Received Speaker Fees Research Articles

Intracytoplasmic sperm injection versus conventional in vitro fertilization in infertile couples with normal total sperm count and motility: does sperm morphology matter?

Among couples with infertility and normal total sperm count and motility, can sperm morphology be used as a biomarker to identify couples who benefit more from ICSI over conventional IVF (c-IVF) on fertility outcomes? Based on this secondary analysis of a large randomized clinical trial (RCT), sperm morphology has limited value as a biomarker to identify couples who benefit more from ICSI over c-IVF on live birth, ongoing pregnancy, clinical pregnancy or total fertilization failure. Our recent RCT showed that ICSI did not result in higher live birth rates in couples with normal total sperm count and motility. It is unclear whether sperm morphology can be used as a biomarker to identify couples who benefit more from ICSI over c-IVF in this population. This was a secondary analysis of an open-label, multi-centre, RCT comparing ICSI versus c-IVF in 1064 couples with infertility and normal total sperm count and motility. In this secondary study, we evaluated the effectiveness of ICSI over c-IVF in relation to sperm morphology. Couples were eligible if they had ≤2 previous IVF/ICSI attempts, and the male partner had normal total sperm count and motility according to the fifth edition of the WHO laboratory manual for the examination and processing of human semen. Sperm morphology was measured from samples obtained during the first consultation and data for sperm morphology were available in partners of all participants in this trial. The outcomes of interest were live birth, ongoing pregnancy, clinical pregnancy, and total fertilization failure. We first conducted a logistic regression analysis with an interaction term (sperm morphology as a continuous variable by treatment (ICSI versus c-IVF)) on the four outcomes. We also used restricted cubic spline analysis to evaluate non-linear interaction and plotted the treatment effects of ICSI over c-IVF at different sperm morphology levels and the predicted probability of these outcomes in both ICSI and c-IVF groups. The median proportion of sperm with normal morphology in both groups was 3% (Interquartile range 1-6%). Live birth rates were (184/532) 34.6% for ICSI versus (166/532) 31.2% for c-IVF. No significant interaction was found between sperm morphology and treatment effect of ICSI versus c-IVF on the rates of live birth, ongoing pregnancy, clinical pregnancy, and total fertilization failure (P = 0.181, 0.153, 0.168, and 0.788 respectively). In the analyses using restricted cubic splines, no evidence of interaction between sperm morphology and the treatment effect was found. Interaction figures showed that the treatment effect of ICSI over c-IVF at different sperm morphology levels was fluctuating around no effect line, and the predicted outcomes for the two groups were mostly overlapping at different sperm morphology levels. This secondary analysis may be underpowered to detect a difference in treatment effects at different sperm morphology levels due to relatively small number of events at some sperm morphology levels. Moreover, sperm morphology assessment was performed during the first consultation, rather than on the day of randomization. In couples with infertility and normal total sperm count and motility, sperm morphology has a limited role as a biomarker to identify couples who benefit more from ICSI over c-IVF on fertility outcomes. This study was funded by My Duc Hospital, Ho Chi Minh City, Vietnam. RW was supported by an NHMRC EL Investigator Grant (GNT2009767). LNV has received speaker and conference fees from Merck, grant, speaker, conference fees from Merck Sharpe and Dohme, and speaker, conference, and scientific board fees from Ferring. TMH has received speaker fees from Merck, Merck Sharp Dohme, and Ferring. BWM reports consultancy, travel support and research funding from Merck and consultancy for Organon and Norgine. BWM holds stock from ObsEva. NCT03428919.

P069 Moving more with Axial Spondyloarthritis - a short survey to help design future exercise studies

Abstract Background/Aims Axial Spondyloarthritis (AxSpA) is an inflammatory arthritis affecting 0.5-1.0% of people in the UK. Physical activity guidance for people living with AxSpA from the National Institute for Health and Care Excellence is vague. Individualised, structured aerobic exercise is recommended without any direction towards exercise type, frequency, intensity, or acknowledgement of physical limitations to an individual’s environment which may prevent exercise participation. Consequently, the proportion of people with AxSpA meeting the World Health Organisation physical activity recommendations (>150 minutes of moderate-intensity exercise per week) is significantly lower than the general population. Therefore, a short survey was administered to people with AxSpA to understand types of physical activities they would like to participate in, and any common barriers to exercise participation. Methods The National Axial Spondyloarthritis Society (NASS) invited subscribers to their e-newsletter with lived experience to complete a short online survey. Respondents were asked ‘which of the following activities would you like to include as part of your usual lifestyle?’ ‘What would prevent you from taking part in the activities above?’ and ‘Do you already include any of the physical activities in your usual lifestyle?’ Respondents were allowed to choose multiple options from a range of activities and barriers. Results 266 people living with AxSpA (68% women, 31% men, 1% non-binary, 94% white British/Irish) responded. Walking was most selected for activities respondents would like to be included as part of their lifestyle (83%), followed by stretching/flexibility exercises (61%), swimming (46%), weight training and resistance exercise (41%), and cycling (33%). Only eight respondents (3%) stated hydrotherapy which is traditionally advocated as exercise therapy in AxSpA. Worries about pain and flare ups (57%), fatigue (45%), time (39%), cost (27%), not knowing enough about how much activity to do (22%), and lack of available facilities (20%) were common barriers. Conclusion To maximise reach and benefit, exercise guidance needs to relate to exercise that people with AxSpA would like to or already do; the benefits of exercise can only be realised if people want to participate. The responses emphasise the need for guidance relating to inclusive models of exercise. This includes exercise such as walking that is flexible and adaptable to limitations of time and does not require additional cost, equipment, or facilities. The results also highlight the importance of including outcome assessments of pain, flare frequency, and fatigue. Disclosure M. Roberts: None. S. Qooja: None. A. Moorthy: Consultancies; AM has received speaker fees from Lilly, Novartis, Galapagos, and UCB. L. Bishop: Grants/research support; NCB has received funding from NASS..

Sugammadex Use for Reversal in Nonobstetric Surgery During Pregnancy: A Reexamination of the Evidence.

