The relationship between clinical phenotype and kallikrein-kinin bioregulation in different forms of arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides. METHODS: Patients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization by bright field microscopy. Levels of plasma biomarkers were measured by ELISA and cytometric bead array. RESULTS: Quality of life (SF-36 domains and summary scores; including pain; and, HAQ) was similar across OA, gout and RA patients; with the exception of worse physical functioning scores between OA and gout patients. Synovial hypertrophy (on ultrasound) differed between groups (p = 0.001), and the dichotomised Power Doppler (PD) score of greater than or equal to 2 (PD-GE2) was marginally significant (p = 0.09). Plasma IL-8 were highest in patients with gout followed by RA and OA (both, P < 0.05). Patients with RA had higher plasma levels of sTNFR1, IL-1ß, IL-12p70, TNF and IL-6, compared to OA and gout patients (all, P < 0.05). Patients with OA had higher expression of K1B and KLK1 on blood neutrophils followed by RA and gout patients (both, P < 0.05). Bodily pain correlated with B1R expression on blood neutrophils (r = 0.334, p = 0.05), and inversely with plasma levels of CRP (r = -0.55), sTNFR1 (r = -0.352) and IL-6 (r = -0.422), all P < 0.05. Expression of B1R on blood neutrophils also correlated with Knee PD (r = 0.403) and PD-GE2 (r = 0.480), both P < 0.05. CONCLUSIONS: Pain levels and quality of life were similar between patients with OA, RA and gout with knee arthritis. Plasma inflammatory biomarkers and B1R expression on blood neutrophils correlated with pain. Targeting B1R to modulate the kinin-kallikrein system may pose as a new therapeutic target in the treatment of arthritis.

Fracture liaison service utilising an emergency department information system to identify patients effectively reduce re-fracture rate is cost-effective and cost saving in Western Australia.

OBJECTIVES: To assess the benefits of the Emergency Department Information System (EDIS)-linked fracture liaison service (FLS). METHODS: Patients identified through EDIS were invited to attend an FLS at the intervention hospital, the Sir Charles Gairdner Hospital (SCGS-FLS). The intervention group was compared to usual care. Retrospective control (RC) at this hospital determined historical fracture risk (SCGH-RC). Prospective control (PC) was from a comparator, Fremantle Hospital (FH-PC). The main outcome measures were cost-effectiveness from a health system perspective and quality of life by EuroQOL (EQ-5D). Bottom-up cost of medical care, against the cost of managing recurrent fracture (weighted basket), was determined from the literature and 2013/14 Australian Refined Diagnosis Related Groups (AR-DRG) prices. Mean incremental cost-effectiveness ratios were simulated from 5000 bootstrap iterations. Cost-effectiveness acceptability curves were generated. RESULTS: The SCGH-FLS program reduced absolute re-fracture rates versus control cohorts (9.2-10.2%), producing an estimated cost saving of AUD$750,168-AUD$810,400 per 1000 patient-years in the first year. Between-groups QALYs differed with worse outcomes in both control groups (p < 0.001). The SCGH-FLS compared with SCGH-RC and FH-PC had a mean incremental cost of $8721 (95% CI -$1218, $35,044) and $8974 (95% CI -$26,701, $69,929), respectively, per 1% reduction in 12-month recurrent fracture risk. The SCGH-FLS compared with SCGH-RC and FH-PC had a mean incremental cost of $292 (95% CI -$3588, $3380) and -$261 (95% CI -$1521, $471) per EQ-5D QALY gained at 12 months respectively. With societal willingness to pay of $16,000, recurrent fracture is reduced by 1% in >80% of patients. CONCLUSIONS: This simple and easy model of identification and intervention demonstrated efficacy in reducing rates of recurrent fracture and was cost-effective and potentially cost saving.

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.

Abdominal aortic calcification, cardiac troponin I and atherosclerotic vascular disease mortality in older women.

