Intra-arterial Pressure Enabled Drug Delivery Significantly Increases Penetration of Glass Microspheres in a Porcine Liver Tumor Model.

PURPOSE: To test the hypothesis that Pressure Enabled Drug Delivery (PEDD) with a TriNav device (TNV-21120-35, TriSalus Life Sciences, Westminster, CO) would improve the delivery of surrogate therapeutic glass microspheres (GM) via hepatic artery infusion (HAI) to liver tumors when compared to a conventional endhole microcatheter. MATERIALS AND METHODS: The study was conducted in transgenic pigs (Oncopigs) with induced liver tumors. Tumors were infused intra-arterially with fluorescently labeled GM. PEDD with a TriNav device was compared to conventional endhole delivery in both lobar and selective infusions. Near-Infrared (nearIR) imaging was used to detect GM fluorescent signal in tumors. Image analysis with a custom Deep Learning algorithm (Visiopharm A/S) was used to quantitate signal intensity in relation to the tumor border. RESULTS: With lobar infusions, significant increases in GM signal intensity were observed in and around tumors after PEDD (n=10) when compared to conventional delivery (n=7), with PEDD increasing penetration into the tumor by 117% (p = 0.004). In selective infusions, PEDD (n=9) increased penetration into the tumor by 39% relative to conventional delivery (n=8, p =0.032). Lobar PEDD delivery of GM to the tumor was statistically equivalent to conventional selective delivery (p=0.497). CONCLUSIONS: PEDD with a TriNav device significantly improved GM uptake in liver tumors relative to conventional infusion in both lobar and selective procedures. Lobar GM delivery with PEDD was equivalent to conventional selective delivery with an endhole device, suggesting that proximal PEDD infusions may enable effective delivery without selection of distal target vessels.

Genetic Counseling, Testing, and Family Communication Into Survivorship After Diagnosis of Breast Cancer.

PURPOSE: To examine receipt of genetic testing and communication with relatives about results into survivorship after diagnosis of breast cancer. METHODS: Women age 20-79 years diagnosed with early-stage breast cancer in 2014-2015 and reported to the Georgia and Los Angeles County SEER registries were surveyed approximately 7 months and 6 years after diagnosis (n = 1,412). We asked about genetic counseling, testing, and communication with relatives about results. We categorized women into indications for testing on the basis of clinical guidelines at the time of diagnosis and at the time of the follow-up survey (FUPs). RESULTS: A total of 47.4% had indications for genetic testing at any time: 28.0% at baseline and an additional 19.4% at the time of the FUPs (only); 71.9% (95% CI, 67.4 to 76.4) of those with a baseline indication reported genetic testing versus 53.3% (95% CI, 47.3 to 59.2) with an indication at FUPs only and 35.0% (95% CI, 31.6 to 38.4) with no indication (P < .001). There were no significant racial or ethnic differences in receipt of testing, controlling for age and clinical indications (P = .239); results for genetic counseling were similar. Only 3.4% of survivors had direct-to-consumer genetic testing (DTCt) for cancer. Testers who reported a pathogenic variant (n = 62) were much more likely to have talked to most or all their first-degree adult relatives about genetic testing than those with a variant of unknown significance (n = 49) or a negative finding (n = 419): 62.7% versus 38.8% and 38.0%, respectively (P < .001). CONCLUSION: Many women with indications for genetic counseling and testing into survivorship do not receive it. But those tested reach out to family members on the basis of the clinical relevance of their results. Very few patients obtained DTCt, which suggests that these tests do not substitute for clinical testing in breast cancer survivors.

Emergency department utilization by persons with rheumatoid arthritis: a population-based cohort study.

Some emergency department (ED) visits by persons with rheumatoid arthritis (RA) may be avoidable. This study aims to describe ED use by persons with RA in Alberta, Canada over a 10-year period. Using linked population-based administrative datasets, the annual frequency of ED visits, timing of visits, acuity at presentation assessed (Canadian Triage Acuity Scale (CTAS)), return visits within 72 h, and final disposition were assessed. Most responsible diagnoses assessed by the ED provider were categorized. Between 2008 and 2017, a total of 48,633 persons with RA had 416,964 unique ED visits. There was a 41% relative increase in visits over the study period and within a fiscal year 37% of persons with RA on average attended an ED. Half of the visits were assessed as CTAS 4 'Less Urgent' (31%) and CTAS 5 'Non-Urgent' (19%). No specific diagnosis could be assigned in 36% of visits and RA was listed as the most responsible diagnosis in 2.5% of all visits. Hospital admissions, occurring on average for 14% of ED visits, increased by 15% over the 10 years, and were rare for CTAS 4 (6.4%) and CTAS 5 (1.4%) presentations. Male patients (difference to female 1.2%, 95%CI 0.6, 1.7) and urban patients (difference to rural 8.4%, 95%CI 7.7, 9.2) were more frequently admitted to hospital. Persons with RA have increased ED utilization over time, with a significant volume of less urgent and non-urgent visits. Opportunities for appropriate ambulatory care provision to reduce acute care use should be identified.

