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British Journal of Anaesthesia

Elsevier BV

Preprints posted in the last 30 days, ranked by how well they match British Journal of Anaesthesia's content profile, based on 14 papers previously published here. The average preprint has a 0.04% match score for this journal, so anything above that is already an above-average fit.

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Drug allergy labels and complications after surgery: a prospective multi-centre cohort study

Savic, L.; Dias, P.; Vairale, J.; Begum, S.; Khan, K.; Fowler, A. J.; Kaura, V.; Watson, S.-L.; Littlejohns, A.; Pearse, R. M.; Abbott, T. E. F.

2026-06-05 allergy and immunology 10.64898/2026.06.04.26354882 medRxiv
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Background One in four surgical patients carries a drug allergy label, of which an estimated 90% are incorrect. Avoidance of first-choice drug therapies may lead to worse postoperative outcomes. We sought to determine the nature and extent of any association between drug allergy labels and postoperative complications. Methods A multicentre observational study in 21 NHS hospitals. Eligible patients were 18 years or older, undergoing common surgical procedures: primary hip or knee replacement; internal fixation of closed long bone fracture; colorectal resection; trans-urethral resection of prostate or bladder tumour; caesarean section; hysterectomy. Exclusion criteria: use of antibiotics in the two weeks prior to surgery, previous participation in the study. Primary outcome was postoperative complications within 30 days following surgery, a composite outcome comprising: all postoperative infections, anastomotic leak, acute respiratory distress syndrome, myocardial infarction, postoperative bleed, pulmonary embolism, stroke, antimicrobial side effects, death. Results Among 13,646 patients, 3924 (29%) carried greater than or equal to1 drug allergy labels. Labelled patients were more likely to develop postoperative complications (989/3924 (25%) vs 1926/9722 (20%); OR 1.21 [1.10-1.34]; p<0.001). They were more likely to develop surgical site infections (337/3924 (9%) vs 760/9722 (8%); OR 1.19 [1.03 -1.38]; p<0.018), and any postoperative infection (750/3924 (19%) vs 1472/9722 (15%); OR 1.24 [1.11-1.38] p<0.001). Labelled patients experienced increased risk of allergic drug reactions (31/3924 (0.01%) vs 29/9722 (<0.01%); OR 3.00 [1.77-5.09]; p<0.001), but no increase in mortality. Conclusions Drug allergy labels are common, but often incorrect. Labelled patients experience worse postoperative outcomes, including infective and non-infective complications and increased risk of allergic drug reactions. Trial registration Registered with ISRCTN registry, ISRCTN15775657.

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Randomised Trial of a Multilingual Conversational AI for Preoperative Education

Ke, Y.; Niu, C.; Liao, J.; Sim, J.; Abdullah, H. R.; Jin, L.; An, J.; Ho, H. S. S.; Tung, J. Y. M.; Tan, H. K.; Sng, B. L.; Ting, D. S. W.; Ong, M. E. H.; Liu, N.

2026-05-26 anesthesia 10.64898/2026.05.24.26353997 medRxiv
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Background Informed consent depends on patients' understanding of anaesthesia risk, yet comprehension remains poor despite routine preoperative consultation. Conversational artificial intelligence (AI) could establish patient-reported understanding before clinician contact, but whether such systems can achieve patient-reported understanding comparable to clinician-delivered education remains unknown. Methods We conducted a randomised equivalence trial (n = 130) of PEAR (Preoperative Education of Anaesthesia Risks), a multilingual retrieval-augmented conversational AI grounded in institutional consent materials, versus standard preoperative consultation in adults undergoing elective surgery. Results A total of 130 adults (mean age 52.4 +/- 14.5 years) were enrolled. Post-consultation understanding scores in the PEAR group met the pre-specified equivalence criterion compared with standard consultation across all three primary measures. Patients who interacted with PEAR before clinician contact achieved understanding scores comparable to those receiving standard face-to-face consultation alone. PEAR reduced documentation and consultation time, corresponding to a projected annual net benefit of approximately SGD 0.99 million (USD 0.78 million) at a single tertiary centre. Conclusions A retrieval-augmented conversational AI achieved patient-reported understanding of anaesthesia risk equivalent to standard preoperative consultation while substantially improving workflow efficiency. These findings support supervised deployment of conversational AI within perioperative care pathways while preserving clinician oversight for verification and patient-specific decision-making.

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Oral Premedication with Tapentadol versus Pregabalin for Acute Postoperative Pain in Lower Limb Surgery Under Neuraxial Anesthesia: A Pilot Randomized Controlled Trial

Escalona-Arroyo, M. d. R.; Lopez-Delgado, P. A.; Delgado-Carlo, M. M.

