ANTIPHOSPHOLIPID ANTIBODIES AND VASCULAR THROMBOSIS IN PATIENTS WITH THE MOST SEVERE FORMS OF COVID-19

BackgroundThe presence of antiphospholipid antibodies (aPL) has been observed in patients with COVID-19 (1,2), suggesting that they may be associated with deep vein thrombosis, pulmonary embolism, or stroke in severe cases (3). Antiphospholipid syndrome (APS) is a systemic autoimmune disorder and the most common form of acquired thrombophilia globally. At least one clinical criterion, vascular thrombosis (arterial, venous or microthrombosis) or pregnancy morbidity and at least one laboratory criterion- positive aPL two times at least 12 weeks apart: lupus anticoagulant (LA), anticardiolipin (aCL), anti-β2-glycoprotein 1 (anti-β2GPI) antibody, have to be met for international APS classification criteria(4). Several reports also associate anti-phosphatidylserine/prothrombin antibodies (aPS/PT) with APS.ObjectivesTo combine clinical data on arterial/venous thrombosis and pregnancy complications before and during hospitalisation with aPL laboratory findings at 4 time points (hospital admission, worsening of COVID-19, hospital discharge, and follow-up) in patients with the most severe forms of COVID-19 infection.MethodsPatients with COVID-19 pneumonia were consequetively enrolled, as they were admitted to the General hospital Pancevo. Exclusion criteria were previous diagnosis of inflammatory rheumatic disease and diagnosis of APS. Clinical data were obtained from the medical records. Laboratory results, including LA, aCL, anti-β2GPI, and aPS/PT antibodies were taken at hospital admission, worsening (defined as cytokine storm, connection of the patient to the respirator, use of the anti-IL-6 drug- Tocilizumab), at hospital discharge and at 3-months follow-up and sent to University Medical Centre Ljubljana, Slovenia for analysis. Statistics was performed by using SPSS 21.Results111 patients with COVID-19 pneumonia were recruited;7 patients died during hospitalisation (none were aPL-positive on admission and at the time of worsening), 3 due to pulmonary artery embolism. All patients were treated according to a predefined protocol which included antibiotics, corticosteroids, anticoagulation therapy and specific comorbidity drugs;patients with hypoxia were supported with oxygen. During hospitalisation, pulmonary artery thrombosis occurred in 5 patients, one was aPL-positive at all time points (was diagnosed with APS), others were negative. In addition, 9/101 patients had a history of thrombosis (5 arterial thrombosis (coronary and cerebral arteries), none of whom was aPL-positive on admission and at follow-up, and 4 venous thrombosis, one of which was aPL-positive at all time points and received an APS diagnosis). Among 9/101 patients with a history of thrombosis, 55.6% were transiently positive at the time of discharge, compared to patients without prior thrombosis, in whom 26.1% were transiently positive at the hospital release (p=0.074). Two patients had a history of pregnancy complications (both had miscarriage after 10th week of gestation), but did not have aPL positivity at any time point.ConclusionAlthough aPL was expected to be associated with vascular disease in the most severe forms of COVID-19, all patients that have died in our cohort were aPL negative. At hospital discharge, 56% of patients with a history of arterial or venous thrombosis had positive aPL that became negative at the 3-months follow-up (were transienlty positive), which should be considered when prescribing therapy after hospitalisation.References[1]Trahtemberg U, Rottapel R, Dos Santos CC, et al. Anticardiolipin and other antiphospholipid antibodies in critically ill COVID-19 positive and negative patients. Annals of the Rheumatic Diseases 2021;80:1236-1240.[2]Stelzer M, Henes J, Saur S. The Role of Antiphospholipid Antibodies in COVID-19. Curr Rheumatol Rep. 2021;23(9):72-4.[3]Xie Y, Wang X, Yang P, Zhang S. COVID-19 complicated by acute pulmonary embolism. Radiology: Cardiothoracic Imaging 2020: 2: e200067.[4]Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, et al. J.Thromb.Haemost. 2006;4: 295-306.Acknowledgements:NIL.Disclosure of nterestsNone Declared.

THE PREVALENCE AND INCIDENCE OF PSORIASIS AND PSORIATIC ARTHRITIS IN ENGLAND FROM 2009-2019: AN OBSERVATIONAL STUDY USING PRIMARY CARE DATA

