Long-term incidence, risk factors and complications for venous thromboembolism in patients with systemic lupus erythematosus.

AIM: To compare frequency, incidence rates (IR), risk factors and outcomes of a first venous thromboembolic event (VTE) between patients with systemic lupus erythematosus (SLE) and controls. METHODS: Using state-wide longitudinal hospital data from Western Australia (WA), we recorded venous thrombosis (VT) and pulmonary embolism (PE) in patients with SLE (n = 1854, median age 40, 86% female) and matched hospitalised controls (n = 12,107, median age 40 years, females 88.6%) in the period 1985-2015. Results presented are medians, frequency, IR per 1000 person years (PY) and odds, rate, or adjusted hazard ratios (OR/RR/a-HR) with 95% confidence intervals (CI). RESULTS: Patients with SLE had significantly higher odds (12.8 vs 3.3%; OR 4.26, CI 3.60-5.05) and IR for a first VTE (10.09 vs 1.52; RR 6.64; CI 5.56-7.79). Over the three study decades, the IR for PE declined in patients with SLE from 7.74 to 3.75/1000 PY (p < .01) with no changes observed for VT or in controls. VTE recurred more frequently in patients with SLE (24.1% vs 10.2 %) (p < .01). Antiphospholipid antibodies (aPL) (a-HR 4.24, CI 2.50-7.19), serositis (a-HR 2.70, CI 1.86-3.91), lupus nephritis (a-HR 1.75 CI 1.25-2.33) and thrombocytopenia (a-HR 1.65 (1.10-2.49) were the strongest disease risk factors for VTE only in patients with SLE, while arterial hypertension, smoking and obesity were independent VTE risk factors for both groups. VTE was not associated with an increased risk for arterial events, but PE increased the risk for pulmonary hypertension (PH) in both patients with SLE (a-HR 6.47, CI 3.73-11.23) and controls (a-HR 9.09, CI 3.50-23.63). VTE increased the risk of death in both patients with SLE (a-HR 2.02, CI 1.50-2.70) and controls (a-HR 6.63, CI 5.21-8.42) after 10 years of follow-up. CONCLUSIONS: VTE affected 12.8% of patients with SLE at six times the VTE rate in controls with aPL as the strongest, but not the only risk factor in SLE. The risk of PH was increased in both groups following PE, but VTE did not associate with an increased risk of arterial events.

Joint surgery rates in lupus: a long-term cohort study.

AIM: With scarce data on the need and type of joint surgery in SLE, we investigated the long-term rates and underlying causes for arthroplasty, arthrodesis and synovectomy in patients with SLE. METHODS: Procedure dates for arthroplasty, arthrodesis or synovectomy were retrieved from the state-wide Hospital Morbidity Data Collection between 1985 and 2015 for patients with SLE (n=1855) and propensity-matched controls (n=12 840). Patients with SLE with ≥two additional diagnostic codes for rheumatoid arthritis were classified as rhupus. ORs and incidence rates (IRs) per 100 person-years for joint procedures (JPs) were compared among patients with rhupus, patients with other SLE and controls across three study decades by regression analysis. RESULTS: More patients with SLE than controls underwent a JP (11.6% vs 1.3%; OR 10.8, CI 8.86 to 13.24) with a higher IR for JP in patients with SLE (1.9 vs 0.1, rate ratio 19.9, CI 16.83 to 23.55). Among patients with SLE, patients with rhupus (n=120, 60.5%) had the highest odds of arthroplasty (OR 4.49, CI 2.87 to 6.92), arthrodesis (OR 6.64, CI 3.28 to 12.97) and synovectomy (OR 9.02,CI 4.32 to 18.23). Over time, the IR for overall JP in patients with rhupus was unchanged (8.7 to 8.6, R2=0.004, p=0.98), although the IR for avascular necrosis underlying arthroplasty decreased for all patients with SLE (0.52 to 0.10, p=0.02). Patients with other SLE also had significantly higher OR and IR for all three JPs than controls with insignificant decreases in synovectomy and increases in arthroplasty over time in this group. CONCLUSIONS: The overall burden of joint surgery in SLE is high and despite a reduction in avascular necrosis, arthroplasty and arthrodesis rates have not decreased over time. These data indicate a need for increased efforts to prevent joint damage in patients with lupus.

Cancer development in patients hospitalized with systemic lupus erythematosus: A population-level data linkage study.