2026-05-19 anesthesia 10.64898/2026.05.14.26353251 medRxiv
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Abstract Background: Acute postoperative pain affects more than 80% of surgical patients, with orthopedic lower limb procedures consistently associated with severe pain intensity and high opioid requirements. Preemptive analgesia with oral agents has been proposed to attenuate central and peripheral sensitization prior to surgical incision. Tapentadol, a dual-mechanism -opioid receptor agonist and norepinephrine reuptake inhibitor, and pregabalin, a voltage-gated calcium channel modulator, represent pharmacologically distinct premedication options; however, direct comparative data in this surgical context are lacking. This pilot randomized controlled trial aimed to compare the analgesic efficacy and safety of 72-hour oral premedication with tapentadol versus pregabalin in patients undergoing elective lower limb surgery under neuraxial anesthesia. Methods: In this double-blind, parallel-group pilot trial, 46 patients scheduled for elective lower limb surgery under neuraxial anesthesia were randomized equally to receive tapentadol 50mg orally every 12 hours (Group A, n = 23) or pregabalin 75mg orally every 24 hours (Group B, n = 23), initiated 72 hours before surgical incision. The primary outcome was postoperative pain intensity assessed using the Numeric Rating Scale (NRS, 0-10) at post-anesthesia care unit (PACU) arrival (T0) and at 30 (T1), 60 (T2), 90 (T3), and 120 (T4) minutes thereafter. Secondary outcomes included Verbal Rating Scale (VRS) scores, rescue morphine consumption, and safety. The primary longitudinal analysis used a linear mixed model (LMM) with Group, Time, and Group x Time interaction as fixed effects and a random intercept per patient; between-group contrasts at each timepoint were derived from estimated marginal means with Holm correction. Effect sizes are reported as Cohen's d. Results: All 46 patients completed the study with no missing data. Both groups were pain-free at T0 (NRS=0). Pain scores diverged progressively from T1 onward, with the pregabalin group reporting consistently higher NRS values at every time point. The LMM revealed a significant main effect of Time (F4,181.6 = 23.61, p < 0.001) and a borderline-significant Group x Time interaction in the continuous-time sensitivity model (F1,187.6 = 3.79, p = 0.053). Post-hoc contrasts identified a statistically significant, large effect between-group difference at T3 (mean NRS difference -0.91, p = 0.006, Cohen's d = -0.96) and a medium-effect trend at T2 (d = -0.59, p = 0.089). Rescue analgesia was required by 4.3% of tapentadol patients versus 21.7% of pregabalin patients. Nausea and vomiting were equally present in both groups (17.4%). No hypersensitivity reactions were observed in either arm. Conclusions: Seventy-two-hour oral premedication with tapentadol 100mg/day provided superior postoperative analgesia compared with pregabalin 75 mg/day at the 90-minute PACU time point, with a large effect size and a fivefold reduction in rescue analgesia requirements. Both agents were well tolerated. These pilot data support the conduct of a fully powered, multicenter randomized controlled trial to confirm the analgesic superiority of tapentadol premedication in orthopedic lower limb surgery.

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Implementation and Evaluation of a Postoperative Virtual Hospital Pathway for Elective Colorectal Surgery: A Propensity-Matched Analysis

Whelan, H.; Thapa, B.; Massias, S.; Reza, L.; Johnson, N.; Kinross, J.; Daulatzai, N.; Patel, V.

2026-05-22 surgery 10.64898/2026.05.20.26353655 medRxiv
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Background Virtual Hospital (VH) pathways enable early discharge and are promoted across the NHS. However, evidence supporting their safety, effectiveness, equity, and patient acceptability in elective colorectal surgery remains limited. Objective To evaluate implementation of a VH pathway following elective colorectal surgery and its impact on clinical outcomes, patient-centred recovery, and equality, diversity and inclusion (EDI). Design Retrospective service evaluation with a historical comparator. A 1:1 propensity-matched analysis was performed in colorectal cancer patients using age, sex, body mass index, ASA grade, Charlson Comorbidity Index, procedure type, tumour site, and anastomosis. Setting West Hertfordshire Teaching Hospitals NHS Trust. Patients Patients undergoing elective colorectal surgery between November 2023 and March 2025 managed via a VH pathway, compared with a non-VH cohort. Main outcome measures Primary outcomes were inpatient length of stay (IPLOS), VH length of stay (VHLOS), and days alive and at home within 30 days (DAH30). Secondary outcomes were patient-reported experience and EDI characteristics. Results Eighty-one patients were managed via VH. Median [Q1 - Q3] IPLOS was 2 [1 - 2] days and VHLOS was 2 [2 - 3] days, with no deaths. Forty-two colorectal cancer patients were propensity matched 1:1 to a pre-VH cohort. IPLOS was shorter in the VH cohort (2 [1 - 2] vs 4 [3 - 5] days; p<0.001), and DAH30 was higher (28 [28 - 29] vs 25.5 [24 - 27] days; p<0.0001). Patient experience was positive, with mean satisfaction >8.5/10 and over 90% preferring VH-supported recovery. Sex and ethnicity distributions were similar, although VH patients were younger (p=0.028). Limitations This single-centre retrospective evaluation had a modest sample size and non-randomised design. VH patients were carefully selected, limiting generalisability. Conclusions A VH pathway following elective colorectal surgery is feasible, safe, and acceptable. Compared with a pre-VH cohort, VH care reduced inpatient stay and improved patient-centred recovery without compromising safety.

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Associations between initial treatments for acute low back pain and opioid use disorder and overdose risk in Medicaid patients

Doan, L. V.; Hung, A. M.; Olfson, M.; Williams, N. T.; Rudolph, K. E.

2026-06-08 pain medicine 10.64898/2026.06.05.26355003 medRxiv
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Introduction: Acute low back pain is a leading cause of disability worldwide. Clinical guidelines recommend non-pharmacological therapies as first-line treatment and advise caution with opioid prescribing. However pharmacological therapies, including opioids and gabapentinoids, remain commonly used. The comparative risks of subsequent opioid use disorder (OUD) and overdose diagnosis associated with initial treatment modality in large, real-world populations is not well characterized. We estimated the incidence of new-onset OUD and overdose diagnosis among opioid-naive, Medicaid-insured adults with newly diagnosed acute low back pain and estimated the association between initial treatment modalities and subsequent OUD and overdose diagnosis risk. Methods: We conducted a retrospective cohort study using Medicaid T-MSIS Analytic files from 25 states (2016-2019). We identified opioid-naive adults with a new diagnosis of acute low back pain who initiated pharmacologic or non-pharmacologic treatment within 1 month of diagnosis. The primary outcome was incident OUD and overdose diagnosis (based on diagnosis codes in claims) during follow-up. Associations between initial treatment modality and OUD and overdose diagnosis risk were estimated using a non-parametric, doubly robust estimator to adjust for measured confounding. Results: The cohort included 525,002 opioid-naive adults initiating treatment for low back pain. The cumulative incidence of OUD and overdose diagnosis was 1.5% and 2.4% at 7 and 13 months, respectively. Compared to non-use, use of gabapentinoids during the first month of treatment was associated with the highest relative risk (increasing risk) by 130.1%, 95% confidence interval (CI): 117.8%, 142.3%), the second-highest relative risk was estimated for higher-dose opioids, defined as > 50 daily Morphine Milligram Equivalents (MME) (118.1%, 95% CI: 99.2%, 137.0%). Lower-dose, short-duration opioids ([&le;] 50 MME, [&le;] 7 days) were also associated with elevated risk, though substantially smaller in magnitude (20.8%, 95% CI: 13.8%, 27.9%). In contrast, non-pharmacologic, non-interventional therapies were associated with reduced OUD and overdose diagnosis risk, with physical therapy demonstrating the largest relative reduction of 34.0% (95% CI: -40.9%, -27.1%). Discussion: In opioid-naive Medicaid patients with acute low back pain, initial non-pharmacologic treatment was associated with reduced OUD and overdose diagnosis risk. Gabapentinoids and opioids were each associated with increased risk; for opioids, the degree of risk increased with higher doses and durations. These results support guideline recommendations favoring non-pharmacologic treatment as first-line therapy and indicate the importance of cautious prescribing when pharmacologic treatment is considered.

