Cancer Risk and Mortality in Hospitalized Patients With Idiopathic Inflammatory Myopathies in Western Australia.

OBJECTIVE: To compare cancer incidence, type, and survival between patients with idiopathic inflammatory myopathies (IIMs) in Western Australia (WA) and the general population. METHODS: Administrative health data for hospitalized patients with incident IIM (n = 803, 56.5% female, median age 62.0 yrs), classified by a validated algorithm as polymyositis (PM; 36.2%), dermatomyositis (DM; 27.4%), inclusion body myositis (IBM; 17.1%), overlap myositis (OM; 10.7%), and other IIM (8.6%), were linked to WA cancer and death registries for the period of 1980 to 2014. Cancer incidence rates (CIRs) before and after IIM diagnosis as well as cancer mortality were compared with age-, sex-, and calendar year-matched controls (n = 3225, 54.9% female, median age 64 yrs) by rate ratios (RRs) and Kaplan-Meier survival estimates. RESULTS: The prediagnosis CIR was similar for patients with IIM and controls (6.57 vs 5.95; RR 1.11, 95% CI 0.88-1.39) and for patients evolving to DM (n = 220) or other IIM subtypes (6.59 vs 6.56; RR 1.01, 95% CI 0.38-3.69). During follow-up, CIR was higher for all DM (4.05, 95% CI 3.04-5.29), with increased CIR for lung cancer vs controls (1.05 vs 0.33; RR 3.18, 95% CI 1.71-5.47). Cancer post diagnosis shortened life span by 59 months for patients with IIM (103 vs 162 months, P < 0.01), but reduced survival rates were observed only in patients with DM and IBM. CONCLUSION: Cancer risk was not increased prior to IIM, but CIR for lung cancer was increased following DM diagnosis. As cancer reduced survival only in patients with DM and IBM, these data support a strategy of limited cancer screening in IIM.

Comparison of pregnancy outcomes between indigenous and non-indigenous lupus patients.

AIM: To compare pregnancy outcomes between IA and non IA lupus patients. BACKGROUND: Pregnancy in lupus patients confers an increased risk of maternal and fetal morbidity. There are no data on pregnancy outcomes for indigenous Australian (IA) patients with lupus. METHODS: Using state-wide longitudinal hospital morbidity data, we studied 702 pregnancies in IA (n = 31) and non-indigenous (NI) patients with lupus (n = 357) in Western Australia and compared rates for live birth (LB), preterm birth (PB) and gestational complications in the period 1985-2015. Results are presented as medians or frequency. RESULTS: IA patients had proportionally more pre-existing renal disease (35 vs 13%, P < 0.01) and lower socio-economic status (P = 0.02). Age at first pregnancy was lower in IA patients (27 vs 30 years, P < 0.001), recorded gravidity was similar (2 vs 2, P > 0.6) and elective termination (n = 138) was more frequent in NI than IA pregnancies (21.1 vs 4.8%, P < 0.01). For continued pregnancies (59 in IA and 505 in NI), respective outcomes were as follows: LB 84.7% versus 91.5% (P = 0.15), spontaneous abortion 13.5% versus 6.9% (P = 0.13), (pre-)eclampsia 8% versus 9.9% (P = 0.89), PB 12% versus 13.4% (P = 0.98) and caesarean delivery 30% versus 47.2% (P = 0.02). Gestational diabetes (26% vs 6.1%), renal flares (20% vs 5.6%) and infections (22% vs 6.3%) were all more frequent in IA lupus pregnancies (all P < 0.001). CONCLUSIONS: The burden of comorbidities was higher in IA patients with lupus due to renal flares, gestational DM and infections. Although PB rates were overall high, they were, however, similar for IA and NI lupus pregnancies, as were LB rates.

The temporal association between adverse drug reactions and antirheumatic drugs utilisation in Western Australia: a retrospective study from real-world data (1995-2015).

