PONV within 48 hours postoperatively. Secondary outcomes include nausea severity (11-point numerical rating scale), time to first PONV episode, number of vomiting/retching episodes, rescue antiemetic use, postoperative pain intensity, cumulative opioid consumption (morphine equivalents), Quality of Recovery-15 scores at 24 and 48 hours, and gastrointestinal recovery indices. Analyses will follow intention-to-treat and per-protocol principles; missing data will be addressed via multiple imputation. Conclusions This trial aims to provide rigorous evidence on the efficacy and safety of perioperative taVNS for PONV prevention in women undergoing gynecologic laparoscopy. If proven effective, taVNS could be integrated into enhanced recovery after surgery (ERAS) pathways as a mechanistically grounded, nonpharmacologic adjunct to standard antiemetic regimens. Trial registration Chinese Clinical Trial Registry ChiCTR2600115965 (prospectively registered).

BackgroundFospropofol disodium is a water-soluble prodrug of propofol that avoids a lipid emulsion carrier. It may therefore reduce injection pain, cardiorespiratory depression and lipid exposure. In May 2021 it was approved in China (H20210017) for induction of general anaesthesia in adults. Randomised trials have since tested it for sedation outside the operating room, but this setting has not been systematically reviewed. MethodsWe followed PRISMA 2020 and PRISMA-S and searched Europe PMC, PubMed, Embase, Cochrane CENTRAL, Web of Science and the Chinese databases CNKI, Wanfang and VIP (the last accessed through the XJMU Library database proxy) from inception to 2026. Eligible patients were adults receiving sedation for purposes other than general anaesthesia induction or maintenance, including continuous sedation during ICU mechanical ventilation and procedural sedation. These uses are referred to here as sedation outside the operating room. We included randomised controlled trials with propofol as the comparator and excluded trials of general anaesthesia induction or maintenance to avoid overlap with the published induction meta-analysis. Binary outcomes were pooled with a DerSimonian-Laird random-effects model, and REML plus modified Hartung-Knapp estimates were reported alongside to improve interval coverage when few studies were available. Outcomes with a high proportion of zero cells were also analysed with the Peto method. We stratified by setting and blinding and performed leave-one-out analysis, trial sequential analysis (TSA) and GRADE assessment. Hypotension reached the prespecified threshold of at least 10 studies, so publication bias was assessed with the Harbord test, with the originally specified Eggers test reported alongside. The protocol was prospectively registered and took effect on 16 September 2026. All searches were completed on 21 September 2026, and screening, extraction and analysis were performed after registration. ResultsTwelve randomised controlled trials were included. Event counts for all 12 studies were checked against the full-text original publications. For Liu 2026, a preprint, counts were taken directly from its Tables 2 and 3. Compared with propofol, fospropofol disodium reduced injection pain under the DerSimonian-Laird model (8 studies, OR 0.09, 0.03-0.21) and increased pruritus/paraesthesia (4 studies, OR 32.56, 12.89-82.26; RD +28.5%). During procedural sedation, it was associated with fewer respiratory adverse events (5 studies, OR 0.19, 0.11-0.32). This composite includes respiratory depression, hypoxaemia and related events reported by individual trials and should not be extrapolated to all adult sedation settings. For hypertriglyceridaemia, the DerSimonian-Laird estimate was OR 0.29 (0.13-0.65), but all four studies were conducted in ICU settings and the REML plus modified Hartung-Knapp estimate was 0.29 (0.08-1.08), with a confidence interval crossing 1. Certainty was very low, so this finding remains hypothesisgenerating. Hypotension differed by setting: OR 0.24 (0.13-0.42) for procedural sedation and 0.90 (0.53-1.55) for continuous ICU sedation, with a significant interaction (P < 0.001). The overall estimate (OR 0.51, 0.28-0.93) is reported for summary only. Under REML plus modified HartungKnapp it was 0.51 (0.25-1.03), crossing 1, so it does not support a claim that the drug lowers blood pressure and should not be extrapolated to the ICU. Bradycardia did not differ significantly (9 studies, OR 0.45, 0.17-1.18), and the direction reversed in the only double-blind study. Two studies reported slower onset or loss of consciousness with fospropofol disodium (MD +2.22 and +0.92 min), but these were not pooled because heterogeneity was extreme (I2 = 99.6%). Recovery, discharge and successful extubation showed no clear differences, although heterogeneity was high (I2 = 85%-92%) and the evidence cannot establish equivalence. Sedation efficacy was not pooled because definitions differed. Patient-important outcomes (death, delirium, ICU length of stay and duration of mechanical ventilation) were each reported by only one or two small studies with inconsistent definitions and time points, so no reliable conclusion can be drawn. Setting-specific results should take priority over the overall mean. Certainty ranged from very low to moderate. O_TBL View this table: org.highwire.dtl.DTLVardef@174a615org.highwire.dtl.DTLVardef@143c610org.highwire.dtl.DTLVardef@807653org.highwire.dtl.DTLVardef@1d857eborg.highwire.dtl.DTLVardef@740a59_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 2:C_FLOATNO O_TABLECAPTIONBinary event counts by study and outcome (fospropofol disodium versus propofol). C_TABLECAPTION C_TBL O_TBL View this table: org.highwire.dtl.DTLVardef@538773org.highwire.dtl.DTLVardef@1e1ccbcorg.highwire.dtl.DTLVardef@1486540org.highwire.dtl.DTLVardef@1ef63f9org.highwire.dtl.DTLVardef@18ca7cb_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 3:C_FLOATNO O_TABLECAPTIONThreshold, recording window and intervention requirement for hypotension in each study (10 studies). C_TABLECAPTION C_TBL ConclusionsDuring procedural sedation, fospropofol disodium may reduce injection pain and respiratory adverse events and may lower the risk of hypotension compared with propofol. This hypotension benefit should not be extrapolated to the ICU. During continuous ICU sedation no data were available for injection pain or respiratory adverse events, so the safety evidence in that setting remains limited. Hypertriglyceridaemia was lower only under the DerSimonian-Laird model. Because the result depends on the method and certainty is very low, it cannot be treated as definitive. The main cost is a clear increase in pruritus and abnormal sensations. Onset may be slower, but the evidence comes from two bolus-dosing studies in procedural sedation, and no such disadvantage was seen during continuous ICU infusion. Evidence on sedation efficacy, recovery time, discharge time and successful extubation is limited, and equivalence between the two drugs cannot be asserted. Because most studies were small and open-label and certainty ranged from very low to moderate, these findings support investigational use only and do not justify a routine clinical recommendation. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Europe PMC, PubMed, Embase, Cochrane CENTRAL, Web of Science Core Collection and Chinese databases (CNKI, Wanfang, VIP) by crossing drug terms (fospropofol, fospropofol disodium, Lusedra, Aquavan) with sedation setting terms (ICU, mechanical ventilation, endoscopy, gastroscopy, hysteroscopy, bronchoscopy, procedural sedation). Within the retrieved literature, the only relevant meta-analysis addressed general anaesthesia induction; no synthesis of the sedation setting was identified. Added value of this studyThe present synthesis focuses on sedation outside the operating room, includes 12 RCTs, and stratifies by setting. It reports eight safety and efficacy outcomes (recovery time and other continuous outcomes are reported narratively), together with heterogeneity, leave-one-out sensitivity analysis, trial sequential analysis and GRADE certainty, and it quantifies the costs of fospropofol disodium (pruritus/paraesthesia; slower onset after bolus dosing). Clinical implicationsFospropofol disodium may reduce injection pain during sedation. For hypertriglyceridaemia the result depends on the estimator and certainty is very low. During procedural sedation it may reduce hypotension and respiratory adverse events, whereas the evidence for a hypotension benefit during continuous ICU sedation is weak. Because the approved indication in China is adult general anaesthesia induction only, these uses remain investigational; they do not constitute a routine clinical recommendation. Applicability to specific patient groups remains an inference from pharmacological mechanism.

