Real-world Experience Research Articles

Methods and techniques to optimize energy delivery using the circular array pulsed field ablation catheter

Pulsed field ablation (PFA) is a novel method of cardiac ablation in which electrical fields are used to create microscopic pores in the cardiomyocyte cell membrane, resulting in cell death. Unlike traditional thermal radiofrequency and cryoablation technologies, PFA is cardiomyocyte preferential, reducing the risk of collateral damage to the esophagus and phrenic nerve. However, achieving durable lesions with PFA is dependent on the proximity to the tissue and presently approved systems do not provide contact force sensing. The PulseSelect PFA system is the first Food and Drug Administration–approved/CE–marked/Pharmaceuticals and Medical Devices Agency–approved system for PFA of atrial fibrillation; however, there is no consensus on workflow and best practices. We present here real-world experience from our centers in the United States, Europe, and Japan, and propose techniques and methods for incorporating fluoroscopy, electroanatomic mapping, and intracardiac echocardiography to assure optimal lesion delivery and predictability.

Clinicogenetic characterization and response to disease-modifying therapies in spinal muscular atrophy: real-world experience from a reference center in Southern Brazil

ObjectiveSpinal Muscular Atrophy linked to chromosome 5q (SMA) is an autosomal recessive neurodegenerative disease characterized by progressive proximal muscle atrophy and weakness. This study addresses the scarcity of research on novel disease-modifying therapies for SMA in Latin America by reporting a real-world experience in Southern Brazil. MethodologyThis is a single-center historical cohort that included all patients diagnosed with spinal muscular atrophy at a Regional Reference Service for rare diseases. ResultsEighty-one patients were included, of whom 7 died during follow-up. Of the remaining 74 patients, 5.4 % were classified as pre-symptomatic, 24.3 % with SMA type 1, 28.4 % with type 2, 36.5 % with type 3, and 5.4 % with type 4. The mean follow-up time ranged from 1.8 years for pre-symptomatic cases to 8.7 years for SMA types 2 and 3. Approximately 42 % of these patients received specific disease-modifying therapy, of these, 96.8 % received Nusinersen, with 19.4 % transitioning to gene therapy using Onasemnogene Abeparvovec, and 6.4 % starting Risdiplam. Most patients with SMA type 1 were on disease-modifying treatment, whereas only slightly over a third of patients with type 2 and about 10 % of type 3 were receiving such treatments. Among treated patients, 80 % demonstrated improvement in motor performance during the follow-up, with a lesser therapeutic response being associated with late initiation of treatment and low motor function scores at baseline. ConclusionThis real-world study reinforces the effectiveness of disease-modifying therapies for SMA in Brazil within the context of low- and middle-income countries, which is greater the earlier and the better the patient's functional status.

ID: 341419 A Multi-Center Real-World European Experience of Treating Painful Diabetic Neuropathy with High-Frequency Spinal Cord Stimulation

ID: 341419 A Multi-Center Real-World European Experience of Treating Painful Diabetic Neuropathy with High-Frequency Spinal Cord Stimulation

368 Real World Experience Using a Rapid Test to Distinguish Bacterial From Viral Infection in the Emergency Department

368 Real World Experience Using a Rapid Test to Distinguish Bacterial From Viral Infection in the Emergency Department

TCT-76 Percutaneous Coronary Intervention in High-Risk Patients With High Syntax Score Left Main Coronary Disease: 17-Year Long-Term Follow-Up Real World Experience of a Single Center Without On-Site Cardiac Surgery

TCT-76 Percutaneous Coronary Intervention in High-Risk Patients With High Syntax Score Left Main Coronary Disease: 17-Year Long-Term Follow-Up Real World Experience of a Single Center Without On-Site Cardiac Surgery

Real-World Experience of the Association of HLADQA1*05 Allele With Loss of Response to Anti-TNF Inhibitors.

