Received Research Funding Research Articles

Cost-effectiveness of the tubeless automated insulin delivery system vs standard of care in the management of type 1 diabetes in the United States.

BACKGROUND: A tubeless, on-body automated insulin delivery (AID) system (Omnipod 5 Automated Insulin Delivery System) demonstrated improved glycated hemoglobin A1c levels and increased time in range (70 mg/dL to 180 mg/dL) for both adults and children with type 1 diabetes in a 13-week multicenter, single-arm study. OBJECTIVE: To assess the cost-effectiveness of the tubeless AID system compared with standard of care (SoC) in the management of type 1 diabetes (T1D) in the United States. METHODS: Cost-effectiveness analyses were conducted from a US payer's perspective, using the IQVIA Core Diabetes Model (version 9.5), with a time horizon of 60 years and an annual discount of 3.0% on both costs and effects. Simulated patients received either tubeless AID or SoC, the latter being defined as either continuous subcutaneous insulin infusion (86% of patients) or multiple daily injections. Two cohorts (children: <18 years; adults: ≥18 years) of patients with T1D and 2 thresholds for nonsevere hypoglycemia (nonsevere hypoglycemia event [NSHE] <54 mg/dL and <70 mg/dL) were considered. Baseline cohort characteristics and treatment effects of different risk factors for tubeless AID were sourced from the clinical trial. Utilities and cost of diabetes-related complications were obtained from published sources. Treatment costs were derived from US national database sources. Scenario analyses and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: Treating children with T1D with tubeless AID, considering an NSHE threshold of less than 54 mg/dL, brings incremental life-years (1.375) and quality-adjusted life-years (QALYs) (1.521) at an incremental cost of $15,099 compared with SoC, resulting in an incremental cost-effectiveness ratio of $9,927 per QALY gained. Similar results were obtained for adults with T1D assuming an NSHE threshold of less than 54 mg/dL (incremental cost-effectiveness ratio = $10,310 per QALY gained). Furthermore, tubeless AID is a dominant treatment option for children and adults with T1D assuming an NSHE threshold of less than 70 mg/dL compared with SoC. The probabilistic sensitivity analyses results showed that compared with SoC, in both children and adults with T1D, tubeless AID was cost-effective in more than 90% of simulations, assuming a willingness-to-pay threshold of $100,000 per QALY gained. The key drivers of the model were the cost of ketoacidosis, duration of treatment effect, threshold of NSHE, and definition of severe hypoglycemia. CONCLUSIONS: The current analyses suggest that the tubeless AID system can be considered a cost-effective treatment compared with SoC in people with T1D from a US payer's perspective. DISCLOSURES: This research was funded by Insulet. Mr Hopley, Ms Boyd, and Mr Swift are full-time Insulet employees and own stock in Insulet Corporation. IQVIA, the employer of Ms Ramos and Dr Lamotte, received consulting fees for this work. Dr Biskupiak is receiving research support and consulting fees from Insulet. Dr Brixner has received consulting fees from Insulet. The University of Utah has received research funding from Insulet. Dr Levy is a consultant with Dexcom and Eli Lilly and has received grant/research support from Insulet, Tandem, Dexcom, and Abbott Diabetes. Dr Forlenza conducted research sponsored by Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly. He has been speaker/consultant/advisory board member for Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly.

Clinical characteristics and health care resource use of patients at risk for wild-type transthyretin amyloid cardiomyopathy identified by machine learning model

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening systemic disorder that is an underrecognized cause of heart failure (HF). When the diagnosis of wild-type ATTR-CM (ATTRwt-CM) is delayed, patients often undergo additional assessments, deferring appropriate management as symptoms potentially worsen. Prompt recognition of patients at risk for ATTRwt-CM is essential to facilitate earlier diagnosis and disease-modifying treatment. A previously developed machine learning model performed well in identifying ATTRwt-CM in patients with HF vs controls with nonamyloid HF using medical claims/electronic health records, providing a systematic framework to raise disease suspicion. OBJECTIVE: To further evaluate this model's performance in identifying ATTRwt-CM using a large claims database of older adults with HF and confirmed ATTRwt-CM or nonamyloid HF; and to explore the characteristics and health care resource utilization (HCRU) of patients with confirmed and suspected ATTRwt-CM. METHODS: In this retrospective study, the prior model was applied using Humana administrative claims for patients diagnosed with ATTRwt-CM (cases) and nonamyloid HF (controls [1:1]). Patients were aged 65-89 years, had at least 2 claims for HF diagnosis (2015-2020), and were continuously enrolled in a Medicare Advantage prescription drug plan for at least 12 months before and at least 6 months after HF diagnosis. For the assessment of characteristics and HCRU, the suspected risk level was categorized based on the predicted probability (PP) from model output (high, moderate, and low risk: PP≥0.70; ≥0.50 and < 0.70; and < 0.50, respectively). RESULTS: Of 267,025 eligible patients, 119 (0.04%) had confirmed ATTRwt-CM; of 266,906 patients with nonamyloid HF, 10,997 (4.1%), 68,174 (25.5%), and 187,735 (70.3%) were categorized as high, moderate, and low risk for ATTRwt-CM, respectively. The model demonstrated sensitivity/specificity/accuracy/receiver operating characteristic area under the concentration-time curve of 88%/65%/77%/0.89, respectively, in differentiating ATTRwt-CM from nonamyloid HF. In patients with confirmed ATTRwt-CM, the mean (SD) time between HF and ATTRwt-CM diagnoses was 751 (528) days; 65% and 48% were hospitalized before and after ATTRwt-CM diagnosis, respectively. Atrial fibrillation was more common in patients with confirmed ATTRwt-CM and high risk (39% and 55%) vs low risk (27%). Hospitalization and emergency department visits after HF diagnosis were reported in 57% and 46% of patients with high ATTRwt-CM risk, respectively. CONCLUSIONS: The ATTRwt-CM predictive model performed well in identifying disease risk in the Humana Research Database. Patients at high risk for ATTRwt-CM had high HCRU and may benefit from the earlier suspicion of ATTRwt-CM. The model may be used as a tool to identify patients with a suspected high risk for the disease to facilitate earlier detection and treatment. DISCLOSURES: This study was sponsored by Pfizer. Medical writing support was provided by Donna McGuire of Engage Scientific Solutions and funded by Pfizer. Drs Bruno and Schepart and Mr Casey are currently employees of Pfizer and equity holders in this publicly traded company. Dr Reed was an employee of Pfizer at the time that this analysis was planned and conducted. Mr Sheer and Dr Simmons are currently employees of Humana, which received research funding from Pfizer. Dr Nair was an employee of Humana at the time that this analysis was planned and conducted.

