Trajectories of self-reported pain-related health outcomes and longitudinal effects on medication use in rheumatoid arthritis: a prospective cohort analysis using the Australian Rheumatology Association Database (ARAD).

OBJECTIVE: To determine distinct trajectories of self-reported pain-related health status in rheumatoid arthritis (RA), their relationship with sociodemographic factors and medication use. METHODS: 988 Australian Rheumatology Association Database participants with RA (71% female, mean age 54 years, mean disease duration 2.3 years) were included. Distinct multi-trajectories over 15-year follow-up for five different self-reported pain-related health outcome measures (Health Assessment Questionnaire Disability Index, visual analogue scores for pain, arthritis, global health and the Assessment of Quality of Life utility index) were identified using latent variable discrete mixture modelling. Random effects models were used to determine associations with medication use and biologic therapy modification during follow-up. RESULTS: Four, approximately equally sized, pain/health status groups were identified, ranging from 'better' to 'poorer', within which changes over time were relatively small. Important determinants of those with poorer pain/health status included female gender, obesity, smoking, socioeconomic indicators and comorbidities. While biologic therapy use was similar between groups during follow-up, biologic therapy modifications (plinear<0.001) and greater tendency of non-tumour necrosis factor inhibitor use (plinear<0.001) were observed in those with poorer pain/health status. Similarly, greater use of opioids, prednisolone and non-steroidal anti-inflammatory drugs was seen in those with poorer pain/health status. CONCLUSION: In the absence of disease activity information, distinct trajectories of varying pain/health status were seen from the outset and throughout the disease course in this RA cohort. More biologic therapy modifications and greater use in anti-inflammatories, opioids and prednisolone were seen in those with poorer pain/health status, reflecting undesirable lived experience of persistent pain in RA.

Mortality estimates and excess mortality in rheumatoid arthritis.

OBJECTIVES: To determine long-term (20 year) survival in RA patients enrolled in the Australian Rheumatology Association Database (ARAD). METHODS: ARAD patients with RA and data linkage consent who were diagnosed from 1995 onwards were included. Death data were obtained through linkage to the Australian National Death Index. Results were compared with age-, gender- and calendar year-matched Australian population mortality rates. Analysis included both the standardized mortality ratio (SMR) and relative survival models. Restricted mean survival time (RMST) at 20 years was calculated as a measure of life lost. Cause-specific SMRs (CS-SMRs) were estimated for International Classification of Diseases, Tenth Revision cause of death classifications. RESULTS: A total of 1895 RA patients were included; 74% were female, baseline median age 50 years (interquartile range 41-58), with 204 deaths. There was no increase in mortality over the first 10 years of follow up, but at 20 years the SMR was 1.49 (95% CI 1.30, 1.71) and the relative survival was 94% (95% CI 91, 97). The difference between observed (18.41 years) and expected (18.68 years) RMST was 4 months. Respiratory conditions were an important underlying cause of death in RA, primarily attributable to pneumonia [CS-SMR 5.2 (95% CI 2.3, 10.3)] and interstitial lung disease [CS-SMR 7.6 (95% CI 3.0, 14.7)], however, coronary heart disease [CS-SMR 0.82 (95% CI 0.42, 1.4)] and neoplasms [CS-SMR 1.2 (95% CI 0.89, 1.5)] were not. CONCLUSION: Mortality risk in this RA cohort accrues over time and is moderately increased at 20 years of follow-up. Respiratory diseases may have supplanted cardiovascular diseases as a major contributor to this mortality gap.

Diagnosis of giant cell arteritis by temporal artery biopsy is associated with biopsy length.