Antitumor necrosis factor (anti-TNF) biologics have revolutionized the treatment of inflammatory bowel disease (IBD). Previously, studies have shown an association between the HLADQA1*05 allele and the development of antibodies and were predictive of loss of response. We sought to investigate the rate of the HLADQA1*05 allele in patients with IBD at a New England center and its association with antibody development and discontinuation of anti-TNF therapy. A single center retrospective cohort study with patients on anti-TNF inhibitor therapy being followed at our IBD clinic who had testing performed for the HLADQA1*05 allele were identified and separated into 2 different groups: HLADQA1*05 positive (HLA carriers) or HLADQA1*05 negative (HLA noncarriers). Persistence of remaining on anti-TNF therapy, measurement of drug/antibody levels, and need for dose escalation were collected and stratified amongst the 2 groups. The prevalence of the HLADQA1*05 allele among all IBD patients followed was 53%. We identified 67 IBD patients being treated with anti-TNF medications, 46 (69%) patients with Crohn's disease and 21 (31%) with ulcerative colitis. Most of the HLA carriers (85%) and HLA noncarriers (92%) remained on anti-TNF therapy at the end of the study period. Thirty-six (84%) patients had therapeutic drug monitoring performed during maintenance therapy. Three patients in the HLA carrier group had meaningful antidrug antibody levels necessitating cessation of therapy compared to one patient in the HLA noncarrier group (P = .61). Only 3 (13%) of HLA carriers and 4 (21%) of HLA noncarriers were on combination therapy with an immunomodulator. 65% of HLA carriers required dose escalation compared to 50% of HLA noncarriers (P = .70). The prevalence of the HLADQA1*05 allele was 53% in our New England IBD patient population, similar to what has previously been reported in European studies. The majority of patients remained on anti-TNF therapy at the end of the study period despite carrier status. While there was a trend toward increased need for dose escalation among HLA carriers, this was not statistically significant. Future studies are needed to determine if the presence of the HLADQA1*05 allele leads to antibody development against anti-TNF inhibitors and treatment failure in patients with IBD.

Real-world experience of vedolizumab use in Colombian patients with inflammatory bowel disease—EXVEDOCOL

BackgroundReal-world studies about the effectiveness and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD) in Latin America are scarce. Our study describes the effectiveness and safety of VDZ in Colombian patients with IBD. MethodsEXVEDOCOL (EXperience of VEDOlizumab in COLombia) was a retrospective, multicenter, observational study. Adults with IBD receiving a first dose of VDZ between July 2016 and October 2018 were included. The co-primary outcomes clinical response, and remission, were determined at week 14 and last visit during the maintenance phase (LVMP). The secondary outcomes, deep remission and loss of response were recorded at LVMP. ResultsThirty-one patients (25 ulcerative colitis (UC), 6 Crohn's disease (CD)) were included. At week 14, clinical response was achieved by 87.1% (27/31) of the patients treated with VDZ, while loss of response was reported in 6.7% (2/30). The remission rate at week 14 was 65.5% (19/29) and 75.9% (22/29) at LVMP. Prior anti-TNF exposure was reported in 61.3% (19 patients) of whom 84.2% (16/19) achieved clinical response at week 14 and 89.5% (17/19) at LVMP. For anti-TNF naïve patients, clinical response was recorded in 91.7% (11/12) at week 14 and 100% (12/12) at LVMP. ConclusionsHigh clinical remission rates and safety profile highlight VDZ as a valuable treatment option for IBD patients. Anti-TNF naïve patients may derive greater benefit from therapy. Studies with larger cohorts could confirm these findings.

668P Pompe Registry: Real-world experience of patients with late-onset Pompe disease who switched therapy from alglucosidase alfa to avalglucosidase alfa

668P Pompe Registry: Real-world experience of patients with late-onset Pompe disease who switched therapy from alglucosidase alfa to avalglucosidase alfa

Perspectives of stakeholders on onboard training: A thematic analysis of qualitative interviews