Myelodysplastic Syndromes/Neoplasms-Insights Into Pathogenesis Leading to Improved Classification, Risk Stratification, and Treatments.

From the ∗VA Connecticut Cancer Center, West Haven †Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Comprehensive Cancer Center, New Haven, CT. Conflicts of Interest and Source of Funding: A.M.Z. is a Leukemia and Lymphoma Society Scholar in Clinical Research. A.M.Z. received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Cardiff oncology, Incyte, Takeda, Novartis, Shattuck Labs, Geron, Aprea, and ADC Therapeutics. A.M.Z. participated in advisory boards and/or had a consultancy with and received honoraria from AbbVie, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Servier, Boehringer-Ingelheim, Novartis, Astellas, Daiichi Sankyo, Geron, Taiho, Seattle Genetics, BeyondSpring, Takeda, Ionis, Amgen, Janssen, Genentech, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, Notable, Orum, Mendus, Foran, Syros, and Tyme. A.M.Z. served on clinical trial committees for Novartis, Abbvie, Gilead, Syros, BioCryst, Abbvie, ALX Oncology, Geron, and Celgene/BMS. For M.G.R., none were declared. Reprints: Michal G. Rose, MD, VA Connecticut Cancer Center, 950 Campbell Avenue (III-d), West Haven, CT 06516. E-mail: [email protected].

Commentary on Laffan et al expert consensus for equitable care for VWD.

In a recent issue of Haemophilia, Laffan et al. report ‘An expert consensus to define how higher standards of equitable care for von Willebrand disease can be achieved in the United Kingdom and Republic of Ireland.’’1 This project aimed to generate recommendations to improve equitable access to care for VWD patients. A modified Delphi approach was used and clear criteria for stopping and consensus were defined. Ultimately, eight recommendations were derived and include four that specifically address standardised and improved history taking about bleeding events, especially heavy menstrual bleeding, as well as additional recommendations focused on care delivery, better evidence for prophylaxis, and equity in terms of time to diagnosis and quality of life assessments. The expert authors are to be applauded for this effort and their focus on gender bias in the bleeding disorder community. A few points raised by this study merit additional discussion. The health care providers included were predominantly Haematologists, with Nurse Specialists as the second most common group; only one Obstetrician was included. Most respondents were from England and Ireland. Notably, a very high level of consensus was achieved after only one round of voting, which while reassuring, is not surprising given the relative homogeneity of the group. VWD patients interact with many parts of the health care system, and as a community, we need to turn our focus outward to other providers if we intend to truly improve the time to diagnosis and care. We also need to consider the specific challenges facing those living in low and middle-income countries, as the solutions must be tailored to the available resources and cultural settings. Certainly, the foundation of change needs to involve rejecting sexist attitudes towards individuals with bleeding disorders and valuing the lived experiences of patients. Along those lines, the patient voice must be included in future efforts directed at improving equitable access to care. We need to listen to patients and patient organizations to understand their priorities and tailor our approaches appropriately. Failure to do so could perpetuate the current state of inequity, no matter how well-meaning the intentions. As an example, the ongoing focus of many national and international organizations on hemophilia (as evidenced by the very names of these organisations) creates a barrier for VWD patients and healthcare providers. Women have been telling us for years that they feel poorly represented within Hemophilia Treatment Centres and by Hemophilia-focused patient organisations.2-4 It is time we listen and act. Of note, the recommendation with the lowest consensus at 80% was ‘Patients should always be involved in treatment options for their VWD’—clearly, there is work left to do to truly achieve patient-centred care. The authors include a detailed discussion of the barriers to care, which are many, especially at the primary care level. Engaging with primary care practitioners (PCP), who are often the first point of contact for someone with bleeding symptoms, seems an additional critical step in creating a functional and integrated system to diagnose and manage these patients. The value of multi-disciplinary clinics has been recognised, but in contrast to these being specialist centred, the inclusion of PCP in these models of care could be considered. Lastly, as highlighted by the authors, the quality of evidence for critical aspects of the care of VWD patients, such as prophylaxis, is poor. Although there are many barriers to performing these studies including the multiple types and subtypes of VWD as well as the numerous bleeding symptoms experienced by patients, the need for high-quality evidence is clear. In the recently published ASH (American Society of Hematology) ISTH (International Society on Thrombosis and Hemostasis) NHF (National Hemophilia Foundation) WFH (World Federation of Hemophilia) VWD Management Guidelines, all 12 recommendations were conditional, due to the lack of high-quality evidence.5 Laffan et al. appropriately identify the need for future studies to further develop the evidence base on which we base management decisions for VWD patients. Paula James receives research funding from Bayer and consultancy fees from Band/Guardian Therapeutics and Star/Vega Therapeutics. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

OA32 Jaw claudication - does the textbook description need updating?