BACKGROUND/OBJECTIVES: Adverse drug reactions (ADRs) can result in morbidity, mortality, and higher healthcare costs. Given the limited information available on ADRs associated with antirheumatic medications, this study aims to analyse and compare ADR reporting for these drugs in the pharmacovigilance datasets of Western Australia (WA) and the United States (US). METHODS: Therapeutic Goods Administration provided WA pharmacovigilance data of selected antirheumatic drugs to from 1995 to 2015. The proportional reporting ratio (PRR) for WA case reports was compared to corresponding USA pharmacovigilance data by assessing the disproportionality of each ADR. clinically significant or true ADRs were determined using the Evans 2001 criteria (n > 2, chi-square > 4, PRR > 2). RESULTS: A total of 232 reports were found in WA, mostly on sixty-nine women aged 45 to 69. Methotrexate, leflunomide, azathioprine, sulfasalazine, and infliximab had the highest reported ADRs, related to gastrointestinal disorders. Patients who used biological agents in WA had 2.7 times the likelihood of reporting true ADRs compared to conventional antirheumatic drugs. The ADR rates in the two datasets were comparable over the study period. CONCLUSIONS: The PRR values of ADRs were consistent between WA and US databases. Methotrexate and infliximab use were commonly associated with ADR reports in WA females, with incidence rates comparable to the US; while patients using biological agents were more likely to report true ADRs than those on conventional antirheumatic drugs in WA.

Systemic juvenile idiopathic arthritis: frequency and long-term outcome in Western Australia.

Systemic juvenile idiopathic arthritis (S-JIA) is a rare but potentially life threatening autoinflammatory condition of childhood. Given the limited data on S-JIA from the Australasian region, we investigated the epidemiological characteristics and long-term disease outcome in S-JIA. All hospitalised patients under the age of 16 years registered with ICD-10-AM code M08.2 in in the period 1999-2014 were identified in longitudinally linked administrative health data across all Western Australian (WA) hospitals. Incidence and point prevalence estimate were per 100,000 population with Poisson regression to analyse the incidence trend. Readmissions with S-JIA as primary diagnosis were considered flares with rates for flare and other complication reported per 100 person years with 95% confidence intervals (CI). Annual S-JIA incidence was 0.61/100,000 (CI 0.28-1.25) (46 incident cases, 71.7% girls, median age 6.5 years) and stable over time as S-JIA point prevalence reached 7.15/100,000 (CI 5.29-7.45) at the end of study. Most incident cases were diagnosed in winter and spring, but documented preceding infections were rare. During a median follow-up of 8 years, disease flares occurred in 24% of patients with higher flares rate in boys (58.3; CI 44.5-74.9) than girls (14.7; CI 9.9-20.9). No deaths occurred and arthroplasty was the main, but uncommon S-JIA complication (4%). However, readmission (86.3; CI 76.4-97.2) and ED visit (73.3; CI 64.2-83.4) rates for illnesses other than S-JIA were substantial. S-JIA is as rare in WA as in other regions and while s-JIA incurred no deaths in the era of biologics, it associated with a significant long-term burden of (co-) morbidity.

Serum immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term maintenance therapy with rituximab in patients with granulomatosis with polyangiitis.

OBJECTIVE: Rituximab (RTX) is a B cell depleting agent used to induce and maintain remission in patients with granulomatosis with polyangiitis (GPA). As the development of hypogammaglobulinaemia in GPA patients on long-term RTX has not been addressed, the aim of this study was to investigate changes in immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term RTX maintenance therapy in GPA. METHODS: We used a single-centre cohort study of 29 GPA patients who received a median total cumulative dose of CYC of 17 g and were treated with 2 g RTX followed by re-treatment with either 2 g once annually, 1 g biannually or a combination of both. Ig levels were measured before each RTX re-treatment and hypogammaglobulinaemia was defined as levels of total immunoglobulin <6 g/l. RESULTS: During a median follow-up of 4 years, patients received a cumulative dose of 9 g RTX. While serum Ig levels decreased during RTX maintenance, the largest decrease occurred after the first infusion. Baseline Ig levels and the CYC cumulative dose predicted Ig levels, whereas the RTX cumulative dose did not. Eight patients (28%) discontinued RTX due to hypogammaglobulinaemia. Male gender [hazard ratio (HR) = 8.7, P = 0.044], kidney involvement (HR = 6.5, P = 0.083) and the 1 g biannual regimen (HR = 8.0, P = 0.024) increased the risk to discontinue RTX due to hypogammaglobulinaemia, whereas orbital-subglottic involvement (HR = 0.23, P = 0.080) decreased it. CONCLUSION: Hypogammaglobulinaemia occurred in one-quarter of GPA patients during RTX maintenance, independent of the RTX cumulative dose. Male gender, kidney involvement and the 1 g biannual RTX regimen constitute risk factors for severe hypogammaglobulinaemia necessitating withdrawal of RTX.

