Interrupting Endocrine Therapy to Attempt Pregnancy after Breast Cancer.

BACKGROUND: Prospective data on the risk of recurrence among women with hormone receptor-positive early breast cancer who temporarily discontinue endocrine therapy to attempt pregnancy are lacking. METHODS: We conducted a single-group trial in which we evaluated the temporary interruption of adjuvant endocrine therapy to attempt pregnancy in young women with previous breast cancer. Eligible women were 42 years of age or younger; had had stage I, II, or III disease; had received adjuvant endocrine therapy for 18 to 30 months; and desired pregnancy. The primary end point was the number of breast cancer events (defined as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer) during follow-up. The primary analysis was planned to be performed after 1600 patient-years of follow-up. The prespecified safety threshold was the occurrence of 46 breast cancer events during this period. Breast cancer outcomes in this treatment-interruption group were compared with those in an external control cohort consisting of women who would have met the entry criteria for the current trial. RESULTS: Among 516 women, the median age was 37 years, the median time from breast cancer diagnosis to enrollment was 29 months, and 93.4% had stage I or II disease. Among 497 women who were followed for pregnancy status, 368 (74.0%) had at least one pregnancy and 317 (63.8%) had at least one live birth. In total, 365 babies were born. At 1638 patient-years of follow-up (median follow-up, 41 months), 44 patients had a breast cancer event, a result that did not exceed the safety threshold. The 3-year incidence of breast cancer events was 8.9% (95% confidence interval [CI], 6.3 to 11.6) in the treatment-interruption group and 9.2% (95% CI, 7.6 to 10.8) in the control cohort. CONCLUSIONS: Among select women with previous hormone receptor-positive early breast cancer, temporary interruption of endocrine therapy to attempt pregnancy did not confer a greater short-term risk of breast cancer events, including distant recurrence, than that in the external control cohort. Further follow-up is critical to inform longer-term safety. (Funded by ETOP IBCSG Partners Foundation and others; POSITIVE ClinicalTrials.gov number, NCT02308085.).

Adjuvant platinum versus capecitabine for residual, invasive, triple-negative breast cancer: Patient-reported outcomes in ECOG-ACRIN EA1131.

BACKGROUND: Patient-reported outcomes (PROs) are a better tool for evaluating the experiences of patients who have symptomatic, treatment-associated adverse events (AEs) compared with clinician-rated AEs. The authors present PROs assessing health-related quality of life (HRQoL) and treatment-related neurotoxicity for adjuvant capecitabine versus platinum on the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) EA1131 trial (ClinicalTrials.gov identifier NCT02445391). METHODS: Participants completed the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) and the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale (platinum arm only) at baseline, cycle 3 day 1 (C3D1), 6 months, and 15 months. Because of early termination, power was insufficient to test the hypothesis that HRQoL, as assessed by the NFBSI-16 treatment side-effect (TSE) subscale, would be better at 6 and 15 months in the capecitabine arm; all analyses were exploratory. Means were compared by using t-tests or the Wilcoxon rank-sum test, and proportions were compared by using the χ2 test. RESULTS: Two hundred ninety-six of 330 eligible patients provided PROs. The mean NFBSI-16 TSE subscale score was lower for the platinum arm at baseline (p = .02; absolute difference, 0.6 points) and for the capecitabine arm at C3D1 (p = .04; absolute difference, 0.5 points), but it did not differ at other times. The mean change in TSE subscale scores differed between the arms from baseline to C3D1 (platinum arm, 0.15; capecitabine arm, -0.72; p = .03), but not from baseline to later time points. The mean decline in Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale scores exceeded the minimal meaningful change (1.38 points) from baseline to each subsequent time point (all p < .05). CONCLUSIONS: Despite the similar frequency of clinician-rated AEs, PROs identified greater on-treatment symptom burden with capecitabine and complemented clinician-rated AEs by characterizing patients' experiences during chemotherapy.

Attempted replication of pharmacogenetic association of variants in PPP1R14C and CCDC148 with aromatase inhibitor-induced musculoskeletal symptoms.

