Real-world Experience Research Articles

Real-world patient experience with medicinal cannabis use for symptom management in an Australian advanced cancer setting: a mixed method, cohort study using the theory of planned behaviour framework.

Patient hesitancy to use MC due to the fear of negative social implications leads to intentional non-adherence and compromises therapeutic outcomes. Hence, we aimed to determine the rate of patient adherence to MC and explore factors influencing patient MC use. Demographic and quantitative data related to MC usage were extracted from medical records for patients prescribed MC at a single cancer centre in metropolitan Sydney. Qualitative data was generated from semi-structured interviews. Interview guides were developed based on the Theory of Planned Behaviour (TBP) domains (i.e. Attitudes, Subjective Norms, Behavioural Intention and Perceived Behavioural Control) to elucidate themes influencing MC use. A mixed method approach involving triangulation of quantitative and qualitative methods was used for data analysis. Twenty patients were included in the study, and the majority of patients showed adherence (n = 14, 70%). The MC formulation used (p = .018), symptom relief (p = .001) and side effects experienced (p = .007) significantly influenced MC adherence. In addition to side effects experienced, findings for barriers to adherence were convergent or complementary for other medication-related factors, including the inconvenience of MC co-administration with food, cost and unpleasant taste. MC adherence is influenced by its effectiveness for symptom relief whereby appropriate MC formulation selection is crucial and should be determined by the indication (or symptom clusters). Social factors such as the views and experiences of close others had little bearing on MC adherence.

Abstract Su1205: The Effect of Targeted Temperature Management on Five-Year Mortality in Comatose Out-of-Hospital Cardiac Arrest Survivors: A Real-World Experience

Background: Hypothermia-Induced Targeted Temperature Management (TTM) is a neuroprotective treatment after the return of spontaneous circulation (ROSC) in comatose survivors of out-of-hospital cardiac arrest (OHCA). However, its effectiveness in all patient subpopulations is debated. While short-term survival has been well studied, the impact of TTM on long-term survival is still unknown. Methods: In a prospective cohort study, 98 comatose survivors of non-traumatic OHCA were recruited from four tertiary-level hospitals in Buffalo, Western New York and followed up for five years. Patients with active cancer, infection, cardiac pathology or surgery in three-month prior to presentation, were excluded. Cardiac arrest characteristics, demographics, comorbidities, and therapeutic interventions were recorded. According to TTM protocols, a target body temperature of 33°C was reached and maintained for 24 hours using either an intravascular cooling catheter or a surface cooling system. This was followed by gradual controlled rewarming over 12-24 hours to normothermia. Factors associated with the receipt of TTM were determined. The effect of TTM on five-year survival was studied using cox-regression analysis. Results: Among comatose patients with mean age of 60.1±14.9 years, 49% received TTM. Females were significantly less likely to receive TTM (35.1% vs 59.3%, p=0.021). In TTM group, the time to ROSC was significantly longer: median [IQR] 14.5 mins (5-19.7) vs 20 mins (12-27), p=0.018. TTM group was more likely to have a history of coronary artery disease (CAD) (12.5% vs 35.4%, p=0.009). Overall, 5-year mortality did not differ significantly between TTM vs. non-TTM: 72.9% vs 66.0%, (HR: 1.134, 95% CI: 0.705-1.826, p=0.603) in univariate and multivariate Cox-regression analysis (Table 1). Conclusion: While females are less likely to receive TTM treatment, TTM is more likely to be used in patients with a longer time to ROSC and a history of CAD. The overall five-year survival remains high in both treatment groups in all eligible patients, as well as in shockable and non-shockable rhythm groups studied separately. Larger cohort studies are needed to determine the patients who may benefit most from TTM.

Abstract 4136804: Effect of Obesity on Arrhythmia Recurrence and Complications following Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation in the REAL-AF Registry