Population-wide long-term study of incidence, renal failure, and mortality rates for lupus nephritis.

OBJECTIVE: Given limited regional data, we investigate the state-wide epidemiology, renal and patient outcomes for lupus nephritis (LN) in Western Australia (WA). METHODS: Patients hospitalized with incident SLE (≥2 diagnostic codes in the state-wide WA Health Hospital Morbidity Data Collection) in the period 1985-2015 were included (n = 1480). LN was defined by the presence of glomerulonephritis and/or raised serum creatinine. Trends over three study decades for annual incidence rate (AIR)/100.000 population, mortality (MR), and end-stage renal disease (ESRD) rates/100 person years were analyzed by least square regression and compared with a matched control group (n = 12 840). RESULTS: Clinical evidence of LN developed in 366 SLE patients (25.9%) after a median disease duration of 10 months (IQR 0-101) with renal biopsy performed in 308 (84.2%). The AIR for LN (0.63/100.000) did not change significantly over time (R2 = .11, p = .85), while point prevalence reached 11.9/100.000 in 2015. ESRD developed in 14.1% (n = 54) of LN patients vs. 0.2% in non-LN SLE patients and 0.05% in controls (all p ≤ 0.01). ESRD rates increased over time in LN patients (0.4 to 0.7, R2 = .52, p = .26). The odds ratio for death was 8.81 (CI 3.78-22.9) for LN and 6.62 (CI 2.76-17.9) for non-LN SLE patients compared to controls and MR for LN patients increased over time (1.3 to 2.2, R2 = .84, p = .26). CONCLUSIONS: The incidence rate of LN in WA remained unchanged over 30 years. A lack of improvement in renal failure and mortality rates illustrates the pressing need for better long-term treatment options and/or strategies in LN.

Long-term efficacy and safety of pre-emptive maintenance therapy with rituximab in granulomatosis with polyangiitis: results from a single centre.

OBJECTIVE: Rituximab (RTX) is an anti-CD20 antibody used successfully in granulomatosis with polyangiitis (GPA) for induction and maintenance of remission. Our study aims to evaluate the long-term efficacy and safety of chronic pre-emptive RTX therapy in GPA. METHODS: Retrospective study of 35 GPA patients treated with RTX between April 2004 and September 2011 for active disease and maintenance. RTX was initiated as two 1 g infusions 2 weeks apart and thereafter 2 g of RTX was readministered annually. Patients were followed for 47 (2-88) months. They received a median RTX dose of 8 g (2-13) over 5 (1-10) rounds. RESULTS: All patients had a clinical response, but nine relapses were recorded (flare rate of 6.6/100 patient-years). At last visit, 13 patients (37%) had discontinued RTX mainly due to hypogammaglobulinaemia (57%). Nine patients (26%) had severe infections (infection rate of 6.6/100 patient-years) and 10 patients (29%) had chronic infections. Risks factors for severe infections are a high cumulative dose of CYC, low CD4 cell count and a significant drop in total immunoglobulins after the first RTX round. Risks factors for chronic infections are low IgG level during RTX maintenance and possibly the cumulative RTX dose. CONCLUSION: Long-term pre-emptive RTX maintenance was efficacious in reducing the risk for relapse but was discontinued in one-third of the patients. The patients' net state of immunodeficiency under RTX changes over time as low immunoglobulin serum levels increased the risk for infections.

Imported case of visceral leishmaniasis presenting as pancytopenia in a Norwegian patient treated with methotrexate and etanercept for psoriasis arthritis.

We report a case of visceral leishmaniasis in a patient from northern Norway with psoriatic arthritis treated with a combination of etanercept and methotrexate. The patient resided extensively in southern Spain, a zone endemic for leishmania.

Trends in Hospitalization for Tuberculosis and Other Opportunistic Infections in Australian Patients with Inflammatory Joint Diseases.

