Unrestricted Educational Grant Research Articles

Community-acquired pneumonia: a US perspective on the guideline gap.

Community-acquired pneumonia continues to be one of the most common causes of morbidity and mortality due to infectious disease. The aetiologies, clinical presentations, diagnostic modalities and therapeutic options are changing and outpacing the creation of management guidelines. This educational article summarizes a roundtable activity sponsored by an unrestricted educational grant by Paratek that included US experts discussing these changes and identifying gaps in the current guidelines.

OA19 Self-reported prevalence and impact of clinical signs, symptoms and events in adults with osteogenesis imperfecta

OA19 Self-reported prevalence and impact of clinical signs, symptoms and events in adults with osteogenesis imperfecta

Resumption of ovulation in anovulatory women with PCOS and obesity is associated with reduction of 11β-hydroxyandrostenedione concentrations.

Is resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity associated with differential changes in endocrine and metabolic parameters (weight, insulin resistance, anti-Müllerian hormone (AMH), and androgens) compared to women with PCOS who remained anovulatory? Resumption of ovulation after a 6-month lifestyle intervention in women with PCOS and obesity is associated with changes in serum 11β-hydroxyandrostenedione (11OHA4) concentrations. Lifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the mechanisms underlying why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response. We used data and samples originating from an earlier randomized controlled trial (RCT), which examined the efficacy of a 6-month lifestyle intervention prior to infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. A total of 577 women with obesity (BMI > 29 kg/m2) were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n = 95) were included in the current analysis. We defined women as having resumed ovulation (RO+) based on the following criteria: spontaneous pregnancy; or assignment to expectant management; or IUI in natural cycles as the treatment strategy after lifestyle intervention. Steroid hormones were measured using liquid chromatography tandem mass spectrometry. Generalized estimating equations with adjustment for baseline measures and interaction between group and time was used to examine differences in changes of endocrine and metabolic parameters between RO+ (n = 34) and persistently anovulatory women (RO-, n = 61) at 3 and 6 months after intervention. At baseline, the mean ± SD age was 27.5 ± 3.6 years in the RO+ group and 27.9 ± 4.1 years in the RO- group (P = 0.65), and the mean ± SD weights were 101.2 ± 9.5 kg and 105.0 ± 14.6 kg, respectively (P = 0.13). Baseline AMH concentrations showed significant differences between RO+ and RO- women (median and interquartile range [IQR] 4.7 [3.2; 8.3] versus 7.2 [5.3; 10.8] ng/ml, respectively). Baseline androgen concentrations did not differ between the two groups. During and after lifestyle intervention, both groups showed weight loss; changes in 11OHA4 were significantly different between the RO+ and RO groups (P-value for interaction = 0.03). There was a similar trend for SHBG (interaction P-value = 0.07), and DHEA-S (interaction P-value = 0.06), with the most pronounced differences observed in the first 3 months. Other parameters, such as AMH and FAI, decreased over time but with no difference between the groups. No high-resolution transvaginal ultrasonography was used to confirm ovulatory status at the end of the lifestyle program. The small sample size may limit the robustness of the results. Reduction of androgen concentrations during and after lifestyle intervention is associated with recovery of ovulatory cycles. If our results are confirmed in other studies, androgen concentrations could be monitored during lifestyle intervention to provide individualized recommendations on the timing of resumption of ovulation in anovulatory women with PCOS and obesity. The study was supported by a grant from ZonMw, the Dutch Organization for Health Research and Development (50-50110-96-518). The Department of Obstetrics and Gynecology of the UMCG received an unrestricted educational grant from Ferring Pharmaceuticals BV, The Netherlands. A.H. reports consultancy for the development and implementation of a lifestyle App MyFertiCoach developed by Ferring Pharmaceutical Company. All other authors have no conflicts to declare. The LIFEstyle RCT was registered at the Dutch trial registry (NTR 1530).

P62: Agitation in Alzheimer’s Disease (AAD): A Decision Tree for Healthcare Providers

Developed by THE GERONTOLOGIC SOCIETY OF AMERICASupported by an unrestricted educational grant from AvanirThe prevalence of agitation in Alzheimer’s Disease (AAD) approaches 80%. Patients with AAD have more severe behavioral,depressive, and frontal lobe symptoms and are at increased risk for hospitalization and nursing home placement.Early agitation is a robust predictor of accelerated progression and mortality and is distressing and dangerous for patients and care partners.This presentation was recently developed by the Gerontologic Society of America (GSA) which convened an expert AD Working Group to develop a “Decision Tree” for healthcare providers relative to the assessment of AAD and the employment of Non-Pharmacologic and Pharmacologic treatment options

RADAR Trial: MRD Response Adapted Trial for Newly Diagnosed Transplant Eligible Myeloma Patients