BackgroundPsoriasis (PsO) and psoriatic arthritis (PsA) can greatly impact quality of life and result in substantial personal and societal costs. Complete and up to date data on the prevalence and incidence of these conditions and whether these change over time and vary by age is important for healthcare service planning so that specialist care and funding can be appropriately allocated.ObjectivesTo determine the prevalence and incidence of PsO and PsA in males and females from 2009-2019 across all age groups in England.MethodsWe used Clinical Practice Research Datalink AURUM, a primary care electronic health record database, including 20% of the English population. The codes used to identify patients with PsO and PsA were selected by rheumatologists and dermatologists and cross-checked with published code lists from other studies to ensure inclusion of all relevant codes. All included patients must have data for at least 1 year before their diagnosis. The annual incidence and point prevalence were calculated from 2009-2019 and stratified by age/sex. The study period ended in 2019 to avoid COVID-19 pandemic affecting results.ResultsThe prevalence of PsO and PsA in males and females increased annually, peaking in 2019 (PsO males 2.41% [95% confidence interval (CI) 2.40, 2.42];PsO females 2.60% [95% CI 2.59-2.61];PsA males 0.20% [95% CI 0.20-0.20];PsA females 0.21% [95% CI 0.21- 0.22]), as illustrated in Table 1. In 2019, the prevalence of PsO and PsA was highest in the over 65 years age group;PsO 4.25% [95% CI 4.22-4.28] and PsA 0.38% [95% CI 0.37-0.38]. The annual incidence (per 100,000 person years) of PsO has gradually decreased in males (from 168 (164-171) in 2009 to 148 (145-151) in 2019) but in females it has been stable with a slight annual decrease (from 180 (177-184) in 2009 to 173 (170-176) in 2019). The annual incidence for PsA has increased in both males and females (13 (12-14) in 2009 and 15 (14-16) in 2019 for males and 12 (11-13) in 2009 and 18 (17-19) in 2019 for females).ConclusionThe increasing prevalence of PsO and PsA highlights the importance of organising healthcare services to meet this need, particularly in the elderly population.ReferencesNIL.Table 1.Prevalence of PsO and PsA from 2009-2019 in EnglandYear20092010201120122013201420152016201720182019Population (n)1073383110910802110318501118036711343299112249341137842211657996119336261223432512420998PsO (n)216841229106239819250667259988268032276804286499295712304568311104PsO prevalence (%, 95%CI)-Male1.98 (1.96-1.99)2.06 (2.05- 2.07)2.13 (2.12-2.14)2.19 (2.18-2.20)2.24 (2.23- 2.25)2.33 (2.32- 2.34)2.37 (2.36- 2.38)2.39 (2.38- 2.40)2.40 (2.39- 2.41)2.40 (2.39- 2.42)2.41 (2.40- 2.42)-Female2.07 (2.05- 2.08)2.14 (2.13- 2.16)2.22 (2.21- 2.23)2.29 (2.28- 2.31)2.35 (2.33- 2.36)2.45 (2.43- 2.46)2.50 (2.49- 2.51)2.53 (2.52- 2.54)2.56 (2.54- 2.57)2.58 (2.56- 2.59)2.60 (2.59- 2.61)PsO incidence (100,000 person years)-Male168 (164-171)158 (155- 162)161 (158-165)153 (150-157)161 (157- 164)156 (153- 159)155 (152- 159)154 (151- 157)153 (150-156)150 (147-153)148 (145-151)-Female180 (177-184)176 (172-179)181 (177-184)171 (167-174)175 (171-178)176 (172-180)179 (176-183)178 (174-181)177 (174-181)174 (170-177)173 (170-176)PsA (n)1444515443164681752218545196182072021994232572451425683PsA prevalence (%, 95%CI)-Male0.14 (0.14- 0.14)0.15 (0.14- 0.15)0.15 (0.15- 0.16)0.16 (0.16- 0.16)0.17 (0.16- 0.17)0.18 (0.17- 0.18)0.18 (0.18- 0.19)0.19 (0.18- 0.19)0.19 (0.19- 0.20)0.20 (0.19- 0.20)0.20 (0.20- 0.20)-Female0.13 (0.13- 0.13)0.14 (0.13- 0.14)0.15 (0.14- 0.15)0.15 (0.15- 0.16)0.16 (0.16- 0.16)0.17 (0.17- 0.18)0.18 (0.18- 0.18)0.19 (0.19- 0.19)0.20 (0.19- 0.20)0.20 (0.20- 0.21)0.21 (0.21- 0.22)PsA incidence (100,000 person years)-Male13 (12- 14)12 (11- 13)13 (12- 14)12 (11- 13)13 (12-14)14 (13- 15)14 (13- 15)14 (13-15)1514-16)14(13- 15)15 (14-16)-Female12 (11- 13)13 (12- 14)13 (12- 14)14 (13-15)14 (13-15)15 (14-16)17 (16- 18)16 (15- 17)17 (16- 18)18 (17-19)18 (17-19)Acknowledgements:NIL.Disclosure of InterestsArani Vivekanantham: None declared, Edward Burn: None dec ared, Marta Pineda-Moncusí: None declared, Sara Khalid Grant/research support from: SK has received research grant funding from the UKRI and Alan Turing Institute outside this work. SK's research group has received grant support from Amgen and UCB Biopharma., Daniel Prieto-Alhambra Grant/research support from: DPA's department has received grant/s from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by DPA's department., Laura Coates Speakers bureau: LC has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB., Consultant of: LC has worked as a paid consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer and UCB., Grant/research support from: LC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Novartis and Pfizer.

Stakeholder Analysis: Medicare Diabetes Prevention Program Awareness and Implementation

Study Design: We conducted a qualitative stakeholder analysis project with suppliers of the MDPP and health care providers. Am J Manag Care. 2023;29(6):In Press _____ Takeaway Points More than 5 years after CMS enacted coverage of the CDC-approved Medicare Diabetes Prevention Program (MDPP) in 2018, little is known about why MDPP uptake is so limited. * Findings of our stakeholder analysis with program suppliers and health care providers reinforced existing evidence on insufficient reimbursement and low awareness of the program. * Newer insights include recommendations about lagged payments, ongoing virtual delivery, and formally diagnosing prediabetes among MDPP participants. * Our findings on barriers and facilitators can inform policy to refine the MDPP and research on the MDPP, particularly within the field of implementation science. _____ Population-level strategies to prevent type 2 diabetes are urgently needed for the more than 24 million older adults with prediabetes in the United States.1 Evidence-based lifestyle interventions can prevent diabetes onset, per evidence from the landmark Diabetes Prevention Program trial.2 Thus, the CDC launched the National Diabetes Prevention Program (NDPP) in 2010.3 Significant reductions in weight and medical spending were observed among Medicare beneficiaries who participated in the NDPP,4 prompting CMS to fully cover the Medicare Diabetes Prevention Program (MDPP) starting in 2018.5 Despite unprecedented Medicare coverage for a disease prevention program, MDPP uptake is limited. Regarding awareness, national guidelines recommend referral to lifestyle intervention for adults aged 40 to 70 years with prediabetes.9 Yet less than 5% of adults eligible for a NDPP reported receiving a referral,10 which may stem from limited awareness among health care providers.11 Thus, we conducted a qualitative stakeholder analysis to learn about regional awareness of, referral to, facilitators of, and barriers to the MDPP. The 8 interviewees included 5 program directors (3 from YMCAs, 1 from a private organization, and 1 from a hospital system) and 3 health care providers (2 family physicians and 1 dietitian).