OBJECTIVE: As immune-modulating therapy has become the standard of care for idiopathic inflammatory joint diseases (IJD), we investigated whether this has changed the rates for hospitalization with opportunistic infections (OI). METHODS: Administrative longitudinal state-wide health data identified patients hospitalized at least twice with diagnostic codes for rheumatoid arthritis (RA, n = 7730), psoriatic arthritis (PsA, n = 529) or axial spondylarthritis (AS, n = 1126) in Western Australia in the period 1985-2015. Overall incidence rates/1000 person-years (IR with 95% CI) for microbiologically confirmed OI (mycobacterial, fungal, and viral infections) during 180,963 person-years were analyzed across 10-year periods with IR trend rates analyzed by least square regression (R2) for all IJD categories. RESULTS: A total of 2584 OI occurred with higher IR rates observed in RA (15.34, CI 14.71-15.99) than PsA (8.73, CI 7.14-10.56) and AS (10.88, CI 9.63-12.24) patients (p < 0.001). IR rates were highest for Candidiasis across all three IJD categories (IR 10.0 vs. 6.32 vs. 6.88, respectively), while Varicella-zoster (VZV) was most frequent non-candida OI (IR 2.83.0 vs. 1.50 vs. 1.49, respectively) followed by mycobacterial (IR 1.14 vs. 0.08 vs. 0.24, respectively) and other mycotic infections (IR 0.60 vs. 0.58 vs. 0.86, respectively). Over time, the IR for tuberculosis and pneumocystosis decreased and remained stable for VZV infections in RA patients, but IR for all other OI increased across all disease categories. OI admission associated with 6.5% (CI 5.6-7.5) in-hospital mortality. CONCLUSIONS: Despite decreasing admission rates for tuberculosis and pneumocystosis in RA patients, an overall increase in mycotic and viral infection rates over time was seen across all three IJD. Together with a significant case fatality rate, this indicates continued efforts are needed to improve OI prevention in the management of IJD patients.

Mortality Trends Among Patients with Rheumatoid Arthritis in Western Australia.

INTRODUCTION: With scarce comparative data on mortality in Australian patients with rheumatoid arthritis (RA), we investigated temporal changes in standardized mortality rates for patients with RA using longitudinal linked population-wide health data in Western Australia (WA) over the period 1980 to 2015. METHODS: The study included 17,125 patients with a first-time hospital contact for RA (ICD-10-AM M05.00-M06.99 and ICD-9-AM 714.00-714.99) in the study period. Standardized mortality rate ratios (SMRRs) for the RA cohort versus the WA general population was estimated using direct age standardization. We analyzed temporal trends over with dates and causes provided by the WA Death Registry. RESULTS: During 356,069 patient-years of follow-up, a total of 8955 (52%) deaths occurred in the RA cohort. The SMRR was 2.24 (95% CI 2.15-2.34) in males and 3.09 (95% CI 3.00-3.19) in females over the study period. SMRR decreased since 2000 to 1.59 (95% CI 1.39-1.81) for the period 2011-2015. Median survival was 26.80 years (95% CI 26.30-27.30), where age and comorbidity independently increased the risk of death. The leading causes of deaths were cardiovascular diseases (26.60%), cancer (16.80%), rheumatic diseases (5.80%), chronic pulmonary disease 491 (5.50%), dementia (3.00%), and diabetes 235 (2.6%). CONCLUSIONS: The mortality rate in patients with RA in WA has decreased but remains 1.59-times higher than in community counterparts, suggesting that there is room for further improvement. Comorbidity is the main modifiable risk factor to further reduce mortality in patients with RA.

Mortality Rates in Patients With Ankylosing Spondylitis With and Without Extraarticular Manifestations and Comorbidities: A Retrospective Cohort Study.

OBJECTIVE: To examine mortality rates in hospitalized patients with ankylosing spondylitis (AS) and the association of extraarticular manifestations (EAMs) and comorbidities with mortality rates. METHODS: This study was a retrospective, population-based cohort study using linked administrative data from patients with AS who were hospitalized (n = 1791) and patients in a matched comparison group (n = 8955). Mortality data for patients were obtained from the Western Australia Death Register. The presence of EAMs and comorbidities was identified from hospital records. Mortality rates were compared between the 2 groups using Cox proportional hazard models overall and stratified by a history of EAMs, comorbidities, and smoking status. RESULTS: Crude mortality rates were significantly higher among patients with AS than among patients in the comparison group (hazard ratio [HR] 1.85, 95% CI 1.62-2.12), with excess mortality in the AS group associated with cardiovascular disease (CVD; HR 5.32, 95% CI 3.84-7.35), cancer (HR 1.68, 95% CI 1.27-2.23), external causes (HR 3.92, 95% CI 2.28-6.77), and infectious diseases (HR 25.92, 95% CI 7.50-89.56). When patients were stratified by history of EAMs, CVD, and smoking, the risk of mortality was elevated in patients both with and without each risk factor. Among patients with AS, histories of CVD (HR 6.33, 95% CI 4.79-8.38), diabetes (HR 2.81, 95% CI 1.99-3.95), smoking (HR 1.49, 95% CI 1.18-1.89), and EAMs (HR 1.62, 95% CI 1.24-2.11) were associated with an increased risk of mortality. CONCLUSION: The presence of comorbidities, EAMs, and smoking contributes to an increased risk of all-cause mortality among patients with AS who are hospitalized compared to patients in the comparison group. These results support the need to prevent or reduce the occurrence of comorbidities and smoking in patients with AS.