OBJECTIVE: Examine if two inexpensive measures of atherosclerotic vascular diseases (ASVD), abdominal aortic calcification (AAC) and high-sensitivity cardiac troponin I (hs-cTnI) provide complementary information for 10-year ASVD mortality and all-cause mortality risk in older women. METHODS: 908 community-dwelling women without prevalent ASVD (≥75 years) were followed-up between 2003 and 2013. AAC and plasma hs-cTnI measures were obtained in 2003. AAC was assessed on lateral spine images using a semiquantitative method (AAC24). Linked health records were used for mortality outcomes. RESULTS: Mean±SD age was 79.9±2.6 years. 276 (30.4%) women died during follow-up, including 138 (15.2%) ASVD-related deaths. AAC24 and hs-cTnI were independently associated with ASVD and all-cause mortality (p<0.001). The cohort was dichotomised into four groups: (1) low AAC24 (AAC24: 0 or 1) and 1) and

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.

Outcomes in buried versus non-buried peritoneal dialysis catheters: A retrospective cohort study.

AIMS: To compare the rates of infections (peritonitis and exit site infections) in patients undergoing non-buried versus buried peritoneal dialysis catheterisation for end-stage renal failure. METHODS: A retrospective review of all patients who underwent peritoneal dialysis catheter placement by one primary surgeon between January 2008 and August 2019. Information collected included, catheter characteristics, immediate post-operative complications, date of catheter exteriorisation, date of peritoneal dialysis commencement, rate of successful catheter function at initiation of peritoneal dialysis and rates of catheter-related complications (i.e. infection, revision status and obstruction). RESULTS: 110 peritoneal dialysis catheters were inserted (43 non-buried and 67 buried peritoneal dialysis catheters). The non-buried group was associated with a higher proportion acquiring an infection than the buried group (15% vs 30%, p = 0.054). Patients with buried catheters also had a 72% and 65% decreased likelihood of experiencing a catheter-related infection and peritonitis, respectively, over time compared to patients with non-buried catheters in the unadjusted (crude incidence rate ratio 0.28, 95% confidence interval 0.11, 0.70; P = 0.003). The proportion of catheter function at first use was 85% in the non-buried group and 78% in the buried group. Patients with non-buried versus buried catheters had similar proportions of complications, including: obstructions (25.6% vs 20.9%, p = 0.770), herniation (7.0% vs 4.0%, p = 0.327) and leaks (7.0% vs 1.5%, p = 0.134). CONCLUSION: The use of the buried peritoneal dialysis catheter technique as compared to the standard technique has revealed fewer overall catheter-related infections, particularly episodes of peritonitis and similar rates of mechanical complications in our series. In addition to that, the other benefits of buried peritoneal dialysis catheters such as lower healthcare cost, patient convenience and a viable option for patients in remote communities should prompt physicians to continue assessing suitable candidates for buried peritoneal dialysis catheters.

Serum Midkine, estimated glomerular filtration rate and chronic kidney disease-related events in elderly women: Perth Longitudinal Study of Aging Women.

Midkine (MDK), a heparin-binding growth factor cytokine, is involved in the pathogenesis of kidney diseases by augmenting leukocyte trafficking and activation. Animal models and small case control studies have implicated MDK as a pathological biomarker in chronic kidney diseases (CKD), however this is yet to be confirmed in prospective human studies. In a prospective study of 499 elderly, predominantly Caucasian women aged over 70 years the association between serum MDK collected in 1998, and renal function change and the risk of CKD-related hospitalisations and deaths at 5 and 14.5 years, respectively, was examined. Baseline serum MDK was not associated with 5-year change in estimated glomerular filtration rate using the CKD Epidemiology Collaboration creatinine and cystatin C equation (Standardised ß = - 0.09, 95% confidence interval - 3.76-0.48, p = 0.129), 5-year rapid decline in renal function (odds ratio = 0.97, 95% confidence interval 0.46-2.02, p = 0.927) or the risk of 14.5-year CKD-related hospitalisations and deaths (hazard ratio = 1.27, 95% confidence interval .66-2.46, p = 0.470) before or after adjusting for major risk factors. In conclusion, in this cohort of elderly women with normal or mildly impaired renal function, serum MDK was not associated with renal function change or future CKD-related hospitalisations and deaths, suggesting that MDK may not be an early biomarker for progression of CKD.