ABSTRACT The training and education of seafarers have evolved significantly with the establishment of the International Maritime Organization (IMO) and the adoption of International Convention on Standards of Training, Certification and Watchkeeping for Seafarers (STCW). This paper explores maritime industry key stakeholders’ perspectives on onboard training (OBT) focusing on its benefits, curriculum, and challenges. The thematic analysis of the opinions of representatives of key stakeholders highlighted the critical role of OBT in providing real-world experience, applying theoretical knowledge in practice, and gaining cultural insights essential for maritime cadets’ professional growth. Some obstacles related to financial constraints of shipping companies, common ship activities, living conditions on board, unexpected weather conditions, regulatory inconsistencies, and characteristics of curriculum, such as trainers’ competencies, number of trainers on board, different implementation of OBT by different companies were revealed. The respondents agreed that the traditional 12-month OBT period is necessary, however proper integration of technological advancements in achieving competences with harmonized international regulations, updated curriculum, and enhanced stakeholder collaboration can be helpful to reduce the duration of OBT. Further research should identify competences to be developed through integration of technologies including simulator training.

160P Risdiplam real-world experience in paediatric patients with spinal muscular atrophy type 2

160P Risdiplam real-world experience in paediatric patients with spinal muscular atrophy type 2

Combined Impact of Residual Mitral Regurgitation and Gradient After Mitral Valve Transcatheter Edge-to-Edge Repair

BackgroundReducing mitral regurgitation (MR) during mitral transcatheter edge-to-edge repair (M-TEER) may come at the cost of increased mitral valve gradient (MVG). The combined impact of residual MR and MVG on clinical outcomes after M-TEER is unknown. ObjectivesThis study sought to evaluate the impact of postprocedure MR and MVG on clinical outcomes after M-TEER. MethodsEXPANDed is a pooled, patient-level cohort of the EXPAND (A Contemporary, Prospective Study Evaluating Real-world Experience of Performance and Safety for the Next Generation of MitraClip Devices) and EXPAND G4 studies, which were designed to evaluate real-world safety and effectiveness of the third- and fourth-generation MitraClip TEER Systems. Subjects were categorized by echocardiographic core laboratory (ECL) assessments into 4 groups according to 30-day MR grade and mean MVG: 1) MR ≤1+/MVG <5 mm Hg; 2) MR ≤1+/MVG ≥5 mm Hg; 3) MR ≥2+/MVG <5 mm Hg; and 4) MR ≥2+/MVG ≥5 mm Hg. ResultsA total of 1,723 subjects had evaluable echocardiograms at 30 days: 72% had MR ≤1+/MVG <5 mm Hg, 18% had MR ≤1+/MVG ≥5 mm Hg, 7% had MR ≥2+/MVG <5 mm Hg, and 3% had MR ≥2+/MVG ≥5 mm Hg. MR≤1+ was sustained through 1 year in 93% of patients who achieved 30-day MR≤1+. MVG decreased from 30 days to 1 year in subjects with MVG ≥5 mm Hg (6.7 ± 4.0 to 5.5 ± 2.5 mm Hg MR ≤1+/MVG ≥5 mm Hg and 6.5 ± 1.5 to 5.5 ± 1.7 mm Hg MR ≥2+/MVG ≥5 mm Hg). One-year rates of all-cause mortality and heart failure hospitalization were lower for subjects who achieved MR ≤1+ at 30 days, regardless of MVG. ConclusionsReduction of MR to mild or less after M-TEER with the latest-generation MitraClip systems was associated with clinical benefit regardless of MVG.

Uptake of Risk-Reducing Surgeries in an International Real-World Cohort of Hispanic Women.

