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A 48-year-old woman presented with isolated sixth cranial nerve palsy. She subsequently developed systemic lupus erythematosus (SLE) based on clinical and laboratory parameters. Three years later, she presented again with sixth cranial nerve palsy affecting the contralateral eye. Within 2 weeks of steroid initiation, complete recovery occurred. The unusual rare presentation of SLE in the current patient, as well as the pathogenesis and treatment of cranial neuropathy in SLE are discussed. [ABSTRACT FROM AUTHOR]

Longitudinal myelitis is an uncommon complication of systemic lupus erythematosus (SLE). We describe an unusual case of longitudinal myelitis and ischemic stroke in the presence of homozygous prothrombin G20210A, heterozygous MTHFR 677T mutations and the absence of antiphospholipid antibodies in a young woman with SLE. [ABSTRACT FROM AUTHOR]

We report a 39‐year‐old primigravida, a case of systemic lupus erythematosus (SLE) and secondary anti‐phospholipid syndrome (APS) with a smooth antenatal course who delivered by caesarean for non‐reassuring foetal heart rate. On day 2 postoperatively, she developed a sudden severe colicky upper abdominal pain with tachypnoea, dyspnoea, and tachycardia, and blood pressure (BP) reaching 150/95 mmHg. Computed tomography of the abdomen revealed lesions consistent with liver infarction. She developed haemolytic anaemia, elevated liver enzymes, and low platelets (HELLP syndrome); heparin and methylprednisolone were started. On day 3, BP normalized, respiratory symptoms improved but abdominal symptoms persisted. Methylprednisolone was increased to 80 mg/day on day 8 when she had significant clinical response and was discharged on day 16. This case emphasizes that a morbid clinical course including liver infarction should be anticipated in patients with SLE and APS complicated with HELLP syndrome. [ABSTRACT FROM AUTHOR]

The objective of the study was to describe the practice patterns of the antiphospholipid syndrome (APS) as compared with consensus guidelines for diagnosis and to determine whether practice patterns correlate with patient demographics and physician specialty. A retrospective medical chart review was conducted at the American University Hospital, in Beirut, Lebanon. All adult and pediatric patients admitted to the hospital between 1 January and 31 December 1998 who underwent either anticardiolipin antibodies (aCL) or lupus anticoagulant (LA) testing were included in the study. Work-up of APS syndrome was compared with: (a) the consensus guidelines for clinical diagnosis; (b) physician specialty; and (c) patient demographics (age, gender, ethnicity, health insurance status). Eighty-seven patients fulfilled at least one clinical criterion for APS; 92% were for work-up of thrombosis and 8% for pregnancy morbidities. Fifty-one percent underwent both aCL and LA. Overall 38% (33) of patients had an abnormal test result, however only 18% (6) underwent retesting, of whom only two satisfied a minimum of 6 weeks between test and retest. The APS diagnostic work-up was requested by 11 different specialties. Rheumatologists were the most consistent in asking for both tests. APS is seen and diagnosed by a variety of medical specialties. Practice patterns as compared with the latest consensus are sub-optimal, and need to be improved. Interventions to help improve this have been discussed and are being implemented. [ABSTRACT FROM AUTHOR]

The biological, physical and functional status change was measured in 104 patients with recent (< 1 year) onset synovitis. Measurements were taken initially and at 1 year. The purpose was to determine which biological and physical measures correlated with poor performance. Patients completed questionnaires quantifying activity, (the Human Activity Profile [HAP] and Sickness Impact Profile [SIP]), pain (Wisconsin Brief Pain Inventory), fatigue (Multidimensional Assessment of Fatigue), sleep, and mood (POMS and CESD). They were evaluated for articular involvement (Ritchie Index) and biological markers of disease activity (platelets, sedimentation rate, C-reactive protein and rheumatoid factor) (RF). In all, 30 men and 74 women participated. A total 445 patients met the American College of Rheumatology criteria for rheumatoid arthritis (RA); of these, 24 were rheumatoid factor (RF) positive, 18 had spondylitis, and 41 had unclassified arthritis. Low activity level at 1 year (HAP and SIP) correlated with high numbers of inflamed joints initially (p < 0.002); with more than 10 involved joints regardless of diagnostic group (p = 0.001); and joint symmetry (p < 0.009) A high platelet count was associated with low activity level at 1 year (p = 0.01); and high sedimentation rate was associated with more pain (p < 0.05). Low activity level (p < 0.09), fatigue (p = 0.03) and sleeplessness (p = 0.02) were correlated with RF + RA. [ABSTRACT FROM AUTHOR]

Familial clustering of elevated antiphospholipid antibody levels has been described, but the reports are heterogeneous with regard to the characterization of the antiphospholipid syndrome (APS), coexisting autoimmune diseases and clinical implications. We report a familial occurrence of APS in two patients, in the presence of SLE in the mother and absence of autoimmune diseases in the daughter along with acquired circulating inhibitors in both cases: platelet inhibitor and factor IX inhibitor, respectively. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in relation to the treatment of Sjogren's syndrome with rituximab.

