Farming and the risk of developing osteoarthritis in Alberta, Canada.

INTRODUCTION: Because farming is a physically demanding occupation, farmers may be susceptible to developing osteoarthritis (OA). The aim of this study was to determine the risk of developing OA in Canadian farm, non-farm rural and urban residents. METHODS: A retrospective cohort study of five Alberta health administrative databases examined the risk of developing OA among three groups: farm (n=143 431), non-farm rural (n=143 431) and urban (n=143 431) residents over the fiscal years 2000-2001 through 2020-2021. The algorithm for OA ascertainment defined cases based on criteria including one hospital admission, two physician visits within a 2-year interval, or two ambulatory care visits within 2 years. Incidence rates, lifetime risk, and mortality rates were calculated. Cox proportional hazard models compared the incidence of OA for the three groups over the 21 years. RESULTS: A total of 26 957 OA cases were identified among 1 706 256 person-years (PYs) in the farm cohort. The crude incidence rate of OA over a period of 21 years ranged from 19.1 (95% confidence interval (CI) 18.6-19.6) per 1000 PYs in 2001 to 10.0 (95% CI 9.6-10.5) per 1000 PYs in 2021. The overall incidence rate was higher in the farm group (15.8 (95%CI 15.6-16.0) per 1000 PYs) as compared to the non-farm rural (14.7 (95%CI 14.5-14.9) per 1000 PYs) and the urban groups (13.3 (95%CI 13.1-13.4) per 1000 PYs). After adjusting for age and sex, the farm (6%; 95%CI 4-8%), and non-farm rural (9%; 95%CI 7-12%) groups had higher incidence rates than the urban group. The unadjusted non-injury mortality rate for the farm group with OA was lower (13.2 (95%CI 12.9-13.5) per 1000 PYs) than both the urban (14.5; 95%CI 14.1-14.8) and rural (18.0; 95%CI 17.6-18.4) groups. After adjusting for mortality, the lifetime risk of developing OA was 27.7% for farm residents, 25.6% for the non-farm rural cohort, and 24.0% for the urban cohort. CONCLUSION: When accounting for age and sex, farm and non-farm rural residents have a higher risk of developing OA as compared to the urban population. The higher mortality-adjusted lifetime risk of developing OA among farm residents highlights the necessity of specific interventions aimed at reducing the impact of this condition in rural communities. Further research is required to identify specific occupational and lifestyle risk factors associated with OA among farmers and to develop effective strategies for prevention and management.

A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

Evaluating Readmission Rates for a Statewide In-Home Ecosystemic Family-Based Treatment Program for Youth with Serious Emotional Disturbance.

Family Based Mental Health Services (FBMHS) with an embedded clinical model, Ecosystemic Structural Family Therapy, is an intervention designed for youth with a serious emotional disturbance (SED) who are at risk of out-of-home placement. The current evaluation examines the association between receipt of FBMHS and rates of out-of-home and community-based care during and after an episode of FBMHS. We identified 25,016 Medicaid-enrolled youth ages 3 to 17 years with receipt of a new FBMHS episode from 1/1/2015 to 6/30/2021. 14% of youth received out-of-home services. Rates of out-of-home service decreased during receipt of FBMHS (14.25-6.98%, p < .0001) and remained lower 6 months following discharge (to 6.95%, p < .0001). Short and longer doses of service were both associated with decreased rates of out-of-home services. FBMHS has been scaled across a large geographic area and is associated with lower rates of out-of-home placement for youth with SED.

Attentional, anticipatory and spatial cognition fluctuate throughout the menstrual cycle: potential implications for female sport.

