ORCID Profile
0000-0001-7205-4807
Current Organisations
Southern Adelaide Local Health Network
,
University of Adelaide
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Publisher: Oxford University Press (OUP)
Date: 05-08-2007
DOI: 10.1093/RHEUMATOLOGY/KEM280
Abstract: This article describes the development of the Sjögren's Systemic Clinical Activity Index (SCAI) for the measurement of systemic disease activity in patients with primary Sjögren's syndrome (PSS). A pilot tool was developed based on expert consensus and previous published data. One hundred and four patients with PSS were evaluated in a cross-sectional analysis, of whom 65 were reviewed at 3-monthly intervals, using this index, over a 12-month period. Factor analysis was used to evaluate the proposed domain structure. External validation was assessed by comparison with relevant domains of the Profile of Fatigue and Discomfort (PROFAD), Medical Outcomes Study Short Form-36 (SF-36) and The World Health Organization Quality of Life-Bref (WHOQOL-BREF). Sensitivity to change was assessed by comparing SCAI-derived flares with physician-designated disease flare and intention-to-treat analysis. A reliability and repeatability workshop was also held. Factor analysis supported the proposed domain structure. There were strong correlations between the SCAI fatigue, musculoskeletal and Raynaud's components and the PROFAD fatigue, arthralgia and vascular domains. There was a significant correlation between change in therapy and SCAI-defined flares (P = 0.01). The mean kappa-test results both for reliability of the SCAI and for physician repeatability were 0.71. This initial evaluation supports the potential for the SCAI as a tool for systemic activity assessment in patients with PSS but additional work is required to assess sensitivity to change in clinical therapeutic trials.
Publisher: Public Library of Science (PLoS)
Date: 07-04-2014
Publisher: Springer Science and Business Media LLC
Date: 04-04-2022
DOI: 10.1186/S12891-022-05251-7
Abstract: Frozen shoulder (adhesive capsulitis) is an inflammatory condition affecting the capsule of the glenohumeral joint. It is characterised by a painful restricted range of passive and active movement in all planes of motion. The impact of frozen shoulder on affected in iduals remains poorly characterised. In this study we sought to better understand the lived experience of people suffering from frozen shoulder to characterise the physical, psychological and socioeconomic impact of the condition. A qualitative study using a phenomenological approach was undertaken. Purposeful s ling was used to identify in iduals for interview. Semi-structured interviews were performed and continued until saturation was achieved. A biopsychosocial framework was used during the analysis in order to generate themes which best described the phenomenon and reflected the lived experience of in iduals’ suffering from this condition. Ten interviews were conducted, and five main themes emerged including the severity of the pain experience, a loss of independence, an altered sense of self, the significant psychological impact, and the variable experience with healthcare providers. These findings offer an insight into the lived experience of in iduals with frozen shoulder, both on a personal and sociocultural level. The pain endured has profound impacts on physical and mental health, with loss of function resulting in a narrative reconstruction and altered sense of self. Our findings illustrate that frozen shoulder is much more than a benign self-limiting musculoskeletal condition and should be managed accordingly. ANZCTR 12620000677909 Registered 28/04/2020 www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379719& isReview=true
Publisher: Elsevier BV
Date: 12-2022
Publisher: AMPCo
Date: 11-2018
DOI: 10.5694/MJA18.00190
Abstract: Alkylating chemotherapy is often used to treat pre-menopausal women for various malignancies and autoimmune diseases. Chemotherapy-associated ovarian failure is a potential consequence of this treatment which can cause infertility, and increases the risk of other long term adverse health sequelae. Randomised trials, predominantly of women undergoing alkylating chemotherapy for breast cancer, have shown evidence for the efficacy of gonadotropin-releasing hormone agonists (GnRHa) in preventing chemotherapy-associated ovarian failure. The European St Gallen and United States National Comprehensive Cancer Network guidelines recommend the use of concurrent GnRHa to reduce the risk of ovarian failure for pre-menopausal women undergoing chemotherapy for breast cancer. The GnRHa goserelin, a monthly 3.6 mg depot subcutaneous injection, has recently been listed on the Australian Pharmaceutical Benefits Scheme to reduce risk of ovarian failure for pre-menopausal women receiving alkylating therapies for malignancy or autoimmune disease. The first dose of goserelin should ideally be administered at least 1 week before commencement of alkylating treatment and continued 4-weekly during chemotherapy. Concurrent goserelin use should now be considered for all pre-menopausal women due to commence alkylating chemotherapy (except those with incurable cancer), regardless of their childbearing status, in an effort to preserve their ovarian function. For women who have not completed childbearing, consideration of other fertility preservation options, such as cryopreservation of embryos or oocytes, is also important.