Introduction: High quality and effective primary healthcare is a national priority in Qatar. Continuing professional development (CPD) for physicians is a cornerstone of this objective, yet little is known about physicians' preferences or barriers to CPD participation., Method: A needs assessment was conducted using a cross-sectional web-based survey of primary care physicians registered with the Department of Healthcare Practitioners (DHP) between March and June 2017., Results: Two-hundred-and-eighty-one complete surveys were submitted representing physicians in both public (N = 129) and private sectors (N = 152). Physicians completed medical degrees and postgraduate training across multiple countries, and most had been practicing in Qatar for 5 years or less. 'Activities during working hours', 'cost' and 'work commitments' were the most common barriers. There was little consensus regarding the optimal timing of CPD activities, although public sector physicians were more likely to indicate weekend activities as a barrier to participation (30% vs. 9%). Over 90% of participants preferred traditional lectures, workshops, case-based sessions, small group and online self-paced learning as formats for CPD delivery, however alternative modes of delivery were also deemed acceptable (> 80% agreement)., Conclusion: Understanding primary care physicians' barriers and preferences is an essential component of a larger necessitated needs assessment of CPD in primary care practitioners in Qatar. Further research is warranted to understand the underlying beliefs driving physicians' choices and the apparent variation between those working in the public and private sectors. CPD developers should consider approaches to mitigate perceived barriers and understand preferences to maximize the quality of participation., (© 2023. The Author(s).)

Established in 2015, the Multi-Stakeholder Engagement (MuSE) Consortium is an international network of over 120 individuals interested in stakeholder engagement in research and guidelines. The MuSE group is developing guidance for stakeholder engagement in the development of health and healthcare guideline development. The development of this guidance has included multiple meetings with stakeholders, including patients, payers/purchasers of health services, peer review editors, policymakers, program managers, providers, principal investigators, product makers, the public, and purchasers of health services and has identified a number of key issues. These include: (1) Definitions, roles, and settings (2) Stakeholder identification and selection (3) Levels of engagement, (4) Evaluation of engagement, (5) Documentation and transparency, and (6) Conflict of interest management. In this paper, we discuss these issues and our plan to develop guidance to facilitate stakeholder engagement in all stages of the development of health and healthcare guideline development., (© 2023. The Author(s).)

Background: Health research teams increasingly partner with stakeholders to produce research that is relevant, accessible, and widely used. Previous work has covered stakeholder group identification., Objective: We aimed to develop factors for health research teams to consider during identification and invitation of individual representatives in a multi-stakeholder research partnership, with the aim of forming equitable and informed teams., Design: Consensus development., Participants: We involved 16 stakeholders from the international Multi-Stakeholder Engagement (MuSE) Consortium, including patients and the public, providers, payers of health services/purchasers, policy makers, programme managers, peer review editors, and principal investigators., Approach: We engaged stakeholders in factor development and as co-authors of this manuscript. Using a modified Delphi approach, we gathered stakeholder views concerning a preliminary list of 18 factors. Over two feedback rounds, using qualitative and quantitative analysis, we concentrated these into ten factors., Key Results: We present seven highly desirable factors: 'expertise or experience', 'ability and willingness to represent the stakeholder group', 'inclusivity (equity, diversity and intersectionality)', 'communication skills', 'commitment and time capacity', 'financial and non-financial relationships and activities, and conflict of interest', 'training support and funding needs'. Additionally, three factors are desirable: 'influence', 'research relevant values', 'previous stakeholder engagement'., Conclusions: We present factors for research teams to consider during identification and invitation of individual representatives in a multi-stakeholder research partnership. Policy makers and guideline developers may benefit from considering the factors in stakeholder identification and invitation. Research funders may consider stipulating consideration of the factors in funding applications. We outline how these factors can be implemented and exemplify how their use has the potential to improve the quality and relevancy of health research., (© 2022. The Author(s).)

Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10 -8 ), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence., Objective: To develop a framework that characterizes the processes of development of living practice guidelines in health care., Design: First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines. Second, the core team drafted the first version of the framework. Finally, the core team refined the framework through an online survey and online discussions with a multidisciplinary international group of stakeholders., Setting: International., Participants: Multidisciplinary group of 51 persons who have experience with guidelines., Measurements: Not applicable., Results: A major principle of the framework is that the unit of update in a living guideline is the individual recommendation. In addition to providing definitions, the framework addresses several processes. The planning process should address the organization's adoption of the living methodology as well as each specific guideline project. The production process consists of initiation, maintenance, and retirement phases. The reporting should cover the evidence surveillance time stamp, the outcome of reassessment of the body of evidence (when applicable), and the outcome of revisiting a recommendation (when applicable). The dissemination process may necessitate the use of different venues, including one for formal publication., Limitation: This study does not provide detailed or practical guidance for how the described concepts would be best implemented., Conclusion: The framework will help guideline developers in planning, producing, reporting, and disseminating living guideline projects. It will also help research methodologists study the processes of living guidelines., Primary Funding Source: None.

