Should all patients with polymyalgia rheumatica have a vascular ultrasound assessment?

There is a growing appreciation that both giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely interrelated conditions that have significant overlap in aetiology, clinical characteristics and treatment regimens. Subclinical GCA in PMR is becoming increasingly recognised, and there is evolving evidence that this may be a more aggressive disease phenotype than PMR. Ultrasound (US) lends itself well as a screening tool for GCA in PMR; it is inexpensive, non-invasive, widely available, lacks ionising radiation, may be performed at the bedside and is recommended by EULAR as a first-line investigation for suspected GCA. There is insufficient evidence to currently recommend that all patients with PMR should have a US assessment for vascular involvement. However, as clinical and laboratory parameters alone do not accurately diagnose patients with subclinical GCA, we suggest that vascular US will be increasingly performed by rheumatologists in practice to identify these patients with PMR, preferably as part of larger prospective outcome studies.

Effectiveness of Ultrasound-guided versus Landmark-based Glucocorticoid Injection in the Treatment of First Carpometacarpal Joint Osteoarthritis.

Background: Osteoarthritis is a debilitating degenerative disease more pronounced in elderly affecting many joints. The first carpometacarpal joint (CMC1) is commonly affected. Pain is the major complaint, which can impact patient's daily activities. Intra-articular glucocorticoid injection can be considered if conservative measures fail and ultrasound guided injection might be superior to the traditional anatomic landmark-guided technique. Objective: The aim of this study is to evaluate the effectiveness of ultrasound-guided versus landmark-based approach to intra-articular CMC1 injection using the Australian Canadian osteoarthritis hand index (AUSCAN). Methods: Adult patients diagnosed with symptomatic CMC1 osteoarthritis who failed conservative measures were enrolled. In this prospective observational cohort study, utilizing a convenience sample, intra-articular corticosteroid injection was administered either by ultrasound-guided technique or landmark-based approach. Pain, stiffness and function in 10-points scale at baseline, 6 and 12 weeks were collected and analyzed using descriptive analysis. Results: There were 33 patients enrolled. Mean age was 63 years, with females making up the majority of participants (n = 28, 84.8%). Mean duration of CMC1 pain was 10 months (SD=2.5) up to the point of receiving the injection. Ultrasound guided injection was performed in 60.6% (n=20), while 39.4% (n=13) had the landmark approach. Both groups achieved a statistically and clinically significant level of change in AUSCAN score at week 6 (P≤ 0.05) but with a recurrence of symptoms at week 12 (P ≤ 0.05). At both intervals the AUSCAN scores were better than baseline (P ≤ 0.05). There was no difference between the two groups regarding baseline pain VAS score (mean ultrasound group= 6.6 vs landmark group= 7.5; P = 0.18). No significant differences were identified between two groups in terms of changes from baseline to 6, 12 and between 6 to 12 weeks in pain, stiffness and hand function (P > 0.05). Conclusion: No difference was found between the ultrasound-guided and landmark-based approaches for CMC1 injection on pain score, stiffness, or function.

Targeted Therapy in Rheumatoid-Arthritis-Related Interstitial Lung Disease.

Rheumatoid arthritis (RA) is a chronic autoimmune multisystem inflammatory disease in which lung involvement is the most common extra-articular manifestation. Parenchymal lung involvement or interstitial lung disease (ILD) is a significant cause of morbidity and mortality and there is a paucity of evidence-based guidance on how to best treat RA-ILD. This review article aims to evaluate the evidence from cohort studies and best real word data from registries. Extensive discussion of the relative merits and drawbacks of glucocorticoids, various biologics, small molecules and anti-fibrotics is presented. The limited available guidelines in RA-ILD are also discussed and a rational treatment algorithm is offered.

Janus Kinase Inhibitors in Rheumatoid Arthritis: An Update on the Efficacy and Safety of Tofacitinib, Baricitinib and Upadacitinib.

Janus kinase inhibitors (JAKis) are the most recent new drug class to arrive to the market for rheumatoid arthritis (RA) treatment. While they have proven to be a very effective treatment option, there remains significant concern regarding the risk of cardiovascular events, thrombosis and malignancy, particularly given the findings of the post-marketing ORAL Surveillance study and FDA black box warnings. This article reviews the key findings of the most impactful cohort of studies and registry data since ORAL Surveillance. It also evaluates the role of JAKis in practice and offers guidance on risk stratifying patients and determining their suitability for a JAKi.

