How the Environmental Influences on Child Health Outcome (ECHO) cohort can spur discoveries in environmental epidemiology.

The Environmental Influences on Child Health Outcome (ECHO) program at the National Institutes of Health is an innovative, large, collaborative research initiative whose mission is to enhance the health of children for generations to come. The goal of the ECHO program is to examine effects of a broad array of early environmental exposures on child health and development. The information includes longitudinal data and biospecimens from more than 100 000 children and family members from diverse settings across the United States ECHO investigators have published collaborative analyses showing associations of environmental exposures-primarily in the developmentally sensitive pre-, peri-, and postnatal periods-with preterm birth and childhood asthma, obesity, neurodevelopment, and positive health. Investigators have addressed health disparities, joint effects of environmental and social determinants, and effects of mixtures of chemicals. The ECHO cohort is now entering its second 7-year cycle (2023-2030), which will add the preconception period to its current focus on prenatal through adolescence. Through a controlled access public-use database, ECHO makes its deidentified data available to the general scientific community. ECHO cohort data provide opportunities to fill major knowledge gaps in environmental epidemiology and to inform policies, practices, and programs to enhance child health. This article is part of a Special Collection on Environmental Epidemiology.

Evaluating Cognitive Impairment in a Large Health Care System: The Cognition in Primary Care Program.

Background: The prevalence of Alzheimer's disease and related disorders (ADRD) is rising. Primary care providers (PCPs) will increasingly be required to play a role in its detection but lack the training to do so. Objective: To develop a model for cognitive evaluation which is feasible in primary care and evaluate its implementation in a large health system. Methods: The Cognition in Primary Care Program consists of web-based training together with integrated tools built into the electronic record. We implemented the program among PCPs at 14 clinics in a large health system. We (1) surveyed PCPs to assess the impact of training on their confidence to evaluate cognition, (2) measured the number of cognitive assessments they performed, and (3) tracked the number of patients diagnosed with mild cognitive impairment (MCI). Results: Thirty-nine PCPs completed the training which covered how to evaluate cognition. Survey response rate from those PCPs was 74%. Six months after the end of the training, they reported confidence in assessing cognition (mean 4.6 on 5-point scale). Cognitive assessments documented in the health record increased from 0.8 per month before the training to 2.5 in the six months after the training. Patients who were newly diagnosed with MCI increased from 4.2 per month before the training to 6.0 per month in the six months after the training. Conclusions: This model for cognitive evaluation in a large health system was shown to increase cognitive testing and increase diagnoses of MCI. Such improvements are essential for the timely detection of ADRD.

Validation of the shortened version of the Canine Behavioral Assessment and Research Questionnaire (C-BARQ) using participants from the Dog Aging Project.

The Canine Behavioral Assessment and Research Questionnaire (C-BARQ) is a 100-item owner-completed survey instrument used for assessing behavior and temperament of companion dogs. The shortened version of the C-BARQ (C-BARQ(S)) consists of 42 items of the long C-BARQ. We aimed to validate the shortened C-BARQ(S) by comparing it with the long questionnaire in the same human-dog pair. We examined data from a nationwide cohort of companion dogs enrolled in the large-scale longitudinal Dog Aging Project (DAP) study. Among 435 participating owners who completed both the long and shortened versions of the C-BARQ within 60 days of each other, agreement between individual questions of the long and shortened C-BARQ using an unweighted kappa statistic and percent agreement was examined. Associations between the two questionnaires for mean behavior and temperament domain scores and mean miscellaneous category scores were assessed using Pearson correlation coefficients. Of 435 dogs in the study, the mean (SD) age was 7.3 (4.3) years and 216 (50%) were female. Kappa values between the long and shortened C-BARQ for individual questions within the 14 behavior and temperament domains and a miscellaneous category ranged from fair to moderate (0.23 to 0.40 for 21 items and 0.41 to 0.58 for 26 items, respectively). Pearson correlation coefficients above 0.60 between both questionnaires for 12 of the 14 mean behavior and temperament domain scores and a category of miscellaneous items were observed. Kappa values for individual questions between the long and shortened C-BARQ ranged from fair to moderate and correlations between mean domain scores ranged from moderate to strong.