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Sphenopalatine Ganglion Block for Post-Dural Puncture Headache: A Pilot Randomized Controlled Trial

Everardo-Salazar, G.; Lopez-Delgado, P. A.; Delgado-Carlo, M. M.

2026-05-15 anesthesia 10.64898/2026.05.06.26352338 medRxiv
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Background: Post-dural puncture headache (PDPH) affects up to 11.2% of patients after neuraxial anesthesia. The sphenopalatine ganglion block (SPGB) is a promising minimally invasive intervention, but high-quality randomized trial data are limited. We conducted a pilot randomized controlled trial to assess feasibility and inform a future definitive trial. Methods: Twenty-six patients with PDPH following accidental dural puncture with 17G Tuohy needles were randomized to conservative management (bed rest, hydration) or SPGB (bilateral intranasal 2% lidocaine). Primary outcomes were feasibility (recruitment, retention, protocol adherence). Secondary outcomes included pain intensity (Numeric Rating Scale, NRS 0-10) at 30 minutes, 12 hours, and 24 hours; rescue analgesia requirements; mobilization time; and adverse events. Results: Feasibility was confirmed: 100% recruitment of target sample, 100% retention, 100% protocol adherence. At 30 minutes, all SPGB patients reported complete pain resolution (NRS=0) versus median NRS 3 (IQR 2) in controls (p<0.001), though this finding is limited by lack of blinding and baseline assessment. No SPGB patients required rescue analgesia or experienced adverse events. Conservative group patients had prolonged hospitalization (46%). Sample size calculation for a definitive trial (90% power, =0.05) yields 120 participants (60/group). Conclusions: A definitive RCT comparing SPGB to conservative management for PDPH is feasible. Preliminary efficacy data suggest rapid analgesia with SPGB, but rigorous confirmation in a sham-controlled trial is required. Trial registration: ClinicalTrials.gov -NCT07494383 (retrospectively registered). Keywords: Post-dural puncture headache, sphenopalatine ganglion block, pilot study, feasibility, regional anesthesia, randomized controlled trial

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Effectiveness of dexamethasone as an adjuvant to intrathecal bupivacaine versus bupivacaine alone in spinal anesthesia among orthopedic surgery patients at KCMC referral hospital, northern Tanzania

Fidelis, K.; Shewiyo, E. J.; Nkenguye, W.; Kawiche, B.; Goodluck, G.; Masika, L. V.; Dohho, A.; Mekere, M.; Adonicam, V.; Mwiga, F.; Sway, H.; Lwiza, A.; Mohammed, S. S.; Vaughan, B.; Chamba, N.

2026-05-21 anesthesia 10.64898/2026.05.18.26353515 medRxiv
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Background: Orthopedic surgeries are associated with significant intraoperative and postoperative pain, necessitating effective anesthesia strategies. Spinal anesthesia is commonly used for lower limb procedures due to its rapid onset and reliability; however, its limited duration may compromise prolonged surgical procedures and early postoperative pain control. Adjuvants such as dexamethasone have been explored to enhance and prolong the effects of local anesthetics. While evidence supports its efficacy, data from low-resource settings remain limited. Objective: To assess the effect of intrathecal dexamethasone as an adjuvant to bupivacaine on sensory block duration, time to first postoperative analgesia, and postoperative pain in patients undergoing lower limb orthopedic surgery at KCMC. Methodology: A randomized, double-blind controlled trial was conducted among 96 adult patients undergoing elective lower limb orthopedic surgery under spinal anesthesia. Participants were allocated using a computer-generated randomization sequence to receive either bupivacaine 15 mg with dexamethasone 4 mg (intervention group) or bupivacaine 15 mg with 1 ml normal saline (control group). Outcomes included sensory and motor block duration, time to first postoperative analgesia, and postoperative pain scores. Results: The dexamethasone group demonstrated a significantly prolonged sensory block duration (231 +/- 6 vs. 156 +/- 9 minutes; mean difference 75.11 minutes, 95% CI: 71.92-78.29; p < 0.001) and delayed time to first postoperative analgesia (252 +/- 7 vs. 181 +/- 7 minutes; mean difference 71.89 minutes, 95% CI: 68.91-74.86; p < 0.001). Motor block duration was also significantly longer (184 +/- 7 vs. 130 +/- 5 minutes; mean difference 53.42 minutes, 95% CI: 50.99-55.85; p < 0.001). Postoperative pain scores were significantly lower at 1 hour (mean difference -1.29 points, 95% CI: -1.52 to -1.05; p < 0.001) and at 2 hours (mean difference -1.97 points, 95% CI: -2.21 to -1.73; p < 0.001). Intraoperative opioid and benzodiazepine use were significantly reduced in the intervention group. Conclusion: The addition of intrathecal dexamethasone to bupivacaine significantly enhances sensory block duration, delays postoperative analgesia need, and improves early pain control. These findings support its use as a potentially practical adjuvant in resource-limited settings.