Sugammadex Use for Reversal in Nonobstetric Surgery During Pregnancy: A Reexamination of the Evidence.

P071 Exercise as an anti-inflammatory treatment in axial spondyloarthritis (axSpA): a proof-of-concept study

Abstract Background/Aims Axial spondyloarthritis (axSpA) is an inflammatory arthritis affecting 0.5-1.0% of people in the UK. The inflammatory profile with axSpA causes pain and loss of mobility but can also contribute to other manifestations such as cardiovascular disease (CVD). Current management of axSpA relies on biologic medication; however, they are expensive, and effectiveness is influenced by disease duration, baseline inflammation and age. Monocytes, a type of white blood cell, express the cell surface markers CD14 ++CD16- (classical), CD14 ++CD16 + (intermediate), and CD14+CD16 ++ (non-classical). CD16+ monocytes are pro-inflammatory and are elevated in populations with CVD. Importantly, regular exercise reduces the relative proportion of CD16+ cells in other populations, but this is unknown in axSpA. Therefore, the present randomised control trial investigated whether exercise reduced the relative percentage of CD16+ monocytes in response to 12-weeks of home-based walking. Subjective measures of disease activity, physical function, spinal pain, and work productivity are included to supplement the findings. Methods 20 participants (10 control, 10 exercise; 8 vs 7 presented here due to ongoing data collection) were recruited, provided written informed consent, and completed baseline assessments before being assigned into a control or exercise group. The control group carried on as normal. The exercise group completed 5 x 30-minute bouts of ‘somewhat hard’ walking per week which was confirmed via heart rate monitoring and a rating of perceived exertion scale. At baseline (week 0) and follow-up (week 12), participants completed questionnaires to assess BASDAI, BASFI, ASAS-HI, WPAI, and spinal pain. Blood samples were also collected for the analysis of monocyte subsets. Data were analysed using a two-way mixed analysis of variance (ANOVA) with time as the within factor. Statistical significance was accepted as P < 0.05. However, description of trends is used throughout due to this being preliminary data with a small sample size. Results Group-by-time interactions revealed a significant reduction in the proportion of non-classical monocytes in the exercise group and an increase in the control group (P < 0.001). This coincided with a significant interaction for the proportion of less inflammatory classical monocytes, with an increase in the exercise group and decrease in the control group (P < 0.001). Overall, the exercise group also responded more favourably for BASDAI (P = 0.026) and spinal pain (P = 0.088) than the control group. Conclusion Preliminary findings suggest regular walking reduces pro-inflammatory immune cell populations in axSpA which coincides with favourable BASDAI and spinal pain responses compared to a control group. This highlights the importance of regular exercise to improve underlying inflammatory profiles in patients with axSpA. Disclosure M. Roberts: None. M. Hamrouni: None. V. Linsley: None. A. Moorthy: Consultancies; A.M has received speaker fees from Lilly, Novartis, Galapagos and UCB. Grants/research support; A.M has received funding from the National Axial Spondyloarthritis Society for this work. N. Bishop: Grants/research support; N.B has received funding from the National Axial Spondyloarthritis Society for this work.

E081 Effectiveness of intravenous belimumab in patients with systemic lupus erythematosus at a UK tertiary referral centre

Abstract Background/Aims Belimumab was approved in the United Kingdom (UK) in 2016 as add-on therapy for patients with auto-antibody positive systemic lupus erythematosus (SLE) and high disease activity refractory to standard treatment. Data regarding the effectiveness of belimumab outside clinical trials has been published in worldwide SLE cohorts but not the UK. Here, we describe the efficacy of add-on belimumab therapy in SLE patients from a large London tertiary centre. Methods We performed a retrospective, intention-to-treat analysis of clinical and biochemical outcomes, at 6 and 12 months, post receipt of at least 1 infusion of belimumab in SLE patients attending Guy’s and St Thomas’ NHS Trust (April 2013-November 2021). Outcomes assessed included: the Safety of Estrogen in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), anti-dsDNA ELISA titre, complement C3 and C4 titres, urine protein:creatinine ratio (uPCR) and daily prednisolone dose. Analyses performed using SPSS statistics 27. Results 63 patients (56 female [88.9%], median age 38 years, self-reported race/ ethnicity; 24 Black [38.1%], 24 White [38.1%], 13 Asian [20.6%]) with SLE as defined by the 1997 ACR criteria were included. An 8-point reduction in median SELENA-SLEDAI was evident at 6 months after commencing belimumab, which increased to 9 points at 12 months (n = 28, p < 0.001)(Table 1). Improvements in C3/ C4 titres were also observed at 6 months (0.13-point and 0.04-point increase in median C3/ C4 titres respectively, n = 45, p < 0.001). At 12 months, significant reductions in median anti-dsDNA titre (16.50-point reduction, n = 42, p < 0.001) and median daily prednisolone dose were evident (2.50mg reduction, n = 51, p < 0.001). No change in uPCR was noted (n = 23, p = 0.956). 40/47 (85%) patients with a SELENA-SLEDAI score recorded at 6 months achieved the National Institute for Health and Care Excellence (NICE) defined target for a >/= 4-point reduction in SELENA-SLEDAI. No significant associations between baseline demographic variables and SELENA-SLEDAI score at 6 months, or prednisolone dose at 12 months, were evident. Conclusion We observed a significant improvement in SLE disease activity as determined by SELENA-SLEDAI score measured at 6 and 12 months after starting belimumab, and a significant steroid-sparing effect at 12 months. These findings are similar to published worldwide data. Disclosure G. Mallett: None. C. Hession: None. M. Fernando: Other; MF has received speaker fees from GlaxoSmithKline (GSK) and Union Chimique Belge (UCB), as well as conference fees from GSK.