Self-Sovereign Identity for Consented and Content-Based Access to Medical Records Using Blockchain

Electronic health records (EHRs) and medical data are classified as personal data in every privacy law, meaning that any related service that includes processing such data must come with full security, confidentiality, privacy, and accountability. Solutions for health data management, as in storing it, sharing and processing it, are emerging quickly and were significantly boosted by the COVID-19 pandemic that created a need to move things online. EHRs make a crucial part of digital identity data, and the same digital identity trends - as in self-sovereign identity powered by decentralized ledger technologies like blockchain, are being researched or implemented in contexts managing digital interactions between health facilities, patients, and health professionals. In this paper, we propose a blockchain-based solution enabling secure exchange of EHRs between different parties powered by a self-sovereign identity (SSI) wallet and decentralized identifiers. We also make use of a consortium IPFS network for off-chain storage and attribute-based encryption (ABE) to ensure data confidentiality and integrity. Through our solution, we grant users full control over their medical data and enable them to securely share it in total confidentiality over secure communication channels between user wallets using encryption. We also use DIDs for better user privacy and limit any possible correlations or identification by using pairwise DIDs. Overall, combining this set of technologies guarantees secure exchange of EHRs, secure storage, and management along with by-design features inherited from the technological stack. © 2023 Marie Tcholakian et al.

Q&A

In this interview, Sujay Jadhav, global vice president, study start-up, Oracle Health Sciences, touches on how COVID has affected study start-up and what new perspectives it has forced the industry to have on its own challenges. [...]assessing site ability to leverage telehealth will be a factor in site selection. Andy Studna is an Assistant Editor for Applied Clinical Trials Sujay Jadhav Global Vice President, Study Start-Up, Oracle Health Sciences Problems with startup, more than any other phase of a clinical trial, have the greatest potential to increase timelines and budgets.

Maternal and Neonatal Outcomes After Monoclonal Antibody Use

INTRODUCTION: The study aimed to evaluate whether the administration of monoclonal antibodies (MABs) in mildly symptomatic unvaccinated COVID-19-positive pregnant patients reduced the need for maternal hospitalization and to evaluate whether this medication affected the rate of adverse neonatal outcomes and severe maternal disease. We hypothesized that MAB use would reduce the need for hospitalization. METHODS: This retrospective cohort study was completed by obtaining electronic medical record data of all pregnant patients between August 2020 and January 2022 who met criteria for MAB therapy. The two comparison groups were patients who received outpatient MAB therapy during pregnancy and those who were eligible for therapy but declined. Demographic and hospitalization data were obtained. Exclusion criteria included severe illness upon diagnosis requiring hospitalization, or patients for whom delivery and neonatal data were not available. RESULTS: During the study period, 49 patients qualified for MAB therapy, of which delivery data were available for 39 patients. Twenty patients (51%) elected to receive MAB therapy and 19 (49%) declined. Among those who received MAB therapy, 10 (26% of the population) were vaccinated, and among those who declined, 6 (15% of the population) were vaccinated. The two groups were similar in gestational age at delivery (38 weeks 4 days versus 37 weeks 5 days) and gestational age at diagnosis (19 weeks 0 days versus 22 weeks 6 days). Among patients who did not receive MABs, both absolute and relative maternal hospitalization rate was higher (26.3% versus 5%, 12.8% versus 3%, P >.05). When stratified by vaccination status, those who were vaccinated had a 5% probability of hospitalization regardless of MAB therapy. The probability of hospitalization was highest among unvaccinated women who did not receive MAB therapy (67%) and lowest among unvaccinated women who received MAB therapy (0%). CONCLUSION: Unvaccinated patients who declined MAB therapy had a higher rate of hospitalization, although not statistically significant. These preliminary findings warrant further study with a larger cohort. [ FROM AUTHOR] Copyright of Obstetrics & Gynecology is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Pandemic Asteroid Defense: DART Integration and Test in the time of COVID-19

NASA's Double Asteroid Redirection Test (DART) successfully intercepted the asteroid Didymos on September 26th of 2022, potentially changing its orbital period with a deflection by kinetic impact. The spacecraft launched aboard a SpaceX Falcon 9 rocket on November 24th, 2021. DART's Integration and Test (I&T) campaign was scheduled to commence in April of 2020 at the Johns Hopkins University Applied Physics Laboratory (JHU/APL) in Laurel, Maryland. In March of that year, one month prior to beginning I&T, the rapid spread of the Coronavirus (COVID-19) forced JHU/APL to rethink how to assemble, test and deliver a spacecraft on schedule during a very challenging period of time. This paper will discuss the details of the successful I&T strategy used by the DART team during the COVID-19 lockdown and subsequent return to post-lockdown life. The team learned how to effectively meet virtually, how to integrate hardware, and how to operate the spacecraft with the least amount of people required. Communication was key in keeping the various DART team members, who were located across the country, connected and safe. The team had also moved documentation online for the first time, which turned out to be very instrumental in keeping everyone on track. A variety of tools to collaborate and document test procedures and results proved valuable for record keeping. Creative solutions were implemented during the test campaign for scheduling both remote and in person monitoring. This paper will conclude with DART lessons learned and recommendations for future I&T programs. © 2023 IEEE.