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Evaluating the Clinical Impact of CYP2C19 and CYP2D6 on Amitriptyline Outcomes in a Real-World Chronic Pain Cohort

Uckac, B.; Ceja, Z.; Ogonowski, N. S.; Lind, P.; Nyholt, D.; Martin, N.; Medland, S.; Renteria, M. E.; Ferreira, G.

2026-06-01 genetic and genomic medicine 10.64898/2026.05.28.26354228 medRxiv
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Amitriptyline is commonly prescribed for chronic pain, yet treatment response and tolerability vary substantially. Genetic variation in CYP2C19 and CYP2D6 influences amitriptyline metabolism, but evidence linking pharmacogene status to clinical outcomes in chronic pain is limited. Amitriptyline is typically prescribed for chronic pain at lower doses than for depression, which may reduce pharmacogenomic effects on clinical outcomes. We analysed 1,146 participants with chronic pain from the Australian Genetics of Depression Study who reported amitriptyline use, treatment outcomes, and genotype data. Metaboliser phenotypes were assigned using PharmCAT. Associations with self-reported effectiveness and discontinuation due to side effects were examined using regression models adjusted for age and sex. Only CYP2C19 intermediate metabolisers showed nominally lower odds of discontinuation and reduced likelihood of reporting moderate effectiveness. Overall, pharmacogenetic phenotypes were not significantly associated with patient-reported amitriptyline outcomes in chronic pain, potentially reflecting the lower doses typically prescribed for pain management.

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Peri Operative deLta rEnin ConcentrATion (POLECAT) Study Protocol and Analysis Plan

Boyer, N.; Haider, S.; Piercy, C.; Zarbock, A.; Samuels, T. L.; Papadopoulou, A.; Forni, L. G.; Creagh Brown, B.

2026-05-27 intensive care and critical care medicine 10.64898/2026.05.26.26352884 medRxiv
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Background: Post-operative hypotension and vasoplegia are well recognised following cardiac surgery but remain poorly characterised after major non-cardiac surgery, despite associations with acute kidney injury (AKI), cardiovascular complications, and increased mortality. Dysregulation of the renin angiotensin aldosterone system (RAAS) may underpin haemodynamic instability in this setting, yet data in abdominal surgery are limited. Objectives: The POLECAT (Perioperative delta Renin) study aims to determine whether changes in circulating renin concentration (delta renin) from pre-operative baseline to the early post-operative period are associated with post-operative vasoplegia in patients undergoing major abdominal surgery requiring intensive care admission. Methods: POLECAT is a single-centre, prospective observational study conducted at a UK tertiary referral hospital. Adult patients undergoing planned or emergency abdominopelvic surgery with anticipated intensive care admission are enrolled. Blood samples are obtained pre-operatively, within four hours post-operatively, and on post-operative day one to measure renin and a panel of endothelial, renal, and immune biomarkers. The primary outcome is post-operative vasoplegia, defined as the requirement for a vasopressor infusion at 08:00 on post-operative day one. Secondary outcomes include alternative vasoplegia definitions, AKI (KDIGO criteria), vasopressor burden, organ dysfunction, cardiovascular complications, length of stay, and mortality. Multivariable regression, receiver operating characteristic analyses, and predefined subgroup analyses will be performed, with sensitivity analyses addressing missing data. Conclusions: This study will clarify the relationship between peri-operative RAAS dysfunction and vasoplegia following major abdominal surgery. Findings may support biomarker-guided risk stratification and inform future interventional trials targeting haemodynamic instability in this high-risk population.

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Procalcitonin Adds Limited Incremental Value to a Simple Bedside Score for Predicting Complicated Appendicitis: A Temporal Validation Study

he, b.; Cheng, S.-B.; Liu, M.; Li, M.

2026-05-21 surgery 10.64898/2026.05.14.26353219 medRxiv
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Background Complicated appendicitis (CA) increases morbidity and resource use.[1,2] In the emergency setting, risk stratification must rely on rapidly available data. Procalcitonin (PCT) is frequently obtained, but its incremental value beyond basic preoperative indicators remains uncertain.[5] We aimed to quantify PCTs incremental predictive value and develop a practical bedside score with temporal validation. Methods We conducted a retrospective cohort study of consecutive laparoscopic appendectomy patients (January 2023-December 2024). CA was defined by postoperative pathology (gangrene/necrosis, perforation, or peri-appendiceal inflammation/abscess; worst-category rule). We compared a base logistic model (age, WBC, neutrophil percentage, fever, symptom-to-surgery interval, shock index) with an extended model adding log-transformed PCT. Discrimination (AUC) and calibration were assessed. Temporal validation used 2023 for development and 2024 for testing. We also created a simple bedside score using pre-specified cutoffs and evaluated CA risk across score strata in 2024. Results In the overall complete-case cohort (n=1,792), 397 patients (22.2%) had CA. Adding PCT modestly improved discrimination in the full cohort (AUC 0.673 to 0.685). For temporal validation, 2023 included 870 patients (CA 26.9%) and 2024 included 921 patients (CA 17.7%); one otherwise eligible patient lacked a usable admission year. In the 2024 test set, discrimination was 0.662 (base) vs 0.673 (base+PCT) with a non-significant AUC difference (DeLong p=0.116); calibration slopes were near 1.0. A 7-item bedside score stratified 2024 CA risk: 9.1% (score 0-1), 14.7% (2-3), and 34.2% [&ge;]4). Using [&ge;]4 points identified a higher-risk subgroup (PPV 34.2%, NPV 87.5%, sensitivity 46.0%, specificity 81.0%). Conclusions PCT adds modest predictive information beyond simple preoperative indicators in the full cohort, but temporal validation suggests that this incremental gain is smaller and not statistically significant in later patients. A pragmatic bedside score can support CA risk stratification and prioritization in emergency care, whereas the role of routine PCT testing may be best reserved for selected situations in which uncertainty remains after initial assessment.