Introduction: Obesity is an important risk factor for atrial fibrillation and its prevalence in the United States is rising. The effect of obesity on outcomes following pulmonary vein isolation in a contemporary setting has not been extensively evaluated. Research Questions: - Is higher body mass index (BMI) associated with increased risk of atrial arrhythmia recurrence following pulmonary vein isolation? - Is higher BMI associated with increased risk of post-procedural complications? Method: - The REAL-AF (Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation; ClinicalTrials.gov Identifier: NCT04088071) Registry is a multicenter, prospective observational registry of patients undergoing radiofrequency catheter ablation of atrial fibrillation. We included 2666 patients with paroxysmal atrial fibrillation undergoing index ablation from January 2018 through April 2023. We excluded patients with missing covariates. - The primary outcome was freedom from atrial arrhythmia following ablation. Rhythm monitoring was standardized using patch monitor at 6 month and 1 year. Time-to-event analysis was performed using a 3-month blanking period. Results: - Baseline characteristics are shown in Table 1. The median follow-up was 382 days (IQR: 363-410). - There was a trend toward higher rate of atrial arrhythmia following ablation for patients in the highest BMI group compared with the reference group (BMI<25) ( BMI≥40: HR = 1.41 (0.94-2.12), p= 0.092). There was no difference in the rate of atrial arrhythmia for other BMI groups ( BMI 25 - <30: HR = 0.90 (0.65-1.23), p = 0.5; BMI 30 - <35: HR = 0.89 (0.64-1.23), p = 0.5; BMI 35 - <40: HR = 0.87 (0.57-1.32), p = 0.5). This trend persisted following adjustment for baseline covariates ( BMI 25 - <30: HR = 1.01 (0.77-1.33), p > 0.9; BMI 30 - <35: HR = 0.97 (0.72-1.32), p = 0.9; BMI 35 - <40: HR = 1.01 (0.66-1.55), p > 0.9; BMI≥40: HR = 1.57 (0.96-2.57), p =0.071). - First-pass isolation rates progressively decreased with higher BMI (Table 2). - Complication rates were low across all BMI groups (Table 2). Conclusions: - Severely obese patients with BMI ≥40 experience higher risk of atrial arrhythmia following radiofrequency catheter ablation of paroxysmal atrial fibrillation compared with normal weight individuals. This corresponds with lower rates of first-pass isolation at higher BMI. - Patients across BMI categories experience similarly low rates of procedural complication.

A phase 4, multicenter, global clinical study to evaluate discontinuation and rechallenge of pexidartinib in patients with tenosynovial giant cell tumor previously treated with pexidartinib.

Pexidartinib is effective in patients with tenosynovial giant cell tumor (TGCT) for whom surgery is not feasible. Durability of response after discontinuation of pexidartinib and the safety and efficacy of restarting pexidartinib have not been previously recorded. This phase 4 study was designed to mimic the real-world experience with pexidartinib to evaluate the effects of discontinuation of and retreatment with pexidartinib in patients with TGCT who previously benefited from the drug. This was a global, multicenter, phase 4 study that enrolled patients with TGCT who were experiencing clinical benefit from pexidartinib in one of four prior phase 1 or phase 3 studies investigating pexidartinib in the disease. Patients could choose to continue pexidartinib at the same dose (the treatment-continuation cohort) or discontinue treatment with the option to restart pexidartinib (the treatment-free/retreatment cohort). Tumor progression determined by Response Evaluation Criteriain Solid Tumors (RECIST) version 1.1, patient-reported outcomes (the Patient-Reported Outcomes Measurement Information System-Physical Function [PROMIS-PF] questionnaire and the EuroQol 5-dimension, 5-level [EQ-5D-5L] visual analog scale), and safety were assessed every 3 months. The primary end point was the proportion of patients in the treatment-free/retreatment cohort who remained treatment-free at month 12 and 24; this did not depend on disease progression. Thirty-two patients were enrolled: 21 chose to enter the treatment-continuation cohort, and 11 entered the treatment-free/retreatment cohort. During the treatment-free period, six of 11 (54.5%) patients in the treatment-free/retreatment cohort had progressive disease (PD) according to RECIST, version 1.1, whereas no patient in the treatment-continuation cohort had disease progression. Over the 24-month study, three of 11 (27.3%) patients in the treatment-free/retreatment cohort restarted treatment because of RECIST version 1.1 PD, symptomatic progression, or both (n=1 each). The probability of remaining treatment-free in the treatment-free/retreatment cohort was 73% (95% confidence interval, 37%-90%). In the treatment-free/retreatment cohort, the median progression-free survival of the treatment-free period was 22.8 months (95% confidence interval, 1.6 months to not estimable). By 6 months of retreatment, all retreated patients achieved new disease stabilization with no new safety concerns; two patients had clinically significant improvements in PROMIS-PF and EQ-5D-5L visual analog scale scores. The mean PROMIS-PF and EQ-5D-5L scores remained stable throughout the study. There was no hepatotoxicity and no new safety signal in either cohort. In this small phase 4 study designed to evaluate outcomes in patients who stopped and restarted pexidartinib, 54.5% of patients who discontinued pexidartinib showed PD, with a median progression-free survival of 22.8 months. Each of the three patients who restarted pexidartinib stopped progressing, and some reported a new gain in physical function. No PD was detected in patients who remained on treatment, and the safety profile did not indicate long-term hepatotoxicity or any new safety concerns. Pexidartinib is a medication for people with tenosynovial giant cell tumor (TGCT) for whom surgery is not recommended. This study examined what happens when patients stop taking pexidartinib (after it has helped them) to see whether it is safe and effective to restart if needed. Thirty-two patients were followed for 2 years: 21 chose to continue pexidartinib and did not experience disease progression, while 11 chose to stop pexidartinib; 54.5% of them had disease progression within 2 years. Three patients who stopped pexidartinib restarted treatment after their tumor size increased or their symptoms worsened. Restarting pexidartinib was safe and effective in these patients.