Publisher: Oxford University Press (OUP)
Date: 29-04-2008
DOI: 10.1093/RHEUMATOLOGY/KEN164
Abstract: To validate a tool for assessment of accumulated damage in patients with Primary SS (PSS). Of the total 114 patients fulfilling American-European Consensus Group (AECG) criteria for PSS 104 were included in the study and assessed by rheumatologists at T (time) = 0 months and T = 12 months. On each occasion, damage and activity data, and autoantibody status were collected. SF-36 and Profile of Fatigue and Discomfort-Sicca Symptoms Inventory (PROFAD-SSI) questionnaires were completed. Cross-sectional analysis of this data was subject to a process of expert validation by 11 ophthalmologists, 14 oral medicine specialists and 8 rheumatologists. Items were removed from the index if >or= 50% of respondents recommended exclusion. Statistical validation was performed on remaining items. Spearman's rank analysis was used to investigate associations between damage scores and other disease status measures and Wilcoxon matched-pair analysis to assess sensitivity to change in the damage score. Based on the expert validation, a 29-item damage score was agreed incorporating ocular, oral and systemic domains. Total damage score correlated with disease duration at study entry (r = 0.436 P < 0.001), physical function as measured by SF-36 (r = 0.250, T = 0 months r = 0.261 T = 12 months) and activity as measured by the Sjögren's Systemic Clinical Activity Index (r = 0.213, T = 0 months r = 0.215, T =12 months). Ocular damage score correlated with the 'eye dry' domain of PROFAD-SSI (r = 0.228, T = 0 months r = 0.365, T = 12 months). Other associations not present on both assessments were considered clinically insignificant. On Wilcoxon analysis, the index was sensitive to change over 12 months (z = -3.262 P < 0.01). This study begins validation of a tool for collection of longitudinal damage data in PSS. We recommend further trial in both the experimental and clinical environment.
Publisher: Elsevier BV
Date: 10-2023
Publisher: SAGE Publications
Date: 13-11-2019
Abstract: To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate % roteinuria .5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. Patients ( N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.
Publisher: Elsevier BV
Date: 10-2007
DOI: 10.1016/J.SEMARTHRIT.2007.02.001
Abstract: To assess the safety and efficacy of combination therapy in recent-onset rheumatoid arthritis (RA), with dose adjustments determined by response, in a clinic setting over 3 years. Disease-modifying antirheumatic drug (DMARD)-naive patients with RA of median duration of 12 weeks (n = 61) attending an early arthritis clinic were treated with methotrexate, sulfasalazine, hydroxychloroquine, and fish oil. Dosage adjustments and additions of further DMARDs were contingent on response to therapy and tolerance. Outcome measures for efficacy were Disease Activity Score (DAS28), clinical remission, and modified Sharp radiographic score and for safety, adverse events, and DMARD withdrawal. At baseline, subjects had at least moderately active disease (mean +/- SD DAS28 was 5.3 +/- 1.1), impaired function as measured by the modified Health Assessment Questionnaire (mHAQ) (0.9 +/- 0.5), and 37% had bone erosions. By 3 months, 29% were in remission this increased to 54% at 3 years. The greatest fall in DAS28 and improvement in mHAQ scores occurred in the first 12 months. Erosions were detected in 62% at 3 years. The mean dose of parenteral glucocorticoid was equivalent to 0.1 mg/d of prednisolone. After 3 years, 48% remained on triple therapy fish oil was consumed by 75% of patients, and 21% used nonsteroidal anti-inflammatory drugs. Gastrointestinal intolerance was the most frequent unwanted event (leading to DMARD withdrawal in 17 patients). Sulfasalazine was most frequently withdrawn (30%). This implementation study demonstrates the feasibility, safety, and efficacy of combination therapy with inexpensive DMARDs, fish oil, and minimal glucocorticoid use, in routine clinical practice using predefined rules for dosage adjustment.