Third-generation aromatase inhibitors (AI) are the standard treatment for patients with hormone receptor positive (HR+) breast cancer. While effective, AI can lead to severe adverse events, including AI-induced musculoskeletal syndrome (AIMSS). Genetic predictors of AIMSS have the potential to personalize AI treatment and improve outcomes. We attempted to replicate results from a previous genome-wide association study that found a lower risk of AIMSS in patients carrying PPP1R14C rs912571 and a higher risk in patients carrying CCDC148 rs79048288. AIMSS data were collected prospectively from patients with HR+ breast cancer prior to starting and after 3 and 6 months of adjuvant AI via the Patient-Reported Outcome Measurement Information System and Functional Assessment of Cancer Therapy-Endocrine Symptom. Germline genotypes for PPP1R14C rs912571 and CCDC148 rs79048288 were tested for a similar association with AIMSS as previously reported via $2 tests. Of the 143 patients with AIMSS and genetics data were included in the analysis. There was no association identified between PPP1R14C rs912571 and AIMSS risk ( P  > 0.05). Patients carrying CCDC148 rs79048288 variant alleles had lower AIMSS incidence in a secondary analysis ( P  = 0.04); however, this was in the opposite direction of the previous finding. The study did not replicate previously reported associations with AIMSS risk for genetic variants in PPP1R14C and CCDC148 and AIMSS risk. Further research is needed to discover and validate genetic predictors of AIMSS that can be used to personalize treatment in patients with HR+ breast cancer.

The Lancet Commission to reduce the global burden of sudden cardiac death: a call for multidisciplinary action.

Despite major advancements in cardiovascular medicine, sudden cardiac death (SCD) continues to be an enormous medical and societal challenge, claiming millions of lives every year. Efforts to prevent SCD are hampered by imperfect risk prediction and inadequate solutions to specifically address arrhythmogenesis. Although resuscitation strategies have witnessed substantial evolution, there is a need to strengthen the organisation of community interventions and emergency medical systems across varied locations and health-care structures. With all the technological and medical advances of the 21st century, the fact that survival from sudden cardiac arrest (SCA) remains lower than 10% in most parts of the world is unacceptable. Recognising this urgent need, the Lancet Commission on SCD was constituted, bringing together 30 international experts in varied disciplines. Consistent progress in tackling SCD will require a completely revamped approach to SCD prevention, with wide-sweeping policy changes that will empower the development of both governmental and community-based programmes to maximise survival from SCA, and to comprehensively attend to survivors and decedents' families after the event. International collaborative efforts that maximally leverage and connect the expertise of various research organisations will need to be prioritised to properly address identified gaps. The Commission places substantial emphasis on the need to develop a multidisciplinary strategy that encompasses all aspects of SCD prevention and treatment. The Commission provides a critical assessment of the current scientific efforts in the field, and puts forth key recommendations to challenge, activate, and intensify efforts by both the scientific and global community with new directions, research, and innovation to reduce the burden of SCD worldwide.

Tranexamic Acid for Traumatic Injury in the Emergency Setting: A Systematic Review and Bias-Adjusted Meta-Analysis of Randomized Controlled Trials.

STUDY OBJECTIVE: Traumatic injury causes a significant number of deaths due to bleeding. Tranexamic acid (TXA), an antifibrinolytic agent, can reduce bleeding in traumatic injuries and potentially enhance outcomes. Previous reviews suggested potential TXA benefits but did not consider the latest trials. METHODS: A systematic review and bias-adjusted meta-analysis were performed to assess TXA's effectiveness in emergency traumatic injury settings by pooling estimates from randomized controlled trials. Researchers searched Medline, Embase, and Cochrane Central for randomized controlled trials comparing TXA's effects to a placebo in emergency trauma cases. The primary endpoint was 1-month mortality. The methodological quality of the trials underwent assessment using the MASTER scale, and the meta-analysis applied the quality-effects method to adjust for methodological quality. RESULTS: Seven randomized controlled trials met the set criteria. This meta-analysis indicated an 11% decrease in the death risk at 1 month after TXA use (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.84 to 0.95) with a number needed to treat of 61 to avoid 1 additional death. The meta-analysis also revealed reduced 24-hour mortality (OR 0.76, 95% CI 0.65 to 0.88) for TXA. No compelling evidence of increased vascular occlusive events emerged (OR 0.96, 95% CI 0.73 to 1.27). Subgroup analyses highlighted TXA's effectiveness in general trauma versus traumatic brain injury and survival advantages when administered out-of-hospital versus inhospital. CONCLUSIONS: This synthesis demonstrates that TXA use for trauma in emergencies leads to a reduction in 1-month mortality, with no significant evidence of problematic vascular occlusive events. Administering TXA in the out-of-hospital setting is associated with reduced mortality compared to inhospital administration, and less mortality with TXA in systemic trauma is noted compared with traumatic brain injury specifically.

