Background: Natalizumab (NTZ) is a highly effective disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS), originally administered intravenously (IV). A subcutaneous formulation (SC_NTZ) became available in Switzerland in 2021, offering potential advantages. Objective: To investigate satisfaction and convenience of use of SC_NTZ in MS patients. Design: Swiss, prospective, multicenter study. Methods: Consecutive RRMS patients treated with either ⩽6 (starters) or > 6 (long-term users) SC_NTZ injections completed the Treatment Satisfaction Questionnaire with Medication-II (TSQM-II, higher scores indicating greater satisfaction) and the Patient Satisfaction Questionnaire (PSQ) at baseline (Visit 1, V1). Starters were reassessed at the 9th SC_NTZ dose (Visit 2, V2). Non-parametric tests were applied to compare long-term users with starters at V1, and changes from V1 to V2 in starters. Results: One hundred six patients (73.6% female, median age 39.6 years, prior IV_NTZ 81.1%) were enrolled, including 79 long-term users and 27 starters. At V1, in the overall group the median (IQR) TSQM-II effectiveness, side effects, convenience and global satisfaction scores were 83 (67–100), 100 (92–100), 83 (72–89) and 83 (75–100), respectively. On the PSQ, the most commonly cited benefit was short administration time (80.2%). SC_NTZ treatment “never” affected work attendance in 54/87 (62.1%) employed patients. Seventy-nine percent participants reported spending ⩽1 h for SC_NTZ administration. Nonetheless, 76/86 (88.4%) of switchers from IV_NTZ found opportunities for discussions with healthcare professionals to be “similar”/”improved,” and 78 (90.7%) preferred SC_NTZ. Findings were consistent across subgroups and time points. Conclusion: This real-world, multicenter Swiss study supports SC_NTZ as a well-tolerated, highly accepted, and patient-preferred alternative to IV_NTZ.

Adverse drug reactions (ADRs) are a major cause of morbidity, hospital admissions, and in-hospital mortality, yet remain incompletely captured by post-marketing pharmacovigilance, which suffers from underreporting. Electronic health records (EHRs) contain clinical narratives that can reveal otherwise unreported ADRs. Natural language processing (NLP) offers a scalable means to extract structured information from clinical narratives, supporting ADR detection and assessment. We conducted a retrospective cross-sectional study within a multisite hospital network in Southern Switzerland to develop and evaluate NLP systems for ADR detection and information extraction from electronic discharge summaries. ADR classification models were trained on 400 discharge summaries and compared across multiple machine learning and vectorization strategies against a regular expression (regex) system. Drug and clinical event extraction were evaluated using 100 manually annotated summaries, benchmarking a dictionary-based approach against a two-step deep learning (DL) pipeline integrating transformer-based named entity recognition (NER) with a pharmacovigilance-oriented contextual relevance classifier. Performance was evaluated using standard metrics and a custom top-k ranking metric aligned with pharmacovigilance experts' daily capacity for reviewing positive cases to confirm the presence of ADRs. Logistic regression with Bag-of-Words achieved the best overall performance, combining high precision and effective case ranking. In a simulated deployment, this model identified nearly twice as many discharge summaries containing confirmed ADRs than as regex system. The two-step DL pipeline outperformed the dictionary-based approach for drug and clinical event recognition and accurately classified them according to pharmacovigilance purposes. These results demonstrate that NLP-based analysis of real-world clinical narratives can enhance pharmacovigilance while maintaining a manageable expert workload.

Background/Objectives: Some product information on pregabalin suggests a potential risk for congenital anomalies (CAs), although evidence remains inconsistent and lacks clear patterns. This study aimed to provide additional safety information on pregabalin use in pregnancy by analyzing VigiBase, the World Health Organization’s global pharmacovigilance database of individual case safety reports (ICSRs). Methods: The analysis included de-duplicated ICSRs related to pregabalin exposure in pregnancy, collected up to 16 January 2024. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated for CA categories reported in at least 10 ICSRs, with a statistical threshold defined as a 95% CI lower bound > 1. Results: Among 410 ICSRs, the majority originated from Europe (64.8%) and North America (26.5%). Of these, 59 (14.4%) ICSRs documented only pregabalin exposure in pregnancy, while 351 (85.6%) also reported adverse events in pregnancy. CAs occurred in 82 ICSRs (23.3%), most commonly involving heart defects (30), nervous system anomalies (18), and limb anomalies (12). No signals of disproportionate reporting were identified for these categories compared to the full database (heart defects: ROR 0.587, 95% CI 0.410–0.839; nervous system anomalies: ROR 0.588, 95% CI 0.370–0.933; limb anomalies: ROR 0.671, 95% CI 0.381–1.183). Conclusions: Future disproportionality analyses, along with pharmacovigilance and pharmacoepidemiological studies using patient registries and large-scale collaborative projects, are essential for the ongoing monitoring of pregabalin safety in pregnancy.