Background: Opioids remain the cornerstone of acute postoperative pain management but are associated with potentially serious adverse effects. We aimed to investigate the effect of oxycodone patient-controlled analgesia with adjunctive S-ketamine on pain after lumbar fusion surgery. Methods: In this secondary analysis, we examined oxycodone and S-ketamine exposure and PCA behaviour during the first 24 h. We assessed current pain versus subsequent PCA activity and whether the association between plasma oxycodone and adequate analgesia changed with postoperative time. Results: Plasma concentrations of administered drugs rose rapidly after PCA initiation, but variation was large. Metabolite concentrations accumulated over time. PCA attempt and delivered-dose rates decreased over postoperative time (RR 0.965 and 0.966 per hour, respectively; both P<0.001). Older age was associated with a lower delivered-dose rate (RR 0.905 per 10 years, 95% CI 0.829-0.987). Each 1-point higher current pain score was associated with more subsequent PCA attempts (RR 1.09, 95% CI 1.04-1.14) and delivered doses (RR 1.07, 95% CI 1.03-1.11). The oxycodone-analgesia association weakened over time [interaction P <0.001; odds ratios (Ors) per 10 ng/mL 1.16, 1.13, and 1.00 at 1, 4, and 24 h, respectively]. In active S-ketamine groups, including S-ketamine, norketamine, and 6-hydroxynorketamine concentrations left the pain-PCA association unchanged (RR 1.09 and 1.07) and preserved the time-dependent oxycodone association (ORs 1.30, 1.26, and 1.02). Conclusions: During PCA, drug exposure develops from patient-generated dosing histories while pain and recovery change. Current pain was associated with subsequent PCA activity, and the oxycodone-analgesia association was time-dependent.