An Examination of the Joint Effect of the Social Environment and Air Pollution on Dementia Among US Older Adults.

Evidence suggests exposure to air pollution increases the risk of dementia. Cognitively stimulating activities and social interactions, made available through the social environment, may slow cognitive decline. We examined whether the social environment buffers the adverse effect of air pollution on dementia in a cohort of older adults. Methods: This study draws from the Ginkgo Evaluation of Memory Study. Participants aged 75 years and older were enrolled between 2000 and 2002 and evaluated for dementia semi-annually through 2008. Long-term exposure to particulate matter and nitrogen dioxide was assigned from spatial and spatiotemporal models. Census tract-level measures of the social environment and individual measures of social activity were used as measures of the social environment. We generated Cox proportional hazard models with census tract as a random effect and adjusted for demographic and study visit characteristics. Relative excess risk due to interaction was estimated as a qualitative measure of additive interaction. Results: This study included 2,564 individuals. We observed associations between increased risk of dementia and fine particulate matter (µg/m3), coarse particulate matter (µg/m3), and nitrogen dioxide (ppb); HRs per 5 unit increase were 1.55 (1.01, 2.18), 1.31 (1.07, 1.60), and 1.18 (1.02, 1.37), respectively. We found no evidence of additive interaction between air pollution and the neighborhood social environment. Conclusions: We found no consistent evidence to suggest a synergistic effect between exposure to air pollution and measures of the social environment. Given the many qualities of the social environment that may reduce dementia pathology, further examination is encouraged.

Change in gait speed and fall risk among community-dwelling older adults with and without mild cognitive impairment: a retrospective cohort analysis.

BACKGROUND: Although slow gait speed is an established risk factor for falls, few studies have evaluated change in gait speed as a predictor of falls or considered variability in effects by cognitive status. Change in gait speed may be a more useful metric because of its potential to identify decline in function. In addition, older adults with mild cognitive impairment are at an elevated risk of falls. The purpose of this research was to quantify the association between 12-month change in gait speed and falls in the subsequent 6 months among older adults with and without mild cognitive impairment. METHODS: Falls were self-reported every six months, and gait speed was ascertained annually among 2,776 participants in the Ginkgo Evaluation of Memory Study (2000-2008). Adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for fall risk relative to a 12-month change in gait speed. RESULTS: Slowing gait speed over 12 months was associated with increased risk of one or more falls (HR:1.13; 95% CI: 1.02 to 1.25) and multiple falls (HR:1.44; 95% CI: 1.18 to 1.75). Quickening gait speed was not associated with risk of one or more falls (HR 0.97; 95% CI: 0.87 to 1.08) or multiple falls (HR 1.04; 95% CI: 0.84 to 1.28), relative to those with a less than 0.10 m/s change in gait speed. Associations did not vary by cognitive status (pinteraction = 0.95 all falls, 0.25 multiple falls). CONCLUSIONS: Decline in gait speed over 12 months is associated with an increased likelihood of falls among community-dwelling older adults, regardless of cognitive status. Routine checks of gait speed at outpatient visits may be warranted as a means to focus fall risk reduction efforts.

Air pollution and plasma amyloid beta in a cohort of older adults: Evidence from the Ginkgo Evaluation of Memory study.

