Clinical Program Research Articles

Advancing Research on and Treatment of Dissociative Identity Disorder With People With Lived Experience.

Dissociative identity disorder is a posttraumatic, psychobiological syndrome that develops over time during childhood. Despite empirical evidence supporting the validity of this diagnosis and its relation to trauma, the disorder remains a misunderstood and stigmatized condition. This article highlights expert consensus guidelines and current empirical research on the treatment of dissociative identity disorder. In addition, the authors describe the Lived Experience Advisory Panel (LEAP), which was designed to leverage the expertise of individuals with dissociative identity disorder to combat stigma and improve research, clinical programming, professional education, and public outreach related to the disorder. This article also describes how LEAP members have partnered with other researchers to create new knowledge through participatory action research in order to advance equitable service provision and effect positive change.

Implementation of a Real-Time Documentation Assistance Tool: Automated Diagnosis (AutoDx).

Clinical documentation improvement programs are utilized by most healthcare systems to enhance provider documentation. Suggestions are sent to providers in a variety of ways, and are commonly referred to as coding queries. Responding to these coding queries can require significant provider time and do not often align with workflows. To enhance provider documentation in a more consistent manner without creating undue burden, alternative strategies are required. The aim of this study is to evaluate the impact of a real-time documentation assistance tool, named AutoDx, on the volume of coding queries and encounter level outcome metrics, including case-mix index (CMI). The AutoDx tool was developed utilizing tools existing within the electronic health record, and is based on the generation of messages when clinical conditions are met. These messages appear within provider notes and required little to no interaction. Initial diagnoses included in the tool were electrolyte deficiencies, obesity, and malnutrition. The tool was piloted in a cohort of Hospital Medicine providers, then expanded to the Neuro Intensive Care Unit (NICU), with addition diagnoses being added. The initial Hospital Medicine implementation evaluation 590 encounters pre and 531 post-implementation. The volume of coding queries decreased 57% (p < 0.0001) for the targeted diagnoses compared to 6% (p = 0.77) in other high volume diagnoses. In the NICU cohort 829 encounters pre-implementation were compared to 680 post. The proportion of AutoDx coding queries compared to all other coding queries decreased from 54.9% to 37.1% (p<0.0001). During the same period, CMI demonstrated a significant increase post-implementation (4.00 vs 4.55, p = 0.02). The real-time documentation assistance tool led to a significant decrease in coding queries for targeted diagnoses in two unique provider cohorts. This improvement was also associated with a significant increase in CMI during the implementation time period.

Etrasimod for the Treatment of Ulcerative Colitis: Analysis of Infection Events From the ELEVATE UC Clinical Program.

Infections are a safety concern in patients with ulcerative colitis (UC). Etrasimod is an oral, once-daily (QD), selective sphingosine 1phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC. It leads to selective and reversible lymphocyte sequestration, and partial peripheral lymphocyte count decrease. We report infection events from the phase 3 ELEVATE program. Proportions, incidence rates (IRs; per 100 patient-years) and descriptive analyses of all, serious, severe, herpes zoster, and opportunistic infections are reported in the Pivotal UC cohort (ELEVATE UC 52 and ELEVATE UC 12). Cox regression models evaluated potential baseline risk factors. In this analysis (n=787), proportions (IRs) of all infection events were similar for patients receiving etrasimod 2mg QD (18.8% [41.1]) or placebo (17.7% [49.0]). Serious infections occurred in three (0.6%) and five (1.9%) patients receiving etrasimod and placebo, respectively. Two herpes zoster events were reported in each group (etrasimod: 0.4%; placebo: 0.8%); all localized and non-serious. One opportunistic infection event was reported in each group. No patient with an absolute lymphocyte count (ALC) <0.2 × 109/L reported serious/severe or opportunistic infections; no baseline risk factors were identified for such events. No deaths occurred. Patients receiving etrasimod demonstrated no increased risk of infection. The incidence of serious infections and herpes zoster was similar in each group. Among patients receiving etrasimod, no association between ALC <0.5 × 109/L and infection events was observed. Longer-term follow-up will further characterize the etrasimod safety profile.

Abstract PO3-09-10: Minority participation in breast cancer therapeutic trials at an NCI-CCC affiliated safety-net system: Advancing equity in clinical research