Deciding to Attend the Emergency Department: Experiences of Patients With Inflammatory Arthritis.

OBJECTIVE: Patients may use emergency departments (EDs) to meet their health needs when ambulatory care systems are not sufficient. We aim to describe contributing factors to the decision made by persons with inflammatory arthritis (IA) to present to the ED, as well as their experiences of ED care and postdischarge follow-up. METHODS: An embedded mixed-methods approach was taken to contextualize quantitative data with associated free-text responses from an online survey distributed to residents of Alberta with a known IA condition and an ED visit. RESULTS: Eighty-two persons (63% aged 16-55 years, 48% female, 50% urban residents) with rheumatoid arthritis (48%), psoriatic arthritis (12%), spondyloarthritis (6%), or gout (34%) completed the survey. Presenting concerns were arthritis flare (37%), chest pain (15%), injury (12%), and infection (11%). Of all visits, 29% proceeded directly to the ED, 35% attempted accessing ambulatory care first, and 32% arrived for a return visit. In presentations for arthritis flare, patients were aware of the rheumatology service being contacted by the ED provider for advice in just 9% of events. Challenges in healthcare system coordination and system pressures resulted in patients requiring ED attendance to assess their concern. The quality of communication and relationality developed between patients with IA and healthcare providers informed experiences of ED care. CONCLUSION: Modifying rheumatology ambulatory care models could better meet patient needs and ultimately reduce avoidable ED use by patients with IA.

The i-gel® supraglottic airway device compared to endotracheal intubation as the initial prehospital advanced airway device: A natural experiment during the COVID-19 pandemic.

Objective: Unlike randomized controlled trials, practical real-world studies can offer important information about implementation of prehospital interventions, particularly in community settings where there may be reluctance to adopt new practices. We present the results of a natural experiment that was driven by mandated COVID-19 pandemic-driven shift from endotracheal intubation (ETI) to the i-gel® supraglottic airway (SGA) as a primary advanced airway management device in the prehospital setting to reduce emergency medical services (EMS) personnel exposure to potentially infectious secretions. The objective was to compare first-pass success and timing to successful airway placement between ETI and the i-gel® SGA under extenuating circumstances. Methods: This pre/post study compared airway placement metrics in prehospital patients requiring advance airway management for non-trauma-related conditions. Data from EMS records were extracted over 2 years, 12 months pre-pandemic, and 12 months post-pandemic. During the pre-COVID-19 year, the EMS protocols utilized ETI as the primary advanced airway device (ETI group). Post-pandemic paramedics were mandated to utilize i-gel® SGA as the primary advanced airway device to reduce exposure to secretions (SGA group). Results: There were 199 adult patients, 83 (42%) in the ETI group and 116 (58%) in the SGA group. First-pass success was significantly higher with SGA 96% (92%-99%) than ETI 68% (57%-78%) with paramedics citing the inability to visualize the airway in 52% of ETI cases. Time to first-pass success was significantly shorter in the SGA group (5.9 min [5.1-6.7 min]) than in the ETI group (8.3 min [6.9-9.6 min]), as was time to overall successful placement at 6.0 min (5.1-6.8 min) versus 9.6 min (8.2-11.1 min), respectively. Multiple placement attempts were required in 26% of ETI cases and 1% of the SGA cases. There were no statistically significant differences in the number and types of complications between the cohorts. Return of spontaneous circulation (on/before emergency department [ED] arrival), mortality at 28 days, intensive care unit length of stay, or ventilator-free days between the groups were not statistically different between the groups. Conclusion: In this natural experiment, the SGA performed significantly better than ETI in first-pass airway device placement success and was significantly faster in achieving first-pass success, and overall airway placement, thus potentially reducing exposure to respiratory pathogens. Practical real-world studies can offer important information about implementation of prehospital interventions, particularly in community settings and in systems with a low frequency of tracheal intubations.

