Is adamgammadex the brother of sugammadex or the next generation of reversal agent?

Sugammadex is now in widespread use to reverse the neuromuscular blocking effects of rocuronium. Adverse effects from sugammadex are rare, but anaphylactic and cardiovascular reactions to the drug have been reported. In an attempt to reduce such side-effects, a modified gamma-cyclodextrin, adamgammadex, has been developed. Phase 3 clinical trials suggest that it is slightly less potent than sugammadex and has a non-inferior speed of onset. In a multicentre trial of 310 patients, there was a suggestion of a lower incidence of allergic responses and recurarisation after adamgammadex compared with sugammadex. The clinical implications of this study are discussed in this editorial.

Under-dosing and over-dosing of neuromuscular blocking drugs and reversal agents: beware of the risks.

The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium were well recognised 60 years ago. But the incidence seemed to decline with the introduction of atracurium and vecuronium. However, recently there have been an increasing number of reports of residual and recurrent neuromuscular block. Some of these reports are a result of inappropriate doses of rocuronium, sugammadex or both, together with inadequate neuromuscular monitoring. We urge clinicians to review their practice to ensure the highest standards of clinical care when using neuromuscular blocking drugs and reversal agents. This includes the use of quantitative neuromuscular monitoring whenever neuromuscular blocking drugs are administered.

Using Unsupervised Machine Learning to Predict Quality of Life After Total Knee Arthroplasty.

BACKGROUND: Patient-reported outcome measures (PROMs) are an important metric to assess total knee arthroplasty (TKA) patients. The purpose of this study was to use a machine learning (ML) algorithm to identify patient features that impact PROMs after TKA. METHODS: Data from 636 TKA patients enrolled in our patient database between 2018 and 2022, were retrospectively reviewed. Their mean age was 68 years (range, 39 to 92), 56.7% women, and mean body mass index of 31.17 (range, 16 to 58). Patient demographics and the Functional Comorbidity Index were collected alongside Patient-Reported Outcome Measures Information System Global Health v1.2 (PROMIS GH-P) physical component scores preoperatively, at 3 months, and 1 year after TKA. An unsupervised ML algorithm (spectral clustering) was used to identify patient features impacting PROMIS GH-P scores at the various time points. RESULTS: The algorithm identified 5 patient clusters that varied by demographics, comorbidities, and pain scores. Each cluster was associated with predictable trends in PROMIS GH-P scores across the time points. Notably, patients who had the worst preoperative PROMIS GH-P scores (cluster 5) had the most improvement after TKA, whereas patients who had higher global health rating preoperatively had more modest improvement (clusters 1, 2, and 3). Two out of Five patient clusters (cluster 4 and 5) showed improvement in PROMIS GH-P scores that met a minimally clinically important difference at 1-year postoperative. CONCLUSIONS: The unsupervised ML algorithm identified patient clusters that had predictable changes in PROMs after TKA. It is a positive step toward providing precision medical care for each of our arthroplasty patients.

Outbreaks of SARS-CoV-2 Infections in Nursing Homes during Periods of Delta and Omicron Predominance, United States, July 2021-March 2022.

SARS-CoV-2 infections among vaccinated nursing home residents increased after the Omicron variant emerged. Data on booster dose effectiveness in this population are limited. During July 2021-March 2022, nursing home outbreaks in 11 US jurisdictions involving >3 infections within 14 days among residents who had received at least the primary COVID-19 vaccine(s) were monitored. Among 2,188 nursing homes, 1,247 outbreaks were reported in the periods of Delta (n = 356, 29%), mixed Delta/Omicron (n = 354, 28%), and Omicron (n = 536, 43%) predominance. During the Omicron-predominant period, the risk for infection within 14 days of an outbreak start was lower among boosted residents than among residents who had received the primary vaccine series alone (risk ratio [RR] 0.25, 95% CI 0.19-0.33). Once infected, boosted residents were at lower risk for all-cause hospitalization (RR 0.48, 95% CI 0.40-0.49) and death (RR 0.45, 95% CI 0.34-0.59) than primary vaccine-only residents.

'To see ourselves as others see us'.

Shaw and colleagues, who are medical historians, have published a detailed review of the social history of the British Journal of Anaesthesia (BJA) to celebrate its first 100 years. In this editorial, we note some additional contributions and financial details that are relevant to the development of the BJA into the international high-impact journal it is today.

Educating anaesthetists on neuromuscular monitoring: the challenges continue.