Air pollution has been linked to Alzheimer's disease and related dementias (ADRD), but the mechanisms connecting air pollution to ADRD have not been firmly established. Air pollution may cause oxidative stress and neuroinflammation and contribute to the deposition of amyloid beta (Aß) in the brain. We examined the association between fine particulate matter<2.5 µm in diameter (PM2.5), particulate matter<10 µm in diameter (PM10), nitrogen dioxide (NO2), and plasma based measures of Aß1-40, Aß1-42 and Aß1-42/Aß1-40 using data from 3044 dementia-free participants of the Ginkgo Evaluation of Memory Study (GEMS). Air pollution exposures were estimated at residential addresses that incorporated address histories dating back to 1980, resulting in one-, five-, 10- and 20- year exposure averages. Aß was measured at baseline (2000-2002) and then again at the end of the study (2007-2008) allowing for linear regression models to assess cross-sectional associations and linear random effects models to evaluate repeated measures. After adjustment for socio-demographic and behavioral covariates, we found small positive associations between each air pollutant and Aß1-40 but no association with Aß1-42 or the ratio measures in cross sectional analysis. In repeat measures analysis, we found larger positive associations between each air pollutant and all three outcomes. We observed a 4.43% (95% CI 3.26%, 5.60%) higher Aß1-40 level, 9.73% (6.20%, 13.38%) higher Aß1-42 and 1.57% (95% CI: 0.94%, 2.20%) higher Aß1-42/Aß1-40 ratio associated with a 2 µg/m3 higher 20-year average PM2.5. Associations with other air pollutants were similar. Our study contributes to the broader evidence base on air pollution and ADRD biomarkers by evaluating longer air pollution exposure averaging periods to better mimic disease progression and provides a modifiable target for ADRD prevention.

Air pollution and dementia in older adults in the Ginkgo Evaluation of Memory Study.

INTRODUCTION: Growing evidence implicates air pollution as a risk factor for dementia, but prior work is limited by challenges in diagnostic accuracy and assessing exposures in the decades prior to disease development. We evaluated the impact of long-term fine particulate matter (PM2.5 ) exposures on incident dementia (all-cause, Alzheimer's disease [AD], and vascular dementia [VaD]) in older adults. METHODS: A panel of neurologists adjudicated dementia cases based on extensive neuropsychological testing and magnetic resonance imaging. We applied validated fine-scale air pollutant models to reconstructed residential histories to assess exposures. RESULTS: An interquartile range increase in 20-year PM2.5 was associated with a 20% higher risk of dementia (95% confidence interval [CI]: 5%, 37%) and an increased risk of mixed VaD/AD but not AD alone. DISCUSSION: Our findings suggest that air pollutant exposures over decades contribute to dementia and that effects of current exposures may be experienced years into the future.

Dysnatremia and risk of bloodstream infection in dialysis patients.

Background: Emerging data suggest that sodium disarrays including hyponatremia are potential risk factors for infection ensuing from impairments in host immunity, which may be exacerbated by coexisting conditions (i.e. mucosal membrane and cellular edema leading to breakdown of microbial barrier function). While dysnatremia and infection-related mortality are common in dialysis patients, little is known about the association between serum sodium levels and the risk of bloodstream infection in this population. Methods: Among 823 dialysis patients from the national Biospecimen Registry Grant Program who underwent serum sodium testing over the period January 2008-December 2014, we examined the relationship between baseline serum sodium levels and subsequent rate of bloodstream infection. Bloodstream infection events were directly ascertained using laboratory blood culture data. Associations between serum sodium level and the incidence of bloodstream infection were estimated using expanded case mix-adjusted Poisson regression models. Results: In the overall cohort, ∼10% of all patients experienced one or more bloodstream infection events during the follow-up period. Patients with both lower sodium levels <134 mEq/l and higher sodium levels ≥140 mEq/l had higher incident rate ratios (IRRs) of bloodstream infection in expanded case mix analyses (reference 136-<138 mEq/l), with adjusted IRRs of 2.30 [95% confidence interval (CI) 1.19-4.44], 0.77 (95% CI 0.32-1.84), 1.39 (95% CI 0.78-2.47), 1.88 (95% CI 1.08-3.28) and 1.96 (95% CI 1.08-3.55) for sodium levels <134, 134-<136, 138-<140, 140-<142 and ≥142 Eq/l, respectively. Conclusions: Both lower and higher baseline serum sodium levels were associated with a higher rate of subsequent bloodstream infections in dialysis patients. Further studies are needed to determine whether correction of dysnatremia ameliorates infection risk in this population.

Association of pre-ESKD hyponatremia with post-ESKD outcomes among incident ESKD patients.

