What is the best referral strategy for axial spondyloarthritis? A prospective multicenter study in patients with suspicious chronic low back pain.

OBJECTIVE: To assess the value of referral strategies for axial spondyloarthritis (axSpA) in patients with suspicious chronic inflammatory low back pain (LBP), to estimate the value of inflammatory back pain (IBP) for referral, and to identify the predictive factors of the final diagnosis of axSpA in Middle Eastern Arab countries. METHODS: The study was multicentric, prospective, and conducted in LBP first-line clinics (rheumatology, internal, family medicine, orthopedic surgery, neurosurgery, and neurology). Consecutive adult patients aged under 45years were included in case of LBP suspicious of inflammatory nature according to the first-line physician. The rheumatologist's final diagnosis was the gold standard. The diagnostic properties of ten referral strategies (Brandt I, II, III, Hermann, RADAR, RADAR 2/3, MASTER, Braun, CAFASPA, and ASAS) and of IBP were calculated. A multivariable logistic regression identified the clinical predictive factors of axSpA. RESULTS: In 515 referred patients, axSpA was confirmed in 48%, refuted in 43%, and diagnosis remained inconclusive in 9%. The optimal referral strategy was the MASTER (PLR 3.3), which comprises IBP, good response to NSAIDs, positive HLA-B27, and SpA family history. Considering strategies without HLA-B27, the RADAR 2/3 had a PLR of 2.9 (IBP, good response to NSAIDs, any extra-musculoskeletal manifestation). The predictive factors for axSpA were MRI sacroiliitis, positive HLA-B27, high CRP, psoriasis, IBP, and longer symptom duration. Of all patients, 35% were self-referred, 16% were referred by primary care physicians, and 15% by neuro/orthopedic surgeons. CONCLUSION: Optimizing physicians' awareness of these clinical features may enhance referral in axSpA.

Adding colchicine to tocilizumab in hospitalized patients with severe COVID-19 pneumonia: An open-label randomized controlled trial.

INTRODUCTION: Colchicine acts upstream in the cytokines cascade by inhibiting the nod-like receptor protein 3 (NLRP3) inflammasome while interleukin 6 (IL-6) receptor antagonists, such as tocilizumab, block the end result of the cytokines cascade. Hence, adding colchicine to tocilizumab with the aim of blocking the early and end products of the cytokines cascade, might reduce the risk of developing cytokine storm. METHODS AND ANALYSIS: We aim to conduct an open-label randomized controlled trial to evaluate the efficacy and safety of adding colchicine to tocilizumab among patients with severe COVID-19 pneumonia to reduce the rate of invasive mechanical ventilation and mortality. We will include patients with severe COVID-19 pneumonia who received tocilizumab according to our local guidelines. Enrolled patients will be then randomized in 1:1 to colchicine versus no colchicine. Patients will be followed up for 30 days. The primary outcome is the rate of invasive mechanical ventilation and will be determined using Cox proportional hazard model. DISCUSSION: Given colchicine's ease of use, low cost, good safety profile, and having different anti-inflammatory mechanism of action than other IL-6 blockade, colchicine might serve as a potential anti-inflammatory agent among patients with severe COVID-19 pneumonia. This study will provide valuable insights on the use of colchicine in severe COVID-19 when added to IL-6 antagonists. ETHICS AND DISSEMINATION: The Medical Research Center and Institutional Review Board at Hamad Medical Corporation in Qatar approved the study protocol (MRC-01-21-299). Results of the analysis will be submitted for publication in a peer-reviewed journal.

Risk of Severe SARS-CoV-2 Infection in Patients with Autoimmune Rheumatic Diseases in Qatar: A Cohort Matched Study.