Mavacamten: Real-World Experience from 22 Months of the Risk Evaluation and Mitigation Strategy (REMS) Program.

Background: Mavacamten is the only cardiac myosin inhibitor approved by the US FDA for treatment of symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) patients. Under the risk evaluation and mitigation strategy (REMS) program for mavacamten, patients are required to be monitored for development of systolic heart failure, and reduction of left ventricular ejection fraction (LVEF) to <50%. We report results from the mavacamten REMS database (28-Apr-2022 to 27-Feb-2024). Methods: Data on healthcare providers and pharmacy certification, patient monitoring (from Patient Status Forms, based partly on echocardiograms), and screening for drug interactions prior to each dispense were collected. Results: Of 6,299 patients who received ≥1 dose of mavacamten, 60.0% were women; 64.6% were >60 years of age. Of 5,573 patients with submitted Patient Status Forms, 256 (4.6%) developed LVEF <50% and 71 (1.3%) experienced heart failure requiring hospitalization (HFH). On the 29,111 status forms in these patients, each representing an assessment of an echocardiogram, LVEF <50% was reported on 276 (0.9%) and HFH was reported on 86 (0.3%). Of 1,929 patients with ≥1 year of treatment, 78 (4.0%) had an LVEF reduction to <50% and 4 (0.2%) experienced LVEF <50% + HFH but later resumed treatment. Of 3,228 patients initiated on 5 mg/day mavacamten and were treated for at least 6 months, 2,391 (74.1%) remained at 5 or 10 mg/day. At 3- and 6-months following mavacamten treatment initiation, 57.2% and 70.3%, respectively, demonstrated post-Valsalva LV outflow tract gradient <30 mmHg. Conclusions: We describe the feasibility and experience of the first 22 months of the REMS program for prescribing mavacamten in >6,000 symptomatic obstructive HCM patients. The need for temporary interruption for LVEF <50% was low, including for patients on therapy ≥1 year, with even fewer LVEF reductions associated with HFH.

German Real-World Experience of Patients with Diverse Features of Acute Intermittent Porphyria Treated with Givosiran

Background/Objectives: Acute intermittent porphyria (AIP) is a metabolic disease characterised by neurovisceral crises with episodes of acute abdominal pain alongside life-altering, and often hidden, chronic symptoms. The elimination of precipitating factors, hemin therapy, and pain relief are strategies used to treat porphyria symptoms, but are often reserved for patients suffering recurrent, acute attacks. Givosiran (siRNA) is an emerging AIP therapy capable of silencing delta-aminolevulinic acid synthase-1 (ALAS1) and, in turn, reducing the accumulation of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) that precede porphyria symptoms. The aim of this study was to investigate the efficacy and safety of givosiran administration in patients with both acute and chronic AIP burden, who were poorly responsive to current therapies, using a personalised medicine approach. Methods: Real-world data were collected in consecutive patients treated with givosiran at an accredited German Porphyria Clinical Center. Biochemical, clinical, and HR-QoL outcomes were monitored alongside adverse events (AEs). Results: Twenty-eight patients treated between 2018 and 2024 were sub-categorised into groups corresponding to Ipnet terms 13 ‘Sporadic Attacks, 5 ‘Symptomatic High Excretors’, 5 ‘Prophylactic Heme’, and 5 “Recurrent Attacks’. The mean time from diagnosis to treatment was 9.2 years (range in months 1–324), and the mean duration of treatment was 30 months (range 3–68). After 6 months of monthly givosiran injection (2.5 mg/kg), all patients’ ALA levels reached &lt;2ULN, and 60% of patients attained PBG levels &lt; 2ULN (p &lt; 0.001). These biochemical responses were not different between sub-groups (p &gt; 0.05). Clinically, 75% of patients’ chronic and acute porphyria symptoms improved. The total patient populations’ annualised attack ratio (AAR) improved; Historical AAR: 2.9 (0–12.0) vs. Givo AAR: 0.45 (0–3.0) (p &lt; 0.01). During follow-up, nine patients experienced minor breakthrough episodes. Of these, three patients required hemin infusion. An association between clinical success and a shorter interim period between diagnosis and treatment was evident (r = −0.522, p = 0.0061). All patients’ indices of HR-QoL improved under givosiran, including mental health (38%, p &lt; 0.0001) and pain (38%, p &lt; 0.0001). Patient-reported health (givosiran 77.9% vs. baseline 37.1%, p &lt; 0.0001) and clinical outcome scores (86.9%: good–very good) were also positive. Two patients withdrew from treatment &lt;6 months, citing fatigue, which was a common side effect. A mild elevation in liver enzymes (AST and/or ALT &lt; 1.5ULN, 15.4%) and reduced glomerular filtration rates (GFR, 11.5%) were also evident, but no life-threatening adverse events (AEs) were attributed to givosiran treatment. Conclusions: Givosiran is effective in preventing severe acute attacks and reducing the chronic health burden in patients with acute intermittent porphyria. Importantly, HR-QoL improved in patients suffering chronic AIP burden with few incidences of historical attacks. All patients experienced substantially improved mental health, ease of living, and self-perceived health.