The need to introduce guidelines on neuromuscular monitoring emphasising the use of quantitative techniques that record the train-of-four ratio is now recognised by an increasing number of national anaesthetic societies in the Western world. But the challenge of convincing individual anaesthetists to adopt and use this practice routinely remains. For >10 yr, it has been recognised that all staff in anaesthetic departments need to have regular training in modern neuromuscular monitoring techniques. We discuss a publication in this journal that describes the challenges of setting up multicentre training in Spain to expand the use of quantitative neuromuscular monitoring and their short-term results.

How robust are the STRONGER and STIL-STRONGER studies?

In 2020, the Sugammadex vs Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER) study provided evidence for the first time that use of sugammadex is associated with fewer postoperative pulmonary complications than use of neostigmine. In a recent publication in the British Journal of Anaesthesia, a secondary analysis of the same data, the Association Between Neuromuscular Blockade Reversal Agent Choice and Postoperative Pulmonary Complications (STIL-STRONGER) study, has produced similar evidence of the advantages of sugammadex over neostigmine in high-risk and older patients undergoing prolonged, elective surgery. Here we consider the implications of the detailed statistical analysis used in these two studies and how its limitations could possibly have enhanced the statistical differences between the two drugs with respect to postoperative pulmonary complications.

The evolution of the British Journal of Anaesthesia: the first 100 years.

At this centenary of the British Journal of Anaesthesia (BJA) in 2023, six of its 12 editors/editors-in-chief detail developments over the decades that have led to the BJA becoming a high-impact international scientific journal. As a charity, the BJA supports academic research and training in anaesthesia, critical care, and pain medicine including funding of research grants and postgraduate education. Building on this foundation, the BJA continues to innovate as it aims to become fully electronic, expand into open access publishing, and increase the diversity of its editorial board.

Predicting Food Sources of Listeria monocytogenes Based on Genomic Profiling Using Random Forest Model.

Listeria monocytogenes can cause severe foodborne illness, including miscarriage during pregnancy or death in newborn infants. When outbreaks of L. monocytogenes illness occur, it may be possible to determine the food source of the outbreak. However, most reported L. monocytogenes illnesses do not occur as part of a recognized outbreak and most of the time the food source of sporadic L. monocytogenes illness in people cannot be determined. In the United States, L. monocytogenes isolates from patients, foods, and environments are routinely sequenced and analyzed by whole genome multilocus sequence typing (wgMLST) for outbreak detection by PulseNet, the national molecular surveillance system for foodborne illnesses. We investigated whether machine learning approaches applied to wgMLST allele call data could assist in attribution analysis of food source of L. monocytogenes isolates. We compiled isolates with a known source from five food categories (dairy, fruit, meat, seafood, and vegetable) using the metadata of L. monocytogenes isolates in PulseNet, deduplicated closely genetically related isolates, and developed random forest models to predict the food sources of isolates. Prediction accuracy of the final model varied across the food categories; it was highest for meat (65%), followed by fruit (45%), vegetable (45%), dairy (44%), and seafood (37%); overall accuracy was 49%, compared with the naive prediction accuracy of 28%. Our results show that random forest can be used to capture genetically complex features of high-resolution wgMLST for attribution of isolates to their sources.

Gender disparity in academic orthopedic programs in Canada: a cross-sectional study.

BACKGROUND: The majority of the literature on gender disparity in orthopedic surgery is from the United States; the Canadian perspective is lacking. The objective of this study was to determine the representation of women faculty members and the proportion of women faculty in published leadership positions in academic orthopedic divisions and departments across Canada. METHODS: In this cross-sectional study, we used a Web-based search strategy to identify faculty listings for all 17 academic orthopedic programs affiliated with the Association of Faculties of Medicine of Canada for the 2018/19 academic year. For each faculty member identified, we determined gender (man or woman), professorial rank and leadership positions. We compared regional gender differences among 3 groups: schools in eastern Canada and Quebec (6), Ontario (6) and western Canada (5). Gender comparisons were made for all variables of interest. RESULTS: We identified 809 orthopedic surgeons at the 17 Canadian academic institutions, of whom 96 (11.9%) were women. In eastern Canada and Quebec, 16.2% of the faculty were women, significantly above the national average (p = 0.03). The corresponding values for Ontario and western Canada were 8.9% (p = 0.1) and 11.4% (p = 0.7). There were no significant differences in the proportions of women and men at lower levels of promotion, but significantly more men than women had attained full professorship (65 [9%] v. 1 [1%], p = 0.002). Women surgeons were not represented in leadership roles or within faculty roles of distinction. CONCLUSION: In 2018/19, women orthopedic surgeons were underrepresented in faculty positions across academic orthopedic training programs in Canada, and were disproportionately underrepresented in promoted academic faculty roles and leadership positions. These data can be used to review and educate on equity in hiring and promotion, as well as to foster mentorship and transition planning.