Background: Emergency conversion from labor epidural analgesia to Category I cesarean section leaves little time for epidural top-up to produce a surgical block. We examined whether low-dose intravenous esketamine could provide short-term bridging analgesia and sedation while maintaining maternal hemodynamics, oxygenation, and early neonatal safety. Methods: In this randomized study, parturients requiring Category I cesarean section after labor epidural analgesia received either esketamine 0.15 mg/kg or normal saline 1 min before skin incision, together with epidural alkalinized lidocaine. The primary outcome was the longitudinal change in maternal systolic blood pressure during the 20-min observation window. Secondary outcomes included heart rate, SpO2, intraoperative pain, surgeon satisfaction with muscle relaxation, Ramsay sedation score, and neonatal Apgar scores. We analyzed repeated continuous outcomes with linear mixed-effects models and repeated binary outcomes with generalized estimating equations. The single post-administration Ramsay outcome was analyzed using logistic regression. Apgar scores were summarized descriptively using medians, interquartile ranges, and counts.Results: We analyzed 55 parturients, 31 in the esketamine group and 24 in the normal saline group. Esketamine did not meaningfully alter the systolic blood pressure trajectory. Heart rate and SpO2 showed broadly similar patterns between groups, with no signal of esketamine-related respiratory deterioration. The esketamine group had lower odds of intraoperative pain at 5, 15, and 20 min and a higher probability of target Ramsay sedation. Surgeon satisfaction with muscle relaxation showed no clear between-group difference. Apgar scores remained high in both groups. Conclusion: Low-dose intravenous esketamine 0.15 mg/kg may be a practical bridging adjunct during emergency conversion from labor epidural analgesia to Category I cesarean section. It improved early pain control and target sedation without a clear adverse signal in systolic blood pressure, heart rate, oxygenation, or early Apgar scores. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2600121948; retrospectively registered.

Interoception is described as the sensitivity to internal bodily stimuli, and plays an important role in pain perception. Heightened interoceptive sensibility (i.e. self-reported interoceptive abilities) may reinforce misinterpretation of stimuli, enhancing pain perception. This study aimed to investigate the relationship between interoceptive sensibility and acute postoperative pain. Interoceptive sensibility was measured using the Private Body Consciousness Scale in two prospective observational surgical cohorts: a Caesarean delivery cohort (C-section cohort) of 146 patients, and a lower extremity orthopaedic surgery cohort (Ortho cohort) of 70 patients. One day after surgery, patients rated pain (primary outcome) and other postoperative symptoms (secondary outcomes) on a 0-10 scale. Bonferroni corrections were applied to secondary outcomes. Interoception positively correlated with pain (C-section cohort: Spearmans rho = 0.182, P = 0.028; Ortho cohort: rho = 0.259, P = 0.031), and with dizziness (C-section cohort: rho = 0.309, P = 0.002; Ortho cohort: rho = 0.348 P = 0.041) in both cohorts. In the C-section cohort, interoception correlated with shivering (rho = 0.321, P < 0.001). In the Ortho cohort, interoception correlated with nausea (rho = 0.366, P = 0.023) and helplessness (rho = 0.363, P = 0.026); whereas no correlation with pain catastrophising was found (rho = 0.240, P = 0.539). In pooled multiple linear regression analysis (n = 216), interoception predicted pain after controlling for age, sex and anaesthetic technique (B = 0.119, 95% CI [0.027-0.210], P = 0.011). These findings highlight the potential role of interoception in identifying patients at risk for acute postsurgical pain.

Background: Depth of anesthesia is routinely monitored using electroencephalographic (EEG) indices such as the Bispectral Index (BIS), which reduce cortical activity to a single numerical real-time series. However, these scalar descriptors fail to capture inter-individual variability, drug-specific EEG signatures, and transitions between brain states. Methods: We analyzed transient EEG patterns during general anesthesia induced by propofol and sevoflurane in 89 patients. Iso-electric suppressions (IES), $\alpha$-suppressions, and spectral power in the $\alpha$ and $\delta$ bands were quantified across controlled concentration plateaus. We compared conventional BIS monitoring with a novel State-Chart representation mapping EEG activity into discrete depth states. Results: Increasing hypnotic concentration produced a consistent shift from $\alpha$-dominant to $\delta$-dominant activity and a reduction in maximal $\alpha$ frequency. IES occurred predominantly at high propofol concentrations and remained infrequent under sevoflurane. Compared with BIS, the State-Chart showed a marked reduction in temporal variability (0.5 $\pm$ 0.6 vs 4.0 $\pm$ 2.9; $p<10^{-90}$). Importantly, our State-Chart separates stable from transition regimes and discriminates identical concentration levels. Statistics computed over prior dosing (ascending vs descending), reveals refined clustering not captured by BIS. Conclusions: Anesthesia depth drugs concentrations vs EEG effects is more accurately described by structured EEG state transitions than by a single numerical index. The State-Chart provides a stable, physiologically interpretable representation of brain activity and reveals transition states preceding deep cortical suppression, supporting individualized and predictive monitoring of anesthesia.