Aims: Temporal artery biopsy (TAB) is a widely used method for establishing a diagnosis of Giant Cell Arteritis (GCA). The optimal TAB length for accurate histological GCA diagnosis has been suggested as 15 mm post-fixation (15-20 mm pre-fixation). The aim of this study was to determine the relationship between a histological GCA diagnosis and optimal TAB length in the South Australian (SA) population. Materials and methods: Pre-fixation TAB length (mm) was reported in 825/859 of all samples submitted to SA Pathology between 2014 and 2020 from people aged 50 and over. When more than one biopsy was taken, the longest length was recorded. Analyses of both TAB length and TAB positive proportions were performed by multivariable linear and logistic regression analysis, including covariates sex, age, and calendar year. Results: The median age of participants was 72 (IQR 65, 79) years, 549 (66%) were female. The TAB positive proportion was 172/825 (21%) with a median biopsy length of 14 mm (IQR 9, 18). Biopsy length (mm) was shorter in females (p = 0.001), increased with age (p = 0.006), and a small positive linear trend with calendar year was observed (p = 0.015). The TAB positive proportion was related to older age (slope/decade: 6, 95% CI 3.6, 8.3, p < 0.001) and to TAB length (slope/mm 0.6, 95% CI 0.2, 0.9, p = 0.002), but not sex or calendar year. Comparison of models with TAB length cut-points at 5, 10, 15, 20 mm in terms of diagnostic yield, receiver operating characteristics and Akaike Information Criteria confirmed ≥ 15 mm as an appropriate, recommended TAB length. However, only 383 (46%) of the biopsies in our study met this criteria. The diagnostic yield at this cut-point was estimated as 25% which equates to an expected additional 30 histologically diagnosed GCA patients. Conclusion: This study confirms that TAB biopsy length is a determinant of a histological diagnosis of temporal arteritis, and confirms that a TAB length ≥ 15 mm is optimal. Approximately half the biopsies in this study were shorter than this optimal length, which has likely led to under-diagnosis of biopsy-proven GCA in SA. Further work is needed to ensure appropriate TAB biopsy length.

Cancer in Anti-Neutrophil Cytoplasm Antibody-Associated Vasculitis and Polyarteritis Nodosa in Australia: A Population-Based Study.

OBJECTIVE: The study objective was to compare incident cancer rates among patients with anti-neutrophil cytoplasm antibody-associated vasculitis (AAV) and polyarteritis nodosa (PAN) in Western Australia (WA) with the general population and perform time-varying analyses to identify periods with greatest excess cancers. METHODS: Administrative health data from patients hospitalized with incident AAV/PAN from 1980 to 2014 were linked to the WA cancer registry, which holds compulsorily reported cancer data (excluding skin squamous cell and basal cell carcinomas). Incident cancer rates in patients with AAV/PAN were compared with age-, sex-, and calendar-year-matched WA population rates. RESULTS: Patients with AAV/PAN had higher overall rates of incident cancer compared with the matched population (standardized incidence ratio [SIR], 1.74; 95% confidence interval [CI], 1.42-2.10). In subgroup analyses, incident cancer rates in patients with granulomatosis with polyangiitis/eosinophilic granulomatosis with polyangiitis were approximately double the general population (SIR, 2.21; 95% CI, 1.73-2.78) but similar to the general population in patients with microscopic polyangiitis/PAN (SIR, 1.21; 95% CI, 0.85-1.68). Patients with AAV/PAN had higher rates of genitourinary, skin, hematological, and lung cancers. Excess rates of hematological and lung cancers peaked early after diagnosis, whereas excess skin and genitourinary cancer rates peaked at 5 and 10 years, respectively. CONCLUSION: This study highlights the importance of long-term cancer surveillance in patients with AAV/PAN and defines time frames of excess risk for specific cancers, which may help inform guidance on cancer screening. Furthermore, it indicates the need for skin surveillance for melanoma in addition to nonmelanoma skin cancers in patients who have greater environmental ultraviolet exposure, such as in Australia.

Mortality and cause of death in patients with ANCA-associated vasculitis and polyarteritis nodosa in Australia-a population-based study.

