Two-sided Fisher Exact Test Research Articles

Using QI to develop a sustainable method for titrating taxane infusions to reduce hypersensitivity reactions.

To develop a sustainable three-step method for titrating first and second taxane exposures through integration of best practices in patient and environmental safety; and to evaluate the impact on immediate hypersensitivity rates. A quality improvement study was initiated at a large, NCI-designated comprehensive cancer center in the U.S. to determine a sustainable method of slow, upward titration for reducing taxane-related hypersensitivity reactions. Multidisciplinary collaboration led to the incorporation of best practices for safe preparation and administration of high risk, hazardous drugs. Retrospective data from the electronic health records of 690 patients who received 1221 taxane doses were analyzed. Non-titrated infusions were compared with infusions titrated using a method initially tested for efficacy; and infusions titrated using a method revised for greater compliance with safety standards. Two-sided Fisher's exact tests at a 0.1 level of significance were used to detect differences in the rate of HSR between the three groups. A method of taxane titration that incorporated standardized, preprogrammed infusion rates and tubing primed with inert IV fluid showed a significant reduction in HSR incidence in comparison to non-titrated infusions (6% v. 19%, P = 0.001) and a similar decrease in the rate of HSR (6%) to the initial method previously studied (7%) (P = 0.659) which was not sustainable due to patient and environmental safety concerns. A three-step titration method using standardized, preprogrammed infusion rates and tubing primed with inert IV fluid reduced taxane-related HSRs and was adopted as sustainable practice in ambulatory cancer care.

The Fragility of Statistically Significant Binary Outcomes for Treating Achilles Tendinopathy: A Systematic Review of Randomized Trials.

Randomized controlled trials (RCTs) are the gold standard for treatment efficacy, but foot and ankle RCTs are often small or inconsistent. The Fragility Index (FI) evaluates the stability of significant findings. This study assessed the fragility of RCT outcomes for Achilles tendon pathology (ATP) interventions. This systematic review queried PubMed up to May 14, 2024, for RCTs on ATP interventions. RCTs with significant binary outcomes were included. Two reviewers assessed eligibility, extracted data, calculated FIs, and evaluated risk of bias. Frequency-weighted means were used for narrative synthesis. Eleven RCTs with 4506 patients (mean cohort size: 409.64 ± 160.54) and a mean age of 36.97 ± 13.51 years (n = 4356; 96.67%) were included, covering 24 binary outcomes. The median FI across all outcomes was 3 (interquartile range 1-4; mean 3.92), indicating that changing the outcome of just a few patients could shift a study's results from statistically significant to nonsignificant. Trials having an FI ≤3 comprised 58.33%. Three outcomes (12.5%) had an FI of zero after recalculating P values using the two-sided Fisher exact test. Half of the outcomes were robust. No RCT reported FIs or adjusted significance for multiple testing. Most studies (81.82%) performed 2 or more statistical tests, with an average of 30.81 ± 41.28 P values reported per study. The overall risk of bias was low in 1 study (9.09%) and moderate in 7 (63.64%). Most studies had low risk of bias in randomization (72.73%) and missing outcome data (90.91%). The FI assesses the fragility of statistically significant binary results, revealing that many ATP RCTs have fragile outcomes due to small sample sizes. A median FI of 3 means that changing the outcome of 3 patients could shift a study's results from statistically significant to nonsignificant.

Abstract B142: The impact of financial toxicity as a barrier to access and participation in early phase clinical trials for underrepresented populations using the COST–FACIT tool