Abstract Background: Mean arterial pressure (MAP) is pharmacologically augmented in selected perioperative and critical care settings, including acute neurological conditions and after cardiac arrest, with the aim of improving cerebral perfusion, although it remains uncertain whether higher arterial pressure translates into increased cerebral blood flow (CBF). We investigated the CBF response to MAP augmentation with norepinephrine (NE), a commonly used vasopressor in perioperative and critical care settings, during propofol-based general anesthesia. Methods: In this prospective within-subject interventional study, 16 neurologically intact patients with ASA physical status I-II undergoing elective surgery were studied using phase-contrast magnetic resonance imaging. CBF was quantified in the awake state and during propofol-based general anesthesia before and after NE-induced MAP augmentation. During general anesthesia, NE was titrated to increase MAP by approximately 25% from baseline. Concurrent systemic hemodynamics were assessed. Results: General anesthesia was associated with a 50.1% (interquartile range, 42.1?55.7%) reduction in CBF and a 24.2% (20.3-29.2%) reduction in MAP compared with the awake state (both P<0.001). During general anesthesia, NE-induced MAP augmentation increased MAP by 25.7% (21.9-32.0%; P<0.001), whereas CBF remained unchanged (P=1.000). Cardiac output remained unchanged (P=0.163), whereas systemic vascular resistance index and cerebrovascular resistance increased by 40.0% (28.7-45.2%) and 36.2% (17.7-42.8%), respectively (both P<0.001). Changes in CBF during MAP augmentation were not associated with concurrent changes in MAP, cardiac output, or systemic vascular resistance index. Conclusions: In neurologically intact patients undergoing propofol-based general anesthesia, clinically relevant NE-induced MAP augmentation did not increase CBF despite an approximately 50% lower CBF than in the awake state. These findings challenge the assumption that pharmacological elevation of an otherwise adequate MAP improves cerebral perfusion in this setting. While maintaining adequate arterial pressure remains essential, further MAP augmentation should not be assumed to increase CBF. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT06855407; NCT06855407.

Lines, drains, and airway devices are commonly used in surgical and inpatient care to support treatment and patient monitoring. While these devices are essential, prolonged device retention is associated with complications such as infection, tissue injury, thrombosis, and extended hospital stay. Understanding how long devices remain in place and how duration varies across device types is important for improving patient safety and guiding device management practices. This study analyzes device duration patterns using Patient Lines, Drains, and Airways (LDA) data containing information on device type, placement time, and removal time across multiple patient encounters. Exploratory data analysis and machine learning approaches are used to examine duration distributions, distinguish short and prolonged device retention, and identify structural patterns across device categories. The findings indicate notable variation in device duration patterns across categories, with identifiable differences in device retention behavior across device groups. This study highlights the value of observational electronic health record data for characterizing device exposure patterns and provides a foundation for future data-driven device management and risk assessment.

INTRODUCTION Large language models (LLMs) have demonstrated substantial performance on medical licensing and board examinations, but their application to anesthesiology remains less well studied. Prior evaluations have not compared current-generation models from different developers or assessed performance on figure-dependent questions that earlier models lacked the capability to interpret. This study evaluates the performance of two current-generation LLMs on a comprehensive anesthesiology in-training examination (ITE) review question bank, including figure-dependent items. METHODS A total of 1,001 single-best-answer questions from an anesthesiology ITE review text, spanning 11 content chapters, were administered to Claude Opus 5 and GPT-5.6. No questions were excluded. Each item was presented once in a fresh, stateless context with no tool access, retrieval, answer key, or explanation provided in the prompt. Performance was analyzed by question format, and all 27 figure-dependent items were administered with their published figures supplied. Accuracy between models was compared using McNemar's test. RESULTS Claude Opus 5 answered 947/1,001 items correctly (94.6%; 95% CI, 93.0-95.8), and GPT-5.6 answered 946/1,001 correctly (94.5%; 95% CI, 92.9-95.8); the difference was not significant (McNemar p=1.00). Accuracy was similar across most question formats. On standard questions, accuracy was 94.3% and 94.6% for Claude Opus 5 and GPT-5.6, respectively; on the 18 figure-based questions with figures supplied, accuracy was 94.4% and 83.3%, respectively; and both models achieved 100% accuracy on image-option items. Withholding figures from the same 18 figure-based questions reduced pooled accuracy from 88.9% to 52.8% (exact McNemar p=0.03 and p=0.04 for Claude Opus 5 and GPT-5.6, respectively). The models agreed on 957/1,001 items (95.6%). Of the 33 items both models answered incorrectly, they selected the same incorrect option on 32 (97%). DISCUSSION Current-generation LLMs achieved approximately 95% accuracy, substantially improving on our prior results with earlier-generation models and placing both models within the highest band of the ITE normative framework, corresponding approximately to the 99th percentile across training levels. By comparison, our prior work with previous models placed ChatGPT-3.5 at the 52nd, 3rd, and 1st percentiles and ChatGPT-4.0 at the 99th, 95th, and 84th percentiles across increasing levels of training. Multimodal capability now permits successful interpretation of many figure-dependent questions, although performance declines markedly when required visual information is unavailable, and highly concordant errors remain. These findings support an increasingly promising role for LLMs as accessible, on-demand educational adjuncts for anesthesiology trainees, provided complete source material is supplied and outputs are critically reviewed.

