Correction: Identifying areas of Australia with high out-of-hospital cardiac arrest incidence and low bystander cardiopulmonary resuscitation rates: A retrospective, observational study.

[This corrects the article DOI: 10.1371/journal.pone.0301176.].

Notch signaling without the APH-2/Nicastrin subunit of Gamma Secretase in C. elegans germline stem cells.

The final step in Notch signaling activation is the transmembrane cleavage of Notch receptor by γ secretase. Thus far, genetic and biochemical evidence indicate that four subunits are essential for γ secretase activity in vivo: presenilin (the catalytic core), APH-1, PEN-2, and APH-2/Nicastrin. Although some γ secretase activity has been detected in APH-2/Nicastrin-deficient mammalian cell lines, the lack of biological relevance for this activity has left the quaternary γ secretase model unchallenged. Here we provide the first example of in vivo Notch signal transduction without APH-2/Nicastrin. The surprising dispensability of APH-2/Nicastrin is observed in C. elegans germline stem cells (GSCs), and contrasts with its essential role in previously described C. elegans Notch signaling events. Depletion of GLP-1/Notch, presenilin, APH-1, or PEN-2 causes a striking loss of GSCs. In contrast, aph-2/Nicastrin mutants maintain GSCs, and exhibit robust and localized expression of the downstream Notch target sygl-1. Interestingly, APH-2/Nicastrin is present in GSCs and becomes essential under conditions of compromised Notch function. Further insight is provided by reconstituting the C. elegans γ secretase complex in yeast, where we find that APH-2/Nicastrin increases, but is not essential for γ secretase activity. Together, our results are most consistent with a revised model of γ secretase in which the APH-2/Nicastrin subunit has a modulatory, rather than obligatory role. We propose that a trimeric presenilin-APH-1-PEN-2 γ secretase complex can provide a low level of γ secretase activity, and that cellular context determines whether or not APH-2/Nicastrin is essential for effective Notch signal transduction.

Robotic-arm assisted versus manual total knee arthroplasty: Functional gait analysis from a randomised controlled trial.

The primary aim of this study was to assess whether measures of functional gait assessment were improved with robotic total knee arthroplasty (rTKA) when compared to manual TKA (mTKA). Gait analysis was performed as part of a randomised controlled trial. Walking and relaxed standing assessments were performed using an instrumented mat system. Spatiotemporal variables included gait cycle parameters, anteroposterior and lateral sway, and plantar pressure ratios. Measurements were recorded at pre-operative baseline and 12 months post-operatively. 100 patients were randomised, 50 to each group. Complete gait cycle data were available for 26 rTKA and 23 mTKA patients. Cadence and walking velocity showed overall improvements following surgery, with no difference between the two groups. In the operated limb, overall step and stride times decreased, while step and stride lengths increased. Subgroup analysis showed reduced propulsion time with rTKA, and decreased foot flat and mid stance times with mTKA. Lateral sway was decreased in the rTKA group. Plantar pressure ratios showed an overall increase in hindfoot loading on the operated limb, with no difference between the two groups. No other significant differences were identified between rTKA and mTKA at 12 months, and limitations may include statistical error. A small sample of the study cohort was followed up; analysis may represent the results of satisfied patients with well-functioning TKA. Further study could incorporate proprioceptive and 3D gait analysis techniques to analyse knee kinetics and kinematics with robotic surgery. Pressure mapping could further subdivide the plantar surfaces to explore any nuances in differential loading.

Identifying areas of Australia with high out-of-hospital cardiac arrest incidence and low bystander cardiopulmonary resuscitation rates: A retrospective, observational study.

AIM: This study aims to explore regional variation and identify regions within Australia with high incidence of out-of-hospital cardiac arrest (OHCA) and low rates of bystander cardiopulmonary resuscitation (CPR). METHOD: Adult OHCAs of presumed medical aetiology occurring across Australia between 2017 and 2019 were mapped onto local government areas (LGA) using the location of arrest coordinates. Bayesian spatial models were applied to provide "smoothed" estimates of OHCA incidence and bystander CPR rates (for bystander-witnessed OHCAs) for each LGA. For each state and territory, high-risk LGAs were defined as those with an incidence rate greater than the state or territory's 75th percentile and a bystander CPR rate less than the state or territory's 25th percentile. RESULTS: A total of 62,579 OHCA cases attended by emergency medical services across 543 LGAs nationwide were included in the study. Nationally, the OHCA incidence rate across LGA ranged from 58.5 to 198.3 persons per 100,000, while bystander CPR rates ranged from 45% to 75%. We identified 60 high-risk LGAs, which were predominantly located in the state of New South Wales. Within each region, high-risk LGAs were typically located in regional and remote areas of the country, except for four metropolitan areas-two in Adelaide and two in Perth. CONCLUSIONS: We have identified high-risk LGAs, characterised by high incidence and low bystander CPR rates, which are predominantly in regional and remote areas of Australia. Strategies for reducing OHCA and improving bystander response may be best targeted at these regions.