Women with pathogenic variants (PVs) in breast cancer (BC) and ovarian cancer (OC) associated genes are candidates for cancer risk-reducing strategies. Limited information is available regarding risk-reducing surgeries (RRS) among Hispanics. The aim of this study was to describe the uptake of RRS in an international real-world experience of Hispanic women referred for genetic cancer risk assessment (GCRA) and to identify factors affecting uptake. Between July 1997 and December 2019, Hispanic women, living in the United States or in Latin America, enrolled in the Clinical Cancer Genomics Community Research Network registry were prospectively included. Demographic characteristics and data regarding RRS were obtained from chart reviews and patient-reported follow-up questionnaires. Median follow-up was 41 months. Among 1,736 Hispanic women referred for GCRA, 27.2% women underwent risk-reducing mastectomy (RRM), 25.5% risk-reducing salpingo-oophorectomy (RRSO) and, 10.7% both surgeries. Among BRCA carriers, rates of RRM and RRSO were 47.6% and 56.7%, respectively. In the multivariate analyses, being a carrier of a BC susceptibility gene (odds ratio [OR], 3.44), personal history of BC (OR, 6.22), living in the US (OR, 3.90), age ≤50 years (OR, 1.68) and, family history of BC (OR, 1.56) were associated with a higher likelihood of undergoing RRM. Carrying an OC susceptibility gene (OR, 6.72) was associated with a higher likelihood of undergoing RRSO. The rate of RRS among Hispanic women is suboptimal. PV carriers, women with personal history of cancer, and those with a family history of cancer were more likely to have RRS, with less uptake outside the US. Understanding personal and systemic factors influencing uptake may enable interventions to increase risk appropriate uptake of RRS.

Real-world experience of lenvatinib-based therapy in patients with advanced hepatocellular carcinoma

Real-world experience of lenvatinib-based therapy in patients with advanced hepatocellular carcinoma

EP.12A.30 Landscape of EGFR Mutations and Real-World Experience of Therapeutic Interventions - A Community Oncology Study

EP.12A.30 Landscape of EGFR Mutations and Real-World Experience of Therapeutic Interventions - A Community Oncology Study

Evaluating Real-World Experience With Maribavir for Treatment of Refractory/Resistant Cytomegalovirus in Renal Transplant Recipients.

Maribavir was recently approved by the FDA, expanding treatment options for post-solid-organ transplant refractory/resistant CMV. We sought to describe the post-marketing experience with maribavir at a large academic transplant center. This was a retrospective observational study of all renal transplant recipients treated with maribavir for refractory/resistant CMV DNAemia/disease. CMV viral loads, immunosuppression regimens and management, resistance testing, and antiviral therapy durations were reviewed. Outcomes of interest included treatment success, defined as undetectable CMV DNAemia for two consecutive weeks or detected but unquantifiable DNAemia for five consecutive weeks, as well as the emergence of antiviral resistance, and recurrent DNAemia. From 2021 to 2023, 5/10 (50%) patients achieved durable virologic suppression with maribavir (classified as responders). Among responders, 2/5 (40%) experienced low-level CMV DNAemia recurrence (defined as a viral load less than 1000 IU/mL) within 8 weeks of antiviral discontinuation. Among nonresponders, 2/3 (66.7%) were found to have UL97 protein mutations associated with maribavir resistance identified 85 and 75 days after initiation of maribavir. Two patients are currently on maribavir with clinical outcomes that are yet to be determined. Responders had a mean reduction of 200mg (SD-274mg) in mycophenolate dosing with nonresponders having a mean increase of 167mg (SD-764mg). Maribavir, often in conjunction with mycophenolate dose reduction, was effective for many patients with refractory/resistant CMV DNAemia at our transplant center, though several experienced recurrent DNAemia. In patients who did not respond to therapy, resistance to maribavir was frequently detected. Clinicians treating these patients should remain vigilant for rebound CMV DNAemia and consider repeat antiviral resistance testing.

The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies.

Cytomegalovirus (CMV) infection is associated with severe clinical disease and high morbidity in immunocompromised hosts. Letermovir and maribavir, are two recently developed antiviral drugs used in the prevention and treatment of resistant and refractory CMV. Following the publication of landmark randomized trials and increased use, both clinical trial data and real-world experience has reported the development of antiviral drug resistance. The aim of this review was to comprehensively review the published literature on letermovir and maribavir drug resistance and to describe the clinical scenarios in which they may emerge. For letermovir, the most frequently detected resistance mutations occur in the UL56 gene (C325Y/W/F) and confer total resistance. Maribavir resistance mutations most often occur in the UL97 gene and resistance-associated variants (RAVs) T409M, H411Y, C480F have all been detected. The clinical context in which letermovir and maribavir resistance occurs include high viral loads at initiation, intensified immunosuppression, subtherapeutic drug exposure because of poor adherence, drug interactions, and inadequate central nervous system (CNS) penetration. Emergence of resistance mutations generally occurs within the first 3 months of initiation. The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV.

