Biomarkers in the Immuno-oncology Interface of Triple Negative Breast Cancer: A Scoping Review with Perioperative Considerations.

PURPOSE OF REVIEW: Identification of biomarkers for immunotherapy treatment in triple negative breast cancer remains crucial for improving outcomes and optimising regimes, particularly in the perioperative setting. There is a need to conduct a scoping review to provide an overview of current research, explore the wider context, and highlight future research considerations in this field. RECENT FINDINGS: The most commonly assessed biomarkers are PD-L1, TILs and CD8 + cells with correlation to outcomes mainly focused on survival. There is a growing interest in evaluating genetic markers. Conclusions are currently limited by knowledge gaps around contextual factors. Important areas of focus for future research include a greater understanding of complex cellular, genetic and metabolic interactions in the perioperative tumour microenvironment, including patient-specific immune profiles. An important challenge remains elucidating the clinical significance of the immunological effects of interventions at each stage of the perioperative period, including the use of anaesthetic agents.

Challenges of acute pain management in older patients.

Adequate management of acute pain in the older population is crucial. However, it is inherently complex because of multiple physiological changes that significantly impact both the pharmacokinetics and pharmacodynamics of medications. Current guidelines promote paracetamol as the first-line analgesic for acute pain in older adults, whereas opioids are advised cautiously for moderate to severe acute pain. However, opioids come with a significant array of side effects, which can be more pronounced in older individuals. Ketamine administered via intranasal (IN) and nebulised inhalation in the emergency department for managing acute pain in older patients shows promising potential for improving pain management and reducing opioid reliance Kampan, Thong-on, Sri-on (2024, Age Ageing, 53, afad255). Nebulised ketamine appears superior in terms of adverse event incidence. However, the adoption of IN or nebulised ketamine in older adult acute pain management remains unclear because of the lack of definitive conclusions and clear guidelines. Nevertheless, these modalities can be valuable options for patients where opioid analgesics are contraindicated or when intravenous morphine titration is impractical or contraindicated. Here, we review these concepts, the latest evidence and propose avenues for research.

Method of Anesthesia and Perioperative Risk Factors, Maternal Anesthesia Complications, and Neonatal Mortality Following Cesarean Delivery in Africa: A Substudy of a 7-Day Prospective Observational Cohort Study.

BACKGROUND: The African Surgical Outcomes Study (ASOS) found that maternal mortality following cesarean delivery in Africa is 50 times higher than in high-income countries, and associated with obstetric hemorrhage and anesthesia complications. Mothers who died were more likely to receive general anesthesia (GA). The associations between GA versus spinal anesthesia (SA) and preoperative risk factors, maternal anesthesia complications, and neonatal outcomes following cesarean delivery in Africa are unknown. METHODS: This is a secondary explanatory analysis of 3792 patients undergoing cesarean delivery in ASOS, a prospective observational cohort study, across 22 African countries. The primary aim was to estimate the association between preoperative risk factors and the outcome of the method of anesthesia delivered. Secondary aims were to estimate the association between the method of anesthesia and the outcomes (1) maternal intraoperative hypotension, (2) severe maternal anesthesia complications, and (3) neonatal mortality. Generalized linear mixed models adjusting for obstetric gravidity and gestation, American Society of Anesthesiologists (ASA) category, urgency of surgery, maternal comorbidities, fetal distress, and level of anesthesia provider were used. RESULTS: Of 3709 patients, SA was performed in 2968 (80%) and GA in 741 (20%). Preoperative factors independently associated with GA for cesarean delivery were gestational age (adjusted odds ratio [aOR], 1.093; 95% confidence interval [CI], 1.052-1.135), ASA categories III (aOR, 11.84; 95% CI, 2.93-46.31) and IV (aOR, 11.48; 95% CI, 2.93-44.93), eclampsia (aOR, 3.92; 95% CI, 2.18-7.06), placental abruption (aOR, 6.23; 95% CI, 3.36-11.54), and ruptured uterus (aOR, 3.61; 95% CI, 1.36-9.63). SA was administered to 48 of 94 (51.1%) patients with eclampsia, 12 of 28 (42.9%) with cardiac disease, 14 of 19 (73.7%) with preoperative sepsis, 48 of 76 (63.2%) with antepartum hemorrhage, 30 of 55 (54.5%) with placenta previa, 33 of 78 (42.3%) with placental abruption, and 12 of 29 (41.4%) with a ruptured uterus. The composite maternal outcome "all anesthesia complications" was more frequent in GA than SA (9/741 [1.2%] vs 3/2968 [0.1%], P < .001). The unadjusted neonatal mortality was higher with GA than SA (65/662 [9.8%] vs 73/2669 [2.7%], P < .001). The adjusted analyses demonstrated no association between method of anesthesia and (1) intraoperative maternal hypotension and (2) neonatal mortality. CONCLUSIONS: Analysis of patients undergoing anesthesia for cesarean delivery in Africa indicated patients more likely to receive GA. Anesthesia complications and neonatal mortality were more frequent following GA. SA was often administered to high-risk patients, including those with eclampsia or obstetric hemorrhage. Training in the principles of selection of method of anesthesia, and the skills of safe GA and neonatal resuscitation, is recommended.