Abstract Background: ASCO has reaffirmed critical role of early phase (EP) clinical trials (CT) in cancer research and treatment that patients (pts) may achieve improvement in quality of life, experience psychological and direct medical benefits. Disparities in access and participation to CT exist and are more profoundly seen in EP CT with challenge of engaging underrepresented populations (UP) in EP CT which are often complex and only available at larger cancer centers in metropolitan areas. NCI’s Create Access to Targeted Cancer Therapy for Underserved Populations (CATCH-UP.2020) helped bring EP CT to UP. To determine the impact of financial toxicity (FT) as a barrier specific to EP CT participation of UP, the validated COST-FACIT tool was used to survey cancer pts undergoing treatment at the University of Kansas Cancer Center. Methods: This study was approved by our Institutional Review Board (Study 00150640). During routine scheduled visits, pts completed COST-FACIT survey on touch screen tablet. A list of validated questions on EP CT awareness, access, and willingness to participate were included in the survey. Pts responded to 12-item COST-FACIT questionnaire describing the relationship between financial stress and treatments (scale 0 to 4). The score was computed using responses captured from COST-FACIT. Based on literature, scores <26 were determined to be higher FT. Two-sided Fisher's Exact Tests were used to test for a significant association at an alpha level of 0.05. UP included racial and ethnic minorities, low socioeconomic status, low education, and rural. Results: Of 108 pts, 101 completed surveys. 45% identified as female and 55% as male. 11.2% 18–35 years (yrs) of age, 13.9% 36 –50 yrs, 24% 51–65 yrs and 54% >65 yrs. 62.4% were white, 17.8% black, and 19.8% others (Asian or Native American). 8.9% completed <12th grade, 23.8% completed high school, 29.7% have some college experience, 22% completed college and 16% have master’s/doctoral degree. COST-FACIT mean score was 25.7 (SD 10.4, r^2 of 0.48) showing significant financial stress. 46% of pts had scores <26. Pts 18-35 yrs (p=0.02), 36–65 yrs (p=0.00), had yearly incomes of >150,000 (p=0.02) or unaware of their yearly income (p=0.05) were more likely to have significant FT. Pts with < 12th grade (14.89%) or some college experiences (34.09%) were likely to have significant FT. Pts identifying as Asian or Native American were more likely to experience FT than white or black. Conclusion: Almost half of our pts suffer from significant FT creating disparities in EP CT access and participation. Data suggest ages 35-65 yrs, low levels of education, and races other than white and black experience higher levels of FT that is a barrier to EP CT participation. These data support our ongoing efforts to bring innovative EP CT to everyone including the VA and our other outreach partners with higher concentrations of UP. Data on rural and health professional shortage areas will be reported during the meeting. This project was supported in part by The University of Kansas Cancer Center P30CA168524. Citation Format: Kamiyah Hicks, Anusha Chidharla, Dinesh Pal Mudaranthakam, Hope Krebil, Issa Espinoza, Asuka Suzuki, Sam Pepper, Angelica Allen, Jill Hamilton - Reeves, Debra Sullivan, Anna Arthur, Saqib Abbasi, Anup Kasi, Rahul Parikh, Elizabeth Wulff - Burchfield, Al - Ola Abdallah, Lori Barbosa, Erin Carroll, Jennifer Heins, Tara Lin, Gary Doolittle, Weijing Sun, Joaquina Baranda. The impact of financial toxicity as a barrier to access and participation in early phase clinical trials for underrepresented populations using the COST–FACIT tool [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B142.

RRx-001 Affects Multiple Toxicities in Patients Receiving Concomitant Chemoradiation for Head and Neck Cancers: Observations of the PREVLAR Phase II Trial

PURPOSE Phase IIa trial results suggested that RRx-001, an nucleotide-binding domain-like receptor protein 3 inhibitor and nuclear factor erythroid 2–related factor 2 activator, attenuated severe oral mucositis (SOM) in patients treated with concomitant chemoradiation (CRT) for oral cancer (OC) and oropharyngeal cancer (OPC). Given the shared pathobiology of CRT injury among other exposed tissues, we initiated a secondary analysis of reported adverse events (AEs) to assess RRx-001's potential benefit on non-SOM regimen-related toxicities. METHODS PREVLAR was an open-label randomized trial that has been completed and published. Patients were treated with CRT for locally advanced OC or OPC. Arms 1-3 received doses of RRx-001 twice a week beginning 2 weeks before the start of CRT. Arm 2 (n = 11) received additional RRx-001 once during weeks 2 and 5. Arm 3 (n = 13) received RRx-001 once a week for the first 6 weeks of CRT. Arm 4 (n = 10) received CRT only. Patients received standard intensity modulated radiation therapy (daily fractions of 2-2.2 Gy/minimum cumulative dose of 55 Gy) plus cisplatin. Comprehensive toxicity assessment was based on reported AEs graded using Common Terminology Criteria for Adverse Events v5.0 and categorized with the Medical Dictionary for Regulatory Activities. A two-sided Fisher's exact test was performed to compare AE incidences between RRx-001 arms and standard of care in a secondary analysis of the data. Overall false-positive rate in Fisher's exact test was controlled via Hochberg's adjustment method. RESULTS Compared with the control cohort, patients receiving RRx-001 demonstrated fewer AEs attributable to their CRT regimen. Statistically significant differences in AE incidences favoring RRx-001 were dependent on the RRx-001 dosing regimen. CONCLUSION This secondary analysis suggests that RRx-001 infusion may reduce multiple, biologically related AEs associated with a standard CRT regimen. More broadly, it suggests that it is possible that agents that effectively target central pathobiology targets may mitigate more than one toxicity.

Professional quality of life in cardiovascular nurses: differences between cardiology and pediatric cardiology clinic - pilot study