Efficacy and Safety of First-Line Palliative Chemotherapy with Fluorouracil Plus Leucovorin, Oxaliplatin, and Docetaxel (FLOT) in HER2-Negative Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: A Single-Institutional Real-World Experience from Eastern India

Background Fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) is one of the preferred perioperative chemotherapy regimens in locally advanced resectable gastric cancer (GC). Till date, there are very few published data from India, regarding the outcomes of this relatively well-tolerated biweekly triplet regimen as first-line palliative chemotherapy in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Materials and Methods In the present retrospective study, we evaluated the efficacy and safety of first-line FLOT regimen in Indian patients with HER2-negative metastatic adenocarcinoma of stomach or GEJ. The primary endpoint was overall survival (OS). Progression-free survival (PFS), overall response rate (ORR), and toxicity profile were taken as secondary endpoints. Results Between January 2021 and June 2024, 88 patients were treated with FLOT. The median age was 52 years (range, 23–68); 69.3% were males and 37.5% of the patients had ≥ 3 metastatic disease sites involvement at baseline. Dose reductions due to toxicity were required in 25% of the patients. The ORR was 68.2%; median PFS and OS were 6.3 months (95% confidence interval [CI]: 5.3–7.4) and 12.5 months (95% CI: 11.3–14.2), respectively. The most frequent grade 3 to 4 adverse events were diarrhea (15.9%), fatigue (13.6%), and neutropenia (12.5%). Younger patients (aged &lt; 55 years) had much less ≥ grade 3 diarrhea (7.5%, n = 4), compared with patients aged ≥ 55 years (28.6%, n = 10). There was one toxicity-related death. Conclusion In the present study, biweekly FLOT regimen with primary prophylactic granulocyte colony-stimulating factor demonstrated encouraging efficacy with a favorable nongastrointestinal toxicity profile in Indian patients with HER2-negative metastatic gastric or GEJ adenocarcinoma. Clearly, this well-tolerated triplet regimen should be explored further through large prospective randomized trials in Asian patients.

Efficacy and safety of a recombinant von Willebrand factor treatment in acquired von Willebrand syndrome in case of bleeding and surgical procedures.

Acquired von Willebrand syndrome (AVWS) is a rare haemorrhagic disorder. The prophylaxis and treatment of bleeding before surgery are complex. Since 2018, a new recombinant VWF (rVWF) concentrate that contains no factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France. To describe the real-world experience of using rVWF in non-surgical bleeding and surgical procedures in patients with AVWS. Fifteen bleeding episodes in seven patients and 16 surgeries in 10 patients were retrospectively analysed in t French haemostasis centres. During bleeding, the median number of infusions was only 1 (range 1-27) with a median loading dose of 58IU/kg (range 17-116) rVWF and a total median dose of 65IU/kg (range 35-1488) rVWF. Bleeding control was rated markedly effective in 73% (11/15) of the cases and ineffective in 27% (4/15). During surgeries, the median number of infusions was 3 (range 1-8) with a preoperative loading dose of 60IU/kg (range 23-118) rVWF and a total median dose of 123IU/kg (range 31-542). The overall clinical efficacy was qualified as excellent, good and poor (ISTH criteria) in respectively 7 (43%), 6 (38%) and 3 (19%) procedures. There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events nor adverse events were reported. This French 'real-world' experience shows that rVWF could be of interest in the treatment and prophylaxis of bleeding in patients with AVWS, with no clinically significant safety concern.

Ubrogepant users' real-world experience: Patients on ubrogepant, characteristics and outcomes (UNIVERSE) study.

