Thioamides antithyroid‐drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD‐induced agranulocytosis is important for clinical management. ...We performed a genome‐wide association study (GWAS) involving 20 patients with ATD‐induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single‐nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD‐induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8–103.7; P = 1.3 × 10‐24) and replication (OR = 37; 95% CI = 3.7–367.4; P = 9.6 × 10‐7). HLA‐B*38:02:01 was in complete linkage disequilibrium with rs185386680. High‐resolution HLA typing confirmed that HLA‐B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)‐induced agranulocytosis (OR = 265.5; 95% CI = 27.9–2528.0; P = 2.5 × 10‐14), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA‐B*38:02:01 in predicting CMZ/MMI‐induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.
Background
Previous observational studies have not found a conclusive association between serum 25‐hydroxyvitamin D (25(OH)D) levels and allergic rhinitis (AR) or allergic sensitization (AS).
...Objective
To investigate a causal association between 25(OH)D levels with risk of AR and AS, using a two‐sample Mendelian randomization (MR) approach.
Methods
Seven single nucleotide polymorphisms (SNPs), previously shown to be associated with serum 25(OH)D levels, were identified as instrumental variables. The primary outcome was AR, and the secondary outcomes were AS and non‐allergic rhinitis (NAR). The genome‐wide association (GWA) summary statistics of the outcomes were obtained from two cohort studies (EAGLE Consortium and UK Biobank). An MR analysis with random‐effects inverse‐variance weighted method was performed as the primary analysis to estimate overall effect size (odds ratio OR and 95% confidence interval CI). Sensitivity analysis using weighted median method and MR‐Egger regression method was conducted. A subgroup analysis based on 25(OH)D synthesis‐related SNPs was further applied.
Results
Serum 25(OH)D levels were not causally associated with risk of AR (OR: 0.960; 95% CI: 0.779‐1.184), AS (OR: 1.059; 95% CI: 0.686 to 1.634) or NAR (OR: 0.937; 95% CI: 0.588‐1.491). Subgroup analysis also showed null association between 25(OH)D synthesis‐related SNPs and the outcomes. Sensitivity analyses yielded similar results.
Conclusions and Clinical Relevance
This MR study found no evidence supporting a causal association between serum 25(OH)D levels and risk of AR, AS and NAR in European‐ancestry population. This argues against the previous postulation that vitamin D supplementation is effective in prevention of allergic diseases.
BackgroundLead is a heavy metal with no physiological role in humans. It is well known that cxcessive exposure to lead is associated with cardiovascular, gastrointestinal and neurological ...complications. However, recent studies have demonstrated that lead can increase the tubular reabsorption of urate, resulting in hyperuricaemia and the development of gout.Although blood lead levels are dropping in the US general population, the association between low blood lead levels ad gout remains inconclusive.ObjectivesTo evaluate the relationship between serum blood lead levels and the development of gout in the US general population.MethodsAdult participants with blood lead measurements and self reported gout in NHANES 2007–2014 were included in the analysis.Results were analysed using SPSS complex sample module version 22. Logistic regression with sample weight adjustment was used to study the association between blood lead levels and gout. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated. Sub-group analysis was conducted in participants with blood lead level <5 µg/dL.Results18837 adult participants were included in the analysis. 18 270 participants had blood lead levels below 5 ug/dL (The current reference range for acceptable blood lead levels in healthy persons without excessive exposure to environment source of lead).The prevalence of gout increased with blood lead levels. In the total population, the odd ratio of gout was 4.96 in subjects with blood lead levels above 2.21 ug/dL. After adjusting for body mass index, hypertension, renal function and use of diuretics, the odd ratio of gout was 2.65 which remained significant.The subgroup analysis of subjects with blood lead levels below 5 ug/ml showed similar findings. The risk of gout is increased when blood lead levels are higher than 1.43 ug/dL.Abstract FRI0222 – Figure 1(A) Prevalence of gout according to quintles of blood level. (B) Association between quintles of blood lead level and gout at blood lead level <5μg/dLConclusionsLow blood lead levels are associated with gout. The risk of gout is increased when the blood lead level is higher than 1.43 ug/dL. Therefore, measures should be taken to minimise the environmental exposure to lead.Disclosure of InterestNone declared