Janus kinase inhibitors (JAKIs) are immunomodulatory drugs used for autoimmune and inflammatory conditions. Their potential impact on pregnancy and fetal development remains a concern due to placental transfer and potential disruption of cytokine and growth factor signaling, with limited human data. This study analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to assess signals of disproportionate reporting (SDRs) for pregnancy-related adverse drug reactions (ADRs) reported with systemic JAKIs, including abrocitinib, baricitinib, deucravacitinib, fedratinib, filgotinib, itacitinib, momelotinib, pacritinib, peficitinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. As of May 26, 2024, 163 ICSRs met inclusion criteria, mainly from North America (41.7%) and Europe (39.3%). The most frequently reported JAKIs were tofacitinib (44.8%) and upadacitinib (34.4%), primarily indicated for rheumatoid arthritis (29.4%). Among 213 pregnancy-related ADRs, spontaneous abortion was the most frequently reported event (47.9%) without representing an SDR compared with other drugs in the database (reporting odds ratio [ROR] 0.37, 95% confidence interval [CI] 0.30-0.46). Congenital anomalies were reported in 16.0% of ICSRs (43 events), but no specific organ-related patterns were identified. Prematurity occurred in 9.2% of ICSRs, without SDR compared to the full database (ROR 0.07, 95% CI 0.04-0.11). Current pharmacovigilance data from VigiBase do not indicate SDRs for spontaneous abortion or prematurity following JAKI exposure during pregnancy. Findings should be interpreted cautiously given the limitations of spontaneous reporting systems and the exploratory nature of the analysis. Further studies are needed to better characterize the JAKI safety in pregnancy.

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have transformed the management of cystic fibrosis (CF), but evidence on their safety during pregnancy remains limited and pregnancy-related adverse drug reactions (ADRs) are not well characterized. Methods: We analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to identify signals of disproportionate reporting (SDRs) for pregnancy-related ADRs associated with elexacaftor, ivacaftor, tezacaftor and lumacaftor, reported until 15 December 2024. Results: Of 1035 pregnancy-related ICSRs with CFTR modulators, 280 met inclusion criteria. Two SDRs were identified: spontaneous abortion (n = 96 events, reporting odds ratio [ROR] 2.43; 95% confidence interval [CI] 1.99-2.97) and pre-eclampsia (n = 17 events, ROR 4.29; 95% CI 2.66-6.92). Reported birth defects were heterogeneous, with no recurring patterns. There was no SDR for prematurity. These findings align with recent observational studies and preclinical data indicating no teratogenic effects of CFTR modulators. Conclusion: CFTR modulators were not associated with the reporting of consistent patterns of congenital anomalies or prematurity in this large pharmacovigilance analysis. SDRs for spontaneous abortion and preeclampsia should be interpreted cautiously given the limitations inherent to the used study design and require confirmation in prospective pregnancy registries and controlled studies.