Abstract Background/Aims Recognition of jaw claudication is crucial to expedite diagnosis and treatment of giant cell arteritis (GCA). The ACR 1990 criteria defined claudication of the jaw, tongue or deglutition as “development or worsening of fatigue or discomfort in muscles of mastication, tongue, or swallowing muscles while eating”. We sought to describe the diverse ways in which patients may describe this key GCA symptom and its impact on health-related quality of life. Methods Secondary analysis of a qualitative dataset originally created for the development of a patient-reported outcome measure for GCA. Participants (n = 36) with GCA confirmed by biopsy/imaging were recruited using purposive sampling from two rheumatology clinics and one ophthalmology clinic in the UK (n = 25) and Australia (n = 11). Interviews transcripts from the original study were organised within QSR NVivo 12 software and analysed using template analysis. Themes were refined through discussion among researchers including a patient partner. Results 20 of 36 participants (56%) reported jaw symptoms. Of these 20, the median age was 76.5 years; 60% were female. Five main themes were identified in the data: physical sensations; impact on function; impact on diet; symptom response to steroids; attribution to other causes (see Table 1). Whilst a large proportion of patients described jaw pain, jaw cramp, jaw stiffness and lockjaw had also been described. Symptom resolution following commencement of steroids varied among participants. Jaw symptom was misjudged as due to dental cavity, ear infection and teeth grinding by healthcare professionals in some cases. Some patients did not seek immediate help from healthcare professionals regarding their jaw symptoms as they were thought to be related to arthritis, age or viral illnesses. Conclusion Patients with GCA described their jaw symptoms in various ways, not exclusive to chewing. When Horton originally described jaw claudication, he also observed that some patients reported ‘lockjaw’. For early recognition and prompt diagnosis of GCA, we suggest that textbooks and teaching should be updated to reflect this. Patient education on the potential significance of jaw symptoms is also crucial to avoid delay in seeking help. Disclosure J. Lim: None. E. Dures: None. L. Bailey: None. C. Almeida: None. C. Ruediger: None. C. Hill: None. J. Robson: None. S.L. Mackie: Consultancies; Roche/Chugai, Sanofi, AbbVie, AstraZeneca. Other; SLM has given talks on behalf of her institution for Pfizer, Vifor and UCB. In all cases fees were paid to her institution and no personal fees were received, SLM was supported by Roche to attend EULAR2019 and by Pfizer to attend ACR2021 virtually, SLM has been an investigator on clinical trials for Sanofi and GSK, As a research grant co-applicant, SLM has received research funding (partial salary support) from Vifor, paid to her institution.

E013 Co-production of a quality improvement project to address glucocorticoid toxicity

Abstract Background/Aims Glucocorticoid toxicities are well-known, but patient involvement work (PMR Voices 2021) had highlighted a need for better patient education/counselling about side-effects, including early neuropsychiatric toxicity, and support for self-management. In our audit of steroid-induced hyperglycaemia, our attempts to improve counselling had proved challenging to implement. Therefore, we sought patient involvement in designing a quality improvement (QI) project informed by their lived experience. Methods Using insight gathered from previous patient involvement and the clinical team, we held a workshop with ten patient partners living with polymyalgia rheumatica (PMR) to share stories and define relevant themes. We then collected narratives using a distributed ethnographic and mixed-methods tool, Sensemaker®, designed to enable multi-perspective narrative methods at scale. The SenseMaker site was disseminated via patient organisations including PMRGCAuk, PMR GCA Scotland and VasculitisUK, along with a parallel survey for professionals. The survey centred around gathering a narrative from the perspective of the patient, healthcare professional (HCP), or carer; and self-signification of that narrative against a conceptual framework based on theory (Leventhal’s Common-sense Model) and themes identified by the patient partners. The group of ten patients discussed the emerging patterns, after which further analysis of the narratives was conducted to link them to feasible actions. Results The clinical team identified access and communication, echoed by the patient team with particular focus on trustworthy information sources, visibility of side-effects, and future health significance. We piloted and improved the survey with patient partners. In 4 weeks we received 198 patient responses, mostly from the UK, and those of 28 HCPs. HCPs informally fed back that the survey was interesting to complete because it prompted thought and reflection. The patient narratives conveyed multi-layered messages; physical and mental health were intertwined. The two groups described the same spectrum of steroid side-effects (mood disturbance commonest). Compared to HCPs, patients chose to share narratives focused less on prevention and more on managing/mitigating, and often spoke of “trustworthy information” coming from the lived experience of themselves or others, rather than medical sources. Many of the narratives suggested simple actions that might improve clinical services, yet might not have been visible in the context of clinical encounters or quantitative survey measures alone. Conclusion We used co-production to inform healthcare improvement. The method can reveal biases of perspective and entrained patterns of thinking amongst both experts and patients that can affect decision-making relevant to health outcomes. Limitations include lack of a defined sampling frame (dissemination via informal networks), and limitations related to digital exclusion; with more time/resources it would be possible to access a wider patient audience. This method helped us prioritise feasible actions to take forward in QI work to evaluate their effectiveness as we incorporate them into our service. Disclosure F. Morgan: None. H. Al-Hilali: None. M. Grover: None. L. Neill: Other; LN is a trustee of PMR GCA Scotland. E. Snowden: Other; The Sensemaker tool is used both in non-profit and commercial contexts. J. Scopes: None. G. Crowther: None. A. Rebane: None. H. Ismail: None. S.L. Mackie: Consultancies; SLM has provided consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie and AstraZeneca. In all cases fees were paid to her institution and no personal fees were received. Member of speakers’ bureau; SLM has given talks on behalf of her institution for Pfizer, Vifor and UCB. In all cases fees were paid to her institution and no personal fees were received. Grants/research support; As a research grant co-applicant, SLM has received research funding (partial salary support) from Vifor, paid to her institution. Other; SLM was supported by Roche to attend EULAR2019 and by Pfizer to attend ACR2021 virtually. SLM has been an investigator on clinical trials for Sanofi and GSK.