Building a community of practice around a community of inquiry: an examination of EFL students' perceptions of a virtual internship

In response to the new policy of English department, the internship program has been shifted to virtual programmes. As part of this initiative, the university has collaborated with other educational sectors to offer a virtual English as a Foreign Language (EFL) internship programme aimed at training individuals as EFL teachers. The aim of the study was to investigate student perceptions of dynamic social structures and communities of practice in technologically mediated environments, particularly in relation to virtual internships. The authors recognised a gap in research regarding how EFL students create meaningful learning experiences and how they build their practical knowledge in mediated communication environments. Quantitative and qualitative research methods were used. 50 students comprised the study subjects. The data were collected from multiple sources: interviews, students’ reflections, and community of inquiry and practice survey instruments. The findings revealed that an unprepared virtual environment led to social anxiety and challenges related to real-world work experience. The study suggests that evidence-based interventions in technologically mediated, virtual learning environments can help to resolve study findings with this goal: fostering a sense of belongingness and community that can promote effective remote interactions between learners and their teachers to ensure that internships serve students best.

Patient and public involvement in the design of an international clinical trial: real world experience

BackgroundThe value of patient and public involvement (PPI) during the earliest stages of clinical trial development, and prior to the award of substantive funding, is widely recognised. However, it is often under-resourced and PPI processes during this phase are rarely reported in detail. Having benefitted from seed funding to develop an international clinical trial proposal, we sought to describe and appraise PPI activities and processes that support pre-award co-development.MethodsA 12-month “accelerator” award facilitated development of a substantive funding application to deliver the Rheumatoid Arthritis Prevention PlatfORm Trial (RAPPORT), conceived to prioritise preventative interventions for people at risk of RA. PPI partners, including individuals at risk of rheumatoid arthritis (RA), RA patients, relatives and members of the public, provided feedback on key trial design issues through online meetings, a feedback form and emails. PPI processes employed during the one-year accelerator project were thereafter evaluated by PPI partners using an anonymous online feedback form with reference to National Institute of Health and Care Research (NIHR) UK standards for public involvement in research.ResultsSixteen out of the 25-strong PPI partner panel completed an online feedback form (64%). Respondents perceived PPI processes positively in relation to all NIHR standard domains. Several key facilitators and challenges were identified, including the need for adequate PPI funding during pre-award phases of research, strategies for creating an inclusive environment, flexibility around levels of involvement, and challenges in achieving representatively diverse participation, and the importance of communicating transparent processes for role-assignment and time-reimbursement.ConclusionsIn general, RAPPORT was considered an example of PPI well done, and in line with UK standards for public involvement in research. Facilitators and challenges of relevance for the development of future translational and clinical trial funding applications are highlighted.

Efficacy and Safety Profile of Different Schedules of Adjuvant Trastuzumab Therapy among Patients with HER2-Positive Breast Cancer: Real-World Experience from a Tertiary Cancer Center in South India

One year of adjuvant trastuzumab is the standard of care for HER2-positive breast cancer. In low–middle income countries, delivery of 1-year trastuzumab is challenging due to significant financial burden. Evidence for shorter durations of adjuvant trastuzumab is gaining popularity in this regard. In this study, we compared the effectiveness and safety of 1 year versus shorter durations of adjuvant trastuzumab practiced in our center. In total, 312 patients were included in this analysis. The median age was 52 years. More than two-thirds of patients (67.6%) had stage 2 disease and majority were hormone-receptor-positive (62.5%). The median follow-up duration was 50 months. The 4-year disease-free survival was 97.3%. The 4-year disease-free survival for shorter durations of adjuvant trastuzumab was 98% compared with 96.7% in 1-year trastuzumab therapy group. In univariate analysis, stage at diagnosis was the only factor which had statistically significant association with disease-free survival. In multivariate analysis, none of the variables were found to be predictive of survival. Two patients (0.6%) had significant left ventricular ejection fraction decline.Shorter durations of adjuvant trastuzumab have comparable 4-year disease-free survival to standard 1-year therapy and is an alternative adjuvant treatment option for HER2-positive breast cancer patients in resource-limited settings.