BACKGROUND: Hyponatremia is one of the most common electrolyte disturbances in advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD) patients, and has been shown to be associated with higher mortality risk. However, the relationship between hyponatremia during late-stage CKD and the risk of poor outcomes after ESKD transition is unknown. METHODS: We conducted a retrospective cohort study including 32 257 US veterans transitioning to ESKD from 1 October 2007 to 30 March 2015. We evaluated adjusted associations between the 3-month averaged pre-transition to ESKD serum sodium and all-cause mortality. Secondary outcomes included cardiovascular (CV) mortality, infection-related mortalities and hospitalization rate. RESULTS: Cohort mean ± standard deviation serum sodium was 139 ± 3 mEq/L, mean age was 67 ± 11 years, 98% were male and 28% were African American. Over a median (interquartile range) follow-up of 702 days (296, 1301) there were 17 162 deaths. Compared with the reference of 135 to <144 mEq/L, the lowest serum sodium group (<130 mEq/L) had a 54% higher all-cause mortality risk [hazard ratio 1.54 (95% confidence interval 1.34-1.76)] in the fully adjusted model. Associations were similar for CV and infection-related mortality, and hospitalization outcomes. CONCLUSIONS: Hyponatremia prior to ESKD transition is associated with higher risk of all-cause, CV and infection-related mortalities, and hospitalization rates after ESKD transition. Future studies evaluating management of pre-ESKD hyponatremia may be indicated to improve patient outcomes for those transitioning to ESKD.

Conceptual models for implementing solution-oriented team science in large research consortia.

Large translational research initiatives can strengthen efficiencies and support science with enhanced impact when practical conceptual models guide their design, implementation, and evaluation. The National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) program brings together data from 72 ongoing maternal-child cohort studies - involving more than 50,000 children and over 1200 investigators - to conduct transdisciplinary solution-oriented research that addresses how early environmental exposures influence child health. ECHO uses a multi-team system approach to consortium-wide data collection and analysis to generate original research that informs programs, policies, and practices to enhance children's health. Here, we share two conceptual models informed by ECHO's experiences and the Science of Team Science. The first conceptual model illuminates a system of teams and associated tasks that support collaboration toward shared scientific goals. The second conceptual model provides a framework for designing evaluations for continuous quality improvement of manuscript writing teams. Together, the two conceptual models offer guidance for the design, implementation, and evaluation of translational and transdisciplinary multi-team research initiatives.

Infective Endocarditis Involving Mitral and Aortic Valves With Interatrial Septal Abscess.

Infectious endocarditis (IE) is an infection of the endocardial surface and frequently refers to the infection of one or more heart valves. The clinical manifestations of IE are highly variable, with fever being the most common symptom, along with other nonspecific symptoms such as chills, anorexia, malaise, and myalgias. IE is associated with various systemic complications including septic emboli, cardiac complications such as valvular vegetations and intracardiac abscess, neurologic complications, and systemic immune reactions. In this case report, we present a patient with an IE that involved both mitral and aortic valves as well as a unique pathology with an interatrial septal abscess.

The Association between Gait Speed and Falls in Community Dwelling Older Adults with and without Mild Cognitive Impairment.

(1) Background: Falls are common in older adults and result in injuries, loss of independence, and death. Slow gait is associated with falls in older adults, but few studies have assessed the association between gait speed and falls among those with mild cognitive impairment (MCI). (2) Methods: The association between gait speed and falls was assessed in 2705 older adults with and without MCI participating in the Ginkgo Evaluation of Memory Study. Gait speed was measured via a 15-foot walk test and fall history through self-report. We used data collected at the 12-month (2001-2003) and 18-month visits (2002-2004). (3) Results: Participant average age was 78.5 years (sd = 3.2); 45% were female, and 14% had MCI at baseline. The average gait speed was 0.93 m/s (sd = 0.20). Sixteen percent (n = 433) and 18% (n = 498) reported at least one fall at the 12-month and 18-month visits, respectively. Faster gait speed was associated with decreased risk of falling (RR: 0.95, 95% CI: 0.91, 0.99) for every 10 cm/s increase in gait speed adjusted for age, gender, study arm, site, and MCI status. (4) Conclusions: The relationship between gait speed and risk of falling did not vary by MCI status (interaction p-value = 0.78).