E038 A common measure of the impact of glucocorticoids in patients with inflammatory and autoimmune conditions - the Steroid PRO: A cross-cultural validation study with Rasch models

Abstract Background/Aims Systemic glucocorticoids are key in the management of life- and organ-threatening rheumatic diseases, but have wide-ranging adverse effects of concern to patients and clinicians. We aimed to validate a Patient Reported Outcome (PRO) measure (the Steroid PRO) for assessing the impact of glucocorticoids on health-related quality of life (HRQoL) in patients receiving glucocorticoids for rheumatic disease. Methods This was a cross-sectional study of adults from the UK, USA, Australia and New Zealand, taking glucocorticoids for a rheumatic disease. An online survey was conducted at two time points: Time 1: (i) demographics - age, gender, country, ethnicity, educational level; (ii) clinical information - diagnosis, glucocorticoid dose; (iii) 40 candidate items for the Steroid-PRO, developed in a previous qualitative study; (iv) EQ5D-5L. Time 2 (optional, completed 3-5 days later): (i) the Steroid PRO candidate items; (ii) a condition change question. The survey was distributed via social media and patient organisations. After descriptive analysis, iterative testing with Rasch measurement model and exploratory factor analysis (EFA) informed item reduction and established structural validity, reliability and unidimensionality of the final Steroid-PRO. Item reduction was based on clinical importance, lack of fit to the Rasch model, and redundancy. Evidence of discriminative validity of the Steroid-PRO was established by comparing its scores for participants receiving lower dose glucocorticoid (up to 10 mg) versus higher dose (&amp;gt;10 mg). Intraclass correlation (ICC) between Time 1 and Time 2 was calculated for patients who reported ‘no change’ compared with 3-5 days ago. Results A total of 946 patients returned complete responses at Time 1 (Time 2: 447 responses). They were from UK, n = 743 (78.5%); USA, n = 139 (14.7%); Australia, n = 59 (6.2%). Their mean age was 57.6 (SD = 13.6); 833 (88%) were women. They were treated for inflammatory arthritis (n = 194), connective tissue disease and/or vasculitis (n = 398), and giant cell arteritis and/or polymyalgia rheumatica (n = 341). A total of 25 items were removed due to floor effects and lack of fit to the Rasch model. The remaining 15 items showed a satisfactory fit to the model. EFA suggested a scale structure with four domains: Participation (4 items), Appearance (3 items), Psychological (5 items), and Treatment concerns (3 items). This 4-domain structure was supported by the Rasch model, confirming construct validity; χ2=47.82 (DF = 36), p = 0.899; and reliability (Person Separation Index, PSI=0.757). Patients on a lower glucocorticoid dose had lower Steroid-PRO domain scores than those receiving higher dose (discriminant validity). ICC between Time 1 and Time 2 ranged from 0.892 to 0.942 (95%CI 0.868 to 0.953) suggesting excellent (test-retest) reliability. Conclusion The final Steroid-PRO is a 15-item, valid and reliable 4-domain scale measuring the impact of glucocorticoid therapy on HRQoL of people with rheumatic diseases. Disclosure S. Bridgewater: Grants/research support; S.B. has received funding for research from Vifor Pharma. M. Ndosi: Grants/research support; M.N. has received funding for research from Vifor Pharma. J. Dawson: None. P. Richards: None. C. Silverthorne: None. E. Dures: Grants/research support; E.D. has received funding for research from Vifor Pharma. S. Goodman: Consultancies; S.G. reports consultancy for UCB. Grants/research support; S.G. has received research support from Novartis. Other; S.G. has given talks for NYU, Case Western, ACR Rheumatology Courses. C. Hill: None. S.L. Mackie: Consultancies; S.L.M. has provided consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca. Grants/research support; S.L.M. has been an investigator on clinical trials for Sanofi and GSK, as a research grant co-applicant, S.L.M. has received research funding (partial salary support) from Vifor, paid to her institution. Other; S.L.M. has given talks on behalf of her institution for Pfizer, Vifor and UCB. In all cases fees were paid to her institution and no personal fees were received, S.L.M. was supported by Roche to attend EULAR2019 and by Pfizer to attend ACR2021 virtually. J.C. Robson: Consultancies; J.C.R. reports: Consultancy for Vifor Pharma. Grants/research support; Funding for research from Vifor Pharma. Other; Speaking fees from Vifor Pharma.