Background: Adaptation of existing guidelines can be an efficient way to develop contextualized recommendations. Transparent reporting of the adaptation approach can support the transparency and usability of the adapted guidelines., Objective: To develop an extension of the RIGHT (Reporting Items for practice Guidelines in HealThcare) statement for the reporting of adapted guidelines (including recommendations that have been adopted, adapted, or developed de novo), the RIGHT-Ad@pt checklist., Design: A multistep process was followed to develop the checklist: establishing a working group, generating an initial checklist, optimizing the checklist (through an initial assessment of adapted guidelines, semistructured interviews, a Delphi consensus survey, an external review, and a final assessment of adapted guidelines), and approval of the final checklist by the working group., Setting: International collaboration., Participants: A total of 119 professionals participated in the development process., Measurements: Participants' consensus on items in the checklist., Results: The RIGHT-Ad@pt checklist contains 34 items grouped in 7 sections: basic information (7 items); scope (6 items); rigor of development (10 items); recommendations (4 items); external review and quality assurance (2 items); funding, declaration, and management of interest (2 items); and other information (3 items). A user guide with explanations and real-world examples for each item was developed to provide a better user experience., Limitation: The RIGHT-Ad@pt checklist requires further validation in real-life use., Conclusion: The RIGHT-Ad@pt checklist has been developed to improve the reporting of adapted guidelines, focusing on the standardization, rigor, and transparency of the process and the clarity and explicitness of adapted recommendations., Primary Funding Source: None.

The Medical Student Performance Evaluation (MSPE) is an important tool of communication used by program directors to make decisions in the residency application process. To understand the perspective and usage of the MSPE across multiple medical specialties now and in anticipation of the planned changes in USMLE Step 1 score-reporting. A survey instrument including quantitative and qualitative measures was developed and piloted. The final survey was distributed to residency programs across 28 specialties in 2020 via the main contact on the ACGME listserv. Of the 28 specialties surveyed, at least one response was received from 26 (93%). Eight percent of all programs (364/4675) responded to the survey, with most respondents being program directors. Usage of the MSPE varied among specialties. Approximately 1/3 of end-users stated that the MSPE is very or extremely influential in their initial screening process. Slightly less than half agreed or strongly agreed that they trust the information to be an accurate representation of applicants, though slightly more than half agree that the MSPE will become more influential once USMLE Step 1 becomes pass/fail. Professionalism was rated as the most important component and noteworthy characteristics among the least important in the decision-making process. Performance in the internal medicine clerkship was rated as the most influential while neurology and psychiatry performances were rated as less influential. Overwhelmingly, respondents suggested that including comparative performance and/or class rank would make the MSPE more useful once USMLE Step 1 becomes pass/fail. MSPE end-users across a variety of specialties utilize this complex document in different ways and value it differentially in their decision-making processes. Despite this, continued mistrust of the MSPE persists. A better understanding of end-users' perceptions of the MSPE offers the UME community an opportunity to transform the MSPE into a highly valued, trusted document of communication.

Background: Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA., Methods: Serum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1 H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation., Results: Using PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP., Conclusions: This study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jutley, Sahota, Sahbudin, Filer, Arayssi, Young and Raza.)

Objective: To develop updated guidelines for the pharmacologic management of rheumatoid arthritis., Methods: We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations., Results: The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional)., Conclusion: This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities., (© 2021, American College of Rheumatology.)

To evaluate the perceptions of patients with rheumatoid arthritis (RA) about self-assessment of their disease activity after watching an educational video. Consecutive patients with RA consulting their rheumatologist in six Middle Eastern Countries were invited to watch an educational video developed to teach self-assessment using Disease Activity Score (DAS-28). Then, a rheumatology nurse conducted a semi-structured interview and collected the patients' perception about the understanding of the video, feasibility, capability and confidence in performing self-assessment using Likert-type items. The degree of confidence with self-assessment was correlated to the patients' socio-demographic characteristics. Sixty-two patients were included and had an overall positive reaction to the video. It was easy to understand in 96% and helped facilitate self-assessment in 92% of cases. Self-assessment was considered totally feasible in 74%, and 66% of patients were capable of always doing it, with a confidence of 60% (always) to 34% (sometimes). Confidence was associated with a higher educational level. Nevertheless, 77% of patients felt that the self-assessment would not fully replace the physician's visit. Open-ended questions identified five themes: better understanding of the disease, easier communication with the rheumatologist, less consultation time, difficulty with the scoring part and importance of practice. Patients with RA felt that self-assessment was feasible and helpful in understanding RA, improving communication with the rheumatologist and shortening the visit time.