Background: Achieving and sustaining minimal disease negativity improves clinical outcomes in newly diagnosed transplant eligible myeloma (NDMM). Outcomes in NDMM are influenced by levels of minimal residual disease (MRD) post therapy and genetic risk by FISH or molecular profiling prior to therapy. Trials exploring response adapted post transplant strategies using MRD as a prognostic tool are going. We provide an update of the current UK-MRA RADAR study. Study Design/Methods: The UK-MRA RADAR study is a national multicentre risk adapted response guided multiarm multistage (MAMS) phase II/III trial which will recruit 1400 patients with NDMM eligible for ASCT. Eligible patients receive induction with 4 cycles of RCyBorD (lenalidomide, cyclophosphamide, bortezomib, dexamethasone), followed by high-dose melphalan and stem cell rescue. Patients with high-risk disease receive Isatuximab in addition to RCyBorD during induction. Genetic risk classification is performed using standard of care FISH testing at local sites. Participants enter the standard or high risk pathway based on presence of atleast two markers: t(4;14), t(14;16), t(14;20), del(17p), del(1p) and gain (1q21). MRD analysis in RADAR uses a multiparametric flow cytometry panel with CD319 and Cd229 used to augment post-isatuximab sample analysis at a central laboratory, with negativity defined at threshold of 10 -5(Figure 1). For standard risk patients, the study addresses two pivotal MRD-related questions: 1) For those with sustained MRD negativity after 12 months of isatuximab maintenance, can treatment be stopped safely to allow patients a treatment-free interval thereby reducing treatment burden? 2) For patients with persistent detectable disease after ASCT, does intensification of consolidation and maintenance therapy augment conversion to MRD negativity compared to lenalidomide maintenance? High risk participants receive intensified consolidation and maintenance regimens post_ASCT aligned to OPTIMUM/MUKnine ( NCT03188172). A further amendment is planned to explore the activity of a BCMA bispecific antibody in high risk patients pre and post transplant. It is hypothesised this will improve both depth (MRD negativity) and ability to sustain response (PFS). Feasibility and benefits of multimodal MRD incorporating imaging and blood-based testing will be tested in the new high risk pathway. In RADAR, we will also gather information on how patients respond to receiving information about their genetic risk assignment and treatment response (MRD). This is a unique opportunity to understand the patients perspective on personalised medicine, which has implications for implementation in clinical care, and future trial design. Trial Progress. RADAR opened to recruitment in May 2021 and is currently recruiting across 87 hospital sites with a further 16 sites in set up. 504 patients have been recruited; 87 are classified as high risk on FISH analysis ( 375 standard risk, 15 unable to determine, 19TBC, 8 withdrawn before FISH analysis). 220 have reached D+100 MRD assessment. Trackable phenotypes were available in 98.2% of patients. Discussion: The RADAR study simultaneously tests escalation and de-escalation strategies, according to disease response, and using MRD to guide post transplant therapy in NDMM patients. Use of central flow cytometry laboratory for MRD has proven feasible in patients to date. Recruitment is on target and outcomes will provide RCT-level evidence for the adaptive use of MRD in treatment allocation and intensification post transplant. The platform design enables adaptation with ability to test new strategies for high risk patients and for standard risk patients who are MRD positive post-transplant. Funding This trial is funded by Cancer Research UK (C9203/A24078), Sanofi Genzyme and Celgene : A BMS company. Sanofi Genzyme and Celgene: A BMS company provide study drug and unrestricted educational grants to support study coordination. This work is also supported by Core Clinical trials unit infrastructure from Cancer Research UK ( C7852/A25447). The funder of the study had no role in study design, data collection, data analysis, data interpretation or writing of the abstract

190. Meta-analysis of Impact of Follow-up Blood Cultures on Mortality in Patients with Gram-negative Bacteremia

Abstract Background It is not clear if follow-up blood cultures are beneficial in patients with Gram-negative bacteremia. It may improve clinical outcomes but have some drawbacks such as the possibility of inaccurate positive findings and extending the length of hospital stay and duration of antibiotic therapy. The aim of this meta-analysis was to evaluate the impact of follow-up blood cultures on mortality in patients with Gram-negative bacteremia. Methods PubMed and EMBASE databases were searched from inception to Jan 2023 for randomized controlled trials or observational studies comparing the mortality in patients with Gram-negative bacteremia who had follow-up blood cultures obtained versus those without these cultures. We estimated odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects models and assessed for heterogeneity (I2). Results A total of six observational studies were included, while no randomized controlled trials were identified. The total number of patients was 4,631. One study used 28-day mortality, two studies used 30-day mortality, and three studies used in-hospital mortality. Follow-up blood cultures were associated with significantly lower odds of mortality ((OR, 0.6; 95%CI, 0.5-0.7; I2, 0%). No publication bias or heterogeneity was observed. Conclusion The use of follow-up blood cultures in patients with Gram-negative bacteremia was associated with lower mortality. Randomized controlled trials are needed. Currently, follow-up blood cultures should be obtained for at least the high-risk patients with Gram-negative bacteremia. Disclosures Khalid Eljaaly, PharmD, MS, BCPS, BCIDP, FCCP, Reckitt Benckiser Healthcare International Ltd, UK: Member of the Global Respiratory Infection Partnership, supported by unrestricted educational grant from Reckitt Benckiser Healthcare Ltd