Abstract Authors: Nasir Qureshi, MBBS Fabian Robles, MS Mai Badran, MBBS Nisha Unni, MD Hsiao C Li, MD Samira Syed, MD Glenda Delgado-Ramos, MD Sangeetha Reddy, MD Heather McArthur, MD Navid Sadeghi, MD Title: Minority participation in breast cancer therapeutic trials at an NCI-CCC affiliated safety-net system: Advancing equity in clinical research. Introduction: Participation of under-represented minorities (URMs) in clinical trials enhances the generalizability of the findings and can also improve clinical outcomes. Multiple factors, such as access, language barrier, distrust, and misconceptions, negatively impact URM enrollments in cancer clinical trials. Here we describe our approach to increase participation of breast cancer URMs in therapeutic trials at an academic-affiliated safety-net system. Methods: Parkland Health (PH) is a large safety-net system in Dallas County, Texas, and is affiliated with the NCI-CCC designated Harold C. Simmons Comprehensive Cancer Center (SCCC) at UT Southwestern. A dedicated team of SCCC research coordinators support the clinical trial operations at PH. In 2020, several steps were taken to increase access and enrollment of URMs in breast cancer trials at PH including review and optimization of the trial portfolio (more trials in curative intent setting), proactive screening, increasing provider awareness, and addition of a bilingual (English/Spanish) patient navigator to the research team. Data for 2018-2019 (pre-intervention) and 2021-2022 (post-intervention) is presented here. Data for 2020 is excluded due to the impact of COVID-19 pandemic on trial operations. Results: Racial and ethnic minorities composed the majority of breast cancer patients at PH (52% Hispanics, 32% Blacks). Ten percent of new patients at PH presented with metastatic disease. In 2018-2019, PH's portfolio included 13 therapeutic trials, 5 of which (38%) were in metastatic setting and 3 required a biomarker. A total of 47 breast cancer patients were enrolled in 11 therapeutic trials at PH, accounting for an average annual accrual rate of 6.1% (7.6% in 2018 and 4.5% in 2019). Accrual to trials in the metastatic setting accounted for 11% (5/47) of enrollments. Two trials in the metastatic setting had zero accruals. In 2021-2022, 16 trials were open at PH, including 7 cooperative group, 4 industry-sponsored (ISTs), and 5 Investigator-Initiated trials (IITs). Five trials (31%) were in metastatic setting and 4 required a genomic biomarker. A total of 87 patients were enrolled in 2021-22, representing an 85% increase in the accruals over the baseline (2018-2019). The annual accrual rates for 2021 and 2022 were 10.5% (43/409) and 10.4% (44/423), respectively. In 2021-22, 63 were enrolled in cooperative group studies, 20 in IITs, and 4 in ISTs. Accrual to trials in the metastatic setting accounted for 6% (5/87) of enrollments. Two studies had zero accruals. The majority of the trial participants (77/87; 89%) belonged to URMs (64 Hispanic, 13 Black). Overall participation rate was 67% (87/129) and was significantly higher in Hispanics compared to Blacks (77% vs 41% - p &amp;lt; 0.001). Among Black patients who declined participation, 42% (8/19) cited lack of interest as the reason, which may reflect distrust or misperceptions regarding clinical trials. Conclusions: The collaboration between academic centers and safety-net systems provides a unique opportunity to promote equity in clinical trials by increasing access and enrollment of URMs. Developing a balanced portfolio that matches the patient population, enhanced screening, and incorporating clinical trial patient navigation at our institution resulted in a sustained increase in the number of URM trial participants. Given the lower participation rate among eligible Black patients, we aim to expand our clinical trial navigation program to better address the distrust and misperceptions regarding clinical trials, as a strategy to further improve trial participation at our institution. Citation Format: Nasir Qureshi, Fabian Robles. Minority participation in breast cancer therapeutic trials at an NCI-CCC affiliated safety-net system: Advancing equity in clinical research [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-10.

Abstract PO5-10-06: A Pilot Study for Clinical Research Nurse Navigation at an Urban NCI-Designated Comprehensive Cancer Center

Abstract Background: Breast cancer is now the leading cause of cancer death for non-Hispanic Black women in Georgia with non-Hispanic Black women 40% more likely to die of breast cancer compared to White women. Inadequate representation of patients in clinical trials may contribute to health care inequity, though prior work has also shown disparate outcomes on similar clinical trials at Emory, suggesting differences in tumor biology may also be contributing to the disparity. Improving diversity in trial participation is imperative to better understand these differences, particularly with newer molecularly targeted therapies. We aimed to utilize Clinical Trials Nurse Navigation to increase clinical trial enrollment at an urban NCI-designated comprehensive care center in Atlanta, Georgia. Methods: A prospective pilot study was conducted investigating the role of a Clinical Research Nurse as a dedicated Clinical Trials Nurse Navigator to identify, pre-screen, and refer potential patients to both breast and next generation sequencing (NGS)-driven basket clinical trials at the Winship Cancer Institute at Emory University. The role also included centralizing all molecular data from patients with stage IV breast cancer into a database as a tool to refer patients to NGS-driven clinical trials. This role expands upon the Institute’s current research nursing scope to better meet the needs of our diverse patient population. Our catchment area is 35% non-Hispanic Black or African American. The nurse prescreened patients with stage IV breast cancer from breast oncology clinic templates and the breast NGS database to match them with clinical trials, with a particular emphasis on patients with stage IV triple negative breast cancer. The study began in January 2022 and is currently ongoing. Results: Since study initiation in January 2022, there has been a 27% increase in breast cancer clinical trial enrollment over a 12-month period. Over the last 6 months from January 2023, this has increased even further with 57 patients enrolled onto breast cancer clinical trials compared to a total enrollment of 70 patients onto breast cancer clinical trials in 2022 (Table 1). Of these patients, 11% enrolled in NGS-driven clinical trials in 2022 to present compared to 0% in 2021. Twenty-two (31.4%) non-Hispanic Black women enrolled onto breast cancer clinical trials in 2022 with another 21 (36.8%) non-Hispanic Black women enrolled thus far in 2023 (Table 1). Conclusion: Disparities in clinical trial enrollment may contribute to racial inequities in breast cancer outcomes. Implementation of clinical research nurse navigation has successfully improved clinical trial enrollment and diversity in clinical trial enrollment at our urban cancer center. Through increasing clinical trial prescreening, centralizing an NGS database, and dedicated nurse support to allow patients to navigate onto clinical trials, we achieved a 21% improvement in clinical trial enrollment from 2021 to 2022 and are on track to increase enrollment by 200% by the end of 2023. Clinical trials nurse navigators serve as an essential link between clinical trial patients and their providers, and should strongly be considered a key component of all clinical trials programs. Table 1 Breast Working Group Patient Enrollment by Race and Ethnicity, 2019-2023 Citation Format: Lizzie Huckaby, Maisey Ratcliffe, Madison Canning, Demetria Smith-Graziani, Kevin Kalinsky, Manali Bhave. A Pilot Study for Clinical Research Nurse Navigation at an Urban NCI-Designated Comprehensive Cancer Center [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-10-06.