Real-world evidence of Pressure-Enabled Drug Delivery for trans-arterial chemoembolization and radioembolization among patients with hepatocellular carcinoma and liver metastases.

OBJECTIVES: Pressure-Enabled Drug Delivery (PEDD), a method using pressure to advance catheter-delivered drug distribution, can improve treatment for hepatocellular carcinoma (HCC) and liver metastases, but real-world evidence is limited. We compared baseline patient characteristics, clinical complexity, and post-procedure healthcare resource utilization (HRUs) and clinical complications for PEDD and non-PEDD procedures. METHODS: This study used a retrospective, longitudinal, cohort design of claims data from Clarivate's Real World Data Repository, which includes 98% of US payers with over 300 million unique patients from all US states. We identified patients with a trans-arterial chemoembolization (TACE) or trans-arterial radioembolization (TARE) from 1 January 2019 to 31 December 2022. Subsamples grouped patients with HCC receiving a TARE procedure at their first embolization and patients with metastatic colorectal cancer (CRC) that received a TARE procedure. We reported descriptive comparisons of our full sample of patients with HCC and liver metastases receiving PEDD versus non-PEDD procedures. We then conducted a matching-adjusted comparison of HRUs and clinical complications for PEDD and non-PEDD patients among our subsamples (HCC receiving a TARE procedure at their first embolization and patients with metastatic CRC that received a TARE procedure). Matching was based on baseline demographic and clinical characteristics using coarsened exact matching and propensity-score matching. HRUs included inpatient, outpatient, and emergency department visits. Clinical complications included ascites, cholecystitis, fatigue, gastric ulcer, gastritis, jaundice, LFT increase, lymphopenia, portal hypertension, and post-embolization syndrome. RESULTS: PEDD procedures were used on patients with worse baseline disease burdens: baseline Charlson comorbidity index (mean of 6.5 vs. 5.8), any prior clinical complication related to underlying disease (33.7 vs. 31.0%), and prior systemic therapy (22.1% vs. 16.2%). PEDD patients had a greater number of procedural codes indicative of technical complexity for TACE (PEDD mean = 226.3; non-PEDD mean = 134.5; p value <.01) and TARE (PEDD mean = 205.56; non-PEDD mean = 94.8; p value <0.01). Matching-adjusted analyses of patients with HCC and CRC demonstrated comparable HRU and clinical complications for PEDD and non-PEDD procedures post-index. CONCLUSION: Despite higher baseline disease burden and complexity, post-procedure HRU and clinical complications for PEDD patients were similar to non-PEDD patients. The complex baseline clinical profile may reflect selection of challenging cases for PEDD use. Future studies should validate the benefits observed with PEDD embolization in larger samples with greater statistical power.

Content validity testing of the INTERMED Self-Assessment in a sample of adults with rheumatoid arthritis and rheumatology healthcare providers.

BACKGROUND: Care complexity can occur when patients experience health challenges simultaneously with social barriers including food and/or housing insecurity, lack of transportation or other factors that impact care and patient outcomes. People with rheumatoid arthritis (RA) may experience care complexity due to the chronicity of their condition and other biopsychosocial factors. There are few standardised instruments that measure care complexity and none that measure care complexity specifically in people with RA. OBJECTIVES: We assessed the content validity of the INTERMEDS Self-Assessment (IMSA) instrument that measures care complexity with a sample of adults with RA and rheumatology healthcare providers (HCPs). Cognitive debriefing interviews utilising a reparative framework were conducted. METHODS: Patient participants were recruited through two existing studies where participants agreed to be contacted about future studies. Study information was also shared through email blasts, posters and brochures at rheumatology clinic sites and trusted arthritis websites. Various rheumatology HCPs were recruited through email blasts, and divisional emails and announcements. Interviews were conducted with nine patients living with RA and five rheumatology HCPs. RESULTS: Three main reparative themes were identified: (1) Lack of item clarity and standardisation including problems with item phrasing, inconsistency of the items and/or answer sets and noninclusive language; (2) item barrelling, where items asked about more than one issue, but only allowed a single answer choice; and (3) timeframes presented in the item or answer choices were either too long or too short, and did not fit the lived experiences of patients. Items predicting future healthcare needs were difficult to answer due to the episodic and fluctuating nature of RA. CONCLUSIONS: Despite international use of the IMSA to measure care complexity, patients with RA and rheumatology HCPs in our setting perceived that it did not have content validity for use in RA and that revision for use in this population under a reparative framework was unfeasible. Future instrument development requires an iterative cognitive debriefing and repair process with the population of interest in the early stages to ensure content validity and comprehension. PATIENT OR PUBLIC CONTRIBUTION: Patient and public contributions included both patient partners on the study team and people with RA who participated in the study. Patient partners were involved in study design, analysis and interpretation of the findings and manuscript preparation. Data analysis was structured according to emergent themes of the data that were grounded in patient perspectives and experiences.