An Experimental Study on the Effect of Nano Zinc Oxide on Reflective Coatings and Building Roof Temperatures

Most roofs on Earth are made of dark materials. Dark roof surfaces can retain heat better than light ones; in Iraq, summer time temperatures on the roofs of dark buildings reached 70–80 degrees Celsius in July and August. The effects of this temperature rise are detrimental to cooling and energy consumption. To lessen heat transfer into the building, use reflective surfaces that can reflect infrared radiation waves. Cool roofs have both short-term and long-term advantages. They can reduce a building's annual air conditioning energy consumption by up to 15%, extend the life of the roof and its service life, improve the energy efficiency of roofs particularly those with inadequate insulation at the front of the roof improve thermal comfort in buildings without air conditioning, and lower greenhouse gas emissions and air pollution. Solar heat is one of the main factors affecting the durability of roofing membranes, according to research and real-world experience with the deterioration of these materials over time. High solar reflectance materials can reflect more sunlight and maintain their coolness in the sun. This study examines a low-cost composite cool coating that uses 60% calcium carbonate and demonstrates a 15°C drop in surface concrete temperature for roof buildings when compared to an uncoated surface. Additionally, compared to 30%wt CaCO3, the effect of 60%CaCO3 in composite coating reduces adhesion strength. According to the study, the weight of CaCO3 in the composite coating increases while adhesion strength, surface roughness, and particle homogeneity distribution decrease. Conversely, the maximum weight of CaCO360% weight percent exhibits good IR reflectance and less tribological properties. While preserving good infrared reflectance, adding 10% ZnO to the coating solution (60% CaCO3/PVac) improves tribological properties. The adhesion strength of the 60% calcium carbonate polymer composite paint increased from 10.9 MPa to 40.2 MPa when the nanomaterial was present, while this material maintained the superior optical qualities of infrared reflection. The coefficient of thermal expansion varies between concrete and coating solutions. For instance, the coating that has 10% weight added ZnO has a peel resistance coefficient of 8*10-6 1/K. The 60%CaCO3/10%ZnO/PVac coating effectively lowers the temperature by 15–12 °C when applied to a building roof.

Addressing the “How” and “Why” of student preparation for community partnerships Book Review: Preparing Students to Engage in Equitable Community Partnerships

“Preparing Students to Engage in Equitable Community Partnerships” by Tryon, Madden, and Sprinkel provides a guide to prepare students for meaningful and transformative community partnerships. The authors emphasize student preparation, critiquing traditional service-learning models and advocating for community-based learning to avoid perpetuating unequal power dynamics. They offer strategies for developing student humility, cultural awareness, and social justice education, aiming to transition from a charity model to critical community engagement focused on systemic change. The book includes tools, resources, and reflections to support educators in implementing effective community engagement strategies, ideally to be incorporated into a semesterlong course prior to entering a community. However, service learning and community engagement is rooted in experiential education. While some advance preparation is essential, frontloading all learning “in theory” and divorced from real-world experience contradicts the principles of experiential learning. Next, given their student demographics and the need to prepare students for engaging with diverse populations, the authors acknowledge that the material they introduce is primarily geared towards preparing (their) white students. Student preparation often focuses on those “crossing a border” during community-engaged work but many students are “returning home.” Overall, the text is a valuable contribution with limitations that must be overcome.

First-year real-world experience of intravitreal brolucizumab injection for refractory neovascular age-related macular degeneration.

To investigate the first-year real-world anatomical and functional outcomes of intravitreal brolucizumab injection in eyes with refractory neovascular age-related macular degeneration (nAMD). Retrospective observational study. nAMD patients who showed poor response to previous anti-vascular endothelial growth factor (VEGF) agents were switched to brolucizumab. Functional and anatomical outcomes were evaluated at initial treatment of nAMD, after treatment with other anti-VEGF agents and after switching and treating with brolucizumab for 1 year. Safety profile was also evaluated after brolucizumab injection. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and the presence of fluid in different compartments (intraretinal fluid [IRF], subretinal fluid [SRF], pigment epithelial detachment [PED]) were assessed at each time point. A total of 40 eyes of 40 patients were included in the study. BCVA remained unchanged throughout treatment (p > 0.05). CFT did not change after treatment with other anti-VEGF agents (p = 0.588) but decreased after switching to brolucizumab (p < 0.001). SFCT decreased after treatment with other anti-VEGF agents (p = 0.025) but not after switching to brolucizumab (p = 0.236). Presence of SRF (p = 0.001) and PED (p = 0.001) decreased significantly after switching to brolucizumab, despite their persistence with prior treatments using other anti-VEGF agents. However, IRF persisted even after switching to brolucizumab (p = 0.745). Intraocular inflammation (IOI)-related adverse events were reported in 3 eyes (7.14%). Analysis of first-year real-world outcomes after switching to brolucizumab in nAMD patients refractory to other anti-VEGF agents showed improved anatomic outcomes, limited functional improvement and low incidence of IOI-related adverse events.