Background:Acute and chronic pain represents an escalating public health concern, necessitating safer and more effective in-hospital management approaches, including mental health. New treatment combinations involving psycholeptics are rising, but real-world evidence is lacking. Objectives:The study's primary objective is to evaluate the impact of combined opioid analgesics and antipsychotics in-hospital medication on pain modulation. The secondary objective is to evaluate pain management. Methods:The cross-sequential study designed by this protocol will analyze retrospective data on 5,000 hospital admissions over four years (2019-2023) gathered from Electronic Health Records (EHR) of a multisite hospital in southern Switzerland. Eligible patients are aged 18 or older and hospitalized in an Internal Medicine ward. All patients with documented pain intensity assessment through a Visual Analogue Scale (VAS ≥ 1) will be included. Cross-sectional data on demographic and clinical variables and type of medication (opioid analgesics, antipsychotics, and selected other drugs according to the Anatomical Therapeutic Chemical classification system) will be screened at hospital admission (T1) and discharge (T2). Pain modulation will be assessed by gravity (VAS mean), intensity (VAS peak/extreme value), and pain treatment effectiveness (ΔT2-T1 VAS). Hospitalization paths (short- and long-term readmissions and total length of hospital stays) will be scrutinized as additional longitudinal indices for pain management and excluded from the cross-sectional analysis. A mixed model approach will assess VAS changes from T1 to T2. Logistic regression and regression models for count data will be used for short- and long-term readmission, respectively. Propensity score matching will be used to mitigate selection bias. Discussion:This methodological approach combines cross-sectional and longitudinal EHR data gathering in a cross-sequential design. This integration allows for a comprehensive examination of pain modulation and management among internal medicine recipients of concomitant opioids and antipsychotic treatment, spanning both hospitalization and post-discharge periods. By leveraging EHR data, the study protocol ensures reliability and standardization while minimizing missing information. Additionally, the protocol addresses the potential limitations of observational designs. Conclusions:This method offers a comprehensive and rigorous approach to investigating pain modulation and management in internal medicine patients receiving combined opioid analgesics and antipsychotics, with potential implications for enhancing clinical practice and healthcare resource utilization.

Introduction: In patients with large vessel occlusion stroke of the anterior circulation who are treated with mechanical thrombectomy (MT) and intravenous thrombolysis (IVT), there is no clear evidence that prior antiplatelet therapy (APT) significantly influences functional outcomes, successful reperfusion rates or the risk of symptomatic intracranial hemorrhage (sICH). Even less studied is the effect of APT - especially dual APT - on the outcomes of direct MT, when IVT is not administered. We therefore aimed to evaluate the effects of prior APT on the outcomes of direct MT. Methods: We analyzed patients from the multicentric international EVA-TRISP database (from 2015 to 2023), comparing outcomes of direct MT based on their previous APT regimen, using propensity score matching and multivariable models to address for confounders. The primary efficacy outcome was a shift in the modified Rankin Scale (mRS) at 90 days. Secondary efficacy outcomes included independence at 90 days (mRS 0-2) and the rate of successful reperfusion (expanded treatment in cerebral infarction ≥2B). The primary safety outcome was the rate of sICH according to the European Cooperative Acute Stroke Study criteria. Results: Out of 4’444 patients, 1’308 were matched successfully: 480 without APT, 764 on single antiplatelet therapy (SAPT), and 64 on dual antiplatelet therapy (DAPT). SAPT was significantly associated with a shift towards lower mRS scores at 90 days (aOR = 1.29, CI: 1.03 - 1.60). In contrast, we couldn’t confirm the same finding for the DAPT group (aOR = 1.54, CI: 0.93 - 2.57). Nevertheless, independence at 90 days was significantly associated with both SAPT (aOR = 1.56, CI: 1.16 - 2.09) and DAPT (aOR = 3.13, CI: 1.63 - 6.00). Successful reperfusion was not influenced by either SAPT (aOR = 0.90, CI: 0.66 - 1.25) or DAPT (aOR = 0.63, CI: 0.28 - 1.39). Lastly, we did not find any significant association between APT and sICH, in either the SAPT (aOR 0.71, CI: 0.41 - 1.23) or DAPT group (aOR 0.42, CI: 0.09 - 1.92). Conclusion: We have found that in patients with large vessel occlusion stroke of the anterior circulation treated with direct MT, SAPT was significantly associated with better functional outcomes at 90 days compared with no previous APT, and that both SAPT and DAPT were safely associated with patient's functional independence at 90 days. These results should be confirmed in a larger randomized controlled trial.