A population-based analysis of rheumatology care patterns for inflammatory arthritis during COVID-19 in Alberta, Canada.

OBJECTIVE: The aim of the study was to understand the impact of the COVID-19 pandemic on inflammatory arthritis (IA) rheumatology care in Alberta, Canada. METHODS: We used linked provincial health administrative datasets to establish an incident cohort of individuals with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and Ankylosing Spondylitis (AS) seen at least once by a rheumatologist. We examined incidence rates (IR) per 100,000 population, and patterns of follow-up care between 2011 and 2022. In a subset of individuals diagnosed five years prior to the pandemic, we report on those lost to follow-up during the pandemic, and those with virtual care visits followed by in-person visit within 30 days. Multivariable logistic regression was used to examine patient characteristics associated with these patterns of care. RESULTS: The IR for RA in 2020 declined compared to previous years (44.6), but not for AS (9.2) or PsA (9.1). In 2021 IRs rose (RA 49.5; AS 11.8; PsA 11.8). Among those diagnosed within 5 years of the pandemic, 632 (6.0 %) were lost to follow-up, with characteristics of those lost to follow-up differing between IA types. 1444 individuals had at least one virtual visit followed within 30 days by an in-person follow-up. This was less common in males (OR 0.69-0.79) and more common for those with a higher frequency of physician visits prior to the pandemic (OR 1.27-1.32). CONCLUSION: Impacts of patterns of care during the pandemic should be further explored for healthcare planning to uphold optimal care access and promote effective use of virtual care.

Doctor Versus Artificial Intelligence: Patient and Physician Evaluation of Large Language Model Responses to Rheumatology Patient Questions in a Cross-Sectional Study.

OBJECTIVE: The objective of the current study was to assess the quality of large language model (LLM) chatbot versus physician-generated responses to patient-generated rheumatology questions. METHODS: We conducted a single-center cross-sectional survey of rheumatology patients (n = 17) in Edmonton, Alberta, Canada. Patients evaluated LLM chatbot versus physician-generated responses for comprehensiveness and readability, with four rheumatologists also evaluating accuracy by using a Likert scale from 1 to 10 (1 being poor, 10 being excellent). RESULTS: Patients rated no significant difference between artificial intelligence (AI) and physician-generated responses in comprehensiveness (mean 7.12 ± SD 0.99 vs 7.52 ± 1.16; P = 0.1962) or readability (7.90 ± 0.90 vs 7.80 ± 0.75; P = 0.5905). Rheumatologists rated AI responses significantly poorer than physician responses on comprehensiveness (AI 5.52 ± 2.13 vs physician 8.76 ± 1.07; P < 0.0001), readability (AI 7.85 ± 0.92 vs physician 8.75 ± 0.57; P = 0.0003), and accuracy (AI 6.48 ± 2.07 vs physician 9.08 ± 0.64; P < 0.0001). The proportion of preference to AI- versus physician-generated responses by patients and physicians was 0.45 ± 0.18 and 0.15 ± 0.08, respectively (P = 0.0106). After learning that one answer for each question was AI generated, patients were able to correctly identify AI-generated answers at a lower proportion compared to physicians (0.49 ± 0.26 vs 0.97 ± 0.04; P = 0.0183). The average word count of AI answers was 69.10 ± 25.35 words, as compared to 98.83 ± 34.58 words for physician-generated responses (P = 0.0008). CONCLUSION: Rheumatology patients rated AI-generated responses to patient questions similarly to physician-generated responses in terms of comprehensiveness, readability, and overall preference. However, rheumatologists rated AI responses significantly poorer than physician-generated responses, suggesting that LLM chatbot responses are inferior to physician responses, a difference that patients may not be aware of.