OA34 To determine the diagnostic test accuracy of different ultrasound diagnostic criteria in the diagnosis of giant cell arteritis: a secondary data analysis

Abstract Background/Aims To determine the diagnostic test accuracy of compression ultrasound compared to combined compression and halo techniques in the diagnosis of giant cell arteritis. Methods A retrospective secondary data analysis was conducted of 111 consecutive patients referred with suspected giant cell arteritis (GCA). All patients had an ultrasound of superficial temporal arteries using halo and compression techniques. All had a temporal artery biopsy (TAB), directed by clinical suspicion. Diagnosis was confirmed at six months based on clinical diagnosis. Exclusion criteria included flare, or relapsing patients. Two by two frequency tables were used to calculate sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios of compression and combined halo and compression in comparison to TAB results and clinical diagnosis at six months. Multiple logistic regressions were calculated adjusting for the identified confounders of gender, steroid dose at time of ultrasound and ischemic symptoms of jaw claudication, transient or permanent vision loss. Local NHS Trust Caldicott approval was given for this study. Results Of the 111 patients referred, 56 were clinically diagnosed with GCA. A positive TAB result was recorded in 33. Compression ultrasound had a high sensitivity of 90.6 % (95%CI 75.0, 98.0) but a low specificity of 32.9 % (95% CI 22.8, 44.4) when compared to TAB. Compression had a sensitivity of 83.6% (95% CI 71.2, 92.2) and specificity 34.5% (95% CI 22.2, 48.6) when compared to clinical diagnosis. This is in contrast to compression and halo combined, which had a sensitivity of 71.9% (95% CI 53.3, 86.3) when compared to TAB and 56.4 % (95% CI 42.3.69.7) when compared to clinical diagnosis. However, specificity of the combined techniques was much higher (73.4% [95% CI 62.3, 82.7] and 76.4% [95% CI 62.3, 86.38]) when compared to TAB and clinical diagnosis respectively. A summary of results can be seen in Table 1. Conclusion Compression ultrasound has a high sensitivity; this coupled with the relatively high negative predictive value suggests compression ultrasound may be useful in screening and stratification of patient management. The perceived ease of compression ultrasound suggests further evaluation of compression ultrasound in clinical practice is required. Disclosure K. Smith: Grants/research support; HEE/NIHR Pre-doctoral clinical academic fellowship. B. Sarker: None. J. Lim: None. C. Burnett: None. D. Taze: None. A. Chakrabarty: None. R.J. Wakefield: None. S.L. Mackie: Consultancies; SLM has provided consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie and AstraZeneca. Honoraria; SLM has given talks on behalf of her institution for Pfizer, Vifor and UCB. In all cases fees were paid to her institution and no personal fees were received. Grants/research support; SLM has been an investigator on clinical trials for Sanofi and GSK. As a research grant co-applicant, SLM has received research funding (partial salary support) from Vifor, paid to her institution.

P203 Comparison of coding of giant cell arteritis in primary and secondary care records: an observational feasibility study

Abstract Background/Aims Giant cell arteritis (GCA) is considered a medical emergency, and relapses are common, affecting around 50% of patients. Many of the early symptoms of GCA are non-specific and highly prevalent in older people, making the diagnosis challenging. The Clinical Practice Research Datalink (CPRD) is a large primary care database that provides the opportunity to study large numbers of people with GCA. General practitioners commonly identify suspected GCA and refer patients to secondary care for specialist evaluation and diagnostic confirmation. We sought to understand how primary and secondary care records correspond. Methods A retrospective observational study was undertaken using data from 2003 to 2020 by linking CPRD Aurum to Hospital Episode Statistics (HES) Admitted Patient Care (APC) and Outpatient (OP) data. We included all permanently registered patients aged 50 years and over in CPRD Aurum who could be linked to HES datasets. We identified individuals with a SNOMED code for GCA in CPRD Aurum and compared them to a list of patients who received an ICD-10 code for GCA in HES APC and OP datasets. We then restricted our comparison to the time-periods 90 and 180 days before or after the first record of GCA in the CPRD Aurum dataset (index code). Results We identified 18,806 individuals with a SNOMED code for GCA in the CPRD Aurum dataset between 2003 and 2020. 9755 (51.87%) of these individuals also received at least one secondary care code for GCA in the HES APC and OP data. 3914 (20.86%) and 4573 (24.37%) individuals received at least one secondary care code for GCA within 90 and 180 days, respectively, of the index primary care code. 7520 (58.96%) of those with two codes in primary care also had at least one code in secondary care, and 6090 (61.09%) of those with three codes. Conclusion Approximately one-half of individuals with an index code in primary care had a secondary care code for GCA. However, less than a quarter of patients had secondary care codes within 90 and 180 days of their index code in primary care. Given that it is unlikely that coding in either primary or secondary care is inaccurate, we conclude that this method of comparing GCA diagnoses is not a suitable approach to assess the accuracy of primary care coding. Further research could explore alternative approaches to understanding the quality of the coding of GCA in primary and secondary care data. Disclosure N. Padmanabhan: Other; NP is an NIHR Academic Clinical Fellow. S. Muller: Other; SM is part-funded by the NIHR Applied Research Collaboration West Midlands (ARC WM). J. Bailey: None. T. Helliwell: None. S.L. Mackie: Consultancies; SLM has provided consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie and AstraZeneca. Other; SLM has given talks on behalf of her institution for Pfizer, Vifor and UCB. In all cases fees were paid to her institution and no personal fees were received, SLM was supported by Roche to attend EULAR2019 and by Pfizer to attend ACR2021 virtually, SLM has been an investigator on clinical trials for Sanofi and GSK. As a research grant co-applicant, SLM has received research funding (partial salary support) from Vifor, paid to her institution. C.D. Mallen: Other; CDM is funded by the NIHR School for Primary Care Research and the NIHR Applied Research Collaboration West Midlands (ARC WM). E. Roddy: None.