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Cardiovascular Outcomes with GLP-1 Receptor Agonists in Patients with Type 2 Diabetes or Obesity Undergoing Surgical Aortic Valve Replacement

Lum, J.; Jordan, A.; Knigh, P.; Hisamoto, K.

2026-06-04 surgery 10.64898/2026.06.02.26354773 medRxiv
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Abstract Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular benefit in type 2 diabetes and obesity, with recent observational data suggesting favorable associations after transcatheter aortic valve replacement. Whether similar associations exist after surgical aortic valve replacement (SAVR) is unknown. Methods: Retrospective propensity-matched cohort analysis using the TriNetX U.S. Collaborative Network. Adults with type 2 diabetes or obesity (BMI [&ge;]30 kg/m2) undergoing SAVR were categorized by GLP-1 RA exposure (any use within 3 months before through 1 year after SAVR) versus no use. One-to-one matching was performed on 44 covariates. Primary outcomes were 1-year all-cause mortality, heart failure, acute kidney injury, acute myocardial infarction, cerebral infarction, and atrial fibrillation. Sensitivity analyses included 30-day landmark restriction and falsification outcomes. Results: After matching, 1,984 patients were retained per cohort. GLP-1 RA use was associated with lower 1-year risks of all-cause mortality (4.8% vs 10.4%; HR, 0.44; 95% CI, 0.34-0.56), acute kidney injury (6.9% vs 10.1%; HR, 0.65; 95% CI, 0.49-0.85), myocardial infarction (3.0% vs 5.1%; HR, 0.57; 95% CI, (0.40-0.82), heart failure (11.3% vs 15.7%; HR, 0.68; 95% CI, (0.51-0.90), and atrial fibrillation or flutter (10.1% vs 13.9%; HR, 0.69; 95% CI, 0.54-0.90; all P[&le;]006). Cerebral infarction did not differ. In landmark analysis, mortality, heart failure, and acute kidney injury associations persisted; myocardial infarction and atrial fibrillation associations were attenuated. Falsification outcomes were null. Conclusions: Perioperative GLP-1 RA use was associated with lower 1-year cardiovascular event rates after SAVR. These hypothesis-generating findings support prospective randomized investigation.

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Clinical Predictors of Emergence Delirium in Children: A Prospective Cohort Study

Myasnikova, V. V.; Mausheva, S. K.; Aksenova, L. E.

2026-06-03 anesthesia 10.64898/2026.06.01.26354640 medRxiv
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Abstract Objective. To determine the incidence and identify independent clinical predictors of emergence delirium (ED) in children aged 2-12 years. Material and methods. A prospective observational study included 56 children aged 2-12 years undergoing elective surgery under general anaesthesia. Preoperative anxiety (m-YPAS), induction behaviour (4 point scale), anaesthesia duration, opioid use, and postoperative pain (FLACC) were assessed. ED was diagnosed when the maximum PAED score was [&ge;]12. Results. The incidence of ED was 55.4% (31/56). Univariate analysis with false discovery rate (FDR) correction identified significant associations with ED for anaesthesia duration (q=0.002), induction behaviour (q=0.007), and surgery type (q=0.027). Multivariable logistic regression revealed three independent predictors: induction behaviour (category 3 vs 1) - odds ratio (OR) 14.2 (95% CI 2.6-78.1); anaesthesia duration (per minute) - OR 1.07 (95% CI 1.02-1.13); opioid use - OR 12.1 (95% CI 1.3-113.0). The model showed good discriminatory ability: area under the ROC curve (AUC) = 0.83 (95% CI 0.72-0.94). Conclusion. Emergence delirium in children aged 2-12 years without pharmacological premedication occurs in 55.4% of cases. The strongest independent predictors are adverse induction behaviour, longer anaesthesia duration, and intraoperative opioid use. The derived model can be used for personalised risk stratification of ED. Keywords: emergence delirium; children; risk factors; PAED; prediction model.

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Hanging on through Omicron, then what? A pre-exit baseline of the U.S. emergency nursing workforce, 2018 to 2022, with implications for the 2026 NSSRN cycle

Squire, K.

2026-06-08 nursing 10.64898/2026.06.07.26355097 medRxiv
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Background. The emergency department in the United States of America functions as a residual access point for healthcare and social services for populations including rural communities, the uninsured, mental health and addiction patients, and the unhoused. The workforce variable that determines unit function (experience density, the concentration of accumulated clinical judgment within a unit workforce) is not measured in hospital accounting systems. Objective. To document workforce composition changes in U.S. emergency nursing across the 2018 and 2022 cycles of the National Sample Survey of Registered Nurses (NSSRN), and to specify falsifiable predictions for the 2026 cycle. Methods. We analyzed NSSRN public-use files using a four-way ED definition extending Castner et al. (2024) and a hospital-bedside-restricted comparator. Variance estimation used jackknife replicate weights for 2018 and Successive Differences Replication for 2022. Burnout was operationalized using the Norful et al. (2023) leaving-reasons proxy across cycles, with sensitivity analysis using the 2022 direct burnout item. Results. A 15-year trajectory (2008-2022) documents progressive experience-density compression: the ED's 15+ year veteran cohort fell from 41.9% to 28.0% over the decade preceding the pandemic, a loss of nearly a third of the senior cohort and a 19.6% decline in mean experience density, before recovering modestly to 33.3% as veteran nurses remained through the pandemic acute phase, leaving the ED as the youngest hospital setting throughout. Hospital non-ED bedside nurses lost senior tenure between cycles (mean 15.65[-&gt;]14.06 years since first licensure; 15+ year share 43.5%[-&gt;]38.7%), while ED nurses retained their senior tail (mean 11.60[-&gt;]12.58). Burnout endorsement rose sharply in both populations (non-ED 27.3%[-&gt;]46.0%; ED 34.2%[-&gt;]61.2%), with the ED-vs-non-ED gap more than doubling. Controlling for tenure, ED status was not independently associated with burnout in 2018 (OR 1.15, 95% CI 0.83-1.59) but was strongly associated in 2022 (OR 1.92, 95% CI 1.44-2.55; p<.001). The direct burnout item showed a parallel pattern (OR 2.92, 95% CI 1.62-5.28). Conclusions. A pandemic-era setting-specific burnout effect emerged in emergency nursing that workforce-composition controls cannot explain. The 2022 cycle establishes a pre-exit baseline against which the 2026 NSSRN will serve as the falsifiable test of post-Omicron veteran exit. Nursing pipeline replacement lag exceeds the interval before 2026 data arrives; the consequences of inaction fall on populations dependent on ED-based residual access.