Eculizumab in refractory myasthenia gravis: a real-world single-center experience.

Immunosuppressive treatment is effective in most Myasthenia gravis patients, but 10-15% of patients areconsidered refractory due to inadequate response or intolerance to therapy. Eculizumab, a humanized monoclonalantibody directed against C5 complement protein, was approved in Italy to treat Ab-AchR generalized refractoryMG (rMG) in October 2022. We aim to describe a real-world Italian experience in a population of refractory myasthenia gravis patients with oneyear follow up. A retrospective data analysis was conducted on patients with refractory generalized MG treated with eculizumabbetween November 2022 and May 2024. Clinical assessment through specific scales (MG ADL - QMG - MGFA -PIS), rescue, and background therapy was recorded after one, three, six, and twelve months. 21 rMG patients were treated with eculizumab with a medium follow up of 10.4 months and 14 patients had at leastone year follow up. A clinically meaningful reduction in total MG-ADL and QMG scores was achieved in the firstmonth. It was maintained throughout the first, third, sixth, and twelfth month along with concomitant reduction ofimmunosuppressive treatments. A drastic reduction of myasthenic exacerbations and crisis was observed duringfollow up and intravenous immunoglobulin treatment was discontinued in all patients except one. The total dailydose of prednisone was significantly reduced. This single-center real-world study confirmes safety and effectiveness of eculizumab. Eculizumab improved rapidlyall clinical outcome measures, leading to discontinuation of intravenous immunoglobulin treatment and remarkable immunosuppressant-sparing benefits.

Real-World Ustekinumab Experience in Ileum-Dominant versus Colonic Crohn’s Disease

Abstract Background Crohn’s disease (CD) presents with diverse phenotypes. It remains unclear if CD location affects therapy efficacy. The aim of this study was to compare the real-world performance of ustekinumab in ileum-dominant and colonic CD. Methods We performed a single center, IRB-approved, retrospective review of all adult CD patients who received ustekinumab. We stratified patients by ileal involvement: ileum-dominant (ileal and ileocolonic) and colonic CD. The primary outcome was absence of ulcers on follow-up colonoscopy. The secondary outcomes included CRP, calprotectin, surgery, and hospitalization. Chi-square tests (or Fisher’s exact test) and two-sample t-tests (or Wilcoxon’s rank sum test) were used to compare categorical and numeric variables between groups, respectively; analyses were performed using R Computing Software versions 3.6.1. Results 84 patients with ileum-dominant CD and 27 patients with colonic CD were treated with ustekinumab. The median time to follow-up endoscopy was 13 months. Follow-up colonoscopy after ustekinumab therapy was ulcer-free in 45% of ileum-dominant CD and 76% of colonic CD (p=0.02). Of patients with ulcers prior to starting ustekinumab, 24% of ileum-dominant CD and 67% of colonic CD were ulcer-free (p=0.01). There were similar rates of hospitalizations and surgery and no significant differences in mean calprotectin and CRP between the two groups on follow-up after ustekinumab therapy. Conclusions This real-world experience of ustekinumab demonstrates higher rates of endoscopic healing among colonic CD when compared to ileum-dominant CD. Disease location may predict endoscopic healing by ustekinumab. Further studies are necessary to expand our understanding of ustekinumab responsiveness to different CD phenotypes.

Real-world experience with glucagon-like peptide 2 analogues in patients with short bowel syndrome and chronic intestinal failure: results from an international survey in expert intestinal failure centers.