Abstract PO5-04-05: Clinical validation of the concordance performance of ERBB2 status by single-cells genomics ERBB2 (HER2) amplification Assay in Circulating Tumor Cells (CTCs) from patients with matched HER2 status from metastatic tissue biopsies

Abstract Background Liquid biopsies are a non-invasive diagnostic approach for detecting CTCs that may provide clinically actionable information for treatment decisions for metastatic breast cancer (MBC) patients when a conventional biopsy is infeasible. Blood-based liquid biopsy has the potential advantage that it allows broad sampling of metastatic tumor clones because it is capable of and likely to obtain cellular and genomic contributions from more than one metastatic site. Here we report the concordance performance of HER2 positivity by single-cell CTC genomics ERBB2 (HER2) amplification in patients with matched HER2 status from metastatic tissue biopsies. Methods A prospective Clinical Experience Program for CTC ERBB2 (HER2) Assay across 25 different United States-based cancer centers, was used to recruit 128 MBC patients with documented standard-of-care metastatic tissue biopsies performed within the last 5 years (Days from tissue biopsy to liquid biopsy, Median: 19.5; interquartile range: 40.75) CTCs from blood collection at each respective clinical site were isolated from plasma, nucleated cells were plated, &amp; slides were bio-banked for Immunofluorescent staining &amp; subsequent imaging in a CAP CLIA lab. CTCs were identified using Epic Sciences digital imaging &amp; machine learning algorithms. Individual CTCs were sequenced for genomic quantification of chromosomal instability (LSTs) and ERBB2 (HER2) amplification. Results Within the clinical validation cohort of 128 MBC patients, 30% (38/128) were HER2-positive by standard pathologic criteria (IHC 3+ or IHC2+/ISH+) in metastatic tissue biopsies. Among the 64 out of 128 cases with reportable results by the CTC ERBB2 (HER2) amplification on chromosomally unstable CTCs, 31% (20/64) of patients had ERBB2 amplification. Concordance between CTC single cell genomics and available tissue results for HER2 positivity showed a sensitivity of 69% and specificity of 78%. We then addressed the effects of two known biological confounders to the use of tissue biopsy for HER2 status determination: 1) tissue biopsies performed on bone metastases, 2) tumor evolution driven by treatment pressure over time leading to potential HER2 conversion and tumor heterogeneity. Thus, we performed subgroup analysis including only validation set patients with tissue biopsies performed on non-bone tissues, which showed slightly improved concordance to the tissue comparator with a Sensitivity of 86%, and Specificity of 75%. Next, to exclude the possibility of tumor evolution we selected only patients with the HER2 status comparator performed on non-bone tissue biopsies contemporaneous (Days from tissue biopsy to liquid biopsy, Median: 14; interquartile range: 22) to the blood draw for the CTC ERBB2 (HER2) amplification assay. This showed dramatically improved concordance performance with a Sensitivity of 100%, and a Specificity of 75%. Conclusions Blood and tissue are two biologically distinct sample types where variations in HER2 and other biomarker results might be expected due to analytic, temporal and clinical differences. These data indicate that determination of HER2 status by single cell genomic ERBB2 (HER2) amplification assay can aid in the clinical assessment of ERBB2 status in patients with metastatic breast cancer (MBC) for whom tissue biopsy for HER2 status is not available, or infeasible. Additionally, these results provide evidence of the contribution of site differences (bone) of metastatic biopsies and also tumor evolution to discordance between the CTC ERBB2 (HER2) Assay and tumor biopsy. Citation Format: Giuseppe Di Caro, Ernest Lam, Megan Slade, Shuguang Huang, Rick Wenstrup, Lee Schwartzberg. Clinical validation of the concordance performance of ERBB2 status by single-cells genomics ERBB2 (HER2) amplification Assay in Circulating Tumor Cells (CTCs) from patients with matched HER2 status from metastatic tissue biopsies [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-05.