OBJECTIVES: We compared survival and causes of death in Western Australian (WA) ANCA-associated vasculitis (AAV) and PAN patients with controls and the WA population. METHODS: In this data linkage study, we identified patients with incident AAV/PAN and age, sex and temporally matched controls 1980-2014 from the WA Rheumatic Disease Epidemiological Registry. Survival analyses and time-varying analyses were performed. RESULTS: Six hundred and fourteen patients with incident AAV/PAN were compared with 6672 controls; 229 AAV/PAN patients died over 5277 person-years of follow-up and 1009 controls died over 73835 person-years. Survival was reduced in patients with AAV/PAN compared with matched controls [hazard ratio (HR) 3.5 (95% CI: 3.1, 4.1)], and matched WA population rates [standardized mortality ratio 3.3 (95% CI: 2.9, 3.8)]. Greatest excess mortality in AAV/PAN patients was observed in the first year after diagnosis and remained higher than controls throughout follow-up. Greater excess mortality was observed in patients >60 years at diagnosis. In cause-specific analyses, mortality HR for vasculitis, infection and non-infective respiratory disease were greatest early after diagnosis and remained persistently elevated. The HRs for malignancy and cerebrovascular disease related deaths increased during follow-up, and were constant for ischaemic heart disease related deaths. CONCLUSION: Mortality was increased in AAV/PAN patients compared with controls, with patients older at diagnosis at greater risk. These findings provide mortality risk for AAV/PAN in an Australian population, highlighting key contributors to mortality at different time periods over follow-up and potential areas of focus for reducing mortality.

Screening for gestational diabetes mellitus based on different risk profiles and settings for improving maternal and infant health.

BACKGROUND: Gestational diabetes mellitus (GDM) is a form of diabetes that occurs in pregnancy. Although GDM usually resolves following birth, it is associated with significant morbidities for mothers and their infants in the short and long term. There is strong evidence to support treatment for GDM. However, there is uncertainty as to whether or not screening all pregnant women for GDM will improve maternal and infant health and if so, the most appropriate setting for screening. This review updates a Cochrane Review, first published in 2010, and subsequently updated in 2014. OBJECTIVES: To assess the effects of screening for gestational diabetes mellitus based on different risk profiles and settings on maternal and infant outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (31 January 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (14 June 2017), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised and quasi-randomised trials evaluating the effects of different protocols, guidelines or programmes for screening for GDM based on different risk profiles and settings, compared with the absence of screening, or compared with other protocols, guidelines or programmes for screening. We planned to include trials published as abstracts only and cluster-randomised trials, but we did not identify any. Cross-over trials are not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included trials. We resolved disagreements through discussion or through consulting a third reviewer. MAIN RESULTS: We included two trials that randomised 4523 women and their infants. Both trials were conducted in Ireland. One trial (which quasi-randomised 3742 women, and analysed 3152 women) compared universal screening versus risk factor-based screening, and one trial (which randomised 781 women, and analysed 690 women) compared primary care screening versus secondary care screening. We were not able to perform meta-analyses due to the different interventions and comparisons assessed.Overall, there was moderate to high risk of bias due to one trial being quasi-randomised, inadequate blinding, and incomplete outcome data in both trials. We used GRADEpro GDT software to assess the quality of the evidence for selected outcomes for the mother and her child. Evidence was downgraded for study design limitations and imprecision of effect estimates. Universal screening versus risk-factor screening (one trial) MotherMore women were diagnosed with GDM in the universal screening group than in the risk-factor screening group (risk ratio (RR) 1.85, 95% confidence interval (CI) 1.12 to 3.04; participants = 3152; low-quality evidence). There were no data reported under this comparison for other maternal outcomes including hypertensive disorders of pregnancy, caesarean birth, perineal trauma, gestational weight gain, postnatal depression, and type 2 diabetes. ChildNeonatal outcomes: large-for-gestational age, perinatal mortality, mortality or morbidity composite, hypoglycaemia; and childhood/adulthood outcomes: adiposity, type 2 diabetes, and neurosensory disability, were not reported under this comparison. Primary care screening versus secondary care screening (one trial) MotherThere was no clear difference between the primary care and secondary care screening groups for GDM (RR 0.91, 95% CI 0.50 to 1.66; participants = 690; low-quality evidence), hypertension (RR 1.41, 95% CI 0.77 to 2.59; participants = 690; low-quality evidence), pre-eclampsia (RR 0.80, 95% CI 0.36 to 1.78; participants = 690;low-quality evidence), or caesarean section birth (RR 1.00, 95% CI 0.80 to 1.27; participants = 690; low-quality evidence). There were no data reported for perineal trauma, gestational weight gain, postnatal depression, or type 2 diabetes. ChildThere was no clear difference between the primary care and secondary care screening groups for large-for-gestational age (RR 1.37, 95% CI 0.96 to 1.96; participants = 690; low-quality evidence), neonatal complications: composite outcome, including: hypoglycaemia, respiratory distress, need for phototherapy, birth trauma, shoulder dystocia, five minute Apgar less than seven at one or five minutes, prematurity (RR 0.99, 95% CI 0.57 to 1.71; participants = 690; low-quality evidence), or neonatal hypoglycaemia (RR 1.10, 95% CI 0.28 to 4.38; participants = 690; very low-quality evidence). There was one perinatal death in the primary care screening group and two in the secondary care screening group (RR 1.10, 95% CI 0.10 to 12.12; participants = 690; very low-quality evidence). There were no data for neurosensory disability, or childhood/adulthood adiposity or type 2 diabetes. AUTHORS' CONCLUSIONS: There are insufficient randomised controlled trial data evaluating the effects of screening for GDM based on different risk profiles and settings on maternal and infant outcomes. Low-quality evidence suggests universal screening compared with risk factor-based screening leads to more women being diagnosed with GDM. Low to very low-quality evidence suggests no clear differences between primary care and secondary care screening, for outcomes: GDM, hypertension, pre-eclampsia, caesarean birth, large-for-gestational age, neonatal complications composite, and hypoglycaemia.Further, high-quality randomised controlled trials are needed to assess the value of screening for GDM, which may compare different protocols, guidelines or programmes for screening (based on different risk profiles and settings), with the absence of screening, or with other protocols, guidelines or programmes. There is a need for future trials to be sufficiently powered to detect important differences in short- and long-term maternal and infant outcomes, such as those important outcomes pre-specified in this review. As only a proportion of women will be diagnosed with GDM in these trials, large sample sizes may be required.