Background and AimsGlucagon-like peptide 2 (GLP-2) analogues are the first available disease-modifying treatments for patients with intestinal failure (IF) due to short bowel syndrome (SBS). Efficacy in terms of reduction of parenteral support (PS) has been demonstrated in multiple studies and real-world reports. However, it remains unclear how many patients are eligible to receive the treatment, when treatment is started after intestinal resection, how treatment efficacy is assessed outside of clinical trials, and how the treatment is modified in case of non-response or adverse events. The aim of this study was to investigate the real-world management of patients treated with GLP-2 analogues in expert centers around the world. MethodsA survey questionnaire was developed by a multidisciplinary working group consisting of 52 questions related to various aspects of multidisciplinary care of SBS-IF patients. The 17 questions related to the use of GLP-2 analogues in clinical practice were analyzed for this study. The online survey was sent to 33 participating centers in a phase 3 study of a long-acting GLP-2 analogue. Only responses from countries with access to commercially available GLP-2 analogues were included in the study. A descriptive analysis was performed for each question. Results are presented as median (interquartile range). ResultsThe responses from the 19 expert IF centers with access to GLP-2 analogues indicated that 10 (10-20) % of patients with SBS-IF were treated with a GLP-2 analogue, which was less than the number of eligible patients (30 (25-40) %). In most centers (10 centers, 53%), GLP-2 therapy was started 6-12 months after the last intestinal resection, with 5 centers (26%) starting later (12-24 months). Multiple parameters were used in combination to determine the response to GLP-2 analogues of which the three most common were >20% decrease in PS (95%), at least 1 day of PS reduction per week (84%) and increased urinary output (68%). In non-responders GLP-2 therapy was stopped within the first year by 67% of the centers. Finally, strategies in case of significant adverse events include stopping the GLP-2 analogue (used by 79% of experts), dose reduction (67%) and temporary treatment interruption (62%). ConclusionThe results of this survey completed by expert IF centers show the real-life use of GLP-2 analogues in clinical practice. Key learning points identified include the accounting for a period of intestinal adaptation before starting GLP-2 analogues and not stopping the treatment too early in case of non-response. The best strategy in case of adverse effects should be studied further.

Effect of Mepolizumab in airway’s remodelling in patients with late-onset severe asthma with an eosinophilic phenotype

BackgroundClinical trials and real-world experience have provided evidence for the clinical benefit of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exists regarding the impact of mepolizumab on airway remodelling. ObjectiveWe thus investigated the effect of mepolizumab on airway structural remodelling in patients treated for severe asthma in routine clinical care. MethodsMESILICO is a multicenter study involving 8 Pulmonology Departments in Greece. This study focused on patients who initiated mepolizumab for severe asthma with an eosinophilic phenotype and had late-onset disease with obstructive patterns (impaired reversibility). Forty-seven patients were recruited, of whom 41 were enrolled in the bronchoscopy sub-study. The findings were related to clinical outcome. ResultsAfter 12 months, mepolizumab treatment was associated with significant improvements in lung function and ACT score, along with a significant decrease in severe exacerbation events (p<0.001). Thirty four of the 41 participants (83%) had paired biopsies for comparative analysis. There was a significant reduction from baseline in sub-basement membrane thickness, airway smooth muscle area, airway smooth muscle layer thickness and extent of epithelial damage, as well as a decrease in tissue eosinophil numbers (all p<0.001). The extent of ASMLT reduction positively correlated with the submucosal eosinophil reduction (r= 0.599, p<0.001). ConclusionThis study identifies that 12 month of mepolizumab treatment in patients with late-onset severe asthma, who are also characterized by eosinophilic and impaired reversibility phenotypes, leads not only to clinical improvement but also reduces indices of airway tissue remodelling suggestive of a disease modifying effect.

Real-World Outcomes for Localised Gastro-Oesophageal Adenocarcinoma Cancer Treated with Perioperative FLOT and Prophylactic GCSF Support in a Single Asian Centre.

Perioperative FLOT (5-fluorouracil, oxaliplatin and docetaxel) is a standard of care for patients with locally advanced gastro-oesophageal adenocarcinoma (GEA) in Western guidelines, but its use is limited in Asian patients. We report outcomes from a single Asian centre of perioperative FLOT with concomitant granulocyte colony-stimulating factor (GCSF) prophylaxis. A retrospective analysis of all 56 stage II to III GEA patients treated with perioperative FLOT at the National Cancer Centre Singapore between June 2017 and February 2024 was performed. All patients were discussed at a multidisciplinary tumour board, underwent preoperative laparoscopic staging, and received prophylactic GCSF with perioperative FLOT. Surgery was performed across four partner institutions. The primary endpoints were the tolerability of FLOT and pathological complete response (pCR). A univariate analysis of factors associated with survival and adverse events was also performed. Overall, 33 patients (58.9%) completed eight cycles of pre- and postoperative FLOT, and 92.9% underwent resection. The commonest grade 3 to 4 adverse events (AEs) were diarrhoea (10.7%) and neutropenia (5.6%). The 30- and 90-day postoperative mortality rates were 0% and 1.9%, respectively. In resected tumours, the pCR was 15.4%. The median DFS was 27.5 months, but the median OS was not reached. The values for 1-, 2-, and 3-year DFS were 74.6%, 61.0%, and 46.5%, respectively. The values for 1-, 2-, and 3-year OS were 85.0%, 67.4%, and 61.0%, respectively. In the univariate analysis of patients who underwent resection, an ECOG status of 0 was associated with better DFS, while ypN0, R0 resection, and pathological stages 0-II were associated with better DFS and OS. Patients ≥ 65 years benefited from FLOT similarly to those <65 years in terms of DFS (HR 1.03; p = 0.940) and OS (HR 1.08; p = 0.869), with similar rates of grade 3 to 4 AEs. Patients with a higher housing index (HI) were less likely to experience ≥grade 3 AEs compared to those with a lower HI (OR 0.16, p = 0.029). This study presents a unique real-world Asian experience of perioperative FLOT with prophylactic GCSF use, with low rates of G3 to 4 neutropenia. The tolerability of FLOT was similar to that reported in Western populations. Furthermore, similar survival and rates of grade 3 to 4 AEs were observed in elderly patients. Patients of lower socioeconomic status were more likely to experience severe AEs, highlighting the need to proactively support vulnerable groups during treatment.

