OBJECTIVES: Social capital consists of features of social organization--such as trust between citizens, norms of reciprocity, and group membership--that facilitate collective action. This article reports a contextual analysis of social capital and individual self-rated health, with adjustment for individual household income, health behaviors, and other covariates. METHODS: Self-rated health ("Is your overall health excellent, very good, good, fair, or poor?") was assessed among 167,259 individuals residing in 39 US states, sampled by the Behavioral Risk Factor Surveillance System. Social capital indicators, aggregated to the state level, were obtained from the General Social Surveys. RESULTS: Individual-level factors (e.g., low income, low education, smoking) were strongly associated with self-rated poor health. However, even after adjustment for these proximal variables, a contextual effect of low social capital on risk of self-rated poor health was found. For example, the odds ratio for fair or poor health associated with living in areas with the lowest levels of social trust was 1.41 (95% confidence interval = 1.33, 1.50) compared with living in high-trust states. CONCLUSIONS: These results extend previous findings on the health advantages stemming from social capital.

To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study 1 . After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, ∼150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10 −3 , GWA scan; P < 10 −6 , replication; P = 10 −9 , combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 × 10 −6 in WTCCC) 2 . We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23.Rheumatoid arthritis is the most common inflammatory arthritis, affecting up to 1% of the adult population 3 . Two loci (HLA-DRB14 and PTPN22 5 ) have previously been associated with rheumatoid arthritis susceptibility in individuals with circulating antibodies to cyclic citrullinated peptides (CCP). Most of the inheritance of rheumatoid arthritis remains unexplained.To identify additional common variants associated with risk of CCP antibody-associated (CCP + ) rheumatoid arthritis, we conducted a GWA study using the Affymetrix 100K GeneChip microarray in a longitudinal case series of individuals with CCP + rheumatoid arthritis (the Brigham Rheumatoid Arthritis Sequential Study (BRASS) cohort). As we lacked epidemiologically matched controls, we compared case data to publicly available genotype data collected using the same platform from 1,211 related Framingham Heart Study (FHS) participants 1 , drawn from the same geographical region as the individuals in our study (near Boston, Massachusetts, USA).Before comparing allele frequencies between cases and controls, we considered biases that may be introduced by the use of shared controls. Such biases, whether due to nonrandom distribution of technical artifacts 6 or to population differences between case and control data 7,8 , would result in a non-null distribution of test statistics with excess false-positive associations. In an initial analysis of unrelated case-control samples, we assessed the median distribution of test statistics with the genomic-control parameter λ GC 9 (where 1.0 indicates no inflation) and examined the tail of the distribution of association statistics in a comparison of observed and expected P values (Q-Q plot; Fig. 1).Using published data quality control parameters from early studies on this genotyping platform (genotype call rates > 90%, minor allele frequency (MAF) >5%) 1 , we observed λ GC = 1.19 and an excess of associations in the e...

Inequality in the distribution of income was associated with an adverse impact on health independent of the effect of household income.

In this first nationwide study evaluating VE under conditions of routine use, RV5 was highly effective in preventing RGE and AGE and in reducing health care resource utilization. Further research is needed to assess VE with an incomplete rotavirus vaccination regimen.

The objective of this review is to report on the progress of the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) Registry data collection and summarize previous research in understanding therapeutic response to DMARDs using clinical and genetic data. The BRASS Registry, established in 2003, is a large, single-centre, prospective and observational cohort of 1100 RA patients. Patients with either new-onset or established RA disease are recruited from the practices of rheumatologists. Annual visits collect information on demographics, 28-joint DAS-CRP3 (DAS-28-CRP3), medication use, comorbidities and functional status (Modified Health Assessment Questionnaire, Short Form Health Survey 12). Two published studies have utilized BRASS to examine genetic predictors of treatment response. In a cross-sectional study, examining the association between candidate single nucleotide polymorphisms (SNPs) and disease activity in a subset of 120 RA patients on MTX monotherapy, the minor allele of ATIC rs4673993 was associated with low disease activity (P=0.01, DAS-28-CRP3≤3.2). In an international collaboration, 55 BRASS patients receiving anti-TNF therapy were genotyped for 31 SNPs associated with the risk of RA. With our collaborators, we discovered an SNP at the protein tyrosine phosphatase, receptor type, C (PTPRC) gene locus that was associated with EULAR 'good response'. With accurate data collection and the capacity to run genome-wide association studies and SNP analyses, the BRASS Registry has the ability to determine the contribution of genetic variants to disease onset and to assess their usefulness as biomarkers for treatment response and drug toxicity.