Factors Associated with Lost Time Injury among Paramedics in Victoria, Australia.

BACKGROUND: The dynamic and uncontrolled nature of paramedic work frequently exposes these workers to physical and psychological injury. Often paramedic injury rates are estimated based on national injury surveillance data or compensation databases. These data sources tend to only capture cases of a more serious nature and overlook the broader factors that contribute to injury. This limits our understanding of the true burden of paramedic injury and the characteristics associated with increased injury severity. OBJECTIVES: To describe the incidence and proportions of paramedic occupational injury in Victoria, Australia, and to determine the injury-related characteristics associated with lost time from work. METHODS: A retrospective analysis of paramedic injury report data from the single state-wide ambulance service in Victoria, Australia - Ambulance Victoria. Injuries reported between 1 January 2015 and 30 June 2020 were included. Chi-square tests of independence were used to explore shift and injury characteristic variables that may be associated with time lost from work. RESULTS: Over the study period, 7,591 paramedic injuries were reported that met the inclusion criteria, of which 2,124 (28%) resulted in lost time from work. The cumulative incidence of paramedic injury was 333.8 injuries per 1,000 FTE workers per year, and the rate of lost time injury was 93.0 per 1,000 FTE workers per year. Musculoskeletal injuries were the most frequently reported injury type irrespective of lost time status. Manual handling followed by psychological stressors were the two leading mechanisms of injury based on incidence. Psychological injury was associated with lost time from work (X2= 384.2, p < 0.001). Conversely, injury to the head and neck (X2= 7.5, p = 0.006), and upper limb injuries (X2= 104.5, p < 0.001), were more strongly associated with no lost time from work. CONCLUSIONS: Paramedics working in Victoria have a higher rate of work-related injury than other Australian workers. Injury-related factors that are often overlooked, such as time, shift type, location, and injury characteristics, all contribute to an increased risk of lost time injury. An understanding of the factors that contribute to an increase in injury severity may facilitate the development and targeting of appropriate interventions.

Characteristics and Outcomes of Patients Referred to a General Practitioner by Victorian Paramedics.

OBJECTIVE: Many patients who are attended by paramedics do not require conveyance to an emergency department (ED). Our study focuses on comparing the characteristics and outcomes of patients who were advised to follow up with a general practitioner (GP) by an attending paramedic with those of patients who were discharged at scene or transported to hospital. METHODS: This was a retrospective data linkage cohort study of ambulance, ED, hospital admission, and death records for all adults attended by paramedics in Victoria, Australia between the 1st of January 2015 and 30th of June 2019. Patients were excluded if they presented in cardiac arrest, resided in a residential aged care facility, or were receiving palliative care services. Outcomes of interest included reattendance by ambulance, ED presentation; and, a high acuity outcome which we defined as a patient who (1) presented to ED and received an Australasian Triage Scale of category 1 (Resuscitation) or 2 (Emergency) AND was admitted to a ward OR (2) was admitted to an Intensive Care Unit, Coronary Care Unit or Catheter laboratory (regardless of triage category) OR (3) died. Outcomes of interest were considered within 48-h of initial EMS attendance. RESULTS: A total of 1,777,950 cases were included in the study of which 3.1% were referred to a GP, 9.0% were discharged at scene without a follow-up recommendation, and 87.9% were transported to hospital. Patients referred to a GP were more likely than those discharged at scene to subsequently present to an ED within 48 h of their attendance (5.3% vs 3.8%). However, GP referral was not associated with any change to high acuity outcome (0.3% vs 0.2%) or ambulance reattendance (6.0% vs 6.0%) compared to discharge at scene. The only factors that were associated with ambulance reattendance, ED presentation, and a high acuity outcome were male gender and elevated temperature. CONCLUSIONS: Despite increasing low and medium-acuity casework in this EMS system, paramedic referral to a GP is not common practice. Referring a patient to a GP did not reduce the likelihood of patients experiencing a high acuity outcome or recalling an ambulance within 48 h, suggesting opportunity exists to refine paramedic to GP referral practices.