Abstract PO5-27-11: A COMPARATIVE STUDY OF DIAGNOSTICS MADE BY FINE NEEDLE ASPIRATION (FNA) BIOPSY VERSUS TRU-CUT FOR BREAST PATHOLOGY IN A ONE STOP CLINIC PROGRAM IN MEDELLIN, COLOMBIA

Abstract Breast cancer is the leading cause of morbidity and mortality among women in Colombia due to non-communicable chronic diseases. This has prompted health insurance companies to develop innovative initiatives to mitigate these negative outcomes. Since September 2018, Ayudas Diagnósticas SURA, in alliance with the Gustave Roussy Hospital and General Electric Healthcare has promoted a “One-stop clinic” program called: “TIEMPO PARA TI”. One of the primary challenges was to demonstrate that breast cytology, based on the Yokohama guidelines approved by The International Academy of Cytology has a high sensitivity, specificity, and diagnostic accuracy. The Yokohama system for classifying breast cytology is comprised of five categories: C1 not satisfactory, C2 benign, C3 atypical, C4 malignancy suspected, and C5 malignant. From September 2018 to December 2022, consecutive patients referred for breast biopsy and suspected of having breast cancer underwent triple assessment of breast tumor and were included in this retrospective study. Descriptive analysis was made using STATA v17 software to compare fine needle aspiration (FNA) biopsy versus Tru-cut. A total of 14,501 patients were included, 14.398 FNA and 14.401 trucut biopsies were performed. The comparative analysis showed a 99% concordance between categories 2, which correspond to benign lesions and 96.7% between categories 5, which correspond to malignant lesions. Our findings demonstrate that a well-executed FNA biopsy is not inferior to a trucut biopsy, as revealed by the Yokohama system, and offers significant advantages, such as cost-effectiveness and prompt diagnosis. Both techniques should be used with caution, considering their advantages and disadvantages. Citation Format: Sara Gil, Carlos Agudelo, Jorge Castaño, Melissa Naranjo, Clara Piedrahita, Daniel Wilches, Kelly Corredor. A COMPARATIVE STUDY OF DIAGNOSTICS MADE BY FINE NEEDLE ASPIRATION (FNA) BIOPSY VERSUS TRU-CUT FOR BREAST PATHOLOGY IN A ONE STOP CLINIC PROGRAM IN MEDELLIN, COLOMBIA [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-11.

Alterations in the gut mycobiome with coronary artery disease severity

BackgroundCoronary artery disease (CAD) is a prevalent cardiovascular condition, and numerous studies have linked gut bacterial imbalance to CAD. However, the relationship of gut fungi, another essential component of the intestinal microbiota, with CAD remains poorly understood. MethodsIn this cross-sectional study, we analyzed fecal samples from 132 participants, split into 31 healthy controls and 101 CAD patients, further categorized into stable CAD (38), unstable angina (41), and acute myocardial infarction (22) groups. We conducted internal transcribed spacer 1 (ITS1) and 16S sequencing to examine gut fungal and bacterial communities. FindingsBased on ITS1 analyses, Ascomycota and Basidiomycota were the dominant fungal phyla in all the groups. The α diversity of gut mycobiome remained unaltered among the control group and CAD subgroups; however, the structure and composition of the mycobiota differed significantly with the progression of CAD. The abundances of 15 taxa gradually changed with the occurrence and progression of the disease and were significantly correlated with major CAD risk factor indicators. The mycobiome changes were closely linked to gut microbiome dysbiosis in patients with CAD. Furthermore, disease classifiers based on gut fungi effectively identified subgroups with different degrees of CAD. Finally, the FUNGuild analysis further categorized these fungi into distinct ecological guilds. InterpretationIn conclusion, the structure and composition of the gut fungal community differed from healthy controls to various subtypes of CAD, revealing key fungi taxa alterations linked to the onset and progression of CAD. Our study highlights the potential role of gut fungi in CAD and may facilitate the development of novel biomarkers and therapeutic targets for CAD. FundingThis work was supported by the grants from the National Natural Science Foundation of China (No. 82170302, 92168117, 82370432), National clinical key specialty construction project- Cardiovascular Surgery, 2024 Reform and Development Program of Beijing Institute of Respiratory Medicine, the Beijing Natural Science Foundation (No. 7222068); the Reform and Development Program of Beijing Institute of Respiratory Medicine (No. Ggyfz202308); and the Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (No. CYFH202209).

Management of peripheral arterial disease in the context of a multidisciplinary limb program

Peripheral artery disease (PAD) continues to increase in prevalence worldwide due to risk factors such as advanced age, diabetes mellitus, and obesity. Critical limb ischemia (CLTI) is the advanced form of PAD that can result in a lack of healing and limb loss as the most devastating consequence. Patients with PAD, especially CLTI, benefit from multidisciplinary care to optimize outcomes by reducing cardiovascular morbidity and mortality and preventing lower extremity amputation. Collaboration between various specialties allows a focus on problems involved in treating the patient with PAD including prevention, screening, medical care, wound care, infection, and revascularization when needed. Although there is no clear definition or consensus on the structure of the PAD team, certain guidelines are applicable to most clinical scenarios emphasizing “provider champions” in leading a clinical program. A vascular specialist (vascular surgery, interventional radiology, interventional cardiology) and a soft tissue specialist (podiatry, plastic surgery) are the typical “champions,” often involving orthopedics, general surgery, vascular medicine, diabetology/endocrinology, infectious disease, nephrology, and rehabilitation medicine. The team should also include wound nurses, nutritionists, occupational therapists, orthotists, pharmacists, physical therapists, prosthetists, and social workers. This paper presents a brief overview of the structure of the multidisciplinary team with key components and functions of such a team to optimize treatment outcomes for PAD and CLTI.