Background: Robust evidence linking individual surgeon technical performance to patient outcomes in complex minimally invasive surgery remains scarce. Crowd-sourced video assessment offers a scalable alternative to expert review, but its clinical relevance in complex oncologic procedures such as robot-assisted minimally invasive esophagectomy (RAMIE) is unestablished. Methods: In this exploratory study, video recordings of 60 consecutive RAMIE procedures performed by 7 surgeons (2018-2023) were segmented into five representative surgical steps and rated by 93 blinded crowd-raters per segment using a modified GEARS instrument. Tertiles were used to compare top-performing operations and steps against the remaining two terciles for overall and step-specific performance, and associations with perioperative outcomes were analyzed. Results: Top-tercile overall performance was associated with significantly shorter operative time (abdominal, thoracic, and total) and less intraoperative blood loss (all p<0.05), without differences in postoperative outcomes. In exploratory step-specific analyses, top-tertile performance during infracarinal lymphadenectomy was associated with significantly fewer surgical complications (30.0% vs 60.0%; p=0.028), fewer severe surgical complications (25.0% vs 52.5%; p=0.043), and higher lymph node yield (22.8 vs 18.9; p=0.037), while the purse-string suture step showed the broadest operative-time benefit. These step-specific findings are hypothesis-generating and were not adjusted for multiple testing. Conclusion: Crowd-sourced video assessment enables scalable, step-specific evaluation of surgical performance in RAMIE associated with intraoperative blood loss and operative time. Exploratory analyses suggest that the relationship between technical performance and clinical outcomes might be step-specific, with infracarinal lymphadenectomy emerging as risky step linked to postoperative morbidity. These findings support further investigation of individualized performance assessment for quality improvement and risk stratification.

Background Opioid-free anaesthesia (OFA) has emerged as an alternative to opioid-based anaesthesia (OBA), but its benefit over OBA for postoperative quality of recovery (QoR) remains unclear. To address this question while limiting variability inherent in clinical studies, such as analgesic regimens and patient psychosocial factors, we investigated the effects of OFA versus OBA on postoperative recovery in a controlled preclinical mouse model. Methods Adult male and female C57BL/6J mice underwent laparotomy or sham procedures under isoflurane anaesthesia, and were randomly assigned to saline (control), fentanyl (OBA), or dexmedetomidine (OFA) as intraoperative analgesic adjuncts. All mice received multimodal postoperative analgesia, including carprofen. We adapted a standardised multidimensional recovery model using six behavioural endpoints reflecting human QoR domains: body weight, food intake, locomotor activity, mechanical sensitivity, sucrose preference, and social interaction. These endpoints were assessed on postoperative days 1, 2, 3, and 7. Plasma inflammatory cytokine and brain-derived neurotrophic factor (BDNF) concentrations were also measured in parallel as potential biological correlates of recovery. Results Over the study period, we observed no treatment effect across behavioural endpoints in laparotomised mice, including body weight (P=0.157), food intake (P=0.884), locomotor activity (P=0.864), mechanical sensitivity (P=0.628), sucrose preference (P=0.615), and social interaction (P=0.442). Composite QoR scores did not differ between OFA and OBA groups (P=0.569), with no differences in postoperative circulating inflammatory cytokine or BDNF concentrations. Conclusions Dexmedetomidine-based OFA and fentanyl-based OBA produced similar postoperative behavioural recovery, circulating inflammatory cytokine and BDNF trajectories in laparotomised mice receiving multimodal postoperative analgesia.

Non-pharmacological adjuncts are needed for chronic non-cancer pain in patients receiving long-term opioid therapy. Music listening may reduce pain, but most previous trials have used passive controls, limiting attribution of effects specifically to music. In this open-label, parallel- group, proof-of-concept randomized controlled trial, adults with chronic non-cancer pain receiving long-term opioid therapy were randomized 1:1 to four weeks of daily home-based music or audiobook listening. Analgesic outcomes included pain intensity, responder rates, quantity of pain relief, and multidimensional pain assessment; secondary outcomes included mood, quality of life, global impression of change, and safety. Of 70 participants entering the run-in period, 56 were randomized (28 per group). Adjusting for baseline pain intensity in a linear mixed-effects model, the between-group difference at end of treatment was -1.26 NRS points (95% CI -1.98 to -0.55; p<0.001; d=-0.70), favoring music. A [&ge;]30% pain-reduction criterion was met by 21.4% of participants in the music group and none in the audiobook group (p=0.023). An exploratory between-group difference in pain intensity favoring music was also observed at follow-up. Other analgesic and secondary outcomes showed no significant between-group differences, although exploratory within-group improvements in mood and health-related quality of life were observed with music. Both groups reported overall improvement in global perceived change, with ratings numerically favoring music. No intervention-related harms were observed. These findings support an analgesic benefit of music beyond the structured listening experience shared with the active comparator. Daily self-administered music listening may represent a feasible, low-cost adjunct for chronic non-cancer pain in patients receiving long-term opioid therapy.