Distributed records in the Rohingya refugee diaspora: Arweave and the R-Archive

Purpose: This article delineates the pilot implementation of the Rohingya Archive (R-Archive). The R-Archive seeks to both confront and exploit the roles of documentation and recordkeeping in forced displacement of Rohingya people through targeted physical and bureaucratic violence in Myanmar. This grassroots activist intervention is located at the intersection of technology, rights, records, jurisdictions and economics. Using Arweave's blockweave, the R-Archive secures copies of records, such as identity documentation, land deeds and personal papers, carried into diaspora by Rohingya refugees against unauthorised alteration, deletion and loss, providing a trust infrastructure for accumulating available evidence in support of rights claims and cultural preservation. Design/methodology/approach: Iterative development of functional requirements, data collection processes and identification of a technological solution for the community-based, post-custodial, blockchain-inspired R-Archive;design and testing of the R-Archive pilot;and analysis of trust and economic concerns arising. Findings: A complex set of interconnecting considerations is raised by this use of emerging technologies in service to a vulnerable and diasporic community. Hostile governments and volatile cryptocurrencies are both threats to the distributed post-custodial R-Archive. However, the strength of the community bonds that form the archive and articulated in its records speak to the possibility of perdurance for a global Rohingya archive, and working through the challenges surfaced by its development offers the possibility to serve as a model that might be adaptable for other grassroots archival activist projects initiated by oppressed, marginalised and diasporic communities. Research limitations/implications: Personal and community safety and accessibility concerns, especially in refugee camps and under Covid-19 restrictions, presented particular challenges to carrying out the research and development that are addressed in the research design and future research plans. Practical implications: The goal of this pilot was to collect and store examples of a range of documents that demonstrate different aspects of Rohingya culture and links to the homeland as well as those that record formal evidentiary relationships between members of the Rohingya community now in diaspora and the Burmese state (e.g. acknowledgements of citizenship). The pilot was intended to demonstrate the viability of using a blockchain-inspired decentralised archival system combined with a community-driven approach to data collection and then to evaluate the results for potential to scale. Social implications: The R-Archive is a community-centred and driven effort to identify and preserve, under as secure and trusted conditions as possible, digital copies of documents that are of juridical, cultural and personal value to the Rohingya people and also of significance as primary documentary evidence that might be used by international legal institutions in investigating genocide taking place in Burma and by academic researchers studying the history of Burma. Originality/value: The R-Archive is novel in terms of its technological application (Arweave), the economic concerns of a vulnerable stateless population it is trying to address, and its functional complexity, in that its goal is simultaneously to serve both legal evidentiary and community archive functions. The R-Archive is also an important addition to other notable efforts in the diasporic Rohingya community that have attempted to employ the tools of technology for cultural preservation. [ FROM AUTHOR] Copyright of Journal of Documentation is the property of Emerald Publishing Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

CLINICAL AND IMMUNOLOGICAL PROFILES OF PATIENTS WITH ANTI-SYNTHETASE SYNDROME: A RETROSPECTIVE COHORT STUDY FROM A TERTIARY CENTRE

BackgroundAnti-synthetase syndrome (ASS) is a rare auto-immune condition that combines autoantibodies and specifics clinical manifestations, including myositis, interstitial lung disease (ILD), polyarthritis, mechanic's hands, Raynaud's phenomenon, and unexplained fever. The hallmark of this syndrome is the presence of anti-aminoacyl-tRNA-synthetase (ARS) antibodies. Several anti-ARS antibodies have been described, anti-Jo1 being the most common, followed by anti-PL7, anti-PL12, anti-OJ, anti-EJ, anti-KS, anti-YRS, and anti-Zo. According to a recent epidemiological survey, the rising number of patients with autoimmune diseases, including idiopathic inflammatory myopathies (IIM) coincides with the COVID-19 pandemic.ObjectivesTo evaluate the clinical characteristics of ASS patients with different anti-ARS antibodies from a tertiary rheumatology center.MethodsWe conducted a retrospective, single-centered study on consecutive patients diagnosed with ASS from 1 January 2015 to 31 December 2022. Clinical and serologic data were obtained by medical records review from hospital database. Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) were tested using commercial ELISA kits. We included all patients fulfilling Connor's criteria for ASS.ResultsSixty-one patients (44 females) with mean age 54.4 (13.8) years were included. The most frequently reported clinical manifestation was arthralgia (68.8%), followed by Raynaud's phenomenon (67.2%), ILD (65.6%), myositis (46%), mechanic's hands (44.3%), arthritis (39.3%), and fever (18.0%). The typical triad for ASS, including myositis, arthritis and ILD was present in 17 patients. Twenty-eight (45.9%) patients were PL7+, 21 (34.4%) were Jo1+, 3 (4.9%) were PL12+, and 2 (3.2%) were OJ+. Seven patients were positive for more than two anti-ARS antibodies. The most frequently found MAA was anti-Ro52 (n=23, 37.7%). Of the 61 patients included, 41 (67.2%) patients were diagnosed in the last 3 years (COVID-19 pandemic). The most frequently detected MSA in ASS patients diagnosed during COVID-19 pandemic was anti-PL7 (25/28), while anti-Jo1 was the most common MSA in ASS patients diagnosed before 2020 (p<0.05) (Fig 1).The anti-Jo1+ patients were younger, have significantly more frequent muscle involvement and significantly higher levels of CK than anti-PL7+ patients (p<0.05). The co-occurance of anti-Ro52 antibodies was more frequently observed in anti-Jo1+ patients (n=11, 52.4%) than in anti-PL7+ patients (n=6, 21.4%) (p<0.05). We did not find statistically significant differences between ASS groups regarding sex, disease duration, clinical manifestations including dermatologic lesions, Raynaud's phenomenon, arthralgia/arthritis, ILD, fever, and cancers (all p>0.05).ConclusionASS patients have heterogenous manifestations, and different types of anti-ARS antibodies are associated to distinct clinical and immunological features. The COVID-19 pandemic led to increase prevalence of ASS cases and to a remarkable shift in the anti-ARS antibodies profile, with increased frequency of anti-PL7 antibodies. Further studies are needed to investigate the link between SARS-CoV-2 infections and myositis.References[1]Witt LJ, et al. The Diagnosis and Treatment of Antisynthetase Syndrome. Clin Pulm Med. 2016 Sep;23(5):218-226.[2]Gracia-Ramos AE, et al. New Onset of Autoimmune Diseases Following COVID-19 Diagnosis. Cells. 2021 Dec 20;10(12):3592.[3]Connors GR, et al. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest. 2010 Dec;138(6):1464-74.[4]García-Bravo Let al. Association of anti-SARS-COV-2 vaccine with increased incidence of myositis-related anti-RNA-synthetases auto-antibodies. J Transl Autoimmun. 2022 Jun 30;5:100160.Figure 1.ASS patients with positive anti-ARS antibodies per year (from 2015 to 2022). The green line shows the PL7+ patients;and the orange line shows the Jo1+ cases.[Figure omitted. See PDF]AcknowledgementsI have no acknowledgements to declare.Disclosure of Inter stsNone Declared.