To assess the real-world effectiveness of ubrogepant by evaluating self-reported satisfaction with pain relief, ability to think clearly, and return to normal function in individuals who had used ubrogepant to treat a migraine episode within the preceding 14 days. Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine in adults. Few studies have evaluated the real-world effectiveness of ubrogepant. The UNIVERSE study was an observational, cross-sectional survey conducted between February 2021 and April 2021 in US adult Migraine Buddy application (app) users currently treated with ubrogepant. Individuals who were 18 years of age or older and reported at least one dose of ubrogepant in the previous 14 days completed a 30-question survey in the app. The survey assessed respondent demographics, migraine history, acute treatment patterns, and treatment satisfaction with ubrogepant. Respondents also reported prior acute medication use and reasons for switching to ubrogepant. Of the 1303 ubrogepant users contacted, 302 (23.2%; 50 mg, 120 participants; 100 mg, 182 participants) were included in this study. The mean (standard deviation) age was 41.9 (11.2) years, and 90.1% (272/302) were female. Satisfaction with migraine relief at 2, 4, and 24 h post-dose was reported by 75.8% (229/302), 83.4% (252/302), and 78.5% (237/302) of participants, respectively. Satisfaction with the ability to think clearly after taking ubrogepant was reported by 85.1% (257/302) of participants, and 83.8% (253/302) were satisfied with their ability to return to normal function. Furthermore, 90.7% (274/302) of participants reported that they were likely to continue using ubrogepant to treat their migraine. Most participants (n = 264 [87%]) reported switching to ubrogepant due to inadequate treatment response with their previous treatment. In this subgroup, comparable outcomes were observed with respect to satisfaction with migraine relief, ability to think clearly, and return to normal function. Ubrogepant demonstrated real-world effectiveness in the acute treatment of migraine, as evidenced by high levels of treatment satisfaction and a strong indication of their intent to continue using the medication.

Performance of An Automated Algorithm in Large and Medium Vessel Occlusion Detection: A Real-World Experience.

Fast, accurate detection of large (LVO) and medium vessel occlusion (MeVO) is critical for triage and management of acute ischemic stroke. Multiple AIbased software products are commercially available. However, their strengths and limitations for detection of vessel occlusion in the context of expanding indications for mechanical thrombectomy are not entirely understood. We aimed to investigate the performance of a fully automated commercial detection algorithm to identify large and medium vessel occlusions in Code Stroke patients. We utilized a single-center, institutional, retrospective registry of all consecutive code stroke patients with CTA and automated processing using Viz.ai presenting at a comprehensive stroke center between March 2020 and February 2023. LVO was categorized as anterior LVO (aLVO), defined as occlusion of the intracranial internal cerebral artery or M1-middle cerebral artery (MCA), and posterior LVO (pLVO), defined as occlusion of the basilar artery or V4-vertebral artery. MeVO was defined as occlusion of the M2-MCA, A1/A2-anterior cerebral artery, or P1/P2-posterior cerebral artery. Reports from 12 board-certified radiologists were considered the gold standard. We analyzed the performance of the automated algorithm using STARD guidelines. Our primary outcome was accuracy of anterior LVO (aLVO) by the software. Secondary outcomes were accuracy of the software to detect three additional categories: all LVO (aLVO and pLVO), aLVO with M2-MCA, and aLVO with MeVO. Of 3,590 code stroke patients, 3,576 were technically sufficient for analysis by the automated software (median age 67 years; 51% female; 68% White), of which 616 (17.2%) had vessel occlusions. The respective sensitivity and specificity for all four pre-specified categories were: aLVO: 91% (87-94%), 93% (92-94%); all LVO: 73% (68-77%), 92% (91-93%); aLVO with M2-MCA:74% (70-78%), 93% (92-94%); aLVO with all MeVO: 65% (61-69%), and 93% (92-94%). The automated algorithm demonstrated high accuracy in identifying anterior LVO with lower performance for pLVO and MeVO. It is crucial for acute stroke teams to be aware of the discordance between automated algorithm results and true rates of LVO and MeVO for timely diagnosis and triage. LVO = large vessel occlusion; aLVO = anterior large vessel occlusion; pLVO = posterior large vessel occlusion; MeVO = medium vessel occlusion; EVT= endovascular thrombectomy; AI = artificial intelligence; ACA = anterior cerebral artery; PCA = posterior cerebral artery; BA = basilar artery; VA = vertebral artery.