Red Cell Distribution Width as a Prognostic Indicator in Acute Medical Admissions.

The red cell distribution width (RDW) is the coefficient of variation of the mean corpuscular volume (MCV). We sought to evaluate RDW as a predictor of outcomes following acute medical admission. We studied 10 years of acute medical admissions (2002-2011) with subsequent follow-up to 2021. RDW was converted to a categorical variable, Q1 < 12.9 fl, Q2-Q4 ≥ 12.9 and <15.7 fL and Q5 ≥ 15.7 fL. The predictive value of RDW for 30-day in-hospital and long-term mortality was evaluated with logistic and Cox regression modelling. Adjusted odds ratios (aORs) were calculated and loss of life years estimated. There were 62,184 admissions in 35,140 patients. The 30-day in-hospital mortality (n = 3646) occurred in 5.9% of admissions. An additional 15,086 (42.9%) deaths occurred by December 2021. Admission RDW independently predicted 30-day in-hospital mortality aOR 1.93 (95%CI 1.79, 2.07). Admission RDW independently predicted long-term mortality aOR 1.04 (95%CI 1.02, 1.05). Median survival post-admission was 189 months. For those with admission RDW in Q5, observed survival half-life was 133 months-this represents a shortfall of 5.7 life years (33.9%). In conclusion, admission RDW independently predicts 30-day in-hospital and long-term mortality.

Preventing infections in immunocompromised patients with kidney diseases: vaccines and antimicrobial prophylaxis.

The coronavirus disease 2019 (COVID-19) pandemic revealed that our understanding of infectious complications and strategies to mitigate severe infections in patients with glomerular diseases is limited. Beyond COVID-19, there are several infections that specifically impact care of patients receiving immunosuppressive measures. This review will provide an overview of six different infectious complications frequently encountered in patients with glomerular diseases, and will focus on recent achievements in terms of vaccine developments and understanding of the use of specific antimicrobial prophylaxis. These include influenza virus, Streptococcus pneumoniae, reactivation of a chronic or past infection with hepatitis B virus in cases receiving B-cell depletion, reactivation of cytomegalovirus, and cases of Pneumocystis jirovecii pneumonia in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Varicella zoster virus infections are particularly frequent in patients with systemic lupus erythematosus and an inactivated vaccine is available to use as an alternative to the attenuated vaccine in patients receiving immunosuppressants. As with COVID-19 vaccines, vaccine responses are generally impaired in older patients, and after recent administration of B-cell depleting agents, and high doses of mycophenolate mofetil and other immunosuppressants. Strategies to curb infectious complications are manifold and will be outlined in this review.

An international survey of current management practices for polymyalgia rheumatica by general practitioners and rheumatologists.

OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.

Metabolic bone health considerations in giant cell arteritis and polymyalgia rheumatica.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two common systemic inflammatory conditions with a combined lifetime risk of approximately 3.5% in women and 1.5% in men. They are intimately associated with the aging process, virtually never occurring prior to 50 years of age and becoming more common over time. The reasons for this are unclear, but likely relate in part to factors related to aging of the immune system. The treatment of both GCA and PMR is traditionally based on glucocorticoids, frequently requiring a prolonged treatment course over long periods of time. Other medications are belatedly entering our treatment armamentarium, but their exact place in treatment algorithms remains to be fully defined and it is likely glucocorticoids will remain a cornerstone of our treatment in GCA and PMR for the foreseeable future. As a result, people with GCA and PMR will continue to be exposed to a significant cumulative glucocorticoid burden with all of the attendant potential adverse events, including osteoporosis. The predominantly post-menopausal female population that most commonly develops PMR and GCA is also the population that is most affected by osteoporosis. Given the risk of glucocorticoid-induced osteoporosis and subsequent fragility fractures, a planned treatment approach from glucocorticoid initiation is needed in these conditions. For the majority of patients, this will entail ensuring sufficiency of calcium and vitamin D as well as antiresorptive treatments. In this article, we discuss considerations around optimisation of metabolic bone health in GCA and PMR.

Outcomes of COVID-19 in people with rheumatic and musculoskeletal disease in Ireland over the first 2 years of the pandemic.