Total Hip Replacement in Patients with Rheumatoid Arthritis: Trends in Incidence and Complication Rates Over 35 Years.

INTRODUCTION: Advances in rheumatoid arthritis (RA) management have made disease remission achievable. We evaluated trends in total hip replacement (THR) and postoperative outcomes in patients with RA in Western Australia (WA) over more than three decades. METHODS: This was a retrospective analysis of routinely collected prospective data from a state-wide registry containing longitudinally linked administrative health data based on International Classification of Diseases (ICD) diagnostic and procedural codes. We included patients with two or more diagnostic codes for RA (between 1980 and 2015) and studied THR incidence rates (THR IR) and complication rates (revision, peri-prosthetic fracture, infection, venous thrombosis, and mechanical loosening). Survival rates were estimated by Kaplan-Meier method and predictors analyzed by Cox regression. RESULTS: We followed 9201 RA patients over 111,625 person-years, during which 1560 patients (16.9%) underwent THR. From 1985 to 2015, THR IR (per 1000 RA patient-years) decreased from 20.8 (95% CI 20.1-21.5) to 7.3 (95% CI 7.2-7.5), and 5-year THR-free survival increased from 84.3 to 95.3% (1980-2015). Ten-year prosthetic survival was 91.2%. Complication rates in the first 5 years post-THR decreased significantly from 13.1 to 3.7% (p < 0.001). Mechanical complications such as loosening and periprosthetic fracture rates decreased significantly (> 35%, P < 0.05), while infection and revision did not change over the observation period (p > 0.05). CONCLUSIONS: Over the last 30 years in RA patients, THR IR and mechanical complication rates decreased significantly, but the medical complication of infection has not changed significantly.

Increased mortality in ankylosing spondylitis is related to disease activity.

BACKGROUND: The onset of disease in ankylosing spondylitis (AS) is generally earlier than in other joint diseases, exposing patients to a prolonged burden of disease. Whether this is associated with excess mortality is still uncertain. Radiation therapy for AS has previously been shown to increase mortality. The present study investigated standardised mortality ratios, causes of death and survival predictors in a large regional cohort of patients with AS. METHOD: A total of 677 patients with AS followed at our hospital since 1977 were matched by gender, age and postal area to three controls from the general population and standardised mortality rates (SMRs) were calculated. Cause of death was established using patients' hospital records. In a subset of 360 patients, clinical and demographic data collected during an earlier research visit (1998-2000) were used in a prospective multivariate analysis of predictors for mortality in AS. RESULTS: The crude mortality among patients with AS in this study was 14.5% (98 patients); SMR was only significantly increased among male patients compared with female patients (1.63 vs 1.38, p<0.001). Circulatory disease was the most frequent cause of death (40.0%), followed by malignant (26.8%) and infectious (23.2%) diseases. Factors independently associated with reduced survival were diagnostic delay (OR 1.05), increasing levels of C-reactive protein (OR 2.68), work disability (OR 3.65) and not using any non-steroidal anti-inflammatory drugs (OR 4.35). CONCLUSIONS: Mortality is increased in patients with AS and circulatory disease is the most frequent cause of death. Parameters reflecting the duration and intensity of inflammation are associated with reduced survival. These results indicate that, to improve long-term survival in AS, there is a need for early detection and anti-inflammatory treatment as well as a vigilant approach for cardiovascular risk factors.

Increased levels of BAFF in patients with systemic lupus erythematosus are associated with acute-phase reactants, independent of BAFF genetics: a case-control study.