Preoperative anaemia is common in adults undergoing cardiac surgery and may identify patients at increased perioperative risk. This systematic review and meta-analysis synthesised contemporary observational evidence in accordance with PRISMA 2020. Five databases were searched for peer-reviewed English language studies published from 2017 to July 2026. Random effects meta-analyses used restricted maximum likelihood estimation with Hartung-Knapp confidence intervals; crude exact count estimates were synthesised primarily and adjusted estimates separately. Fourteen observational cohort studies involving 74,571 adults, including 17,349 (23.3%) with anaemia, were included. Preoperative anaemia was associated with red cell transfusion (OR, 3.66; 95% CI, 2.14-6.24), acute kidney injury or renal failure (OR, 2.43; 95% CI, 1.84-3.21), early mortality (OR, 2.11; 95% CI, 1.40-3.17), and postoperative infection (OR, 1.49; 95% CI, 1.21-1.82), but not postoperative stroke (OR, 1.16; 95% CI, 0.43-3.17). Certainty was low for renal outcomes and very low for the other outcomes. Preoperative anaemia is an important perioperative risk marker, particularly for transfusion and renal complications, although causality cannot be established.

Importance: Pain varies in its intensity and course, yet much of our understanding of pain is based on cross-sectional assessments or longitudinal studies of selected clinical populations. Routinely collected electronic health record data may enable characterization of longitudinal pain patterns at scale. Objective: To identify longitudinal pain profiles among U.S. Veterans and characterize their clinical and polygenic correlates. Design: Cohort study using electronic health record and genomic data from the Million Veteran Program, with up to 16 years of pain assessments collected between 2000 to 2025. Setting: U.S. Department of Veterans Affairs health care system. Participants: Million Veteran Program participants assigned to African-like, Admixed American-like, East Asian-like, European-like, or South Asian-like genetically inferred ancestry groups who have at least three years of outpatient numeric rating scale pain records. Exposures: Outpatient pain ratings and polygenic scores for psychiatric, sleep, and substance use traits. Main Outcomes and Measures: Pain profiles were identified using Gaussian finite mixture modeling of pain intensity, directional change, and within-person variability. Profiles were characterized by pain, psychiatric and substance use diagnoses, opioid exposure, body mass index, and polygenic scores. Results: Among 624,996 participants (Mean [SD] age at first pain rating=53.4 [13.5] years; 568,833 [91.0%] male), 51,731,567 outpatient pain ratings were analyzed. Three profiles were identified: stable no pain, stable mild pain, and mild-to-moderate increasing pain. Compared with the stable no pain profile, the increasing pain profile had higher odds of chronic pain (OR=21.14 [95% CI: 18.96-23.57]), opioid use disorder (OR=9.32 [95% CI: 8.31-10.45]), opioid exposure (OR=8.61 [95% CI: 8.41-8.83]), major depressive disorder (OR=3.77 [95% CI: 3.67-3.87]), and posttraumatic stress disorder (OR=3.72 [95% CI: 3.61-3.84]). Associations were attenuated but remained after adjustment for mean pain severity. Polygenic scores for depression, insomnia, attention-deficit/hyperactivity disorder, and tobacco use disorder were the most consistent predictors of increasing pain across the three largest genetically inferred ancestry groups. Conclusions and Relevance: Longitudinal modeling of routinely collected pain scores identified pain profiles associated with clinical burden and polygenic liability. These profiles captured clinically meaningful information beyond mean pain severity alone, highlighting the value of longitudinal pain phenotyping in electronic health record data.

Background: Clinical decision support (CDS) systems may improve chronic pain management by providing guideline-based recommendations within clinical workflows. However, low clinician use can limit their effectiveness. Understanding the association between CDS use and guideline-recommended care may help distinguish implementation challenges from limitations in CDS functionality. Objective: To estimate the association of OneSheet, a CDS system for chronic pain management, and guideline-recommended care when the system was used during patient encounters. Methods: We conducted a per-protocol secondary data analysis of data from a pragmatic randomized clinical trial conducted from October 2020 to May 2022 across 25 primary care clinics at 2 academic health systems in Indiana and North Carolina. The parent trial enrolled 137 primary care clinicians. This analysis included 145511 eligible chronic pain encounters and 15480 long term opioid therapy (LTOT) encounters that occurred after OneSheet implementation. OneSheet use at a patient encounter was the exposure of interest. Propensity score matching was used to create comparable groups of encounters with and without OneSheet use. Outcomes included documentation of pain-related goals, documentation of pain and function using the Pain, Enjoyment of Life and General Activity (PEG) scale, prescription drug monitoring (PDMP) review, urine drug screening (UDS) orders, and naloxone orders. Results: OneSheet was used in 959 of 145511 chronic pain encounters (0.7%) and 582 of 15480 LTOT encounters (4.0%). In matched analyses, OneSheet use was associated with increased documentation of pain-related goals (relative risk (RR)=11.70 (95% CI 4.25-32.50) and PEG score documentation (RR=9.70 (95% CI 4.14-22.31). Among LTOT encounters, OneSheet use was associated with increased UDS ordering (RR=1.52 (95% CI 1.40-1.65) and PDMP review (RR=1.06 (95% CI 1.03-1.09), but decreased naloxone ordering (RR=0.13 (95% CI, 0.02-0.90). Conclusions: OneSheet use was associated with several guideline-recommended chronic pain management actions, suggesting that they system may support care quality when clinicians use it. However, use was rare, indicating that increasing routine use through better workflow integration may be necessary to achieve population-level improvements in chronic pain care.