P128 Long-term safety and efficacy of upadacitinib in patients with rheumatoid arthritis: final results from the BALANCE-EXTEND open-label extension study

Abstract Background/Aims Upadacitinib (UPA) was previously evaluated in two Phase 2, randomized, controlled trials (RCTs) in patients (pts) with rheumatoid arthritis (RA) and inadequate response to tumor necrosis factor inhibitors (BALANCE-1) or methotrexate (BALANCE-2). Objectives: To assess the final safety and efficacy of UPA in BALANCE-EXTEND, a 312-week open-label extension (OLE) enrolling pts who completed either BALANCE1 or BALANCE-2. Methods All pts initially received UPA 6 mg twice daily (BID). Increase to 12 mg BID was required for pts with <20% improvement in swollen or tender joint counts (S/TJC) at Week 6 or 12, and permitted for those not achieving Clinical Disease Activity Index (CDAI) low disease activity (LDA). Pts with <20% improvement in SJC or TJC 6 weeks after escalation, or at any two consecutive visits, discontinued. Return to 6 mg BID was permitted for safety or tolerability reasons. After January 2017, the 6 and 12 mg BID doses were replaced by 15 and 30 mg once-daily (QD) extended-release equivalents. As-observed efficacy data are shown at Week 312 for three subgroups: pts who received 6 mg BID/15 mg QD throughout (“Never titrated”), those titrated up to 12 mg BID/30 mg QD for efficacy (“Titrated up”), and those titrated up to 12 BID/30 mg QD and then back to 6 mg BID/15 mg QD due to safety concerns (“Titrated up and down”). Exposure-adjusted adverse events (EAERs) per 100 patient-years (PY) of exposure were summarized from OLE Day 1 in all pts who received UPA (Any UPA). Results Overall, 493 pts entered the OLE, receiving UPA for ≤6.2 years (Never titrated, n = 306; Titrated up, n = 149; Titrated up and down, n = 38), and 270 pts (54.8%) discontinued, mostly due to withdrawal of consent (16.8%; n = 83) or AEs (14.6%; n = 72). Mean (standard deviation) duration of UPA exposure was 3.8 (2.4) years (range <1-6.2 years); cumulative exposure was 1863 PY. The AE profile in pts receiving UPA 15 mg was generally similar to the Any UPA population, and to that observed in the Phase 3 UPA 15 mg clinical trial population. Efficacy was maintained to Week 312, with 84.5% and 86.6% of pts in the Never titrated group achieving DAS28-CRP ≤3.2 and CDAI LDA, respectively. Conclusion In this OLE, UPA treatment over ∼312 weeks showed sustained long-term efficacy in pts with RA who had completed Phase 2 RCTs. Overall safety results showed that UPA was well tolerated over time; the types and frequencies of AEs were consistent with those in pts with similar populations of moderately to severely active RA receiving Janus kinase inhibitors. Disclosure A. Kivitz: Consultancies; A Kivitz has received consulting fees and/or honoraria from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Flexion, Genzyme, Gilead, Horizon, Janssen, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sanofi Aventis, SUN Pharma Advanced Research, and UCB. Shareholder/stock ownership; A Kivitz owns stocks or options in Amgen, Gilead, GlaxoSmithKline, Novartis, Pfizer, and Sanofi. Honoraria; A Kivitz has received honoraria from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Flexion, Genzyme, Gilead, Horizon, Janssen, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sanofi Aventis, SUN Pharma Advanced Research, and UCB. Grants/research support; A Kivitz's institution received fees from AbbVie for his role as a Principal Investigator in the study. A.F. Wells: Consultancies; AF Wells has received consulting fees from AbbVie. J.I. Vargas: Honoraria; JI Vargas has received honoraria from AbbVie. Grants/research support; JI Vargas has received fees from AbbVie as Principal Investigator in the study. H.S.B. Baraf: Consultancies; HSB Baraf has acted as a consultant for Gilead and Janssen. Grants/research support; HSB Baraf has received grant/research support from AbbVie, Eli Lilly, Genentech, Gilead, and Janssen. M. Rischmueller: Consultancies; M Rischmueller has acted as a consultant for AbbVie, Bristol-Myers Squibb, CSL Behring, Eli Lilly, Gilead Sciences, Janssen Global Services, Pfizer, Sanofi US Services, and UCB Biosciences. Grants/research support; M Rischmueller has received grant/research support from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen Global Services, Novartis, Pfizer, Sanofi Pasteur Biologics, and UCB Biosciences. J. Klaff: Shareholder/stock ownership; J Klaff is employee of AbbVie and may own stocks or options. N. Khan: Shareholder/stock ownership; N Khan is an employee of AbbVie and may own stocks or options. Y. Li: Shareholder/stock ownership; Yihan Li is an employee of AbbVie and may own stocks and options. K. Carter: Shareholder/stock ownership; K Carter is an employee of AbbVie and may own stocks and options. A. Friedman: Shareholder/stock ownership; A Friedman is an employee of AbbVie and may own stocks and options. P. Durez: Corporate appointments; P Durez has received speaker fees from Eli Lilly and Galapagos.

P073 Comparative effectiveness of different exercise interventions on central sensitisation indices in humans: A systematic review and network meta-analysis

