Health-related quality of life after 12 months post discharge in patients hospitalised with COVID-19-related severe acute respiratory infection (SARI): a prospective analysis of SF-36 data and correlation with retrospective admission data on age, disease severity, and frailty.

Long-term outcome and 'health-related quality of life' (HRQoL) following hospitalisation for COVID-19-related severe acute respiratory infection (SARI) is limited. OBJECTIVE: To assess the impact of HRQoL in patients hospitalised with COVID-19-related SARI at 1 year post discharge, focusing on the potential impact of age, frailty, and disease severity. METHOD: Routinely collected outcome data on 1207 patients admitted with confirmed COVID-19 related SARI across all three secondary care sites in our NHS trust over 3 months were assessed in this retrospective cohort study. Of those surviving 1 year, we prospectively collected 36-item short form (SF-36) HRQoL questionnaires, comparing three age groups (<49, 49-69, and the over 69-year-olds), the relative impact of frailty (using the Clinical Frailty Score; CFS), and disease severity (using National Early Warning Score; NEWS) on HRQoL domains. RESULTS: Overall mortality was 46.5% in admitted patients. In our SF-36 cohort (n=169), there was a significant reduction in all HRQoL domains versus normative data; the most significant reductions were in the physical component (p<0.001) across all ages and the emotional component (p<0.01) in the 49-69 year age group, with age having no additional impact on HRQoL. However, there was a significant correlation between physical well-being versus CFS (the correlation coefficient=-0.37, p<0.05), though not NEWS, with no gender difference observed. CONCLUSION: There was a significant reduction in all SF-36 domains at 1 year. Poor CFS at admission was associated with a significant and prolonged impact on physical parameters at 1 year. Age had little impact on the severity of HRQoL, except in the domains of physical functioning and the overall physical component.

Identification, Monitoring, and Management of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Interstitial lung disease (ILD) is a frequent complication of rheumatoid arthritis (RA) that is associated with a significant increase in mortality. Several risk factors for the development of ILD in patients with RA have been identified, but ILD can still develop in the absence of these risk factors. Screening tools for RA-ILD are required to facilitate early detection of RA-ILD. Close monitoring of patients with RA-ILD for progression is crucial to enable timely implementation of treatment strategies to improve outcomes. Patients with RA are commonly treated with immunomodulatory therapies, although their efficacy in slowing the progression of RA-ILD remains the subject of debate. Clinical trials have shown that antifibrotic therapies slow decline in lung function in patients with progressive fibrosing ILDs, including patients with RA-ILD. The management of patients with RA-ILD should be based on multidisciplinary evaluation of the severity and progression of their ILD and the activity of their articular disease. Close collaboration between rheumatologists and pulmonologists is essential to optimize patient care.

Four-factor risk score for the prediction of interstitial lung disease in rheumatoid arthritis.

OBJECTIVE: Interstitial lung disease (ILD) is one of the commonest systemic complications in patients with rheumatoid arthritis (RA) and carries a significant morbidity and mortality burden. We aimed to identify key variables to risk-stratify RA patients in order to identify those at increased risk of developing ILD. We propose a probability score based on the identification of these variables. METHODS: A retrospective, multicentre study using clinical data collected between 2010 and 2020, across 20 centres. RESULTS: A total of 430 RA (210 with ILD confirmed on high-resolution computed tomography (HRCT)) patients were evaluated. We explored several independent variables for the risk of developing ILD in RA and found that the key significant variables were smoking (past or present), older age and positive rheumatoid factor/anti-cyclic citrullinated peptide. Multivariate logistic regression models were used to form a scoring system for categorising patients into high and low risk on a scale of 0-9 points and a cut-off score of 5, based on the area under the receiver operating characteristic curve of 0.76 (CI 95% 0.71-0.82). This yielded a sensitivity of 86% and a specificity of 58%. High-risk patients should be considered for investigation with HRCT and monitored closely. CONCLUSION: We have proposed a new model for identifying RA patients at risk of developing ILD. This approach identified four simple clinical variables: age, anti-cyclic citrullinated peptide antibodies, Rheumatoid factor and smoking, which allowed development of a predictive scoring system for the presence of ILD in patients with RA.