Axial Postural Abnormalities in Parkinsonism: Gaps in Predictors, Pathophysiology, and Management.

Axial Postural Abnormalities in Parkinsonism: Gaps in Predictors, Pathophysiology, and Management.

Zanubrutinib, Alone and in Combination With Tislelizumab, for the Treatment of Richter Transformation of Chronic Lymphocytic Leukemia.

Zanubrutinib, Alone and in Combination With Tislelizumab, for the Treatment of Richter Transformation of Chronic Lymphocytic Leukemia.

Prolonged oral corticosteroid treatment in patients with systemic lupus erythematosus: An evaluation of 12-month economic and clinical burden.

BACKGROUND: Prolonged, high-dose corticosteroid treatment for systemic lupus erythematosus (SLE) is associated with substantial health care costs, health care resource utilization (HCRU), and adverse events (AEs). OBJECTIVE: To compare all-cause health care costs, HCRU, and oral corticosteroid (OCS)-related AEs among patients with prevalent OCS use and patients without OCS use. METHODS: This retrospective, longitudinal cohort study (GSK study 214100) used claims data from the IQVIA Real-World Data Adjudicated Claims - US, IQVIA, Inc, database between January 1, 2006, and July 31, 2019, to identify patients with SLE. Patients with at least 1 OCS pharmacy claim during the study period and continuous OCS use during the 6-month pre-index (baseline) period (index date is the date of the first OCS claim following 6 months' continuous use) formed the "prevalent OCS use cohort." This cohort was subdivided based on the level of OCS exposure during the 12-month observation period, ie, the number of 6-month periods of greater than 5 mg/day OCS use (0, 1, or 2). Patients without OCS claims formed the "no OCS use cohort." All patients had continuous enrollment during the baseline and observation periods, had at least 1 inpatient or at least 2 outpatient SLE diagnosis codes during baseline, and were aged at least 5 years at index. A 2-part model, a generalized linear regression model with a negative binomial distribution, and a multivariate logistic regression model were used to compare health care costs, HCRU, and the odds of developing an OCS-related AE between cohorts, respectively. RESULTS: The no OCS use and prevalent OCS use cohorts included 21,517 and 16,209 patients, respectively. Adjusted health care cost differences (95% CI) were significantly lower for the no OCS use cohort vs all prevalent OCS use exposure categories ($5,439 [$4,537-$6,371] vs $17,856 [$16,368-$19,498]), driven by inpatient stays and outpatient visits; HCRU was also significantly lower (adjusted incidence rate ratios vs no OCS use cohort [95% CI]: 1.20 [1.16-1.23] vs 1.47 [1.41-1.52]). Health care costs and HCRU increased with increasing length of OCS exposure. OCS-related AEs occurred more frequently for all prevalent OCS use exposure categories vs the no OCS use cohort (odds ratio [95% CI]: 1.39 [1.25-1.55] vs 2.32 [2.02-2.68]), driven by hematologic/oncologic and immune system-related AEs. The mean (SD) average daily dose of OCS increased with increasing periods of prevalent OCS use (2.5 [1.3], 6.9 [31.1], and 34.6 [1,717.3] mg/day, respectively, for patients with 0, 1, and 2 periods of OCS use). CONCLUSIONS: Prevalent OCS use incurs a substantial clinical and economic burden, highlighting the need for restricted OCS doses and durations. DISCLOSURES: This study (GSK Study 214100) was funded by GSK. GSK was involved in designing the study, contributing to the collection, analysis, and interpretation of the data, supporting the authors in the development of the manuscript, and funding the medical writing assistance. All authors, including those employed by GSK, approved the content of the submitted manuscript and were involved in the decision to submit the manuscript for publication. Dr DerSarkissian, Dr Duh, and Mr Benson are employees of Analysis Group, which received research funding from GSK to conduct this study. Dr Wang, Ms Gu, and Mr Vu are former employees of Analysis Group. Mr Bell is an employee of GSK and holds stocks and shares in the company. Ms Averell and Dr Huang are former employees of GSK and held stocks and shares in the company at the time of the study.

Lecanamab Ushers in a New Era of Anti-Amyloid Therapy for Alzheimer's Disease.

Erik S. Musiek has received research funding from Eisai Pharmaceuticals for preclinical work on sleep that is unrelated to lecanemab or any other antibody therapy, and was approved through a sponsored research agreement with Washington University. Erik S. Musiek has received no personal income related to this topic and has no financial stake in these companies. Eric McDade receives research funding from Eisai Pharmaceuticals for Clinical Trials in the Dominantly Inherited Alzheimer Network Trials Unit testing lecanemab and E2814; he has co-authored a recent publication with Eisai employees based on lecanemab phase II data and has presented data from the phase II studies at a scientific conference. Eric McDade has received research funding form Eli Lilly and Roche-Genentech for Clinical Trials in the Dominantly Inherited Alzheimer Network Trials Unit testing solanezumab and gantenerumab. He has received no personal income related to these activities and has no financial stake in these companies. David M. Holtzman is on the scientific advisory board of C2N diagnostics and has equity. David M. Holtzman is on the scientific advisory board of Denali Therapeutics, Genentech, and Cajal Therapeutics, and consults for Alector.