BACKGROUND: Poor COVID-19 outcomes occur with higher frequency in people with rheumatic and musculoskeletal diseases (RMD). Better understanding of the factors involved is crucial to informing patients and clinicians regarding risk mitigation. AIM: To describe COVID-19 outcomes for people with RMD in Ireland over the first 2 years of the pandemic. METHODS: Data entered into the C19-GRA provider registry from Ireland between 24th March 2020 and 31st March 2022 were analysed. Differences in the likelihood of hospitalisation and mortality according to demographic and clinical variables were investigated. RESULTS: Of 237 cases included, 59.9% were female, 95 (41.3%) were hospitalised, and 22 (9.3%) died. Hospitalisation was more common with increasing age, gout, smoking, long-term glucocorticoid use, comorbidities, and specific comorbidities of cardiovascular and pulmonary disease, and cancer. Hospitalisation was less frequent in people with inflammatory arthritis and conventional synthetic or biologic disease-modifying antirheumatic drug use. Hospitalisation had a U-shaped relationship with disease activity, being more common in both high disease activity and remission. Mortality was more common with increasing age, gout, smoking, long-term glucocorticoid use, comorbidities, and specific comorbidities of cardiovascular disease, pulmonary disease, and obesity. Inflammatory arthritis was less frequent in those who died. CONCLUSION: Hospitalisation or death were more frequently experienced by RMD patients with increasing age, certain comorbidities including potentially modifiable ones, and certain medications and diagnoses amongst other factors. These are important 'indicators' that can help risk-stratify and inform the management of RMD patients.

Musculoskeletal education in undergraduate medical curricula-A systematic review.

Rheumatic and musculoskeletal diseases encompass a vast spectrum of up to 200 conditions that are increasingly prevalent, with significant associated disability and socioeconomic burden. Their impact is pervasive, with musculoskeletal conditions being the second leading cause of years lived with disability worldwide, in addition to the 9th most common cause of disability-adjusted life years. It is therefore imperative that all graduating medical physicians are competent in their management, and that the quality of undergraduate musculoskeletal education is commensurate with patient and societal needs. A systematic literature review was conducted between April 1, 2021 and June 1, 2021 assessing the quality of undergraduate musculoskeletal education in medical schools. Educational interventions in musculoskeletal medicine were also included. Quality assessment appraisal of the studies was done using a Mixed Methods Appraisal Tool. One thousand and thirty-three titles were screened, and 44 studies were included in the final analysis. Our analysis of these studies showed that the quality of undergraduate musculoskeletal education, as determined by the cognitive mastery and clinical confidence of undergraduate medical students remains inadequate. Multiple educational interventions were assessed with mixed results. Despite the prevalence, and burden associated with rheumatic and musculoskeletal diseases, the musculoskeletal education of undergraduate medical students remains inadequate. Urgent international collaboration is required to devise teaching strategies and curriculum initiatives that are globally and reproducibly applicable and effective. Further research into educational interventions and teaching strategies is also required.

Hospital mortality and length of stay differences in emergency medical admissions related to 'on-call' specialty.

BACKGROUND: The outcomes of acute medical admissions have been shown to be influenced by a variety of factors including system, patient, societal, and physician-specific differences. AIM: To evaluate the influence of on-call specialty on outcomes in acute medical admissions. METHODS: All acute medical admissions to our institution from 2015 to 2020 were evaluated. Admissions were grouped based on admitting specialty. Thirty-day in-hospital mortality and length of stay (LOS) were evaluated. Data was analysed using multivariable logistic regression and truncated Poisson regression modelling. RESULTS: There were 50,347 admissions in 30,228 patients. The majority of admissions were under Acute Medicine (47.0%), and major medical subspecialties (36.1%); Elderly Care admitted 12.1%. Acute Medicine admissions were older at 72.9 years (IQR 57.0, 82.9) vs. 67.2 years (IQR 50.1, 80.2), had higher Acute Illness Severity (grades 4-6: 85.9% vs. 81.3%; p < 0.001), Charlson Index (> group 0; 61.5% vs. 54.6%; p < 0.001), and Comorbidity Score (40.7% vs. 36.7%; p < 0.001). Over time, there was a small (+ 8%) but significant increase in 30-day in-hospital mortality. Mortality rates for Acute Medicine, major medical specialties, and Elderly Care were not different at 5.1% (95% CI: 4.7, 5.5), 4.7% (95% CI: 4.3, 5.1), and 4.7% (95% CI: 3.9, 5.4), respectively. Elderly Care admissions had shorter LOS (7.8 days (95% CI: 7.6, 8.0)) compared with either Acute Medicine (8.7 days (95% CI: 8.6, 8.8)) or major medical specialties (8.7 days (95% CI: 8.6, 8.9)). CONCLUSION: No difference in mortality and minor differences in LOS were observed. The prior pattern of improved outcomes year on year for emergency medical admissions appears ended.