Background: HLA-DRB1 shared epitope (HLA-SE), PTPN22 and CTLA4 alleles are associated with cyclic citrullinated peptide (CCP) and rheumatoid arthritis (RA). Objective: We examined associations between HLA-SE, PTPN22, CTLA4 genotypes and RA phenotypes in a large cohort to (a) replicate prior associations with CCP status, and (b) determine associations with radiographic erosions and age of diagnosis. Methods: A total of 689 RA patients from the Brigham RA Sequential Study (BRASS) were genotyped for HLA-SE, PTPN22 (rs2476601) and CTLA4 (rs3087243). Association between genotypes and CCP, rheumatoid factor (RF) erosive phenotypes and age at diagnosis were assessed with multivariable models adjusting for age, sex and disease duration. Novel causal pathway analysis was used to test the hypothesis that genetic risk factors and CCP are in the causal pathway for predicting erosions. Results: In multivariable analysis, presence of any HLA-SE was strongly associated with CCP+ (odds ratio (OR) 3.05, 95% CI 2.18-4.25), and RF+ (OR 2.53, 95% CI 1.83-3.5) phenotypes; presence of any PTPN22 T allele was associated with CCP+ (OR 1.81, 95% CI 1.24-2.66) and RF+ phenotypes (OR 1.84, 95% CI 1.27-2.66). CTLA4 was not associated with CCP or RF phenotypes. While HLA-SE was associated with erosive RA phenotype (OR 1.52, 95% CI 1.01-2.17), this was no longer significant after conditioning on CCP. PTPN22 and CTLA4 were not associated with erosive phenotype. Presence of any HLA-SE was associated with an average 3.6 years earlier diagnosis compared with absence of HLA-SE (41.3 vs 44.9 years, p = 0.002) and PTPN22 was associated with a 4.2 years earlier age of diagnosis (39.5 vs 43.6 years, p = 0.002). CTLA4 genotypes were not associated with age at diagnosis of RA. Conclusions: In this large clinical cohort, we replicated the association between HLA-SE and PTPN22, but not CTLA4 with CCP+ and RF+ phenotypes. We also found evidence for associations between HLA-SE, and PTPN22 and earlier age at diagnosis. Since HLA-SE is associated with erosive phenotype in unconditional analysis, but is not significant after conditioning on CCP, this suggests that CCP is in the causal pathway for predicting erosive phenotype.Genetic factors are thought to be responsible for up to 50%-60% of rheumatoid arthritis (RA) risk.

Key PointsQuestionWas the Centers for Medicare & Medicaid Services Oncology Care Model (OCM), an alternative payment model for cancer patients undergoing chemotherapy, associated with differences in Medicare spending, utilization, quality, and patient experience over the model’s first 3 years?FindingsIn this exploratory difference-in-differences study of Medicare fee-for-service beneficiaries with cancer undergoing chemotherapy (483 310 beneficiaries with 987 332 episodes treated at 201 OCM participating practices and 557 354 beneficiaries with 1 122 597 episodes treated at 534 comparison practices), OCM was associated with a statistically significant relative decrease in total episode payments of $297 that was not sufficient to cover the costs of care coordination or performance-based payments. There were no statistically significant differences in most measures of utilization, quality, or patient experiences.MeaningIn its first 3 years, the OCM was significantly associated with modestly lower Medicare episode payments that did not offset model payments to participating practices, and there were no significant differences in most utilization, quality, or patient experience outcomes.

Objective. Among rheumatoid arthritis (RA) patients who have had the disease for 10 years, more than half have focal erosions, and the risk of fracture is doubled. However, there is little information about the potential relationship between focal erosions and bone mineral density (BMD). The aim of this study was to determine whether lower BMD is associated with higher erosion scores among patients with RA.Methods. We enrolled 163 postmenopausal women with RA, none of whom were taking osteoporosis medications. Patients underwent dual x-ray absorptiometry at the hip and spine and hand radiography, and completed a questionnaire. The hand radiographs were scored using the Sharp method, and the relationship between BMD and erosions was measured using Spearman's correlation coefficients and adjusted linear regression models.Results. Patients had an average disease duration of 13.7 years, and almost all were taking a diseasemodifying antirheumatic drug. Sixty-three percent were rheumatoid factor (RF) positive. The median modified Health Assessment Questionnaire score was 0.7, and the average Disease Activity Score in 28 joints was 3.8. The erosion score was significantly correlated with total hip BMD (r ‫؍‬ ؊0.33, P < 0.0001), but not with lumbar spine BMD (r ‫؍‬ ؊0.09, P ‫؍‬ 0.27). Hip BMD was significantly lower in RF-positive patients versus RFnegative patients (P ‫؍‬ 0.02). In multivariable models that included age, body mass index, and cumulative oral glucocorticoid dose, neither total hip BMD nor lumbar spine BMD was significantly associated with focal erosions.Conclusion. Our results suggest that hip BMD is associated with focal erosions among postmenopausal women with RA, but that this association disappears after multivariable adjustment. While BMD and erosions may be correlated with bone manifestations of RA, their relationship is complex and influenced by other disease-related factors.Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis, affecting ϳ1% of the