Searched for: school:SOM
Department/Unit:Population Health
Apolipoprotein L1 risk variants associate with prevalent atherosclerotic disease in African American systemic lupus erythematosus patients
Blazer, Ashira; Wang, Binhuan; Simpson, Danny; Kirchhoff, Tomas; Heffron, Sean; Clancy, Robert M; Heguy, Adriana; Ray, Karina; Snuderl, Matija; Buyon, Jill P
OBJECTIVE: Atherosclerosis is exaggerated in African American (AA) systemic lupus erythematosus (SLE) patients, with doubled cardiovascular disease (CVD) risk compared to White patients. The extent to which common Apolipoprotein L1 (APOL1) risk alleles (RA) contribute to this trend is unknown. This retrospective cohort study assessed prevalent atherosclerotic disease across APOL1 genotypes in AA SLE patients. METHODS: One hundred thirteen AA SLE subjects were APOL1-genotyped and stratified as having: zero risk alleles, one risk allele, or two risk alleles. Chart review assessed CVD manifestations including abdominal aortic aneurysm, angina, carotid artery disease, coronary artery disease, myocardial infarction, peripheral vascular disease, stroke, and vascular calcifications. Associations between the genotypes and a composite endpoint defined as one or more CVD manifestations were calculated using logistic regression. Symptomatic atherosclerotic disease, excluding incidental vascular calcifications, was also assessed. RESULTS: The 0-risk-allele, 1-risk-allele and 2-risk-allele groups, respectively, comprised 34%, 53%, and 13% of the cohort. Respectively, 13.2%, 41.7%, and 60.0% of the 0-risk allele, 1-risk-allele, and 2-risk-allele groups met the composite endpoint of atherosclerotic CVD (p = 0.001). Adjusting for risk factors-including smoking, ESRD, BMI >25 and hypertension-we observed an association between carrying one or more RA and atherosclerotic CVD (OR = 7.1; p = 0.002). For symptomatic disease, the OR was 3.5 (p = 0.02). In a time-to-event analysis, the proportion of subjects free from the composite primary endpoint, symptomatic atherosclerotic CVD, was higher in the 0-risk-allele group compared to the 1-risk-allele and 2-risk-allele groups (chi2 = 6.5; p = 0.04). CONCLUSIONS: Taken together, the APOL1 RAs associate with prevalent atherosclerotic CVD in this cohort of AA SLE patients, perhaps reflecting a potentiating effect of SLE on APOL1-related cardiovascular phenotypes.
PMCID:5574561
PMID: 28850570
ISSN: 1932-6203
CID: 2679052
New Promising Strategies in Oncofertility
Hudson, Janella N; Stanley, Nathanael B; Nahata, Leena; Bowman-Curci, Meghan; Quinn, Gwendolyn P
INTRODUCTION/BACKGROUND:Approximately 70,000 adolescent and young adults (AYA) are diagnosed with cancer each year. While advancements in treatment have led to improved prognosis and survival for patients, these same treatments can adversely affect AYA reproductive capacity. Localized treatments such as surgery and radiation therapy may affect fertility by removing or damaging reproductive organs, and systemic therapies such as chemotherapy can be toxic to gonads, (ovaries and testicles), thus affecting fertility and/or endocrine function. This can be traumatic for AYA with cancer as survivors often express desire to have genetic children and report feelings of regret or depression as a result of infertility caused by cancer treatments. AREAS COVERED/UNASSIGNED:Emerging technologies in the field of assisted reproductive technology offer new promise for preserving the reproductive capacity of AYA cancer patients prior to treatment as well as providing alternatives for survivors. The following review revisits contemporary approaches to fertility preservation as well newly developing technologies. EXPERT COMMENTARY/UNASSIGNED:There are several advances in ART that hold promise for patients and survivors. However there are challenges that inhibit uptake including poor communication between providers and patients about risks and fertility preservation options; high costs; and lack of insurance coverage for fertility preservation services.
PMCID:5612405
PMID: 28959743
ISSN: 2380-9000
CID: 2903372
Comment [Comment]
Reiss, Philip T; Goldsmith, Jeff
PMCID:5823540
PMID: 29479124
ISSN: 0162-1459
CID: 2965402
Using repeated measures to correct correlated measurement errors through orthogonal decomposition
Yu, Chang; Zhang, Sanguo; Friedenreich, Christine; Matthews, Charles E
In a physical activity study, the 7-day physical activity log viewed as an alloyed gold standard was used to correct the measurement error in the physical activity questionnaire. Due to correlations between the errors in the two measurements, the usual regression calibration may result to a biased estimate of the calibration factor. We propose a method of removing the correlation through orthogonal decomposition of the errors, then the usual regression calibration can be applied. Simulation studies show that our method can effectively correct the bias.