Abstract Background/Introduction Nursing can be a rewarding profession as it involves helping others. However, it is demanding, particularly for Cardiovascular nurses who may be exposed to stressful situations, patient suffering, and death. Additionally, work-related issues such as shift work, work overload, and excessive bureaucracy can pose challenges. It is necessary to consider that caring for children presents unique challenges compared to caring for adults, which can impact the Professional Quality of Life (ProQoL) and its domains. Purpose In this study, we aimed to investigate differences in ProQoL between nurses working in pediatric cardiology and adult cardiology units. Methods Nurses working in pediatric cardiology and adult cardiology units were enrolled in the study. The Polish version of the ProQoL 5 questionnaire was collected using a paper form. The specific domains of satisfaction, job burnout, and stress were calculated according to the questionnaire key. Moreover, data on age, additional places of employment and working hours were collected. The study examined the relationship between these factors and ProQoL domain scores using the R-Spearman correlation. Scores from each domain were compared between clinics using U-Mann-Whitney tests and a two-sided Fisher's exact test. Results The study involved 13 pediatric cardiology staff: six midwives, six nurses, one paramedic, and 29 adult cardiology staff: 26 nurses, two paramedics and one medical caretaker. No differences were found in any of the ProQoL domains between those working with children and those working with adults: p=0.74 for satisfaction, p=0.90 for burnout and p=0.77 for stress. A trend of lower age was observed among those working in the Paediatric Cardiology Department. The majority of nurses, regardless of ward, reported high or intermediate job satisfaction, as well as low or moderate levels of stress and burnout. Only one person employed in the adult Cardiology department reported a low level of job satisfaction. Older age was associated with higher job satisfaction (R=0.32; p=0.04) and lower levels of burnout (R=-0.31; p=0.048). Additionally, a higher number of working hours per month was associated with burnout (R=0.41; p=0.007). Satisfaction was negatively associated with burnout (R=-0.51; p<0.001) and positively correlated with stress (R=0.35; p=0.04). However, burnout was not associated with stress (p=0.56). Conclusions Regardless of the different work specifications in departments, related to working with children or adults, the ProQoL does not differ significantly. Older age may be positively associated with ProQoL. It may be the result of greater work experience. A higher number of working hours per month is associated with burnout, so it is therefore appropriate to emphasize the importance of occupational health and encourage not to overwork. A multicentre study could further define the differences in ProQoL and the influencing factors.

AGE, SEX, AND TYPES OF OCCUPATION WITH HISTOPATHOLOGICAL TYPES IN PATIENTS WITH OCULAR SURFACE SQUAMOUS NEOPLASIA (OSSN) IN A TERTIARY HOSPITAL IN SURABAYA, INDONESIA

Highlights The histopathological types of OSSN were significantly associated with age and occupation. The study's findings enhance the understanding of OSSN in Indonesia and emphasize the importance of UV exposure, occupation, and age in its development. Abstract Background: Ocular Surface Squamous Neoplasia (OSSN) is a spectrum of tumors affecting the conjunctiva and cornea, in which a more invasive type of OSSN has a higher recurrence rate. As a tropical country, Indonesia is constantly exposed to intense ultraviolet (UV) radiation, the main risk factor for OSSN. Despite this, there are very few studies regarding OSSN in Indonesia. Objective: This study aimed to analyze the association between sociodemographic characteristics such as age, sex, and types of occupation (outdoor and indoor) and histopathological types of OSSN to fill the gap in research and contribute to early diagnostic strategies. Material and Method: Sociodemographic and histopathological data were extracted from the medical records of patients who were histopathologically diagnosed with OSSN at Dr. Soetomo General Hospital from 2017 to 2021. Data from 88 samples that met the inclusion and exclusion criteria were classified and analyzed with descriptive statistics and a two-sided Fisher's exact test using SPSS version 27.0 (IBM Corp., Armonk, N.Y., USA). Result: The exact test results of the two-sided fisher revealed a statistically significant relationship between age (p = 0.0004) and occupation type (p = 0.049) with histopathological types of OSSN. However, no significant association was found between sex and histopathological types of OSSN (p = 0.130). Conclusion: Age and occupation were found to have a significant association with the histopathological types of OSSN, reinforcing the need for further exploration of its strength and nature to be considered by future researchers.

Effect of Education on Adherence to Recommended Prenatal Practices among Indigenous Ngäbe-Buglé Communities of Panama.

Background and Objectives: The primary objective of this study was to assess the adherence of Ngäbe-Buglé women to WHO-recommended prenatal practices. The secondary objective was to compare adherence levels between women who received prenatal education from official medical providers and those educated through traditional or community-based sources within Ngäbe-Buglé communities. Materials and Methods: An eight-question survey was verbally administered to 137 Ngäbe-Buglé women at clinics set up by the non-profit NGO Floating Doctors in eight communities. A two-sided Fisher's Exact test with a p = 0.05 was used to compare the results of mothers who received prenatal education from evidence-based sources to other groups. Results: Out of the 137 surveyed women, 65 reported taking prenatal vitamins, 21 had prenatal check-ups, 136 avoided alcohol, 31 increased caloric intake, and 102 maintained their activity levels. Significant differences were observed in prenatal vitamin adherence between those educated by official sources versus unofficial sources (p = 0.0029) and official sources compared to those with no prenatal education (p < 0.0001). The difference was also significant for education from an unofficial source versus no education (p = 0.0056). However, no significant differences were found in other prenatal practices based on education sources. Conclusions: Our findings highlight deficiencies in both prenatal education and adherence to recommended practices among Ngäbe-Buglé women. Prenatal education significantly improved adherence to taking prenatal vitamins, suggesting its effectiveness as an intervention. Future interventions should prioritize culturally competent prenatal education and address barriers to accessing prenatal healthcare in Ngäbe-Buglé communities.

Psychosocial and supportive care concerns of young women living with advanced breast cancer: baseline findings from a prospective virtual support intervention study.