P270 Real-world experience of neoadjuvant chemotherapy in muscle invasive bladder cancer at a university center: Role of nodal yield and prognostic value of pathological response and nutritional index

P270 Real-world experience of neoadjuvant chemotherapy in muscle invasive bladder cancer at a university center: Role of nodal yield and prognostic value of pathological response and nutritional index

A Real-world, prospective, observational, Investigator Initiated Trial to evaluate early discharge following Angio-Seal™ vascular closure device in patients undergoing percutaneous coronary intervention.

BackgroundCardiac catheterization procedures such as percutaneous coronary intervention (PCI) are widely used but with complications of access site bleeding. Manual compression (MC )is the well accepted technique to control bleeding but time consuming (15-20 mins); vascular closure devices (VCDs) are used increasingly as an alternative to MC and require <5 minutes for deployment.We aimed to document the real-world experience with a bioabsorbable collagen closure device (Angio-Seal™ ) with absorbable traction suture in patients undergoing PCI. ObjectiveThe primary objective was time (hours) to discharge from hospital after the procedure; to document the incidence of vascular access site complications, time to ambulation and time to hemostasis were the secondary objectives. MethodThis was a prospective, observational, investigator-initiated clinical trial wherein adult patients who underwent PCI procedure through femoral access route, with deployment of Angio-Seal™ femoral closure device were included. ResultsAmongst the 100 patients enrolled, 68% were males. systemic hypertension (63%), and type-2 diabetes mellitus (37%) were the major comorbidities reported. Mean overall time from the end of procedure to hemostasis was 2.32±0.99min. Time to ambulation was 156.08±36.81min and to hospital discharge was 25.21±4.49 hours, One subject experienced hematoma. No other complications particularly pertaining to vascular access site were observed. ConclusionAngio-Seal™ is an effective and safe VCD and results in early ambulation, rapid hemostasis, and discharge in patients undergoing PCI.

Home infusion experience in patients with Pompe disease receiving avalglucosidase alfa during three clinical trials

During three previously reported clinical trials of avalglucosidase alfa in patients with Pompe disease, 17 out of 142 participants were considered by the investigators to be appropriate candidates for home infusion. During their respective trials, these participants received a total of 419 avalglucosidase alfa infusions at home under healthcare professional supervision. They were clinically stable with no history of moderate or severe infusion-associated reactions within at least 12 months prior to starting home infusions. As of February 25, 2022, the 15 participants with late-onset Pompe disease (LOPD) had received between 2 and 48 home infusions and the 2 participants with infantile-onset Pompe disease (IOPD) had received 19 and 20 infusions. Adverse events occurred in 8 (53 %) participants with LOPD and neither of the participants with IOPD. Seven participants with LOPD had a total of 15 non-treatment-related, non-serious adverse events. One participant with LOPD experienced infusion-associated reactions of eyelid edema and flushing during the first home infusion; both were non-serious adverse events classified as grade 1 (mild). Home infusion was later resumed for this participant. Among LOPD participants, event rates for home infusions were comparable to those for clinic infusions: overall adverse events (0.028 vs 0.039 participants with events/infusion)and adverse events classified as infusion-associated reactions (0.003 vs. 0.006). No medication errors occurred during home infusion. These data suggest that infusion of avalglucosidase alfa at home is feasible and does not compromise safety for patients who have not experienced an infusion-associated reaction during the preceding 12 months of infusions in a clinical setting. Evaluation of real-world experience with avalglucosidase alfa home infusion in countries where it is already approved is ongoing.