Burnout and fatigue amongst internal medicine residents: A cross-sectional study on the impact of alternative scheduling models on resident wellness.

BACKGROUND: Fatigue and burnout are prevalent among resident physicians across Canada. Shifts exceeding 24 hours are commonly purported as detrimental to resident health and performance. Residency training programs have employed strategies towards understanding and intervening upon the complex issue of resident fatigue, where alternative resident scheduling models have been an area of active investigation. This study sought to characterize drivers and outcomes of fatigue and burnout amongst internal medicine residents across different scheduling models. METHODS: We conducted cross-sectional surveys were among internal medicine resident physicians at the University of Alberta. We collected anonymized socioeconomic demographics and medical education background, and estimated associations between demographic or work characteristics and fatigue and burnout outcomes. RESULTS: Sixty-nine participants competed burnout questionnaires, and 165 fatigue questionnaires were completed (response rate of 48%). The overall prevalence of burnout was 58%. Lower burnout prevalence was noted among respondents with dependent(s) (p = 0.048), who identified as a racial minority (p = 0.018), or completed their medical degree internationally (p = 0.006). The 1-in-4 model was associated with the highest levels of fatigue, reported increased risk towards personal health (OR 4.98, 95%CI 1.77-13.99) and occupational or household harm (OR 5.69, 95%CI 1.87-17.3). Alternative scheduling models were not associated with these hazards. CONCLUSIONS: The 1-in-4 scheduling model was associated with high rates of resident physician fatigue, and alternative scheduling models were associated with less fatigue. Protective factors against fatigue are best characterized as strong social supports outside the workplace. Further studies are needed to characterize the impacts of alternative scheduling models on resident education and patient safety.

Pressure-Enabled Drug Delivery (PEDD) of a class C TLR9 agonist in combination with checkpoint inhibitor therapy in a murine pancreatic cancer model.

BACKGROUND: Systemic immunotherapy has had limited clinical benefit in pancreatic ductal adenocarcinoma. This is thought to be due to its desmoplastic immunosuppressive tumor microenvironment in addition to high intratumoral pressures that limit drug delivery. Recent preclinical cancer models and early-phase clinical trials have demonstrated the potential of toll-like receptor 9 agonists, including the synthetic CpG oligonucleotide SD-101, to stimulate a wide range of immune cells and eliminate suppressive myeloid cells. We hypothesized that Pressure-Enabled Drug Delivery via Pancreatic Retrograde Venous Infusion of toll-like receptor 9 agonist would improve responsiveness to systemic anti-programmed death receptor-1 checkpoint inhibitor therapy in a murine orthotopic pancreatic ductal adenocarcinoma model. METHODS: Murine pancreatic ductal adenocarcinoma (KPC4580P) tumors were implanted into the pancreatic tails of C57BL/6J mice and treated 8 days after implantation. Mice were assigned to one of the following treatment groups: Pancreatic Retrograde Venous Infusion delivery of saline, Pancreatic Retrograde Venous Infusion delivery of toll-like receptor 9 agonist, systemic anti-programmed death receptor-1, systemic toll-like receptor 9 agonist, or the combination of Pancreatic Retrograde Venous Infusion delivery of toll-like receptor 9 agonist and systemic anti-programmed death receptor-1 (Combo). Fluorescently labeled toll-like receptor 9 agonist (radiant efficiency) was used to measure uptake of the drug on day 1. Changes in tumor burden were evaluated by necropsy at 2 different time points, 7 and 10 days after toll-like receptor 9 agonist treatment. Blood and tumors were collected at necropsy 10 days after toll-like receptor 9 agonist treatment for flow cytometric analysis of tumor-infiltrating leukocytes and plasma cytokines. RESULTS: All mice analyzed survived to necropsy. Site of tumor fluorescence measurements revealed 3-fold higher intensity fluorescence in Pancreatic Retrograde Venous Infusion delivery of toll-like receptor 9 agonist compared to systemic toll-like receptor 9 agonist mice. Tumor weights were significantly lower in the Combo group compared to Pancreatic Retrograde Venous Infusion delivery of saline. Flow cytometry of the Combo group demonstrated significantly increased overall T-cell number, specifically CD4+ T-cells, and a trend toward increased CD8+ T-cells. Cytokine analysis showed significantly decreased IL-6 and CXCL1. CONCLUSION: Pressure-Enabled Drug Delivery of toll-like receptor 9 agonist by Pancreatic Retrograde Venous Infusion with systemic anti-programmed death receptor-1 demonstrated improved pancreatic ductal adenocarcinoma tumor control in a murine pancreatic ductal adenocarcinoma model. These results support study of this combination therapy in pancreatic ductal adenocarcinoma patients and expansion of ongoing Pressure-Enabled Drug Delivery clinical trials.