Refining ambulance clinical response models: The impact on ambulance response and emergency department presentations.

OBJECTIVE: The ambulance service in Victoria, Australia implemented a revised clinical response model (CRM) in 2016 which was designed to increase the diversion of low-acuity Triple Zero (000) calls to secondary telephone triage and reduce emergency ambulance dispatches. The present study evaluates the influence of the revised CRM on emergency ambulance response times and ED presentations. METHODS: A retrospective study of emergency calls for ambulance between 1 January 2015 and 31 December 2018. Ambulance data were linked with ED presentations occurring up to 48 h after contact. Interrupted time series analyses were used to evaluate the impact of the revised CRM. RESULTS: A total of 2 365 529 calls were included. The proportion allocated a Code 1 (time-critical, lights/sirens) dispatch decreased from 56.6 to 41.0% after implementation of the revised CRM. The proportion of calls not receiving an emergency ambulance increased from 10.4 to 19.6%. Interrupted time series analyses demonstrated an improvement in Code 1 cases attended within 15 min (Key Performance Indicator). However, for patients with out-of-hospital cardiac arrest or requiring lights and sirens transport to hospital, there was no improvement in response time performance. By the end of the study period, there was also no difference in the proportion of callers presenting to ED when compared with the estimated proportion assuming the revised CRM had not been implemented. CONCLUSION: The revised CRM was associated with improved Code 1 response time performance. However, there was no improvement in response times for high acuity patients, and no change in the proportion of callers presenting to ED.

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.

Identifying subgroups of patients that may benefit from robotic arm-assisted total knee arthroplasty: Secondary analysis of data from a randomised controlled trial.

BACKGROUND: The aims were to assess whether a specific subgroup(s) of patients had a clinically significant benefit in their knee specific outcome or health-related quality of life (HRQoL) when undergoing robotic total knee arthroplasty (rTKA) when compared to manually performed TKA (mTKA). METHODS: One hundred patients were randomised to either rTKA or mTKA, 50 to each group, of which 46 and 41 were available for functional review at 6-months, respectively. Subgroup analysis was undertaken for sex, age (<67-years versus ≥ 67-years), preoperative WOMAC score (<40 versus ≥ 40) and EQ-5D utility (<0.604 versus ≥ 0.604). RESULTS: Male patients undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (mean difference (MD) 16.3, p = 0.011) at 2-months, function (MD 12.6, p = 0.032) and total score (MD 12.7, p = 0.030), and OKS (MD 6.0, p = 0.030) at 6-months. Patients < 67-years old undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 10.3, p = 0.039) at 2-months, and function (MD 12.9, p = 0.040) and total (MD 13.1, p = 0.038) scores at 6-months. Patients with a preoperative WOMAC total score of < 40 points undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 14.6, p = 0.044) at 6-months. Patients with a preoperative EQ-5D utility of <0.604 undergoing rTKA had a clinically and statistically significant greater improvement in WOMAC pain (MD 15.5, p = 0.011) at 2-months. CONCLUSION: Patients of male sex, younger age, worse preoperative knee specific function and HRQoL had a clinically significantly better early functional outcome with rTKA when compared to mTKA.

Patients undergoing robotic arm-assisted total knee arthroplasty have a greater improvement in knee-specific pain but not in function.

Aims: The aim was to assess whether robotic-assisted total knee arthroplasty (rTKA) had greater knee-specific outcomes, improved fulfilment of expectations, health-related quality of life (HRQoL), and patient satisfaction when compared with manual TKA (mTKA). Methods: A randomized controlled trial was undertaken (May 2019 to December 2021), and patients were allocated to either mTKA or rTKA. A total of 100 patients were randomized, 50 to each group, of whom 43 rTKA and 38 mTKA patients were available for review at 12 months following surgery. There were no statistically significant preoperative differences between the groups. The minimal clinically important difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was defined as 7.5 points. Results: There were no clinically or statistically significant differences between the knee-specific measures (WOMAC, Oxford Knee Score (OKS), Forgotten Joint Score (FJS)) or HRQoL measures (EuroQol five-dimension questionnaire (EQ-5D) and EuroQol visual analogue scale (EQ-VAS)) at 12 months between the groups. However, the rTKA group had significantly (p = 0.029) greater improvements in the WOMAC pain component (mean difference 9.7, 95% confidence interval (CI) 1.0 to 18.4) over the postoperative period (two, six, and 12 months), which was clinically meaningful. This was not observed for function (p = 0.248) or total (p = 0.147) WOMAC scores. The rTKA group was significantly (p = 0.039) more likely to have expectation of 'Relief of daytime pain in the joint' when compared with the mTKA group. There were no other significant differences in expectations met between the groups. There was no significant difference in patient satisfaction with their knee (p = 0.464), return to work (p = 0.464), activities (p = 0.293), or pain (p = 0.701). Conclusion: Patients undergoing rTKA had a clinically meaningful greater improvement in their knee pain over the first 12 months, and were more likely to have fulfilment of their expectation of daytime pain relief compared with patients undergoing mTKA. However, rTKA was not associated with a clinically significant greater knee-specific function or HRQoL, according to current definitions.