Prevalence and Predictors of Emergency Medical Service Use in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

AIM: We aim to describe prevalence of Emergency Medical Service (EMS) use, investigate factors predictive of EMS use, and determine if EMS use predicts treatment delay and mortality in our ST-elevation myocardial infarction (STEMI) cohort. METHOD: We prospectively collected data on 5,602 patients presenting with STEMI for primary percutaneous coronary intervention (PCI) transported to PCI-capable hospitals in Victoria, Australia, from 2013-2018 who were entered into the Victorian Cardiac Outcomes Registry (VCOR). We linked this dataset to the Ambulance Victoria and National Death Index (NDI) datasets. We excluded late presentation, thrombolysed, and in-hospital STEMI, as well as patients presenting with cardiogenic shock and out-of-hospital cardiac arrest. RESULTS: In total, 74% of patients undergoing primary PCI for STEMI used EMS. Older age, female gender, higher socioeconomic status, and a history of prior ischaemic heart disease were independent predictors of using EMS. EMS use was associated with shorter adjusted door-to-balloon (53 vs 72 minutes, p<0.001) and symptom-to-balloon (183 vs 212 minutes, p<0.001) times. Mode of transport was not predictive of 30-day or 12-month mortality. CONCLUSIONS: EMS use in Victoria is relatively high compared with internationally reported data. EMS use reduces treatment delay. Predictors of EMS use in our cohort are consistent with those prevalent in prior literature. Understanding the patients who are less likely to use EMS might inform more targeted education campaigns in the future.

COVID-19 Pivoted Virtual Skills Teaching Model: Project ECHO Ontario Skin and Wound Care Boot Camp.

OBJECTIVE: To describe a virtual, competency-based skin and wound care (SWC) skills training model. The ECHO (Extension for Community Healthcare Outcomes) Ontario SWC pivoted from an in-person boot camp to a virtual format because of the COVID-19 pandemic. METHODS: An outcome-based program evaluation was conducted. Participants first watched guided commentary and videos of experts performing in nine SWC multiskills videos, then practiced and video-recorded themselves performing those skills; these recordings were assessed by facilitators. Data were collected using pre-post surveys and rubric-based assessments. Descriptive statistics and thematic analysis were applied to data analysis. RESULTS: Fifty-five healthcare professionals participated in the virtual boot camp, measured by the submission of at least one video. A total of 216 videos were submitted and 215 assessment rubrics were completed. Twenty-nine participants completed the pre-boot camp survey (53% response rate) and 26 responded to the post-boot camp survey (47% response rate). The strengths of the boot camp included the applicability of virtual learning to clinical settings, boot camp supplies, tool kits, and teaching strategies. The analysis of survey responses indicated that average proficiency scores were greater than 80% for three videos, 50% to 70% for three of the videos, and less than 50% for three of the videos. Participants received lower scores in local wound care and hand washing points of contact. The barriers of the boot camp included technical issues, time, level of knowledge required at times, and lack of equipment and access to interprofessional teams. CONCLUSIONS: This virtual ECHO SWC model expanded access to practical skills acquisition. The professional development model presented here is generalizable to other healthcare domains.

Developing a consensus-based definition of out-of-hospital clinical deterioration: A Delphi study.

BACKGROUND: Clinical deterioration is a time-critical medical emergency requiring rapid recognition and intervention. Deteriorating patients are seen across various healthcare settings, including the out-of-hospital (OOH) environment. OOH care is an evolving area of medicine where decisions are made regarding priority and timing of clinical interventions, ongoing management, and transport to appropriate care. To date, the literature lacks a standardised definition of OOH clinical deterioration. OBJECTIVE: The objective of this study was to create a consensus-based definition of OOH clinical deterioration informed by emergency medicine health professionals. METHODS: A Delphi study consisting three rounds was conducted electronically between June 2020 and January 2021. The expert panel consisted of 30 clinicians, including emergency physicians and paramedics. RESULTS: A consensus-based definition of OOH clinical deterioration was identified as changes from a patient's baseline physiological status resulting in their condition worsening. These changes primarily take the form of measurable vital signs and assessable symptoms but should be evaluated in conjunction with the history of events and pertinent risk factors. Clinicians should be suspicious that a patient could deteriorate when changes occur in one or more of the following vital signs: respiratory rate, heart rate, blood pressure, Glasgow Coma Scale, oxygen saturation, electrocardiogram, and skin colour. Almost all participants (92%) indicated an early warning system would be helpful to assist timely recognition of deteriorating patients. CONCLUSION: The creation of a consensus-based definition of OOH clinical deterioration can serve as a starting point for the development and validation of OOH-specific early warning systems. Moreover, a standardised definition allows meaningful comparisons to be made across health services and ensures consistency in future research. This study has shown recognition of OOH clinical deterioration to be a complex issue requiring further research. Improving our understanding of key factors contributing to deterioration can assist timely recognition and intervention, potentially reducing unnecessary morbidity and mortality.