Association of Pre-ESRD Serum Bicarbonate with Post-ESRD Mortality in Patients with Incident ESRD.

BACKGROUND: Serum bicarbonate or total carbon dioxide (CO2) concentrations decline as chronic kidney disease (CKD) progresses and rise after dialysis initiation. While metabolic acidosis accelerates the progression of CKD and is associated with higher mortality among patients with end stage renal disease (ESRD), there are scarce data on the association of CO2 concentrations before ESRD transition with post-ESRD mortality. METHODS: A historical cohort from the Transition of Care in CKD (TC-CKD) study includes 85,505 veterans who transitioned to ESRD from October 1, 2007, through March 31, 2014. After 1,958 patients without follow-up data, 3 patients with missing date of birth, and 50,889 patients without CO2 6 months prior to ESRD transition were excluded, the study population includes 32,655 patients. Associations between CO2 concentrations averaged over the last 6 months and its rate of decline during the 12 months prior to ESRD transition and post-ESRD all-cause, cardiovascular (CV), and non-CV mortality were examined by using hierarchical adjustment with Cox regression models. RESULTS: The cohort was on average 68 ± 11 years old and included 29% Black veterans. Baseline concentrations of CO2 were 23 ± 4 mEq/L, and median (interquartile range) change in CO2 were -1.8 [-3.4, -0.2] mEq/L/year. High (≥28 mEq/L) and low (<18 mEq/L) CO2 concentrations showed higher adjusted mortality risk while there was no clear trend in the middle range. Consistent associations were observed irrespective of sodium bicarbonate use. There was also a U-shaped association between the change in CO2 and all-cause, CV, and non-CV mortality with the lowest risk approximately at -2.0 and 0.0 mEq/L/year among sodium bicarbonate nonusers and users, respectively, and the highest mortality was among patients with decline in CO2 >4 mEq/L/year. CONCLUSION: Both high and low pre-ESRD CO2 levels (≥28 and <18 mEq/L) during 6 months prior to dialysis transition and rate of CO2 decline >4 mEq/L/year during 1 year before dialysis initiation were associated with greater post-ESRD all-cause, CV, and non-CV mortality. Further studies are needed to determine the optimal management of CO2 in patients with advanced CKD stages transitioning to ESRD.

The National Children's Study Archive Model: A 3-Tier Framework for Dissemination of Data and Specimens for General Use and Secondary Analysis.

The National Children's Study (NCS) Archive was created as a repository of samples, data, and information from the NCS Vanguard Study-a longitudinal pregnancy and birth cohort evaluating approaches to study influence of environmental exposures on child health and development-to provide qualified researchers with access to NCS materials for use in secondary research. The National Children's Study Archive (NCSA) model is a 3-tiered access model designed to make the wealth of information and materials gathered during the NCS Vanguard Study available at a user appropriate level. The NCSA model was developed as a 3-tier framework, for users of varying access levels, providing intuitive data exploration and visualization tools, an end-to-end data and sample request management system, and a restricted portal for participant-level data access with a team of experts available to assist users. This platform provides a model to accelerate transformation of information and materials from existing studies into new scientific discoveries. Trial Registration: ClinicalTrials.gov Identifier: NCT00852904 (first posted February 27, 2009).

Association of lactate dehydrogenase with mortality in incident hemodialysis patients.