Publisher: Springer Science and Business Media LLC
Date: 09-11-2016
Publisher: Wiley
Date: 05-11-2019
Publisher: Springer Science and Business Media LLC
Date: 06-06-2019
DOI: 10.1007/S10067-019-04609-Y
Abstract: Despite close management in specialized clinics, medication adherence remains a significant problem for some patients. The study aims to explore factors affecting medication adherence in patients attending a biologics clinic. Participants completed surveys including the Compliance Questionnaire Rheumatology (CQR) to quantify adherence rates. Purposive s ling targeting poorly adherent patients was used to select in iduals for qualitative evaluation. Semi-structured interviews were performed and continued until saturation was achieved. Interviews were transcribed and coded using NVivo. Principles of grounded theory were used for data analysis. A total of 123 patients completed the survey (72 RA, 33 PsA, 18 AS). Of which, 96 patients completed all CQR items, of these 72% were identified as adequately adherent. A major theme which emerged from patient interviews was that the presence of active symptoms significantly influenced adherence. Patients tended not to prioritize medication taking until they had a recurrence of symptoms. Despite describing biologics as "life-changing", patients expressed concern regarding potential long-term side effects of these medications which affected adherence. Patients identified their relationship with their rheumatologist as pivotal and perceived diet, exercise and stress as critical. Intentional factors were the predominant drivers for non-adherence patients made a risk-benefit analysis based on their beliefs and chose to not take their medications as prescribed. Medication adherence to traditional and biological therapies was lower than expected by treating clinicians in this patient group, who are closely supported in a dedicated biologics clinic. Several of the identified themes suggest that shared decision making and enhancing patient education may improve adherence in this group. Key Points • Adherence rates are suboptimal even in supported, educated, English-speaking patients in the biologics era. • Contributing factors were 'intentional' as patients chose to be non-adherent based on their beliefs. • Emergent themes suggest that enhancing patient education could improve adherence.
Publisher: Oxford University Press (OUP)
Date: 10-03-2021
DOI: 10.1093/RHEUMATOLOGY/KEAB217
Abstract: The prevalence and associations of leucopenia in SLE remain incompletely understood. We evaluated associations of disease activity and medication use with leucopenia (lymphopenia and neutropenia) in a multinational, prospectively followed SLE cohort. Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count & .8 × 109/l) and neutropenia (neutrophil count & .5 × 109/l) were examined using multiple failure, time-dependent survival analyses. Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia. Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE.
Publisher: Frontiers Media SA
Date: 27-09-2021
Abstract: Aims: To determine real-life biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) retention rates in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), explore reasons for switching and to compare results to previously published data. Methods: Time-to-event analysis for mean treatment duration (estimated as the Restricted Mean Survival Time), b/tsDMARD failure, and b/tsDMARDs switching was performed for 230 patients ( n = 147 RA, 46 PsA, 37 AS) who commenced their first b/tsDMARD between 2008 and 2018. Patients were managed in a dedicated “biologics” clinic in a tertiary hospital the choice of b/tsDMARD was clinician driven based on medical factors and patient preferences. The effect of covariates on switching risk was analysed by a conditional risk-set Cox proportional-hazards model. Treatment retention data was compared to a historical analysis (2002–2008). Results: The proportions remaining on treatment (retention) were similar, throughout follow-up, for the first, second and third b/tsDMARDs across all patients ( p = 0.46). When compared to RA patients, the risk of b/tsDMARD failure was halved in PsA patients [Hazard Ratio (HR) = 0.50], but no different in AS patients (HR = 1.0). The respective restricted mean (95%CI) treatment durations, estimated at 5 years of follow-up, were 3.1 (2.9, 3.4), 4.1 (3.7, 4.6), and 3.3 (2.8, 3.9) years, for RA, PsA, and AS, respectively. Age, gender, disease duration, smoking status and the use of concomitant csDMARDS were not associated with the risk of bDMARD failure. The most common reasons for switching in the first and subsequent years were secondary ( n = 62) and primary ( n = 35) failure. Comparison with historical data indicated no substantive differences in switching of the first biologic for RA and PsA. Conclusion: Similar retention rates of the second and third compared to the first b/tsDMARD in RA, PsA, and AS support a strategy of differential b/tsDMARDs use informed by patient presentation. Despite greater availability of b/tsDMARDs with differing mechanisms of action, retention rates of the first b/tsDMARD remain similar to previous years.