Sickle Cell Disease Education in Low and Middle Income Countries Using a Smartphone Clinical Case Discussion App

Introduction Sickle cell disease (SCD) is one of the world's most common hemoglobinopathies, affecting over 400,000 newborns annually (Archer et al., 2022). Despite the World Health Organisation's (WHO) 2006 long-term goals to address the SCD burden, the disease's mortality, particularly within low- and middle-income countries (LMICs) such as India and Sub-Saharan Africa (SSA), remains high (WHO 2006). Barriers to improving outcomes for SCD patients in LMICs include a lack of awareness around treatment guidelines and inadequate clinical knowledge among healthcare professionals (HCPs). While effective medical education programs are essential to the provision of high-quality healthcare services, the delivery of such programs in LMICs is challenging due to limited budgets, poor training infrastructure and equipment, and insufficient educators (Barteit et al., 2020). Recently, consideration has been given to the role that digital learning platforms could play in supporting medical education in LMICs (Nicoll et al., 2018). Aim To assess the impact of a smartphone app delivered medical education program in improving HCP clinical knowledge around SCD in LMICs, focused on SSA (Kenya, Ghana, Zambia, Uganda,Tanzania) and India. Methods The SCD program was developed by subject matter experts with MedShr, a secure app- and web-based clinical case discussion platform freely accessible to HCPs worldwide. The program's focus was determined at the outset through a needs-based approach. Analysis of MedShr's proprietary data enabled the identification of key knowledge gaps among HCPs that could be addressed with case-based education, forming the basis for three themes: 1) Acute SCD presentations 2) Chronic SCD complications 3) Long-term SCD management 9 clinical cases comprising a patient vignette, open question and integrated poll were developed by MedShr in line with the program themes. A case example is displayed in Figure 1. Content delivery via the MedShr platform was from August 2022 to February 2023, during which time the cases were promoted to relevant HCPs via email, push notifications and social media. All content was featured within a SCD Global Education Network group on MedShr, connecting target HCPs and facilitating peer-to-peer discussion. Results During the 6 month program, over 173,000 HCPs were reached globally with the educational content, including 75,070 clinicians in SSA and 64,210 in India. HCPs reached included community health workers (28%), GPs (24%), acute physicians (16%), emergency physicians (32%), pediatricians (13%), hematologists (3%), and nurses (8%). The program achieved over 73,000 engagements (case follows, likes, votes and comments) from target HCPs, including 26,419 engagements from HCPs in SSA and 11,173 from those in India. Stand-alone poll questions aligned to the three educational themes were implemented pre- and post-program delivery to assess the program's educational impact. An improvement in clinician knowledge was demonstrated across all three themes (Figure 2). Participant surveys were also used to determine the program's impact on HCP knowledge and clinical behaviors. 84% of participants deemed the content ‘very valuable’ to their clinical decision-making, while 90% stated that they had implemented knowledge obtained from the program in clinical practice. Conclusions The SCD program delivered via the MedShr smartphone app provided a low-cost, high-impact mechanism to deliver effective medical education in LMICs. MedShr's unique SCD professional network provides a digital interface for HCPs, through which peer engagement, interactive discussion and sharing feedback drive learning and behavioral change. The program's metrics highlight the potential scale for digital learning platforms to reach and engage HCPs across diverse geographies, and the program polling and participant surveys demonstrate impact, and that there is scope to improve HCPs' knowledge and practice without costly face-to-face education. Future work should aim to develop tailored learning programs designed to fit local contexts in LMICs, and explore the use of technology-based learning programs in other commonly encountered disease areas. The educational program was funded by an unrestricted educational grant from Novartis. Novartis had no input into content development and their employees could not access the MedShr platform or members.

