Treating to low disease activity is routine in rheumatoid arthritis, but no comparable goal has been defined for systemic lupus erythematosus (SLE). We sought to define and validate a Lupus Low ...Disease Activity State (LLDAS).
A consensus definition of LLDAS was generated using Delphi and nominal group techniques. Criterion validity was determined by measuring the ability of LLDAS attainment, in a single-centre SLE cohort, to predict non-accrual of irreversible organ damage, measured using the Systemic Lupus International Collaborating Clinics Damage Index (SDI).
Consensus methodology led to the following definition of LLDAS: (1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents. Achievement of LLDAS was determined in 191 patients followed for a mean of 3.9 years. Patients who spent greater than 50% of their observed time in LLDAS had significantly reduced organ damage accrual compared with patients who spent less than 50% of their time in LLDAS (p=0.0007) and were significantly less likely to have an increase in SDI of ≥1 (relative risk 0.47, 95% CI 0.28 to 0.79, p=0.005).
A definition of LLDAS has been generated, and preliminary validation demonstrates its attainment to be associated with improved outcomes in SLE.
We evaluated the discriminant capacity of the Lupus Low Disease Activity State (LLDAS) in post-hoc analysis of data from the BLISS-52 and BLISS-76 trials of belimumab in systemic lupus erythematosus ...(SLE).
LLDAS attainment, discrimination between belimumab and placebo arms, and the effects in subgroups with high disease activity at recruitment were evaluated at week 52 using appropriate descriptive statistics, χ
test and logistic regression.
At week 52, for belimumab 10 mg/kg, 17.0% and 19.3% of patients who achieved a Systemic Lupus Erythematosus Responder Index-4 also attained LLDAS in BLISS-52 and BLISS-76, respectively. Significantly more patients attained LLDAS on belimumab 10 mg/kg compared with placebo (12.5% vs 5.8%, OR 2.32, p=0.02 for BLISS-52; 14.4% vs 7.8%, OR 1.98, p=0.04 for BLISS-76). In a subgroup analysis, the difference in week 52 LLDAS attainment between belimumab 10 mg/kg and placebo was greater in patients who had higher disease activity at baseline, compared with the overall group.
LLDAS was able to discriminate belimumab 10 mg/kg from placebo in the BLISS-52 and BLISS-76 trials. Our findings support the validity of LLDAS as an outcome measure in SLE clinical trials.
Objective
To determine mortality and causes of death in a multinational inception cohort of subjects with systemic sclerosis (SSc).
Methods
We quantified mortality as standardized mortality ratio ...(SMR), years of life lost, and percentage mortality in the first decade of disease. The inception cohort comprised subjects recruited within 4 years of disease onset. For comparison, we used a prevalent cohort, which included all subjects irrespective of disease duration at recruitment. We determined a single primary cause of death (SSc related or non–SSc related) using a standardized case report form, and we evaluated predictors of mortality using multivariable Cox regression.
Results
In the inception cohort of 1,070 subjects, there were 140 deaths (13%) over a median follow‐up of 3.0 years (interquartile range 1.0–5.1 years), with a pooled SMR of 4.06 (95% confidence interval 95% CI 3.39–4.85), up to 22.4 years of life lost in women and up to 26.0 years of life lost in men, and mortality in the diffuse disease subtype of 24.2% at 8 years. In the prevalent cohort of 3,218 subjects, the pooled SMR was lower at 3.39 (95% CI 3.06–3.71). In the inception cohort, 62.1% of the primary causes of death were SSc related. Malignancy, sepsis, cerebrovascular disease, and ischemic heart disease were the most common non–SSc‐related causes of death. Predictors of early mortality included male sex, older age at disease onset, diffuse disease subtype, pulmonary arterial hypertension, and renal crisis.
Conclusion
Early mortality in SSc is substantial, and prevalent cohorts underestimate mortality in SSc by failing to capture early deaths, particularly in men and those with diffuse disease.
