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UNLABELLED: Few studies have prospectively examined long-term associations between neighborhood socioeconomic status (nSES) and mortality risk, independent of demographic and lifestyle risk factors. METHODS: We assessed associations between nSES and all-cause, nonaccidental mortality among women in the Nurses Health Study (NHS) 1986-2014 (N = 101,701) and Nurses Health Study II (NHSII) 1989-2015 (N = 101,230). Mortality was ascertained from the National Death Index (NHS: 19,228 deaths; NHSII: 1556 deaths). Time-varying nSES was determined for the Census tract of each residential address. We used principal component analysis (PCA) to identify nSES variable groups. Multivariable Cox proportional hazards models were conditioned on age and calendar period and included time-varying demographic, lifestyle, and individual SES factors. RESULTS: For NHS, hazard ratios (HRs) comparing the fifth to first nSES quintiles ranged from 0.89 (95% confidence interval [CI] = 0.84, 0.94) for percent of households receiving interest/dividends, to 1.11 (95% CI = 1.06, 1.17) for percent of households receiving public assistance income. In NHSII, HRs ranged from 0.72 (95% CI: 0.58, 0.88) for the percent of households receiving interest/dividends, to 1.27 (95% CI: 1.07, 1.49) for the proportion of households headed by a single female. PCA revealed three constructs: education/income, poverty/wealth, and racial composition. The racial composition construct was associated with mortality (HRNHS: 1.03; 95% CI = 1.01, 1.04). CONCLUSION: In two cohorts with extensive follow-up, individual nSES variables and PCA component scores were associated with mortality. nSES is an important population-level predictor of mortality, even among a cohort of women with little individual-level variability in SES.

Rationale & objectiveAmong individuals with chronic kidney disease (CKD), poor self-reported health is associated with adverse outcomes including hospitalization and death. We sought to examine the association between health-related quality-of-life (HRQoL) and depressive symptoms in advanced CKD and subsequent access to the kidney transplant waiting list.Study designProspective cohort study.Setting & population1,676 Chronic Renal Insufficiency Cohort (CRIC) study participants with estimated glomerular filtration rates ≤ 30 mL/min/1.73 m2 at study entry or during follow-up.ExposuresHRQoL ascertained by 5 scales of the Kidney Disease Quality of Life-36 Survey (Physical Component Summary [PCS], Mental Component Summary, Symptoms, Burdens, and Effects), with higher scores indicating better HRQoL, and depressive symptoms ascertained using the Beck Depression Inventory.OutcomesTime to kidney transplant wait-listing and time to pre-emptive wait-listing.Analytic approachTime-to-event analysis using Cox proportional hazards regression.ResultsDuring a median follow-up of 5.1 years, 652 (39%) participants were wait-listed, of whom 304 were preemptively wait-listed. Adjusted for demographics, comorbid conditions, estimated glomerular filtration rate slope, and cognitive function, participants with the highest scores on the Burden and Effects scales, respectively, had lower rates of wait-listing than those with the lowest scores on the Burden (wait-listing adjusted hazard ratio [aHR], 0.70; 95% CI, 0.57-0.85; P

We aimed to examine the association between the use of metformin and other anti‐diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994–2016) and the NHSII (1995–2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti‐diabetes medications, and other covariates was self‐reported at baseline and repeatedly assessed by follow‐up questionnaires every 2 years. Breast cancer cases were self‐reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person‐years of follow‐up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81–1.15) nor other anti‐diabetic medications use (HR = 1.11; 95% CI = 0.90–1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74–1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48–0.94), current use (HR = 1.01; 95% CI = 0.80–1.27) and longer duration of metformin use were not associated with breast cancer (each 2‐year interval: HR = 1.01; 95% CI = 0.95–1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D. [ABSTRACT FROM AUTHOR]

BackgroundIt is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy.Study designProspective cohort study.Setting & participantsThe Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation.PredictorsThe primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point.OutcomesAll-cause mortality within 1 year after initiating hemodialysis therapy.MeasurementsMultivariable Cox proportional hazards.ResultsAmong 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76).LimitationsRelatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data.ConclusionsAbrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD.