How a thrombectomy service can reduce hospital deficit: a cost-effectiveness study.

BACKGROUND: There is level 1 evidence for cerebral thrombectomy with thrombolysis in acute large vessel occlusion. Many hospitals are now contemplating setting up this life-saving service. For the hospital, however, the first treatment is associated with an initial high cost to cover the procedure. Whilst the health economic benefit of treating stroke is documented, this is the only study to date performing matched-pair, patient-level costing to determine treatment cost within the first hospital episode and up to 90 days post-event. METHODS: We conducted a retrospective coarsened exact matched-pair analysis of 50 acute stroke patients eligible for thrombectomy. RESULTS: Thrombectomy resulted in significantly more good outcomes (mRS 0-2) compared to matched controls (56% vs 8%, p = 0.001). More patients in the thrombectomy group could be discharged home (60% vs 28%), fewer were discharged to nursing homes (4% vs 16%), residential homes (0% vs 12%) or rehabilitation centres (8% vs 20%). Thrombectomy patients had fewer serious adverse events (n = 30 vs 86) and were, on average, discharged 36 days earlier. They required significantly fewer physiotherapy sessions (18.72 vs 46.49, p = 0.0009) resulting in a median reduction in total rehabilitation cost of £4982 (p = 0.0002) per patient. The total cost of additional investigations was £227 lower (p = 0.0369). Overall, the median cost without thrombectomy was £39,664 per case vs £22,444, resulting in median savings of £17,221 (p = 0.0489). CONCLUSIONS: Mechanical thrombectomy improved patient outcome, reduced length of hospitalisation and, even without procedural reimbursement, significantly reduced cost to the thrombectomy providing hospital.

Characteristics and Outcomes of Patients With Frailty Admitted to ICU With Coronavirus Disease 2019: An Individual Patient Data Meta-Analysis.

Frailty is often used in clinical decision-making for patients with coronavirus disease 2019, yet studies have found a variable influence of frailty on outcomes in those admitted to the ICU. In this individual patient data meta-analysis, we evaluated the characteristics and outcomes across the range of frailty in patients admitted to ICU with coronavirus disease 2019. DATA SOURCES: We contacted the corresponding authors of 16 eligible studies published between December 1, 2019, and February 28, 2021, reporting on patients with confirmed coronavirus disease 2019 admitted to ICU with a documented Clinical Frailty Scale. STUDY SELECTION: Individual patient data were obtained from seven studies with documented Clinical Frailty Scale were included. We classified patients as nonfrail (Clinical Frailty Scale = 1-4) or frail (Clinical Frailty Scale = 5-8). DATA EXTRACTION: We collected patient demographics, Clinical Frailty Scale score, ICU organ supports, and clinically relevant outcomes (ICU and hospital mortality, ICU and hospital length of stays, and discharge destination). The primary outcome was hospital mortality. DATA SYNTHESIS: Of the 2,001 patients admitted to ICU, 388 (19.4%) were frail. Increasing age and Sequential Organ Failure Assessment score, Clinical Frailty Scale score greater than or equal to 4, use of mechanical ventilation, vasopressors, renal replacement therapy, and hyperlactatemia were risk factors for death in a multivariable analysis. Hospital mortality was higher in patients with frailty (65.2% vs 41.8%; p < 0.001), with adjusted mortality increasing with a rising Clinical Frailty Scale score beyond 3. Younger and nonfrail patients were more likely to receive mechanical ventilation. Patients with frailty spent less time on mechanical ventilation (median days [interquartile range], 9 [5-16] vs 11 d [6-18 d]; p = 0.012) and accounted for only 12.3% of total ICU bed days. CONCLUSIONS: Patients with frailty with coronavirus disease 2019 were commonly admitted to ICU and had greater hospital mortality but spent relatively fewer days in ICU when compared with nonfrail patients. Patients with frailty receiving mechanical ventilation were at greater risk of death than patients without frailty.