CONSUMER EXPERIENCE OF AN AUSTRALIAN MULTIDISCIPLINARY LONG COVID CLINIC THAT INCORPORATES PERSONALISED EXERCISE PRESCRIPTION: A QUALITATIVE ANALYSIS

INTRODUCTION &amp; AIMS Little is known about the Australian experience of Long COVID recovery, particularly with respect to exercise prescription. The aim of this study was to understand the consumer experience and acceptability of a novel Australian Long COVID Recovery Clinic that incorporates personalised exercise prescription, including respiratory and peripheral strengthening and carefully monitored cardiovascular training. METHODS Qualitative study; semi-structured interviews with a convenience sample of participants who have completed a multidisciplinary, individually-tailored and supervised programme at our Long COVID Recovery Clinic. Interviews were conducted by a researcher external to the clinic delivery. Major themes were identified by inductive thematic analysis. RESULTS 15 participants were interviewed. 14/15 (93%) participants described the clinic model as acceptable or highly acceptable. Five core themes were identified, including (1) encouraging staff and light-filled facilities are key to support recovery; (2) individually tailored, supervised exercise and pacing helped to improve confidence in building exercise capacity; (3) peer support and group therapy augments recovery; (4) recovery from Long COVID is incomplete, and other services augment the Long COVID Recovery Clinic model; and (5) importance of GP involvement in connection with clinic participation. Suggestions for improvement included extending the duration of the clinic programme beyond 2 months, reducing wait times by increasing staffing levels and adjusting the clinic schedule to broaden access options. CONCLUSION The majority of participants found the Long COVID Recovery Clinic, which incorporates both supervised exercise and pacing, acceptable and would recommend it to others. From the consumer perspective, the Long COVID Recovery Clinic aids recovery alongside GP management through a combination of peer support and an individually tailored program.

FEASIBILITY, ACCEPTABILITY, AND EFFICACY OF A PILOT EXERCISE PHYSIOLOGY GROUP SERVICE FOR OLDER ADULTS WITH TYPE 2 DIABETES

INTRODUCTION &amp; AIMS Type 2 diabetes prevalence increases with ageing, affecting over half a million older Australians. Medicare type 2 diabetes group interventions can support older adults’ diabetes management. However, Accredited Exercise Physiologist (AEP) delivered service feasibility and acceptability is yet to be assessed. This study aimed to assess feasibility, acceptability and preliminary efficacy of a Medicare type 2 diabetes group exercise and education intervention for older adults. METHODS This study was a single arm feasibility, acceptability, and preliminary efficacy trial of an AEP delivered type 2 diabetes group service for older adults. Participants attended the Diabetes Clinic once per week for 8 weeks, for a group exercise and education session. Attendance, participation, enjoyment, suitability, usefulness, and pre-post clinical health outcomes were assessed. RESULTS The intervention was feasible and acceptable, with 40 participants (71.8±4.5 years old, range 65-81 years, 45% female) attending 87% of sessions, with high treatment compliance within sessions (aerobic training: 86%; resistance training: 86%; education: 87%). Almost all participants (97%) strongly agreed that the program was enjoyable. Significant post intervention improvements (mean difference [95% CI]) were observed for right arm systolic blood pressure (SBP) (-7mmHg [-12, -2], p=0.007), left arm diastolic blood pressure (DBP) (-3mmHg [-5, -0], p=0.021), body weight (-0.7kg [-1.3, -0.0], p=0.039), waist circumference (-1.3cm [-2.2, -0.4], p=0.006), 6-minute walk test (22.8m, [9.1. 36.5], p=0.002), 5 times sit to stand (-0.8sec [-1.2, -0.5], p&amp;lt;0.001), short physical performance battery ordinal scale (0.3 [0.1, 0.5], p=0.009), and whole-body muscle strength (32.2kg [22.3, 42.1], p&amp;lt;0.001). CONCLUSION Older adults attended and enjoyed the AEP led Diabetes Clinic program, while also improving fitness and cardiometabolic health outcomes. Ways to enhance referrals and engage older adults in the programs warrant further investigation. The potential for additional sessions to achieve greater physical activity engagement and diabetes self-management should be further investigated.

Once-weekly insulin efsitora alfa: Design and rationale for the QWINT phase 3 clinical development programme.

Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This review describes the study design and rationale of the efsitora phase 3 Once Weekly (QW) Insulin Therapy (QWINT) clinical development programme, including the five trials, QWINT-1 through QWINT-5. The five trials included insulin-naïve adults (QWINT-1 and -2) with type 2 diabetes (T2D), adults with T2D previously treated with basal insulin (QWINT-3 and -4), and QWINT-5 in adults with type 1 diabetes. All five trials were designed as multicentre, randomized, controlled, open-label, treat-to-target studies to investigate the efficacy and safety of efsitora versus active once-daily basal insulin comparators (insulin glargine U100 or insulin degludec U100). The primary objective of each trial is to compare the change in HbA1c from baseline to week 26 or 52 between efsitora and the active comparator. The key secondary objectives include change in fasting glucose, insulin dose and continuous glucose monitoring variables, and patient-reported outcome questionnaires. The QWINT development programme includes a racially and geographically diverse population to provide important information regarding the efficacy and safety of efsitora and its clinical management of people with diabetes.