De novo Propionibacterium acnes septic arthritis.

We report the third identifiable case of septic arthritis due to Propionibacterium acnes arising in the absence of prior surgical intervention. This anaerobic Gram-positive bacillus is now recognised as an important cause of postoperative infections, typically presenting in an indolent fashion some months after surgery. Reports of de novo septic arthritis due to P. acnes are exceedingly rare. Our case adds to the literature and significantly broadens the reported pathogenic potential of the organism, which in this instance has caused rapid and serious joint destruction.

Primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a relatively common autoimmune systemic rheumatic disease. In addition to sicca syndrome and swollen salivary glands, systemic features manifest in the majority of patients, and are severe in 15%, particularly affecting the joints, skin, lungs, and peripheral nervous system. A recent meta-analysis estimated a pooled relative risk of 13.76 for the development of non-Hodgkin lymphoma, particularly in pSS patients who have parotid enlargement, vasculitis, cryoglobulinemia, and antibodies to Ro and La. pSS is the underlying diagnosis in one-third of mothers of neonates affected by congenital heart block. The diagnosis of pSS is complex and requires a stepwise approach to evaluate symptoms of ocular and oral dryness, objective measures of lacrimal and salivary gland dysfunction, and evidence of autoimmunity with Ro/La autoantibodies and labial salivary gland biopsy. It is essential to eliminate other autoimmune diseases, as well as non-autoimmune causes of sicca syndrome, such as menopause, endocrine diseases, anticholinergic effects of drugs, and fibromyalgia, to delineate pSS patients who are at risk of systemic complications. Recent major advances in the diagnosis of pSS have been the development of classification criteria, which serve as a template for clinical diagnosis, and outcome measures for use in clinical trials and prospective patient cohorts. Clinical data and biological samples from longitudinal cohorts, embedded into clinical practice, will be essential to further improve the diagnosis and management of pSS, increase knowledge about the natural history of the disease, gain insights into its pathogenesis, and stratify patients according to their risk of systemic disease and NHL. At present, there is a gap in evidence regarding the role of structured protocols in the management of pSS. Recent recommendations for the management of sicca symptoms and clinical trials of disease-modifying therapy are discussed.

Screening and subsequent management for gestational diabetes for improving maternal and infant health.