Experiences and perspectives of adults on using opioids for pain management in the postoperative period: A scoping review.

BACKGROUND: Opioids play an important role in peri-operative pain management. However, opioid use is challenging for healthcare practitioners and patients because of concerns related to opioid crises, addiction and side effects. OBJECTIVE: This review aimed to identify and synthesise the existing evidence related to adults' experiences of opioid use in postoperative pain management. DESIGN: Systematic scoping review of qualitative studies. Inductive content analysis and the Theoretical Domains Framework (TDF) were applied to analyse and report the findings and to identify unexplored gaps in the literature. DATA SOURCES: Ovid MEDLINE, PsycInfo, Embase, CINAHL (EBSCO), Cochrane Library and Google Scholar. ELIGIBILITY CRITERIA: All qualitative and mixed-method studies, in English, that not only used a qualitative approach that explored adults' opinions or concerns about opioids and/or opioid reduction, and adults' experience related to opioid use for postoperative pain control, including satisfaction, but also aspects of overall quality of a person's life (physical, mental and social well being). RESULTS: Ten studies were included; nine were qualitative ( n  = 9) and one used mixed methods. The studies were primarily conducted in Europe and North America. Concerns about opioid dependence, adverse effects, stigmatisation, gender roles, trust and shared decision-making between clinicians and patients appeared repeatedly throughout the studies. The TDF analysis showed that many peri-operative factors formed people's perceptions and experiences of opioids, driven by the following eight domains: Knowledge, Emotion, Beliefs about consequences, Beliefs about capabilities, Self-confidence, Environmental Context and Resources, Social influences and Decision Processes/Goals. Adults have diverse pain management goals, which can be categorised as proactive and positive goals, such as individualised pain management care, as well as avoidance goals, aimed at sidestepping issues such as addiction and opioid-related side effects. CONCLUSION: It is desirable to understand the complexity of adults' experiences of pain management especially with opioid use and to support adults in achieving their pain management goals by implementing an individualised approach, effective communication and patient-clinician relationships. However, there is a dearth of studies that examine patients' experiences of postoperative opioid use and their involvement in opioid usage decision-making. A summary is provided regarding adults' experiences of peri-operative opioid use, which may inform future researchers, healthcare providers and guideline development by considering these factors when improving patient care and experiences.

Perioperative opioids: a narrative review contextualising new avenues to improve prescribing.