Abstract Background/Aims Exercise has shown a promising effect in reducing central sensitisation (CS), but it is unknown which exercise type is the most effective. This review aimed to rank and compare the effectiveness of different exercise interventions on CS in people with or without chronic musculoskeletal pain. This will help to identify the optimal exercise intervention to improve pain by reducing CS for subsequent use in clinical trials. Methods We searched MEDLINE, EMBASE, AMED, CINAHL, SPORTDiscus, CENTRAL, PEdro, SCOPUS, as well as references cited in the selected papers, and grey literature from inception to February 2022. We included randomized controlled trials (RCTs) that assessed the effect of exercise interventions on CS indices in humans. RCTs where a specific effect of exercise could not be determined were excluded. Pairwise and network meta-analyses (frequentist and Bayesian) were conducted using random effects models. Effect sizes were calculated using standardized mean difference (SMD). P-score as well as SUCRA score were used to rank the exercise interventions (from best to worst) in both frequentist and Bayesian approaches, respectively. Results The search returned 93,657 records, of which 143 RCTs (5,362 participants [4890 participants had musculoskeletal pain (122 studies), and 427 were pain free (21 studies)]) were eligible. Firstly, we performed the pairwise meta-analysis to examine the effect of all exercise interventions on all CS outcomes. It showed moderate improvement of CS outcomes (SMD - 0.77, 95% confidence interval (95%CI) -0.89 to -0.65, I2 = 87%, p < 0.01). After that, 80 RCTs were included in the network meta-analysis (NMA) using inactive controls as a common comparator. In terms of efficacy at improving indices of CS, all exercise interventions were more effective than control. Combined strengthening and stretching exercise exhibited the highest probability to be the optimal intervention reducing CS (P-score: 0.8896, SUCRA score: 0.8719, SMD= -2.02, 95%CI: -2.83: -1.20), followed by strengthening, stretching and aerobic combination (P-score: 0.8557, SUCRA score: 0.8517, SMD = -1.92, 95%CI: -2.90: -0.95), and stretching with aerobic exercise (P-score: 0.7794, SUCRA score: 0.7198, SMD = -1.70, 95%CI: -2.79: -0.62). However, differences between these three interventions’ effect sizes were small, and 95% CI were overlapping. Other interventions included, mind body exercise, aerobic plus strengthening exercise, strengthening exercise, stretching exercise, aerobic exercise. Conclusion Our meta-analysis suggested that various exercise interventions are effective in improving CS. Multicomponent exercise tends to be the most effective, but some exercise combinations might be better than others. Strengthening and stretching combination shows the greatest likelihood among other combinations of being the optimal exercise type. These findings might have utility informing future treatment recommendations for people with CS features. However, Further research should be considered to explore cost-effectiveness of different interventions. Disclosure A.A. Abd Elkhabir: None. D.F. McWilliams: Grants/research support; grant support from Pfizer and Eli Lilly. S. Smith: None. W. Chaplin: None. M. Salimian: None. V. Georgopoulos: None. A. Kouraki: None. D.A. Walsh: Consultancies; Since 2015 DAW has undertaken consultancy through the University of Nottingham to AbbVie Ltd, Pfizer Ltd, Eli Lilly and Company, Love Productions,, Reckitt Benckiser Health Limited and GSK (each non-personal, pecuniary). Honoraria; He has contributed to educational materials through the University of Nottingham, supported by Medscape Education, New York,, International Association for the Study of Pain, and Osteoarthritis Research Society International (OARSI), each of which received financial support from commercial and non-commercial entities, (each non-personal, pecuniary).. Member of speakers’ bureau; He has received speaker fees from the Irish Society for Rheumatology (personal pecuniary).. Grants/research support; He has been responsible for research funded by Pfizer, Eli Lilly, UCB Pharma (non-personal, pecuniary). Other; He receives salary from the University of Nottingham, who have received funding for that purpose from Sherwood Forest Hospitals NHS Foundation Trust,, Nottingham University Hospitals NHS Trust and UKRI/Versus Arthritis (personal, pecuniary).

A66 PROTON PUMP INHIBITORS AND THE RISK OF INFLAMMATORY BOWEL DISEASE: A REAL WORLD POPULATION-BASED COHORT STUDY

Abstract Background Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are acid suppressant drugs indicated in highly prevalent conditions such as gastroesophageal reflux disease and peptic ulcer disease. A recent observational study reported an increased risk of inflammatory bowel disease (IBD) with the use of PPIs. However, this association may have been driven by certain methodological shortcomings, such as failure to properly account for protopathic bias, a conclusion-altering bias. Purpose To determine whether the use of PPIs compared with the use of H2RAs is associated with an increased risk of IBD. Method Using the longitudinal primary care records from the United Kingdom Clinical Practice Research Datalink database, we identified 1,498,416 initiators of PPIs and 322,474 initiators of H2RAs from January 1, 1990, through December 31, 2018, with follow-up until December 31, 2019. Standardized morbidity ratio weighted Cox proportional hazards models were used to estimate marginal hazard ratios (HRs) and 95% confidence intervals (CIs). Patients were analyzed according to the timing of the IBD events after treatment initiation (early versus late). In the early-event analysis, IBD events were assessed within the first two years of treatment initiation, an analysis subject to potential protopathic bias. In the late-event analysis, all exposures were lagged by two years to account for latency and minimize protopathic bias. Result(s) In the early-event analysis, the use of PPIs was associated with an increased risk of IBD within the first two years of treatment initiation, compared with H2RAs (HR: 1.39, 95% CI: 1.14-1.69). In contrast, the use of PPIs was not associated with an increased risk of IBD in the late-event analysis (HR: 1.05, 95% CI: 0.90 to 1.22). The results remained consistent in several sensitivity analyses. Image Conclusion(s) Compared with H2RAs, PPIs were not associated with an increased risk of IBD, after accounting for protopathic bias. Please acknowledge all funding agencies by checking the applicable boxes below CIHR Disclosure of Interest R. Yanofsky: None Declared, D. Abrahami Employee of: pfizer, R. Pradhan: None Declared, H. Yin: None Declared, E. McDonald: None Declared, A. Bitton Consultant of: Member of Advisory Boards for Abbie, Pfizer, Takeda, Jansen, and Merck, Speakers bureau of: Has received speaker fees for Abbie, Jansen, Takeda, and Pfizer, L. Azoulay Consultant of: Has received consults fees from Jansen, Pfizer, and Roche, Speakers bureau of: Has received speaker fees from Jansen, Pfizer, and Roche

Oxylipin Profiles during the First Day of Mechanical Ventilation in an Intensive Care Unit Cohort: Research Letter.