Objectives: The primary objective was to develop an educational video to teach patients with rheumatoid arthritis (RA) self-assessment of their disease activity. Secondary objectives were to validate the video, identify the challenges in producing it, and the responses to these challenges., Methods: Rheumatologists from 7 Middle Eastern Arab countries (MEAC) discussed unmet needs in the education of patients with RA. They reviewed pre-existing educational audiovisual material and drafted the script for a new video in Arabic. The video was produced in collaboration with a technical team, then validated by patients using a standardized interview. At each step of production, challenges were identified., Results: Twenty-three rheumatologists from MEAC identified unmet needs in patients' education. A video was produced, explaining the concepts of treat-to-target and showing a patient performing self-assessment using DAS-28. Sixty-two patients were interviewed for validation and found the video to be useful and easy to understand, albeit not replacing the physician's visit. Most common challenges encountered included acceptance of patient empowerment, agreement on DAS-28 as composite measure, production of a comprehensible written Arabic text, and addressing the population cultural mix., Conclusion: Despite challenges, the video was well accepted among patients and can be used for clinical and research purposes. It is particularly useful in pandemic periods where social distancing is recommended., (© 2021 The Mediterranean Journal of Rheumatology (MJR).)

Introduction: Due to the Covid-19 social distancing restrictions, in March 2020, Weill Cornell Medicine-Qatar decided to replace students' clinical instruction with novel online electives. Hence, we implemented an innovative online and remote pathology curriculum, anchored on virtual microscopy and Zoom videoconferencing: ideal tools to support online teaching., Objective: To assess a new curriculum implementation at Weill Cornell Medicine-Qatar., Materials and Methods: This for-credit, 2-week elective included 6 synchronous Zoom sessions where complex clinicopathological cases were discussed in small groups. We used open access digital microscopy slides from the University of Leeds' Virtual Pathology Library (http://www.virtualpathology.leeds.ac.uk/slides/library/). Students independently prepared for these sessions by reviewing cases, slides, readings, and questions in advance (asynchronous self-directed learning anchored on a flipped classroom model), and wrote a final review of a case. An assessment and feedback were given to each student., Results: Four elective iterations were offered to a total of 29 students, with learners and faculty spread over 4 countries. During the Zoom sessions, students controlled the digital slides and offered their own diagnoses, followed by group discussions to strengthen autonomy and confidence. We surveyed learners about the elective's performance (program evaluation). Students conveyed high levels of satisfaction about the elective's overall quality, their pathology learning and online interactions, with minimal challenges related to the remote nature of the course., Discussion and Conclusions: Technological innovations mitigate sudden disruptions in medical education. A remote curriculum allows instruction at any distance, at any time, from anywhere, enhancing educational exchanges, flexibility and globalization in medical education., Competing Interests: Conflict of InterestNone. The authors have no relevant financial or non-financial interests to disclose., (© The Author(s) 2021.)

Purpose: Meaningful participation in research for both faculty and residents is generally viewed to be an essential component of residency training. To better understand best practices in residency research, the authors conducted a survey among Internal Medicine (IM) Residency Programs with experience in research., Methods: Phone interviews were conducted with a convenience sample of Residency Program Directors (PDs). Survey responses were analyzed across the following domains: size and makeup of the residency and research programs, resources for research, role of the PD/research director (RD), profile of trainees doing research, curriculum description, scope of research, role of mentors, career choices and determinants of success., Results: Fifteen programs were included in the study. Across these programs, approximately two-thirds of residents were involved in research during their training . Eighty percent of the programs required an application for residents to engage in research. Ninety-two percent of the programs had a RD but only 58% had a formal research curriculum. Clinical research projects were the most common types of research. On average, two-thirds of residents involved in research submitted abstracts to regional and/or national meetings. The factor most frequently associated with resident research success was an effective faculty research mentor., Conclusions: Research success during residency is multifactorial. The authors propose that having a robust structure for research that is led by a residency RD, and the presence of effective mentors and strong administrative support are critical for success., (Published by Elsevier Inc.)

Background: Communication skills is a core area of competency for healthcare practitioners. However, trainees deficient in those skills are not identified early enough to address the deficiency. Furthermore, faculty often struggle to identify effective remediation strategies for those who fail to meet expectations. We undertook a systematic review to determine which assessment methods are appropriate to identify learners that struggle with communication skills and the strategies used to remediate them., Methods: The literature was searched from January 1998 through to May 2019 using academic databases and grey literature. Trainees were defined as healthcare practitioners in undergraduate, graduate and continuing education. Characteristics of studies, assessment and intervention strategies and outcomes were synthesized qualitatively and summarized in tables., Results: From an initial 1636 records, 16 (1%) studies met the review criteria. Majority of the learners were medical students. A few studies (44%) included students from other disciplines, residents and physicians in practice. The remediation programs, in the studies, ranged from 1 week to 1 year. Around half of the studies focused solely on learners struggling with communication skills. The majority of studies used a format of a clinical OSCE to identify struggling learners. None of the studies had a single intervention strategy with the majority including an experiential component with feedback., Conclusions: A few studies collectively described the diagnosis, remediation intervention and the assessment of the outcomes of remediation of communication skills. For a remediation strategy to be successful it is important to ensure: (i) early identification and diagnosis, (ii) the development of an individualized plan and (iii) providing reassessment with feedback to the learner.