Opioids have dominated the management of perioperative pain in recent decades with higher doses than ever before used in some circumstances. Through the expanding use of opioids, growing research has highlighted their associated side-effects and the intertwined phenomena of acute withdrawal syndrome, opioid tolerance, and opioid-induced hyperalgesia. With multiple clinical guidelines now endorsing multimodal analgesia, a diverse array of opioid-sparing agents emerges and has been studied to variable degrees, including techniques of opioid-free anaesthesia. It remains unclear to what extent such methods should be adopted, yet current evidence does suggest dependence on opioids as the primary perioperative analgesic might not meet the principles of 'rational prescribing' as described by Maxwell. In this narrative review we describe how, using current evidence, a patient-centred rational-prescribing approach can be applied to opioids in the perioperative period. To contextualise this approach, we discuss the historical adoption of opioids in anaesthesia, our growing understanding of associated side-effects and emerging strategies of opioid-sparing and opioid-free anaesthesia. We discuss avenues and challenges for improving opioid prescribing to limit persistent postoperative opioid use and how these may be incorporated into a rational-prescribing approach.

Tumour excisional surgery, anaesthetic-analgesic techniques, and oncologic outcomes: a narrative review.

Cancer is a growing global burden; there were an estimated 18 million new cancer diagnoses worldwide in 2020. Excisional surgery remains one of the main treatments for solid organ tumours in cancer patients and is potentially curative. Cancer- and surgery-induced inflammatory processes can facilitate residual tumour cell survival, growth, and subsequent recurrence. However, it has been hypothesised that anaesthetic and analgesic techniques during surgery might influence the risk of cancer recurrence. This narrative review aims to provide an updated summary of recent observational studies and new randomised controlled clinical trials on whether certain specific anaesthetic and analgesic techniques or perioperative interventions during tumour resection surgery of curative intent materially affect long-term oncologic outcomes.

Developing expert international consensus statements for opioid-sparing analgesia using the Delphi method.

INTRODUCTION: The management of postoperative pain in anaesthesia is evolving with a deeper understanding of associating multiple modalities and analgesic medications. However, the motivations and barriers regarding the adoption of opioid-sparing analgesia are not well known. METHODS: We designed a modified Delphi survey to explore the perspectives and opinions of expert panellists with regard to opioid-sparing multimodal analgesia. 29 anaesthetists underwent an evolving three-round questionnaire to determine the level of agreement on certain aspects of multimodal analgesia, with the last round deciding if each statement was a priority. RESULTS: The results were aggregated and a consensus, defined as achievement of over 75% on the Likert scale, was reached for five out of eight statements. The panellists agreed there was a strong body of evidence supporting opioid-sparing multimodal analgesia. However, there existed multiple barriers to widespread adoption, foremost the lack of training and education, as well as the reluctance to change existing practices. Practical issues such as cost effectiveness, increased workload, or the lack of supply of anaesthetic agents were not perceived to be as critical in preventing adoption. CONCLUSION: Thus, a focus on developing specific guidelines for multimodal analgesia and addressing gaps in education may improve the adoption of opioid-sparing analgesia.

A survey on the availability, usage and perception of neuromuscular monitors in Europe.

PURPOSE: Neuromuscular blocking agents (NMBAs) are routinely administered to patients in a multiplicity of anesthetic settings. Absence of postoperative residual neuromuscular block is widely considered an anesthetic patient safety mandate. Despite the increasing availability of a wider range of commercial quantitative neuromuscular monitors, the availability and use of neuromuscular monitoring devices is deemed to be suboptimal even in countries with above-average health system ratings. The present study aims to more precisely characterize the perceived availability, cost sensitivity and usability of neuromuscular monitoring devices within European anesthesia departments. METHODS: A pre-registered internet-based survey assessing the availability, cost sensitivity and usability of neuromuscular monitoring devices was distributed as e-mail newsletter by the European Society of Anaesthesiology and Intensive Care (ESAIC) to all of its active full members. The survey was available online for a total of 120 days. RESULTS: Having targeted a total of 7472 ESAIC members, the survey was completed by a total of 692 anesthesiologists (9.3%) distributed across 37 different European countries. Quantitative monitors were reported to be proportionally more available than qualitative ones (87.6% vs. 62.6%, respectively), as well as in greater monitor-per-operating room ratios. Most anesthesiologists (60.5%) expressed moderate confidence in quantitative monitors, with artifactual recordings and inaccurate measurements being the most frequently encountered issues (25.9%). The commercial pricing of quantitative devices was considered more representative of a device's true value, when compared to qualitative instruments (average cost of €4.500 and €1.000 per device, respectively). CONCLUSION: The availability of quantitative NMM in European operating theaters has increased in comparison with that reported in previous decades, potentially indicating increasing monitoring rates. European anesthesiologists express moderate confidence in quantitative neuromuscular monitors, along with a sentiment of adequate pricing when compared to their qualitative counterparts. Trust in quantitative monitors is marked by caution and awareness for artifactual recordings, with a consequent expectation that developments focusing on accuracy, reliability and ergonomics of neuromuscular monitors be prioritized.