BACKGROUND: Lactate dehydrogenase (LDH) plays a role in the glucose metabolism of the human body. Higher LDH levels have been linked to mortality in various cancer types; however, the relationship between LDH and survival in incident hemodialysis (HD) patients has not yet been examined. We hypothesized that higher LDH level is associated with higher death risk in these patients. METHODS: We examined the association of baseline and time-varying serum LDH with all-cause, cardiovascular and infection-related mortality among 109 632 adult incident HD patients receiving care from a large dialysis organization in the USA during January 2007 to December 2011. Baseline and time-varying survival models were adjusted for demographic variables and available clinical and laboratory surrogates of malnutrition-inflammation complex syndrome. RESULTS: There was a linear association between baseline serum LDH levels and all-cause, cardiovascular and infection-related mortality in both baseline and time-varying models, except for time-varying infection-related mortality. Adjustment for markers of inflammation and malnutrition attenuated the association in all models. In fully adjusted models, baseline LDH levels ≥360 U/L were associated with the highest risk of all-cause mortality (hazard ratios = 1.19, 95% confidence interval 1.14-1.25). In time-varying models, LDH >280 U/L was associated with higher death risk in all three hierarchical models for all-cause and cardiovascular mortality. CONCLUSIONS: Higher LDH level >280 U/L was incrementally associated with higher all-cause and cardiovascular mortality in incident dialysis patients, whereas LDH <240 U/L was associated with better survival. These findings suggest that the assessment of metabolic functions and monitoring for comorbidities may confer survival benefit to dialysis patients.

Mortality Risk in Chronic Kidney Disease Patients Transitioning to Dialysis: Impact of Opiate and Non-Opiate Use.

BACKGROUND: Population-based studies show there is a high prevalence of chronic kidney disease (CKD) patients suffering from chronic pain. While opiates are frequently prescribed in non-dialysis-dependent CKD (NDD-CKD) patients, there may be toxic accumulation of metabolites, particularly among those progressing to end-stage renal disease (ESRD). We examined the association of opiate versus other analgesic use during the pre-ESRD period with post-ESRD mortality among NDD-CKD patients transitioning to dialysis. METHODS: We examined a national cohort of US Veterans with NDD-CKD who transitioned to dialysis over 2007-14. Among patients who received ≥1 prescription(s) in the Veterans Affairs (VA) Healthcare System within 1 year of transitioning to dialysis, we examined associations of pre-ESRD analgesic status, defined as opiate, gabapentin/pregabalin, other non-opiate analgesic, versus no analgesic use, with post-ESRD mortality using multivariable Cox models. RESULTS: Among 57,764 patients who met eligibility criteria, pre-ESRD opiate and gabapentin/pregabalin use were each associated with higher post-ESRD mortality (ref: no analgesic use), whereas non-opiate analgesic use was not associated with higher mortality in expanded case-mix analyses: HRs (95% CIs) 1.07 (1.05-1.10), 1.07 (1.01-1.13), and 1.00 (0.94-1.06), respectively. In secondary analyses, increasing frequency of opiate prescriptions exceeding 1 opiate prescription in the 1-year pre-ESRD period was associated with incrementally higher post-ESRD mortality (ref: no analgesic use). CONCLUSIONS: In NDD-CKD patients transitioning to dialysis, pre-ESRD opiate and gabapentin/pregabalin use were associated with higher post-ESRD mortality, whereas non-opiate analgesic use was not associated with death. There was a graded association between increasing frequency of pre-ESRD opiate use and incrementally higher mortality.

Serum albumin is incrementally associated with increased mortality across varying levels of kidney function.

OBJECTIVES: Serum albumin (sAlb) may be a strong predictor of longevity in the general population and in chronic kidney disease. This study aimed to determine the relationship between sAlb concentrations and mortality risk independent of kidney function. METHODS: This was a retrospective cohort study of 31 274 adults from the 1999-2010 National Health and Nutrition Examination Survey. The estimated glomerular filtration rate (eGFR) was examined as both a confounder and modifier of the association of sAlb with mortality risk. We examined the association of sAlb (categorized as <3.8, 3.8 to <4.0, 4.0 to <4.2, 4.2 to <4.4, 4.4 to <4.6, 4.6 to <4.8, and ≥4.8 g/dL) with mortality using Cox models. Subsequently, we conducted spline analyses to estimate the association of sAlb with all-cause mortality across varying eGFR levels. RESULTS: In unadjusted analyses, participants with incrementally lower sAlb concentrations of <4.6 g/dL had an increasingly higher mortality risk compared with those with sAlb levels ranging from 4.6 to <4.8 g/dL (reference), whereas those with higher sAlb levels of ≥4.8 g/dL had a lower mortality risk (hazard ratios [95% confidence interval]: 3.88 [3.26-4.62], 3.59 [3.01-4.27], 2.79 [2.37-3.29], 2.10 [1.79-2.48], 1.72 [1.45-2.03], and 0.71 [0.55-0.92] for sAlb concentrations of <3.8, 3.8 to <4.0, 4.0 to <4.2, 4.2 to <4.4, 4.4 to <4.6, and ≥4.8 g/dL, respectively). Adjusted analyses showed similar findings, although the association of higher sAlb levels of ≥4.8 g/dL with better survival was attenuated to the null. Spline analyses showed that participants with sAlb levels of <4.6 g/dL had higher mortality across all concentrations of eGFR, ranging from 30 to 120 mL/min/1.73 m2 (reference: sAlb ≥ 4.6 g/dL). CONCLUSIONS: Among a nationally representative U.S. cohort, a graded association was observed between lower sAlb concentrations and higher death risk, which was robust across varying levels of kidney function.