Adolescent and young adults (AYAs) with metastatic breast cancer (MBC) experience high physical and psychosocial burdens compounded by a disrupted life trajectory. We sought to determine the psychosocial and supportive care concerns of this population to better understand and address unmet needs. AYAs diagnosed with MBC (18-39years) participating in a prospective interventional study (Young, Empowered, and Strong) at Dana-Farber Cancer Institute completed an electronic survey following enrollment. Measures evaluated sociodemographics, health behaviors, quality of life, and symptoms, among others. We used two-sided Fisher's exact tests to determine associations between concerns (e.g., cancer progression, side effects, lifestyle, finances, fertility) and demographic variables. Among 77 participants enrolled from 9/2020-12/2022, average age at MBC diagnosis and survey was 35.9 (range: 22-39) and 38.3years (range: 27-46), respectively. Most were non-Hispanic white (83.8%) and 40.3% reported their diagnosis caused some financial problems. Many were concerned about fertility (27.0%), long-term treatment side effects (67.6%), exercise (61.6%), and diet (54.1%). Select concerns varied significantly by age, race/ethnicity, and education. Younger women at survey reported greater concern about familial cancer risk (p = 0.028). Women from minority racial/ethnic groups more frequently reported issues talking about their cancer to family/friends (p = 0.040) while those with more education were more frequently concerned with long-term effects of cancer on their health (p = 0.021). Young women living with MBC frequently report psychosocial, health, and cancer management concerns. Tailoring supportive care and communications to address prevalent concerns including disease progression and treatment side effects may optimize wellbeing.

Drug trials are more likely to disclose full placebo control information than non-drug trials: A cross-sectional study of participant information leaflets of placebo-controlled trials

BackgroundThis study aimed to investigate whether placebo control is differently disclosed in drug and non-drug randomised clinical trial (RCT) participant information leaflets (PILs) and how this might affect participant blinding and direction of study outcomes. MethodsPILs were obtained from trials registered in the International Standard Randomised Controlled Trial Number database via email. Placebo descriptions in PILs were categorised as Full Disclosure (FD), Partial Disclosure (PD), or Missing Information (MI). Associations between intervention type (drug or non-drug)/placebo disclosure (FD or PD/MI) and participant blinding success/trial outcome direction (positive or non-positive) were examined using a two-sided Fisher's exact test. ResultsOf 116 collected PILs, 56 % were for drug trials and 44 % were for non-drug trials. Among them, 88 PILs had the corresponding publications available and 68 reports specified primary outcomes. Drug trials were more likely to fully disclose placebo information than non-drug trials (92.3 % vs. 74.5 %, p < 0.05). However, the success rate of blinding was only reported in 3 out of 88 trial publications (3.4 %), precluding further analysis. Furthermore, there was no significant association between the direction of trial results and the type of intervention or placebo disclosure. ConclusionOur study findings suggest that drug and non-drug RCTs might differ in the way they reveal placebo control information. Further research is warranted to understand what leads to more common PD of placebo information in non-drug trials than drug trials and to determine the optimal placebo control disclosure in specific trial context.

Highly variable timing renders immunotherapy efficacy and toxicity impractical biomarkers of one another in clinical practice.

A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAE) have been associated with therapeutic benefit, irAE may have delayed and highly variable onset. To determine whether ICI efficacy and irAE could serve as clinically useful biomarkers for predicting each other, we determined the temporal relationship between initial efficacy assessment and irAE onset in a diverse population treated with ICI. Using two-sided Fisher exact and Cochran-Armitage tests, we determined the relative timing of initial efficacy assessment and irAE occurrence in a cohort of 155 ICI-treated patients (median age 68 years, 40% women). Initial efficacy assessment was performed a median of 50 days [interquartile range (IQR) 39-59 days] after ICI initiation; median time to any irAE was 77 days (IQR 28-145 days) after ICI initiation. Median time to first irAE was 42 days (IQR 20-88 days). Overall, 58% of any irAE and 47% of first irAE occurred after initial efficacy assessment. For clinically significant (grade ≥2) irAE, 60% of any and 53% of first occurred after initial efficacy assessment. The likelihood of any future irAE did not differ according to response (45% for complete or partial response vs. 47% for other cases; P=1). In landmark analyses controlling for clinical and toxicity follow-up, patients demonstrating greater tumor shrinkage at initial efficacy assessment were more likely to develop future grade ≥2 (P=0.05) and multi-organ (P=0.02) irAE. In contrast to that seen with chemotherapy and molecularly targeted therapies, the temporal relationship between ICI efficacy and toxicity is complex and bidirectional. In practice, neither parameter can be routinely relied on as a clinical biomarker to predict the other.

Massive Transfusion in Pediatric Patients on Extracorporeal Membrane Oxygenation: A Secondary Analysis of the Massive Transfusion in Children (MATIC) Study.

Few data describe pediatric patients who receive massive transfusion for life-threatening hemorrhage (LTH) while on extracorporeal membrane oxygenation (ECMO). We present a retrospective secondary analysis of a multicenter prospective observational study to describe resource utilization and mortality in pediatric patients with LTH while on ECMO. Children who were on ECMO during an LTH were compared to children with LTH who were not on ECMO. Primary outcomes were volumes of blood products administered and 28 day mortality. Comparisons were assessed by two-sided Fisher's exact test or Wilcoxon rank sum test. A total of 449 children, including 36 on ECMO, were included. Compared to those not on ECMO, children on ECMO received a higher volume of blood products (110 [50-223] vs . 59 [28-113]) ml/kg, p = 0.002) and were more likely to receive antifibrinolytic therapy (39% vs . 10%, p < 0.001). Blood product ratios were similar. Extracorporeal membrane oxygenation patients had higher 28 day mortality (64% vs. 35%, p = 0.001), although 24 hour mortality was similar (17% vs . 23%, p = 0.5). In conclusion, children on ECMO with LTH experience high resource utilization and 28 day mortality. Studies are needed to identify children at risk for LTH and to evaluate ECMO-specific treatment strategies.

