Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trial (SPRINT): A Randomized Clinical Trial

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of ≤ 120 mm Hg (intensive treatment) reduced cardiovascular disease (CVD) events compared to SBP of ≤ 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups. METHODS: We analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death. RESULTS: Average postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57–0.86), 0.71 (0.51–0.98), 0.62 (0.33–1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29–0.81), 0.77 (0.37–1.57), and 0.17 (0.01–1.08). All-cause mortality HRs were 0.61 (0.47–0.80), 0.92 (0.63–1.35), and 1.58 (0.73–3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons. CONCLUSION: Targeting a SBP goal of ≤ 120 mm Hg compared to ≤ 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications

Revealing and re-valuing cultural intermediaries in the 'real' creative city : insights from a diary-keeping exercise

From critics and cultural commentators to professionals who mediate between production and consumption for economic gain, the term ‘cultural intermediaries’ has been variously interpreted over recent decades. Often framed as self-interested entrepreneurs seeking to maximise economic value the wider set of political, social and moral motivations of cultural workers have been often overlooked.Drawing on a diary-keeping exercise with 20 cultural workers in Greater Manchester and Birmingham in 2013, we suggest that a ‘third’ wave of studies of cultural intermediaries is needed, which emphasises socially engaged practices and non-economic values. The study reveals a field of cultural work which mediates between professionalised and everyday cultural ecologies, one which is often invisible and undervalued. Combining methodological insights into diary-keeping as a reflexive exercise, the study suggests that we should reclaim and re-value the term ‘cultural intermediary’ to make visible this socially grounded cultural work, particularly in the current era of austerity and cuts to the arts in England

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Predictors of timely follow-up after abnormal cancer screening among women seeking care at urban community health centers

BACKGROUND: We sought to measure time and identify predictors of timely follow-up among a cohort of racially/ethnically diverse inner city women with breast and cervical cancer screening abnormalities. METHODS: Eligible women had an abnormality detected on a mammogram or Papanicolaou (Pap) test between January 2004 and December 2005 in 1 of 6 community health centers in Boston, Massachusetts. Retrospective chart review allowed us to measure time to diagnostic resolution. We used Cox proportional hazards models to develop predictive models for timely resolution (defined as definitive diagnostic services completed within 180 days from index abnormality). RESULTS: Among 523 women with mammography abnormalities and 474 women with Pap test abnormalities, \u3e90% achieved diagnostic resolution within 12 months. Median time to resolution was longer for Pap test than for mammography abnormalities (85 vs 27 days). Site of care, rather than any sociodemographic characteristic of individuals, including race/ethnicity, was the only significant predictor of timely follow-up for both mammogram and Pap test abnormalities. CONCLUSIONS: Site-specific community-based interventions may be the most effective interventions to reduce cancer health disparities when addressing the needs of underserved populations

APOL1 Renal-Risk Variants Do Not Associate With Incident Cardiovascular Disease or Mortality in the Systolic Blood Pressure Intervention Trial

Relationships between apolipoprotein L1 gene (APOL1) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between APOL1 and CVD, a total of 2568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including nonfatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and CVD death), renal outcomes, and all-cause mortality. Methods: Cox proportional hazards regression models were used, adjusting for age, sex, African ancestry proportion, and treatment group (systolic blood pressure target of <120 mm Hg vs. <140 mm Hg). Results: Of the participants, 14% had 2 APOL1 RRVs; these individuals also had lower baseline estimated GFR and higher levels of albuminuria and BMI. After a median follow-up of 39 months, no significant association was observed between APOL1 RRVs and the primary composite CVD outcome, any of its components, or all-cause mortality (recessive or additive genetic models). APOL1 demonstrated a trend toward association with sustained 30% reduction in estimated GFR to <60 ml/min/1.73 m2 in those with normal kidney function at baseline (hazard ratio 1.64; 95% confidence interval = 0.85−2.93; P = 0.114, recessive model). Discussion: APOL1 RRVs were not associated with incident CVD in high-risk hypertensive, nondiabetic African American participants in SPRINT