BACKGROUND: It remains unclear whether patients with autoimmune rheumatic diseases (ARDs) are at a higher risk of poor outcomes from a SARS-CoV-2 infection. We evaluated whether patients with an ARDs infected with SARS-CoV-2 were at a higher risk of a poorer outcome than those without an ARDs. METHODS: Patients with an ARDs infected with SARS-CoV-2 were matched to control patients without a known ARDs. Matching was performed according to age ( ± 6 years) and sex at a case-to-control ratio of 1:3. Demographic and clinical data were extracted from the databases and were compared between the two groups. Severe SARS-CoV-2 infection was the primary outcome and was defined as the requirement for oxygen therapy support, the need for invasive or noninvasive mechanical ventilation, or the use of glucocorticoids. RESULTS: A total of 141 patients with an ARDs were matched to 398 patients who formed the control group. The mean ages (SD) of the ARDs and non-ARDs groups were 44.4 years (11.4) and 43.4 years (12.2). Women accounted for 58.8% of the ARDs group and 56.3% of the control group (p = 0.59). Demographics and comorbidities were balanced between the groups. ARDs included connective tissue disease in 43 (30.3%) patients, inflammatory arthritis in 92 (65.2%), and other ARDs in 8 (5.7%). ARDs medications included biological/targeted synthetic disease-modifying antirheumatic drugs (b/ts-DMARDs) in 28 (15.6%) patients, conventional synthetic DMARDs in 95 (67.4%), and immunosuppressive antimetabolites in 13 (9.2%). The ARDs group had more respiratory and gastrointestinal symptoms related to SARS-CoV-2 infection than the control group (24.8% and 20.6% vs. 10% and 5.3%, respectively; p <  0.001 for both). Severe SARS-CoV-2 infection was more common in the ARDs group than in the control group (14.9% vs. 5.8%; p <  0.001). CONCLUSIONS: In this single-center matched cohort study, patients with an ARDs experienced more respiratory and gastrointestinal symptoms related to SARS-CoV-2 infection and had more severe infection than those from the control group. Therefore, patients with an ARDs require close observation during the coronavirus disease 2019 pandemic.

Demyelinating Neurological Adverse Events following the Use of Anti-TNF-α Agents: A Double-Edged Sword.

Background: Tumor necrosis factor antagonists (anti-TNF-α) are an established therapeutic option for several autoimmune and inflammatory bowel diseases. Despite their clinical effectiveness, neurological adverse events have been reported, and literature data suggest a potential role of anti-TNF-α in the induction of demyelination. Case Presentation. In this series, we present three cases of demyelination after the use of anti-TNF-α agents. The first case involved a 21-year-old man with HLA-B27 negative peripheral spondylarthritis who had been taking adalimumab for 2 years. He developed headache, urinary incontinence, and bilateral lower extremity numbness that progressed to the middle of the trunk for 2 days. Magnetic resonance imaging (MRI) showed multiple hyperintense enhancement lesions in the left paramedian anterior pons consistent with multiple sclerosis (MS). The second case included a 17-year-old woman who was on 2 years of adalimumab treatment for juvenile idiopathic arthritis and chronic anterior uveitis and developed new-onset dizziness and tremors. The clinical examination showed signs of cerebellar dysfunction. MRI findings were consistent with multiple sclerosis. The third case was a 34-year-old male who was on 5 years of infliximab treatment for ankylosing spondylitis when he developed left hand numbness and weakness. Cerebrospinal fluid (CSF) analysis and MRI findings were consistent with demyelination. Discontinuation of tumor necrosis factor antagonists (anti-TNF-α) resulted in resolution of the symptoms with no recurrence in the first case, but there was evidence of recurrence in the other 2 cases, where one was managed with rituximab and the second one improved with pulse steroid therapy. Conclusion: Despite the small number of patients, our series adds to the growing body of evidence supporting a causal link between anti-TNF-α agents and demyelination. Thus, we can conclude that on suspicion of any neurological side effects, early discontinuation of the TNF-α blockers and requesting urgent MRI scan to confirm the diagnosis is of utmost importance.

Incidence rate of osteoporotic hip fracture in Qatar.

The incidence rate of osteoporotic hip fracture is essential to formulate a national fracture risk assessment tool (FRAX). In this epidemiological study, the incidence rate of osteoporotic hip fracture in Qatar was comparable to that in regional countries, and lower than that in North America and European countries. PURPOSE: Estimate the annual incidence rate (IR) of osteoporotic hip fractures (OHF) in Qatar from January 2017 to December 2019. METHODS: Hamad Medical Corporation is a government-based tertiary medical institute. Hip fractures were captured by using the International Classification of Diseases-10 hip fracture codes. The patient records were reviewed retrospectively to identify fracture mechanisms. The observed census in 2017 and the estimated censuses of 2018 and 2019 were used to calculate the age-sex-specific annual IR of OHF in the population aged ≥ 40 years. The world population in 2010 was used to calculate the age-adjusted standardized IR in the population aged ≥ 50 years. RESULTS: In total, 458 hip fractures were identified; 75 (16.4%) were due to high-energy trauma, and 9 (2%) were pathological hip fractures. The total number of OHF was 374 (81.7%). OHF was slightly higher in men (215, 57.5%). The median age (IQR) of the patients was 69 years (56-78 years). In 2017, 2018, and 2019, the age-adjusted standardized IR of OHF per 100,000 with the corresponding 95% CI was 141.7 (141.1-142.2), 140.8 (140.2-141.3), and 162.7 (162.0-163.2) for the whole Qatar population; 154.2 (153.6-154.7), 105.2 (104.7-105.7), and 176.6 (175.9-177.1) for Qataris; and 134.8 (134.3-135.4), 183.9 (183.3-184.6), and 160.4 (159.8-161.0) for non-Qataris, respectively. CONCLUSION: The annual age-adjusted standardized IR of OHF per 100,000 inhabitants aged ≥ 50 years in Qatar was comparable to that in regional countries, and lower than that in North America and European countries.