The diversity in our genome is crucial to understanding the demographic history of worldwide populations. However, we have yet to know whether subtle genetic differences within a population can be disentangled, or whether they have an impact on complex traits. Here we apply dimensionality reduction methods (PCA, t-SNE, PCA-t-SNE, UMAP, and PCA-UMAP) to biobank-derived genomic data of a Japanese population (n = 169,719). Dimensionality reduction reveals fine-scale population structure, conspicuously differentiating adjacent insular subpopulations. We further enluciate the demographic landscape of these Japanese subpopulations using population genetics analyses. Finally, we perform phenome-wide polygenic risk score (PRS) analyses on 67 complex traits. Differences in PRS between the deconvoluted subpopulations are not always concordant with those in the observed phenotypes, suggesting that the PRS differences might reflect biases from the uncorrected structure, in a trait-dependent manner. This study suggests that such an uncorrected structure can be a potential pitfall in the clinical application of PRS.

Introduction: The adaptation of guidelines is an increasingly used methodology for the efficient development of contextualised recommendations. Nevertheless, there is no specific reporting guidance. The essential Reporting Items of Practice Guidelines in Healthcare (RIGHT) statement could be useful for reporting adapted guidelines, but it does not address all the important aspects of the adaptation process. The objective of our project is to develop an extension of the RIGHT statement for the reporting of adapted guidelines (RIGHT-Ad@pt Checklist)., Methods and Analysis: To develop the RIGHT-Ad@pt Checklist, we will use a multistep process that includes: (1) establishment of a Working Group; (2) generation of an initial checklist based on the RIGHT statement; (3) optimisation of the checklist (an initial assessment of adapted guidelines, semistructured interviews, a Delphi consensus survey, an external review by guideline developers and users and a final assessment of adapted guidelines); and (4) approval of the final checklist. At each step of the process, we will calculate absolute frequencies and proportions, use content analysis to summarise and draw conclusions, discuss the results, draft a report and refine the checklist., Ethics and Dissemination: We have obtained a waiver of approval from the Clinical Research Ethics Committee at the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain). We will disseminate the RIGHT-Ad@pt Checklist by publishing into a peer-reviewed journal, presenting to relevant stakeholders and translating into different languages. We will continuously seek feedback from stakeholders, surveil new relevant evidence and, if necessary, update the checklist., Competing Interests: Competing interests: EAA and HJS have intellectual CoIs related to his contribution to the development of methods of guideline adaptation, the RIGHT statement and methodological studies in the field. SB is the Analyses Advisor for BMJ and Associate Editor at BMJ Global Health and BMC Systematic Reviews. All other members have nothing to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Medical School Performance Evaluation (MSPE) is an important factor for application to residency programs. Many medical schools are incorporating recent recommendations from the Association of American Medical Colleges MSPE Task Force into their letters. To date, there has been no feedback from the graduate medical education community on the impact of this effort., Objective: We surveyed individuals involved in residency candidate selection for internal medicine programs to understand their perceptions on the new MSPE format., Methods: A survey was distributed in March and April 2018 using the Association of Program Directors in Internal Medicine listserv, which comprises 4220 individuals from 439 residency programs. Responses were analyzed, and themes were extracted from open-ended questions., Results: A total of 140 individuals, predominantly program directors and associate program directors, from across the United States completed the survey. Most were aware of the existence of the MSPE Task Force. Respondents read a median of 200 to 299 letters each recruitment season. The majority reported observing evidence of adoption of the new format in more than one quarter of all medical schools. Among respondents, nearly half reported the new format made the MSPE more important in decision-making about a candidate. Within the MSPE, respondents recognized the following areas as most influential: academic progress, summary paragraph, graphic representation of class performance, academic history, and overall adjective of performance indicator (rank)., Conclusions: The internal medicine graduate medical education community finds value in many components of the new MSPE format, while recognizing there are further opportunities for improvement., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Objectives: There is limited information on the epidemiology and treatment patterns of rheumatoid arthritis (RA) across the Arab region. We aim in this study to describe the demographic characteristics, clinical profile, and treatment patterns of patients of Arab ancestry with RA., Methods: This is a cross sectional study of 895 patients with established rheumatoid arthritis enrolled from five sites (Jordan, Lebanon, Qatar, Kingdom of Saudi Arabia (KSA), and United Arab Emirates). Demographic characteristics, clinical profile, and treatment patterns are compared between the five countries., Results: The majority of our patients are women, have an average disease duration of 10 years, are married and non-smokers, with completed secondary education. We report a high (>80%) ever-use of methotrexate (MTX) and steroids among our RA population, while the ever-use of disease modifying anti-rheumatic drugs (DMARDs) and TNF-inhibitors average around 67% and 33%, respectively. There are variations in RA treatment use between the five country sites. Highest utilization of steroids is identified in Jordan and KSA (p-value < 0.001), while the highest ever-use of TNF-inhibitors is reported in KSA (p-value < 0.001)., Conclusion: Disparities in usage of RA treatments among Arab patients are noted across the five countries. National gross domestic product (GDP), as well as some other unique features in each country likely affect these. Developing treatment guidelines specific to this region could contribute in delivering standardized therapies to RA patients., Competing Interests: The authors have declared that no competing interests exist.