3D printed chamber for live cell imaging on an upright epifluorescence microscope.

Live cell imaging is a standard technique in experimental biology that enables the observation of isolated cells and tissue slices in real time; and the testing of cellular responses to changes in buffer composition. However, most live cell imaging devices require the use of dedicated microscopes and/or specialized stage adaptors, and come at a reasonably high cost. We employed 3D printing technology to create a low-cost imaging chamber with side ports to exchange fluids, to be used on upright microscopes. The chamber increased the functionality of a standard upright epifluorescent microscope to allow dynamic, real-time calcium imaging of cultured hypothalamic astrocytes from mice, and to test the effects of ATP stimulation upon calcium signaling. It was also used on slices obtained from mouse brain using a brain matrix slicer. The advantages of this chamber include a very simple design that can be used with upright epifluorescence microscopes, does not require any special stage adaptor, and includes ports to permit fluid exchange during imaging. This chamber is ideal for educational settings with undergraduate laboratories that do not have access to dedicated inverted fluorescent microscopes for tissue culture experiments.

IL-8 concurrently promotes idiopathic pulmonary fibrosis mesenchymal progenitor cell senescence and PD-L1 expression enabling escape from immune cell surveillance.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease. We discovered fibrogenic mesenchymal progenitor cells (MPCs) in the lungs of IPF patients that display cell-autonomous fibrogenicity and drive fibrotic progression. In a study of the IPF MPC nuclear proteome, we identified DNA damage as one of the most altered functions in IPF MPCs. In prior work we found that IL-8 drives IPF MPC self-renewal. IL-8 can promote replicative stress and DNA damage and induce senescence through the CXCR2 receptor. We hypothesized that IL-8 promotes DNA damage-mediated senescence in IPF MPCs. We show that IL-8 induces DNA damage and promotes IPF MPC senescence. We discovered that IL-8 concurrently promotes senescence and upregulation of the programmed death ligand 1 (PD-L1) in a CXCR2-dependent manner. Disruption of programmed cell death protein-1 (PD-1)-PD-L1 interaction promotes natural killer (NK) cell killing of IPF MPCs in vitro and arrests IPF MPC-mediated experimental lung fibrosis in vivo. Immunohistochemical (IHC) analysis of IPF lung tissue identified PD-L1-expressing IPF MPCs codistributing with NK cells and ß-galactosidase-positive cells. Our data indicate that IL-8 simultaneously promotes IPF MPC DNA damage-induced senescence and high PD-L1 expression, enabling IPF MPCs to elude immune cell-targeted removal. Disruption of PD-1-PD-L1 interaction may limit IPF MPC-mediated fibrotic progression.NEW & NOTEWORTHY Here we show that IL-8 concurrently promotes senescence and upregulation of PD-L1 in IPF MPCs. IHC analysis identifies the presence of senescent IPF MPCs intermingled with NK cells in the fibroblastic focus, suggesting that senescent MPCs elude immune cell surveillance. We demonstrate that disruption of PD-1/PD-L1 interaction promotes NK cell killing of IPF MPCs and arrests IPF MPC-mediated experimental lung fibrosis. Disruption of PD-1/PD-L1 interaction may be one means to limit fibrotic progression.

Optimizing Trauma Systems: A Geospatial Analysis of the Victorian State Trauma System.

OBJECTIVE: The aim of this study was to develop a data-driven approach to assessing the influence of trauma system parameters and optimizing the configuration of the Victorian State Trauma System (VSTS). SUMMARY BACKGROUND DATA: Regionalized trauma systems have been shown to reduce the risk of mortality and improve patient function and health-related quality of life. However, major trauma case numbers are rapidly increasing and there is a need to evolve the configuration of trauma systems. METHODS: A retrospective review of major trauma patients from 2016 to 2018 in Victoria, Australia. Drive times and flight times were calculated for transport to each of 138 trauma receiving hospitals. Changes to the configuration of the VSTS were modeled using a Mixed Integer Linear Programming algorithm across 156 simulations. RESULTS: There were 8327 patients included in the study, of which 58% were transported directly to a major trauma service (MTS). For adult patients, the proportion of patients transported directly to an MTS increased with higher transport time limit, greater probability of helicopter emergency medical service utilization, and lower hospital patient threshold numbers. The proportion of adult patients transported directly to an MTS varied from 66% to 90% across simulations. Across all simulations for pediatric patients, only 1 pediatric MTS was assigned. CONCLUSIONS: We have developed a robust and data-driven approach to optimizing trauma systems. Through the use of geospatial and mathematical models, we have modeled how potential future changes to trauma system characteristics may impact on the optimal configuration of the system, which will enable policy makers to make informed decisions about health service planning into the future.