Immunological Insights into Opioid-Free Anaesthesia in Oncological Surgery: A Scoping Review.

PURPOSE OF REVIEW: The influence of opioids on outcomes after cancer surgery when used, or avoided, intraoperatively remains unclear. There is a need to conduct a scoping review to explore the wider context and provide direction for future research. The review will examine the current state of evidence in humans, with a focus on immunological biomarkers and clinically relevant cancer outcomes in trials comparing opioid-free to opioid-based general anaesthesia. RECENT FINDINGS: There is limited research on this subject area, which is mainly focused on breast cancer. The most frequently evaluated immunological parameter is the neutrophil-to-lymphocyte ratio. Cancer outcomes are mainly focused on recurrence. The central knowledge gap is understanding how the cellular effects of opioids translate into longer-term patient outcomes. The major challenge for future research is accounting for the immunomodulatory effects of a wide range of confounding factors, which have yet to be clarified.

Postoperative Outcomes Associated With Procedural Sedation Conducted by Physician and Nonphysician Anesthesia Providers: Findings From the Prospective, Observational African Surgical Outcomes Study.

BACKGROUND: There is an unmet need for essential surgical services in Africa. Limited anesthesia services are a contributing factor. Nonphysician anesthesia providers are utilized to assist with providing anesthesia and procedural sedation to make essential surgeries available. There is a paucity of data on outcomes following procedural sedation for surgery in Africa. We investigated the postoperative outcomes following procedural sedation by nonphysicians and physicians in Africa. We hypothesized that the level of training of the sedation provider may be associated with the incidence of severe postoperative complications and death. METHODS: A secondary analysis of a prospective cohort of inhospital adult surgical patients representing 25 African countries was performed. The primary outcome was a collapsed composite of inhospital severe postoperative complications and death. We assessed the association between receiving procedural sedation conducted by a nonphysician (versus physician) and the composite outcome using logistic regression. We used the inverse probability of treatment weighting propensity score method to adjust for potential confounding variables including patient age, hemoglobin level, American Society of Anesthesiologists (ASA) physiological status, diabetes mellitus, urgency of surgery, severity of surgery, indication for surgery, surgical discipline, seniority of the surgical team, hospital level of specialization, and hospital funding system using public or private funding. All patients who only received procedural sedation for surgery were included. RESULTS: Three hundred thirty-six patients met the inclusion criteria, of which 98 (29.2%) received sedation from a nonphysician provider. The incidence of severe postoperative complications and death was 10 of 98 (10.2%) in the nonphysician group and 5 of 238 (2.1%) in the physician group. The estimated association between procedural sedation conducted by a nonphysician provider and inhospital outcomes was an 8-fold increase in the odds of severe complications and/or death, with an odds ratio (95% confidence interval [CI]) of 8.3 (2.7-25.6). CONCLUSIONS: The modest number of observations in this secondary data analysis suggests that shifting the task of procedural sedation from physicians to nonphysicians to increase access to care may be associated with severe postoperative complications and death in Africa. Research focusing on identifying factors contributing to adverse outcomes associated with procedural sedation is necessary to make this practice safer.

Opioid-free versus opioid-based anesthesia in pancreatic surgery.