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.

Case finding with GARVAN fracture risk calculator in primary prevention of fragility fractures in older people.

BACKGROUND: Fracture risk calculators (FRC) with DXA can guide osteoporosis (OP) management in the absence of dual X-ray absorptiometry (DXA). There is little information of the role of FRC without DXA. OBJECTIVES: Determine the accuracy of age-stratified Garvan FRC thresholds without DXA to manage OP. METHODS: Cross-sectional study of 531 participants, ≥70 years old who underwent DXA and had Garvan FRC scores with and without DXA calculated. Age-stratified Garvan scores without DXA, generated low (no action), moderate (order DXA) or high (treat without DXA) risk thresholds of OP. Accuracy of our thresholds were assessed against DXA confirmed OP. RESULTS: Age-specific GARVAN thresholds resulted in the correct decision in 85-88% of cases; "over-treated" OP in 7-8%; and, missed OP in 5-8%. 256 (48%) DXAs were unnecessary. Compared to recommended guidelines, Garvan HF and MOF thresholds improved accuracy of clinical decisions by 31% and 12%, respectively. CONCLUSIONS: Age-specific FRC score thresholds successfully identified who required treatment or DXA, with potential to reduce unnecessary DXA.

Post-stroke sleep disturbances and rehabilitation outcomes: a prospective cohort study.

BACKGROUND: Poor sleep is common after stroke, and data regarding its effect on rehabilitation outcomes are limited. Controversial evidence was found concerning the effect of sedatives on improving sleep quality in poor sleepers after stroke. AIM: To assess the prevalence of poor sleep in post-stroke patients and its effect on rehabilitation outcomes. METHOD: A total of 104 stroke patients from two major stroke rehabilitation units in Western Australia was enrolled. Sleep quality was assessed using the Pittsburgh Sleep Quality Indexes at baseline and after stroke. The main outcome measures were Functional Independence Measure (FIM) change and length of stay (LOS). Sedative use during this period was also recorded. RESULTS: A total of 29.8% post-stroke patients suffered from poor sleep. There was no relationship between poor sleep and the stroke characteristics, such as severity, side and type, or demographics, such as age and gender. Poor sleep quality was inversely associated with rehabilitation outcomes measured by FIM (Rs. -0.317, P = 0.005). However, there was no significant association between sleep quality and LOS (P = 0.763). Sedatives were used in 18.2% of patients but had no impact on sleep quality or rehabilitation outcomes. CONCLUSION: This research supported that poor sleep was frequent after stroke and had negative effects on rehabilitation outcomes. Use of sedatives was of limited benefit to improve sleep quality, and further studies are required to search for strategies to improve sleep problems after stroke.

Rehabilitation Indices associated with sustaining a minimal trauma fracture within 12 months of a stroke in Western Australia.

OBJECTIVE: To identify Rehabilitation Indices associated with a minimal trauma fracture (MTF) within 12 months poststroke. METHODS: Retrospective case-control study. Stroke survivors with MTF were matched 5:1 with stroke survivors without MTF. Logistic regression determined whether Rehabilitation Indices, such as Physiotherapy Ambulation score (PhysioAmb), were associated with a MTF within 12 months poststroke. RESULTS: Forty-three stroke survivors (mean age: 79.8; 55.81% female) experienced a MTF (median time to MTF of 1.79 years [IQR 0.70, 4.48]). Those with a MTF within 12 months had lower PhysioAmb (4.53 vs 8.29) and Berg Balance Scale (BBS; 12.25 vs 40.57) scores on admission, lower BBS score on discharge (30.33 vs 49.29) and a greater change in PhysioAmb (+5.67 vs +3.24) and BBS scores (+21.50 vs +8.71) after rehabilitation, all P < 0.05. Greater changes in PhysioAmb score increased the odds of a MTF within 12 months by 18%. CONCLUSION: Rehabilitation Indices are associated with a MTF within 12 months poststroke.