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.

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.

TBCRC 057: Survey about willingness to participate in cancer clinical trials during the pandemic.

BACKGROUND: Breast cancer patients experienced heightened anxiety during the pandemic. Also, modifications to clinical trial activities allowing for virtual platforms, local assessments, and greater flexibility were introduced to facilitate participation. We sought to evaluate the association between pandemic-related anxiety and willingness to participate in trials and how pandemic-era modifications to trial activities affect the decision to participate. METHODS: We conducted an online survey from August to September, 2021 of patients with breast cancer assessing pandemic-related anxiety; clinical trials knowledge and attitudes; willingness to participate during and before the pandemic; and how each modification affects the decision to participate. Fisher's exact tests evaluated differences in proportions and two-sample t-tests evaluated differences in means. The association of pandemic-related anxiety with a decline in willingness to participate during compared to prior to the pandemic was modeled using logistic regression. RESULTS: Among 385 respondents who completed the survey, 81% reported moderate-severe pandemic-related anxiety. Mean willingness to participate in a trial was lower during the pandemic than prior [2.97 (SD 1.17) vs. 3.10 (SD 1.09), (p < 0.001)]. Severe anxiety was associated with higher odds of diminished willingness to participate during the pandemic compared to prior (OR 5.07). Each of the modifications, with the exception of opting out of research-only blood tests, were endorsed by >50% of respondents as strategies that would increase their likelihood of deciding to participate. CONCLUSIONS: While pandemic-related anxiety was associated with diminished willingness to participate in trials, the leading reasons for reluctance to consider trial participation were unrelated to the pandemic but included worries about not getting the best treatment, side effects, and delaying care. Patients view trial modifications favorably, supporting continuation of these modifications, as endorsed by the National Cancer Institute and others.

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.

High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81.

Hyperglycemia, lipotoxicity, and insulin resistance are known to increase the secretion of extracellular matrix from cardiac fibroblasts as well as the activation of paracrine signaling from cardiomyocytes, immune cells, and vascular cells, which release fibroblast-activating mediators. However, their influences on vascular smooth muscle cells (vSMCs) have not been well examined. This study aimed to investigate whether contractile vascular vSMCs could develop a more synthetic phenotype in response to hyperglycemia. The results showed that contractile and synthetic vSMCs consumed high glucose in different ways. Lactate/GPR81 promotes the synthetic phenotype in vSMCs in response to high glucose levels. The stimulation of high glucose was associated with a significant increase in fibroblast-like features: synthetic vSMC marker expression, collagen 1 production, proliferation, and migration. GPR81 expression is higher in blood vessels in diabetic patients and in the high-glucose, high-lipid diet mouse. The results demonstrate that vSMCs assume a more synthetic phenotype when cultured in the presence of high glucose and, consequently, that the high glucose could trigger a vSMC-dependent cardiovascular disease mechanism in diabetes via lactate/GPR81.

The dynamics of fishing villages along the South Atlantic Coast of North America (ca. 5000-3000 years BP).

We present new chronologies that inform the timing and tempo of shell ring and shell mound construction on the South Atlantic Bight. Our project combines recently acquired dates with legacy radiocarbon dates from over 25 rings and mounds to provide a higher-resolution chronology regarding the occupation and formation of this larger landscape of the earliest fishing villages along the East Coast of the United States. We resolve the ordering and timing of occupation of these rings and mounds through Bayesian statistical modeling. These new models historicize and contextualize these shell rings in ways previously impossible. Specifically, our new chronologies of these villages indicate that the earliest villages were established prior to the invention of pottery. The early period of village establishment evidences isolated village rings, whereas later periods seem to have more villages, but these appear to have been relocated to other areas and/or islands over time. Shell mounds are fewer in number, are spread throughout the time period, and may represent special purpose sites compared to shell-rings. Once villages spread, they quickly adopted new technologies (i.e., pottery) and created new institutions and practiced village relocation, which allowed this way of life to persist for more than a thousand years.

Impact of socioeconomic status on presentation, care quality and outcomes of patients attended by emergency medical services for dyspnoea: a population-based cohort study.