Introduction: This study assessed sex differences in outcomes after mechanical thrombectomy (MT) with prior antiplatelet use using the EVA-TRISP multinational registry. Patients and methods: A cohort of consecutive patients (2015-2023) treated with MT was analysed by sex and prior antiplatelet use in multivariable logistic regression models. Primary outcomes were in-hospital symptomatic intracranial haemorrhage (sICH) and the 3-month modified Rankin Scale (mRS) score. Results: Among 7472 patients (47.9% females, older than males: 77 vs 72 years, p < 0.0001), sICH rates were similar (females 4.6%, males 4.4%, p = 0.405). The odds of sICH were not influenced by sex (adjusted odds ratio, aOR, 0.99, 95% confidence interval, CI, 0.77-1.28) or prior antiplatelet use (single therapy: aOR 1.28, 95% CI 0.95-1.73; dual therapy: aOR 0.81, 95% CI 0.29-2.31). No significant interactions were found between sex and antiplatelet use (p = 0.73 for single, p = 0.71 for dual therapy). Females had worse 3-month ordinal mRS scores than males (p < 0.0001), but the odds of a higher mRS score were not associated with sex (aOR 1.03, 95% CI 0.93-1.13) or prior antiplatelet use (single: aOR 1.03, 95% CI 0.91-1.16; dual: aOR 1.16, 95% CI 0.82-1.64). No interactions were found between sex and antiplatelet use for mRS (p = 0.78 for single, p = 0.29 for dual therapy). Discussion and conclusions: This study showed that there is no apparent interaction between patient sex and prior use of antiplatelets in relation to safety and functional outcomes of MT. Therefore, there is no reason to support a different decision-making approach by practicing physicians regarding MT in females and males previously taking antiplatelets.

In pharmacovigilance, disproportionality analyses based on individual case safety reports are widely used to detect safety signals. Unfortunately, publishing disproportionality analyses lacks specific guidelines, often leading to incomplete and ambiguous reporting, and carries the risk of incorrect conclusions when data are not placed in the correct context. The REporting of A Disproportionality analysis for drUg Safety signal detection using individual case safety reports in PharmacoVigilance (READUS-PV) statement was developed to address this issue by promoting transparent and comprehensive reporting of disproportionality studies. While the statement paper explains in greater detail the procedure followed to develop these guidelines, with this explanation paper we present the 14 items retained for READUS-PV guidelines, together with an in-depth explanation of their rationale and bullet points to illustrate their practical implementation. Our primary objective is to foster the adoption of the READUS-PV guidelines among authors, editors, peer reviewers, and readers of disproportionality analyses. Enhancing transparency, completeness, and accuracy of reporting, as well as proper interpretation of their results, READUS-PV guidelines will ultimately facilitate evidence-based decision making in pharmacovigilance.

Introduction Cannabis is the most common recreational drug worldwide and synthetic cannabinoid receptor agonists are currently the largest group of new psychoactive substances. The aim of this study was to compare the clinical features and outcomes of lone acute cannabis toxicity with lone acute synthetic cannabinoid receptor agonist toxicity in a large series of presentations to European emergency departments between 2013-2020. Methods Self-reported drug exposure, clinical, and outcome data were extracted from the European Drug Emergencies Network Plus which is a surveillance network that records data on drug-related emergency department presentations to 36 centres in 24 European countries. Cannabis exposure was considered the control in all analyses. To compare the lone cannabis and lone synthetic cannabinoid receptor agonist groups, univariate analysis using chi squared testing was used for categorical variables and non-parametric Mann-Whitney U- testing for continuous variables. Statistical significance was defined as a P value of < 0.05. Results Between 2013-2020 there were 54,314 drug related presentations of which 2,657 were lone cannabis exposures and 503 lone synthetic cannabinoid receptor agonist exposures. Synthetic cannabinoid receptor agonist presentations had statistically significantly higher rates of drowsiness, coma, agitation, seizures and bradycardia at the time of presentation. Cannabis presentations were significantly more likely to have palpitations, chest pain, hypertension, tachycardia, anxiety, vomiting and headache. Discussion Emergency department presentations involving lone synthetic cannabinoid receptor agonist exposures were more likely to have neuropsychiatric features and be admitted to a psychiatric ward, and lone cannabis exposures were more likely to have cardiovascular features. Previous studies have shown variability in the acute toxicity of synthetic cannabinoid receptor agonists compared with cannabis but there is little comparative data available on lone exposures. There is limited direct comparison in the current literature between lone synthetic cannabinoid receptor agonist and lone cannabis exposure, with only two previous poison centre series and two clinical series. Whilst this study is limited by self-report being used to identify the drug(s) involved in the presentations, previous studies have demonstrated that self-report is reliable in emergency department presentations with acute drug toxicity. Conclusion This study directly compares presentations with acute drug toxicity related to the lone use of cannabis or synthetic cannabinoid receptor agonists. It supports previous findings of increased neuropsychiatric toxicity from synthetic cannabinoid receptor agonists compared to cannabis and provides further data on cardiovascular toxicity in lone cannabis use.

