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TNFAIP3 encodes the ubiquitin modifying enzyme, A20, a key regulator of inflammatory signaling pathways. We previously reported association between TNFAIP3 variants and systemic lupus erythematosus (SLE). In order to further localize the risk variant(s), we performed a meta-analysis using genetic data available from two Caucasian case/control datasets (1453 total cases, 3381 total controls) and 713 SLE trio families. The best result was found at rs5029939 (P = 1.67 × 10−14, OR = 2.09, 95% CI 1.68–2.60). We then imputed SNPs from the CEU Phase II HapMap using genotypes from 431 SLE cases and 2155 controls. Imputation identified eleven SNPs in addition to three observed SNPs, which together, defined a 109 kb SLE risk segment surrounding TNFAIP3. When evaluating whether the rs5029939 risk allele was associated with SLE clinical manifestations, we observed that heterozygous carriers of the TNFAIP3 risk allele at rs5029939 have a two-fold increased risk of developing renal or hematologic manifestations compared to homozygous non-risk subjects. In summary, our study strengthens the genetic evidence that variants in the region of TNFAIP3 influence risk for SLE, particularly in patients with renal and hematologic manifestations, and narrows the risk effect to a 109 kb DNA segment that spans the TNFAIP3 gene.

IntroductionAddressing pain is a crucial aspect of emergency medicine. Prescription opioids are commonly prescribed for moderate to severe pain in the emergency department (ED); unfortunately, prescribing practices are variable. High variability of opioid prescribing decisions suggests a lack of consensus and an opportunity to improve care. This quality improvement (QI) initiative aimed to reduce variability in ED opioid analgesic prescribing.MethodsWe evaluated the impact of a three-part QI initiative on ED opioid prescribing by physicians at seven sites. Stage 1: Retrospective baseline period (nine months). Stage 2: Physicians were informed that opioid prescribing information would be prospectively collected and feedback on their prescribing and that of the group would be shared at the end of the stage (three months). Stage 3: After physicians received their individual opioid prescribing data with blinded comparison to the group means (from Stage 2) they were informed that individual prescribing data would be unblinded and shared with the group after three months. The primary outcome was variability of the standard error of the mean and standard deviation of the opioid prescribing rate (defined as number of patients discharged with an opioid divided by total number of discharges for each provider). Secondary observations included mean quantity of pills per opioid prescription, and overall frequency of opioid prescribing.ResultsThe study group included 47 physicians with 149,884 ED patient encounters. The variability in prescribing decreased through each stage of the initiative as represented by the distributions for the opioid prescribing rate: Stage 1 mean 20%; Stage 2 mean 13% (46% reduction, p<0.01), and Stage 3 mean 8% (60% reduction, p<0.01). The mean quantity of pills prescribed per prescription was 16 pills in Stage 1, 14 pills in Stage 2 (18% reduction, p<0.01), and 13 pills in Stage 3 (18% reduction, p<0.01). The group mean prescribing rate also decreased through each stage: 20% in Stage 1, 13% in Stage 2 (46% reduction, p<0.01), and 8% in Stage 3 (60% reduction, p<0.01).ConclusionED physician opioid prescribing variability can be decreased through the systematic application of sharing of peer prescribing rates and prescriber specific normative feedback.

This study evaluated the efficacy of an integrated Total Worker Health® program, “All the Right Moves”, designed to target the conditions of work and workers’ health behaviors through an ergonomics program combined with a worksite-based health promotion Health Week intervention. A matched-pair cluster randomized controlled trial was conducted on ten worksites (five intervention (n = 324); five control sites (n = 283)). Worker surveys were collected at all sites pre- and post- exposure at one- and six-months. Linear and logistic regression models evaluated the effect of the intervention on pain and injury, dietary and physical activity behaviors, smoking, ergonomic practices, and work limitations. Worker focus groups and manager interviews supplemented the evaluation. After controlling for matched intervention and control pairs as well as covariates, at one-month following the ergonomics program we observed a significant improvement in ergonomic practices (B = 0.20, p = 0.002), and a reduction in incidences of pain and injury (OR = 0.58, p = 0.012) in the intervention group. At six months, we observed differences in favor of the intervention group for a reduction in physically demanding work (B = −0.25, p = 0.008), increased recreational physical activity (B = 35.2, p = 0.026) and higher consumption of fruits and vegetables (B = 0.87, p = 0.008). Process evaluation revealed barriers to intervention implementation fidelity and uptake, including a fissured multiemployer worksite, the itinerant nature of workers, competing production pressures, management support, and inclement weather. The All the Right Moves program had a positive impact at the individual level on the worksites with the program. For the longer term, the multi-organizational structure in the construction work environment needs to be considered to facilitate more upstream, long-term changes.