MP80-16 BLACK PATIENTS HAVE WORSE CONTINENCE OUTCOMES AT 12 MONTHS FOLLOWING ROBOTIC-ASSISTED RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP80-16 BLACK PATIENTS HAVE WORSE CONTINENCE OUTCOMES AT 12 MONTHS FOLLOWING ROBOTIC-ASSISTED RADICAL PROSTATECTOMY Findlay MacAskill, Majed Shabbir, Arun Sahai, Cathcart Paul, and Noel Jonathan Findlay MacAskillFindlay MacAskill More articles by this author , Majed ShabbirMajed Shabbir More articles by this author , Arun SahaiArun Sahai More articles by this author , Cathcart PaulCathcart Paul More articles by this author , and Noel JonathanNoel Jonathan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003357.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: It is known that racial disparities exist for oncological outcomes following prostate cancer, with black patients having a higher mortality. There remains a paucity of specific data regarding functional outcomes and ethnicity in robotic-assisted radical prostatectomy (RARP). The aim of this study was to investigate if racial disparity exists in outcomes following RARP at our institution, which covers a diverse population. METHODS: This single site study utilised an institution approved (10128) prospective database of patients that underwent primary RARP from 2020-2021 with a minimum follow up of 12 months. All 5 surgeons perform a retropubic approach. Logistic regression was performed to investigate the continence rate at 3, 6 and 12 months for significance (p<0.05). Continence is defined as 0 pads/24 hours. Further analysis was performed using propensity score matching for 12-month continence rate only. RESULTS: In this study, 232 men were included of which 37% (86) were black. On average black men underwent surgery at a younger age (59 versus 63 year). However, no difference was observed between black and white men for mean prostate volume, ISUP grade or T stage. While difference in urinary continence recovery was not significant at 3 months (36% versus 52%) and 6 months (49% versus 63%), recovery of urinary continence recovery was inferior for black men at 12 months after surgery (57% versus 75%, p=0.01). After propensity score matching, 95 white and 95 black patients were evaluated. Mean age was 61 (44-67) and 59 (43-73) years, ISUP grade 2.55 and 2.6, MRI 39 (16-112) and 28 (12-112) cc for white and black patients, respectively. Continence rate at 12 months was 76% and 60% (p=0.02), for respectively. CONCLUSIONS: The study demonstrates a racial disparity for return of urinary continence following robotic-assisted laparoscopic prostatectomy with black men having inferior recovery of urinary continence. Further work is required to investigate the reasons for the different outcome. Source of Funding: FM, MS and AS have received an unrestricted educational grant from Boston Scientific © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1159 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Findlay MacAskill More articles by this author Majed Shabbir More articles by this author Arun Sahai More articles by this author Cathcart Paul More articles by this author Noel Jonathan More articles by this author Expand All Advertisement PDF downloadLoading ...

A35 FORECASTING THE INCIDENCE AND PREVALENCE OF INFLAMMATORY BOWEL DISEASE: A CANADIAN NATION-WIDE ANALYSIS

A35 FORECASTING THE INCIDENCE AND PREVALENCE OF INFLAMMATORY BOWEL DISEASE: A CANADIAN NATION-WIDE ANALYSIS

A169 THE DIRECT COSTS OF INFLAMMATORY BOWEL DISEASE IN CANADA: A POPULATION-BASED ANALYSIS OF HISTORICAL AND CURRENT COSTS

A169 THE DIRECT COSTS OF INFLAMMATORY BOWEL DISEASE IN CANADA: A POPULATION-BASED ANALYSIS OF HISTORICAL AND CURRENT COSTS

A210 THE BURDEN OF IBD HOSPITALIZATION IN CANADA: AN ASSESSMENT OF THE CURRENT AND FUTURE BURDEN IN A NATION-WIDE ANALYSIS

A210 THE BURDEN OF IBD HOSPITALIZATION IN CANADA: AN ASSESSMENT OF THE CURRENT AND FUTURE BURDEN IN A NATION-WIDE ANALYSIS

Meaningful cognitive decline is uncommon in virally suppressed HIV, but sustained impairment, subtle decline and abnormal cognitive aging are not

High antiretroviral therapy (ART) coverage and viral suppression among people with HIV (PWH) in Australia provide a unique context to study individual cognitive trajectories, cognitive aging and factors associated with longitudinal cognitive function during chronic and stable HIV disease. Participants from the Predictors of Adherence to Antiretroviral Therapy study (n=457, recruited between September 2013 and November 2015, median age=52 years, and all with HIV RNA <50 copies mL) completed a cognitive assessment with CogState Computerized Battery (CCB) at baseline, Month-12, and Month-24. Demographics, psycho-social and socioeconomic factors, healthcare seeking behaviors, HIV disease characteristics and comorbidities were assessed. The CCB data were corrected for age, sex and practice effect and averaged into a global z-score (GZS). Cognitive impairment was defined with the global deficit score method (GDS>0.5). Meaningful cognitive change was statistically defined (decline or improvement versus stability, i.e., 90% CI, that is p<0.05, 2-tailed) using a novel evidence-based change score: the linear mixed-effect regression (LMER)-based GZS change score. A separate LMER model with a top-down variable selection approach identified the independent effects of age and other demographic, HIV disease characteristics, socioeconomic and health-related factors on the demographically corrected GZS. The combined definitions of change and cross-sectional impairment enabled the identification of cognitive trajectories. At Month-12 and Month-24, 6% and 7% showed meaningful cognitive decline and 4% and 3% improved respectively. Only 1% showed sustained decline. Incident impairment due to subtle cognitive decline (i.e., below the threshold of meaningful cognitive decline) was 31% and 25% at Month-12 and Month-24, while 14% showed sustained impairment (i.e., cognitively impaired at all study visits). Older age (≥50 years) and time interaction was associated with lower demographically corrected GZS (β=-0.31, p<0.001). Having a regular relationship, excellent English proficiency, and perceived stigma (avoidance) were associated with higher GZS (all p<0.05). Relying on government subsidy, severe depression, and lower belief in ART necessity and higher concerns were associated with lower GZS (all p<0.05). No HIV disease characteristics had a significant effect. Meaningful cognitive decline was not different from normal expectation in chronic stable HIV disease. Despite this, subtle cognitive decline, sustained cognitive impairment, and greater than normative-age cognitive aging were evident. Funding for the PAART study was provided in part by unrestricted educational grants from Gilead Sciences (www.gilead.com) (Grant Number: IN-AU-264- 0131), the Balnaves Foundation (www.balnavesfoundation.com), the Victorian Department of Health and Human Services (Australia) (www.dhs.vic.gov.au/home), Western Australia Health (www.health.wa.gov.au), the ACT Ministry of Health (Australia) (www.health.act.gov.au), and in-kind support from the Queensland Department of Health (Australia) (www.health.qld.gov.au), and NHMRC Partnership grant APP1058474 (PI: Carr, Andrew).