Abstract 790: Sex and race-dependent variations in the mutational landscape of clonal hematopoiesis

Abstract Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a significant precursor to hematological malignancies and is associated with several age-related diseases. Recent studies in relatively small disease specific cohorts have suggested that CHIP may exhibit variations among different races and between males and females raising intriguing questions about potential genetic and environmental influences. Understanding the differences in CHIP across races and between males and females may have implications for personalized cancer risk assessment and targeted therapeutic strategies. Methods: Patient’s data were obtained from the Cancer Therapy and Clonal hematopoiesis via cBioportal. The original study was designed to examine clonal hematopoiesis mutations that were found in blood samples obtained from 24,146 patients with non-hematological cancers and their tumor-blood pairs were analyzed using targeting sequencing data MSK-IMPACT (Memorial Sloan Kettering-IMPACT). The cohort consisted of 45.7% males and 54.3% females; including 6.8% Asians, 6.2% Blacks, and 76.3% Whites. We examined mutation frequencies among these racial groups and between genders, employing the two-sided Fisher's exact test and adjusting p-values for multiple comparisons. Differences were considered significant when both P value and Q values are less than 0.05. Results: DNMT3A mutations were substantially more prevalent in females than in males (38.94% vs 31.37%, p-value: &amp;lt;10−10, q-value: 6.19e−09), While ASXL1 mutations were more frequent in males than females (5.82% vs 2.69%, p-value: &amp;lt;10−10, q-value: 6.19e−09). In the racial cohorts with sufficient sample sizes, STAT5B and CSF1R mutations were most frequent in Asian (1.40% and 0.84%), followed by Black (0.98% and 0.24%) and White populations (0.29% and 0.09%), (p-value: 8.099e−04 and 7.490e−04, q-value: 0.0234 and 0.0232). Several other CHIP mutations were enriched in Black: RARA, SMAD2, CDKN1B, CENPA, CTLA4, EIF1AX, ELF3, MSI1, MYC, SOX17, AURKA. On the other hand, H3C1, H3C4, MYCL were enriched in the Asian cohort. Conclusion: Our analysis provides insights into the complex interplay of sex and racial factors in shaping CHIP mutation frequencies. As CHIP continues to gain recognition as a critical precursor to malignancies, understanding these variations contributes to refining our understanding of its underlying mechanisms and clinical implications. Citation Format: Kanaka Dhuri, Houda Alachkar. Sex and race-dependent variations in the mutational landscape of clonal hematopoiesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 790.

Abstract 12421: Guided Advanced Cardiovascular Life Support Mobile App Improves Trainee Experience and Performance During Simulated Cardiac Arrest: A Randomized Controlled Trial

Introduction: Leading hospital code teams is stressful for resident physicians, and variability in training and experience may result in inconsistent care and outcomes. Nearly all bedside aids like AHA advanced cardiovascular life support (ACLS) pocket cards and third-party ACLS mobile apps lack step-by-step guidance or reminders. Our team designed a guided ACLS mobile app to help trainees lead more effective hospital resuscitations and conducted a randomized controlled trial to assess user experience and performance according to 2020 AHA ACLS guidelines. Hypothesis: A guided ACLS app will improve subjective user experience and adherence to AHA ACLS guidelines. Methods: The ACLS mobile app was developed using Swift UIKit. Internal Medicine, Emergency Medicine, Surgery, and Anesthesia residents (N = 46) were randomized to lead a simulated code for cardiac arrest due to massive pulmonary embolism using either AHA pockets cards (N = 22) or the ACLS app (N = 24). User experience was assessed via surveys. Code outcomes, guideline adherence, and errors were analyzed from video recordings. A focus group of 22 residents provided feedback. Statistical analysis was conducted using R software and included two-sided t-tests and Fisher exact tests. Results: App users showed significantly increased confidence (1.0 vs 0.3; p = 0.005), backboard use (96% vs 27%; p &lt;0.001), end-tidal CO2 monitoring (58% vs 27%; p = 0.042), correct thrombolytic administration (54% vs 23%; p = 0.035), and achieving return of spontaneous circulation (50% vs 18%; p = 0.032) compared to controls. Focus group results showed that 100% of the participants would use the app and that 82% preferred the guided app to AHA pocket cards. Conclusions: The guided app improves user confidence and adherence to AHA ACLS guidelines and addresses the need for greater standardization in hospital code management. Validation studies are necessary to confirm its effectiveness in clinical practice.