Germline Genetic Testing After Cancer Diagnosis.

Importance: Germline genetic testing is recommended by practice guidelines for patients diagnosed with cancer to enable genetically targeted treatment and identify relatives who may benefit from personalized cancer screening and prevention. Objective: To describe the prevalence of germline genetic testing among patients diagnosed with cancer in California and Georgia between 2013 and 2019. Design, Setting, and Participants: Observational study including patients aged 20 years or older who had been diagnosed with any type of cancer between January 1, 2013, and March 31, 2019, that was reported to statewide Surveillance, Epidemiology, and End Results registries in California and Georgia. These patients were linked to genetic testing results from 4 laboratories that performed most germline testing for California and Georgia. Main Outcomes and Measures: The primary outcome was germline genetic testing within 2 years of a cancer diagnosis. Testing trends were analyzed with logistic regression modeling. The results of sequencing each gene, including variants associated with increased cancer risk (pathogenic results) and variants whose cancer risk association was unknown (uncertain results), were evaluated. The genes were categorized according to their primary cancer association, including breast or ovarian, gastrointestinal, and other, and whether practice guidelines recommended germline testing. Results: Among 1 369 602 patients diagnosed with cancer between 2013 and 2019 in California and Georgia, 93 052 (6.8%) underwent germline testing through March 31, 2021. The proportion of patients tested varied by cancer type: male breast (50%), ovarian (38.6%), female breast (26%), multiple (7.5%), endometrial (6.4%), pancreatic (5.6%), colorectal (5.6%), prostate (1.1%), and lung (0.3%). In a logistic regression model, compared with the 31% (95% CI, 30%-31%) of non-Hispanic White patients with male breast cancer, female breast cancer, or ovarian cancer who underwent testing, patients of other races and ethnicities underwent testing less often: 22% (95% CI, 21%-22%) of Asian patients, 25% (95% CI, 24%-25%) of Black patients, and 23% (95% CI, 23%-23%) of Hispanic patients (P < .001 using the χ2 test). Of all pathogenic results, 67.5% to 94.9% of variants were identified in genes for which practice guidelines recommend testing and 68.3% to 83.8% of variants were identified in genes associated with the diagnosed cancer type. Conclusions and Relevance: Among patients diagnosed with cancer in California and Georgia between 2013 and 2019, only 6.8% underwent germline genetic testing. Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.

Primary care provider attitudes about and tendency to use non-recommended surveillance tests after curative breast cancer treatment.

PURPOSE: Little is known about the factors contributing to the receipt of non-recommended surveillance testing among early-stage breast cancer survivors. We assessed primary care providers (PCP) attitudes about and tendency to order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors post-adjuvant chemotherapy. METHODS: A stratified random sample of PCPs identified by early-stage breast cancer survivors were surveyed (N = 518, 61% response rate). PCPs were asked how likely they would be to order bone scans, imaging and/or tumor marker testing using a clinical vignette of an early-stage asymptomatic patient where these tests are non-recommended. A composite tendency to order score was created and categorized by tertiles (low, moderate, high). PCP-reported factors associated with high and moderate tendency to order non-recommended testing (vs. low) were estimated using multivariable, multinomial logistic regression. RESULTS: In this sample, 26% reported a high tendency to order non-recommended surveillance tests during survivorship for early-stage breast cancer survivors. PCPs who identified as family practice physicians and PCPs reporting more confidence in ordering surveillance testing were more likely to report a high tendency to order non-recommended testing (vs. low) ((aOR family practice 2.09, CI 1.2, 3.8; aOR more confidence 1.9, CI 1.1, 3.3). CONCLUSIONS: In this population-based sample of PCPs caring for breast cancer survivors, over a quarter of PCPs reported they would order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors. Efforts to better support PCPs and disseminate information about appropriate surveillance for cancer survivors are warranted.

Cascade Genetic Risk Education and Testing in Families With Hereditary Cancer Syndromes: A Pilot Study.