REFERRAL BEHAVIOUR OF PRIMARY CARE DOCTORS TO RHEUMATOLOGY CLINIC IN MALAYSIA

BackgroundThe workload at rheumatology clinics have been growing relentlessly and an audit on new.referrals helps to identify referral behaviour of primary care doctors and improvement can be done by providing further training.ObjectivesTo audit on new referral cases to rheumatology clinic from 2020-2022 and to identify new cases with misdiagnosis for future training purpose.MethodsThis was a retrospective study. The medical records of all new referral to rheumatology clinic Hospital Sultan Ismail and Hospital Pakar Sultanah Fatimah from 1st January 2020 to 31th November 2022 were reviewed. The referral diagnosis and final diagnosis were identified and analysed.ResultsThere were total of 927 new cases referral throughout the 35 months during Covid-19pandemic. Majority of them were diagnosed to have rheumatoid arthritis (217/927)followed by systemic lupus erythematosus (190/927), psoriatic arthritis (147/927),gout (62/927), osteoarthritis (58/927), systemic sclerosis (25/927), ankylosing spondylitis (25/927), soft tissue rheumatism (24/927), Sjogren syndrome (24/927),mixed connective tissue disease (14/927), vasculitis (11/927), fibromyalgia (10/927),polymyositis (7/927) and miscellaneous (39/927).45 out of the new cases were diagnosed as unlikely rheumatic diseases. There were 29pending cases awaiting final diagnosis.212 of the referrals were identified as misdiagnosis with the highest as nodal osteoarthritis.(55/212) followed by unlikely rheumatic disease (43/212), soft tissue rheumatism (24/212),psoriatic arthritis (20/212), Sjogren syndrome (14/212), gout (8/212), rheumatoid arthritis (7/212), fibromyalgia (6/212), systemic lupus erythematosus (5/212), ankylosing spondylitis (4/212), mixed connective tissue disease (3/212), systemic sclerosis (2/212), polymyositis (2/212) and others (19/212): diffuse idiopathic skeletal hyperostosis, hypermobility syndrome, RS3PE syndrome, idiopathic uveitis, graft versus host disease, juvenile idiopathic arthritis, antiphospholipid syndrome, hypothyroidism, post streptococcal arthritis, prolapsed intervertebral disc, cerebrovascular disease, traumatic sternoclavicular joint subluxation, ledderhose disease, paraspinal muscle spasm and viral myalgia).ConclusionNodal osteoarthritis and soft tissue rheumatism can be great mimicker for inflammatory.arthritis and if wrongly diagnosed will lead to unnecessary anxiety or wrong treatment. More training is needed to improve clinical skills amongst primary care doctors.ReferencesNA.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Healthcare costs vis-à-vis economic growth in pandemic crisis with technology adoption

COVID-19 pandemic brought up issues with healthcare costs, national economic development and welfare of the society in forefront. Nations across the globe followed different approaches to deal with COVID-19, such as zero tolerance, herd immunity, containment to build treatment capability. National healthcare became a contentious sociopolitical issue involving healthcare costs, technologies and societal health. In the United States even during the COVID-19 pandemic, the government approach was pursuing a sustainable improvement in patient care through adoption of medical and information technologies. The national healthcare policies are framed around technological interventions with the assumption that deployment of technologies could keep healthcare costs under control and at the same time improve health outcomes. However, evidences show that the healthcare costs are in the rise even with impressive progress in technological deployment. This article highlights some of the recent trends in healthcare costs, technological preparedness, medical technology developments in managing COVID-19 pandemic. The US government mandated electronic health record (EHR) systems implementation and assess its impact on healthcare costs and health outcomes. This article emphasizes the need for understanding the interconnectedness of costs, technology and societal health.