Introduction: The WHO recommends antiretroviral treatment (ART) for all HIV-positive patients regardless of CD4 count or disease stage, referred to as 'Early Access to ART for All' (EAAA). The health systems effects of EAAA implementation are unknown. This trial was implemented in a government-managed public health system with the aim to examine the 'real world' impact of EAAA on care retention and viral suppression. Methods: In this stepped-wedge randomized controlled trial, 14 public sector health facilities in Eswatini were paired and randomly assigned to stepwise transition from standard of care (SoC) to EAAA. ART-naive participants [greater than or equal to]18 years who were not pregnant or breastfeeding were eligible for enrolment. We used Cox proportional hazard models with censoring at clinic transition to estimate the effects of EAAA on retention in care and retention and viral suppression combined. Results: Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and EAAA respectively, 12-month HIV care retention rates were 80% (95% Cl: 77 to 83) and 86% (95% CI: 83 to 88). The 12-month combined retention and viral suppression endpoint rates were 44% (95% Cl: 40 to 48) under SoC compared to 80% (95% CI: 77 to 83) under EAAA. EAAA increased both retention (HR: 1x60, 95% Cl: 1x15 to 2x21, p = 0.005) and retention and viral suppression combined (HR: 4.88, 95% Cl: 2.96 to 8.05, p < 0.001). We also identified significant gaps in current health systems ability to provide viral load (VL) monitoring with 80% participants in SoC and 66% in EAAA having a missing VL at last contact. Conclusions: The observed improvement in retention in care and on the combined retention and viral suppression provides an important co-benefit of EAAA to HIV-positive adults themselves, at least in the short term. Our results from this 'rea world' health systems trial strongly support EAAA for Eswatini and countries with similar HIV epidemics and health systems. VL monitoring needs to be scaled up for appropriate care management. Keywords: universal treatment; HIV retention; viral suppression; Eswatini; Sub-Saharan Africa; antiretroviral therapy Additional information may be found under the Supporting Information tab for this article., 1 | INTRODUCTION In 2018, nearly 38 million people were living with human immunodeficiency virus (HIV), of whom 20.64 million live in sub-Saharan Africa. There has been a 56% decline [...]

BackgroundCardiometabolic disease is a major cause of morbidity and mortality in persons with chronic kidney disease (CKD). Fractalkine (CX3CL1) is a potential mediator of both atherosclerosis and metabolic disease. Studies of the relationship of CX3CL1 with risk of cardiovascular disease (CVD) events and metabolic traits are lacking, particularly in the high-risk setting of CKD.Study designCross-sectional and longitudinal observational analysis.Setting & participantsAdults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study.PredictorQuartiles of plasma CX3CL1 levels at baseline.OutcomesBaseline estimated glomerular filtration rate from a creatinine and cystatin C-based equation, prevalent and incident CVD, diabetes, metabolic syndrome and its criteria, homeostatic model assessment of insulin resistance, hemoglobin A1c level, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality.ResultsAmong 3,687 participants, baseline CX3CL1 levels were associated positively with several CVD risk factors and metabolic traits, lower estimated glomerular filtration rate, and higher levels of inflammatory cytokines, as well as prevalent CVD (OR, 1.09; 95% CI, 1.01-1.19; P=0.03). Higher CX3CL1 level also was associated with prevalent diabetes (OR, 1.26; 95% CI, 1.16-1.38; P

Although subjects with chronic kidney disease (CKD) are at markedly increased risk for cardiovascular mortality, the relation between CKD and aortic valve calcification has not been fully elucidated. Also, few data are available on the relation of aortic valve calcification and earlier stages of CKD. We sought to assess the relation of aortic valve calcium (AVC) with estimated glomerular filtration rate (eGFR), traditional and novel cardiovascular risk factors, and markers of bone metabolism in the Chronic Renal Insufficiency Cohort (CRIC) Study. All patients who underwent aortic valve scanning in the CRIC study were included. The relation between AVC and eGFR, traditional and novel cardiovascular risk factors, and markers of calcium metabolism were analyzed using both unadjusted and adjusted regression models. A total of 1,964 CRIC participants underwent computed tomography for AVC quantification. Decreased renal function was independently associated with increased levels of AVC (eGFR 47.11, 44.17, and 39 ml/min/1.73 m2, respectively, p

Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this, we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331-420 days) of baseline. Baseline plasma FGF23 was not associated with the prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its coreceptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms.