Lipid mediators derived from arachidonic acid and other precursor polyunsaturated fatty acids, collectively known as oxylipins, are metabolized along different distinct pathways and play important roles in the modulation of inflammation.1,2 Blood oxylipin profiles have been shown to correlate with the survival and development of acute respiratory distress syndrome in patients with sepsis or septic shock.3–5 We aimed to explore serum oxylipin profiles using liquid chromatography coupled to tandem mass spectrometry quantification as previously described6 during the first day of mechanical ventilation in the intensive care unit (ICU). Previously, we have noted elevated plasma concentrations of thromboxane B2, prostaglandin E2, 15-hydroxyeicosatetraenoate, and 11-hydroxyeicosatetraenoate in response to experimental hyperinflation lung injury7 in a large animal model. Based on this, we hypothesized that these metabolites would increase in response to mechanical ventilation in patients. Decreases in a subset of oxylipins have been observed, however, in relation to critical illness.8With ethical approval (Linköping, 2010/427-31 and 2018/16-32), all consecutive adult patients (n = 589) with indwelling arterial cannulas after admission to the ICU in Östersund Hospital, Sweden, between February 1, 2012, and January 31, 2013, were screened for inclusion in the study cohort unless transferred from another ICU.9 Blood samples were collected in EDTA tubes during 2012 and 2013. Within 30 min, the samples were spun for 10 min at 2,000g. The plasma was then frozen in aliquots to –70°C, then unfrozen, and analyzed in 2021. In the cohort,9 147 cases with complete data and samples were identified. Of these, 22 men and 3 women with mixed diagnoses were intubated and included in the study with case characteristics in Supplemental Table 1 (https://links.lww.com/ALN/D48). Samples were collected at the time of intubation and on the following morning.Of 67 oxylipins in the analysis panel, 57 were detected (fig. 1). Of these, 23 were above the limit of quantification in at least 80% of the samples, which was the predetermined limit for oxylipins to be included in formal analysis. The detected metabolites included all major metabolic pathways, cyclooxygenase, lipoxygenase, and cytochrome P450. Complete oxylipin analysis results are given in Supplemental Table 1 (https://links.lww.com/ALN/D48). None of the oxylipins was assumed to be normally distributed. After log transformation, 19 oxylipins were deemed to be normally distributed and were thus evaluated with paired Student’s t test and Hedges’ g. The remaining four oxylipins were compared using the Wilcoxon signed-rank test (table 1). Correction for multiple comparisons was performed with the false discovery rate set to 10% for α = 0.05, yielding a significance level at P < 0.001.For samples after up to 1 day of mechanical ventilation (after intubation), 12-hydroxyeicosatetraenoate showed significantly lower plasma concentrations, and no oxylipin increased (table 1).The current study supports decreased concentrations of 12-hydroxyeicosatetraenoate in response to mechanical ventilation in contrast to previous reports of 12-hydroxyeicosatetraenoate being considered a proinflammatory mediator.10 Thromboxane B2 and prostaglandin E2 were not among the oxylipins with sufficient detection frequencies for formal analysis. In contrast to the main hypothesis, 15-hydroxyeicosatetraenoate and 11-hydroxyeicosatetraenoate did not increase during the first day of mechanical ventilation.In conclusion, this study demonstrates that several oxylipins may be detected in intensive care patients and that plasma concentration of 12-hydroxyeicosatetraenoate decreases during the first day of mechanical ventilation in the ICU.This work was supported by the Swedish Research Council VR (2014–6354; Stockholm, Sweden), Marie Sklodowska Curie Actions, Cofund, Project INCA 600398 (European Union), Åke Wiberg’s Foundation (M17-0219; Stockholm, Sweden), research funding from Umeå University (Umeå, Sweden), and the ALF-LUA cooperative Region Västerbotten-Umeå University (Umeå, Sweden) intramural research funding system.Dr. Larsson has received speaker fees for lecturing in clinical symposia sponsored by Dräger Medical (Götesburg, Sweden), and not related to this specific topic. We do not consider this relevant to the report. The authors declare no other conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.Supplemental Digital Content, https://links.lww.com/ALN/D48

Factors associated to renin-angiotensin-aldosterone system inhibitors discontinuation or down-titration due to hyperkalaemia in patients with chronic cardiovascular conditions

Abstract Background/Introduction The renin-angiotensin-aldosterone system inhibitors (RAASI) are one of the keystones of the medical treatment in chronic cardiovascular disorders and have shown improvements in clinical outcomes in many clinical trials. Hyperkalaemia is a well-defined non-desirable effect of RAASI that occasionally forces to interrupt these medications. That enforced RAASI discontinuation or down-titration due to hyperkalaemia may have adverse prognostic consequences. Purpose Describe the demographical, clinical and pharmacological variables associated to a higher risk of RAASI discontinuation or down-titration due to hyperkalaemia among individuals with chronic cardiovascular conditions. Methods We used data from more than 375,000 individuals 55 years of age or older, included in the population-based healthcare database of a public Institute of Health between 2015 and 2017. We included participants with at least one relevant condition: chronic heart failure, chronic kidney disease, diabetes mellitus, ischemic heart disease or hypertension. They had to be under RAASI treatment as of January 1st, 2016, and with evidence of at least one episode of hyperkalaemia (serum potassium &amp;gt;5.0 mmol/L) during 2016. Then, were classified in one of the two following profiles: RAASI treatment discontinuation or down-titration versus RAASI treatment unchanged or up-titrated. For the statistical analysis, we used logistic regression to calculate the multivariable-adjusted odds ratios of each study variable, comparing RAASI discontinuation or down-titration group to RAASI treatment unchanged or up-titrated controls (reference group). Results In the multivariable-adjusted model, the risk of RAASI treatment discontinuation or down-titration due to hyperkalaemia was significantly associated with the use of RAASI, very high comorbidity index, potassium derangements (both hypokalaemia and hyperkalaemia), prior hospitalizations and prior emergency visits. Among RAASI treatments, the use of Angiotensin receptor blockers (OR 2.518, 95% CI 2.317–2.735) and Angiotensin-converting enzyme inhibitors (OR 2.341, 95% CI 2.149–2.549) were associated with a higher risk of RAASI discontinuation or down-titration due to hyperkalaemia than Aldosterone inhibitors (1.428, 95% CI 1.285–1.584). Conclusion These results suggest that vulnerable populations such as those with very high comorbidity index, potassium derangements or prior emergency visits or hospitalizations have a higher risk of RAASI treatment discontinuation or down-titration due to hyperkalaemia. A more careful and exhaustive management of RAASI should be advised in those patients. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Josep Comin-Colet has received speaker fees from Vifor Pharma.