BACKGROUND: Opioid-free anesthesia (OFA) is associated with significantly reduced cumulative postoperative morphine consumption in comparison with opioid-based anesthesia (OBA). Whether OFA is feasible and may improve outcomes in pancreatic surgery remains unclear. METHODS: Perioperative data from 77 consecutive patients who underwent pancreatic resection were included and retrospectively reviewed. Patients received either an OBA with intraoperative remifentanil (n = 42) or an OFA (n = 35). OFA included a combination of continuous infusions of dexmedetomidine, lidocaine, and esketamine. In OBA, patients also received a single bolus of intrathecal morphine. All patients received intraoperative propofol, sevoflurane, dexamethasone, diclofenac, neuromuscular blockade. Postoperative pain management was achieved by continuous wound infiltration and patient-controlled morphine. The primary outcome was postoperative pain (Numerical Rating Scale, NRS). Opioid consumption within 48 h after extubation, length of stay, adverse events within 90 days, and 30-day mortality were included as secondary outcomes. Episodes of bradycardia and hypotension requiring rescue medication were considered as safety outcomes. RESULTS: Compared to OBA, NRS (3 [2-4] vs 0 [0-2], P < 0.001) and opioid consumption (36 [24-52] vs 10 [2-24], P = 0.005) were both less in the OFA group. Length of stay was shorter by 4 days with OFA (14 [7-46] vs 10 [6-16], P < 0.001). OFA (P = 0.03), with postoperative pancreatic fistula (P = 0.0002) and delayed gastric emptying (P < 0.0001) were identified as only independent factors for length of stay. The comprehensive complication index (CCI) was the lowest with OFA (24.9 ± 25.5 vs 14.1 ± 23.4, P = 0.03). There were no differences in demographics, operative time, blood loss, bradycardia, vasopressors administration or time to extubation among groups. CONCLUSIONS: In this series, OFA during pancreatic resection is feasible and independently associated with a better outcome, in particular pain outcomes. The lower rate of postoperative complications may justify future randomized trials to test the hypothesis that OFA may improve outcomes and shorten length of stay.

System-level policies on appropriate opioid use, a multi-stakeholder consensus.

BACKGROUND: This consensus statement was developed because there are concerns about the appropriate use of opioids for acute pain management, with opposing views in the literature. Consensus statement on policies for system-level interventions may help inform organisations such as management structures, government agencies and funding bodies. METHODS: We conducted a multi-stakeholder survey using a modified Delphi methodology focusing on policies, at the system level, rather than at the prescriber or patient level. We aimed to provide consensus statements for current developments and priorities for future developments. RESULTS: Twenty-five experts from a variety of fields with experience in acute pain management were invited to join a review panel, of whom 23 completed a modified Delphi survey of policies designed to improve the safety and quality of opioids prescribing for acute pain in the secondary care setting. Strong agreement, defined as consistent among> 75% of panellists, was observed for ten statements. CONCLUSIONS: Using a modified Delphi study, we found agreement among a multidisciplinary panel, including patient representation, on prioritisation of policies for system-level interventions, to improve governance, pain management, patient/consumers care, safety and engagement.

Anaesthesia for elite athletes.

BACKGROUND: Sports participation has been growing rapidly since the 1960s. Anaesthesiologists are increasingly confronted with athletes in a peri-operative setting. The right choice of type of anaesthesia technique, pain management of injuries, specific physiologic adaptations of the athlete and knowledge of prohibited substances are eminent for a correct approach of this subpopulation. PURPOSE: This review aims to give an overview of athletes' specific anaesthetic management in peri-operative and postoperative settings and to guide the nonspecialised anaesthetist. METHODS: We comprehensively reviewed the literature, gathered all the information available on, and synthesised it in a narrative way, regarding preoperative evaluation, intraoperative implications and postoperative pain management of the elite athlete undergoing a surgical procedure. RESULTS: An anaesthesiologist should recognise the most common benign ECG findings in athletes like bradycardia, isolated left ventricle hypertrophy on voltage criteria and early repolarisation as normal features in the athlete's heart. Isotonic physiology typically produces four-chamber dilation. In contrast, isometric stress creates high intravascular pressure leading to left ventricular hypertrophy. Pre-operative evaluation should also identify possible consumers of performance-enhancing drugs. Intraoperative points of interest for the anaesthesiologist is mainly avoiding drugs on the prohibited list of the World Anti-Doping Agency (WADA). Postoperative and chronic pain management are still developing fields in this population. The International Olympic Committee (IOC) proposed treating acute pain with a combination of paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), topical analgesics, injectable NSAIDs and local anaesthetics. It may be suggested that chronic pain management in elite athletes could benefit from treatment in specialised multidisciplinary pain clinics. CONCLUSION: This literature review aims to serve as a guide for the anaesthesiologist taking care of the elite athlete.