SPANISH NATIONAL REGISTRY OF BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

BackgroundBelimumab (BLM) is a monoclonal antibody that inhibits B-lymphocyte stimulating factor (BlyS) approved as a specific treatment for systemic lupus erythematosus (SLE) in 2011. We present the experience with BLM in a Spanish cohort with more than 460 patients.ObjectivesTo describe demographic characteristics, efficacy and safety of BLM in patients with SLE in Spanish population since its approval.MethodsDescriptive, retrospective, multicenter study in patients diagnosed with SLE according to EULAR/ACR 2019, SLICC and/or ACR 1997 diagnostic criteria. Data regarding SLE patients treated with BLM were collected from medical records (2011-2022). Demographic features, efficacy, laboratory variables, SLEDAI, renal involvement, steroid dose, administration routes and safety were assessed. To see whether a trend in BLM prescription had changed or not over time, two periods of time were analyzed: 2011-2016 (period1) and 2017-2022 (period2).ResultsBaseline characteristics of patients are summarized in Table 1.A total of 462 patients (36 hospitals) were included, 50.9% were on intravenous (IV), 34% on subcutaneous (SC) and 15.1% switched from IV to SC route. The median number of pre-BLM csDMARD use was 2.0 (2.0-3.0), being hydroxychloroquine (HCQ) the most frequently used (94.5%). Fifty-two patients were treated with IV cyclophosphamide with a median of 6 bolus received. At the time of BLM start, 443 patients were on prednisone with a median dose of 6.2 mg (5.0-10.0). Significant decreases in prednisone dose, SLEDAI and anti-DNA antibodies were observed from baseline until the last visit, whereas complement C3 and C4 values raised (Figure 1). A total of 118 patients (27.4%) had renal involvement with a median proteinuria of 1.0 g/day (0.5-2.4). Renal biopsy was done in 102 out of 118 patients, being class IV (33%), class III (21%) and class V (16%) the most frequently reported. After BLM, 73.3% of these patients improved (median proteinuria of 0.2 g/day (0.1-0.7).In period1, 100 patients started BLM compared to 362 in period2. The median time from SLE diagnosis to BLM begin was 7.1 (4.0-13.7) and 6.2 (2.1 -14.4) years in period1 and period2, respectively (p=0.454). We found a trend to use more csDMARD before BLM treatment in period1: 2.5 (2-3) vs. 2 (2-3) (p=0.088).A total of 143 (30.5%) patients discontinued treatment mostly due to inefficacy (55.9%) and infections (11.9%). In fact, 116 patients developed infections, mostly mild;2 patients died, 16 had COVID-19 and 4 patients developed tumors requiring discontinuation of the drug.ConclusionIn our cohort of SLE patients in a real-world setting, BLM has been effective, safe and seems to be a good choice to treat renal involvement.References[1]Navarra SV, Guzmán RM, Gallacher AE, et al. Lancet. 2011;377(9767):721-31.[2]Stohl W, Hiepe;rt al. Arthritis Rheum. 2012;64(7):2328-37.[3]Furie R, Rovin BH, Houssiau F, et al. N Engl J Med. 2020;383(12):1117-1128.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

COVID-19 OUTCOMES IN KOREAN PATIENTS WITH GOUT

BackgroundPatients with autoimmune inflammatory rheumatic diseases are at higher risk for coronavirus disease (COVID)-19 hospitalization and worse clinical outcomes compared with the general population. However, data on the association between COVID-19 outcomes and gout, or gout-related medications are still lacking.ObjectivesWe aimed to compare COVID-19 related clinical outcomes in gout vs. non-gout patients.MethodsWe conducted a retrospective cohort study using the electronic health record-based databases of Seoul National University hospital (SNUH) from January 2021 to April 2022 mapped to a common data model. Patients with gout and without gout were matched using a large-scale propensity score (PS) algorithm. The clinical outcomes of interest were COVID-19 infection, severe COVID-19 outcomes defined as the use of mechanical ventilation, tracheostomy or extracorporeal membrane oxygenation, and death within 30 days of COVID-19 diagnosis. The hazard ratio (HR) for gout vs. non-gout patients derived by Cox proportional hazard models were estimated utilizing a 1:5 PS-matched cohort.Results2,683 patients with gout and 417,035 patients without gout were identified among the patients who visited SNUH. After 1:5 PS matching, 1,363 gout patients and 4,030 non-gout patients remained for the analysis. The risk of COVID-19 infection was not significantly different between patients with gout and those without gout (HR 1.07 [95% CI 0.59-1.84]). Within the first month after the COVID-19 diagnosis, there was also no significant difference in the risk of hospitalization (HR 0.57 [95% CI 0.03-3.90], severe COVID-19 outcomes (HR 2.90 [95% CI 0.54-13.71]), or death (HR 1.35 [95% CI 0.06-16.24]).ConclusionPatients with gout did not have an increased risk of COVID-19 infection or worse clinical outcomes. Updates of temporal trends of COVID-19 outcomes in gout patients are yet warranted as new SARS-CoV-2 variants emerge.References[1]Shin YH, et al. Autoimmune inflammatory rheumatic diseases and COVID-19 outcomes in South Korea: a nationwide cohort study. Lancet Rheumatol. 2021 Oct;3(10):e698-e706.[2]Topless RK, et al. Gout and the risk of COVID-19 diagnosis and death in the UK Biobank: a population-based study. Lancet Rheumatol. 2022 Apr;4(4):e274-e281.[3]Xie D, et al. Gout and Excess Risk of Severe SARS-CoV-2 Infection Among Vaccinated Individuals: A General Population Study. Arthritis Rheumatol.2023 Jan;75(1):122-132.Table 1.Clinical outcomes of COVID-19 infection in patients with goutOutcomesUnmatched populationPopulation with PS stratification using 10 strata1:5 PS matched populationHazard ratio (95% CI)p-valueHazard ratio (95% CI)p-valueHazard ratio (95% CI)p-valueCOVID-19 infection1.68 (1.03-2.57)0.031.20 (0.72-1.87)0.461.07 (0.59-1.84)0.82Hospitalization due to COVID-191.92 (0.32-6.05)0.391.63 (0.26-5.77)0.540.57 (0.03-3.90)0.66Severe COVID-19 infection4.72 (1.44-11.28)<0.014.22 (1.17-12.21)0.022.90 (0.54-13.71)0.20Death due to COVID-191.15 (0.07-5.18)0.900.77 (0.04-3.81)0.821.35 (0.06-16.24)0.84Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Building Research Capacity in Primary Care Practices That Serve Predominantly Racial and Ethnic Minority Populations