PSXIV-27 Liver Abscesses in Feedlot Cattle: Further Studies on Etiology and Pathogenesis Liver Abscesses in Feedlot Cattle: Further Studies on Etiology and Pathogenesis

Abstract Liver abscesses (LA) are a polymicrobial infection and the causative agents include two subspecies of Fusobacterium necrophorum, necrophorum and funduliforme, and Trueperella pyogenes. Nucleic acid-based analysis of the purulent material of LA has indicated that Proteobacteria and Bacteroidetes were the dominant phyla, next to phylum Fusobacteria. The sporadic isolations of bacterial species of the Proteobacteria and Bacteroidetes in LA have been reported. An aspect of the pathogenesis that has not been investigated is whether bacterial pathogens in LA originate, besides the rumen, from the colon? Therefore, our objectives were to target detection and isolations of Salmonella enterica, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Bacteroides fragilis, in addition to routine isolations of F. necrophorum and T. pyogenes, from LA and also from ruminal and colonic epithelial tissues of the same animals. Liver abscesses, matched with ruminal and colonic epithelial tissue samples from 96 steers and heifers, originating from 15 feedlots, were collected at slaughter, transported to the laboratory and processed within 24 hours. Samples were subjected to anaerobic and aerobic culture methods, including enrichment and selective media for detection and isolation of S. enterica, E. coli, K. pneumonia, P. aeruginosa, and B. fragilis. Prevalence of bacterial species were shown in table 1. For each bacterium, two-sided Fisher's exact test was used to evaluate the association of its prevalence in LA with that in colon and rumen at 0.05 level. Overall, prevalence of subsp. necrophorum, subsp. funduliforme, T. pyogenes and S. enterica in liver abscesses were 86.4% (83/96), 21.8% (21/96), 35.4% (34/96) and 6.2% (6/96), respectively (Table 1). In ruminal tissue samples, prevalence of subsp. necrophorum, subsp. funduliforme, T. pyogenes and S. enterica were 6.6% (6/96), 40.6% (39/96), 11.4% (11/96) and 4.1% (4/96), respectively. Prevalence of subsp. necrophorum, subsp. funduliforme, T. pyogenes and S. enterica in colonic tissues were 18.7% (18/96), 36.4% (35/96), 0% (0/96) and 7.2% (7/96), respectively. Prevalence of E. coli, Klebsiella spp., and P. aeruginosa in LA samples were 70.8% (68/96), 92.7% (89/96), and 91.6% (88/96), respectively. Prevalence of E. coli, Klebsiella spp., and P. aeruginosa in rumen epithelial tissue samples were 17.7% (17/96), 50.0%, (48/96), and 15.6% (15/96), respectively. Prevalence of E. coli, Klebsiella spp., and P. aeruginosa in colonic tissue samples were 16.6% (16/96), 24.0% (26/96), and 12.5% (12/96), respectively. Prevalence of subsp. funduliforme in ruminal and colonic tissues was greater than subsp. necrophorum. None of the liver abscess samples yielded B. fragilis. In conclusion, E. coli was the second most dominant species detected and isolated from LA, next only to subsp. necrophorum. The greater frequencies of isolations of subsp. necrophorum and S. enterica from colonic epithelial than ruminal epithelial tissues suggest that hindgut could also be a source of pathogens involved in LA.

Feedback Culture Perceived by Trainees in an Academic Institution: A Mixed Methods Study.

Lack of a well-functioning institutional feedback culture can undermine acquisition of skills essential for high quality patient care. The objective of this study was to assess feedback culture perceived by resident and fellow trainees, utilizing a mixed methods design. Pediatric fellows and residents completed an anonymous feedback environment survey consisting of 7 constructs: source credibility, feedback quality, feedback delivery, reinforcing feedback, constructive feedback, source availability, and promotion of feedback seeking, using a 7-point Likert scale. Trainee ratings were compared using two-sided Fisher's exact tests. Multivariable analyses used a linear regression model. For the qualitative study, semistructured interviews of residents were conducted. The constant comparative method was used to incrementally code, categorize data, and derive themes. Fifty-two residents and 21 fellows completed the survey (response rates 65% and 47%, respectively). Scores were more favorable for fellows compared with residents in 6 of 7 feedback constructs (P < .05), including on multivariate analysis. Hispanic ethnicity and female gender were associated with lower scores on source credibility (P = .04) and constructive feedback (P = .03), respectively. Two qualitative themes were identified: expectation of efficiency in patient care compromises the quality and quantity of feedback, and a culture that prioritizes courtesy over candor negatively impacts feedback quality. These themes were more pronounced when residents worked with pediatric subspecialists compared with hospitalists. We described the feedback culture, which was less favorable in the residency program. The need for efficient patient care and a culture of courtesy adversely impacted the quality of feedback, especially among subspecialists.