A112 MEASURING COLORECTAL POLYP SIZE USING A NOVEL VIRTUAL SCALE FUNCTION DURING ENDOSCOPIES: A CLINICAL PILOT STUDY

Abstract Background Although accurate polyp size measurement is essential for adequately managing patients, we still rely on the endoscopists' subjective visual estimation of polyp size in routine practice. Purpose We therefore conducted a clinical pilot study to evaluate relative accuracy of measuring colorectal polyp size during live colonoscopies using a novel virtual scale endoscope (VSE) that superimposes a virtual linear or circular ruler onto objects in the endoscopist's field of view. Method We conducted a pilot phase 1 study to evaluate the relative accuracy of VSE for polyp size measurement. We measured polyp size from fresh polypectomy specimens before formalin fixation using a digital vernier caliper. These reference measurements were compared to visual size estimations and VSE measurements obtained during live colonoscopies. The primary outcome was the relative accuracy of visual size estimation versus size estimation using VSE. The secondary outcome was the percentage of measurements that fall within 25% of true polyp size. Result(s) 43 patients (mean age: 63.3 years; 44.2% male) undergoing screening, surveillance, or diagnostic colonoscopies were included in the pilot study. Colonoscopies were performed by two endoscopists, including one trainee and one staff gastroenterologist. Visual, VSE, and reference size measurements was performed for 17 polyps. VSE during live colonoscopies had a higher relative accuracy of polyp size measurements when compared with visual polyp size estimation 84.3% (95% confidence interval (CI) 77.22% to 91.41%) vs 69.3% (95%CI 61.13% to 77.39%) (p=0.005). The percentage of size measurements that were within 25% of sizes as measured by caliper were 41.2% for visual polyp size estimation and 88.2% for VSE (p=0.02). Conclusion(s) We found that a novel endoscope equipped with a virtual scale allowed for significantly higher accuracy in polyp size measurement. A prospective randomized controlled trial is currently underway to validate these results. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding below: Fujifilm Disclosure of Interest R. Djinbachian: None Declared, M. Zarandi-Nowroozi: None Declared, M. Taghiakbari: None Declared, D. von Renteln Grant / Research support from: Daniel von Renteln is supported by a “Fonds de Recherche du Québec Santé” (FRQS) career development award and has received research funding from ERBE, Ventage, Pendopharm, Fujifilm, and Pentax., Consultant of: Boston Scientific and Pendopharm,

Respiratory Rate as a Factor in Lung Injury-Not Just What You Set, but How You Set.

Respiratory Rate as a Factor in Lung Injury-Not Just What You Set, but How You Set.

A232 RISK OF TOTAL METACHRONOUS ADVANCED NEOPLASIA AT SURVEILLANCE COLONOSCOPY AFTER DETECTION OF SERRATED LESIONS: A MATCHED COHORT STUDY

Abstract Background Serrated lesions (SLs), including sessile serrated lesions (SSL) and traditional serrated adenomas (TSA) have become subject of increased interest for their role as CRC precursors. Purpose Study aim was to evaluate the risk to develop total metachronous advanced neoplasia (T-MAN) at follow-up in patients with index SL compared to a matched cohort without SL. Method Patients 45-74y with SLs were identified through pathology database search. SL patients were matched 2:1 by sex; age; synchronous polyps (high-risk adenoma [HRA], low-risk adenoma [LRA], no-adenoma); timing of index, to patients without SL. Primary outcome was risk of T-MAN (advanced adenoma or high-risk SL) at follow-up. Secondary outcomes included risk of T-MAN stratified by synchronous polyps and SL characteristics. Result(s) 1425 patients were included (475 patients, 642 SLs; 950 controls (mean follow-up 2.9 vs 3.9y). The SL group had greater risk of T-MAN compared to the non-SL group [Hazard-ratio (HR)=6.12 (95%confidence-interval (CI)3.91-9.58)]. Patients with SL+HRA had higher risk of T-MAN compared to HRA alone [HR=2.62 (95%CI 1.45-4.71)], as well as patients with SL+LRA compared to LRA alone [HR=7.03 (95%CI 2.78-18.44)], and SL without adenoma compared to no-adenoma [HR=14.87 (95%CI 6.51-33.95)]. Presence of proximal SSL (HR=9.30), large SSL (HR=17.87) and proximal large SSL (HR=24.99), but not distal SSL, was associated with greater risk for T-MAN. Conclusion(s) Patients with SLs are at greater risk for developing T-MAN regardless of synchronous adenomas. Patients with SL and HRA, and those with large or proximal SSLs appear to be at greatest risk for T-MAN. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; ACG Disclosure of Interest R. Djinbachian Grant / Research support from: Grant from the American College of Gastroenterology for the conduction of this project, M.-L. Lafontaine: None Declared, J. Anderson: None Declared, H. Pohl: None Declared, T. Dufault: None Declared, M. Boivin: None Declared, M. Bouin: None Declared, D. von Renteln Grant / Research support from: Daniel von Renteln is supported by a “Fonds de Recherche du Québec Santé” (FRQS) career development award and has received research funding from ERBE, Ventage, Pendopharm, Fujifilm, and Pentax., Consultant of: Boston Scientific and Pendopharm,

A123 COMPARING SIZE MEASUREMENT OF SIMULATED COLORECTAL POLYPS WHEN USING A NOVEL VIRTUAL SCALE ENDOSCOPE, ENDOSCOPIC RULER OR FORCEPS: A BLINDED RANDOMIZED TRIAL