OBJECTIVES: To determine whether increased levels of B-cell activating factor (BAFF) in patients with SLE are due to disease activity or genetic variations in the promoter region of the BAFF gene and BAFF gene expression. METHODS: The case-control study included 101 SLE patients and 111 healthy controls. Five single nucleotide polymorphisms (SNPs) in the BAFF promoter region were investigated by melting point analysis: c.-2841 (T > C), c.-2704 (T > C), c.-2701 (A > T), c.-871 (C > T) and c.-514 (A > G). BAFF mRNA levels were determined by real-time PCR (BAFF-RQ) and serum BAFF (s-BAFF) levels were measured by ELISA. Independent predictors that might be correlated with increased s-BAFF in SLE patients were analysed by multivariate regression methods. RESULTS; Although s-BAFF levels were increased in SLE patients (1.73 vs 0.98 ng/µl, P < 0.001), no specific BAFF genotype was found to associate with SLE. The different genotypes defined by the investigated SNPs were identified both in SLE patients and healthy controls with similar frequencies. No association was found between BAFF genotype and BAFF-RQ. s-BAFF was independent of other factors, correlated with CRP (ß = 0.40, P < 0.001) and physician's visual analogue score (R = 0.21, P = 0.046) and inversely with haemoglobin (ß = -0.32, P < 0.001) and IgA (ß = -0.33, P = 0.001). CONCLUSIONS: Increased s-BAFF levels in SLE patients are associated with the acute-phase responses, CRP and haemoglobin, but probably not dependent on BAFF genotype or expression. This indicates that s-BAFF production occurs at sites of inflammation.

Decreased incidence of lupus nephritis in northern Norway is linked to increased use of antihypertensive and anticoagulant therapy.

BACKGROUND: Lupus nephritis (LN) remains a severe complication in systemic lupus erythematosus (SLE). Over the last decade, antiphospholipid antibodies have become a part of SLE classification criteria, and awareness of cardiovascular morbidity and its risk factors in SLE has increased. This study investigated the potential effect of these alterations on the presentation and severity of LN. METHODS: This is an observational study of two subsequent SLE inception cohorts based on 1982 American College of Rheumatology (acr) classification criteria (82acr; n=87, enrolled 1978-95) and the updated version in 1997 (97acr: n=62, enrolled 1996-2006). Annual incidence rates (AIR), point prevalence, clinical and histological features, and outcome of LN (defined as proteinuria with urinary casts and/or haematuria) were compared between both cohorts. RESULTS: Between 1978 and 2006, the AIR for LN decreased from 0.7 to 0.45/100 000, while LN prevalence rose from 7 to 14/100 000. The relative risk reduction in the 97acr for early- and late-onset LN (> 3 months after SLE diagnosis) was 39% and 42%, respectively. Patients developing LN in the 97acr cohort (97LN+; n=11) had similar demographics, more often low avidity anti-dsDNA antibodies (Ab) and/or anti-cardiolipin Ab at SLE diagnosis, lower proteinuria and diastolic blood pressure, and similar histological findings to those in the 83acr cohort (82LN +; n=28). Following LN diagnosis, more 97LN + patients received pulse corticosteroids (55% vs. 7%), anticoagulants (46% vs. 4%) and antihypertensive drugs (46% vs. 11%). Three 82LN+ patients (11%) developed end-stage renal disease versus none in 97LN + during a 10-year follow-up. CONCLUSIONS: Early detection of low avidity anti-dsDNA and antiphospholipid antibodies, probably in combination with early use of protective cardiovascular measures from SLE diagnosis onwards may contribute to reduced incidence and improved renal survival in LN.

Septic Arthritis in Children: A Longitudinal Population-Based Study in Western Australia.