Current research suggests that menstruating female athletes might be at greater risk of musculoskeletal injury in relation to hormonal changes throughout the menstrual cycle. A separate body of work suggests that spatial cognition might also fluctuate in a similar manner. Changes in spatial cognition could, in theory, be a contributing risk factor for injury, especially in fast-paced sports that require precise, millisecond accuracy in interactions with moving objects in the environment. However, existing theories surrounding causes for increased injury risk in menstruating females largely focus on biomechanical mechanisms, with little consideration of possible cognitive determinants of injury risk. Therefore, the aim of this proof-of-principle study was to explore whether menstruating females exhibit fluctuations in cognitive processes throughout their cycle on a novel sport-oriented cognitive test battery, designed to measure some of the mental processes putatively involved in these sporting situations. A total of 394 participants completed an online cognitive battery, a mood scale and a symptom questionnaire twice, 14 days apart. After exclusions, 241 eligible participants were included in the analyses (mean: 28 ± 6 years) (male = 96, female(menstruating) = 105, female(contraception) = 47). Cycle phase for menstruating females was based on self-reported information. The cognitive battery was designed to measure reaction times, attention, visuospatial functions (including 3D mental rotation) and timing anticipation. Three composite scores were generated using factor analysis with varimax rotation (Errors, Reaction Time, Intra-Individual Variability). Mixed model ANOVAs and repeated measures ANOVAs were performed to test for between and within-subject effects. There was no group difference in reaction times and accuracy between males and females (using contraception and not). However, within subject analyses revealed that regularly menstruating females performed better during menstruation compared to being in any other phase, with faster reaction times (10ms c.ca, p < .01), fewer errors (p < .05) and lower dispersion intra-individual variability (p < .05). In contrast they exhibited slower reaction times (10ms c.ca, p < .01) and poorer timing anticipation (p < .01) in the luteal phase, and more errors in the predicted ovulatory phase (p < .01). Self-reported mood, cognitive and physical symptoms were all worst during menstruation (p < .01), and a significant proportion of females felt that their symptoms were negatively affecting their cognitive performance during menstruation on testing day, which was incongruent with their actual performance. These findings suggest that visuospatial and anticipatory processes may fluctuate throughout the menstrual cycle in the general population, with better performance during the menstrual phase and poorer performance during the luteal phase. If these extend to associations between phase-specific cognitive performance and injury incidence, they would support a cognitive theory of determinants of injury risk in cycling female athletes, opening an opportunity to develop mitigation strategies where appropriate.

Outcome and feasibility of radiotherapy bridging in large B-cell lymphoma patients receiving CD19 CAR T in the UK.

Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy. 169/717 (24%) received RT bridging, 129 as single modality and 40 as combined modality treatment (CMT). Of 169 patients, 65.7% had advanced stage, 36.9% bulky disease, 86.5% elevated LDH, 41.7% international prognostic index (IPI) ≥3 and 15.2% double/triple hit at the time of approval. Use of RT bridging varied from 11% to 32% between centres and increased over time. Vein-to-vein time and infusion rate did not differ between bridging modalities. RT-bridged patients had favourable outcomes with 1-year progression-free survival (PFS) of 56% for single modality and 47% for CMT (1-year PFS 43% for systemic bridging). This is the largest cohort of LBCL patients receiving RT bridging prior to CAR T reported to date. Our results show that RT bridging can be safely and effectively used even in advanced stage and high-risk disease, with low dropout rates and excellent outcomes.

Bone-anchored prostheses for transfemoral amputation: a systematic review of outcomes, complications, patient experiences, and cost-effectiveness.