Prognostic value and clinical utility of NT-proBNP in acute emergency medical admissions.

BACKGROUND: NT-proB-type natriuretic peptide (NT-proBNP) is a frequently utilized test in congestive cardiac failure. There is little data on its utility in unselected emergency medical admissions. AIM: This study aims to investigate the clinical utility and prognostic value of NT-proBNP in emergency medical admissions and to determine whether such testing influenced downstream investigations and length of stay (LOS). METHODS: We report on NT-proBNP tests performed in emergency medical admissions in a 2005/2006 and subsequent 7-year (2014-2020) retrospective cohort. We assessed 30-day in-hospital mortality with a multivariable logistic regression model. The utilization of procedures/services was related to LOS with zero-truncated Poisson regression. RESULTS: There were 64,212 admissions in 36,252 patients. Patients with a NT-proBNP test were significantly older at 75.3 years vs. 63.0 years and had longer LOS -9.4 days vs. 4.9 days. They had higher acute illness severity and comorbidity scores. Thirty-day in-hospital mortality was higher in those with a NT-proBNP test (8.8%) vs. no request (3.2%). NT-proBNP test level was prognostic in univariate - OR 2.87 (2.61, 3.15), and multivariate analyses - OR 1.40 (1.26, 1.56). Higher NT-proBNP levels predicted higher 30-day in-hospital mortality. Multivariable thirty-day in-hospital mortality was 3.8% (3.6%, 3.9%) for those without a test, increasing to 4.9% (4.7%, 5.2%) for ≥ 250 ng/L and 5.8% (5.8%, 6.3%) for ≥ 3000 ng/L. LOS was linearly related to the total number of procedures/services performed. CONCLUSION: NT-proBNP is prognostic in emergency medical admissions. Downstream resource utilization differed following an NT-proBNP test; this may reflect different case complexity or the 'uncertainty' surrounding such admissions.

Systemic sclerosis associated interstitial lung disease: a conceptual framework for subclinical, clinical and progressive disease.

OBJECTIVES: To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD). METHODS: A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification. RESULTS: Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%) and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT [HRCT]); risk of progression was influenced primarily by disease duration. CONCLUSIONS: Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT.

Are Janus kinase inhibitors safe and effective in treating the key clinical domains of psoriatic arthritis? A systematic review and meta-analysis.

OBJECTIVES: Psoriatic arthritis (PsA), is a complex inflammatory arthropathy with a heterogenous spectrum of disease presentation. Despite the vast therapeutic armamentarium, disease control in a considerable proportion of patients is suboptimal. The aim of this study was to assess the safety and efficacy of Janus kinase inhibitors (JAKi), in the management of key clinical domains of PsA including peripheral arthritis, psoriasis, enthesitis and dactylitis. METHOD: Randomized placebo-controlled trials (RCTs) of JAKi in PsA were identified by a systematic literature search using EMBASE, PubMed and CENTRAL. All included studies underwent meta-analysis. RESULTS: A total of 5 RCTs were included. Patients were randomized to tofacitinib (n = 474), filgotinib (n = 65), upadacitinib (n = 1281) or placebo (n = 937). JAKi treatment was associated with superior efficacy across all primary outcome measures vs placebo: American College of Rheumatology (ACR) 20 (risk ratio [RR] 2.10, [95% CI 1.86-2.37], P < .00001, I2 = 19%); ACR 50 (RR 3.43, [95% CI 2.37-4.96], P < .00001, I2 = 66%); ACR 70 (RR 4.57, [95% CI 1.83-11.44], P = .001, I2 = 82%); Psoriasis Area and Severity Index 75 (RR 2.96, [95% CI 2.44-3.58], P < .00001, I2 = 0%); enthesitis resolution (RR 1.82, [95% CI 1.56-2.12], P < .00001, I2 = 0%); and dactylitis resolution (RR 1.85, [95% CI 1.57-2.16], P < .00001, I2 = 0%). JAKi were associated with an overall increased risk of adverse events (RR 1.14, [95% CI 1.07-1.21], P = .0001, I2 = 0%) with increased risk of infection (RR1.23, [95% CI 1.08-1.39], P = .001, I2 = 0%) vs placebo. CONCLUSION: This pooled analysis demonstrates the efficacy of JAKi in treating key clinical domains of PsA. However, they are associated with an increased risk of adverse events, including infection. Further studies are required to corroborate these findings and further elucidate the safety profile.