Objectives To update the Australian System for Cardiac Operative Risk Evaluation (AusSCORE) model for operative estimation of 30-day mortality risk after isolated coronary artery bypass grafting in ...the Australian population. Methods Data were collected by the Australian and New Zealand Society of Cardiac and Thoracic Surgeons registry from 2001 to 2011 in 25 hospitals. A total of 31,250 patients underwent isolated coronary artery bypass grafting and the outcome was 30-day mortality. A total of 2154 (6.9%) patients had 1 or multiple missing values. Missing values were estimated assuming missing completely at random and logistic regression with a generalized estimating equation was used to address within-hospital variance. Bootstrapping methods were used to construct and validate the updated model (AusSCORE II). Also the model was validated on an out-of-creation sample of 4700 patients who underwent bypass surgery in 2012. Results The average age of the patients was 65.6 ± 12.9 years and 78.6% were male. Thirteen variables were selected in the updated model. The bootstrap discrimination and calibration of the AusSCORE II was very good (receiver operating characteristics ROC, 82.0%; slope calibration, 0.987). The overall observed/AusSCORE II predicted mortality was 1.63% compared with the original AusSCORE predicted mortality of 1.01%. The validation of the AusSCORE II on the out-of-sample data also showed a high performance of the model (ROC, 84.5%; Hosmer-Lemoshow P value, .7654). Conclusions The AusSCORE II model provides improved prediction of 30-day mortality and successfully stratifies patient risk. The model will be useful to improve the preoperative consultation regarding risk stratification in terms of 30-day mortality.
Pulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc). We sought to determine survival, predictors of mortality, and health-related quality of life (HRQoL) ...related to PAH in a large SSc cohort with PAH.
We studied consecutive SSc patients with newly diagnosed (incident) World Health Organization (WHO) Group 1 PAH enrolled in a prospective cohort between 2009 and 2015. Survival methods were used to determine age and sex-adjusted standardised mortality ratio (SMR) and years of life lost (YLL), and to identify predictors of mortality. HRQoL was measured using the Short form 36 (SF-36) instrument.
Among 132 SSc-PAH patients (112 female (85%); mean age 62 ± 11 years), 60 (45.5%) died, with a median (±IQR) survival time from PAH diagnosis of 4.0 (2.2-6.2) years. Median (±IQR) follow up from study enrolment was 3.8 (1.6-5.8) years. The SMR for patients with SSc-PAH was 5.8 (95% CI 4.3-7.8), with YLL of 15.2 years (95% CI 12.3-18.1). Combination PAH therapy had a survival advantage (p < 0.001) compared with monotherapy, as did anticoagulation compared with no anticoagulation (p < 0.003). Furthermore, combination PAH therapy together with anticoagulation had a survival benefit compared with monotherapy with or without anticoagulation and combination therapy without anticoagulation (hazard ratio 0.28, 95% CI 0.1-0.7). Older age at PAH diagnosis (p = 0.03), mild co-existent interstitial lung disease (ILD) (p = 0.01), worse WHO functional class (p = 0.03) and higher mean pulmonary arterial pressure at PAH diagnosis (p = 0.001), and digital ulcers (p = 0.01) were independent predictors of mortality.
Despite the significant benefits conferred by advanced PAH therapies suggested in this study, the median survival in SSc PAH remains short at only 4 years.
Up to 12% of patients with systemic sclerosis (SSc) have anti-neutrophil cytoplasmic antibodies (ANCA). However, the majority of these patients do not manifest ANCA-associated vasculitis (AAV) and ...the significance of ANCA in these patients is unclear. The aim of this study is to determine the prevalence of ANCA in a well-characterised SSc cohort and to examine the association between ANCA and SSc clinical characteristics, other autoantibodies, treatments and mortality.
Clinical data were obtained from 5 centres in the Australian Scleroderma Cohort Study (ASCS). ANCA positive was defined as the presence of any one or combination of cytoplasmic ANCA (c-ANCA), perinuclear ANCA (p-ANCA), atypical ANCA, anti-myeloperoxidase (anti-MPO) or anti-proteinase-3 (anti-PR3). Associations of demographic and clinical features with ANCA were investigated by logistic or linear regression. Survival analysis was performed using Kaplan-Meyer curves and Cox regression models.