Molecular examination of the endogenous opioid system in rhesus macaque monkeys with self-injurious behavior.

Self-injurious behavior (SIB) can lead to serious injury and occurs in approximately 1%-4% of the adult population, with higher incidences in adolescent and institutionalized populations, as well as in children with developmental disorders such as Autism. SIB also spontaneously occurs in a low percentage of captive monkeys. Rhesus macaque (Macaca mulatta) monkeys are evolutionarily and physiologically similar to humans, share 93% genetic sequence similarity to humans, and have long been used as testing subjects for vaccine and clinical trials. Previous studies hypothesized that altered endogenous opioid expression occurs in the brains of individuals and animals that self-injure. We examined the regional mRNA expression of opioid signaling genes in sixteen rhesus macaques that exhibited SIB and eight sex- and age- matched controls. The brain regions examined are linked to reward reinforcement and stress adaptation including the hypothalamus, orbital frontal cortex, nucleus accumbens, hippocampus, caudate, and the amygdala. We found decreased µ-opioid receptor (OPRM1) in the amygdala of monkeys with SIB, and reduced prodynorphin (PDYN) in the hypothalamus. Our data suggest dysfunction in the regulation of opioid peptide precursors and calls for further investigation of the endogenous opioid system in SIB.

Mental health and wellbeing of health and aged care workers in Australia, May 2021 - June 2022: a longitudinal cohort study.

OBJECTIVES: To assess the mental health and wellbeing of health and aged care workers in Australia during the second and third years of the coronavirus disease 2019 (COVID-19) pandemic, overall and by occupation group. DESIGN, SETTING, PARTICIPANTS: Longitudinal cohort study of health and aged care workers (ambulance, hospitals, primary care, residential aged care) in Victoria: May-July 2021 (survey 1), October-December 2021 (survey 2), and May-June 2022 (survey 3). MAIN OUTCOME MEASURES: Proportions of respondents (adjusted for age, gender, socio-economic status) reporting moderate to severe symptoms of depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder scale, GAD-7), or post-traumatic stress (Impact of Event Scale-6, IES-6), burnout (abbreviated Maslach Burnout Inventory, aMBI), or high optimism (10-point visual analogue scale); mean scores (adjusted for age, gender, socio-economic status) for wellbeing (Personal Wellbeing Index-Adult, PWI-A) and resilience (Connor Davidson Resilience Scale 2, CD-RISC-2). RESULTS: A total of 1667 people responded to at least one survey (survey 1, 989; survey 2, 1153; survey 3, 993; response rate, 3.3%). Overall, 1211 survey responses were from women (72.6%); most respondents were hospital workers (1289, 77.3%) or ambulance staff (315, 18.9%). The adjusted proportions of respondents who reported moderate to severe symptoms of depression (survey 1, 16.4%; survey 2, 22.6%; survey 3, 19.2%), anxiety (survey 1, 8.8%; survey 2, 16.0%; survey 3, 11.0%), or post-traumatic stress (survey 1, 14.6%; survey 2, 35.1%; survey 3, 14.9%) were each largest for survey 2. The adjusted proportions of participants who reported moderate to severe symptoms of burnout were higher in surveys 2 and 3 than in survey 1, and the proportions who reported high optimism were smaller in surveys 2 and 3 than in survey 1. Adjusted mean scores for wellbeing and resilience were similar at surveys 2 and 3 and lower than at survey 1. The magnitude but not the patterns of change differed by occupation group. CONCLUSION: Burnout was more frequently reported and mean wellbeing and resilience scores were lower in mid-2022 than in mid-2021 for Victorian health and aged care workers who participated in our study. Evidence-based mental health and wellbeing programs for workers in health care organisations are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12621000533897 (observational study; retrospective).

Professional care workforce: a rapid review of evidence supporting methods of recruitment, retention, safety, and education.