Evaluation of a Virtual Training to Enhance Public Health Capacity for COVID-19 Infection Prevention and Control in Nursing Homes.

CONTEXT: Between April 2020 and May 2021, the Centers for Disease Control and Prevention (CDC) awarded more than $40 billion to health departments nationwide for COVID-19 prevention and response activities. One of the identified priorities for this investment was improving infection prevention and control (IPC) in nursing homes. PROGRAM: CDC developed a virtual course to train new and less experienced public health staff in core healthcare IPC principles and in the application of CDC COVID-19 healthcare IPC guidance for nursing homes. IMPLEMENTATION: From October 2020 to August 2021, the CDC led training sessions for 12 cohorts of public health staff using pretraining reading materials, case-based scenarios, didactic presentations, peer-learning opportunities, and subject matter expert-led discussions. Multiple electronic assessments were distributed to learners over time to measure changes in self-reported knowledge and confidence and to collect feedback on the course. Participating public health programs were also assessed to measure overall course impact. EVALUATION: Among 182 enrolled learners, 94% completed the training. Most learners were infection preventionists (42%) or epidemiologists (38%), had less than 1 year of experience in their health department role (75%), and had less than 1 year of subject matter experience (54%). After training, learners reported increased knowledge and confidence in applying the CDC COVID-19 healthcare IPC guidance for nursing homes (≥81%) with the greatest increase in performing COVID-19 IPC consultations and assessments (87%). The majority of participating programs agreed that the course provided an overall benefit (88%) and reduced training burden (72%). DISCUSSION: The CDC's virtual course was effective in increasing public health capacity for COVID-19 healthcare IPC in nursing homes and provides a possible model to increase IPC capacity for other infectious diseases and other healthcare settings. Future virtual healthcare IPC courses could be enhanced by tailoring materials to health department needs, reinforcing training through applied learning experiences, and supporting mechanisms to retain trained staff.

Investigation of a Suspect Severe Acute Respiratory Syndrome Coronavirus-2 and Influenza A Mixed Outbreak: Lessons Learned for Long-Term Care Facilities Nationwide.

A suspected outbreak of influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at a long-term care facility in Los Angeles County was, months later, determined to not involve influenza. To prevent inadvertent transmission of infections, facilities should use highly specific influenza diagnostics and follow Centers for Disease Control and Prevention (CDC) guidelines that specifically address infection control challenges.

First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. METHODS: Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient's symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested. FINDINGS: Patient 1-a woman in her 60s-returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2. INTERPRETATION: Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected. FUNDING: None.

Implementing a digital mental health intervention for individuals with psychosis - a multi-country qualitative study.

BACKGROUND: Implementation of psychosocial interventions in mental health services has the potential to improve the treatment of psychosis spectrum disorders (PSD) in low- and middle-income countries (LMICs) where care is predominantly focused on pharmacotherapy. The first step is to understand the views of key stakeholders. We conducted a multi-language qualitative study to explore the contextual barriers and facilitators to implementation of a cost-effective, digital psychosocial intervention, called DIALOG+, for treating PSD. DIALOG+ builds on existing clinician-patient relationships without requiring development of new services, making it well-fitting for healthcare systems with scarce resources. METHODS: Thirty-two focus groups were conducted with 174 participants (patients, clinicians, policymakers and carers), who were familiarized with DIALOG+ through a presentation. The Southeast European LMICs included in this research were: Bosnia and Herzegovina, Kosovo, (Kosovo is referred throughout the text by United Nations resolution) North Macedonia, Montenegro and Serbia. Framework analysis was used to analyse the participants' accounts. RESULTS: Six major themes were identified. Three themes (Intervention characteristics; Carers' involvement; Patient and organisational benefits) were interpreted as perceived implementation facilitators. The theme Attitudes and perceived preparedness of potential adopters comprised of subthemes that were interpreted as both perceived implementation facilitators and barriers. Two other themes (Frequency of intervention delivery; Suggested changes to the intervention) were more broadly related to the intervention's implementation. Participants were exceedingly supportive of the implementation of a digital psychosocial intervention such as DIALOG+. Attractive intervention characteristics, efficient use of scarce resources for its implementation and potential to improve mental health services were seen as the main implementation facilitators. The major implementation barrier identified was psychiatrists' time constrains. CONCLUSIONS: This study provided important insights regarding implementation of digital psychosocial interventions for people with PSD in low-resource settings by including perspectives from four stakeholder groups in five LMICs in Southeast Europe - a population and region rarely explored in the literature. The perceived limited availability of psychiatrists could be potentially resolved by increased inclusion of other mental health professionals in service delivery for PSD. These findings will be used to inform the implementation strategy of DIALOG+ across the participating countries. The study also offers insights into multi-country qualitative research.