BackgroundThe prevalence of gout has been increasing worldwide. Previous study using National Health and Nutritional Examination Survey (NHANES) showed an increase of 1.2% in the prevalence of gout ...in the US general population from 1988 to 2007. However, it is unknown if this trend continued over the past decades. Therefore, we would like to determine the prevalence of gout in the US general population using NHANES 2007 to 2016. In addition, the use of urate lowering agents among patients with gout was analysed.ObjectivesTo estimate the prevalence of gout and the use of urate lowering agents using the National Health and Nutritional Examination Survey from 2007 to 2016MethodsAdult participants in NHANES 2007–2016 were included in the analysis. NHANES is a continuous national survey conducted by the US Centres for Disease Control and Prevention and is designed to evaluate the health and nutritional status of adults and children in the US. They are based on a representative sample of the non-institutionalised US civilian population. Each participant represents approximately 50000 Americans.The primary outcome was self-reported gout. Factors associated with gout, such as body weight, drinking habit, history of chronic kidney disease, use of aspirin and thiazide diuretics were evaluated. Prescriptions of allopurinol, febuxostat or probenacid were retrieved from the NHANES dataset to evaluate the use of urate lowering agents among patients with gout.Results were analysed using SPSS complex sample module version 22. Multiple regression was used to analyse the difference in prevalence of gout and utilisation of urate lowering agents.Results23482 adults participants were included in the analysis. There was no further increase in the prevalence of gout in the general US population. The prevalence was 3.82% and 3.84% in NHANES 2007–2010 and 2011–2016, respectively (p=0.966).Although there is a decreasing trend in the serum urate levels among patients with gout, the utilisation of urate lowering agents remained low. Only 28.2% and 29.4% of patients with gout were prescribed urate lowering agents in 2007–2010 and 2011–2014, respectively.Among patients with gout, history of chronic kidney disease and use of thiazide diuretics are the most significant negative predictors for achieving the therapeutic target of SUV <6 mg/dL (Odds ratio of 0.23 and 0.41, respectively). Use of aspirin was not a significant predictor for treatment failure.ConclusionsThe prevalence of gout in the US general population has not increased over the past 10 years. Although the use of urate lowering agents among patients with gout remained low, the percentage of patients with gout achieving the therapeutic target has increased over the past 10 years.History of chronic kidney disease and use of thiazide diuretics are the most significant negative predictors for treatment success.Disclosure of InterestNone declared
Observational studies have found associations between urinary sodium (UNa) with obesity, body shape and composition; but the findings may be biased by residual confounding. The objective of this ...two-sample Mendelian randomization (MR) study was to analyze their causal associations in both sex-combined and sex-specific models. Genome-wide association studies of UNa, body mass index (BMI), BMI-adjusted waist-to-hip ratio (WHR), body fat (BF) percentage and estimated glomerular filtration rate (eGFR) were identified. We initially extracted fifty SNPs associated with UNa at significance level of 5 × 10
, but further removed those SNPs with potential horizontal pleiotropy. Univariable and multivariable MR with adjustment for eGFR were performed. Inverse-variance weighted MR was performed as the primary analysis, with MR-Egger methods as sensitivity analysis. The potential bidirectional association between BMI and UNa was investigated. All exposure and outcomes were continuous, and the effect measure was regression coefficients (beta) and their 95% confidence intervals (95% CI). The total sample size was up to 322 154. UNa was causally associated with increased BMI in both men eGFR-adjusted beta 0.443 (0.163-0.724) and women 0.594 (0.333-0.855). UNa caused BF percentage increase in men 0.622 (0.268-0.976) and women 0.334 (0.007-0.662). UNa significantly elevated BMI-adjusted WHR in men 0.321 (0.094-0.548), but not in women 0.170 (- 0.052 to 0.391). Additionally, we found that BMI causally increased UNa 0.043 (0.023-0.063). UNa increased BMI and BF percentage. Salt intake affects male body shape by increasing BMI-adjusted WHR, but showed no effects on female body shape. The bidirectional association between BMI and UNa suggested that salt reduction measures and weight reduction measures should be implemented simultaneously to break the vicious cycle and gain more health benefits.
Methods As described previously,2 for several critical outcomes we computed unadjusted RR and NNT)/year values and corresponding 95% CIs for empagliflozin treatment, using pooled data for 10 and 25 ...mg/day recipients (n=4687). The only significant adverse effect was genital infection; respective RR and ‘number-needed-to-harm’/year values were 3.57 (2.57-4.96) and 67...