Publisher: Elsevier BV
Date: 08-2013
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JAUT.2014.12.005
Abstract: Recent advances in mass spectrometry-based proteomic methods have allowed variable (V)-region peptide signatures to be derived from human autoantibodies present in complex serum mixtures. Here, we analysed the clonality and V-region composition of immunoglobulin (Ig) proteomes specific for the immunodominant SmD protein subunit of the lupus-specific Sm autoantigen. Precipitating SmD-specific IgGs were eluted from native SmD-coated ELISA plates preincubated with sera from six patients with systemic lupus erythematosus (SLE) positive for anti-Sm/RNP. Heavy (H)- and light (L)-chain clonality and V-region sequences were analysed by 2-dimensional gel electrophoresis and combined de novo database mass spectrometric sequencing. SmD autoantibody proteomes from all six patients with SLE expressed IgG1 kappa restricted clonotypes specified by IGHV3-7 and IGHV1-69 H-chains and IGKV3-20 and IGKV2-28 L-chains, with shared and in idual V-region amino acid replacement mutations. Clonotypic sharing and restricted V-region ersity of systemic autoimmunity can now be extended from the Ro/La cluster to Sm autoantigen and implies a common pathway of anti-Sm autoantibody production in unrelated patients with SLE.
Publisher: Springer Science and Business Media LLC
Date: 20-03-2017
Publisher: Springer Science and Business Media LLC
Date: 14-03-2022
DOI: 10.1186/S13075-022-02756-3
Abstract: The unmet need in systemic lupus erythematosus (SLE) with the current standard of care is widely recognised, but few studies have quantified this. The recent definition of treat-to-target endpoints and other thresholds of uncontrolled disease activity provide an opportunity to formally define unmet need in SLE. In this study, we enumerated the prevalence of these states and examined their association with adverse outcomes. Data were collected prospectively in a 13-country longitudinal SLE cohort between 2013 and 2019. Unmet need was defined as never attaining lupus low disease activity state (LLDAS), a time-adjusted mean SLEDAI-2K (AMS) 4, or ever experiencing high disease activity status (HDAS SLEDAI-2K ≥10). Health-related quality of life (HRQoL) was assessed using SF36 (v2) and damage accrual using the SLICC-ACR SLE Damage Index (SDI). A total of 3384 SLE patients were followed over 30,313 visits (median [IQR] follow-up 2.4 [0.4, 4.3] years). Eight hundred thirteen patients (24%) never achieved LLDAS. Median AMS was 3.0 [1.4, 4.9] 34% of patients had AMS 4. Twenty-five per cent of patients had episodes of HDAS. Each of LLDAS-never, AMS , and HDAS-ever was strongly associated with damage accrual, higher glucocorticoid use, and worse HRQoL. Mortality was significantly increased in LLDAS-never (adjusted HR [95% CI ] = 4.98 [2.07, 12.0], p .001) and HDAS-ever (adjusted hazard ratio (HR) [95% CI ] = 5.45 [2.75, 10.8], p .001) patients. Failure to achieve LLDAS, high average disease activity, and episodes of HDAS were prevalent in SLE and were significantly associated with poor outcomes including organ damage, glucocorticoid exposure, poor quality of life, and mortality.