There are similarities between rheumatic disease with lung involvement and COVID-19 pneumonia.

INTRODUCTION: There is considerable overlap between the clinical manifestations of covid-19 pneumonia and the acute interstitial lung disease seen in certain rheumatic disorders. In addition, pulmonary fibrosis is increasingly recognised as a potentially serious consequence of both. METHODS: This review explores this overlap of clinical features, risk factors and causation, offering insights into the immune mechanisms that contribute to both sets of disorders. RESULTS: The therapeutic role of immunosuppression and biologic agents in the treatment of covid-19 is explained in the light of this. DISCUSSION: We propose how lessons learned from the insights recently gained into each disorder can improve our insight into immunological mechanisms and application of therapeutic interventions in the other.

Rheumatological complications of Covid 19.

INTRODUCTION: COVID-19 has caused unprecedented hardships in the 21st century with more than 150 million infections. Various immunological phenomena have been described during the course of the infection, and this infection has also triggered autoimmunity. Rheumatological illnesses have been described following resolution of the acute infection; hence we sought to conduct a review of the rheumatological complications of COVID-19. METHODS: We conducted a literature search for articles relating to sequelae of COVID-19 from Jan 2020 to 30th April 2021. RESULTS: We found a number of reports of inflammatory arthritis after SARS-CoV-2 infection. SLE and renal disease have been described, and vasculitis also appears to be a common complication. Rhabdomyolysis and myositis has also been reported in a number of patients. We also found some evidence of large vessel vasculitis in 'long COVID' patients. CONCLUSIONS: This review highlights a number of important complications such as inflammatory arthritis, lupus-like disease, myostis and vasculitis following SARS-CoV-2 infection.

Clinical frailty score as an independent predictor of outcome in COVID-19 hospitalised patients.

PURPOSE OF THE STUDY: We explored potential predictive variables associated with outcomes using baseline clinical parameters of 500 hospitalised patients with COVID -19 in a single centre, UK. METHODS: Retrospective study collecting demographic and clinical characteristics of patients admitted at Southend University Hospital from 20th February to 7th May 2020. RESULTS: The mean age of the cohort admitted to hospital with Covid-19 was 69.4 and 58% were over 70. Comorbidities were more frequently observed in non-survivors, whose mean Clinical Frailty Scale was significantly higher (5 vs 3) than survivors, p < 0.001. In addition, mean C-reactive protein was significantly higher. CONCLUSION: Older and frailer patients with high inflammatory markers were at risk of poor outcomes. Integrated frailty and age-based risk stratification is essential, in addition to monitoring saturation /FiO2 ratio (SFR) and inflammatory markers throughout the disease course to allow for early intervention to improve patient outcomes. A frailty-based risk-stratification approach, rather than age may prove more valuable when considering interventions in patients with multiple comorbidities.

Patient perceptions of co-morbidities in inflammatory arthritis.

OBJECTIVE: Longer life expectancy has resulted in people living with an increasing number of co-morbidities. The average individual with inflammatory arthritis has two co-morbidities, which contribute to higher mortality, poorer functional outcomes and increased health-care utilization and cost. A number of studies have investigated the prevalence of co-morbidities, whereas this study was designed to look at patient perspectives. METHODS: The study comprised two parts: a patient questionnaire and an interview. Individuals with physician-verified inflammatory arthritis along with one or more Charlson co-morbidities were invited to participate. In-depth data were obtained by interviews with 12 willing participants. RESULTS: One hundred and forty-six individuals were recruited; 50 (35%) had one co-morbidity, 69 (48%) had two and 25 (17%) had more than four co-morbidities. Seventy-seven individuals (53%) reported that co-morbidities affected their health as much as their arthritis, and 82 (56%) reported dependence on others for activities of daily living. Lack of education was highlighted by 106 (73%) participants. Qualitative data provided further support for the challenges, with participants highlighting the lack of time to discuss complex or multiple problems, with no-one coordinating their care. This, in turn, led to polypharmacy and insufficient discussion around drug and disease interactions, complications and self-help measures. CONCLUSION: This study highlights the challenges for individuals with inflammatory arthritis who suffer with multiple co-morbidities. The challenges result from limited resources or support within the current health-care environments. Individuals highlighted the poor quality of life, which is multifactorial, and the need for better educational strategies and coordination of care to improve outcomes.