A multicentre observational study comparing patient reported outcomes to assess reliability of swollen and tender joint assessments and response to certolizumab treatment as compared to clinician assessments in rheumatoid arthritis.

AIMS: The use of swollen (SJC) and tender joint counts (TJC) for rheumatoid arthritis (RA) disease activity and treatment effectiveness is well established. Patient-reported outcomes (PRO) are important. However, it is unknown if patient scoring is as reliable as that of trained professionals. METHODS: PRO including SJC and TJC were assessed at baseline, 6 and 12 weeks by patients and clinicians. Data were collected using ePRO (electronic) and pPRO (paper). The Least Squares Method (LSM), Pearson correlation (Rs) and weighted Kappa scores were used to assess inter-rater reliability and agreement of responses between the patient, nurse and physician for changes in TJC and SJC from 0 to 12 weeks of treatment. RESULTS: There was a total of 341 evaluable matched joint assessment in 52 patients with RA: 157 nurse, 106 patient and 78 physician. There were matched joint count pairs for 104 patient-nurse, 72 physician-nurse and 21 patient-physician. Correlation (R) of TJC scores were as follows: patient-nurse 0.83 (P < 0.001), physician-nurse 0.85 (P < 0.001) and physician-patient 0.59 (P = 0.005). The inter-rater reliability (agreement) of the patient-nurse pairs had a weighted Kappa of 0.59 (0.53, 0.68). Correlation (R) of SJC scores were as follows: patient-nurse 0.69 (P < 0.001), physician-nurse 0.66 (P < 0.001) and physician-patient 0.42 (P = 0.058). The inter-rater reliability (agreement) of the patient-nurse pairs had a weighted Kappa of 0.48 (0.41, 0.55). CONCLUSIONS: There is a moderate to high level of agreement between clinicians and patient TJC and SJC assessments that suggest it may be a useful option in assessing joints and response in RA. Further evaluation of RA activity tools such as Disease Activity Score of 28 joints, Crohn Disease Activity Index or Simple Disease Activity Index utilizing patient assessments may be worth exploring.

Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation.

BACKGROUND: von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. METHODS: Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry. VWF function was determined by ristocetin-induced platelet aggregation (VWF ristocetin cofactor, VWF:RCo) and VWF levels by turbidimetric assay (VWF antigen, VWF:Ag). The platelet-aggregating activity per VWF unit was estimated by the VWF RCo/Ag ratio. Healthy controls served as comparators and associations were evaluated by non-parametric methods. RESULTS: VWF:Ag (142% vs 107%, p=0.001) and VWF:RCo levels (123% vs 78%, p<0.041) were increased in patients with SLE, but VWF RCo/Ag ratio was similar as in controls (0.83 vs 0.82, p=0.8). VWF:Ag levels were higher in patients experiencing serositis but unrelated to other manifestations, thrombotic disease, Systemic Lupus Erythematous Disease Activity Index 2000 or Systemic Lupus International Collaborative Clinics-Damage Index. VWF:Ag levels correlated significantly with VWF:RCo levels (Rs 0.8, p<0.001), erythrocyte sedimentation rate (ESR) (Rs 0.32, p<0.01), anti-dsDNA Ab (Rs 0.27, p<0.01), total IgG (Rs 0.33 p<0.01), fibrinogen (Rs 0.28, p<0.01) and ceruloplasmin (Rs 0.367, p<0.01) levels. VWF:RCo levels were not related to clinical findings but were correlated with ESR, anti-dsDNA and transferrin levels. No serological associations existed for VWF RCo/Ag ratio (all p>0.2). CONCLUSIONS: In this SLE cohort, VWF:Ag behaved similarly to acute-phase reactants, but VWF:Ag increases were not matched by increases in functional activity per unit of VWF. Thus, more VWF did not increase the propensity for platelet aggregation in SLE.