Clinical practice guidelines can assist rheumatologists in the proper prescription of newer treatment for rheumatoid arthritis (RA). The objective of this paper is to report on the recommendations for the management of patients with RA in the Eastern Mediterranean region. We adapted the 2015 American College of Rheumatology guidelines in two separate waves. We used the adolopment methodology, and followed the 18 steps of the "Guidelines 2.0" comprehensive checklist for guideline development. For each question, we updated the original guidelines' evidence synthesis, and we developed an Evidence Profile (EP) and an Evidence to Decision (EtD) table. In the first wave, we adoloped eight out of the 15 original questions on early RA. The strength changed for five of these recommendations from strong to conditional, due to one or more of the following factors: cost, impact on health equities, the balance of benefits, and harms and acceptability. In the second wave, we adoloped eight out of the original 44 questions on established RA. The strength changed for two of these recommendations from strong to conditional, in both cases due to cost, impact on health equities, balance of benefits and harms, and acceptability. The panel also developed a good practice recommendation. We successfully adoloped 16 recommendations for the management of early and established RA in the Eastern Mediterranean region. The process proved feasible and sensitive to contextual factors.

In the original version of this article the first name of the co-author was incorrectly spelled as "Khaled A. Alnaqbi". The correct spelling should have been "Khalid A. Alnaqbi". This is now presented correctly in this article.

Background: It has been hypothesized that adaptation of health practice guidelines to the local setting is expected to improve their uptake and implementation while cutting on required resources. We recently adapted the published American College of Rheumatology (ACR) Rheumatoid Arthritis (RA) treatment guideline to the Eastern Mediterranean Region (EMR). The objective of this paper is to describe the process used for the adaptation of the 2015 ACR guideline on the treatment of RA for the EMR., Methods: We used the GRADE-Adolopment methodology for the guideline adaptation process. We describe in detail how adolopment enhanced the efficiency of the following steps of the guideline adaptation process: (1) groups and roles, (2) selecting guideline topics, (3) identifying and training guideline panelists, (4) prioritizing questions and outcomes, (5) identifying, updating or conducting systematic reviews, (6) preparing GRADE evidence tables and EtD frameworks, (7) formulating and grading strength of recommendations, (8) using the GRADEpro-GDT software., Results: The adolopment process took 6 months from January to June 2016 with a project coordinator dedicating 40% of her time, and the two co-chairs dedicating 5% and 10% of their times respectively. In addition, a research assistant worked 60% of her time over the last 3 months of the project. We held our face-to-face panel meeting in Qatar. Our literature update included five newly published trials. The certainty of the evidence of three of the eight recommendations changed: one from moderate to very low and two from low to very low. The factors that justified a very low certainty of the evidence in the three recommendations were: serious risk of bias and very serious imprecision. The strength of five of the recommendations changed from strong to conditional. The factors that justified the conditional strength of these 5 recommendations were: cost (n = 5 [100%]), impact on health equities (n = 4 [80%]), the balance of benefits and harms (n = 1 [20%]) and acceptability (n = 1 [20%])., Conclusion: This project confirmed the feasibility of GRADE-Adolopment. It also highlighted the value of collaboration with the organization that had originally developed the treatment guideline. We discuss the implications for both guideline adaptation and future research to advance the field.

Recent metabolomics studies of Rheumatoid Arthritis (RA) reported few metabolites that were associated with the disease, either due to small cohort sizes or limited coverage of metabolic pathways. Our objective is to identify metabolites associated with RA and its cofounders using a new untargeted metabolomics platform. Moreover, to investigate the pathomechanism of RA by identifying correlations between RA-associated metabolites. 132 RA patients and 104 controls were analyzed for 927 metabolites. Metabolites were tested for association with RA using linear regression. OPLS-DA was used to discriminate RA patients from controls. Gaussian Graphical Models (GGMs) were used to identify correlated metabolites. 32 metabolites are identified as significantly (Bonferroni) associated with RA, including the previously reported metabolites as DHEAS, cortisol and androstenedione and extending that to a larger set of metabolites in the steroid pathway. RA classification using metabolic profiles shows a sensitivity of 91% and specificity of 88%. Steroid levels show variation among the RA patients according to the corticosteroid treatment; lowest in those taking the treatment at the time of the study, higher in those who never took the treatment, and highest in those who took it in the past. Finally, the GGM reflects metabolite relations from the steroidogenesis pathway.