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

QUESTION ADDRESSED BY THE STUDY: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD. METHODS: Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. RESULTS: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001). ANSWER TO THE QUESTION: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.

Rheumatoid arthritis related interstitial lung disease - improving outcomes over 25 years: a large multicentre UK study.

OBJECTIVE: This study explores whether the prognosis of interstitial lung disease in rheumatoid arthritis (RA-ILD) has improved over time and assesses the potential influence of drug therapy in a large multicentre UK network. METHODS: We analysed data from 18 UK centres on patients meeting criteria for both RA and ILD diagnosed over a 25-year period. Data included age, disease duration, outcome and cause of death. We compared all cause and respiratory mortality between RA controls and RA-ILD patients, assessing the influence of specific drugs on mortality in four quartiles based on year of diagnosis. RESULTS: A total of 290 RA-ILD patients were identified. All cause (respiratory) mortality was increased at 30% (18%) compared with controls 21% (7%) (P =0.02). Overall, prognosis improved over quartiles with median age at death rising from 63 years to 78 years (P =0.01). No effect on mortality was detected as a result of DMARD use in RA-ILD. Relative risk (RR) of death from any cause was increased among patients who had received anti-TNF therapy [2.09 (1.1-4.0)] P =0.03, while RR was lower in those treated with rituximab [0.52(0.1-2.1)] or mycophenolate [0.65 (0.2-2.0)]. Patients receiving rituximab as their first biologic had longer three (92%), five (82%) and seven year (80%) survival than those whose first biologic was an anti-TNF agent (82%, 76% and 64%, respectively) (P =0.037). DISCUSSION: This large retrospective multicentre study demonstrates survival of patients with RA-ILD has improved. This may relate to the increasing use of specific immunosuppressive and biologic agents.

Accuracy of musculoskeletal imaging for the diagnosis of polymyalgia rheumatica: systematic review.

OBJECTIVES: To review the evidence for accuracy of imaging for diagnosis of polymyalgia rheumatica (PMR). METHODS: Searches included MEDLINE, EMBASE and PubMed. Evaluations of diagnostic accuracy of imaging tests for PMR were eligible, excluding reports with <10 PMR cases. Two authors independently extracted study data and three authors assessed methodological quality using modified QUADAS-2 criteria. RESULTS: 26 studies of 2370 patients were evaluated: 10 ultrasound scanning studies; 6 MRI studies; 1 USS and MRI study; 7 18-fluorodeoxyglucose-positron emission tomography (PET) studies; 1 plain radiography and 1 technetium scintigraphy study. In four ultrasound studies, subacromial-subdeltoid bursitis had sensitivity 80% (95% CI 55% to 93%) and specificity 68% (95% CI 60% to 75%), whereas bilateral subacromial-subdeltoid bursitis had sensitivity 66% (95% CI 43% to 87%) and specificity 89% (95% CI 66% to 97%). Sensitivity for ultrasound detection of trochanteric bursitis ranged from 21% to 100%. In four ultrasound studies reporting both subacromial-subdeltoid bursitis and glenohumeral synovitis, detection of subacromial-subdeltoid bursitis was more accurate than that of glenohumeral synovitis (p=0.004). MRI and PET/CT revealed additional areas of inflammation in the spine and pelvis, including focal areas between the vertebrae and anterior to the hip joint, but the number of controls with inflammatory disease was inadequate for precise specificity estimates. CONCLUSIONS: Subacromial-subdeltoid bursitis appears to be the most helpful ultrasound feature for PMR diagnosis, but interpretation is limited by study heterogeneity and methodological issues, including variability in blinding and potential bias due to case-control study designs. Recent MRI and PET/CT case-control studies, with blinded readers, yielded promising data requiring validation within a diagnostic cohort study.

Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics--a large multicentre UK study.

OBJECTIVES: The prevalence of interstitial lung disease (ILD) in RA is ∼5%. Previous work identified increasing age, active articular disease and articular damage as risk factors for RA-associated ILD (RA-ILD). The roles of high-resolution CT (HRCT) and lung function testing in defining the nature and extent of pulmonary involvement have recently been explored. This study is the first to examine predictive and prognostic factors for the development of RA-ILD and to report on the physiological and radiological characteristics of the condition from a large multicentre UK network. METHODS: We collected data from centres across the UK on patients with both RA and ILD (proved on HRCT) diagnosed over a 25-year period from 1987 to 2012 using a standard pro forma. Potential predictors of RA-ILD were analysed. Baseline lung function data were recorded and related to HRCT findings. We analysed HRCT for subtype and extent of lung involved and examined the relationship between these and both all-cause and pulmonary mortality. We compared our results with case controls matched for age and gender using computer-generated selection from the RA population from one contributing centre. RESULTS: A total of 230 patients were identified from across the UK with proven RA-ILD diagnosed over 25 years. Median age at diagnosis was 64 years and the male:female ratio was 1:1.09. Univariate analysis showed anti-CCP antibody titres to be the single most strongly associated predictor of RA-ILD. Male gender, age at onset, smoking and RF were all independently associated with RA-ILD on multivariate analysis. Vital capacity (VC) was preserved in limited disease but reduced in extensive disease, while gas transfer was reduced in both. Usual interstitial pneumonia (UIP) was the most common subtype on HRCT and both this and extensive disease were associated with increased all-cause mortality. CONCLUSION: This is the largest study of RA-ILD in the UK. Anti-CCP antibodies were strongly associated with RA-ILD in both sexes. Smoking was strongly associated with ILD in males, which may explain the higher frequency of RA-ILD in men. The predominant HRCT pattern was UIP and most patients had limited disease at presentation. The presence of UIP and extensive disease are associated with increased mortality. Baseline gas transfer is a useful screening tool for ILD, while the preservation of VC at baseline might predict limited disease on HRCT.

A study of baseline prevalence and cumulative incidence of comorbidity and extra-articular manifestations in RA and their impact on outcome.

OBJECTIVES: To study the prevalence at diagnosis and cumulative incidence of comorbidity in RA, associations with clinical features and impact on outcome. METHODS: Standard clinical, laboratory and radiological measures of RA, and details of comorbidity and extra-articular features were recorded at baseline and yearly in an inception cohort of 1460 patients with recently diagnosed RA from nine regions in the UK. The General Practice Research Database was used to compare the incidence of common comorbid conditions (International Classification for Disease-10 codes). RESULTS: Baseline prevalence was 31.6% and 8.6% for all comorbidities and extra-articular features, respectively, and 15-year cumulative incidence was 81% and 53%, respectively. Rates of hypertension [standardized incidence ratio (SIR) = 1.61; 95% CI 1.43, 1.79] and ischaemic heart disease (SIR = 1.60; 95% CI 1.35, 1.84) were raised compared with figures for the general population, as was stroke in females (SIR = 1.34; 95% CI 1.02, 1.77) and chronic obstructive pulmonary disorder in males (SIR = 1.63; 95% CI 1.17, 2.26). Comorbidity was associated with risk of both all-cause and cardiovascular mortality (hazard ratio = 1.09; 95% CI 1.02, 1.17) and increased rates of functional decline over 10 years (b = 0.011; 95% CI 0.004, 0.019). Comorbidity was not related to disease activity or structural damage. CONCLUSION: Significant comorbidity was present at the outset of RA, increasing with follow-up, mainly in cardiovascular, non-cardiac vascular and respiratory systems. Specific conditions (e.g. hypertension) occurred more frequently than in the general population. Comorbidity was related to mortality and functional decline, and more intensive therapies may need consideration in these patients. As many co-existent conditions are amenable to preventative/therapeutic measures, comorbidity needs earlier detection and management in order to reduce its impact on outcome in RA.

Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort.

OBJECTIVES: Pulmonary complications of RA are well described. Although some are benign, interstitial lung disease (ILD) has a poor prognosis. Few RA inception cohorts have reported the natural history of ILD related to RA (RA-ILD). We examine its incidence, outcome and prognostic indicators. METHODS: Extra-articular features and comorbidity have been recorded yearly in a well-established inception cohort of RA with a 20-year follow-up. Standard clinical, laboratory and radiological measures of RA were recorded at baseline and yearly. Details of deaths were provided by a national central register. RESULTS: Out of 1460 patients, 52 developed RA-ILD, half either at baseline or within 3 years of onset. The annualized incidence was 4.1/1000 (95% CI 3.0, 5.4) and the 15-year cumulative incidence 62.9/1000 (95% CI 43.0, 91.7). Incidence of RA-ILD was associated with older age, raised baseline ESR and HAQ. Evidence to implicate any drug effect (e.g. MTX) was lacking. Of these patients, 39 died, attributed to RA-ILD in 28. Median survival following diagnosis of RA-ILD was 3 years. CONCLUSIONS: RA-ILD is an important and early feature of RA. It is related to disease activity and has a poor prognosis. Further studies are required to determine whether screening for pulmonary disease would identify these patients at an earlier stage.

Extra-articular manifestations and complications of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic inflammatory disease that can involve other tissues and organs as well as synovial joints. This chapter reviews the clinical aspects of extra-articular RA, from the early descriptions in rheumatology texts to reports from more recent cross-sectional and inception cohort studies. There is no agreed classification for these manifestations and, because criteria and definitions vary so much, this report includes not only the classic extra-articular features but also the non-articular complications of RA, for example normochromic normocytic anaemia and chronic leg ulcers, and the important disease-associated comorbidities, including non-Hodgkin's lymphoma, ischaemic heart disease and osteoporosis. Incidence and frequency figures for extra-articular RA vary according to study design. Nodules are the most common extra-articular feature, and are present in up to 30%; many of the other classic features occur in 1% or less in normal clinic settings. Sjögren's syndrome, anaemia of chronic disease and pulmonary manifestations are relatively common - in 6-10% - are frequently present in early disease and are all related to worse outcomes measures of rheumatoid disease, in particular functional impairment and mortality. Currently, there are no reliable predictors for these features in early RA, although they are associated with men, smokers, more severe joint disease, worse function, high levels of inflammatory markers, and the presence of rheumatoid factor (RF), antinuclear antibodies (ANA) and the RA HLA-related shared epitope. Many of these manifestations are related to the more active and severe RA, so early and more aggressive RA drug therapies are being employed and, although evidence from randomised studies is not available, this approach would seem appropriate in view of the adverse effect of extra-articular manifestations on RA outcomes. Unfortunately, specific therapies for extra-articular manifestations of RA are largely disappointing or unavailable, except for steroids and cyclophosphamide for vasculitis. The place for biological therapies is still not clear. Pulmonary fibrosis in RA has a poor prognosis whether treated with large doses of steroids, cytotoxic or disease modifying drugs like cyclosporine, or biologics. In summary, extra-articular features and non-articular complications of RA are common and are generally related to worse disease. They need to be recognised early and managed promptly.