Increased Fracture Risk After Bariatric Surgery: a Case-Controlled Study with a Long-Term Follow-Up.

PURPOSE: Bariatric surgeries are common procedures due to the high prevalence of obesity. This study aimed to investigate whether bariatric surgery increases fracture risk. MATERIAL AND METHODS: It was a case-controlled study. Patients who underwent bariatric surgery during 2011 and 2012 were matched for age (± 5 years) and gender to patients on medical weight management during the same period with a ratio of 1:2. The index date was defined as the date of bariatric surgery for both groups. The subject's electronic medical records were reviewed retrospectively to identify fractures documented by radiology during January 2020. RESULTS: Randomly selected 403 cases were matched to 806 controls with a median age of 36.0 years (IQR 14.0) and 37.0 years (IQR 14.0), respectively. Seventy per cent of the cohort were females. Eighty per cent received sleeve gastrectomy, and the remaining (17%) underwent gastric bypass. The mean duration of follow-up was 8.6 years. The fracture rate was higher in the surgical group as compared to the controls (9.4% vs 3.5%) with a crude odds ratio of 2.71 (95% CI 1.69-4.36). The median duration for time to fracture was 4.17 years for the surgical group and 6.09 years for controls (p-value = 0.097). The most common site of fractures was feet, followed by hands. Apart from a few wrist fractures, there was no typical osteoporotic sites fracture. CONCLUSION: Subjects who underwent bariatric procedures had more non-typical osteoporotic site fractures affecting mainly feet and hands, and fractures tend to occur earlier as compared to controls.

Prevalence and clinical significance of antiphospholipid antibodies in patients with coronavirus disease 2019 admitted to intensive care units: a prospective observational study.

Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19-induced coagulopathy, its clinical significance remains uncertain. Therefore, this study aimed to evaluate the prevalence and clinical significance of aPLs among critically ill patients with COVID-19. This prospective observational study included 60 patients with COVID-19 admitted to intensive care units (ICU). The study outcomes included prevalence of aPLs, and a primary composite outcome of all-cause mortality and arterial or venous thrombosis between antiphospholipid-positive and antiphospholipid-negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. A total of 60 critically ill patients were enrolled. Among them, 57 (95%) were men, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found be antiphospholipid-positive; 21 of them were positive for lupus anticoagulant, whereas one patient was positive for anti-ß2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during their ICU stay did not differ between antiphospholipid-positive and antiphospholipid-negative patients (4 [18%] vs. 6 [16%], adjusted odds ratio 0.98, 95% confidence interval 0.1-6.7; p value = 0.986). The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.

Clinical utility of ANA-ELISA vs ANA-immunofluorescence in connective tissue diseases.

We investigated the performance of ANA-ELISA for CTDs screening and diagnosis and comparing it to the conventional ANA-IIF. ANA-ELISA is a solid-phase immune assay includes 17 ANA-targeted recombinant antigens; dsDNA, Sm-D, Rib-P, PCNA, U1-RNP (70, A, C), SS-A/Ro (52 and 60), SS-B/La, Centromere B, Scl-70, Fibrillarin, RNA Polymerase III, Jo-1, Mi-2, and PM-Scl. During the period between March till December 2016 all requests for ANA from primary, secondary, and tertiary care centers were processed with both techniques; ANA-IIF and ANA-ELISA. The electronic medical record of these patients was reviewed looking for CTD diagnosis documented by the Senior rheumatologist. SPSS 22 is used for analysis. Between March and December 2016, a total of 12,439 ANA tests were requested. 1457 patients were assessed by the rheumatologist and included in the analysis. At a cut-off ratio ≥ 1.0 for ANA-ELISA and a dilutional titre ≥ 1:80 for ANA-IIF, the sensitivity of ANA-IIF and ANA-ELISA for all CTDs were 63.3% vs 74.8% respectively. For the SLE it was 64.3% vs 76.9%, Sjogren's Syndrome was 50% vs 76.9% respectively. The overall specificity of ANA-ELISA was 89.05%, which was slightly better than ANA-IIF 86.72%. The clinical performance of ANA-ELISA for CTDs screening showed better sensitivity and specificity as compared to the conventional ANA-IIF in our cohort.

Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment.

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.