Introduction: Bone-anchored prostheses (BAP) are an advanced reconstructive surgical approach for individuals who had transfemoral amputation and are unable to use the conventional socket-suspension systems for their prostheses. Access to this technology has been limited in part due to the lag between the start of a new procedure and the availability of evidence that is required before making decisions about widespread provision. This systematic review presents as a single resource up-to-date information on aspects most relevant to decision makers, i.e., clinical efficacy, safety parameters, patient experiences, and health economic outcomes of this technology. Methods: A systematic search of the literature was conducted by an information specialist in PubMed, MEDLINE, Embase, CINAHL, Cochrane Library, the Core Collection of Web of Science, CADTH's Grey Matters, and Google Scholar up until May 31, 2023. Peer-reviewed original research articles on the outcomes of clinical effectiveness (health-related quality of life, mobility, and prosthesis usage), complications and adverse events, patient experiences, and health economic outcomes were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence and ROBINS-I, as appropriate. Results: Fifty studies met the inclusion criteria, of which 12 were excluded. Thirty-eight studies were finally included in this review, of which 21 reported on clinical outcomes and complications, 9 case series and 1 cohort study focused specifically on complications and adverse events, and 2 and 5 qualitative studies reported on patient experience and health economic assessments, respectively. The most common study design is a single-arm trial (pre-/post-intervention design) with varying lengths of follow-up. Discussion: The clinical efficacy of this technology is evident in selected populations. Overall, patients reported increased health-related quality of life, mobility, and prosthesis usage post-intervention. The most common complication is a superficial or soft-tissue infection, and more serious complications are rare. Patient-reported experiences have generally been positive. Evidence indicates that bone-anchored implants for prosthesis fixation are cost-effective for those individuals who face significant challenges in using socket-suspension systems, although they may offer no additional advantage to those who are functioning well with their socket-suspended prostheses.

A novel electronic health record-based, machine-learning model to predict severe hypoglycemia leading to hospitalizations in older adults with diabetes: A territory-wide cohort and modeling study.

BACKGROUND: Older adults with diabetes are at high risk of severe hypoglycemia (SH). Many machine-learning (ML) models predict short-term hypoglycemia are not specific for older adults and show poor precision-recall. We aimed to develop a multidimensional, electronic health record (EHR)-based ML model to predict one-year risk of SH requiring hospitalization in older adults with diabetes. METHODS AND FINDINGS: We adopted a case-control design for a retrospective territory-wide cohort of 1,456,618 records from 364,863 unique older adults (age ≥65 years) with diabetes and at least 1 Hong Kong Hospital Authority attendance from 2013 to 2018. We used 258 predictors including demographics, admissions, diagnoses, medications, and routine laboratory tests in a one-year period to predict SH events requiring hospitalization in the following 12 months. The cohort was randomly split into training, testing, and internal validation sets in a 7:2:1 ratio. Six ML algorithms were evaluated including logistic-regression, random forest, gradient boost machine, deep neural network (DNN), XGBoost, and Rulefit. We tested our model in a temporal validation cohort in the Hong Kong Diabetes Register with predictors defined in 2018 and outcome events defined in 2019. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) statistics, and positive predictive value (PPV). We identified 11,128 SH events requiring hospitalization during the observation periods. The XGBoost model yielded the best performance (AUROC = 0.978 [95% CI 0.972 to 0.984]; AUPRC = 0.670 [95% CI 0.652 to 0.688]; PPV = 0.721 [95% CI 0.703 to 0.739]). This was superior to an 11-variable conventional logistic-regression model comprised of age, sex, history of SH, hypertension, blood glucose, kidney function measurements, and use of oral glucose-lowering drugs (GLDs) (AUROC = 0.906; AUPRC = 0.085; PPV = 0.468). Top impactful predictors included non-use of lipid-regulating drugs, in-patient admission, urgent emergency triage, insulin use, and history of SH. External validation in the HKDR cohort yielded AUROC of 0.856 [95% CI 0.838 to 0.873]. Main limitations of this study included limited transportability of the model and lack of geographically independent validation. CONCLUSIONS: Our novel-ML model demonstrated good discrimination and high precision in predicting one-year risk of SH requiring hospitalization. This may be integrated into EHR decision support systems for preemptive intervention in older adults at highest risk.

Systematic Review of Hypofractionated Radiation Therapy for the Treatment of Oesophageal Squamous Cell Carcinoma and Oesophageal Adenocarcinoma.