1293. Calling Attention to Pre-Exposure Prophylaxis (PrEP) for Women: A Novel Social Media Educational Campaign for Potential PrEP Users and Clinicians

Abstract Background We designed and implemented an educational campaign using social media to provide information about HIV risk and prevention to Black heterosexual women (BHW) to promote PrEP awareness and enhance their relationships with clinicians. Methods In July and August 2021, 3 physician social media influencers who are Black women with large Black audiences shared content focusing on sexual health and PrEP on Instagram and TikTok with links to 2 surveys. An accredited webcast for clinicians followed in October 2021. It incorporated key points from the surveys and covered integrating HIV prevention into the routine care of BHW and addressing misconceptions about PrEP. Results The social media campaign reached over 171,000 followers and garnered 3,700 engagements, 62,441 total views, and 1.4 million impressions. Among the 171 comments, common themes included women not realizing that they could use PrEP and appreciation that the posts advocated for their health. In total, 41 Black women responded to the surveys. 64% said they would be extremely/moderately comfortable talking with a provider about HIV prevention and PrEP (N=14). 89% would be extremely comfortable asking their provider for PrEP if they thought they needed it, but their provider did not offer it (N=9). However, some respondents still felt uncomfortable because they didn’t know what questions to ask, were embarrassed to ask questions, or were afraid of being seen as promiscuous. To date, the webcast had 767 participants (75% in primary care and OB/GYN), and matched pre/post-test data were available for 49 learners. Learners’ confidence in their ability to integrate HIV prevention into the routine care of their BHW patients increased (53% moderately/very confident at baseline vs. 74% at post-test). Learners were more likely to ask their BHW patients about the risk behaviors of their partner(s) when taking a sexual history (51% very/extremely likely at baseline vs. 78% at post-test). Conclusion These results highlight the educational needs of BHW and illuminate needed improvements in clinician-patient dialogues about sexual health. Although Instagram and TikTok are known for brevity of content, they were effective in informing BHW about PrEP use for women and taking charge of their sexual health. Disclosures Jaime Symowicz, PhD, Gilead Sciences, Inc: Unrestricted educational grant for the educational initiative described in the abstract.

Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study

Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p<0·0001), BA.1 (107·3 [86·40-133·2] vs 648·9 [523·5-804·5]; p<0·0001), and BA.4/5 (40·63 [31·99-51·60] vs 223·0 [183·1-271·4]; p<0·0001) variants. Breakthrough infection was significantly more frequent in patients treated with infliximab (119 [13·7%; 95% CI 11·5-16·2] of 871) than in those treated with vedolizumab (29 [7·0% [4·8-10·0] of 417; p=0·00040). Cox proportional hazards models of time to breakthrough infection after the third dose of vaccine showed infliximab treatment to be associated with a higher hazard risk than treatment with vedolizumab (hazard ratio [HR] 1·71 [95% CI 1·08-2·71]; p=0·022). Among participants who had a breakthrough infection, we found that higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and, hence, a longer time to breakthrough infection (HR 0·87 [0·79-0·95]; p=0·0028). Our findings underline the importance of continued SARS-CoV-2 vaccination programmes, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies. Royal Devon University Healthcare NHS Foundation Trust; Hull University Teaching Hospital NHS Trust; NIHR Imperial Biomedical Research Centre; Crohn's and Colitis UK; Guts UK; National Core Studies Immunity Programme, UK Research and Innovation; and unrestricted educational grants from F Hoffmann-La Roche, Biogen, Celltrion Healthcare, Takeda, and Galapagos.