Background: When intravenous insulin is stopped in critically ill patients, the basal insulin dose that balances rebound hyperglycemia against hypoglycemia is uncertain, because randomized trials were small and not designed to quantify this trade-off. We examined how the first glargine dose, relative to the preceding intravenous insulin requirement, was associated with both outcomes. Methods: In this retrospective cohort study of the Medical Information Mart for Intensive Care IV database (2008-2022), we included transitions from intravenous insulin infusions of at least 6 hours to subcutaneous glargine in adults without diabetic ketoacidosis or hyperosmolar hyperglycemic state. The exposure was the ratio of the first glargine dose to 24 times the mean infusion rate over the final 6 hours. The primary outcomes, rebound hyperglycemia (glucose >180 mg/dL within 24 hours) and hypoglycemia (glucose <70 mg/dL within 48 hours) during intensive care unit follow-up, were analyzed with multivariable Cox models after multiple imputation. Results: Among 6,220 transitions in 5,924 patients (87.5% after cardiac surgery), the median ratio was 0.41 (interquartile range 0.30-0.46). Kaplan-Meier cumulative incidences were 44.4% for rebound hyperglycemia (2,109 events) and 6.4% for hypoglycemia (211 events). Each 0.1 increase in the ratio was associated with less rebound hyperglycemia (hazard ratio 0.96, 95% confidence interval 0.93-0.99) and more hypoglycemia (1.11, 1.04-1.18), consistently across 21 sensitivity analyses. Rebound within the first 6 hours (57.6% of events) was not associated with the ratio (0.99, 0.95-1.02), whereas later rebound was (0.91, 0.86-0.96). Standardized to the cohort, a ratio of 0.60 versus 0.40 corresponded to 2.7 (0.6-4.9) fewer rebound and 1.7 (-0.2 to 3.5) more hypoglycemia episodes per 100 transitions. In secondary analyses, rebound was less frequent with glargine given at least 2 hours before discontinuation (0.86, 0.77-0.96) and more frequent with an oral diet (1.49, 1.30-1.71). Conclusions: In critically ill adults, mostly after cardiac surgery, higher glargine doses relative to the preceding intravenous requirement were associated with less rebound hyperglycemia after the first 6 hours and more hypoglycemia, a gradual trade-off. Which basal fraction is preferable depends on the weight given to each outcome; a randomized trial including the guideline-implied fraction of about 0.30 is warranted.

Background: Temporary 60-day percutaneous peripheral nerve stimulation (PNS) can relieve pain in refractory occipital neuralgia (ON), but whether it alters acute healthcare utilization relative to the natural trajectory of the disease is unknown, because prior studies have lacked a concurrent comparator. Methods: We performed a secondary analysis of prospectively collected data from a tertiary interventional pain center. Adults with medically refractory ON (primary diagnosis occipital neuralgia, ICD-10-CM M54.81) who underwent 60-day occipital PNS (n = 42) were compared with concurrent patients who were clinically eligible for PNS but were denied insurance authorization and continued optimized non-PNS management (usual care; n = 63). Headache-related emergency department (ED) encounters - index (occipital neuralgia) and non-index (other headache/facial-pain diagnoses) - were ascertained over the 12 months before and after the treatment window via the electronic record and the statewide health information exchange. Patients were 1:1 propensity-matched on a priori confounders (age, sex, baseline total headache-related ED utilization, HIT-6, and baseline headache-medication use). The primary analysis was a difference-in-differences (DiD) comparison of the change in headache-related ED utilization, reported as the additive difference (Hodges-Lehmann estimate, distribution-free 95% CI) and, alongside, as a multiplicative rate ratio (RR). Results: Thirty-six matched pairs were well balanced. Baseline headache-related ED utilization was nearly identical between matched groups (6.3 vs. 6.2 visits/year). Over the following year, PNS patients' utilization fell to 2.5 while usual-care patients' rose to 6.9. The DiD was 5.0 fewer headache-related ED visits per patient (95% CI 3.0-6.0; p < 0.001), corresponding to a rate ratio of 0.36 (95% CI 0.27-0.48; p < 0.001). Results were consistent in the full sample, in covariate-adjusted models, and after excluding controls denied for incomplete conservative-therapy trials. The effect was driven by non-index headache visits. Conclusions: Relative to a concurrent, matched usual-care cohort whose headache related ED utilization rose over time, 60-day occipital PNS was associated with a substantial reduction in acute-care use, strengthening the case for a role of PNS on healthcare utilization in refractory ON.