Melanoma incidence, stage, and survival after solid organ transplant: A population-based cohort study in Ontario, Canada.

BACKGROUND: Risk of melanoma is increased with potentially worse outcomes after solid organ transplant. OBJECTIVE: To estimate the incidence, stage, and survival in transplant recipients with melanoma. METHODS: Population-based, retrospective, observational study using linked administrative databases. Adults receiving their first solid organ transplant from 1991 through 2012 were followed to December 2013. RESULTS: We identified 51 transplant recipients with melanoma, 11 369 recipients without melanoma, and 255 matched patients with melanoma from the nontransplant population. Transplant recipients were at increased risk of melanoma (standardized incidence ratio, 2.29; 95% confidence interval [CI], 2.07-2.49) and more likely to be diagnosed at stages II through IV (adjusted odds ratio, 4.29; 95% CI, 2.04-9.00) compared with the nontransplant population. Melanoma-specific mortality was increased in transplant recipients compared with the nontransplant population (adjusted hazard ratio, 1.93; 95% CI, 1.03-3.63). Among transplant recipients, all-cause mortality was increased after melanoma compared with those without melanoma (stage T1/T2: adjusted hazard ratio, 2.18; 95% CI, 1.13-4.21; T3/T4: adjusted hazard ratio, 4.07; 95% CI, 2.36-7.04; III/IV: adjusted hazard ratio, 7.92; 95% CI, 3.76-16.70). LIMITATIONS: The databases did not contain data on immunosuppressive drugs; ascertainment of melanoma metastasis relied on pathology reports. CONCLUSION: Melanoma after solid organ transplant is more often diagnosed at a later stage and leads to increased mortality, even for early-stage tumors.

Eosinophil count and mortality risk in incident hemodialysis patients.

BACKGROUND: Eosinophils are traditionally known as moderators of allergic reactions; however, they have now emerged as one of the principal immune-regulating cells as well as predictors of vascular disease and mortality in the general population. Although eosinophilia has been demonstrated in hemodialysis (HD) patients, associations of eosinophil count (EOC) and its changes with mortality in HD patients are still unknown. METHODS: In 107 506 incident HD patients treated by a large dialysis organization during 2007-11, we examined the relationships of baseline and time-varying EOC and its changes (ΔEOC) over the first 3 months with all-cause mortality using Cox proportional hazards models with three levels of hierarchical adjustment. RESULTS: Baseline median EOC was 231 (interquartile range 155-339) cells/µL and eosinophilia (>350 cells/µL) was observed in 23.4% of patients. There was a gradual increase in EOC over time after HD initiation with a median ΔEOC of 5.1 (IQR -53-199) cells/µL, which did not parallel the changes in white blood cell count. In fully adjusted models, mortality risk was highest in subjects with lower baseline and time-varying EOC (<100 cells/µL) and was also slightly higher in patients with higher levels (≥550 cells/µL), resulting in a reverse J-shaped relationship. The relationship of ΔEOC with all-cause mortality risk was also a reverse J-shape where both an increase and decrease exhibited a higher mortality risk. CONCLUSIONS: Both lower and higher EOCs and changes in EOC over the first 3 months after HD initiation were associated with higher all-cause mortality in incident HD patients.