BACKGROUND AND AIM: There has been limited progress made in improving the suboptimal outcomes delivered by conventionally fractionated radiotherapy (RT) for oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). A greater biological effect may be achieved using hypofractionated RT (HFRT), though the toxicity, tolerability and efficacy of this approach in OAC and OSCC is uncertain. METHODS: A systematic literature review was carried out in accordance with Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane, CINAHL, Scopus and Web of Science databases were searched for terms relating to HFRT (>2.4Gy per fraction) for OAC or OSCC. All relevant clinical studies published between January 2000 and April 2023 were included. Study quality was assessed using predefined criteria. RESULTS: Ninety-six studies were screened and 20 subsequently included, together incorporating 1208 patients. Fourteen studies focussed on neoadjuvant or definitive treatment. These were predominantly retrospective (n = 10, 71%) though two (n = 2, 14%) early phase trials were identified. Most focussed on OSCC (n = 7, 47%) or mixed OSCC/OAC (n = 6, 43%) populations. Four (28.6%) included a conventionally fractionated chemoradiotherapy (CRT) comparator, against which median overall (mOS) and progression free survival outcomes from HFRT did not differ. Reported mOS for HFRT ranged between 29-36 months at 2.5-3.125Gy per fraction (total dose 50-60Gy) for OAC and OSCC combined. Toxicity and tolerability with HFRT was comparable with conventionally fractionated CRT up to, but not exceeding, 5Gy. Three (50%) of the six palliative-intent studies were early phase trials and most (n = 4, 67%) focussed on OAC and OSCC. Response rates with HFRT in the palliative setting were 63.6-88.0%. CONCLUSION: These data provide evidence in OAC/OSCC for promising efficacy and an acceptable toxicity profile for moderately HFRT, alone or with concurrent chemotherapy. These data should prompt prospective, randomised comparisons of HFRT and conventionally fractionated CRT and single-modality RT schedules. REGISTRATION DETAILS: PROSPERO; CRD42023457791.

Using Inundation Extents to Predict Microbial Contamination in Private Wells after Flooding Events.

Disaster recovery poses unique challenges for residents reliant on private wells. Flooding events are drivers of microbial contamination in well water, but the relationship observed between flooding and contamination varies substantially. Here, we investigate the performance of different flood boundaries─the FEMA 100 year flood hazard boundary, height above nearest drainage-derived inundation extents, and satellite-derived extents from the Dartmouth Flood Observatory─in their ability to identify well water contamination following Hurricane Florence. Using these flood boundaries, we estimated about 2600 wells to 108,400 private wells may have been inundated─over 2 orders of magnitude difference based on boundary used. Using state-generated routine and post-Florence testing data, we observed that microbial contamination rates were 7.1-10.5 times higher within the three flood boundaries compared to routine conditions. However, the ability of the flood boundaries to identify contaminated samples varied spatially depending on the type of flooding (e.g., riverine, overbank, coastal). While participation in testing increased after Florence, rates were overall still low. With <1% of wells tested, there is a critical need for enhanced well water testing efforts. This work provides an understanding of the strengths and limitations of inundation mapping techniques, which are critical for guiding postdisaster well water response and recovery.

'I do hope more people can benefit from it.': The qualitative experience of individuals living with osteoarthritis who participated in the GLA:D™ program in Alberta, Canada.