Zooming in on mechanistic predator-prey ecology: Integrating camera traps with experimental methods to reveal the drivers of ecological interactions.

Camera trap technology has galvanized the study of predator-prey ecology in wild animal communities by expanding the scale and diversity of predator-prey interactions that can be analysed. While observational data from systematic camera arrays have informed inferences on the spatiotemporal outcomes of predator-prey interactions, the capacity for observational studies to identify mechanistic drivers of species interactions is limited. Experimental study designs that utilize camera traps uniquely allow for testing hypothesized mechanisms that drive predator and prey behaviour, incorporating environmental realism not possible in the laboratory while benefiting from the distinct capacity of camera traps to generate large datasets from multiple species with minimal observer interference. However, such pairings of camera traps with experimental methods remain underutilized. We review recent advances in the experimental application of camera traps to investigate fundamental mechanisms underlying predator-prey ecology and present a conceptual guide for designing experimental camera trap studies. Only 9% of camera trap studies on predator-prey ecology in our review use experimental methods, but the application of experimental approaches is increasing. To illustrate the utility of camera trap-based experiments using a case study, we propose a study design that integrates observational and experimental techniques to test a perennial question in predator-prey ecology: how prey balance foraging and safety, as formalized by the risk allocation hypothesis. We discuss applications of camera trap-based experiments to evaluate the diversity of anthropogenic influences on wildlife communities globally. Finally, we review challenges to conducting experimental camera trap studies. Experimental camera trap studies have already begun to play an important role in understanding the predator-prey ecology of free-living animals, and such methods will become increasingly critical to quantifying drivers of community interactions in a rapidly changing world. We recommend increased application of experimental methods in the study of predator and prey responses to humans, synanthropic and invasive species, and other anthropogenic disturbances.

Use of a train-of-four ratio of 0.95 versus 0.9 for tracheal extubation: an exploratory analysis of POPULAR data.

BACKGROUND: The prospective observational European multicentre cohort study (POPULAR) of postoperative pulmonary complications (NCT01865513) did not demonstrate that adherence to the recommended train-of-four ratio (TOFR) of 0.9 before extubation was associated with better pulmonary outcomes from the first postoperative day up to hospital discharge. We re-analysed the POPULAR data as to whether there existed a better threshold for TOFR recovery before extubation to reduce postoperative pulmonary complications in patients who had quantitative neuromuscular monitoring (87% acceleromyography). METHODS: To identify the optimal TOFR, the complete case cohort of patients with quantitative neuromuscular monitoring (n=3150) was split into several pairs of sub-cohorts related to TOFR values from 0.86 to 0.96; values of 0.97 and higher could not be used as the sub-cohorts were too small. The optimal TOFR was considered to have the lowest P-value from multivariate logistic regression calculated for each of the TOFR values. Data are presented as adjusted absolute risk reduction or median difference with 95% confidence interval. RESULTS: Extubating patients with TOFR >0.95 rather than >0.9 reduced the adjusted risk of postoperative pulmonary complications by 3.5% (0.7-6.0%) from that reported in POPULAR (11.3%). Increasing the recommended TOFR from 0.9 to 0.95 reduced the adjusted risk by 4.9% (1.2-8.5%). Sub-cohorts resulting from 1:1 propensity score matching revealed that sugammadex had been given in higher doses by 0.30 (0.13-0.48) mg kg-1 in the sub-cohort with TOFR > 0.95. CONCLUSIONS: A post hoc analysis of patients receiving quantitative monitoring of neuromuscular function suggests that postoperative pulmonary complications are reduced for TOFR > 0.95 before tracheal extubation compared with TOFR > 0.9. TRIAL REGISTRATION NUMBER: NCT01865513.

Imaging individual neurons in the retinal ganglion cell layer of the living eye.