PURPOSE: Cascade genetic risk evaluation in families with hereditary cancer can reduce the burden of disease but the rate of germline genetic testing in relatives of patients at risk is low. METHODS: We identified all 277 women diagnosed with breast cancer in Georgia in 2017 who linked to a clinically actionable germline pathogenic variant through a Surveillance, Epidemiology, and End Results registry-variant linkage initiative. We surveyed them, and then invited eligible respondents to an online platform hosted by a navigator that offered cancer genetic risk education and germline genetic testing to untested relatives. We randomly assigned patient-family clusters at the time of the patient enrollment offer to free versus $50 (USD) test cost. Patients invited relatives to join the study through personalized e-mail. Enrolled relatives received online cancer genetic education and the opportunity to order clinical germline genetic testing through the platform. The primary outcome was the number of relatives who ordered genetic testing. RESULTS: One hundred twenty-five of 277 patients completed surveys (45.2%). Most respondents were eligible for the trial offer (113 of 125; 90.4%). In the free testing arm, 20 of 56 eligible patients participated (35.7% of eligible respondents) and they invited 28 relatives: 12 relatives enrolled and 10 ordered testing. In the $50 (USD) arm, 16 of 57 eligible patients participated (28.1%) and they invited 38 relatives: 18 relatives enrolled and 17 ordered testing. CONCLUSION: Cascade genetic testing in families with hereditary cancer syndromes accrued through a population-based cancer registry can be achieved through an online platform that offers genetic risk education and low-cost testing to relatives. A modest charge did not appear to influence the percentage of participating patients, numbers of participating relatives, and numbers of relatives who received genetic testing.

Rheumatology Image of the Month: A Low Resource Innovation With Measurable Results.

OBJECTIVES: Strategies to increase confidence in rheumatology knowledge are valuable for medical trainees and residents. A web-based teaching innovation was implemented in an attempt to increase rheumatology exposure for internal medicine residents. METHODS: An Image of the Month webpage was established, where a practicing rheumatologist would post a new image that could be answered online by internal medicine residents. Cumulative data was analyzed to determine the extent and change in rheumatology exposure. RESULTS: The Image of the Month webpage posted images for a total of 76 months between July 2010 to May 2017, with a total of 1326 submitted responses. The proportion of residents who only participated in Image of the Month and only did a rheumatology rotation averaged 36.1% and 16.5%, respectively. The proportion of residents who only participated in Image of the Month was higher than the proportion who only did a rheumatology rotation for all of the 7 time periods assessed. A total of 491 residents participated in Image of the Month, with an average of 54.9% of residents participating each year. Overall, on average, 52 residents had 1 or more submissions, 3.6 entries were submitted per resident, and 17.4 entries were submitted per month. Junior residents (PGY1) participated more often than senior residents (PGY3). CONCLUSIONS: The Image of the Month webpage successfully improves internal medicine resident exposure to rheumatology with minimal resources and manpower required. Further study is necessary to determine the impact this exposure may have on the abilities and confidence levels of internal medicine residents.

Biological Sex Inequality in Rheumatology Wait Times During the COVID-19 Pandemic.

OBJECTIVE: To examine the effect of biological sex on wait times to first rheumatology appointment in a central triage system before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Deidentified data of all referred patients between November 2019 and June 2022 were extracted from the electronic medical record. Variables, including time from referral to first appointment, biological sex, referral period, urgency status, age, and geographic location were collected and analyzed. RESULTS: Twelve thousand eight hundred seventeen referrals were identified. Wait times increased by 24.23 days in the peri-COVID period (P < 0.001). In the pre-COVID period, there was no significant difference in wait times by biological sex or age. Triage urgency was a predictor of wait time, with semiurgent referrals seen 8.94 days (95% CI -15.90 to -1.99) sooner than routine referrals and urgent referrals seen 25.42 days (95% CI -50.36 to -0.47) sooner than routine referrals. In the peri-COVID period, there was a significant difference in wait time by biological sex with women waiting on average 10.03 days (95% CI 6.98-13.09) longer than men (P < 0.001). Older patients had shorter wait times than younger patients, with a difference of -4.64 days for every 10-year increase in age (95% CI -5.49 to -3.78). Triage urgency continued to be a predictor of wait time. CONCLUSION: Women and younger patients appear to have been affected by wait time increases during the COVID-19 pandemic. This finding should be further investigated to determine its pervasiveness across other specialities and to better understand the underlying cause of this finding.

Orbital fat swelling: A biomechanical theory and supporting model for spaceflight-associated neuro-ocular syndrome (SANS).