Introduction: Retention on antiretroviral therapy (ART) is critical for the successful adoption of the test and treat policy by sub-Saharan African countries, and for realizing the United Nations programme on HIV and AIDS target of 90-90-90. This qualitative study explores HIV positive clients' reasons for discontinuing ART under the MaxART test and treat implementation study in Swaziland. Methods: Clients identified as lost to follow-up (LTFU) in the programme database, who had initiated ART under the intervention arm of the MaxART study, were purposively selected from two facilities. LTFU was defined as stopping ART refill for three months or longer from the date of last appointment, and not being classified as transferred out or deceased. Semi-structured face-to-face interviews were conducted with nine clients and one treatment supporter between July and August 2017. All interviews were conducted in the local language, audio-recorded, summarized or transcribed and translated to English for thematic analysis. Results: Respondents described mobility as the first step in a chain of events that affected retention in care. It was entwined with precarious employment, care delivery, interactions with health workers, lack of social support, anticipated stigma and ART-related side-effects, including the exacerbation of hunger. The chains of events involved several intersecting reasons that occurred one after the other as a series of contiguous and linked events that led to clients' eventual discontinuation of ART. The individual accounts of step-by-step decision-making revealed the influence of multi-layered contexts and the importance of critical life-events. Conclusions: Clients' reasons for abandoning ART are a complex, inextricably interwoven chain of events rather than a single occurrence. Mobility is often the first step in the process and commonly results from precarious economic and social circumstances. Currently the health system poorly caters to the reality of people's mobile lives. Interventions should seek to increase healthcare workers' understanding of the chain of events leading up to discontinuation on ART and the social dilemmas that clients face. Keywords: ARV; Retention; Linkage to care; Intervention; Swaziland; Test and Treat, 1 | INTRODUCTION Between 2000 and 2015, the number of people living with HIV (PLHIV) who access antiretroviral therapy (ART) saw a thirty-fold global increase: from 250,000 to more than [...]

Brachial pulse pressure (bPP) predicts kidney function in CKD. Pulse wave velocity (PWV) may provide additional prediction of CKD progression, and was evaluated longitudinally in CKD patients enrolled in the CRIC cohort. bPP was used because it shows superior CKD progression prediction in humans.There were 2821 participants in CRIC who underwent an assessment of PWV most of whom were studied at their second year follow-up visit. Of these 43 % were women, 48% diabetic, mean age 60 years and mean estimated GFR of 44.6 mL/min/1.73m2. Blacks were 40%, whites 44%, and Hispanics 12%. Mean blood pressure was 127/70 mmHg; mean bPP was 54 mmHg. The interaction of PWV with bPP on the occurrence of ESRD (dialysis or a transplant) [left panel of figure] and a combined endpoint of halving of the eGFR or ESRD [right panel], was analyzed used Cox regression. Events by tertiles of PWV (<7.9 msec; 7.9-10.3 m/sec; >10.3m/sec) and bPP (<46 mmHg, 46-62 mmHg, >62 mmHg) are shown in the figure.There were significant interactions between PWV and bPP for both outcomes. For ESRD the hazard ratio of the highest tertiles of PWV/bPP compared with the lowest was 3.18 (p<0.001). For the combined ESRD or halving of eGFR the HR was 2.65 (p<0.001). In multivariable regression important predictors of CKD progression in this model were age, male gender, non-white race/ethnicity, initial eGFR, and proteinuria.PWV showed a strong and graded interaction with bPP in the prediction of ESRD and the combined outcome of halving of GFR or ESRD. A greater appreciation of the role of arterial stiffness in CKD is an important step towards pursuing the mechanisms underlying how this measure may influence the course of kidney disease progression. [ABSTRACT FROM AUTHOR]