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Impact of GLP-1 Receptor Agonists on Chronic Low Back Pain in Patients with Obesity: A Prospective Pilot Cohort Study

Benedict, B.; White-Gilliam, D.; Pradhan, A.; Yakdan, S.; Hammo, A.; Budd, L.; Arkam, F.; Tang, S. Y.; Schechtman, K. B.; Cheng, A. L.; Robinson Reeds, S.; Goodin, B. R.; Greenberg, J. K.

2026-05-22 pain medicine 10.64898/2026.05.20.26353666 medRxiv
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Objective: To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with improvements in pain severity, disability, quality of life, and physical function in adults with obesity and chronic low back pain (cLBP), and to explore potential mechanisms. Design: Prospective, single-arm cohort study. Subjects: Thirty-five adults (median age 41 years; 86% women) with obesity (median BMI 39.9 kg/m2) and cLBP initiating GLP-1 RAs (tirzepatide, n=24; semaglutide, n=11). Methods: Participants completed questionnaires at baseline, 3, 6, 9, and 12 months. The primary outcome was Brief Pain Inventory-Short Form (BPI-SF) pain severity. Secondary outcomes included body mass index (BMI), BPI-SF pain interference, Numerical Rating Scale (NRS) back pain, Oswestry Disability Index (ODI), and Short Form-12 (SF-12). At baseline and 6 months, a subset (n=24) underwent quantitative sensory testing, physical performance testing, and blood draws for inflammatory biomarkers (C-reactive protein, TNF-, IL-6, IL-10), adipokines (leptin, adiponectin), and hemoglobin A1c. Results: Over 12 months, BMI decreased by 12.5% (median 39.9 to 34.9 kg/m2, 95% CI [-6.6, -4.2]). BPI-SF pain severity improved (median 4.8 to 2.0, 95% CI [-2.1, -0.8]), as did pain interference, ODI, NRS back pain, and SF-12 physical component scores. Hemoglobin A1c, leptin, and C-reactive protein decreased. Adiponectin increased and physical performance improved, but neither reached significance. Experimental pain sensitivity was unchanged. Conclusions: GLP-1 RAs were associated with clinically meaningful improvements in pain, disability, and quality of life. These findings suggest GLP-1 RAs may be a promising nonsurgical therapy for cLBP; randomized controlled trials are needed to establish causality and mechanisms.

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Genetic Susceptibility to Incisional Hernia: Evaluation of Hernia Polygenic Risk Scores

Pregnall, A. M.; Hornick, M. M.; Broach, R. B.; Judy, R.; DePaolo, J.; Yuan, S.; Levin, M.; Fischer, J. P.; Damrauer, S. M.; Wachtel, H.

2026-06-11 genetic and genomic medicine 10.64898/2026.06.10.26355374 medRxiv
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Objectives: Incisional hernia (IH) affects 13-30% of people after abdominal surgery, resulting in substantial morbidity and costs. While clinical risk factors have been studied extensively, genomic risk for IH is incompletely understood. We aimed to evaluate the impact of polygenic risk scores (PRS) on IH risk prediction. Methods] We created and evaluated three PRS for abdominal hernia, ventral hernia and latent hernia susceptibility for prediction of IH in an institutional biobank. The primary outcome was defined as the diagnosis or repair of an IH based on ICD-9/10-CM/PCS and CPT codes. Clinical covariates included age, sex, body mass index (BMI), smoking status, index procedure type, and perioperative surgical site infection. A phenome-wide association study (PheWAS) was performed to assess clinical associations with increased PRS. We then tested the ability of the PRS to improve prediction for IH by modeling clinical covariates with and without PRS in patients who underwent abdominal surgery. Model performance was assessed using 10 iterations of 5-fold cross-validation to estimate Brier scores and area under the receiver operating characteristic curve (AUROC), which were compared using cross-model Bayesian analysis of variance. Results: In 55,809 subjects, assessed PRS was significantly associated with incisional, umbilical, and ventral hernia on PheWAS, with 1.19 greater odds of developing IH per 1-SD increase in PRS (95% CI: 1.13-1.25, P \< 0.001). Of 9,909 subjects who underwent qualifying abdominal surgery, 706 developed IH. In this cohort, the latent hernia susceptibility PRS was associated with a 16% increased hazard of developing IH per 1-SD increase (HR 1.16; 95% CI: 1.07-1.26; P \< 0.001). Compared to a predictive model using clinical covariates (Brier score = 0.047, 95% CI: 0.046-0.048; AUROC = 0.660, 95% CI: 0.653-0.666), addition of the PRS showed similar Brier score and AUROC estimates (Brier score = 0.047, 95% CI: 0.046-0.048; AUROC: 0.667, 95% CI: 0.661-0.673) at five years. Cross-model Bayesian analysis demonstrated \>99% probability of practical equivalence when trying to detect a difference of [&ge;] 0.02. Conclusion: All three PRS for hernia were independently associated with IH, suggesting that genomic factors contribute significantly to IH development. However, none of the three PRS meaningfully improved clinical IH risk prediction in patients who underwent abdominal surgery. This suggests that clinical comorbidities and surgical techniques may be equally as important as genomic architecture.