Spaceflight-Associated Neuro-ocular Syndrome (SANS) is a descriptor of several ocular and visual signs and symptoms which commonly afflicts those exposed to microgravity. We propose a new theory for the driving force leading to the development of Spaceflight-Associated Neuro-ocular Syndrome which is described via a finite element model of the eye and orbit. Our simulations suggest that the anteriorly directed force produced by orbital fat swelling is a unifying explanatory mechanism for Spaceflight-Associated Neuro-ocular Syndrome, as well as producing a larger effect than that generated by elevation in intracranial pressure. Hallmarks of this new theory include broad flattening of the posterior globe, loss of tension in the peripapillary choroid, decreased axial length, consistent with findings in astronauts. A geometric sensitivity study suggests several anatomical dimensions may be protective against Spaceflight-Associated Neuro-ocular Syndrome.

Investigating Associations Between Access to Rheumatology Care, Treatment, Continuous Care, and Healthcare Utilization and Costs Among Older Individuals With Rheumatoid Arthritis.

OBJECTIVE: To examine the association between rheumatologist access, early treatment, and ongoing care of older-onset rheumatoid arthritis (RA) and healthcare utilization and costs following diagnosis. METHODS: We analyzed data from a population-based inception cohort of individuals aged > 65 years with RA in Ontario, Canada, diagnosed between 2002 and 2014 with follow-up to 2019. We assessed 4 performance measures in the first 4 years following diagnosis, including access to rheumatology care, yearly follow-up, timely treatment, and ongoing treatment with a disease-modifying antirheumatic drug. We examined annual healthcare utilization, mean direct healthcare costs, and whether the performance measures were associated with costs in year 5. RESULTS: A total of 13,293 individuals met inclusion criteria. The mean age was 73.7 (SD 5.7) years and 68% were female. Total mean direct healthcare cost per individual increased annually and was CAD $13,929 in year 5. All 4 performance measures were met for 35% of individuals. In multivariable analyses, costs for not meeting access to rheumatology care and timely treatment performance measures were 20% (95% CI 8-32) and 6% (95% CI 1-12) higher, respectively, than where those measures were met. The main driver of cost savings among individuals meeting all 4 performance measures were from lower complex continuing care, home care, and long-term care costs, as well as fewer hospitalizations and emergency visits. CONCLUSION: Access to rheumatologists for RA diagnosis, timely treatment, and ongoing care are associated with lower total healthcare costs at 5 years. Investments in improving access to care may be associated with long-term health system savings.

Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases.

OBJECTIVE: Programmed cell death protein 1 (PD-1) checkpoint inhibition and adoptive cellular therapy have had limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM). We sought to evaluate the effect of interleukin 10 (IL-10) blockade on endogenous T cell and chimeric antigen receptor T (CAR-T) cell antitumour function in CRLM slice cultures. DESIGN: We created organotypic slice cultures from human CRLM (n=38 patients' tumours) and tested the antitumour effects of a neutralising antibody against IL-10 (αIL-10) both alone as treatment and in combination with exogenously administered carcinoembryonic antigen (CEA)-specific CAR-T cells. We evaluated slice cultures with single and multiplex immunohistochemistry, in situ hybridisation, single-cell RNA sequencing, reverse-phase protein arrays and time-lapse fluorescent microscopy. RESULTS: αIL-10 generated a 1.8-fold increase in T cell-mediated carcinoma cell death in human CRLM slice cultures. αIL-10 significantly increased proportions of CD8+ T cells without exhaustion transcription changes, and increased human leukocyte antigen - DR isotype (HLA-DR) expression of macrophages. The antitumour effects of αIL-10 were reversed by major histocompatibility complex class I or II (MHC-I or MHC-II) blockade, confirming the essential role of antigen presenting cells. Interrupting IL-10 signalling also rescued murine CAR-T cell proliferation and cytotoxicity from myeloid cell-mediated immunosuppression. In human CRLM slices, αIL-10 increased CEA-specific CAR-T cell activation and CAR-T cell-mediated cytotoxicity, with nearly 70% carcinoma cell apoptosis across multiple human tumours. Pretreatment with an IL-10 receptor blocking antibody also potentiated CAR-T function. CONCLUSION: Neutralising the effects of IL-10 in human CRLM has therapeutic potential as a stand-alone treatment and to augment the function of adoptively transferred CAR-T cells.