Addressing Sexually Transmitted Infections Due to Neisseria gonorrhoeae in the Present and Future

It was in the 1800s when the first public publications about the infection and treatment of gonorrhoea were released. However, the first prevention programmes were only published a hundred years later. In the 1940s, the concept of vaccination was introduced into clinical prevention programmes to address early sulphonamide resistance. Since then, tons of publications on Neisseria gonorrhoeae are undisputed, around 30,000 publications today. Currently, the situation seems to be just as it was in the last century, nothing has changed or improved. So, what are we doing wrong? And more importantly, what might we do? The review presented here aims to review the current situation regarding the resistance mechanisms, prevention programmes, treatments, and vaccines, with the challenge of better understanding this special pathogen. The authors have reviewed the last five years of advancements, knowledge, and perspectives for addressing the Neisseria gonorrhoeae issue, focusing on new therapeutic alternatives.

Personalization above anonymization? A role for considering the humanity and spirituality of the dead in anatomical education.

Clinical anatomy education is meant to prepare students for caring for the living, often by working with the dead. By their nature many clinical anatomy education programs privilege topographical form over the donor's humanity. This inbalance between the living and the dead generates tensions between the tangible and the spiritual insofar as semblances of the humanity of donors endure even in depictions and derivatives. This article argues that considering the relevance of spirituality, and what endures of a donor's humanity after death, would enhance contemporary anatomy education and the ethical treatment of human body donors (and derivatives). In developing this argument, we (the authors) address the historical connection between spirituality and anatomy, including the anatomical locations of the soul. This serves as a basis for examining the role of the mimetic-or imitative-potential of deceased human donors as representations of the living. We deliberate on the ways in which the depersonalization and anonymization of those donating challenge themimetic purpose of human body donorsand the extent to which such practicesare misaligned with the health care shift from a biomedical to a biopsychosocial model. Weighing up the risks and opportunities of anonymization versus personalization of human body donors, we propose curricula that could serve to enhance the personalization of human donors to support students learning topographical form. In doing so, we argue that the personalization of human donors and depictions could prevent the ill effects of digital representations going "viral," and enhance opportunities for donors to help the general public learn more about the human form.

Assisted Reproductive Technologies: A New Player in the Foetal Programming of Childhood and Adult Diseases?

Assisted reproductive technology (ART) is an emerging field in medicine that incorporates complex procedures and has profound ethical, moral, social, religious, and economic implications not just for the individuals who have access to this method but also for society. In this narrative review, we summarise multiple aspects of ART procedures and the possible consequences on the mother and newborn. Moreover, we provide an overview of the possible long-term consequences of ART procedures on the health of newborns, although longitudinal evidence is particularly scant. Users should be informed that ART procedures are not risk-free to prepare them for the possible negative outcomes that may occur in the perinatal period or even in childhood and adulthood. Indeed, risk estimates point to increased liability for major nonchromosomal birth defects; cardiovascular, musculoskeletal, and urogenital (in male newborns) defects; and any other birth defects. Less certainty is present for the risk of neuropsychiatric sequelae in children conceived through ART. Thus, its application should be accompanied by adequate counselling and psychological support, possibly integrated into specific multidisciplinary clinical programmes.

P172 An integrated safety analysis of treatment-emergent fungal infections in patients with psoriasis, psoriatic arthritis, or axial spondyloarthritis treated with ixekizumab from 26 clinical studies