Comparison of Molecular and Clinicopathologic-Based Classifications and the Transition of Adjuvant Treatment Mode for Early-Stage Endometrial Cancer

Due to the division in classification strategies based on different molecular and clinicopathologic guidelines, the current emergence of multiple molecular typing methods greatly challenges the traditional classification-guided hierarchical treatment model. The early-stage ECs who underwent a total hysterectomy and comprehensive molecular analyses were analyzed consecutively between May 2021 and December 2022. All enrolled patients were performed with immunohistochemistry for lymph-vascular space invasion (LVSI), p53, and mismatch repair (MMR) proteins, NGS-panel Sanger sequencing for POLE exonuclease domain, and TP53. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) classifier and the ESGO/ESTRO/ESP guidelines with and without molecular character were respectively employed to reclassify the enrolled patients. Categorical variables of the risk-group shift were compared by Pearson's χ2 or two-sided Fisher's exact test. A total of 81 early-stage ECs patients were enrolled. Molecular analyses identified four subgroups across the 81 ECs: 9 (11%) POLE mut, 22 (27.1%) MMRd, 38 (46.9%) NSMP, and 12 (14.8%) p53 abn. Compared with ESGO/ESTRO/ESP 2016 classifier, 26 (32.1%) and 23 (28.4%) patients in ESGO/ESTRO/ESP 2020 cohort with and without molecular classification, respectively, were risk-group downshifted (p>0.05). Ten (12.3%) patients were upshifted in ESGO/ESTRO/ESP 2020 molecular classification comparing to clinical classifier. Remarkably, two patients demonstrated discordance between the ProMisE and TCGA classifiers since the different sequences of classification strategies. On the other hand, 48 of 81 patients received adjuvant radiotherapy, and 12 patients received external beam radiation therapy (EBRT). According to the final molecular test, eight of 12 were classified into low and intermediate risk. The treatment of endometrial cancer is in a period of transition from the clinicopathologic-based model to the era of molecular precision. Discordance between different classifiers and overtreatment remain in clinical practice. Therefore, we should be cautious about using molecular typing to guide adjuvant treatment decisions until it is finally validated in prospective trials.

Pretest Video Education Versus Genetic Counseling for Patients With Prostate Cancer: ProGen, A Multisite Randomized Controlled Trial.

Germline genetic testing (GT) is recommended for men with prostate cancer (PC), but testing through traditional models is limited. The ProGen study examined a novel model aimed at providing access to GT while promoting education and informed consent. Men with potentially lethal PC (metastatic, localized with a Gleason score of ≥8, persistent prostate-specific antigen after local therapy), diagnosis age ≤55 years, previous malignancy, and family history suggestive of a pathogenic variant (PV) and/or at oncologist's discretion were randomly assigned 3:1 to video education (VE) or in-person genetic counseling (GC). Participants had 67 genes analyzed (Ambry), with results disclosed via telephone by a genetic counselor. Outcomes included GT consent, GT completion, PV prevalence, and survey measures of satisfaction, psychological impact, genetics knowledge, and family communication. Two-sided Fisher's exact tests were used for between-arm comparisons. Over a 2-year period, 662 participants at three sites were randomly assigned and pretest VE (n = 498) or GC (n = 164) was completed by 604 participants (VE, 93.1%; GC, 88.8%), of whom 596 participants (VE, 98.9%; GC, 97.9%) consented to GT and 591 participants completed GT (VE, 99.3%; GC, 98.6%). These differences were not statistically significant although subtle differences in satisfaction and psychological impact were. Notably, 84 PVs were identified in 78 participants (13.2%), with BRCA1/2 PV comprising 32% of participants with a positive result (BRCA2 n = 21, BRCA1 n = 4). Both VE and traditional GC yielded high GT uptake without significant differences in outcome measures of completion, GT uptake, genetics knowledge, and family communication. The increased demand for GT with limited genetics resources supports consideration of pretest VE for patients with PC.

Comparing the Denver criteria sets for blunt trauma: a retrospective study of cases in Edmonton, Alberta.

To determine whether a more conservative Denver criterion set could reduce unnecessary CT angiography (CTA) studies when screening for blunt cerebrovascular injury (BCVI) following blunt trauma. Following ethics approval, a retrospective chart review of 447 consecutive patients undergoing emergency CTA at two large teaching hospitals was conducted to determine the presence of risk factors for each Denver criterion set. Imaging studies of adults conducted between January 2016 and June 2020 containing sufficient clinical information for accurate classification were included in the study. Specificity, sensitivity, and predictive values were calculated. A two-sided Fisher exact test was used to evaluate the association between each iteration of the Denver criteria and the presence of BCVI. The specificities of the Original, Modified, and Expanded Denver criteria were 43.58%, 34.32%, and 24.85%, respectively. Positive-predictive values (PPV) followed a different trend, with respective values of 2.77%, 3.06%, and 2.78%. Sensitivity and negative-predictive values (NPV) were found to be 100% for each criterion set. Being positive for a criterion set, and the presence of BCVI, was statistically significant for the original Denver criteria (p = 0.021, n = 443), but not the modified (p = 0.100, n = 345) or expanded Denver criteria (p = 0.202, n = 333). Use of the modified and expanded Denver criteria leads to the overuse of cerebrovascular imaging on patients suffering blunt force trauma. The original Denver criteria may more appropriately identify subjects for further evaluation with CTA than the current standard, while retaining diagnostic efficacy for BCVI.