Management of renin-angiotensin-aldosterone system inhibitors in patients with chronic cardiovascular conditions and its association with clinical outcomes

Abstract Background In chronic cardiovascular diseases, the renin-angiotensin-aldosterone system inhibitors (RAASI) are one of the keystones of the medical treatment and have revealed improvements in clinical outcomes in many clinical trials. In contrast, is well defined as non-desirable effect of RAASI the development of hyperkalemia, which could force to interrupt these treatments. Hyperkalemia has been associated with worse outcomes in observational studies. Though, it is controversial if those negative outcomes in hyperkalemic patients could be because the potassium derangement itself or the circumstance that in these individuals could be enforced to discontinue RAASI medications with prognostic consequences at mid- to long-term. Purpose Assess associations between management of RAASI and clinical outcomes among individuals with chronic cardiovascular conditions and hyperkalemia. Methods Data from more than 375,000 individuals 55 years of age or older were analyzed, in a population-based healthcare database of a public Institute of Health between 2015 and 2017. We conducted a longitudinal analysis, in which participants with at least one relevant condition were included: chronic heart failure, chronic kidney disease, diabetes mellitus, ischemic heart disease or hypertension. They had to be under RAASI treatment as of January 1st, 2016, and with evidence of at least one episode of hyperkalemia (serum potassium &amp;gt;5.0 mmol/L) during 2016. Then, were classified in one of the two following profiles: RAASI treatment discontinuation or down-titration versus RAASI treatment unchanged or up-titrated. Subsequently, all-cause death and hospitalization has been assessed in the follow-up period as clinical outcomes. For the statistical analysis, we calculated unadjusted incidence rate ratios and Cox Proportional Hazards Regression models to calculate the multivariable-adjusted risk ratios for the clinical endpoints comparing both groups. Results There was found an association with mortality and hospitalization for the RAASI treatment interruption/down-titration group when compared unadjusted incidence rate ratios of each clinical endpoints to RAASI treatment unchanged patients (reference group). We presented these results in a Kaplan-Meier survivor curves for endpoint mortality (Figure 1). In the multivariable-adjusted model, the risk of mortality and hospitalization was associated mainly with older age, hypokalemia and down-titration of RAASI treatments, achieving statistical significance (Table 1). The risk ratio for mortality associated with down-titration and with hyperkalemia compared with the reference group was 1.676 (95% CI 1.54–1.82) and 1.161 (95% CI 1.07–1.26) respectively. Conclusion These results suggest that the worse outcomes in hyperkalemia individuals could be influenced more for the discontinuation of RAASI prognostic drugs then for the hyperkalemia itself. It is necessary clinical randomized trials to confirm this observational hypothesis. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Josep Comin-Colet has received speaker fees from Vifor Pharma

Sleep disorders and increased risk of dementia.

Sleep disorders and increased risk of dementia.

The effectiveness and safety of mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines among individuals with chronic kidney diseases

The effectiveness and safety of mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines among individuals with chronic kidney diseases

Impact of invasive VNS on depression severity and the need of concomitant drug and neuromodulatory treatment dose

IntroductionInvasive vagus nerve stimulation (VNS) is an adjunctive long-term treatment option for chronic and recurrent difficult-to-treat depression (DTD).ObjectivesIn this prospective observational open-label case series we report on the effects of invasive VNS on depression severity, medication load and the need of maintenance electroconvulsive therapy (ECT) and esketamine treatment after 12 months.MethodsPatients were treated with invasive VNS according to clinical indication. All patients were included in the Restore-Life-Study. The assessment of depression severity (MADRS) and concomitant treatment was performed at baseline and in 3-months intervals postoperatively over a 12 months period.ResultsTwelve patients were treated with adjunctive VNS due to unipolar (n=10) and bipolar (n=2) depression. The majority of patients were female (n=9). The mean age at baseline was 53.8 years (range 38-66). Patients were severely affected by a variety of depression symptoms which was reflected in high MADRS Scores (median 29, mean 28) at baseline. All patients received at least 2 or more psychotropic drugs at baseline. After 12 months of VNS a clear reduction of MADRS Scores (41 % on average) was seen (12-months MADRS Score median 17, mean 18). After 12 months, one patient each was discontinued from maintenance ECT and esketamine, respectively. The median of drug load was reduced from 4,56 to 4,06 after 12 months.ConclusionsInvasive VNS is an effective treatment option in the long-term management of DTD to reduce the need of concomitant drug dose and maintenance treatment.DisclosureE Kavakbasi received speaker fees from Livanova. BT Baune received speaker and advisor fees from Livanova. The patients were included in the Restore-Life Study sponsored by LivaNova.

Antibody response to herpes simplex virus-1 is increased in autoimmune encephalitis.

Antibody response to herpes simplex virus-1 is increased in autoimmune encephalitis.

P265 Current UK wide use of the BASMI outcome measure in axial spondyloarthritis: an AStretch survey