PSUN326 An Interim Analysis of Healthcare Professionals’ Gaps in Incretin Knowledge Before and After Education

Abstract Background Patients with type 2 diabetes (T2D) who have poor glycemic control are at increased risk for macrovascular and microvascular disease. The growing body of cardiovascular (CV) and renal outcomes data for newer agents such as glucagon-like peptide 1 (GLP-1) receptor agonists has shifted management approaches toward therapies that provide extra glycemic benefits in addition to glucose-lowering ability. The rapidly evolving role of these new agents and new data on the potential role of a glucose-dependent insulinotropic polypeptide (GIP) agonist/GLP-1 agonist combination agent may create confusion among healthcare professionals (HCPs) treating patients with T2D. Greater competence is needed on the actions and clinical applications of current and emerging incretin-based therapies. Therefore, Clinical Care Options (CCO) created a series of online-based microlearning modules on the topic of incretin therapy in patients with T2D and cardiometabolic comorbidities for HCPs. This ongoing program, which was supported by an unrestricted medical education grant, is providing us with rich outcomes data that characterizes HCPs’ learning and current knowledge gaps regarding the use of incretins in patients with T2D. Aim The goal of this analysis was to determine the interim educational impact as well as remaining knowledge gaps among HCPs following education on incretin therapies. This information could inform future medical education that closes knowledge gaps and arms HCPs with the tools to effectively manage patients with T2D. Methods CCO produced an online educational program on incretin therapies, released in August 2021. We used pre/post questions to mine data on HCPs’ gaps. Questions measuring HCPs’ knowledge and competence were asked at baseline ("pre") and then repeated after the education was delivered ("post"). To uncover key educational gaps, we identified questions with the lowest correct responses at baseline as well as persistence of incorrect responses post education. Interim Results HCP Demographics N = 9837; MD: 61%; RPh: 10%; NP/PA: 12%; RN: 5%; other HCP: 5%, non-HCP: 8% Baseline and Remaining Gaps Incretin-based questions with topics including GLP-1 effects on glucose homeostasis, metabolic effects of GIP/GLP-1 coagonists, and the A1C-lowering ability of tirzepatide all scored &amp;lt;50% at baseline. Following education, the GLP-1 effect on glucose homeostasis increased only slightly from 36% to 40%, and the metabolic effects of GIP/GLP-1 coagonists increased from 19% to 54%, indicating that HCPs still struggle with understanding the effects of these agents. Conclusions This analysis demonstrates that HCPs who care for patients with T2D have significant knowledge gaps in the effects of newer incretin agents. As guidelines are placing more emphasis on the use of newer incretin agents as first-line therapy, HCPs must have the knowledge and competence of their actions to initiate incretin therapy in the primary care setting. Comparison to a similar program with an alternative format may provide further insight. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Vascular access in complex high-risk but indicated percutaneous coronary interventions (CHiP) types, trends, and outcomes

Abstract Background Radial access improves the safety of PCI; however, its role in Complex, High-risk but indicated Percutaneous coronary interventions (CHiP) remains poorly studied. Objectives To examine CHiP types, clinical and procedural characteristics and clinical outcomes according to vascular access. Methods Data was obtained from the British Cardiovascular Intervention Society. We compared the baseline characteristics of 125,662 CHiP procedures performed electively between 2006 and 2017 stratified by access site. Multivariate regression analyses was used to investigate the access site specific odds for in-hospital death, bleeding, and major cardiovascular and cerebral events (MACCE). Results Overall, 61,825 CHiP procedures (49.2%) were performed via transradial access (TRA) and 63,837 (50.8%) via trans-femoral access (TFA). TRA use increased over time (14.6% in 2006 to 78.4% in 2017). The patients who had PCI through TRA were older (Median age: TRA, 71.2 vs TFA, 70.2 years). Cardiovascular risks were more prevalent in the TRA than TFA (stroke: 5.3 vs 4.3%; hypertension: 67.4 vs 64.3%; peripheral vascular disease: 7.2 vs 6.7%; smoking: 9.6 vs 8.9% respectively; p&amp;lt;0.001 for all). TRA patients had higher rates of multi-vessel PCI than TFA (two or more vessel PCI: 27.2 vs 24.2% respectively; p&amp;lt;0.001) and longer lesions (median stent length: 24mm vs 23mm). TFA group had higher rates of diabetes (26.6 vs 25.8%), previous myocardial infarction (44.2 vs 40.2%), previous PCI (38.7 vs 37.1%), heart failure (10.3 vs 9.3%), respectively (p&amp;lt;0.001 for all) suggesting operators' tendency to choose TFA in patients with greater cardiometabolic burden. TRA adoption was more prevalent in most CHiP types (elderly (54%), chronic renal failure (55.7%), poor LV function (51.4%), left main PCI (51.2%), treatment for severe vascular calcifications (53.1%)). Following adjustment for differences in clinical and procedural characteristics, TFA was independently associated with increased odds for mortality (aOR: 1.4 (1.1–1.8), p=0.004), bleeding (aOR: 2.9 (2.4–3.5), p&amp;lt;0.001), and MACCE (aOR: 1.2 (1.1–1.3), p&amp;lt;0.001). Conclusion Over the 12 years, TRA has become the predominant access site used in CHiP PCI and is associated with significantly lower mortality, major bleeding and MACCE odds than TFA. Addressing the cardiometabolic burden-treatment paradox by preferentially selecting TRA as the baseline cardiovascular burden increases may potentially improve CHiP clinical outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): An unrestricted educational grant from Abbott supports Warkaa Shamkhani's salary. However, the company had no role in the study design, manuscript preparation, or access to the manuscript's contents before submission. The authors are solely responsible for this study design and conduct and all analysis, drafting, and editing of the manuscript and its final content.