AIM: To explore the association between systemic lupus erythematosus (SLE) with the risk of cancer development and subsequent 5-year mortality in Western Australia (WA). METHODS: Population-level, data linkage study of SLE patients (n = 2111) and general population comparators (n = 21 110) hospitalized between 1980 and 2014. SLE patients (identified by ICD-9-CM: 695.4, 710.0, and ICD-10-AM: L93.0, M32.0) were nearest matched (10:1) for age, sex, Aboriginality, and temporality. Follow up was from time zero (index SLE hospitalization) to cancer development, death or 31 December 2014. We assessed the risk of cancer development and subsequent 5-year mortality between SLE patients and comparators with univariate and multivariate-adjusted Cox proportional hazards regression models. RESULTS: SLE patients had similar multivariate-adjusted risk (adjusted hazard ratio [aHR] 1.03, 95% confidence interval [CI] 0.93-1.15; p = .583) of cancer development. Cancer development risk was higher in SLE patients <40 years old (aHR 1.58, 95% CI 1.29-1.94; p < .001), and from 1980 to 1999 (aHR 1.16, 95% CI 1.02-1.31; p < .001). SLE patients had higher risk of developing cancer of the oropharynx (aHR 2.13, 95% CI 1.30-3.50), vulvo-vagina (aHR 3.22, 95% CI 1.34-7.75), skin (aHR 1.20, 95% CI 1.01-1.43), musculoskeletal tissues (aHR 2.26, 95% CI 1.16-4.40), and hematological tissues (aHR 1.78 95% CI 1.25-2.53), all p < .05. After cancer development, SLE patients had increased risk of 5-year mortality (aHR 1.31, 95% CI 1.06-1.61); highest in patients <50 years old (aHR 2.03, 95% CI 1.03-4.00), and in those with reproductive system and skin cancers. CONCLUSIONS: Hospitalized SLE patients had increased risk of multiple cancer sub-types. Following cancer development, SLE patients had increased risk of 5-year mortality. There is scope to improve cancer prevention and surveillance in SLE patients. TRIAL REGISTRATION: Not applicable. This low-risk risk study used de-identified administrative linked health data.

The influence of acculturation on the risk of preterm birth and low birthweight in migrant women residing in Western Australia.

BACKGROUND: The risk of preterm birth (PTB) and low birthweight (LBW) may change over time the longer that immigrants reside in their adopted countries. We aimed to study the influence of acculturation on the risk of these outcomes in Australia. METHODS: A retrospective cohort study using linked health data for all non-Indigenous births from 2005-2013 in Western Australia was undertaken. Acculturation was assessed through age on arrival, length of residence, interpreter use and having an Australian-born partner. Adjusted odds ratios (aOR) for term-LBW and PTB (all, spontaneous, medically-indicated) were calculated using multivariable logistic regression in migrants from six ethnicities (white, Asian, Indian, African, Maori, and 'other') for different levels of acculturation, compared to the Australian-born population as the reference. RESULTS: The least acculturated migrant women, those from non-white non-Maori ethnic backgrounds who immigrated at age ≥18 years, had an overseas-born partner, lived in Australia for < 5 years and used a paid interpreter, had 58% (aOR 1.58, 95% CI 1.15-2.18) higher the risk of term-LBW and 40% (aOR 0.60, 95% CI 0.45-0.80) lower risk of spontaneous PTB compared to the Australian-born women. The most acculturated migrant women, those from non-white non-Maori ethnic backgrounds who immigrated at age <18 years, had an Australian-born partner, lived in Australia for > 10 years and did not use an interpreter, had similar risk of term-LBW but 43% (aOR 1.43, 95% CI 1.14-1.78) higher risk of spontaneous PTB than the Australian-born women. CONCLUSION: Acculturation is an important factor to consider when providing antenatal care to prevent PTB and LBW in migrants. Acculturation may reduce the risk of term-LBW but, conversely, may increase the risk of spontaneous PTB in migrant women residing in Western Australia. However, the effect may vary by ethnicity and warrants further investigation to fully understand the processes involved.

Hospitalisation for systemic lupus erythematosus associates with an increased risk of mortality in Australian patients from 1980 to 2014: a longitudinal, population-level, data linkage, cohort study.