INTRODUCTION: The Good Life with osteoArthritis: Denmark (GLA:DTM) is an evidence-based program designed for individuals with symptomatic hip and knee osteoarthritis (OA). This program has reported improvement in pain, quality of life and self-efficacy, as well as delays in joint replacement surgery for adults with moderate to severe hip or knee OA. Evaluations of GLA:DTM implementation in several countries have focused on effectiveness, training, and feasibility of the program primarily from the provider perspective. Our objective was to examine how the GLA:DTM program was perceived and experienced by individuals with hip and knee OA to inform on-going program refinement and implementation. METHODS: Thirty semi-structured telephone interviews were conducted with participants who completed the GLA:DTM program in Alberta. An interpretive description approach was used to frame the study and thematic analysis was used to code the data and identify emergent themes and sub-themes associated with participants' experience and perception of the GLA:DTM program. RESULTS: Most participants had a positive experience of the GLA:DTM program and particularly enjoyed the group format, although some participants felt the group format prevented one-on-one support from providers. Three emergent themes related to acceptability were identified: accessible, adaptable, and supportive. Participants found the program to be accessible in terms of location, cost, and scheduling. They also felt the program was adaptable and allowed for individual attention and translatability into other settings. Finally, most participants found the group format to be motivating and fostered connections between participants. CONCLUSION: The GLA:DTM program was perceived as acceptable by most participants, yet the group format may not be useful for all individuals living with OA. Recommended improvements included adapting screening to identify those suited for the group format, providing program access earlier in the disease progression trajectory, modifying educational content based on participants' knowledge of OA and finally, providing refresher sessions after program completion.

Generating a list of potentially important contextual factors covering randomized trials, cohorts, and measurement property studies: An OMERACT initiative.

OBJECTIVES: To generate candidates for contextual factors (CFs) for each CF type (i.e., Effect Modifying Contextual Factors (EM-CFs), Outcome Influencing Contextual Factors (OI-CFs), and Measurement Affecting Contextual Factors (MA-CFs)) considered important within rheumatology. METHODS: We surveyed OMERACT working groups and conducted a Special Interest Group (SIG) session at the OMERACT 2023 meeting, where the results were reviewed, and additional CFs suggested. RESULTS: The working groups suggested 44, 49, and 21 generic EM-CFs, OI-CFs, and MA-CFs, respectively. SIG participants added 49, 44, and 55 factors, respectively. CONCLUSION: Candidate CFs were identified, next step is a consensus-based set of endorsed (important) CFs.

Clinical and Histological Response to Talimogene Laherparepvec Therapy in Advanced Melanoma: Impact on Overall Survival.

BACKGROUND: Talimogene laherparepvec (T-VEC) is an FDA-approved oncolytic herpesvirus therapy used for unresectable stage IIIB through IV metastatic melanoma. However, the correlation between clinical complete response (cCR) and pathologic complete response (pCR) in patients treated with T-VEC is understudied. STUDY DESIGN: We conducted a retrospective study from a prospectively maintained IRB-approved melanoma single-center database in patients treated with T-VEC from October 2015 to April 2022. Patients were categorized into 3 groups: cCR with pCR, cCR without pCR, and less than cCR. The primary endpoint was overall survival. We used descriptive statistics, chi-square tests, and Wilcoxon rank-sum tests to compare key covariates among exposure groups. We used survival analysis to compare survival curves and reported hazard ratio of death (95% CI) across exposure groups. RESULTS: We included 116 patients with a median overall survival (interquartile range) of 22.7 (14.8-39.3) months. The majority were men (69%) and White (97.4%), with a median age of 74.5 years. More than half of patients (n = 60, 51.6%) achieved cCR. Distribution among the groups was as follows: cCR with pCR (35.3%), cCR without pCR (16.3%), and less than cCR (48.4%). Median overall survival time (interquartile range) was 26.5 (18.6-36.0) months for cCR with pCR, 22.7 (14.4-35.5) months for cCR without pCR, and 17.8 (9.2-47.0) months for less than cCR (log-rank p value = 0.0033). CONCLUSIONS: Patients achieving cCR with pCR after T-VEC therapy have the most favorable overall survival outcomes, whereas those achieving cCR without pCR have inferior survival and those achieving less than cCR have the poorest overall survival outcomes. These findings emphasize the importance of histological confirmation and provide insights for optimizing T-VEC therapy in patients with advanced melanoma.