Abstract Background Accurate polyp size measurement is important for guideline conforming choice of polypectomy techniques and subsequent surveillance interval assignments. Some endoscopic tools (forceps or endoscopic rulers [ER]) exist to help with visual size estimation. A virtual scale endoscope (VSE) has been developed that allows superimposing a virtual measurement scale during live endoscopies. Purpose Our aim was to evaluate the performance of VSE when compared to ER and forceps-based measurement. Method We conducted a randomized trial to evaluate the relative accuracy of size measurement of simulated colorectal polyps when using: VSE, ER, and forceps. Six endoscopists performed 60 measurements randomized at a 1:1:1 ratio using each method. Primary outcome was relative accuracy in polyp size measurement. Secondary outcomes included misclassification of sizes at the 5, 10, and 20mm thresholds. Result(s) A total of 360 measurements were performed. The relative accuracy of biopsy forceps, ER, and VSE was 78.9% (95%CI=76.2-81.5), 78.4% (95%CI=76.0-80.8), and 82.7% (95%CI=80.8-84.8). VSE had significantly higher accuracy compared to biopsy forceps (p=0.02) and ER (p=0.006). VSE misclassified a lower percentage of polyps &amp;gt;5mm as ≤5mm (9.4%) compared to forceps (15.7%) and ER (20.9%). VSE misclassified a lower percentage of ≥20mm polyps as &amp;lt;20mm (8.3%) compared with forceps (66.7%) and ER (75.0%). 25.6%, 25.5%, and 22.5% of polyps ≥10mm were misclassified as &amp;lt;10mm with ER, forceps, and VSE, respectively. Conclusion(s) VSE had significantly higher relative accuracy in measuring polyps compared to ER or forceps assisted measurement. VSE improves correct classification of polyps at clinically important size thresholds. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest R. Djinbachian: None Declared, M. Taghiakbari: None Declared, C. Haumesser: None Declared, M. Zarandi-Nowroozi: None Declared, M. Abou-Khalil: None Declared, S. Sidani: None Declared, J. Liu: None Declared, B. Panzini: None Declared, D. von Renteln Grant / Research support from: Daniel von Renteln is supported by a “Fonds de Recherche du Québec Santé” (FRQS) career development award and has received research funding from ERBE, Ventage, Pendopharm, Fujifilm, and Pentax., Consultant of: Boston Scientific and Pendopharm,

Suggestions for Canada’s Opioid Use Disorder Management Guidelines

1Centre for Addiction and Mental Health, Toronto, ON, Canada 2Department of Psychiatry, University of Toronto, Toronto, ON, Canada Corresponding Author: Robert A. Kleinman, MD, 100 Stokes Street, 3rd Floor, Toronto, ON, Canada, M6J 1H4. Tel: 416-535-8501; fax: 416-595-6821. E-mail: [email protected] Dr. R.A.K. has received research funding through the Centre for Addiction and Mental Health Discovery Fund and research funding and training support through the Research in Addiction Medicine Scholars Program, R25DAO33211 (NIDA) and travel awards from the American Psychiatric Association and American Academy of Addiction Psychiatry. Dr R.A.K. has been invited to take part in the review of the upcoming CRISM National Guideline for Clinical Management of OUD when they become available in 2023 as part of the panel of reviewers from Ontario but has not had any further involvement in the review or other aspects of the project.

Non-invasive neurostimulation in OCD – implications for widescale application.

AbstractBrain-imaging findings implicate aberrant cortico-striatal neurocircuitry in the underlying pathology of OCD, so representing a potential treatment target. Ablative neurosurgery or deep brain (invasive) stimulation (DBS) of tracts or nodes within this circuitry is sometimes found to improve OCD, possibly by enhancing information-processing functions. Non-invasive neurostimulation, targeting superficial cortical nodes within cortico-striatal circuitry, is a safer and more acceptable alternative, with potential for scaling up and applying to a larger patient population, earlier in the course of illness.Repetitive transcranial magnetic stimulation (rTMS) is the form of neuromodulation studied most in OCD. The orbitofrontal cortex (OFC), dorsolateral prefrontal cortex and supplementary motor area (SMA) have been identified as promising targets. The effect is larger for those not resistant to SSRI or failing to respond to only one SSRI trial. Thus, r-TMS may be best implemented earlier in the care pathway. rTMS is also relatively costly, involves specialist technical equipment and staff, and cannot be delivered in patients’ homes.Transcranial direct current stimulation (tDCS) involves applying a low-amplitude (1-3mA) electric current to the brain via electrodes placed on the scalp. Compared with rTMS, tDCS tends to electrically modulate a more diffuse and superficial brain area, but it could represent a preferable option for patients with common mental disorders such as OCD, as it is cheaper, portable, simple and safe to use. In a recent randomised controlled feasibility study, the L-OFC represented the optimal target based on clinical changes. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol, longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, home-based approaches represent a rational next step.Disclosure of InterestN. Fineberg Grant / Research support from: In the past three years I have received research funding from the NIHR, COST and Orchard; . I have additionally received financial support to attend meetings from the British Association for Psychopharmacology, European College for Neuropsychopharmacology, Royal College of Psychiatrists, International College for Neuropsychopharmacology, World Psychiatric Association, International Forum for Mood and Anxiety Disorders, American College for Neuropsychopharmacology. In the past I have received funding from various pharmaceutical companies for research into the role of SSRIs and other forms of medication as treatments for OCD., Consultant of: payment for expert advisory work on psychopharmacology for the Medicines and Healthcare Products Regulatory Agency, royalties from Oxford University Press and an honorarium from Elsevier for editorial work., Paid Instructor of: payment for lectures for the Global Mental Health Academy.

Prognostic implications of high-sensitivity cardiac troponin in patients with suspected myocardial infarction with or without psoriasis

Prognostic implications of high-sensitivity cardiac troponin in patients with suspected myocardial infarction with or without psoriasis