BACKGROUND: Gestational diabetes mellitus (GDM) is a form of diabetes that occurs in pregnancy. Although GDM usually resolves following birth, it is associated with significant morbidities for mother and baby both perinatally and in the long term. There is strong evidence to support treatment for GDM. However, there is little consensus on whether or not screening for GDM will improve maternal and infant health and if so, the most appropriate protocol to follow. OBJECTIVES: To assess the effects of different methods of screening for GDM and maternal and infant outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 December 2013). SELECTION CRITERIA: Randomised and quasi-randomised trials evaluating the effects of different methods of screening for GDM. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and quality assessment. We resolved disagreements through discussion or through a third author. MAIN RESULTS: We included four trials involving 3972 women in the review. One quasi-randomised trial compared risk factor screening with universal or routine screening by 50 g oral glucose challenge testing. Women in the universal screening group were more likely to be diagnosed with GDM (one trial, 3152 women, risk ratio (RR) 0.44, 95% confidence interval (CI) 0.26 to 0.75). This trial did not report on the other primary outcomes of the review (positive screen for GDM, mode of birth, large-for-gestational age, or macrosomia). Considering secondary outcomes, infants of mothers in the risk factor screening group were born marginally earlier than infants of mothers in the routine screening group (one trial, 3152 women, mean difference (MD) -0.15 weeks, 95% CI -0.27 to -0.03).The remaining three trials evaluated different methods of administering a 50 g glucose load. Two small trials compared glucose monomer with glucose polymer testing, with one of these trials including a candy bar group. One trial compared a glucose solution with food. No differences in diagnosis of GDM were found between each comparison. However, in one trial significantly more women in the glucose monomer group screened positive for GDM than women in the candy bar group (80 women, RR 3.49, 95% CI 1.05 to 11.57). The three trials did not report on the primary review outcomes of mode of birth, large-for-gestational age or macrosomia. Overall, women drinking the glucose monomer experienced fewer side effects from testing than women drinking the glucose polymer (two trials, 151 women, RR 2.80, 95% CI 1.10 to 7.13). However, we observed substantial heterogeneity between the trials for this result (I² = 61%). AUTHORS' CONCLUSIONS: There was insufficient evidence to determine if screening for gestational diabetes, or what types of screening, can improve maternal and infant health outcomes.

Screening and subsequent management for gestational diabetes for improving maternal and infant health.

BACKGROUND: Gestational diabetes mellitus (GDM) is a form of diabetes that occurs in pregnancy. Although GDM usually resolves following birth, it is associated with significant morbidities for mother and baby both perinatally and in the long term. There is strong evidence to support treatment for GDM. However, there is little consensus on whether or not screening for GDM will improve maternal and infant health and if so, the most appropriate protocol to follow. OBJECTIVES: To assess the effects of different methods of screening for gestational diabetes mellitus and maternal and infant outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2010). SELECTION CRITERIA: Randomised and quasi-randomised trials evaluating the effects of different methods of screening for gestational diabetes mellitus. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and quality assessment. We resolved disagreements through discussion or through a third author. MAIN RESULTS: We included four trials involving 3972 women were included in the review. One quasi-randomised trial compared risk factor screening with universal or routine screening by 50 g oral glucose challenge testing. Women in the universal screening group were more likely to be diagnosed with GDM (one trial, 3152 women, risk ratio (RR) 0.44 95% confidence interval (CI) 0.26 to 0.75). Infants of mothers in the risk factor screening group were born marginally earlier than infants of mothers in the routine screening group (one trial, 3152 women, mean difference -0.15 weeks, 95% CI -0.27 to -0.53).The remaining three trials evaluated different methods of administering a 50 g glucose load. Two small trials compared glucose monomer with glucose polymer testing, with one of these trials including a candy bar group. One trial compared a glucose solution with food. No differences in diagnosis of GDM were found between each comparison. Overall, women drinking the glucose monomer experienced fewer side effects from testing than women drinking the glucose polymer (two trials, 151 women, RR 2.80, 95% CI 1.10 to 7.13). However, we observed high heterogeneity between the trials for this result (I(2) = 61%). AUTHORS' CONCLUSIONS: There was insufficient evidence to determine if screening for gestational diabetes, or what types of screening, can improve maternal and infant health outcomes.