BACKGROUND: Across the care economy there are major shortages in the health and care workforce, as well as high rates of attrition and ill-defined career pathways. The aim of this study was to evaluate current evidence regarding methods to improve care worker recruitment, retention, safety, and education, for the professional care workforce. METHODS: A rapid review of comparative interventions designed to recruit, retain, educate and care for the professional workforce in the following sectors: disability, aged care, health, mental health, family and youth services, and early childhood education and care was conducted. Embase and MEDLINE databases were searched, and studies published between January 2015 and November 2022 were included. We used the Quality Assessment tool for Quantitative Studies and the PEDro tools to evaluate study quality. RESULTS: 5594 articles were initially screened and after applying the inclusion and exclusion criteria, 30 studies were included in the rapid review. Studies most frequently reported on the professional nursing, medical and allied health workforces. Some studies focused on the single domain of care worker education (n = 11) while most focused on multiple domains that combined education with recruitment strategies, retention strategies or a focus on worker safety. Study quality was comparatively low with a median PEDro score of 5/10, and 77% received a weak rating on the Quality Assessment tool for Quantitative Studies. Four new workforce strategies emerged; early career rural recruitment supports rural retention; workload management is essential for workforce well-being; learning must be contextually relevant; and there is a need to differentiate recruitment, retention, and education strategies for different professional health and care workforce categories as needs vary. CONCLUSIONS: Given the critical importance of recruiting and retaining a strong health and care workforce, there is an immediate need to develop a cohesive strategy to address workforce shortfalls. This paper presents initial evidence on different interventions to address this need, and to inform care workforce recruitment and retention. Rapid Review registration PROSPERO 2022 CRD42022371721 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022371721.

Intubation Rates following Prehospital Administration of Ketamine for Acute Agitation: A Systematic Review and Meta-Analysis.

BACKGROUND: Ketamine is a fast-acting, dissociative anesthetic with a favorable adverse effect profile that is effective for managing acute agitation as a chemical restraint in the prehospital and emergency department (ED) settings. However, some previously published individual studies have reported high intubation rates when ketamine was administered prehospitally. OBJECTIVE: This systematic review aims to determine the rate and settings in which intubation following prehospital administration of ketamine for agitation is occurring, as well as associated indications and adverse events. METHODS: We searched PubMed, Scopus, Ovid MEDLINE, Embase, CINAHL Plus, PsycINFO, the Cochrane Library, ClinicalTrials.gov, OpenGrey, Open Access Theses and Dissertation, and Google Scholar from the earliest possible date until 13/February/2022. Inclusion criteria required studies to describe agitated patients who received ketamine in the prehospital setting as a first-line drug to control acute agitation. Reference lists of appraised studies were screened for additional relevant articles. Study quality was assessed using the Newcastle-Ottawa quality assessment scale. Synthesis of results was completed via meta-analysis, and the GRADE tool was used for certainty assessment. RESULTS: The search yielded 1466 unique records and abstracts, of which 50 full texts were reviewed, resulting in 18 being included in the analysis. All studies were observational in nature and 15 were from USA. There were 3476 patients in total, and the overall rate of intubation was 16% (95% confidence interval [CI] = 8%-26%). Most intubations occurred in the ED. Within the studies, the prehospital intubation rate ranged from 0% to 7.9% and the ED intubation rate ranged from 0 to 60%. The overall pooled prehospital intubation rate was 1% (95% CI = 0%-2%). The overall pooled ED intubation rate was 19% (95% CI = 11%-30%). The most common indications for intubation were for airway protection and respiratory depression/failure. CONCLUSIONS: There is wide variation in intubation rates between and within studies. The majority of intubations performed following prehospital administration of ketamine for agitation took place in the ED.

Inconsistent discharge diagnoses for young cardiac arrest episodes: insights from a statewide registry.