Anesthetics and Long Term Cancer Outcomes: May Epigenetics Be the Key for Pancreatic Cancer?

Knowledge shows a divergence of results between preclinical and clinical studies regarding anesthesia and postoperative progression of cancer. While laboratory and animal data from then 2000s onwards raised much enthusiasm in this field of research leading to several clinical investigations worldwide, data from randomized trials seem to have killed off hope for many scientists. However several aspects of the actual knowledge should be reevaluated and there is space for new strategies of investigation. In this paper, we perform a critical review of actual knowledge and propose new research strategies with a special focus on anesthetic management and repurposed anesthetic adjuvants for pancreatic cancer.

Perioperative NSAIDs and Long-Term Outcomes After cancer Surgery: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: This review investigated the use of perioperative non-steroidal anti-inflammatory drugs (NSAIDs) and long-term outcomes in cancer surgery patients, and whether this is dependent on cancer type, type of NSAID and timing of administration. FINDINGS: Perioperative NSAID use was found to be associated with longer disease-free survival (hazard ration, HR = 0.84 (95% CI, 0.73-0.97)) and overall survival (HR = 0.78 (95% CI, 0.64-0.94)). No difference was found between different types of NSAID for disease-free survival, although in overall survival ketorolac use was significant (HR = 0.63 (95% CI, 0.42-0.95)). Analysis on the timing of NSAID administration found no subgroup to be associated with cancer outcomes. The cancer-type analysis found an association with outcomes in breast and ovarian cancers. However, the level of certainty remains very low, mostly due to the heterogeneity and the retrospective nature of most studies. Perioperative NSAID use may be associated with increased disease-free and overall survival after cancer surgery. This may be dependent on the type of cancer and type of NSAID, and further research is needed to support this. These data may inform future prospective trials, which are needed to determine the clinical impact, as well as optimal NSAID regimen.

Propofol for Induction and Maintenance of Anesthesia in Patients With Brugada Syndrome: A Single-Center, 25-Year, Retrospective Cohort Analysis.

BACKGROUND: Propofol administration in patients with Brugada syndrome (BrS) is still a matter of debate. Despite lacking evidence for its feared arrhythmogenicity, up to date, expert cardiologists recommend avoiding propofol. The main aim of this study is to assess the occurrence of malignant arrhythmias or defibrillations in patients with BrS, during and 30 days after propofol administration. The secondary aim is to investigate the occurrence of adverse events during propofol administration and hospitalization, as the 30-day readmission and 30-day mortality rate. METHODS: We performed a retrospective cohort study on patients with BrS who received propofol anytime from January 1, 1996 to September 30, 2020. Anesthesia was induced by propofol in both groups. In the total intravenous anesthesia (TIVA) group, anesthesia was maintained by propofol, while in the BOLUS group, volatile anesthesia was provided. The individual anesthetic charts and the full electronic medical records up to 30 postprocedural days were scrutinized. RESULTS: One hundred thirty-five BrS patients who underwent a total of 304 procedures were analyzed. The TIVA group included 27 patients for 33 procedures, and the BOLUS group included 108 patients for 271 procedures. In the TIVA group, the median time of propofol infusion was 60 minutes (interquartile range [IQR] = 30-180). The estimated plasma or effect-site concentration ranged between 1.0 and 6.0 µg·mL-1 for target-controlled infusion (TCI). The infusion rate for manually driven TIVA varied between 0.8 and 10.0 mg·kg-1·h-1. In the BOLUS group, the mean propofol dose per kilogram total body weight was 2.4 ± 0.9 mg·kg-1. No malignant arrhythmias or defibrillations were registered in both groups. The estimated 95% confidence interval (CI) of the risk for malignant arrhythmias in the BOLUS and TIVA groups was 0-0.011 and 0-0.091, respectively. CONCLUSIONS: The analysis of 304 anesthetic procedures in BrS patients, who received propofol, either as a TIVA or as a bolus during induction of volatile-based anesthesia, revealed no evidence of malignant arrhythmias or defibrillations. The present data do not support an increased risk with propofol-based TIVA compared to propofol-induced volatile anesthesia. Prospective studies are needed to investigate the electrophysiologic effects of propofol in BrS patents.