BackgroundNovel therapeutic agents are more effective than DMARDs in the management of psoriatic arthritis. However, direct comparisons of efficacy between these novel therapeutic agents are ...lacking.ObjectivesThis network meta-analysis aims to compare the relative efficacies between different novel therapeutic agents.MethodsLiterature searching was conducted in MEDLINE, EMBASE, Scopus, ISI Web of Science, Cochrane Library, Clinicaltrials.gov and recent rheumatology conference abstracts up to Nov 2016. 2 independent researchers analysed the articles. For inclusion, randomised, placebo-controlled trials must report the proportion of patients achieving ACR20, ACR50, ACR70 and PASI75 responses.The outcomes of this network meta-analysis were the proportion of patients achieving ACR20, ACR50, ACR70 and PASI75 responses with reference to placebo and etanercept.Results were analysed using random effect model by R statistics (version 3.3.1) with statistical package netmeta (version 0.9–2). The heterogeneity of the study results was determined by the I2 statistics.Results18 trials were included into this study. In general, all novel therapeutic agents demonstrated superior efficacies than placebo. With reference to etanercept, apremilast and ustekinumab were associated with less proportions of patients achieving ACR20 response (odds ratio 95% confidence interval: 20mg apremilast: 0.18 0.07–0.48; 30mg apremilast: 0.24 0.09–0.62; 45mg ustekinumab: 0.26 0.09–0.73; 90mg ustekinumab: 0.32 0.11–0.90).Etanercept was not different from apremilast, ustekinumab, golimumab, adalimumab, ixekizumab, certolizumab, ixekizumab and secukinumab in terms of ACR20 and ACR50 responses.Golimumab and infliximab were associated with greater proportions of patients achieving PASI75 response, though the difference did not reach statistical significance. (odds ratio 95% confidence interval: golimumab: 3.51 0.44–28.2; infliximab: 5.97 0.89–40.2).Table 1.Network meta-analysis on proportion of patients achieved ACR20 and PASI75 response with reference to etanerceptACR20 responsePASI75 response 10mg Tofacitinib BID0.38 0.12; 1.220.68 0.13; 3.54150mg Secukinumab0.64 0.22; 1.900.49 0.07; 3.1920mg Apremilast BID0.18 0.07; 0.490.39 0.08; 1.83300mg Secukinumab0.77 0.21; 2.800.67 0.10; 4.5630mg Apremilast BID0.24 0.09; 0.630.48 0.10; 2.2245mg Ustekinumab0.26 0.09; 0.751.18 0.15; 9.095mg Tofacitinib BID0.25 0.08; 0.810.64 0.12; 3.2980mg Ixekizumab Q2w0.40 0.12; 1.272.74 0.49; 15.3780mg Ixekizumab Q4w0.35 0.11; 1.111.73 0.32; 9.3190mg Ustekinumab0.32 0.11; 0.921.40 0.18; 10.74Adalimumab0.33 0.13; 0.860.77 0.17; 3.50Certolizumab0.42 0.12; 1.39NAEtanercept (reference)1.001.00Golimumab0.93 0.25; 3.403.51 0.44; 28.22Infliximab0.74 0.26; 2.125.97 0.89; 40.22Placebo0.10 0.04; 0.220.09 0.03; 0.35NA: not applicable.ConclusionsApremilast and ustekinumab were less efficacious than etanercept in terms of ACR20 response. All the novel therapeutic agents demonstrated comparable efficacies in terms of ACR50, ACR70 and PASI75 responses.Disclosure of InterestNone declared
BackgroundThe prevalence of gout has increased significantly over the past decade, espeically in developed countries and Oceanic populations. The estimated prevalence of gout in the US, Canada and ...European countries was 3%. Asian countries, except Taiwan, were considered to have a lower prevalence of gout due to differences in ethnicity and lifestyle.Since there are no recent epidemiological data on gout in Hong Kong, we conducted this population study to determine the incidence and prevalence of gout in Hong Kong as well as the utilisation of urate lowering agents among patients with gout.ObjectivesTo determine the incidence, prevalence of gout and use of urate lowering agents in Hong KongMethodsData were retrieved from the Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority. The Hospital Authority is the only public healthcare provider in Hong Kong. Since treatment is heavily subsidised and available to all residents, it covers more than 90% of all medical care for the general population in Hong Kong.Clinical data including demographic, diagnosis of gout, serum urate levels and prescriptions of urate lowering agents were retrieved from CDARS from 2006 to 2016. For inclusion, subjects must have attended any out-patient clinics or accident and emergency department (with or without hospitalisation) in 2005. Subjects with a diagnosis of gout who died before 2006 were excluded. All subjects were followed until the cut-off date or death.Gout was defined as the physician diagnosis and coding in CDARS. The serum urate levels achieved after prescribing urate lowering agents were the means of all serum urate levels 6 months after prescriptions.Results were analysed by R statistics version 3.3.3. with package ‘prevalence’ version 0.4.0.Results2741862 participants were included in the analysis. Both the incidence and prevalence of gout in Hong Kong have increased over the past 10 years. In 2016, the crude and age-standardised prevalence of gout were 2.92% and 1.44%, respectively. 6.26% of the general populaton aged 80 years or older was diagnosed to have gout.Despite the increase in incidence and prevalence of gout in Hong Kong, the utilisation of urate lowering agents remained low. in 2016, only 25.55% of patients with gout were prescribed urate lowering agents. More importantly, only 35.8% of those could achieve the therapeutic target of serum urate level <6 mg/dL.ConclusionsPopulation ageing has led to increases in incidence and prevalence of gout in Hong Kong. In 2016, the crude prevalence of gout in Hong Kong was 2.92%, which is similar to figures reported in western countries. Despite an increase in prevalence of gout, the utilisation of urate lowering agents remained low. Only 1 in 4 patients with gout were prescribed urate lowering agents.AcknowledgementsThe Hospital Authority of Hong KongDisclosure of InterestNone declared
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