OBJECTIVE: To describe the incidence, risk factors and long-term outcomes in children hospitalised with septic arthritis (SA) in Western Australia (WA). METHODS: We extracted state-wide longitudinally linked administrative health data for patients aged < 16 years with a first diagnostic code of 711.X (ICD9-CM) and M00.X (ICD10-AM) in WA in the period 1990-2010. Annual incidence rates (AIR) per 100,000 with 95% confidence intervals (CIs), prior conditions during a median lookback period of 63.2 [interquartile range (IQR) 19.8-117.1] months and outcomes, including standardised mortality rates (SMR), during a median follow-up of 10 years are reported. RESULTS: A total of 891 patients [62% male, median age 6.4 (IQR 1.9-10.6) years with 34% aged < 3 years] were admitted for SA during the observation period. The overall AIR (per 100,000) was 9.85 (95% CI 4.79-14.41), and was higher in Indigenous Australians [34.9 vs. 5.5 (non-Indigenous), p < 0.001] and in males [11.9 vs. 7 (females), p < 0.01]; AIR showed no temporal or seasonal variation. Knees (43.9%), hips (34.6%) and ankles (13.3%) were most frequently affected, with Staphylococci predominant (49%) in patients with positive cultures (41.5%). Prior infection(s) (40.4%) and respiratory disease (7%) were the main pre-existing morbidities. Median hospital stay was 4.0 (IQR 2-8) days, with 1.9% requiring admission to the intensive care unit and 10.4% requiring readmission within 30 days. During follow-up, 26 patients (3.1%) developed osteomyelitis, nine patients were diagnosed with osteoarthrosis (1.1%) and five patients (0.6%) underwent joint replacement. Female patients developed other serious infections more often than male patients (40.5 vs. 27.1%, p < 0.01), as well as other comorbidities (Charlson Comorbidity Index > 0: 34.6 vs. 27.2%, p = 0.02), including diabetes (4.2 vs. 0%; p = 0.001), cardiovascular events (4.2 vs 1.4%, p = 0.002) and chronic arthritis (1 vs. 0%, p = 0.05). The crude mortality rate was low (0.3%), with 99.4% survival at 180 months and no increase in the SMR. CONCLUSIONS: The incidence of SA in children in WA did not change over the 20-year observation period. SA did not lead to excess mortality, but bone and joint complications developed in 5% of patients. The high propensity to comorbid conditions in this young cohort suggests an underlying role of comorbidity in SA development.

As more children are living with complex and chronic conditions, we investigated whether children in Western Australia (WA) have become more prone to joint infections. During a 20-year observation period we collected health data for all children admitted to any hospital in the state with an infected joint and recorded their health outcomes. We found that joint infection occurs in nearly ten out of 100,000 children each year, but we saw no change in the frequency over time. We did observe higher rates in Indigenous children (35/100,000) than in non-indigenous children (6/100,000) but found no noticeable influence of the seasons on the frequency of joint infections. Knees, hips and ankles were most often affected, and 15% had additional bone infection. Children needed to be treated in hospital for 4­5 days, and only a small minority (1.2%) were so ill they needed intensive care. Joint infections led to chronic, long-term complications in about 5% of patients, but we found no evidence that joint infections increased the risk of death compared to children in the general population.

The Prevalence of Rheumatoid Arthritis: A Systematic Review of Population-based Studies.

OBJECTIVE: To estimate the prevalence of rheumatoid arthritis (RA) from international population-based studies and investigate the influence of prevalence definition, data sources, classification criteria, and geographical area on RA prevalence. METHODS: A search of ProQuest, MEDLINE, Web of Science, and EMBASE was undertaken to identify population-based studies investigating RA prevalence between 1980 and 2019. Studies were reviewed using the Joanna Briggs Institute approach for the systematic review and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Sixty studies met the inclusion criteria. There was a wide range of point prevalence reported (0.00-2.70%) with a mean of 0.56% (SD 0.51) between 1986 and 2014, and a mean period prevalence of 0.51% (SD 0.35) between 1955 and 2015. RA point and period prevalence was higher in urban settings (0.69% vs 0.48%) than in rural settings (0.54% vs 0.25%). An RA diagnosis validated by rheumatologists yielded the highest period prevalence of RA and was observed in linked databases (0.80%, SD 0.1). CONCLUSION: The literature reports a wide range of point and period prevalence based on population and method of data collection, but average point and period prevalence of RA were 51 in 10,000 and 56 in 10,000, respectively. Higher urban vs rural prevalence may be biased due to poor case findings in areas with less healthcare or differences in risk environment. The population database studies were more consistent than sampling studies, and linked databases in different continents appeared to provide a consistent estimate of RA period prevalence, confirming the high value of rheumatologist diagnosis as classification criteria.

Infection Rates Before and After Diagnosis of IgA Vasculitis in Childhood: A Population-wide Study Using Non-exposed Matched Controls.