Abstract Background/Aims Interleukin (IL)-17 plays a role in host defense against common extracellular pathogens, including fungi. Treatment with IL-17 inhibitors has been associated with fungal infections. Ixekizumab (IXE) is an anti-IL-17A monoclonal antibody approved for the treatment of psoriasis (PsO) in adults and children, psoriatic arthritis (PsA) in adults, and axial spondyloarthritis (axSpA) in adults. This integrated post-hoc analysis investigates treatment-emergent fungal infections in IXE-treated patients across the approved indications. Methods Safety data on fungal infections were pooled from the IXE paediatric and adult clinical trial programs, comprising 26 clinical studies. Here, we describe the types of fungal infections, number of infections, recurrence (defined by at least two separate events irrespective of location), severity (defined at the investigator’s discretion), events that lead to discontinuation, and anti-fungal medications. Data are presented as frequency or incidence rate per 100 person-years (IR). Results Fungal infections were reported in patients with PsO (IR = 4.0), PsA (IR = 4.1), and axSpA (IR = 2.7). Across indications, most fungal infections were not recurrent and were classified as mild or moderate in severity. There were few severe fungal infections in patients with PsO (IR = 0.1), PsA (IR = 0.0), and axSpA (IR = 0.0). Most fungal infections in patients with PsO, PsA, and axSpA were candidiasis (IR = 1.9, IR = 2.5, IR = 1.4, respectively) and superficial dermatophytosis (IR = 1.5, IR = 1.0, IR = 1.0, respectively). No cases of subcutaneous and systemic mycosis infections were reported. The proportions of patients with PsO, PsA, and axSpA who received a topical vs systemic anti-fungal medication were 53.6% vs 1.1%, 47.8% vs 0.0%, and 45.6% vs 3.5%, respectively (Table 1). Most fungal infections did not lead to discontinuation of IXE (Table 1). Conclusion Consistent with previously disclosed IXE data, the majority of treatment-emergent fungal infections observed in patients with PsO, PsA, or axSpA treated with IXE were: (i) not recurrent; (ii) mild or moderate in severity, (iii) associated with candidiasis and superficial dermatophytosis, (iv) managed with topical anti-fungal medications or no treatment reported, and (v) not leading to drug discontinuation. Disclosure S. Schwartzman: Corporate appointments; SS reports being a board member of the National Psoriasis Foundation. Consultancies; S. Schwartzman has served as a speaker and/or consultant for AbbVie, Janssen, Eli Lilly and Company, Pfizer, UCB, Myriad, Novartis, Regeneron, Sanofi, Stelexis, Jubilant, Teijin. L. Puig: Corporate appointments; Board member of the International Psoriasis Council. Consultancies; AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Leo Pharma, Eli Lilly and Company, Novartis, Pfizer, Sandoz, Sanofi, UCB. Honoraria; Boehringer Ingelheim, Janssen, Eli Lilly and Company, Novartis, UCB, travel support from Janssen, Eli Lilly and Company, Pfizer, UCB. Grants/research support; L. Puig reports receiving grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Leo Pharma, Eli Lilly and Company, Novartis, Pfizer, Sanofi, UCB. A.D. Cohen: Honoraria; AbbVie, Amgen, Boehringer Ingelheim, Dexcel Pharma; Janssen, Eli Lilly and Company, Neopharm, Novartis, Perrigo, Pfizer, Rafa. Grants/research support; A. D. Cohen has served on advisory board for Samsung, and reports receiving grants from AbbVie, Janssen, Novartis, Pfizer, travel support from AbbVie. S. Khattri: Consultancies; S. Khattri reports being part of Eli Lilly and Company speaker’s bureau, receiving consulting fees and honoraria from Eli Lilly and Company, AbbVie, UCB, Janssen, BI, Regeneron, Leo Pharma. C. Jossart: Shareholder/stock ownership; C. Jossart is a stockholder of Eli Lilly and Company and was an employee of Eli Lilly and Company when this study was conducted. C. Diaz: Shareholder/stock ownership; C. Diaz is employee and stockholder of Eli Lilly and Company. A. Garrelts: Shareholder/stock ownership; A. Garrelts is employee and stockholder of Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; D. Zhu is employee and stockholder of Eli Lilly and Company. N. Eberhart: Shareholder/stock ownership; N. Eberhart is employee and stockholder of Eli Lilly and Company. A. Eleftheriadi: Shareholder/stock ownership; A. Eleftheriadi is employee and stockholder of Eli Lilly and Company. N. Tangsirisap: Shareholder/stock ownership; N. Tangsirisap is employee and stockholder of Eli Lilly and Company. C. Schuster: Shareholder/stock ownership; C. Schuster is an employee and stockholder of Eli Lilly and Company. A.B. Gottlieb: Consultancies; Xbiotech (stock options for an RA project). Honoraria; Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dice Therapuetics, Dermavant, Lilly, Janssen, Leo, Pharma, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma. Grants/research support; AnaptysBio, Moonlake Immunotherapeutics, Novartis, BMS, and UCB Pharma; all funds go to the Icahn School of Medicine at Mount Sinai. M. Sheesh: Shareholder/stock ownership; MS is a full-time employee and minor share holder of Eli-Lilly and Company.

The development of a framework for clinical education programme of undergraduate nursing students in Ghana

IntroductionClinical education is an important aspect of the training of nursing students but it is faced with challenges in Ghana. The development of a framework will respond to the need for improvement in the quality of clinical nursing education. This study describes part of a larger study which culminated in the development of a framework for a clinical education programme for undergraduate nursing students in Ghana. The aim of the current study was to integrate findings from a scoping review and situational analysis to develop a framework for clinical education in nursing.MethodsA sequential multimethod design approach was used to conduct the study. A scoping review on the practices that facilitate clinical nursing education and situational analysis were first conducted. The lessons learnt from the scoping review and the situational analysis provided the data matrix that was triangulated to develop the framework. The framework was developed using the model for clinical education developed by South African Nursing Education Stakeholders in consultation with experts in nursing education. An implementation plan was developed from the framework and evaluated using a Delphi technique.FindingsThe resulting framework indicates the need for effective communication and collaboration between nursing education institution and the service setting to ensure that there is a well-structured clinical placement, formal supervision system and effective clinical assessment of students. The framework also proposes that to ensure quality clinical nursing education there is the need for Nursing Education Institutions to implement innovative and cost-effective clinical teaching methods.ConclusionThe framework spells out the functions of the various stakeholders in nursing education and how these can be integrated and implemented to enhance quality clinical nursing education. Effectiveness of the thematic areas of the framework will increase the quality of clinical nursing education.

Opinion & Special Article: Community Approach Toward Inclusion of Sex and Gender Diversity in Graduate Neurology Education.