Objective: Genetic factors underlying susceptibility to rheumatoid arthritis (RA) in Arab populations are largely unknown. This genome-wide association study (GWAS) was undertaken to explore the generalizability of previously reported RA loci to Arab subjects and to discover new Arab-specific genetic loci., Methods: The Genetics of Rheumatoid Arthritis in Some Arab States Study was designed to examine the genetics and clinical features of RA patients from Jordan, the Kingdom of Saudi Arabia, Lebanon, Qatar, and the United Arab Emirates. In total, >7 million single-nucleotide polymorphisms (SNPs) were tested for association with RA overall and with seropositive or seronegative RA in 511 RA cases and 352 healthy controls. In addition, replication of 15 signals was attempted in 283 RA cases and 221 healthy controls. A genetic risk score of 68 known RA SNPs was also examined in this study population., Results: Three loci (HLA region, intergenic 5q13, and 17p13 at SMTNL2/GGT6) reached genome-wide significance in the analyses of association with RA and with seropositive RA, and for all 3 loci, evidence of independent replication was demonstrated. Consistent with the findings in European and East Asian populations, the association of RA with HLA-DRB1 amino acid position 11 conferred the strongest effect (P = 4.8 × 10 -16 ), and a weighted genetic risk score of previously associated RA loci was found to be associated with RA (P = 3.41 × 10 -5 ) and with seropositive RA (P = 1.48 × 10 -6 ) in this population. In addition, 2 novel associations specific to Arab populations were found at the 5q13 and 17p13 loci., Conclusion: This first RA GWAS in Arab populations confirms that established HLA-region and known RA risk alleles contribute strongly to the risk and severity of disease in some Arab groups, suggesting that the genetic architecture of RA is similar across ethnic groups. Moreover, this study identified 2 novel RA risk loci in Arabs, offering further population-specific insights into the pathophysiology of RA., (© 2017, American College of Rheumatology.)

Background: The Arab world has seen an increase in the burden of musculoskeletal diseases. No bibliometric studies have characterized rheumatology research in the Arab world. This study evaluates the productivity and impact of rheumatology research in the Arab world., Methods: We searched the Web of Science Core Collection for rheumatology publications, from 1976 to 2014, for each of the Arab League (AL) countries, North America, Europe and Asia. For the AL countries, the overall trend of publications and citations was analyzed, while considering the paper type and collaborations., Results: The AL countries published 944 rheumatology papers over the period studied. The number of publications increased by a factor of 2.77 (95 % CI, 2.75-2.78) each decade, and citations increased by a factor of 2.36 (95 % CI, 0.96-5.82). The absolute number of papers included in the top-10 rheumatology journals remained constant but the proportion decreased. Papers involving collaboration among AL countries were found to increase over time., Conclusions: Overall, the AL countries lag in research productivity and impact compared to other regions. Three countries are responsible for the majority of publications, while four countries receive the majority of citations.

A panel of experts commissioned by the American College of Rheumatology have recently reviewed the literature related to the treatment of patients with ankylosing spondylitis and nonradiographic axial spondyloarthritis. They published a set of recommendations for the management of common clinical questions for both active and stable disease, including the appropriate use of nonsteroidal anti-inflammatory drugs, tumor necrosis factor inhibitors, rehabilitation, education, and preventive care. This article summarizes these recommendations and provides key practical messages for physicians taking care of these patients.

This study aims at identifying metabolites that significantly associate with self-reported joint symptoms (diagnostic) and metabolites that can predict the change from a symptom-free status to the development of self-reported joint symptoms after a 7 years period (prognostic). More than 300 metabolites were analyzed for 2246 subjects from the longitudinal study of the KORA (Cooperative Health Research in the Region of Augsburg, Germany), specifically the fourth survey S4 and its 7-year follow-up study F4. Two types of self-reported symptoms, chronic joint inflammation and worn out joints, were used for the analyses. Diagnostic analysis identified dysregulated metabolites in cases with symptoms compared with controls. Prognostic analysis identified metabolites that differentiate subjects in S4 who remained symptom-free after 7 years (F4) from those who developed any combination of symptoms. 48 metabolites were identified as nominally significantly (p < 0.05) associated with the self-reported symptoms in the diagnostic analysis, among which steroids show Bonferroni significance. 45 metabolites were identified as nominally significantly associated with developing symptoms after 7 years, among which hippurate showed Bonferroni significance. We show that metabolic profiles of self-reported joint symptoms are in line with metabolites known to associate with various forms of arthritis and suggest that future studies may benefit from that by investigating the possible use of self-reporting/questionnaire along with metabolic markers for the early referral of patients for further diagnostic workup and treatment of arthritis.