OBJECTIVE: Clinical data suggest that infections can trigger IgA vasculitis (IgAV), but longterm observations are lacking. We compared rates, types, and microorganisms for serious infection before and after diagnosis for children with IgAV and non-exposed controls. METHODS: Using population-based administrative linked health datasets we estimated incidence rates (IR) for serious infection per 1000 person-months for patients with IgAV (n = 504, age 5 yrs, 59.1% males) and controls matched for age, sex, and year of presentation (n = 1281, age 6 yrs, 66% males). Time zero (T0) was the date of IgAV diagnosis or equivalent date in controls, lookback (median 38 mos) was the period prior to T0, and followup (median 239 mos) was the period after T0. RESULTS: During lookback, prevalence of serious infection was similar in patients with IgAV and controls (11.5% vs 9.5%, respectively), but patients with IgAV had a higher rate of upper respiratory tract infections [incidence rate ratio (IRR) 1.79; 95% CI 1.39-2.31] with shorter time between first serious infection and T0 (27 vs 43 mos; p = 0.02). During followup, patients were at a constant increased risk for serious infections (IRR 1.46, 95% CI 1.35-1.58). These rates were higher during followup: sepsis (IRR 12.6), pneumonia (IRR 6.19), upper respiratory tract infections (IRR 2.36), and skin infections (IRR 1.85). There was little overlap between patients with serious infections in the lookback and followup periods. CONCLUSION: In patients with childhood IgAV there is an increased longterm risk for a broader spectrum of infections, which is unrelated to serious infections prior to diagnosis or treatment. This suggests disease-specific factors may have a lasting effect on immune competence in childhood IgAV.

The Risk and Consequences of Vertebral Fracture in Patients with Ankylosing Spondylitis: A Population-based Data Linkage Study.

OBJECTIVE: To compare the long-term prevalence, incidence, and outcomes of vertebral fracture (VF) between ankylosing spondylitis (AS) patients and matched controls, including the role of extraarticular manifestations (EAM) and osteoporosis. METHODS: This was a statewide observational study using linked health data for 2321 patients with AS and 22,976 controls presenting to hospital from 1980 to 2015. Data were analyzed using incidence rates (per 1000 person-yrs) and ratios (IRR), multivariable Cox proportional hazards regression, and Kaplan-Meier survival curves. RESULTS: Over a median 13.92 (interquartile range 7.58-21.67) years of follow-up, patients with AS had a greater VF prevalence and greater incidence of developing a new VF compared to controls (9.3% vs 2.5%, 6.8% vs 1.9%, respectively, all P < 0.001). Patients with AS had an increased risk of developing a VF after adjustments for age, sex, and osteoporosis (HR 2.55, 95% CI 2.11-3.09) compared to controls; this risk remained throughout the study period. Patients with AS were 5 years younger at time of first VF (P = 0.008) and had a greater likelihood of a recurrent VF (IRR 4.64; 95% CI 4.54-4.75) compared to respective controls. Mortality overall was comparable between patients with AS and controls after adjustment for age, sex, osteoporosis, and VF status (HR 0.90; 95% CI 0.80-1.01). CONCLUSION: The significantly increased risk of VF in patients with AS has not altered following the introduction of tumor necrosis factor inhibitor treatment. Although patients with AS experience a first VF at a younger age than controls, this does not lead to an increased risk of death.

IL-1A gene variation in relation to cytokine levels and clinical characteristics in ankylosing spondylitis.

OBJECTIVE: Variations in the IL-1 alpha (IL-A) gene increase the risk for ankylosing spondylitis (AS), but the pathway underlying this association is not fully understood. As IL-1A is primarily a regulatory cytokine, we investigated the influence of IL-1A gene variation on disease severity and cytokine expression in AS. METHODS: This was a cross sectional study of tumor necrosis factor inhibitors (TNFi)-naïve AS patients (n=334, 90% B27 +, age 45 years) fulfilling the modified New York criteria. We recorded demographics, clinical findings, spinal mobility, Bath AS Functional Index (BASFI), and routine lab findings. IL-1A genotyping for three AS-associated single nucleotide polymorphism (SNP; rs2856836, rs17561 and rs1894399) was performed using Taqman RT-PCR, with TNF, IL-6, IL-17A, and IL-23 levels measured using ELISA. Genotypic associations included logistic regression analysis for genotype (codominant model) and global haplotype (threshold 5%) associations with cytokine levels and clinical features. RESULTS: The three variants were in near complete linkage disequilibrium and formed two only common haplotypes (ACC 67%, GAT 33%). The levels for TNF, IL-6, IL-17A, IL-23, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were similar across genotypes and haplotypes (all p-values >0.4) as were the measures for spinal mobility and BASFI. The TAQ haplotype showed a borderline significant trend with reduced heart disease and mortality during follow-up. CONCLUSION: IL-1A gene cluster variations do not have an impact on the clinical disease measures or cytokine levels in AS, suggesting that IL-1A has no direct role in AS.