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Effects of oxycodone versus sufentanil on postoperative sleep quality and analgesia in patients after modified radical mastectomy: study protocol for a randomized, double-blind, controlled trial using wearable sleep monitoring

deng, q.; Hu, J.; Huang, L.; Zheng, J.; Zheng, L.; Wu, A.

2026-05-22 anesthesia 10.64898/2026.05.20.26353683 medRxiv
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Background Postoperative sleep disorder, a frequently observed complication, is associated with heightened pain sensitivity, exacerbated inflammatory reactions, and compromised tissue repair. Sufentanil, a highly selective -opioid receptor agonist, is widely used in patient-controlled intravenous analgesia (PCIA) and has been associated with reduced sleep efficiency. Oxycodone, as a /{kappa} dual receptor agonist, has shown a lower incidence of adverse effects in clinical practice. Despite these pharmacological differences, the comparative effects of oxycodone- versus sufentanil-based PCIA on postoperative sleep remain poorly characterized. Recent advances in wearable devices demonstrate strong agreement with polysomnography (PSG) in intergroup comparisons of sleep efficiency and total sleep time, enabling continuous, non-invasive, multi-night sleep monitoring and offering a viable alternative for clinical postoperative sleep research. Hence, we design this clinical trial to compare postoperative sleep efficiency between patients receiving oxycodone-based versus sufentanil-based PCIA under wearable sleep monitoring. Methods This study is a randomized, double-blind, placebo-controlled trial that was conducted at a single center. A sample size of 68 patients was determined through calculation, and these patients will be randomly assigned to either the oxycodone group or the sufentanil group. Sleep monitoring was initiated using a wristband device one day before surgery after recruitment. The sleep quality data at different setting time will be monitored. All patients will be followed up by blinded evaluators at baseline and 1, 2, and 30 days after the intervention. The follow-up included pain scores, postoperative complications and adverse events, etc. Discussion By integrating a modern photoelectric device with first-line analgesics, we hope the result of the study will inform perioperative sleep management, guide clinical analgesic selection, and improve patient recovery quality.

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Surgical outcomes in complicated appendicitis: does timing or surgeon seniority matter? A propensity score-matched analysis from the RIFT Turkey cohort

Yalcinkaya, A.; Demirli Atici, S.; Ozen, C.; Karasoy, D.; Kamer, E.; Yalcinkaya, A.; Leventoglu, S.; RIFT Turkey Study Collaborators,

2026-05-26 surgery 10.64898/2026.05.19.26353556 medRxiv
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Background: Complicated acute appendicitis carries a higher risk of postoperative morbidity relative to uncomplicated cases. It remains unclear whether surgical timing (night vs. day; weekend vs. weekday) or surgeon seniority influence short-term outcomes in this high-risk population. Methods: This was a retrospective analysis of the RIFT Turkey dataset restricted to histologically confirmed cases of complicated appendicitis who had undergone laparoscopic appendectomy. Primary exposures were surgical timing (day [n=92] vs. night [n=123]; weekday [n=172] vs. weekend [n=43]) and surgeon seniority (trainee [n=89] vs. consultant [n=126]). The primary outcome was unplanned readmission and/or reintervention within 60 days. Secondary outcomes were conversion to open surgery and length of stay (LOS) >3 days. Propensity score matching (PSM) using RIPASA score (caliper 0.05, SMD <0.1) was performed as a pre-specified sensitivity analysis for each comparison. Results: Night-time surgery was associated with higher frequencies of unplanned readmission / reintervention (12.2% vs. 6.5%; OR 1.99 [95% CI 0.74-5.35], p=0.166) and surgical conversion (9.8% vs. 3.3%; OR 3.21 [0.88-11.72], p=0.064) compared with daytime surgery, neither reaching significance. Trainee surgeons had significantly higher readmission/reintervention rates than consultants (15.7% vs. 5.6%; OR 0.32 [0.12-0.82], p=0.013). PSM-adjusted results also showed similar relationships: night vs. day (readmission OR 2.45 [0.85-7.03], p=0.09; conversion OR 2.84 [0.73-11.1], p=0.13), weekend vs. weekday (readmission OR 1.53 [0.24-9.72], p=0.65), and trainee vs. consultant (readmission OR 0.25 [0.08-0.79], p=0.013). Conclusion: Surgical timing was not significantly associated with short-term outcomes in complicated appendicitis, though night-time surgery showed a consistent trend towards higher complication rates. Surgeon seniority was the only factor independently and significantly associated with unplanned readmission and reintervention in both primary and PSM analyses, indicating the need for senior supervision during out-of-hours procedures. Keywords: complicated appendicitis; surgical timing; night surgery; weekend effect; surgeon seniority; propensity score matching; RIFT Turkey

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Wearables Anticipate Postoperative Complications: A Prospective Cohort Study

Lederer, L.; Roghanizad, A. R.; Howell, T. C.; Turnage, K.; Blazer, D. G.; Knackstedt, R.; Hwang, S.; Dunn, J.