Of 1303 patients, 116 (8.9%) were ANCA positive. Anti-PR3 was more common than anti-MPO (13.8% and 11.2% of ANCA-positive patients, respectively). Only 3 ANCA-positive patients had AAV. Anti-Scl-70 was more common in ANCA positive vs ANCA negative (25% vs 12.8%, p < 0.001), anti-MPO positive vs anti-MPO negative (38.5% vs 13.6%, p = 0.006) and anti-PR3 positive vs anti-PR3 negative patients (44.4% vs 13.4%, p < 0.001). A higher prevalence of interstitial lung disease (ILD) was found in the ANCA positive (44.8% vs 21.8%, p < 0.001) and the anti-PR3 positive groups (50.0% vs 23.4%, p = 0.009). In multivariable analysis, ANCA-positive status remained associated with ILD after adjusting for anti-Scl-70 antibodies. Pulmonary embolism (PE) was more common in ANCA-positive patients (8.6% vs 3.0%, p = 0.002) and anti-PR3-positive patients (16.7% vs 3.3%, p = 0.022). ANCA-positive status remained associated with PE in a multivariable analysis adjusting for anti-phospholipid antibodies. Kaplan-Meier analysis revealed increased mortality in ANCA-positive patients (p = 0.006). In Cox regression analysis, ANCA was associated with increased mortality, after adjusting for age and sex.
ANCA is associated with increased prevalence of ILD and PE in SSc. ANCA should be tested in SSc, as it identifies individuals with worse prognosis who require close monitoring for adverse outcomes.
Seroprevalence of SARS-CoV-2 IgG among health care workers (HCWs) is crucial to inform infection control programs. Conflicting reports have emerged on the longevity of SARS-CoV-2 IgG. Our objective ...is to describe the prevalence of SARS-CoV-2 IgG in HCWs and perform 8 months longitudinal follow-up (FU) to assess the duration of detectable IgG. In addition, we aim to explore the risk factors associated with positive SARS-CoV-2 IgG. The study was conducted at a large COVID-19 public hospital in Riyadh, Saudi Arabia. All HCWs were recruited by social media platform. The SARS-CoV-2 IgG assay against SARS-CoV-2 nucleocapsid antigen was used. Multivariable logistic regression was used to examine association between IgG seropositive status and clinical and epidemiological factors. A total of 2528 (33% of the 7737 eligible HCWs) participated in the survey and 2523 underwent baseline serological testing in June 2020. The largest occupation groups sampled were nurses n = 1351(18%), physicians n = 456 (6%), administrators n = 277 (3.6%), allied HCWs n = 205(3%), pharmacists n = 95(1.2%), respiratory therapists n = 40(0.5%), infection control staff n = 21(0.27%, and others n = 83 (1%). The total cohort median age was 36 (31-43) years and 66.3% were females. 273 were IgG seropositive at baseline with a seroprevalence of 10.8% 95% CI (9.6%-12.1%). 165/185 and 44/112 were persistently IgG positive, at 2-3 months and 6 months FU respectively. The median (25.sup.th - 75.sup.th percentile) IgG level at the 3 different time points was 5.86 (3.57-7.04), 3.91 (2.46-5.38), 2.52 (1.80-3.99) respectively. Respiratory therapists OR 2.38, (P = 0.035), and those with hypertension OR = 1.86, (P = 0.009) were more likely to be seropositive. A high proportion of seropositive staff had prior symptoms 214/273(78%), prior anosmia was associated with the presence of antibodies, with an odds ratio of 9.25 (P<0.001), as well as fever and cough. Being a non-smoker, non-Saudi, and previously diagnosed with COVID-19 infection by PCR were statistically significantly different by seroprevalence status. We found that the seroprevalence of IgG against SARS-CoV-2 nucleocapsid antigen was 10.8% in HCWs at the peak of the pandemic in Saudi Arabia. We also observed a decreasing temporal trend of IgG seropositivity over 8 months follow up period.