Sex and gender diverse (SGD) neurology trainees include transgender, nonbinary, and intersex people. There has been historical exclusion of SGD trainees from participating in clinical care, medical research, and academic training programs. Therefore, neurology educators have unique opportunities to support SGD trainees and colleagues, but may lack the education to appropriately do so. Training programs and professional organizations can collaborate to create safe pathways for SGD trainees to disclose their identities in professional settings. Referral to community support and resources is important for SGD trainees considering professional disclosure. Educators should address the challenges and discrimination unique to SGD graduate trainees in neurology, such as lack of inclusion, affirming environments, supportive policies, and medical accommodations. Faculty training on sensitivity, bias, and bystander effects should be ongoing among institutions. Topics regarding sex and gender diversity are lacking in graduate medical education. Educational curricula often use outdated terminology or binary paradigms to teach about sex and gender. Health care training inequities may cause downstream harm to SGD patients; therefore, training curricula that are reflective of an accurate and affirming understanding of sex and gender may mitigate the potential for inequities. This article provides recommendations to support SGD neurology trainees and to incorporate specific training on sex and gender diversity in academic neurology curricula. Such support is critical to the career success and development of SGD neurology trainees.

SEEIIST – a new research facility for tumor treatment and biomedical investigations with proton and ion beams

Abstract Purpose A project for the establishment of an international intergovernmental scientific organization in the region of South East Europe (South East European Institute for Sustainable Technologies - SEEIIST) is currently in progress. SEEIIST is an intergovernmental effort supported by nine countries from the region (Albania, Bosnia and Herzegovina, Bulgaria, Greece, Kosovo (This designation is without prejudice to positions on status, and is in line with UNSC 1244 and the ICJ Opinion on the Kosovo Declaration of Independence.), Montenegro, North Macedonia, Serbia and Slovenia, while Switzerland is an observer). The main goals of the project are to establish a unique research infrastructure and to form a research nucleus in the region of South-East Europe, to boost the technology transfer from European laboratories like CERN and others, to promote collaboration between science, technology, and industry, to mitigate tensions between countries in the region, and to provide platforms for the development of education. Methods The research infrastructure will include a powerful next-generation accelerator that will provide proton and ion beams for tumor treatment and biomedical research. The center will comprise of three rooms for patient treatment and two large experimental halls. Results A wide pre-clinical and clinical research program in the fields of radiobiology, medical physics, medical imaging, biophysical modeling and planning of patient treatment, design and investigation of new materials, production of isotopes for diagnosis, and treatment of patients are envisaged. Conclusions This infrastructure is unique for Europe and will attract researchers from all European countries to perform their investigations.

Pegvaliase for the treatment of phenylketonuria: Final results of a long-term phase 3 clinical trial program

Phenylketonuria (PKU) is a genetic disorder caused by deficiency of the enzyme phenylalanine hydroxylase (PAH), which results in phenylalanine (Phe) accumulation in the blood and brain, and requires lifelong treatment to keep blood Phe in a safe range. Pegvaliase is an enzyme-substitution therapy approved for individuals with PKU and uncontrolled blood Phe concentrations (>600 μmol/L) despite prior management. Aggregated results from the PRISM clinical trials demonstrated substantial and sustained reductions in blood Phe with a manageable safety profile, but also noted individual variation in time to and dose needed for a first response. This analysis reports longer-term aggregate findings and characterizes individual participant responses to pegvaliase using final data from the randomized trials PRISM-1 (NCT01819727) and PRISM-2 (NCT01889862), and the open-label extension study 165–304 (NCT03694353). In 261 adult participants with a mean of 36.6 months of pegvaliase treatment, 71.3%, 65.1%, and 59.4% achieved clinically significant blood Phe levels of ≤600, ≤360, and ≤ 120 μmol/L, respectively. Some participants achieved blood Phe reductions with <20 mg/day pegvaliase, although most required higher doses. Based on Kaplan-Meier analysis, median (minimum, maximum) time to first achievement of a blood Phe threshold of ≤600, ≤360, or ≤ 120 μmol/L was 4.4 (0.0, 54.0), 8.0 (0.0, 57.0), and 11.6 (0.0, 66.0) months, respectively. Once achieved, blood Phe levels remained below clinical threshold in most participants. Sustained Phe response (SPR), a new method described within for measuring durability of blood Phe response, was achieved by 85.5%, 84.7%, and 78.1% of blood Phe responders at blood Phe thresholds of ≤600, ≤360, or ≤ 120 μmol/L, respectively. Longer-term safety data were consistent with previous reports, with the most common adverse events (AEs) being arthralgia, injection site reactions, headache, and injection site erythema. The incidence of most AEs, including hypersensitivity AEs, was higher during the early treatment phase (≤6 months) than later during treatment. In conclusion, using data from three key pegvaliase clinical trials, participants treated with pegvaliase were able to reach clinically significant blood Phe reductions to clinical thresholds of ≤600, ≤360, or ≤ 120 μmol/L during early treatment, with safety profiles improving from early to sustained treatment. This study also supports the use of participant-level data and new ways of looking at durable blood Phe responses to better characterize patients' individual PKU treatment journeys.