2026-06-03 surgery 10.64898/2026.06.02.26354556 medRxiv
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Consumer wearable devices enable continuous passive physiologic monitoring in free-living conditions, yet their capacity to detect early postoperative deterioration following hospital discharge remains poorly characterized. Here we report a prospective observational cohort study evaluating multimodal wearable-derived physiologic signals across the perioperative period in adults undergoing elective oncologic surgery at Duke University Health System. Participants were monitored using an Oura Ring Gen 2 and Garmin Vivosmart 4 from at least two weeks preoperatively through up to 90 days postoperatively, alongside daily electronic patient-reported pain surveys. Devices captured 3,705 participant-days and 82,833 hours of physiologic data across 46 surgical patients. Oura adherence averaged 21.0 hours/day and was significantly higher than Garmin throughout the study period (17.6 hours/day). Garmin wear time declined significantly following surgery, while Oura adherence remained comparatively stable. Postoperative complications occurred in 17 participants (37%), including 10 major complications (Clavien-Dindo grade IIIb or higher) with a median onset of 13 days after surgery. Patients with major complications demonstrated significantly greater peak deviations from baseline in the first 10 postoperative days across resting heart rate, sleep temperature deviation, and readiness metrics. In the days before clinically documented major complications, wearable and patient-reported signals diverged from those of participants without major complications, with reduced activity appearing as early as four days before the event, followed by higher reported pain and later elevations in resting heart rate and sleep temperature deviation. These findings support the feasibility of prolonged perioperative wearable monitoring and suggest that physiologic deterioration preceding major surgical complications may be detectable days before clinical documentation, motivating further development and validation of wearable-based postoperative surveillance strategies.

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Patient perceptions towards psychedelics for musculoskeletal pain: A cross-sectional survey

Li, E. J.; Mosharraf, B.; Ali, H.; Noyes, M.; Doshi, P.; Wallace, C.; Petranker, R.; Adili, A.; Khan, M.; Busse, J. W.; MacKillop, J.; Madden, K.

2026-06-01 pain medicine 10.64898/2026.05.29.26354422 medRxiv
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Background: Psychedelics are emerging as potential management options for chronic musculoskeletal pain due to preliminary evidence of effectiveness and low addictive potential, but patients perceptions remain unknown. This study assessed patient perceptions regarding psilocybin for musculoskeletal pain. Methods: We conducted a cross-sectional survey of adults ([&ge;]19) with musculoskeletal pain attending a hospital-based orthopaedic clinic. Participants reported demographics, perceptions of psychedelics for pain management, and willingness to participate in psychedelic research. Multivariable regression explored factors associated with perceived analgesic potential, and willingness to try a full therapeutic dose of psilocybin or a microdose. Results: Among 295 participants, 73% reported moderate-to-severe pain; 75% used analgesics; of these, 41% used opioids (86/209). While 24% reported prior psychedelic use, only 3% had discussed psychedelics with a healthcare provider. Most perceived that psilocybin had moderate-to-high effectiveness for pain (76%). Most respondents endorsed a moderate-to-high willingness to try microdoses (58%) and macrodoses (53%) of psilocybin for pain. Prior non-therapeutic psychedelic use predicted a 1.05-unit increase in perceived analgesic potential on the 10-point scale (p=.013). Willingness to try a macrodose of psilocybin was most strongly associated with prior non-therapeutic (B=3.16) and therapeutic (B=2.42) psychedelic use; in contrast, pain severity had a significant but modest association, with a 0.21-point increase in willingness for every 1-unit increase in pain severity (p=.017). Similarly, willingness to try a microdose of psilocybin was predicted by non-therapeutic (B=2.82) and therapeutic (B=2.48) use, whereas the effects of pain severity (B=0.20) and younger age (B=-0.30) were significant but small. Most respondents (52%) reported moderate-to-high willingness to participate in a trial of psilocybin for pain relief, and health risks were the primary concern (33%). Conclusions: Study findings suggest a majority hold neutral-to-positive perceptions of psilocybin for pain. Addressing perceived barriers, including health effects and gaps in patient knowledge, should be considered when designing future trials.

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Prognostic Impact of Early Lactate Trajectory Among Patients Admitted with Cardiogenic Shock

Caraballo, C.; Victoria-Castro, A. M.; Rali, A. S.; Hall, E. J.; Safiriyu, I.; Katz, J. N.; Gage, A.; Notarianni, A. P.; Dudzinski, D. M.; Alviar, C. L.; Tavazzi, G.; Miller, P. E.

2026-05-19 cardiovascular medicine 10.64898/2026.05.14.26353259 medRxiv
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Background: The importance of lactate trajectory during the first day of cardiogenic shock is increasingly recognized. We aimed to assess the association between admission-day lactate trajectory and in-hospital mortality, and to identify same-day interventions predictive of lactate clearance. Methods: We analyzed adult patients admitted with cardiogenic shock between October 2015 and June 2023, using the Vizient(R) Clinical Data Base. Early lactate clearance was defined as lactate <2.5 mmol/L by the end of the admission day. We used multivariable logistic regression to assess the association between lactate change and in-hospital mortality, and to identify interventions associated with lactate clearance. Results: Among 40,434 patients with cardiogenic shock, 30.1% achieved same-day lactate normalization, which was associated with lower in-hospital mortality (aOR 0.51; 95% CI 0.48-0.54). Lactate change showed the greatest prognostic importance, with observed mortality exceeding 80% among those with lactate increase >5 mmol/L regardless of baseline values. After adjustment, lactate change showed a positive exponential relationship with mortality, with aORs ranging from 0.25 (95% CI 0.23-0.27) for a -10 mmol/L change to 3.99 (95% CI 3.58-4.40) for a +10 mmol/L change. The intervention most strongly associated with early lactate clearance was pulmonary artery catheter (PAC; aOR 1.28 [95% CI 1.19-1.37]). Conclusions: Nearly 1 in 3 patients with cardiogenic shock achieved early lactate clearance, which was associated with lower mortality. The magnitude of lactate change had profound prognostic implications regardless of the initial value. Among day 1 interventions, PAC use had the strongest association with lactate clearance.