The diagnostic Accuracy of Visual versus automated dipstick proteinuria testing in Pregnancy: A systematic review and Meta-Analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of point-of-care (POC) tests for detecting proteinuria in pregnant women. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE and EMBASE databases were searched from inception to 13 November 2020. ELIGIBILITY CRITERIA AND DATA ANALYSIS: Included studies measured the sensitivity and specificity ofPOC proteinuria testing compared to laboratory reference standards (protein-creatinine ratio (PCR), 24-hour urine collection). Bivariate meta-analyses determined pooled sensitivity and specificity. Random-effects inverse-variance model determinedheterogeneity. MAIN OUTCOME MEASURES: The primary outcome was overall sensitivity and specificity, stratified by method of POC testing and reference standard. Secondary outcomes were sensitivity and specificity within thesubgroupstest brand, reference standard, and hypertension status. RESULTS: 1078 studies were identified, 17 studies comprising 23 comparisons were included. The meta-analysis included 13 studies with 19 comparisons. Pooled sensitivity and specificity of visual dipsticks against PCR was 72 % (95 % CI: 56 % to 84 %) and 92 % (95 % CI: 76 % to 98 %), respectively. Pooled sensitivity and specificity of visual dipsticks against 24-hour collection was 69 % (55 % to 80 %) and 70 % (51 % to 84 %), respectively. Pooled sensitivity and specificity for automated readers against PCR was 73 % (53 % to 86 %) and 91 % (83 % to 95 %), respectively. Pooled sensitivity and specificity of automated readers against 24-hour collection was 65 % (42 % to 83 %) and 82 % (46 % to 96 %), respectively. CONCLUSION: Visual dipsticks have comparable accuracy to automated readers, yet are notadequate as a rule-out test for proteinuria. Proteinuria POC testing maybe beneficial inantenatal care when repeatfollow-up tests are performed. PROSPERO Registration Number: CRD42021231914.

Safety, tolerability, and effect of a single aural dose of Dornase alfa at the time of ventilation tube surgery for otitis media: A Phase 1b double randomized control trial.

BACKGROUND: One third of children require repeat ventilation tube insertion (VTI) for otitis media. Disease recurrence is associated with persistent middle ear bacterial biofilms. With demonstration that Dornase alfa (a DNase) disrupts middle ear effusion biofilms ex vivo, we identified potential for this as an anti-biofilm therapy to prevent repeat VTI. First, safety and tolerability needed to be measured. METHODS: This was a phase 1B double-blinded randomized control trial conducted in Western Australia. Children between 6 months and 5 years undergoing VTI for bilateral middle ear effusion were recruited between 2012 and 2014 and followed for two years. Children's ears were randomized to receive either Dornase alfa (1 mg/mL) or 0.9 % sodium chloride (placebo) at time of surgery. Children were followed up at 2 weeks post-VTI and at 3-monthly intervals for 2 years. Outcomes assessed were: 1) safety and tolerability, 2) otorrhoea frequency, 3) blocked or extruded ventilation tube (VT) frequency, 4) time to blockage or extrusion, 5) time to infection recurrence and/or need for repeat VTI. RESULTS: Sixty children (mean age 2.3 years) were enrolled with 87 % reaching study endpoint. Treatment did not change otorrhoea frequency. Hearing improved in all children following VTI, with no indication of ototoxicity. Dornase alfa had some effect on increasing time until VT extrusion (p = 0.099); and blockage and/or extrusion (p = 0.122). Frequency of recurrence and time until recurrence were similar. Fourteen children required repeat VTI within the follow-up period. CONCLUSION: A single application of Dornase alfa into the middle ear at time of VTI was safe, non-ototoxic, and well-tolerated. TRIAL REGISTRATION: ACTRN12623000504617.

Development and external validation of a machine learning model for prediction of survival in undifferentiated pleomorphic sarcoma.