BackgroundTo date, evidence on late-onset immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICIs) is limited to a small number of clinical cases. This study aimed to identify drug- and patient-related characteristics potentially associated with the reporting of late-onset irAEs with ICIs in VigiBase, the WHO global database of individual case safety reports (ICSRs).MethodsObservational study comparing deduplicated ICSRs with ICIs reporting late-onset irAEs (occurred >90 days after ICI discontinuation) versus ICSRs with ICIs not reporting late-onset irAEs, collected in VigiBase from 2011 to December 31, 2022. Logistic regression was used to model the relationship between drug-related and patient-related characteristics of ICSRs and the reporting of late-onset irAEs. Significance was determined for variables with the lower bound of the 95% CI of the reporting OR (ROR) higher than 1 and a p value <0.05.ResultsThe study population consisted of 6006 ICSRs with ICI-related irAEs (4574, 76.2%, originated from Europe; 3900, 64.9%, involved males; median patient age was 67 years, IQR 59–74 years). Of these, 344 (5.7%) ICSRs reported a total of 388 late-onset irAEs, among which the most frequent were thyroiditis (n=45), pneumonitis (n=37), interstitial lung disease (n=25), hepatitis (n=23) and vitiligo (n=19). Median time to onset since ICI discontinuation was 167 days (IQR 115–294 days), with negligible proportion (3.2%) of co-reported antineoplastic agents during the discontinuation period. Logistic regression models showed disproportionate reporting of late-onset irAEs with ICI combination therapy (ROR 2.33, 95% CI 1.19 to 4.57), reporting of multiple irAEs (ROR 3.96, 95% CI 2.85 to 5.52), reporting of cutaneous irAEs (ROR 1.83, 95% CI 1.24 to 2.71), and melanoma (ROR 1.47, 95% CI 1.04 to 2.06).ConclusionsThis global pharmacovigilance study provides the largest case series of late-onset irAEs with ICIs to date and identifies characteristics of ICSRs associated with disproportionate reporting. Dedicated prospective observational studies focused on long-term sequelae, quality of life and survival of patients developing late-onset irAEs with ICIs should be planned to confirm whether these reporting characteristics are predictors of actual occurrence. Furthermore, translational research should be encouraged to clarify the molecular mechanisms underlying late-onset irAE development.

Background Current evidence on the safety of calcitonin gene–related peptide antagonists (CGRP-A) in pregnancy for the treatment of both episodic and chronic migraine is scarce and does not yet provide definitive information. By querying VigiBase ® , the World Health Organization global pharmacovigilance database, this study aimed to detect differences in the reporting frequency between CGRP-A and triptans in relation to pregnancy. Methods Disproportionality analyses on de-duplicated safety reports collected in VigiBase ® as of 31.05.2023 reporting exposure to CGRP-A in pregnancy with or without pregnancy outcomes. A Reporting Odds Ratio (ROR) with a 95% confidence interval (CI) was used as a measure of disproportionality and the threshold for the detection of a signal of disproportionate reporting was set with a 95% CI lower limit > 1. Findings Four hundred sixty-seven safety reports reported exposure to CGRP-A in pregnancy, mostly originating from the United States of America (360/467, 77%), more frequently reported by patients (225/467, 48%), who were mainly females (431/467, 92%), and more frequently reported exposure to CGRP-A during pregnancy (400/467, 86%). Compared to triptans, no signals of disproportionate reporting were detected with CGRP-A either for the overall reporting of pregnancy-related safety reports (ROR 0.91, 95% CI 0.78–1.06), for the reporting of pregnancy outcomes (maternal and/or foetal/neonatal, ROR 0.54, 95% CI 0.45–0.66), or for the reporting of foetal/neonatal outcomes (ROR 0.53, 95% CI 0.41–0.68). Conclusions This study showed that, to date, there are no signals of increased reporting with CGRP-A compared to triptans in relation to pregnancy in VigiBase ® . Future pharmacovigilance studies are needed to confirm these findings.