Assessment of disease activity in systemic sclerosis (SSc) is limited by the absence of a fully validated, multisystem measure of disease activity. The European Scleroderma Trials and Research Group ...(EUSTAR) SSc activity index (EScSG-AI) was recently revised, and a validation study within the EUSTAR cohort was performed. In this study, we evaluated the performance of the revised EScSG-AI in an external Australian cohort. The association between the EScSG-AI and the physician global assessment of disease activity (PhGA), both collected prospectively at each annual visit over up to 12 years follow-up, was evaluated using Pearson’s correlation coefficient and Cohen’s kappa coefficient. Generalized linear modelling and time-dependent Cox regression analysis were performed to determine the association of disease activity measured by the EScSG-AI and the summed Medsger Severity Scale (MSS) and death, respectively. There was a moderate correlation between EScSG-AI and PhGA scores (
r
0.42,
p
< 0.001) and moderate association between rising EScSG-AI and summed MSS (
r
0.60,
p
< 0.001). High disease activity, measured by the EScSG-AI at any time during follow-up, was associated with a hazard ratio of 2.07 (95% CI 1.51–2.79) for mortality. The EScSG-AI has a moderate correlation with physician-assessed SSc disease activity. This suggests that the criterion and construct validity of the EScSG-AI are yet to be demonstrated in an external cohort of SSc patients.
Key Points
•There remains no gold standard measure of SSc disease activity.
•The revised 2017 EUSTAR SSc disease activity index shows moderate correlation with physician-rated global disease activity.
•Significant work remains to develop a validated multisystem measure of disease activity in SSc.
Background: In routine clinical practice, the implantation of a drug-eluting stent (DES) versus a bare metal stent (BMS) for percutaneous coronary intervention (PCI) has been guided by criteria for ...appropriate use. The cost-effectiveness (CE) of adopting these guidelines, however, is not clear, and was investigated from the perspective of the Australian healthcare payer.
Methods and results: Baseline and 12-month follow-up data of 12,710 PCI patients enrolled in the Melbourne Interventional Group (MIG) registry between 2004 and 2011 were analysed. Costs inputs were derived from a clinical costing database and published sources. Propensity-score-matching was performed for DES and BMS groups within sub-groups. Incremental cost-effectiveness ratios (ICERs) were evaluated for all patients, and sub-groups of patients with '0', 1, 2, or ≥3 indications for a DES. The incremental cost per target vessel revascularization avoided for the overall population was $24,683, and for patients with 0, 1, and 2 indications for a DES was $44,635, $33,335, and $23,788, respectively. However, for those with >3 indications, DES compared with BMS was associated with cost savings. At willingness to pay thresholds of $45,000-$75,000, the probability of cost-effectiveness of DES for the overall cohort was 71-91%, '0' indications, 49-67%, 1 indication, 56-82%, 2 indications, 70-90%, and ≥3 indications, 97-99%.
Conclusions: The cost-effectiveness of DES compared with BMS increased with increasing risk profile of patients from those who had 1, 2, to ≥3 indications for a DES. When compared with BMS, DES was least cost effective among patients with '0' indications for a DES. Based on these results, selective use of DES implantation is supported. These findings may be useful for evidence-based clinical decision-making.
Background
Indigenous Australians have higher rates of cardiovascular disease and comorbidities compared to their non‐indigenous counterparts.
Aims
We sought to evaluate whether indigenous status per ...se portends a worse prognosis following isolated coronary artery bypass grafting (CABG).
Methods
The outcomes of 778 Indigenous Australians (55 ± 10 years; 32% female) enrolled in the Australian and New Zealand Society of Cardiac and Thoracic Surgeons registry were compared to 36 124 non‐Indigenous Australians (66 ± 10 years; 21% female) following isolated CABG. In a secondary analysis, patients were propensity‐matched by age, sex, renal function, diabetes and ejection fraction (778 individuals in each group).
Results
Indigenous Australians were younger and more likely to be female and current smokers and to have diabetes, hypertension, renal impairment, heart failure and previous CABG (all P < 0.04). Indigenous patients had fewer bypasses with arterial conduits (including less internal mammary artery use) and a higher number of distal vein anastomoses (P < 0.001). Postoperative bleeding rates were higher in indigenous patients (P = 0.001). However, in‐hospital and 30‐day all‐cause mortality and rates of 30‐day readmission were similar between both groups, although cardiac mortality was higher in the indigenous cohort (1.5% vs 0.8%, P = 0.02). With propensity‐matching, rates of postoperative complications were similar among the two groups, with the exception of bleeding, which remained higher in Indigenous Australians (P = 0.03).
Conclusions
Despite procedural differences and higher rates of baseline comorbidities, Indigenous Australians do not have worse short‐term outcomes following isolated CABG. Given the higher rates of baseline comorbidities and lower rates of arterial conduit use, it will be essential to determine long‐term outcomes.
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