BACKGROUND: Administrative coding of out-of-hospital cardiac arrest (OHCA) is heterogeneous, with the prevalence of noninformative diagnoses uncertain. AIM: To characterize the prevalence and type of non-informative diagnoses in a young cardiac arrest population. METHODS: Hospital discharge diagnoses provided to a statewide OHCA registry were characterised as either 'informative' or 'noninformative.' Informative diagnoses stated an OHCA had occurred or defined OHCA as occurring due to coronary artery disease, cardiomyopathy, channelopathy, definite noncardiac cause, or no known cause. Noninformative diagnoses were blank, stated presenting cardiac rhythm only, provided irrelevant information or presented a complication of the OHCA as the main diagnosis. Characteristics of patients receiving informative versus noninformative diagnoses were compared. RESULTS: Of 1479 patients with OHCA aged 1 to 50 years, 290 patients were admitted to 15 hospitals. Ninety diagnoses (31.0%) were noninformative (arrest rhythm = 50, blank = 21, complication = 10 and irrelevant = 9). Two hundred diagnoses (69.0%) were informative (cardiac arrest = 84, coronary artery disease = 54, noncardiac diagnosis = 48, cardiomyopathy = 8, arrhythmia disorder = 4 and unascertained = 2). Only 10 diagnoses (3.5%) included both OHCA and an underlying cause. Patients receiving a noninformative diagnosis were more likely to have survived OHCA or been referred for forensic assessment (P = 0.011) and had longer median length of stay (9 vs 5 days, P = 0.0019). CONCLUSION: Almost one third of diagnoses for young patients discharged after an OHCA included neither OHCA nor any underlying cause. Underestimating the burden of OHCA impacts ongoing patient and at-risk family care, data sampling strategies, international statistics and research funding.

Construct validity of the international standards to document remaining autonomic function after spinal cord injury (ISAFSCI) (1st edition).

STUDY DESIGN: Observational study. OBJECTIVES: To assess the construct validity of the International Standards to Document Remaining Autonomic Function after Spinal Cord Injury (ISAFSCI) (2012 1st Edition). SETTING: Two Canadian spinal cord injury (SCI) centers. METHODS: Data were collected between 2011-2014. Assessments included the ISAFSCI, standardized measures of autonomic function and a clinical examination. Construct validity of ISAFSCI was assessed by testing a priori hypotheses on expected ISAFSCI responses to standard measures (convergent hypotheses) and clinical variables (clinical hypotheses). RESULTS: Forty-nine participants with an average age of 45 ± 12 years were included, of which 42 (85.7%) were males, 37 (77.6%) had a neurological level of injury at or above T6, and 23 (46.9%) were assessed as having motor and sensory complete SCI. For the six General Autonomic Function component hypotheses, two hypotheses (1 clinical, 1 convergent) related to autonomic control of blood pressure and one clinical hypothesis for temperature regulation were statistically significant. In terms of the Lower Urinary Tract, Bowel and Sexual Function component of the ISAFSCI, all the hypotheses (5 convergent, 3 clinical) were statistically significant except for the hypotheses on female sexual items (2 convergent, 2 clinical), likely due to small sample size. CONCLUSION: The construct validity of ISAFSCI (2012 1st Edition) for the General Autonomic Function component was considered to be weak while it was much stronger for the Lower Urinary Tract, Bowel and Sexual Function component based on a priori hypotheses. These results can inform future psychometric studies of the ISAFSCI (2021 2nd Edition).

Outcomes of paediatric patients who are not transported to hospital by Emergency Medical Services: a data linkage study.

BACKGROUND: Data on the safety of non-transport decisions for paediatric patients attended by Emergency Medical Services (EMS) are lacking. We describe the characteristics and outcomes of paediatric non-transported patients in Victoria, Australia. METHODS: A retrospective data linkage study of consecutive paediatric (aged <18 years) non-transported patients between January 2015 and June 2019. Patients were linked to ED, hospital admission and death records. Multivariable logistic regression analyses were used to determine factors associated with EMS recontact, ED presentation, hospital admission and an adverse event (death/cardiac arrest, intensive care unit admission or highest ED triage category) within 48 hours of the initial emergency call. RESULTS: In total, 62 975 non-transported patients were included. The mean age was 7.1 (SD 6.0) years and 48.9% were male. Overall, 2.2% recontacted the EMS within 48 hours, 13.7% self-presented to a public ED, 2.4% were admitted to hospital and 0.1% had an adverse event, including two deaths. Among patients with paramedic-initiated non-transport (excluding transport refusals and transport via other means), 5.6% presented to a public ED, 1.1% were admitted to hospital and 0.05% had an adverse event. In the overall population, an abnormal vital sign on initial assessment increased the odds of hospital admission and an adverse event. Among paramedic-initiated non-transports, cases occurring in the early hours of the morning (04:00-08:00 hours) were associated with increased odds of subsequent hospital admission, while the odds of ED presentation and hospital admission also increased with increasing prior exposure to non-transported cases. CONCLUSION: Adverse events were rare among paramedic-initiated non-transport cases. Vital sign derangements and attendance by paramedics with higher prior exposure to non-transports were associated with poorer outcomes and may be used to improve safety.