Although imaging of the living retina with adaptive optics scanning light ophthalmoscopy (AOSLO) provides microscopic access to individual cells, such as photoreceptors, retinal pigment epithelial cells, and blood cells in the retinal vasculature, other important cell classes, such as retinal ganglion cells, have proven much more challenging to image. The near transparency of inner retinal cells is advantageous for vision, as light must pass through them to reach the photoreceptors, but it has prevented them from being directly imaged in vivo. Here we show that the individual somas of neurons within the retinal ganglion cell (RGC) layer can be imaged with a modification of confocal AOSLO, in both monkeys and humans. Human images of RGC layer neurons did not match the quality of monkey images for several reasons, including safety concerns that limited the light levels permissible for human imaging. We also show that the same technique applied to the photoreceptor layer can resolve ambiguity about cone survival in age-related macular degeneration. The capability to noninvasively image RGC layer neurons in the living eye may one day allow for a better understanding of diseases, such as glaucoma, and accelerate the development of therapeutic strategies that aim to protect these cells. This method may also prove useful for imaging other structures, such as neurons in the brain.

Coverage of cancer services in Australia and providers' views on service gaps: findings from a national cross-sectional survey.

BACKGROUND: In response to the increasing cancer prevalence and the evolving health service landscape across the public and private health sectors in Australia, this study aimed to map cancer services and identify factors associated with service provision and important service gaps. METHODS: A prospective, cross-sectional survey was conducted throughout 2016. Extensive search strategies identified Government or privately-owned, hospital or community-based healthcare organisations with dedicated cancer services. One nominated staff member from each organisation answered a purpose specific online/paper questionnaire. Descriptive statistics, standardised rates, and single level and multilevel multinomial logistic regression were used to analyse the data. Analysis was augmented with a qualitative descriptive analysis of open-ended questions. RESULTS: From the 295 eligible organisations with a cancer service in Australia, 93.2% participated in the survey. After adjusting for remoteness, for-profit companies were significantly more likely than Government operated services to provide only one or two types of cancer services (e.g. radiotherapy) in a limited range of settings (e.g. day hospital with no in-patient or home care) (p < 0.001) and less likely to provide comprehensive cancer services (p < 0.001). After adjusting for ownership and the respondent's role in the organisation, respondents located in remote regions of Australia were more likely to identify cancer services that are dependent upon specialist medical practitioners as the most important service gaps in their region (p = 0.003). Despite 76.0% of organisations across Australia offering some type of supportive care or survivorship services, providers identified this group of services as the most pressing service gaps in major cities, rural and remote regions alike (standardised rate: 47.9% (95%CI: 43.6-57.4%); p < .000). This included the need for improved integration, outreach and affordability. CONCLUSIONS: The broad range of cancer services, settings and ownership identified by this survey highlights the complexity of the Australian healthcare system that cancer survivors must navigate and the challenges of providing comprehensive cancer care particularly in rural and remote regions. Whilst the significant role of supportive care and survivorship services are increasingly being recognised, the findings from this survey support calls for innovative service models and funding mechanisms that expand the focus from preventing and treating cancer to supporting cancer survivors throughout the cancer continuum and promoting the delivery of integrated and equitable cancer care across the public and private sectors.

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: infection and sepsis.

BACKGROUND: Perioperative infection and sepsis are of fundamental concern to perioperative clinicians. However, standardised endpoints are either poorly defined or not routinely implemented. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of infection and sepsis used in the perioperative literature. A multi-round Delphi consensus process that included more than 60 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: A literature search yielded 1857 titles of which 255 met inclusion criteria for endpoint extraction. A long list of endpoints, with definitions and timescales, was generated and those potentially relevant to infection and sepsis circulated to the theme subgroup and then the wider StEP-COMPAC working group, undergoing a three-stage Delphi process. The response rates for Delphi rounds 1, 3, and 3 were 89% (n=8), 67% (n=62), and 80% (n=8), respectively. A set of 13 endpoints including fever, surgical site, and organ-specific infections as defined by the US Centres for Disease Control and Sepsis-3 are proposed for future use. CONCLUSIONS: We defined a consensus list of standardised endpoints related to infection and sepsis for perioperative trials using an established and rigorous approach. Each endpoint was evaluated with respect to validity, reliability, feasibility, and patient centredness. One or more of these should be considered for inclusion in future perioperative clinical trials assessing infection, sepsis, or both, thereby permitting synthesis and comparison of future results.