LDL levels and long-term all-cause mortality in patients from nationwide LIPIDOGRAM 2004–2015 cohort studies

Abstract Background Data from multiple randomized clinical trials show that lowering LDL cholesterol with statins is associated with significant reduction of outcomes both in primary and secondary prevention. Despite this some epidemiological studies reported increased risk with lowest LDL levels. The reason for this apparent discrepancy is probably due to unbalanced confounding in epidemiological studies. Purpose To assess long term survival in propensity matched cohort from the LIPIDOGRAM study in patients on statin therapy. Methods Lipidogram studies were carried out in Poland in 2004, 2006 and 2015 in the population representative for patients in primary care setting. The median follow up was 5570 days. Patients were recruited in all 16 administrative regions in Poland and physicians (n&amp;gt;1100) were proportionally distributed to the number of inhabitants in a given administrative region. Each patient was asked to fill the questionnaire on chronic diseases, treatment and lifestyle. Questionnaire was supervised by physician. Patients who were taking statins at the time of enrollment were matched to patients who were not on statin therapy. Groups were matched with regard to age, sex, body mass index, LDL cholesterol, diabetes mellitus, hypertension, previous myocardial infarction, chronic kidney disease, previous ischemic stroke, and atrial fibrillation. Nearest neighbor matching method was employed. Results To 13676 patients (28.9% of the LIPIDOGRAM 2004–2015 cohort) that took statin at the time of enrollment and 13676 patients not on statin treatment were matched. There were no significant differences between two groups with regard to all variables used in matching procedure including LDL cholesterol level. After 15 years of follow up There were 2585 deaths (18.9%) in patients who were treated with statin at the time of enrollment as compared to 2824 (20.6%) in patients with no treatment for dyslipidemia (absolute risk reduction (ARR) of −1.7%, p=0.003) Hazard ratio for mortality in patients who were not treated with statin at the enrollment in this propensity matched cohort was 1.11 (95% CI; 1.05–1.17, p=0.0002). Conclusions Despite similar LDL levels patients treated with statin at the time of enrollment had lower mortality risk as compared to patients not taking statins in long-term follow-up. Lower LDL levels that are not due to statin therapy might imply other underlying conditions that influence prognosis. Therefore, data from epidemiological studies that contradict results of balanced randomized trials due to intrinsic limitations should be approached with skepticism. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The present study was funded by an unrestricted educational grant from Valeant. As a supporter of the study, Valeant played no role in the study design, data analysis, data interpretation, or writing of the report. The present study was also supported by Silesian Analytical Laboratories (SLA, Katowice, Poland).

Relationship of obesity to mortality in 47,399 patients from nationwide LIPIDOGRAM 2004–2015 cohort studies