PURPOSE: Machine learning (ML) algorithms to predict cancer survival have recently been reported for a number of sarcoma subtypes, but none have investigated undifferentiated pleomorphic sarcoma (UPS). ML is a powerful tool that has the potential to better prognosticate UPS. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for cases of histologically confirmed undifferentiated pleomorphic sarcoma (UPS) (n = 665). Patient, tumor, and treatment characteristics were recorded, and ML models were developed to predict 1-, 3-, and 5-year survival. The best performing ML model was externally validated using an institutional cohort of UPS patients (n = 151). RESULTS: All ML models performed best at the 1-year time point and worst at the 5-year time point. On internal validation within the SEER cohort, the best models had c-statistics of 0.67-0.69 at the 5-year time point. The Multi-Layer Perceptron Neural Network (MLP) model was the best performing model and used for external validation. Similarly, the MLP model performed best at 1-year and worst at 5-year on external validation with c-statistics of 0.85 and 0.81, respectively. The MLP model was well calibrated on external validation. The MLP model has been made publicly available at https://rachar.shinyapps.io/ups_app/ . CONCLUSION: Machine learning models perform well for survival prediction in UPS, though this sarcoma subtype may be more difficult to prognosticate than other subtypes. Future studies are needed to further validate the machine learning approach for UPS prognostication.

Online Oncology Careers Events to Attract the Future Oncology Medical Workforce: An Exemplar Event and Review of the Literature.

AIMS: There are too few oncologists to meet the increasing burden imposed by the rising incidence of cancer. This results from issues with the retention of established oncologists and longstanding challenges to the recruitment of adequate numbers of trainees. To counter this, the British Oncology Network for Undergraduate Societies (BONUS) devised an online oncology careers event for medical students and junior doctors who are yet to select a specialty. MATERIALS AND METHODS: An online careers event was devised with a focus on oncology practice and related subspecialties, as well as research. Event attendees were asked to respond to piloted pre- and post-event surveys. Knowledge and attitudes towards a career in oncology were evaluated using Likert scale and multiple-choice questions. A systematic literature search was carried out to contextualise these data. RESULTS: Of the 73 attendees, 44 (60%) participants completed both the pre- and post-event surveys; 79.5% of attendees believed that information on a career in oncology is lacking in medical training. This viewpoint was supported by the systematic review, which highlighted a need for relevant focussed interventions targeted at medical students and fledgling doctors. The education event led to an increase in the median reported understanding of the oncology career pathway from 6.0 to 8.0 (P < 0.05 and P < 0.001), as well as the likelihood of pursuing a career in oncology (8.0-9.0; P < 0.05). It was also associated with a proportional increase in medical and surgical oncology interest, albeit with a fall in interest in clinical and interventional oncology as well as academia. CONCLUSION: A targeted online careers event increases knowledge of and interest in a career in oncology, albeit predominantly for medical and surgical subspecialties. Broader initiatives based on our model should be developed and careers in academia as well as clinical and interventional oncology emphasised.

Improved outcomes of large B-cell lymphoma patients treated with CD19 CAR T in the UK over time.

The success of CD19 Chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) has been partially offset by toxicity and logistical challenges, which off-the-shelf agents like CD20xCD3 bispecific antibodies might potentially overcome. However, when using CAR T outcomes as the 'standard-of-care comparator̕ for relapsed/refractory (r/r) LBCL, a potential learning curve with implementing a novel, complex therapy like CAR T needs to be considered. To address this, we analysed 726 UK patients intended to be treated with CD19 CAR T for r/r LBCL and compared outcomes between the first year of the national CAR T programme (Era 1; 2019) and the more recent treatment era (Era 2; 2020-2022). We identified significant improvements for Era 2 versus Era 1 in dropout rate (17% vs. 27%, p = 0.001), progression-free survival (1-year PFS 50% vs. 32%, p < 0.001) and overall survival (1-year OS 60% vs. 40%, p < 0.001). We also observed increased use of bridging therapy, improvement in bridging outcomes, more tocilizumab/corticosteroid use, reduced high-grade cytokine release syndrome (4% vs. 9%, p = 0.01) and intensive care unit admissions (20% vs. 32%, p = 0.001). Our results demonstrate significant improvement in CAR T outcomes over time, highlighting the importance of using up-to-date clinical data when comparing CAR T against new treatment options for r/r LBCL.