In this commentary, we report on lessons learned over 2 years (2020-2022) from conducting primary care research through a novel alliance of an ACO consisting of independent practices, a health plan, and several academic researchers, with the support of a private foundation. Am J Manag Care. 2023;29(6):In Press _____ Takeaway Points The process of collaborating on research was mutually beneficial for a network of independent practices and a group of academic researchers. * The process benefited the practices by facilitating more precise thinking about quality improvement, motivating the staff, and enabling readiness for health system change. * The process benefited the researchers by illuminating nuances of clinical and organizational workflow and revealing the practices' in-depth understanding of the communities they serve. * If practices have more federally funded opportunities to consistently participate in research, it could help speed greater adoption of payment reform models to promote health equity at the state and national levels. _____ A 2021 National Academies of Sciences, Engineering, and Medicine report, Implementing High-Quality Primary Care, has called out the persistent "neglect of basic primary care research" in the United States.1 A 2020 study by the RAND Corporation found that primary care research represents only 1% of all federally funded projects (including projects funded by the National Institutes of Health, the Agency for Healthcare Research and Quality [AHRQ], and the Veterans Health Administration).2 However, innovation in primary care is central to advancing health care delivery. Leaders in health care innovation recently called for CMS to test a proposal for primary care payment reform in accountable care organizations (ACOs) composed of independent practices (ie, practices not owned by hospitals).3 By innovating in independent practices, these leaders argued that CMS would provide incentives for those practices to stay independent, thereby potentially decreasing the vertical market consolidation that contributes to rising health care costs.3 Yet these same practices may have less experience with the kind of systematic innovation that leads to generalizable insights, because what little funding is available for primary care research is mostly awarded to large academic medical centers.1 AHRQ's practice-based research networks have not fully addressed this gap, as they have struggled to find infrastructure and maintain funding.1 In this commentary, we report on the lessons we learned over 2 years (2020-2022) from conducting primary care research through a novel alliance of an ACO consisting of independent practices, a health plan, and several academic researchers, with the support of a private foundation. [...]ACPNY found that experience with research facilitates innovation and readiness for health system change (lesson 1C).

Overcoming the Challenges of COVID-19

Agile and inventive pandemic response augurs in future-ready clinical trial management The onset of a global health emergency set innovation engines rolling, with active participation across the clinical research spectrum to find effective solutions. Here are 5 landmark solutions that were woven into the existing clinical trial fabric, with agility and innovation, to strengthen processes and make it relevant to current needs and beyond. 1.Accelerated trials to market lifesaving drugs faster When scientists began the process of developing a vaccine against COVID-19 in early 2020, the fastest vaccine that had been developed till then was the mumps vaccine in 4 years during the early 1960s. Navitas Life Sciences' OneClinical® Analytics platform is an artificial intelligence tool that has been shown to reduce clinical trial monitoring costs by 50% while bringing down cycle time by 30%.3 The near-real-time data insights gained from such tools aid in taking proactive corrective action helps resolve critical clinical trial issues at the onset, allowing intelligent deployment of resources.

HLA-B evolutionary divergence is associated with poor outcomes after SARS-CoV-2 infection

Objectives Human leukocyte antigens (HLA) are highly diverse transmembrane proteins that present viral peptides to T cells and launch pathogen-specific immune responses. We aim to investigate the correlation between HLA evolutionary divergence (HED), a surrogate for the capacity to present different peptides, and the outcomes of SARS-CoV-2 infection in a cohort from the St. Louis Metropolitan area. Methods We enrolled adult patients with SARS-CoV-2 infection confirmed by RT-PCR who were hospitalized at two tertiary hospitals in St. Louis between March and July 2020. Genomic DNA was extracted from peripheral blood and genotyped by next-generation sequencing (NGS). HLA alleles were assigned based on key-exon sequences (G group) and limited to the 2-field resolution. HED was calculated by Grantham distance, which considers the difference in composition, polarity, and molecular volume between each pair of amino acids from maternal and paternal HLA. The HED score was obtained for HLA class I (HLA-A, -B, and -C) genotypes using the HLAdivR package in R. Clinical data were collected retrospectively from electronic medical records. A poor outcome was defined as an admission to the intensive care unit (ICU), a need for mechanical ventilation, or death. A favorable outcome was defined as the absence of the above poor outcomes. Results A total of 234 patients were enrolled in this study, 96 being females (41%). The median age and BMI were 66 years old and 28.30 kg/m2, respectively. African Americans comprised 71.4% of the cohort. Only 19 patients (8.1%) presented with no comorbidity;the rest had one or more comorbidities, with cardiovascular diseases being the most common. A total of 137 (58.5%) patients had poor outcomes from SARS-CoV-2 infection, while 97 (41.5%) patients had a favorable outcome. We detected a significant association between higher HLA-B HED and favorable outcomes, with each 1-point increase in HLA-B HED associated with 8% increased probability for the composite endpoint (OR 1.08, 95% CI=1.01-1.16, P = 0.04). The HED scores calculated for HLA-A or HLA-C were not significantly different between patients with favorable or poor outcomes. In a multivariate logistic regression analysis, increased HLA-B HED score, younger age, and no comorbidity were independently associated with favorable outcomes (P = 0.02, P = 0.01, and P = 0.05, respectively). Conclusion Our study shows a significant correlation between lower HLA-B HED scores and poor outcomes after SARS-CoV-2 infection. This finding suggests that maximizing the presentation of diverse SARS-CoV-2 peptides by HLA-B alleles may improve the clearance of SARS-CoV-2. Further studies are warranted to understand the functional and mechanistic implications of this finding.