Mortality by opioid poisoning in children and teenagers and opioid prescriptions.

BACKGROUND: No comparisons between mortality from opioids in children and teenagers and opioid prescription patterns have been made in England. AIM: To investigate if an association exists between mortality rates from opioid poisoning in persons aged 19 years old and under and community opioid prescription in England. METHODS: A retrospective analysis was undertaken for 2016 to 2019, comparing community opioid prescriptions and mortality rates from opioid poisoning. RESULTS: The number of opioid prescriptions decreased over the study period (- 2.4%, p < 0.001). Most deaths due to opioid poisoning in children and teenagers were seen in those under one year old and those aged between 15 and 19 years old (Kruskal-Wallis: p = 0.12; Dunn's test: p = 0.01). Deaths in all age ranges did not change significantly (Poisson Regression Analysis: p > 0.05). CONCLUSION: Despite the reduction in community opioid prescriptions, there was no decrease in the number of deaths in children and teenagers due to opioid poisoning.

Exploratory Outlier Detection for Acceleromyographic Neuromuscular Monitoring: Machine Learning Approach.

BACKGROUND: Perioperative quantitative monitoring of neuromuscular function in patients receiving neuromuscular blockers has become internationally recognized as an absolute and core necessity in modern anesthesia care. Because of their kinetic nature, artifactual recordings of acceleromyography-based neuromuscular monitoring devices are not unusual. These generate a great deal of cynicism among anesthesiologists, constituting an obstacle toward their widespread adoption. Through outlier analysis techniques, monitoring devices can learn to detect and flag signal abnormalities. Outlier analysis (or anomaly detection) refers to the problem of finding patterns in data that do not conform to expected behavior. OBJECTIVE: This study was motivated by the development of a smartphone app intended for neuromuscular monitoring based on combined accelerometric and angular hand movement data. During the paired comparison stage of this app against existing acceleromyography monitoring devices, it was noted that the results from both devices did not always concur. This study aims to engineer a set of features that enable the detection of outliers in the form of erroneous train-of-four (TOF) measurements from an acceleromyographic-based device. These features are tested for their potential in the detection of erroneous TOF measurements by developing an outlier detection algorithm. METHODS: A data set encompassing 533 high-sensitivity TOF measurements from 35 patients was created based on a multicentric open label trial of a purpose-built accelero- and gyroscopic-based neuromuscular monitoring app. A basic set of features was extracted based on raw data while a second set of features was purpose engineered based on TOF pattern characteristics. Two cost-sensitive logistic regression (CSLR) models were deployed to evaluate the performance of these features. The final output of the developed models was a binary classification, indicating if a TOF measurement was an outlier or not. RESULTS: A total of 7 basic features were extracted based on raw data, while another 8 features were engineered based on TOF pattern characteristics. The model training and testing were based on separate data sets: one with 319 measurements (18 outliers) and a second with 214 measurements (12 outliers). The F1 score (95% CI) was 0.86 (0.48-0.97) for the CSLR model with engineered features, significantly larger than the CSLR model with the basic features (0.29 [0.17-0.53]; P<.001). CONCLUSIONS: The set of engineered features and their corresponding incorporation in an outlier detection algorithm have the potential to increase overall neuromuscular monitoring data consistency. Integrating outlier flagging algorithms within neuromuscular monitors could potentially reduce overall acceleromyography-based reliability issues. TRIAL REGISTRATION: ClinicalTrials.gov NCT03605225; https://clinicaltrials.gov/ct2/show/NCT03605225.