Behçet's disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Behçet's disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria - there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time.

Behçet disease is a chronic inflammatory systemic disorder, characterized by a relapsing and remitting course. It manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. The main histopathological finding is a widespread vasculitis of the arteries and veins of any size. The cause of this disease is presumed to be multifactorial involving infectious triggers, genetic predisposition, and dysregulation of the immune system. As the clinical expression of Behçet disease is heterogeneous, pharmacological therapy is variable and depends largely on the severity of the disease and organ involvement. Treatment of Behçet disease continues to be based largely on anecdotal case reports, case series, and a few randomized clinical trials.

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2 × 10(-6)). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted.

Aim: To estimate the prevalence of rheumatic diseases in Lebanon and to explore their distribution by geographic location, age, and gender., Method:   Using the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) methodology, a random sample of 3530 individuals aged 15 and above was interviewed from the six Lebanese governorates. Positive respondents were evaluated by rheumatologists using the internationally accepted classification criterion of the American College of Rheumatology for the diagnosis of rheumatic diseases., Results: Prevalence rates of current and past musculoskeletal problems were 24.4% and 8.4%, respectively. Shoulder (14.3%), knee (14.2%) and back (13.6%) were the most common pain sites. Point prevalence of rheumatic diseases was 15.0%. The most frequent types of rheumatic diseases were of mechanical origin, namely soft tissue rheumatism (5.8%) and osteoarthritis (4.0%). Rheumatoid arthritis (1.0%) and spondylathropathies (0.3%) constituted the most common inflammatory diseases. Coastal areas had the lowest prevalence of all diseases except for fibromyalgia. All diseases showed an increasing prevalence pattern with age and a higher prevalence among women than men., Conclusion: This is the first study to give population-based estimates of rheumatic diseases in Lebanon. The high burden calls for public health attention for early detection, control and prevention of these conditions. Point prevalence of individual diseases was within the range of results from other COPCORD surveys with some variations that can be attributed to differences in methodology and geo-ethnic factors., (© 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.)

Objectives: Musculoskeletal conditions have only recently been acknowledged and research on their burden is scarce in the Middle East and North African (MENA) region. For the first time, a population based study was conducted in Lebanon to assess the prevalence, level of disability, and health seeking behaviours related to musculoskeletal pain and rheumatic disorders., Methods: A random sample of 500 participants aged ≥ 15 years from Southern Lebanon was interviewed using the COPCORD (Community Oriented Program for Control of Rheumatic Diseases) questionnaire., Results: The prevalence of current musculoskeletal pain was 31.2% [CI (27.0-35.2%)]. Being a female [OR=1.8, CI (1.2-2.8)] and of advancing age [OR=1.03, CI (1.01-1.05)] were the only significant factors associated with current musculoskeletal pain. Prevalence of current functional disability was 6.4% [CI (4.2-8.5%)]. Around quarter (26.0%) [CI (22.3-30.1%)] of our sample sought some kind of treatment. The overall prevalence rate of rheumatic disease was 17.0% [CI (13.7-20.3%)]., Discussion: Our findings indicate that musculoskeletal conditions are common in Lebanon. This is a timely public health issue that needs further investigation and solid recognition by health authorities. Community-based interventions should target patients to prompt them to seek early help in order to prevent the development of musculoskeletal pain into disorders.

Background: Currently, there is one Behçet's disease (BD) specific self reporting questionnaire developed and published in the literature, The Leeds BD-quality of life (QoL). We conducted a cross-cultural adaptation and validation of the Arabic version of the Leeds BD-QoL METHODS: A cross-sectional study was conducted among 41 consecutive patients attending rheumatology clinics at the American University of Beirut Medical Center between June and December 2007. The BD-QoL questionnaire, the Katz Index of Activities of Daily Living (ADL) and the Lawton Instrumental Activities of Daily Living (IADL) questionnaires were co-administered during the same visit, and severity scores were calculated. Cross-cultural adaptation of BD-QoL was performed using forward and backward translations of the original questionnaire. Internal consistency and test-retest reliability of the final version were determined. Exploratory Factor Analysis (EFA) was used to assess the dimensionality of the scale items. External construct validity was examined by correlating Arabic BD-QoL with the severity score, ADL and IADL., Results: The 30 items of the adapted Arabic BD-QoL showed a high internal consistency (KR-20 coefficient 0.89) and test-retest reliability (Spearman's test 0.91). The convergence of all 30 items suggests that the 30-item adapted Arabic BD-QoL scale is unidimensional. BD-QoL did not correlate with any of the patients' demographics. Still, it was positively correlated with patient severity score (r 0.4, p 0.02), and IADL (but not ADL)., Conclusions: This cross-cultural adaptation has produced an Arabic BD-QoL questionnaire that is now available for use in clinical settings and in research studies, among Arabic speaking patients.