Research in brief

The deadly complication Scientists failed to find evidence that COVID-19 causes a "cytokine storm” leading to death in patients with COVID-19 but they did find that secondary bacterial pneumonia that does not resolve was a key driver of death in patients with COVID-19 and may have exceeded death rates from the viral infection itself. The approach grouped similar ICU patient-days into clinical states based on electronic health record data and allowed the scientists to discover how complications such as bacterial pneumonia impacted the course of illness. For more on complications in COVID19 see J Clin Investig 2023;published online April 27. https://doi.org/10.1172/JCI170682 For more on efficacious monoclonal antibodies see Ann Intern Med 2023;published online April 18. https://doi.org/10.7326/M22-3428 For more on targets for herpes virus see Sci Adv 2023;9: eadf3977 For more on an RSV vaccine in pregnancy see N Engl J Med 2023;388: 1451–64 For more on Pillar[5]arene see Nat Commun 2023;14: 2141 For more on doxycycline for STIs see N Engl J Med 2023;388: 1296–306 For more on immunity in tuberculosis see Nat Immunol 2023;24: 753–54

Economics of a Health System's Direct-to-Consumer Telemedicine for Its Employees

Am J Manag Care. 2023;29(6):In Press _____ Takeaway Points The value of direct-to-consumer (DTC) telemedicine services offered by academic health systems is understudied. * DTC telemedicine services for low-acuity or minor illnesses are increasingly offered as an employee benefit, but any per-episode unit cost advantage may be offset by overuse of care. * DTC telemedicine staffed by an academic health system and offered to its employees resulted in lower per-episode unit costs for care within 7 days and only marginally increased the use of services. * DTC telemedicine staffed by an academic health system and offered directly to employees was cost-saving. _____ Employers in the United States have increasingly been offering a direct-to-consumer (DTC) telemedicine benefit for low-acuity or minor illnesses to their employees.1-3 By 2021, more than 95% of employers with 50 or more employees provided some coverage for DTC telemedicine in their largest health plan;more than 75% felt that offering telemedicine was important and nearly 20% either limited or eliminated cost sharing for telemedicine.4 Despite these trends among general employers, few health systems have directly provided DTC telemedicine to their own employees. [...]because these services are easy to access (often available immediately, around the clock, and without travel), they may induce overuse of care, especially for self-limited conditions such as viral upper respiratory infections for which the alternative to in-person care is no care at all, thus increasing the overall cost of care.5-11 Telemedicine will save money relative to in-person care if any unit price advantages are not overwhelmed by the increased use of care overall, induced by its convenience. Employers provide health insurance coverage for 158 million Americans or nearly 50% of the population. Since the COVID-19 pandemic began, telemedicine has represented a significantly larger portion of all medical claims—consistently more than 5% of all medical claims by mid-202112-15—and the estimated value of the global telemedicine industry is projected to reach a quarter of a trillion dollars by 2024.13 Yet, the future of telemedicine remains undetermined with reimbursement rates in debate,16-18 driven in large part because its economic value is understudied and uncertain. Penn Medicine is self-insured and more than 95% of employees use its only employer-sponsored plan—a preferred provider organization (PPO) plan—rather than insurance obtained individually or through a family member. Since 2017, these PPO-insured employees have been offered Penn Medicine OnDemand,19 a 24/7 DTC telemedicine benefit to employees and their adult (≥ 18 years) dependents.

Q&A

In this interview, Jody Casey, vice president, healthcare partnerships at EUigo Health Research, highlights how the pandemic has put the spotlight on diversity in trials, how EUigo is working with physicians to make studies more accessibie, as well as what is in store for the future of appropriate representation in trials. There needs to be a greater breadth of population and diversity in trials. Because a COVID vaccine is so critically important for all Americans, it's been brought to light the fact that trials are generally lacking in diversity. Casey: A unique aspect of Elligo is that we securely access electronic health record (EHR) data from our physician partners.

Clinical Trial Technology: New Kids on the Block are Changing Industry Dynamics

Machine learning depends on training algorithms on large sets of data, Limaye notes, but many pharmaceutical companies securely protect their own clinical trial data in a way that's impenetrable to machine learning algorithms. Limaye adds that federated learning technologies, in which algorithms access data that never leaves its secure location, are emerging solutions to this problem that many drug manufacturers are embracing. According to Ngang, Amgen takes great pains to ensure that everyone, regardless of language or literacy level, understands what they are agreeing to as they begin a clinical trial, and says the same care can be taken with ensuring that all clinical trial participants know how to use a wearable sensor or other digital device. [...]ObvioHealth has developed a platform that continuously collects data gathered from wearables such as blood pressure levels, oxygenation levels, or heart rates of patients in clinical trials for different treatments-with the data fed to the research site in real time (or as soon as possible if the patient loses connectivity).