Publisher: The Journal of Rheumatology
Date: 04-2010
Abstract: To estimate the indirect costs associated with primary Sjögren’s syndrome (pSS) compared with rheumatoid arthritis (RA) and community controls. Data were obtained from 84 women patients with pSS as part of a study to develop a systemic activity measure, from 87 consecutive women patients with RA attending a hospital clinic, and from 96 women community controls on a general practice list. A modified economic component of the Stanford Health Assessment Questionnaire was used to assess lost productivity. Using a conservative model, the estimated total annual indirect costs (95% CI) were £7677 (£5560, £9794) for pSS, £10,444 (£8206, £12,681) for RA, and £892 (£307, £1478) for controls. Using a model that maximizes the estimates, the equivalent figures were £13,502 (£9542, £17,463), £17,070 (£13,112, £21,028), and £3382 (£2187, £4578), respectively. These were all significantly greater at p 0.001 for patient groups than for the control group. pSS is associated with significantly increased indirect costs equivalent to 69%–83% of that for patients with RA. This needs to be taken into account when evaluating the overall economic consequences of pSS.
Publisher: Wiley
Date: 25-08-2020
Publisher: Wiley
Date: 05-2016
DOI: 10.1111/CEO.12749
Abstract: Gout is a clinical disorder that is characterized by the deposition of monosodium urate crystals (MSU) in joints and tendons, usually in the presence of prolonged hyperuricaemia. Following an asymptomatic phase of hyperuricaemia, gout usually presents as acute monoarthritis followed by periods of remission and exacerbation. Conjunctival hyperaemia and subconjunctival haemorrhage exacerbated by purine intake are two of the more common manifestations that may go unrecognized. Other ocular and adnexal structures can be affected by urate crystal deposition and associated inflammation, with potentially vision-threatening consequences however, ocular manifestations of gout are rare and may have been over-reported in the older literature, but our understanding of the clinic-pathological features of ocular urate deposits remains limited.
Publisher: Wiley
Date: 22-08-2022
DOI: 10.1002/ACR.24740
Abstract: Evidence for the utility of medications in settings lacking randomized trial data can come from studies of treatment persistence. The present study was undertaken to examine patterns of medication use in systemic lupus erythematosus (SLE) using data from a large multicenter longitudinal cohort. Prospectively collected data from the Asia Pacific Lupus Collaboration cohort including disease activity (SLE Disease Activity Index 2000 [SLEDAI‐2K]) and medication details, captured at every visit from 2013–2018, were used. Medications were categorized as glucocorticoids (GCs), antimalarials (AM), and immunosuppressants (IS). Cox regression analyses were performed to determine the time‐to‐discontinuation of medications, stratified by SLE disease activity. Data from 19,804 visits of 2,860 patients were analyzed. Eight medication categories were observed: no treatment GC, AM, or IS only GC plus AM GC plus IS AM plus IS and GC plus AM plus IS (triple therapy). Triple therapy was the most frequent pattern (31.4% of visits) single agents were used in 21% of visits, and biologics in only 3%. Time‐to‐discontinuation analysis indicated that medication persistence varied widely, with the highest treatment persistence for AM and lowest for IS. Patients with a time‐adjusted mean SLEDAI‐2K score of ≥10 had lower discontinuation of GCs and higher discontinuation of IS. Most patients received combination treatment. GC persistence was high, while IS persistence was low. Patients with high disease activity received more medication combinations but had reduced IS persistence, consistent with limited utility. These data confirm unmet need for improved SLE treatments.
Publisher: Oxford University Press (OUP)
Date: 19-05-2023
DOI: 10.1093/RHEUMATOLOGY/KEAD231
Abstract: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56 95% CI: 1.30, 1.87 P & 0.001) and fluctuating cohort (adjusted HR 1.46 95% CI: 1.28, 1.66), both for a ratio & . Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33 95% CI: 1.08, 1.65 P = 0.008) and the persistently positive cohort (adjusted HR 1.36 95% CI: 1.08, 1.71 P = 0.009). Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.
No related grants have been discovered for Fiona Goldblatt.