Purpose Delirium affects around 40% of intensive care unit (ICU) patients and adversely affects survival, length of stay, and cognitive recovery. Despite this, implementation of systematic clinical delirium assessments is variable. We sought to validate a point-of-care electroencephalography (EEG)-based system (Ceribell, Inc.) for the detection of delirium in the ICU. Methods In this multicenter, prospective cohort study, we monitored adult ICU patients with the Ceribell EEG system for 6-8 hours for a minimum of three days. Up to three times per day, expert clinicians assessed participants for delirium and research coordinators completed Confusion Assessment Method for the ICU (CAM-ICU) assessments, which we used to calculate CAM-ICU-7 severity scores. We compared expert clinician diagnoses with Ceribell EEG algorithm output using data from 30-minute periods surrounding each clinician assessment. Results Among 225 participants analyzed (median age: 64 years, 60% male, 21% mechanically ventilated), expert clinicians performed 857 assessments and found 24% of participants were delirious during at least one assessment. The Ceribell EEG system detected delirium with a sensitivity of 81% (95% CI: 76% to 87%) and specificity of 81% (95% CI: 78% to 84%). The continuous Ceribell EEG system score correlated with CAM-ICU-7 delirium severity scores (bootstrapped median rho 0.58, IQR: 0.54-0.62, p <0.001). Conclusion In a mixed adult ICU population, the Ceribell EEG system identified delirium with good sensitivity and specificity. Its continuous output was associated with delirium severity, highlighting its potential ability to characterize underlying physiological patterns across the clinical delirium spectrum.

BackgroundEvaluating fairness in artificial intelligence (AI) is essential before clinical implementation to prevent unintended harm across diverse patient populations. This study assesses performance differences of an image-based surgical site infection (SSI) detection model across age, gender, geography, race, and skin color. MethodsModel development/validation study using retrospective, multicenter data across surgical subspecialties from adults who submitted an image of their incision via the electronic health record within 30 days of their procedure between 2019-2024. Area under receiver operating curve (AUROC) was compared by age (<55 vs. [&ge;]55 years old), gender (male vs. female), geography (Rochester, Minnesota vs. Jacksonville, Florida vs. Scottsdale, Arizona vs. regional Minnesota/Wisconsin areas), race (White/Caucasian vs. non-White/Caucasian), and skin color (Fitpatrick I-III vs. IV-VI and Monk A-E vs. F-J). ResultsTraining data contained 13,702 images from 4,274 patients between 2019-2022 (50.1% [&ge;]55 years old; 63.2% female; 91.6% White/Caucasian; 58.5% Rochester, 17.3% Florida, 10.5% Arizona; 96.3% light skin tone), of which 1,348 images (9.8%) had an SSI. No differences in SSI detection existed for age, gender, race, or skin color (AUROC 0.83-0.87, p>0.09), however geographical differences were significant: lowest AUROC 0.83 (95% CI 0.77-0.88) vs. highest AUROC 0.87 (95% CI 0.84-0.89, p=0.01). Temporal validation using 4,242 images from 1,353 patients between 2022-2023 showed intact fairness across subgroups ({Delta}AUROC [&le;]0.06) except geography ({Delta}AUROC [&le;]0.16). ConclusionsThe model behaved fairly across age, gender, race, and skin color, however geographical differences persisted. These findings have practical implications underscoring the importance of evaluating bias in clinical AI before deployment.

Detection of postoperative pain in mice is challenging, and there is a need for unbiased, automated methods. Home-cage monitoring systems are promising, but their ability to detect mild pain remains unclear. We evaluated whether home-cage activity measures can be used to detect pain-related changes in a plantar incision model of postoperative pain. First, we confirmed the presence of local hypersensitivity using von Frey filaments on 48 C57BL/6JRj mice (24 males, 24 females). Subsequently, we pair-housed 64 mice (32 males, 32 females) and allocated them to receive either a 4 mm plantar incision on the hind paw under anaesthesia, or anaesthesia alone. Baseline locomotion and voluntary wheel-running activity were recorded over five days, followed by four days of postprocedural monitoring in the home cages. Both procedure groups (incision and anaesthesia-only) showed reduced locomotion and running wheel activity relative to baseline. However, activity measures did not differ between incised and anaesthesia-only mice, and we detected no sex-related effects. Under these conditions, home cage activity measures did not reliably discriminate pain-related behavioural changes in the model, despite the model showing local mechanical hypersensitivity in the von Frey test. Together, these findings indicate that, given the mild and localised nature of the plantar incision mouse model, commonly used home-cage metrics cannot yet reliably detect subtle pain-related behavioural changes.