Abstract Background/Aims The Bath Ankylosing Spondylitis Metrology Index (BASMI) is used in the monitoring of those living with axial spondyloarthritis (axSpA); it is the recommended and validated measure of movement in this patient group. As a physical outcome measure its use has been challenging during the COVID-19 pandemic. The aim of this project is to assess the current application of the BASMI in axSpA services across the UK. Methods A survey was devised to explore when the BASMI is used, by whom and the reasons for its use. The AStretch committee reviewed and re-drafted the questions. The survey was shared across multiple platforms and email professional distribution lists, and was open 2nd-12th October 2021. Results 74 UK healthcare professionals completed the survey. It is mostly physiotherapists who undertake the BASMI (69%); some other clinicians also measure: nurses (10%), medics (9%), physiotherapy support workers (10%), healthcare support workers (2%). Confidence in performing the BASMI averaged at 3.5/5. The majority of respondents record the BASMI in the electronic record (73%); app-based solutions are developing (7%) and paper-only recording diminishing (20%). When asked about frequency, most respondents (73%) recorded “it depends”, implying that the BASMI is used on an individual patient basis. Table 1 presents data with regards to why the BASMI is undertaken, scored by participant ranking, and free text responses about reasons for use. Conclusion A large sample size was recruited for this survey, implying a good level of interest in better understanding the current application of the BASMI. It is evident clinicians use the BASMI on newly-diagnosed patients as a priority in their assessment and shared-decision making. Other aspects such as addressing poor movement and adherence to exercise are ranked highly. The reported reasons for BASMI use are varied, and its application not standardised across UK rheumatology teams. This might reflect the diverse trajectory of axSpA and the importance of seeing patients as individuals. How and why we undertake physical outcome measures is crucial for consideration as we currently consider remote versus face-to-face consult pathways for our axSpA cohort. There is enough evidence here to recommend ongoing, regular application of the BASMI in a traditional face-to-face setting. Disclosure K. Weight: None. W.J. Gregory: Honoraria; W.G. has received speaker, conference registration and advisory board fees from Abbvie, Pfizer Novartis and UCB. H. Chambers: None. E. Clarke: Honoraria; E. C. has received speaker fees from Novartis UK. M. Daly: None. A. Davie: None. J.C. Elkins: None. S. Gaikwad: None. H. Harrison: None. C. Longton: Shareholder/stock ownership; C.L. is a shareholder in Astra Zeneca. Honoraria; C.L. has received speaker fees from Novartis. M. Martin: Honoraria; M.M. has received speaker, conference registration and advisory board fees from Abbvie, Novartis (not since 2018). Grants/research support; M.M. received grant monies from the National Axial Spondyloarthritis Society in 2017. M. Motion: None. S. Voules: None. M. McDonald: None. C. Jeffries: Honoraria; C.J. has received speaker, conference registration and advisory board fees from Abbvie, Pfizer, Novartis and UBC.

P255 Collaboration in the treatment of psoriasis and psoriatic arthritis: a survey of UK clinical practice

Abstract Background/Aims Treatment guidelines for psoriatic arthritis consider both skin and joint involvement and recommend collaborative multidisciplinary team (MDT) working when selecting therapy. However, multidisciplinary practice for psoriatic disease (PD) has not been well studied, with little data on service models and current practice. This survey explored collaborative working in PD treatment by rheumatology and dermatology healthcare professionals (HCPs) to provide a better understanding of current working patterns, collaborating specialties, as well as benefits and challenges of combined clinics for PD management. Methods An online survey was emailed to rheumatology and dermatology HCPs using professional networks. We requested information on role, collaborating specialties, benefits and barriers to collaborative working in PD, and the impact of COVID-19. The ideal service model and additional comments completed the survey. Results We received 80 responses between October 2020 and April 2021, covering England, Wales, Scotland and Northern Ireland. Of these, 56 respondents (70.0%) were consultants, 22 (27.5%) clinical nurse specialists and one each a lead pharmacist (1.3%) and specialist registrar (1.3%). Rheumatology HCPs accounted for 40.0% of respondents (n = 32) and dermatology HCPs for 60.0% (n = 48). As part of their PD MDT, most respondents (n = 60, 75.0%) worked collaboratively with other specialties. Combined clinics, whether virtual, face to face or an MDT, accounted for 51.5% of collaborative working for rheumatology HCPs and 58.9% for dermatology HCPs. Collaboration with other specialists mainly occurred by email or written referrals (Table 1). The most important perceived benefits of combined clinics were shared knowledge, better patient outcomes and patient satisfaction. The biggest challenges to setting up combined clinics were job plan time (rated as ‘difficult’ or ‘very difficult’ by 78.8% of respondents), logistics (67.5%) and unsupportive senior management (66.3%), while 77.5% felt COVID-19 had partial or significant impact on combined clinics. Conclusion This is the first survey to explore UK collaborative working in PD. Approaches varied, with different models of working and little consistency. While HCPs appreciated the benefits of collaborative working, numerous challenges in establishing formal arrangements were identified. More evidence is needed to demonstrate the perceived benefits of collaborative working in improving patient outcomes by standardising best practice. Disclosure A. Kaul: Consultancies; AK has received payment for advisory boards from AbbVie, Janssen, Leo, MSD, Novartis and Pfizer. Honoraria; AK has received speaker fees from AbbVie, Eli Lilly, Janssen, Leo, MSD, Novartis and Pfizer. L. Savage: Consultancies; LS has received payment for advisory boards from AbbVie, Almirall, Biogen, Eli Lilly, Galderma, Janssen-Cilag, Leo, Novartis, Pfizer and UCB. Honoraria; LS has received speaker fees from AbbVie, Amgen, Almirall, Celgene, Celltrion, Eli Lilly, Galderma, Janssen-Cilag, Leo, Novartis, Pfizer, MSD and UCB. Grants/research support; LS has received grants/research funding from Pfizer. P. Gorecki: Other; PG is an employee of Janssen-Cilag Ltd.

P220 Long-term safety profile of upadacitinib in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis

P220 Long-term safety profile of upadacitinib in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis

P244 The use of anti-malarial therapy in UK Rheumatology practice. A UK-based pilot survey for the BILAG group