BackgroundThis study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS).MethodsConsecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke.ResultsA total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th–75th percentiles 67–84 years versus 70 years, 25th–75th percentiles 60–80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01–2.19, value of p 0.044).ConclusionThis study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

Safety data on the use of monoclonal antibodies inhibiting proprotein convertase subtilisin/kexin type 9 in pregnancy are scarce. This study queried VigiBase®, the World Health Organization global pharmacovigilance database, to search for signals of disproportionate reporting for pregnancy outcomes with alirocumab and evolocumab. As of November 22, 2023, there were 45 safety reports of exposure to evolocumab (N = 31) and alirocumab (N = 14) in pregnancy. Most of them originated from Europe (N = 25, 55.6%) and were more frequently reported by healthcare professionals (N = 35, 77.8%). Median patient age was 37 years (25th-75th percentiles; 32-41 years). Drug exposure occurred during pregnancy in 36 (80.0%) safety reports, via paternal exposure during pregnancy in four (8.9%), during lactation in three (6.7%), and in two safety reports the time of drug exposure remained unknown. Twenty safety reports (57.8%) merely reported drug exposure, while 19 (42.2%) also reported pregnancy outcomes, however, without specific maternal toxicities or patterns of birth defects. Spontaneous abortion was reported in eight safety reports without representing a signal of disproportionate reporting compared with either the full database (reporting odds ratio, ROR, 0.06 95% confidence interval, CI 0.03-0.12) or statins (ROR 0.16, 95% CI 0.08-0.32). In conclusion, this study showed that, currently, there are no signals of increased reporting of spontaneous abortion with alirocumab and evolocumab compared with the full database and statins in VigiBase®. Notwithstanding, lack of disproportionality is not synonymous with safety and, as disproportionality analyses depend on the number of safety reports that progressively accumulate in VigiBase®, they should be repeated at regular intervals to confirm the results of the present study.

Background Self-discharge is a risk factor for readmission and excess mortality. We assess the rate of self-discharge from the emergency department (ED) among presentations for acute recreational drug toxicity and identify factors associated with self-discharge. Methods From the Euro-DEN Plus database of presentations to the ED with acute recreational drug toxicity, we extracted data from 11 centres in seven European countries from 2014 to 2017. Self-discharge was defined as taking one’s own discharge or escaping from the ED before being medically cleared. We used multiple logistic regression analyses to look for factors associated with self-discharge. Results Among 15,135 included presentations, 1807 (11.9%) self-discharged. Self-discharge rates varied from 1.7 to 17.1% between centres. Synthetic cannabinoids were associated with self-discharge, adjusted odds ratio 1.44 (95% confidence interval 1.10–1.89), as were heroin, 1.44 (1.26–1.64), agitation, 1.27 (1.10–1.46), and naloxone treatment, 1.27 (1.07–1.51), while sedation protected from self-discharge, 0.38 (0.30–0.48). Conclusion One in eight presentations self-discharged. There was a large variation in self-discharge rates across the participating centres, possibly partly reflecting different discharge procedures and practices. Measures to improve the management of agitation and cautious administration of naloxone to avoid opioid withdrawal symptoms may be approaches worth exploring to reduce self-discharge.

The prognosis and disease-free survival rates for head and neck squamous cell carcinoma (HNSCC) have remained relatively stagnant for the last several decades. Moreover, as is the case with other malignancies, locoregional recurrence and distant metastasis are all too common even after seemingly successful oncologic surgery and adjuvant therapy. Recently, increased focus has been placed on understanding the influence of perioperative factors on tumor cell behavior and surgical outcomes. More specifically, emerging research suggests that anesthetic agents may play a role in cancer recurrence by interacting with prosurvival protein signaling pathways which harden tumor cells against oncologic treatments. In the present pilot study, we tested the hypothesis that inhalational anesthesia and total intravenous anesthesia (TIVA) exert differential effects on the proteomic expression of HNSCC. Ten patients with previously untreated oral cavity or oropharyngeal HNSCC were randomized to receive either sevoflurane and remifentanil or propofol and remifentanil for the duration of their respective surgeries. Morphoproteomic analysis using 10 pro-oncogenic protein markers was performed on both pre- and postanesthesia tumor samples to qualitatively grade changes in protein expression. The results of this analysis demonstrated differential expression of several protein markers. Specifically, the exposure to sevoflurane but not TIVA resulted in a statistically significant increase in the expression of cytoplasmic hypoxia-inducible factor-2alpha (P = 0.049) and nuclear p-p38 mitogenic-activated protein kinase (P = 0.041). This study represents one of the first to evaluate the effects of anesthesia on the molecular biology of HNSCC in vivo, and the results suggest that the exposure to sevoflurane may increase the expression of pro-oncogenic protein markers in HNSCC tumor cells.