Abstract Background Evidence suggests that obesity may be associated with lower mortality rates in various cohorts of patients (obesity paradox). One possible explanation is unmeasured confounding factors induced by selection bias (collider stratification bias). Therefore, data from large cohorts with few exclusion criteria are of value as they may minimize this effect. Purpose To assess the association between two obesity measures body mass index (BMI; kg/m2) and waist circumference (WC; cm) with mortality in nationwide cohort of 47,399 patients. Methods Lipidogram studies were carried out in Poland in 2004, 2006 and 2015 in the population representative for patients in primary care setting. The median follow up was 5570 days. Patients were recruited in all 16 administrative regions in Poland and physicians were proportionally to the number of inhabitants in a given administrative region. Each patient was given a questionnaire on chronic diseases, treatment and lifestyle. Questionnaire was administered by physician. Association between BMI, WC and mortality was assessed by multivariate Cox regression and spline regression models. Weight status was classified as underweight (BMI &amp;lt;18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25–29.9), class I obesity (BMI 30–34.9), class II obesity BMI (35–39.9), and class III obesity BMI (&amp;gt;40). Results The prevalence of hypertension, dyslipidemia, diabetes and coronary artery disease, showed a graded association with BMI, whilst smoking was most frequent in underweight patients. Correlation between BMI and WC was 0.748. As compared to normal weight patients' class III obese patients had highest mortality (HR 1.91; 95% CI: 1.650–2.202), following by class II obesity (HR 1.47, 95% CI: 1.33–1.62) and underweight patients (HR 1.47; 95% CI 1.1–1.8). Overweight patients had also slightly increased risk of dying as compared to normal weight patients (HR 1.12; 95% CI: 1.05–1.19). Similar U-shaped curve was observed for waist circumference. After adjustment for age, sex, smoking, diabetes, hypertension and LDL cholesterol highest mortality was observed for underweight patients (HR 1.88; 95% CI: 1.44–2.45), following by class III obesity (HR–1.51; 95% CI 1.31–1.75). Class I obesity and being overweight was associated with lower risk (HR 0.88; 95% CI: 0.82–0.94 and HR 0.86; 95% CI: 0.81–0.92, respectively). Conclusions No evidence of obesity paradox was present in unadjusted analysis. Lower mortality was observed in overweight and class I obese patients only after adjustment for risk factors and diseases typically associated with obesity. Results of multivariate analysis indicate that diseases that develop in obese patients are significantly associated with mortality more than obesity itself. Confounding may be responsible for discussed obesity paradox in literature therefore preventive measures to maintain BMI within normal range and prevent development of its complications should not be abolished. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The present study was funded by an unrestricted educational grant from Valeant. As a supporter of the study, Valeant played no role in the study design, data analysis, data interpretation, or writing of the report. The present study was also supported by Silesian Analytical Laboratories (SLA, Katowice, Poland).

Lean metabolic syndrome is associated with similar long-term prognosis as metabolic syndrome in overweight/obese patients. Analysis 47,399 Patients from nationwide LIPIDOGRAM 2004–2015 cohort studies

Abstract Background Obesity was once though as an indispensable component of metabolic syndrome. Therefore, there a lot of definitions of metabolic syndrome with only few not including obesity as a criterion. The necessity of the obesity criterion in the metabolic health assessment is being questioned, as similar metabolic disturbances can occur in normal weight individuals. This relatively new concept is often referred as lean metabolic syndrome. Data on long term prognosis is scarce. Purpose To evaluate association between metabolic health and long-term prognosis. Methods Lipidogram studies were carried out in Poland in 2004, 2006 and 2015 in the population representative for patients in primary care setting. Patients were recruited in all 16 administrative regions in Poland and physicians were proportionally to the number of inhabitants in a given administrative region. Each patient was given a questionnaire on chronic diseases, treatment and lifestyle. Questionnaire was administered by physician. The diagnosis of metabolic syndrome was based on the presence of at least two of the following: 1) systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥85 mmHg, 2) triglycerides (TG) &amp;gt;150 mg/dl, 3) high-density lipoprotein cholesterol (HDL-C) &amp;lt;40 mg/dl men and &amp;lt;50 mg/dl in women, 4) total cholesterol (TC) &amp;gt;200 mg/dl, and 5) fasting glucose (FBG) &amp;gt;100 mg/dl. Basing on those criteria and BMI with a cut off value of 25 kg/m2, patients were divided into four categories: healthy slim, metabolically healthy overweight/obese, lean metabolic syndrome and overweight/obese metabolic syndrome. The median follow up was 5570. this analysis data were censored at 3650 days. Results The median age of the study participants was 56.4 years. 7901 (16.7%) fell into category healthy slim, 14607 (30.8%) were classified as metabolically healthy overweight/obese, 3827 (8.1%) fulfilled criteria for lean metabolic syndrome whilst the remaining 21063 (44.4%) patients were diagnosed with overweight/obese metabolic syndrome. There were 4065 deaths during 10 years follow-up. Patients with lean metabolic syndrome had similar risk as patients with overweight/obese metabolic syndrome (HR=1.33, 95% CI: 1.17–1.52, p&amp;lt;0.001 and HR=1.32, 95% CI: 1.20–1.45, p&amp;lt;0.001). Metabolically heathy overweight/obese patients had only slightly higher risk of dying than healthy slim patients but this difference was less pronounced (HR=1.11, 95% CI: 1.08–1.23, p=0.03). Conclusions Lean metabolic syndrome confers similar risk as metabolic syndrome in overweigh/obese patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The present study was funded by an unrestricted educational grant from Valeant. As a supporter of the study, Valeant played no role in the study design, data analysis, data interpretation, or writing of the report. The present study was also supported by Silesian Analytical Laboratories (SLA, Katowice, Poland).

TEAD4 regulates trophectoderm differentiation upstream of CDX2 in a GATA3-independent manner in the human preimplantation embryo.

TEAD4 regulates trophectoderm differentiation upstream of CDX2 in a GATA3-independent manner in the human preimplantation embryo.