Real-time x-ray abnormality alerts for emergency departments using a radiographer comment model - a multisite pilot study.

INTRODUCTION: The timely communication of clinically significant image appearances to Emergency Department (ED) referrers is necessary for optimum patient care. Australian reliance on verbal communication only is time-limited, open to misinterpretation and lacks transparency. A combined radiographer alert and comment model was designed to reliably communicate image abnormalities to ED referrers in real-time. METHODS: A multidisciplinary steering group designed the model for all ED general imaging. Protocols were developed to document radiographer comments (critical, urgent and clinically significant) in patients' medical records. Critical findings were communicated directly to ED. Five NSW hospitals varying in size, complexity and population demographics piloted the model between three to twelve months during 2021-2022. Site auditors compared comments with the radiology report and designated each as True Positive (TP), False Positive (FP), indeterminate and clinically significant. Indeterminate cases were analysed by an external radiologist. Inter-observer consensus was obtained for all classifications via two independent auditors. The Positive Predictive Value (PPV), or precision of the comment, was calculated for each site. RESULTS: Radiographers (n = 69) provided comments for 1102 cases. The pooled average PPV for TP was 0.96; (0.947-0.971; 95% CI). The weighted mean error (FP comments) was 3.9%; (2.9% - 5.3%.; 95% CI). CONCLUSION: The Radiographer Comment model provided consistent levels of commenting precision and reproducibility across a range of sites with a pooled average PPV (0.96). The False Positive rate or weighted mean error (FP) of 3.9% (2.9% - 5.3%.; 95% CI) was low. IMPLICATIONS FOR FUTURE PRACTICE: A strategic, interprofessional approach in the implementation of an image alert combined with a Radiographer Comment can be adapted across a variety of hospital settings for ED and other departments.

A park-based group mobility program for older adults with difficulty walking outdoors: a quantitative process evaluation of the Getting Older Adults Outdoors (GO-OUT) randomized controlled trial.

BACKGROUND: Process evaluations of randomized controlled trials (RCTs) of community exercise programs are important to help explain the results of a trial and provide evidence of the feasibility for community implementation. The objectives of this process evaluation for a multi-centre RCT of outdoor walking interventions for older adults with difficulty walking outdoors, were to determine: 1) implementation fidelity (the extent to which elements of the intervention were delivered as specified in the original protocol) and 2) participant engagement (the receipt of intervention components by the participants) in the Getting Older Adults Outdoors (GO-OUT) trial. METHODS: GO-OUT participants attended an active 1-day workshop designed to foster safe, outdoor walking skills. After the workshop, 190 people at 4 sites were randomized to an outdoor walk group (OWG) (n = 98) which met 2x/week for 10 weeks, or the weekly reminders (WR) group (n = 92) which received a phone reminder 1x/week for 10 weeks. The OWG had 5 components - warm-up, continuous distance walk, task-oriented walking activities, 2nd continuous distance walk, and cool-down. Data on implementation fidelity and participant engagement were gathered during the study through site communications, use of standardized forms, reflective notes of the OWG leaders, and accelerometry and GPS assessment of participants during 2 weeks of the OWG. RESULTS: All sites implemented the workshop according to the protocol. Participants were engaged in all 8 activity stations of the workshop. WR were provided to 96% of the participants in the WR intervention group. The 5 components of the OWG sessions were implemented in over 95% of the sessions, as outlined in the protocol. Average attendance in the OWG was not high - 15% of participants did not attend any sessions and 64% of participants in the OWG attended > 50% of the sessions. Evaluations with accelerometry and GPS during week 3 and 9 OWG sessions suggest that participants who attended were engaged and active during the OWG. CONCLUSIONS: This process evaluation helps explain the main study findings and demonstrates the flexibility required in the protocol for safe and feasible community implementation. Future research could explore the use of additional behaviour change strategies to optimize attendance for community implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03292510 Date of registration: September 25, 2017.