BACKGROUND: Low socioeconomic status (SES) has been linked to poor outcomes in many conditions. It is unknown whether these disparities extend to individuals presenting with dyspnoea. We aimed to evaluate the relationship between SES and incidence, care quality and outcomes among patients attended by emergency medical services (EMS) for dyspnoea. METHODS: This population-based cohort study included consecutive patients attended by EMS for dyspnoea between 1 January 2015 and 30 June 2019 in Victoria, Australia. Data were obtained from individually linked ambulance, hospital and mortality datasets. Patients were stratified into SES quintiles using a composite census-derived index. RESULTS: A total of 262 412 patients were included. There was a stepwise increase in the age-adjusted incidence of EMS attendance for dyspnoea with increasing socioeconomic disadvantage (lowest SES quintile 2269 versus highest quintile 889 per 100 000 person years, ptrend<0.001). Patients of lower SES were younger and more comorbid, more likely to be from regional Victoria or of Aboriginal or Torres Strait Islander heritage and had higher rates of respiratory distress. Despite this, lower SES groups were less frequently assigned a high acuity EMS transport or emergency department (ED) triage category and less frequently transported to tertiary centres or hospitals with intensive care unit facilities. In multivariable models, lower SES was independently associated with lower acuity EMS and ED triage, ED length of stay>4 hours and increased 30-day EMS reattendance and mortality. CONCLUSION: Lower SES was associated with a higher incidence of EMS attendances for dyspnoea and disparities in several metrics of care and clinical outcomes.

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.

Incorporation of emergent symptoms and genetic covariates improves prediction of aromatase inhibitor therapy discontinuation.

Objectives: Early discontinuation is common among breast cancer patients taking aromatase inhibitors (AIs). Although several predictors have been identified, it is unclear how to simultaneously consider multiple risk factors for an individual. We sought to develop a tool for prediction of AI discontinuation and to explore how predictive value of risk factors changes with time. Materials and Methods: Survival machine learning was used to predict time-to-discontinuation of AIs in 181 women who enrolled in a prospective cohort. Models were evaluated via time-dependent area under the curve (AUC), c-index, and integrated Brier score. Feature importance was analysis was conducted via Shapley Additive Explanations (SHAP) and time-dependence of their predictive value was analyzed by time-dependent AUC. Personalized survival curves were constructed for risk communication. Results: The best-performing model incorporated genetic risk factors and changes in patient-reported outcomes, achieving mean time-dependent AUC of 0.66, and AUC of 0.72 and 0.67 at 6- and 12-month cutoffs, respectively. The most significant features included variants in ESR1 and emergent symptoms. Predictive value of genetic risk factors was highest in the first year of treatment. Decrease in physical function was the strongest independent predictor at follow-up. Discussion and Conclusion: Incorporation of genomic and 3-month follow-up data improved the ability of the models to identify the individuals at risk of AI discontinuation. Genetic risk factors were particularly important for predicting early discontinuers. This study provides insight into the complex nature of AI discontinuation and highlights the importance of incorporating genetic risk factors and emergent symptoms into prediction models.

Overuse of Computed Tomography Pulmonary Angiography and Low Utilization of Clinical Prediction Rules in Suspected Pulmonary Embolism Patients at a Regional Australian Hospital.

A pulmonary embolism (PE) is an obstruction in the pulmonary arterial system and may include non-specific signs and symptoms. Clinical prediction rules (CPRs) assess the pretest probability (PTP) of a PE to prevent the overuse of computed tomography pulmonary angiography (CTPA). CTPA overuse results in patient harm and health system waste. This study aimed to evaluate CTPA usage in an Australian regional hospital through analyzing CTPA encounters. A retrospective chart analysis was undertaken of 100 CTPAs conducted at an Australian regional hospital from April to May 2023. Analysis was undertaken for parameters including risk factors, signs and symptoms, investigations, and the use of CPRs. Overall, 86% of patients had signs and/or symptoms of a PE within a week of examination, and 6% of the population had signs of deep vein thrombosis. More than half of the population had no risk factors, while the most prevalent risk factors were a recent history of immobilization/trauma and/or having surgery that required general anesthesia in the last 4 weeks. The most common co-morbidity was chronic lung disease (11%). For the pre-test diagnostic workup, the ECG was the most ordered investigation. The Wells' score was used at 10%, while most patients did not have any CPRs applied. The prevalence of PEs discovered on CTPAs was 9%. CPRs were under-utilized in this Australian regional hospital. The D-dimers for ruling out subjects with low PTP derived from CPRs were also underused. This led to the inappropriate overordering of CTPAs, resulting in negative implications for patients and unnecessary costs to the health system.

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.

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.