OBJECTIVE: Mortality rates for patients with SLE have not been reported in Australia. This study determined the association between a hospitalisation for SLE with mortality. METHODS: Population-level cohort study of patients with SLE (n=2112; 25 710 person-years) and general population comparators (controls) (n=21, 120; 280 637 person-years) identified from hospital records contained within the WA Rheumatic Disease Epidemiological Registry from 1980 to 2013. SLE was identified by ICD-9-CM: 695.4, 710.0, ICD-10-AM: L93.0, M32.0. Controls were nearest matched (10:1) for age, sex, Aboriginality and temporality. Using longitudinal linked health data, we assessed the association between a hospitalisation for SLE mortality and mortality with univariate and multivariate Cox proportional hazards and competing risks regression models. RESULTS: At timezero, patients with SLE were similar in age (43.96 years), with higher representation of females (85.1% vs 83.4%, p=0.038), Aboriginal Australians (7.8% vs 6.0%) and smokers (20.5% vs 13.2%). Before study entry, patients with SLE (mean lookback 9 years) had higher comorbidity accrual (Charlson Comorbidity Index ≥1 item (42.0% vs 20.5%)), especially cardiovascular disease (CVD) (44.7% vs 21.0%) and nephritis (16.4% vs 0.5%), all p<0.001. During follow-up (mean 12.5 years), 548 (26.0%) patients with SLE and 2450 (11.6%) comparators died. A hospitalisation for SLE increased the unadjusted (HR 2.42, 95% CI 2.20 to 2.65) and multivariate-adjusted risk of mortality (aHR 2.03, 95% CI 1.84 to 2.23), which reduced from 1980 to 1999 (aHR 1.42) to 2000-2014 (aHR 1.27). Females (aHR 2.11), Aboriginal Australians (aHR 3.32), socioeconomically disadvantaged (aHR 2.49), and those <40 years old (aHR 7.46) were most vulnerable. At death, patients with SLE had a higher burden of infection (aHR 4.38), CVD (aHR 2.09) and renal disease (aHR 3.43), all p<0.001. CONCLUSIONS: A hospitalisation for SLE associated with an increased risk of mortality over the 1980-2014 period compared with the general population. The risk was especially high in younger (<40 years old), socioeconomically disadvantaged and Aboriginal Australians.

The impact of implementing the 2016 WHO Recommendations on Antenatal Care for a Positive Pregnancy Experience on perinatal deaths: an interrupted time-series analysis in Mpumalanga province, South Africa.

OBJECTIVES: To investigate if the implementation of the 2016 WHO Recommendations for a Positive Pregnancy Experience reduced perinatal mortality in a South African province. The recommendations were implemented which included increasing the number of contacts and also the content of the contacts. METHODS: Retrospective interrupted time-series analysis was conducted for all women accessing a minimum of one antenatal care contact from April 2014 to September 2019 in Mpumalanga province, South Africa. Retrospective interrupted time-series analysis of province level perinatal mortality and birth data comparing the pre-implementation period (April 2014-March 2017) and post-implementation period (April 2018-September 2019). The main outcome measure was unadjusted prevalence ratio (PR) for perinatal deaths before and after implementation; interrupted time-series analyses for trends in perinatal mortality before and after implementation; stillbirth risk by gestational age; primary cause of deaths (and maternal condition) before and after implementation. RESULTS: Overall, there was a 5.8% absolute decrease in stillbirths after implementation of the recommendations, however this was not statistically significant (PR 0.95, 95% CI 0.90% to 1.05%; p=0.073). Fresh stillbirths decreased by 16.6% (PR 0.86, 95% CI 0.77% to 0.95%; p=0.003) while macerated stillbirths (p=0.899) and early neonatal deaths remained unchanged (p=0.499). When stratified by weight fresh stillbirths >2500 g decreased by 17.2% (PR 0.81, 95% CI 0.70% to 0.94%; p=0.007) and early neonatal deaths decreased by 12.8% (PR 0.88, 95% CI 0.77% to 0.99%; p=0.041). The interrupted time-series analysis confirmed a trend for decreasing stillbirths at 0.09/1000 births per month (-0.09, 95% CI -1.18 to 0.01; p=0.059), early neonatal deaths (-0.09, 95% CI -0.14 to 0.04; p=<0.001) and perinatal mortality (-1.18, 95% CI -0.27 to -0.09; p<0.001) in the post-implementation period. A decrease in stillbirths, early neonatal deaths or perinatal mortality was not observed in the pre-implementation period. During the period when additional antenatal care contacts were implemented (34-38 weeks), there was a decrease in stillbirths of 18.4% (risk ratio (RR) 0.82, 95% CI 0.73% to 0.91%, p=0.0003). In hypertensive disorders of pregnancy, the risk of stillbirth decreased in the post-period by 15.1% (RR 0.85; 95% CI 0.76% to 0.94%; p=0.002). CONCLUSION: The implementation of the 2016 WHO Recommendations for a Positive Pregnancy Experience may be an effective public health strategy to reduce stillbirths in South African provinces.

The influence of acculturation on the risk of stillbirth in migrant women residing in Western Australia.

