This study surveyed the frequency of autoantibodies among un-affected first-degree relatives (FDRs) of Filipino systemic lupus erythematosus (SLE) patients compared with healthy un-related Filipino controls. The sensitivity, specificity and predictive value of the autoantibodies for SLE diagnosis were also assessed in this Filipino cohort. Filipino patients included in the University of Santo Tomas (UST) Lupus Database and un-affected FDRs were recruited. Healthy controls included those with no known personal or family history of autoimmune disease. The following autoantibodies were tested in all subjects: anti-nuclear antibody (ANA), anti-dsDNA, anti-Ro/SSA, anti-chromatin, anti-thyroid microsome, and anti-cardiolipin antibodies. Participants included 232 SLE patients, 546 FDRs, and 221 healthy controls. Median age of patients was 27 (range 8-66) years with median disease duration of 27.5 (range 1-292) months. Median age of FDRs was 42.0 (range 5-87) years. Compared with healthy controls, there were significantly more FDRs with positive ANA at titers 1 : 40 to 1 : 160 (p < 0.001) and 1 : 320 (p = 0.003), anti-Ro/SSA (4.94% versus 0.45%, p = 0.003), and anti-dsDNA ≥ 5.0 IU/ml (4.58% versus 1.36%, p = 0.031). ANA titer ≥1 : 160, anti-dsDNA, anti-Ro/SSA and anti-chromatin had the highest predictive value for SLE diagnosis. These findings reinforce the role of genetic influence in SLE risk among Filipinos, with a significant proportion of un-affected FDRs of SLE patients testing positive for autoantibodies compared with healthy Filipino controls. A longitudinal observational study in this same cohort will determine which proportion of these un-affected FDRs will evolve into clinical SLE disease in the future.
Objectives With aging of the HIV‐positive population, cardiovascular disease (CVD) increasingly contributes to morbidity and mortality. We investigated CVD‐related and other causes of death (CODs) and factors associated with CVD in a multi‐country Asian HIV‐positive cohort. Methods Patient data from 2003–2017 were obtained from the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD). We included patients on antiretroviral therapy (ART) with > 1 day of follow‐up. Cumulative incidences were plotted for CVD‐related, AIDS‐related, non‐AIDS‐related, and unknown CODs, and any CVD (i.e. fatal and nonfatal). Competing risk regression was used to assess risk factors of any CVD. Results Of 8069 patients with a median follow‐up of 7.3 years [interquartile range (IQR) 4.4–10.7 years], 378 patients died [incidence rate (IR) 6.2 per 1000 person‐years (PY)], and this total included 22 CVD‐related deaths (IR 0.36 per 1000 PY). Factors significantly associated with any CVD event (IR 2.2 per 1000 PY) were older age [sub‐hazard ratio (sHR) 2.21; 95% confidence interval (CI) 1.36–3.58 for age 41–50 years; sHR 5.52; 95% CI 3.43–8.91 for ≥ 51 years, compared with < 40 years], high blood pressure (sHR 1.62; 95% CI 1.04–2.52), high total cholesterol (sHR 1.89; 95% CI 1.27–2.82), high triglycerides (sHR 1.55; 95% CI 1.02–2.37) and high body mass index (BMI) (sHR 1.66; 95% CI 1.12–2.46). CVD crude IRs were lower in the later ART initiation period and in lower middle‐ and upper middle‐income countries. Conclusions The development of fatal and nonfatal CVD events in our cohort was associated with older age, and treatable risk factors such as high blood pressure, triglycerides, total cholesterol and BMI. Lower CVD event rates in middle‐income countries may indicate under‐diagnosis of CVD in Asian‐Pacific resource‐limited settings.
Background In multi-site HIV observational cohorts, clustering of observations often occur within sites. Ignoring clustering may lead to “Simpson's paradox” (SP) where the trend observed in the aggregated data is reversed when the groups are separated. This study aimed to investigate the SP in an Asian HIV cohort and the effects of site-level adjustment through various Cox-regression models. Methods Survival time from combination antiretroviral therapy (cART) initiation was analysed using four Cox models: (i) no site adjustment; (ii) site as a fixed effect; (iii) stratification through site; and (iv) shared frailty on site. Results A total of 6454 patients were included from 23 sites in Asia. SP was evident in the year of cART initiation variable. Model (i) shows the hazard ratio (HR) for years 2010-2014 was higher than the HR for 2006-2009, compared to 2003-2005 (HR = 0.68 vs 0.61). Models (ii)-(iv) consistently implied greater improvement in survival for those who initiated in 2010-2014 than 2006-2009 contrasting findings from Model (i). The effects of other significant covariates on survival were similar across four models. Conclusions Ignoring site can lead to SP causing reversal of treatment effects. Greater emphasis should be made to include site in survival models when possible.
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