Abstract Background/Aims Antimalarials have an important role in the management of autoimmune rheumatic disease, especially lupus (SLE) and other connective tissue diseases (CTD). A large North American study demonstrated a risk of retinopathy with hydroxychloroquine, increasing at doses above 5mg/kg and after 10 years or more of continuous therapy. This has influenced the development of specific monitoring ocular guidance for hydroxychloroquine although there has been less attention to potential side effects in routine use. Our aim was to examine hydroxychloroquine use including the effect of changes in ophthalmology guidance Methods We designed a 21-question internet-based survey. This requested information on antimalarials including hydroxychloroquine brand, dosing, monitoring and concerns about use. We requested information about alternatives to hydroxychloroquine including mepacrine and chloroquine, barriers to and indications for prescribing these alternative antimalarials. Results We received 69 responses, 59 (86%) Consultants, 10 (14%) ST’s from across the United Kingdom of which 51% worked in a district general hospital (DGH) setting. Of the Consultants, 28 (47%) ran dedicated CTD clinics. Regarding hydroxychloroquine, 39 respondents (57%) used a defined local pathway for Hydroxychloroquine retinopathy screening. While 59/69 (86%) did not know which hydroxychloroquine brand their pharmacy dispensed, of the remainder, 14/19 (74%) used Quinoric. Regarding hydroxychloroquine dosing, 83% targeted weight-based maintenance dosing with most of these (77%) maintaining at the currently recommended 5mg/kg body weight or less, while 23% used 6.5mg/Kg. No participants measured hydroxychloroquine drug levels. Potential ocular toxicity, cardiac arrythmias and skin hyperpigmentation were reported as the most significant concerns with hydroxychloroquine usage. Of the alternatives, mepacrine was never used by 39%, (77% for chloroquine) while only 4% used either often or very often. Barriers to prescription of these alternative antimalarials were most commonly GP or local Pharmacy unavailability (39% and 17 retrospectively). However, mepacrine/ hydroxychloroquine combination was used by 32% of respondents, most often for refractory skin disease (21 respondents), refractory joint disease (five respondents) and as a steroid sparing drug (six respondents). Conclusion Our results suggest several aspects in which hydroxychloroquine use could be improved. Although recent evidence demonstrates the potential for significant ocular toxicity with Hydroxychloroquine in those taking &amp;gt; 5mg/kg body weight and for &amp;gt;10 years we found practice still varied with 43% Rheumatologists not using a dedicated ocular screening pathway making monitoring long term potentially hazardous. Alternatives to hydroxychloroquine are not considered by 39% perhaps reflecting paucity of data for mepacrine and chloroquine, especially in circumstances including pregnancy but also cost and lack of availability. Our results suggest a need for standardised hydroxychloroquine monitoring processes including improved ophthalmic screening with Optical Coherence Tomography, a need for more evidence about the potential benefits and hazards of hydroxychloroquine and alternative antimalarials and availability of prescribing guidelines. Disclosure A. Kaul: Consultancies; Dr Kaul has received fees for Advisory Boards for AbbVie, Janssen, Novartis, Lilly. Member of speakers’ bureau; r Kaul has received speaker fees from AbbVie, Novartis, Janssen, Leo, Pfizer. A. Mason: None. C. Edwards: None. E. Vital: None.

OA04 COVID-19 admissions and mortality in patients with early inflammatory arthritis: results from a national cohort

Abstract Background/Aims Patients with inflammatory arthritis were identified as a potentially vulnerable group during the COVID-19 pandemic, with recommendations from the UK government to shield. We set out to describe the risks of COVID-19 according to initial treatment strategy amongst patients recruited to the National Early Inflammatory Arthritis Audit (NEIAA). Methods NEIAA is an observational cohort design. It includes adults in England with a new diagnosis of inflammatory arthritis between May 2018 and March 2021. The outcomes of interest were death due to COVID-19 (COVID-19 stated on a death certificate) and hospitalisation due to COVID-19 (primary admission reason or nosocomial acquisition), identified using NHS Digital linkage. Cox proportional hazards models were used to calculate hazard ratios, with adjustment for patient factors (age, gender, smoking status, comorbidity) and disease factors (seropositivity, disease severity (DAS28), patient-reported disability (HAQ) and functional impact (MSK-HQ)) recorded at baseline. Individuals were considered at risk from February 2020 or date of diagnosis (whichever was later) and censored at a COVID-19 event, May 2021 or death (whichever was sooner). Results 14,127 patients were included. Mean age was 57 (+/-16); 62% were female. Smoking status: 19% current; 29% ex-smokers. Comorbidities: 19% hypertension; 9% diabetes; and 9% lung disease. Overall, 20% had two or more comorbidities. Rheumatoid Factor or CCP antibodies were positive in 56%. At presentation, mean scores were 4.6 (+/-1.5) for DAS28, 1.1 (+/-0.7) for HAQ and 25 (+/-11) for MSK-HQ. Initial DMARD therapy was known for 13,682/14,127 patients; methotrexate was most common (54%), then hydroxychloroquine (23%) and sulfasalazine (11%). There were 143 COVID-19 hospital admissions and 47 deaths, corresponding to incidence rates per 100 person-years for hospitalisation: 0.94 (95% CI: 0.79-1.10) and death: 0.31 (95% CI: 0.23-0.41). Increasing age, male gender, diabetes, hypertension, lung disease and smoking status all predicted COVID-19 events. Higher baseline DAS28 predicted COVID-19 admission (HR 1.24 (95% CI: 1.10-1.39)) and mortality (HR 1.33 (95% CI: 1.09-1.63)). Higher HAQ predicted both COVID-19 admission and death. Seropositivity was not a significant predictor of any COVID-19 event, nor was MSK-HQ. Unadjusted, corticosteroids associated with COVID-19 death (HR 2.29 (95% CI: 1.02-5.13)), and sulfasalazine monotherapy associated with COVID-19 admission (HR 1.93 (95% CI: 1.04-3.56)). In adjusted models, associations for corticosteroids and sulfasalazine were no longer significant. Only age, smoking status, and comorbidities independently predicted COVID-19 events. Conclusion The burden of COVID-19 amongst early arthritis patients was substantial during the pandemic. Patient characteristics and rheumatoid disease severity at diagnosis appear to be the more important predictors of COVID-19 events than initial treatment strategy. An important limitation is that we have not looked at treatment changes over time, and must acknowledge that many patients, especially those recruited in 2019, may have changed therapy prior to the pandemic. Disclosure M.A. Adas: None. M.D. Russell: Grants/research support; has received speaker fees and educational grants from Janssen, Lilly, Menarini, Pfizer and UCB. E. Cook: None. E. Alveyn: None. S. Oyebanjo: None. P. Amlani-Hatcher: None. J. Ledingham: Other; is a BSR trustee. J.B. Galloway: Honoraria; has received honoraria from AbbVie, Celgene, Chugai, Gilead, Janssen, Eli Lilly, Pfizer, Roche and UCB.