OBJECTIVE: To investigate the influence of acculturation, demonstrated by age on arrival, length of residence, interpreter use and having an Australian-born partner, on disparities observed in the risk of stillbirth between migrant and Australian-born populations in Western Australia (WA). METHODS: A retrospective cohort study using linked administrative health data for all non-Indigenous births in WA from 2005-2013 was performed. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Adjusted odds ratios (aOR) for stillbirth in migrants from six ethnicities of white, Asian, Indian, African, Maori, and 'other', with different levels of acculturation, were compared with Australian-born women using multivariable logistic regression analysis and marital status, maternal age group, socioeconomic status, parity, plurality, previous stillbirth, any medical conditions, any pregnancy complications, sex of baby, and smoking during pregnancy as the covariates. RESULTS: From all births studied, 172,571 (66%) were to Australian-born women and 88,395 (34%) to migrant women. Women from African, Indian and Asian backgrounds who gave birth in the first two years after arrival in Australia experienced the highest risk of stillbirth (aOR 3.32; 95% CI 1.70-6.47, aOR 2.71; 95% CI 1.58-4.65, aOR 1.93; 95% CI 1.21-3.05 respectively) compared with Australian-born women. This association attenuated with an increase in the length of residence in Asian and Indian women, but the risk of stillbirth remained elevated in African women after five years of residence (aOR 1.96 [1.10-3.49]). Interpreter use and an Australian-born partner were associated with 56% and 20% lower odds of stillbirth in migrants (p<0.05), respectively. CONCLUSIONS: Acculturation is a multidimensional process and may lower the risk of stillbirth through better communication and service utilisation and elevate such risk through increase in prevalence of smoking in pregnancy; the final outcome depends on how these factors are in play in a population. It is noteworthy that in women of African background risk of stillbirth remained elevated for longer periods after immigrating to Australia extending beyond five years. For migrants from Asian and Indian backgrounds, access to services, in the first two years of residence, may be more relevant. Enhanced understanding of barriers to accessing health services and factors influencing and influenced by acculturation may help developing interventions to reduce the burden of stillbirth in identified at-risk groups.

Live delivery outcome after tubal sterilization reversal: a population-based study.

OBJECTIVE: To determine the cumulative incidence of live delivery in women who underwent reversal of tubal sterilization. DESIGN: Population-based retrospective cohort study. SETTING: Hospitals in Western Australia. PATIENT(S): All women aged 20-44 years, with a history of hospital admission for tubal sterilization, who subsequently underwent reversal of sterilization during the period 1985 to 2009 in Western Australia (n = 1,898). INTERVENTION(S): Data regarding reversal of sterilization and prior tubal sterilization were extracted from routinely collected administrative hospital separation records, until commencement of IVF treatment. MAIN OUTCOME MEASURE(S): First live-delivery rates. RESULT(S): There were 969 first live deliveries observed during the study period. The overall cumulative live-delivery rate was 20% (95% confidence interval [CI] 18-23) within the first year after reversal, 40% (95% CI 38-42) at 2 years, 51% (95% CI 48-53) at 5 years, and 52% (95% CI 50-55) at 10 years. The 5-year cumulative live-delivery rate was significantly lower in women who were aged 40-44 years (26%) compared with younger women (aged 20-29, 30-34, and 35-39 years) (50%, 56%, and 51%, respectively). CONCLUSION(S): Women undergoing reversal of sterilization before they reach age 40 years have at least a 50% chance of delivering a live baby within the next 5 years. Up to that age, there is no significant difference in live deliveries. The live-delivery rate halves after the age of 40 years.

Long-term risk of ectopic pregnancy varies by method of tubal sterilization: a whole-population study.

OBJECTIVE: To evaluate the risk of ectopic pregnancy (EP) associated with different methods of tubal sterilization. DESIGN: Population-based retrospective cohort study. SETTING: Hospitals in Western Australia. PATIENT(S): All women aged 18-44 years undergoing tubal sterilization between 1990 and 2010 at Western Australian hospitals (n = 44,829). INTERVENTION(S): Data on tubal sterilization were extracted from hospital records. MAIN OUTCOME MEASURE(S): Long-term risk of EP. RESULT(S): There were 89 EPs recorded during the observation period in women previously sterilized. The 10-year and 15-year cumulative probability of EP for all methods of tubal sterilization were 2.4/1,000 and 2.9/1,000 procedures, respectively. The 10-year cumulative probability of EP was 3.5 times higher in women sterilized before the age of 28 years than in those sterilized after the age of 33 years. An increased risk of EP existed in women who received laparoscopic partial salpingectomy (adjusted hazard ratio = 14.57, 95% confidence interval 3.50-60.60) and electrodestruction (adjusted hazard ratio = 5.65, 95% confidence interval 2.38-13.40), compared with those who had laparoscopic unspecified destruction of fallopian tubes. CONCLUSION(S): Women undergoing tubal sterilization at a young age are at particular risk for subsequent EP. The risk among younger women doubled between 5 and 15 years after sterilization. Laparoscopic electrodestruction and partial salpingectomy carried the highest risk of EP.