O-077 Time-lapse imaging analysis of segmental aneuploid embryos: a multicenter study identifies morpho-kinetic patterns associated with chromosomal mosaicism

Abstract Study question Do segmental aneuploid (SA) embryos display unique morpho-kinetic patterns at early developmental stages? Summary answer The first three cell division cycles of embryos carrying segmental aneuploidies are significantly slower than euploid and whole-chromosome aneuploid (WCA) embryos. What is known already Segmental aneuploidies in blastocyst-stage human embryos prevalently originate (i.e., 70% of cases) from mitotic errors. Their clinical management is challenging because it is impossible to establish their meiotic/mitotic origin from PGT-A analysis of a single trophectoderm biopsy. Morpho-kinetic analysis based on Time-lapse microscopy (TLM) has been proposed as a valuable tool for systematic embryo evaluation, although it is unclear whether this approach alone can predict chromosomal abnormalities. This study aims to pinpoint morphokinetic patterns associated with the occurrence of segmental aneuploidies and/or mitotic errors, possibly improving DNA-based diagnostic interpretation and their clinical management. Study design, size, duration This is a retrospective multicenter study including a total of 7,693 embryos from 2,370 IVF cycles and 2,127 couples, cultured between 2016 and 2021 in 4 European IVF centers. Embryos with no more than 4 chromosomal alterations were considered in the analysis, resulting in 3,288 euploids, 3,155 WCA, 715 SA, and 535 complex aneuploids (CA). Overall, the dataset contained 3,742 distinct euploid-SA embryo sibling pairs. Participants/materials, setting, methods Standard morpho-kinetic features were annotated using various TLM systems. Blastocysts were subjected to comprehensive chromosomal screening via PGT-A. Morpho-kinetic timings across different embryo groups were compared using Kolmogorov-Smirnov (KS) test and binomial test, and associations with cleavage features were assessed via two-sided Fisher Exact (FS) test. Multi-center and center-specific logistic regression models were calibrated using a subset of data (70%), and their predictive performance was evaluated on independent test data using Area-Under-ROC curve (AUROC) metrics. Main results and the role of chance SA embryos cleaved at significantly slower rate than their euploid siblings in the first 3 cell cycles, from the appearance of the second blastomere t2 (average delay delta=0.49h, KS p = 0.006, fraction of pairs in which SA was delayed compared to euploid sibling F = 54.2%, binomial p = 0.002) up to t8 (delta=2.16h, KS p = 4e-4, F = 57.9%, binomial p = 1e-8). The developmental delay was partially compensated at full blastocyst stage tB (delta=1.71h, KS = 0.0008, F = 57.5%, binomial p = 5e-8). SA timings also differed from WCA ones: SA embryos were significantly slower than their WCA siblings during early cell cycles, with maximum delay reached at t8 (delta=1.67h, KS p = 0.009, F = 55.4%, binomial p = 0.003), but they fully caught-up at tB, with no significant difference observed. These morpho-kinetic patterns were consistently observed in each center separately, but with different effect sizes. The presence of segmental aneuploidies was significantly associated with multinucleation (OR = 1.99, FS test p = 0.05) and morula cell exclusion (OR = 2.69, p = 0.006). A logistic model based on morpho-kinetic data and cleavage features from a single center dataset and regressed against embryo aneuploidy class (euploid vs. SA embryos) displayed adequate predictive performance on independent data from the same center (AUROC=0.70), although predictivity diminished when tested on data from other centers (AUROC=0.52-0.55). Limitations, reasons for caution We cannot rule out inter-center variability in the annotation procedures of morpho-kinetic parameters. Standardized and automated annotation would increase the performance of predictive models and their transferability. Further work is needed to assess whether the morpho-kinetic signal is driven by mitotic errors and if an association with clinical outcomes exists. Wider implications of the findings These findings might help uncovering biological events contributing to preimplantation mosaicism. Moreover, the developed predictive framework might help improving decision-making in PGT-A cycles, providing interpretation for segmental aneuploidies and possibly helping in the evaluation of embryos showing intermediate copy number values for whole chromosomes that are suggestive of mosaicism. Trial registration number Not applicable

International medical tourism of US cancer patients for alternative cancer treatments: Financial, demographic, and clinical profiles of online crowdfunding campaigns.

Previous research has found that individuals may travel outside their home countries in pursuit of alternative cancer therapies (ACT). The goal of this study is to compare individuals in the United States who propose plans for travel abroad for ACT, compared with individuals who seek ACT domestically. Clinical and treatment data were extracted from campaign descriptions of 615 GoFundMe® campaigns fundraising for individuals in the United States seeking ACT between 2011 and 2019. We examined treatment modalities, treatment location, fundraising metrics, and online engagement within campaign profiles. Clinical and demographic differences between those who proposed international travel and those who sought ACT domestically were examined using two-sided Fisher's exact tests. Differences in financial and social engagement data were examined using two-sided Mann-Whitney tests. Of the total 615 campaigns, 237 (38.5%) mentioned plans to travel internationally for ACT, with the majority (81.9%) pursuing travel to Mexico. Campaigns that proposed international treatment requested more money ($35,000 vs. $22,650, p < 0.001), raised more money ($7833 vs. $5035, p < 0.001), had more donors (57 vs. 45, p=0.02), and were shared more times (377 vs. 290.5, p=0.008) compared to campaigns that did not. The median financial shortfall was greater for campaigns pursuing treatments internationally (-$22,640 vs. -$13,436, p < 0.003). Campaigns proposing international travel for ACT requested and received more money, were shared more online, and had more donors. However, there was significantly more unmet financial need among this group, highlighting potential financial toxicity on patients and families.