Persistent postoperative opioid use in Europe: A systematic review.

BACKGROUND: In the United States, postoperative opioid prescriptions have been implicated in the so-called 'opioid epidemic'. In Europe, the extent of overprescribing or misuse of opioids is not known. OBJECTIVES: To describe the proportion of persistent postoperative opioid use in adults (>18 years) in European countries. DESIGN: Systematic review of the published data. DATA SOURCES: We searched the electronic literature databases MEDLINE (Ovid), Embase (Ovid), PubMed/MEDLINE and Scopus. ELIGIBILITY CRITERIA: Studies describing opioid use in adult patients (>18 years) at least 3 months after surgery. RESULTS: One thousand three hundred and seven studies were found, and 12 studies were included in this review. The rate of opioid use after 3 to 6 months was extracted from the studies and categorised by the type of surgery. Nine studies investigated opioid use after total hip or total knee arthroplasties (THA and TKA) and reported opioid user rates between 7.9 and 41% after 3 months. In all the included studies, a proportion between 2 and 41% of patients were opioid users 3 months after surgery. The level of evidence varied from high to very low. CONCLUSION: To describe persistent opioid use in relation to specific countries or types of surgery is not possible. Because of the wide ranges observed, we can neither confirm nor rule out a possible public health problem linked to the persistent use of opioids in Europe. STUDY REGISTRATION: PROSPERO: CRD42019154292.

High-Dose Spinal Cord Stimulation Reduces Long-Term Pain Medication Use in Patients With Failed Back Surgery Syndrome Who Obtained at Least 50% Pain Intensity and Medication Reduction During a Trial Period: A Registry-Based Cohort Study.

OBJECTIVES: High-dose spinal cord stimulation (HD-SCS) revealed positive results for obtaining pain relief in patients with failed back surgery syndrome (FBSS). However, it is less clear whether HD-SCS also is able to reduce pain medication use. The aim of this registry-based cohort study is to explore the impact of HD-SCS on pain medication use in FBSS patients. MATERIALS AND METHODS: Data from the Discover registry was used in which the effectiveness of HD-SCS was explored in neurostimulation-naïve FBSS patients as well as in rescue patients. All neurostimulation-naïve FBSS patients positively responded to a four-week SCS trial period in which at least 50% pain relief and 50% medication reduction were obtained. Medication use was measured with the Medication Quantification Scale III (MQS) in 259 patients at baseline and at 1, 3, and 12 months of HD-SCS. Additionally, defined daily doses (DDD) and morphine milligram equivalents (MME) were calculated as well. RESULTS: One hundred thirty patients reached the visit at 12 months. In neurostimulation-naïve patients, a statistically significant decrease in MQS (χ2 = 62.92, p < 0.001), DDD (χ2 = 11.47, p = 0.009), and MME (χ2 = 21.55, p < 0.001) was found. In rescue patients, no statistically significant improvements were found. In both patient groups, statistically significant reductions in the proportion of patients on high-risk MME doses ≥90 were found over time. At the intraindividual level, positive correlations were found between MSQ scores and pain intensity for back (r = 0.56, r = 0.31, p < 0.001) and leg pain (r = 0.61, r = 0.22, p < 0.001) in neurostimulation-naïve and rescue patients, respectively. CONCLUSIONS: Registry data on HD-SCS in FBSS patients revealed a statistically significant and sustained decrease in pain medication use, not only on opioids, but also on anti-neuropathic agents in neurostimulation-naïve patients, who positively responded to an SCS trial period with at least 50% pain relief and 50% pain medication decrease, but not in rescue patients.