PMCID:6428444
PMID: 30906107
ISSN: 0361-0926
CID: 5162872
Vascular Access Placement Order and Outcomes in Hemodialysis Patients: A Longitudinal Study
Murea, Mariana; Brown, W Mark; Divers, Jasmin; Moossavi, Shahriar; Robinson, Todd W; Bagwell, Benjamin; Burkart, John M; Freedman, Barry I
BACKGROUND:Arteriovenous accesses (AVA) in patients performing hemodialysis (HD) are labeled "permanent" for AV fistulas (AVF) or grafts (AVG) and "temporary" for tunneled central venous catheters (TCVC). Durability and outcomes of permanent vascular accesses based on the sequence in which they were placed or used receives little attention. This study analyzed longitudinal transitions between TCVC-based and AVA-based HD outcomes according to the order of placement. METHODS:All 391 patients initiating chronic HD via a TCVC between 2012 and 2013 at 12 outpatient academic dialysis units were included in this study. Chronological distributions of HD vascular accesses were recorded over a mean (SD) of 2.8 (0.9) years and sequentially grouped into periods for TCVC-delivered and AVA-delivered (AVF or AVG) HD. Primary AVA failure and cumulative access survival were evaluated based on access placement sequence and type, adjusting for age. RESULTS:In total, 92.3% (361/391) of patients underwent 497 AVA placement surgeries. Analyzing the initial 3 surgeries, primary AVF failure rates increased with each successive fistula placement (p = 0.008). Among the 82.9% (324/391) of TCVC patients successfully converted to an AVA, 30.9% returned to a TCVC, followed by a 58.0% conversion rate to another AVA. Annual per-patient vascular access transition rates were 2.02 (0.09) HD periods using a TCVC and 0.54 (0.03) HD periods using an AVA. Comparing the first AVA used with the second, cumulative access survivals were 701.0 (370.0) vs. 426.5 (275.0) days, respectively. Excluding those never converting to an AVF or AVG, 169 (52.2%) subsequently converted from a TCVC to a permanent access and received HD via AVA for ≥80% of treatments. CONCLUSIONS:HD vascular access outcomes differ based on the sequence of placement. In spite of frequent AVA placements, only half of patients effectively achieved a "permanent" vascular access and used an AVA for the majority of HD treatments.
PMID: 28930719
ISSN: 1421-9670
CID: 4318632
Pre-Migration Trauma Exposure and Mental Health Functioning among Central American Migrants Arriving at the US Border
Keller, Allen; Joscelyne, Amy; Granski, Megan; Rosenfeld, Barry
In recent years, increasing numbers of families and individuals have arrived at the U.S. border from Central America, in particular, from Honduras, El Salvador, and Guatemala. This study sought to examine pre-migration trauma exposure and current mental health functioning of migrant families arriving at the U.S. border from the Northern Triangle region, with specific attention to the reasons offered for leaving their home country and the frequency with which migrant families appear to satisfy legal criteria for asylum We interviewed 234 adults in McAllen, Texas, using a structured interview and standardized questionnaires to assess exposure to trauma prior to migration, reasons for leaving their home country and symptoms of posttraumatic stress and depression. We found that 191 participants (83%) cited violence as a reason for fleeing their country, 119 individuals (69%) did not report the events to the police out of fear of gang-related retaliation or police corruption, and 90% (n = 204) reported being afraid to return to their native country. Based on self-report symptom checklists, 32% of the sample met diagnostic criteria for PTSD (n = 51), 24% for depression (n = 36), and 17% for both disorders (n = 25). Examining these data against the criteria for asylum in the U.S., we found that 70% of the overall sample (n = 159) met criteria for asylum, including 80% of those from El Salvador, 74% from Honduras, and 41% from Guatemala. These findings suggest that the majority of Central American migrants arriving at the U.S. border have significant mental health symptoms in response to violence and persecution, and warrant careful consideration for asylum status.
PMCID:5224987
PMID: 28072836
ISSN: 1932-6203
CID: 2400692
Receptor for advanced glycation end-products and World Trade Center particulate induced lung function loss: A case-cohort study and murine model of acute particulate exposure
Caraher, Erin J; Kwon, Sophia; Haider, Syed H; Crowley, George; Lee, Audrey; Ebrahim, Minah; Zhang, Liqun; Chen, Lung-Chi; Gordon, Terry; Liu, Mengling; Prezant, David J; Schmidt, Ann Marie; Nolan, Anna
World Trade Center-particulate matter(WTC-PM) exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI). The receptor for advanced glycation end-products (RAGE) is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV). Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-induced lung disease. We know from previous work that early intense exposure at the time of the WTC collapse was most predictive of WTC-LI therefore we utilized a murine model of intense acute PM-exposure to determine if loss of RAGE is protective and to identify signaling/cytokine intermediates. This study builds on a continuing effort to identify serum biomarkers that predict the development of WTC-LI. A case-cohort design was used to analyze a focused cohort of male never-smokers with normal pre-9/11 lung function. Odds of developing WTC-LI increased by 1.2, 1.8 and 1.0 in firefighters with soluble RAGE (sRAGE)>/=97pg/mL, CRP>/=2.4mg/L, and MMP-9=397ng/mL, respectively, assessed in a multivariate logistic regression model (ROCAUC of 0.72). Wild type(WT) and RAGE-deficient(Ager-/-) mice were exposed to PM or PBS-control by oropharyngeal aspiration. Lung function, airway hyperreactivity, bronchoalveolar lavage, histology, transcription factors and plasma/BAL cytokines were quantified. WT-PM mice had decreased FEV and compliance, and increased airway resistance and methacholine reactivity after 24-hours. Decreased IFN-gamma and increased LPA were observed in WT-PM mice; similar findings have been reported for firefighters who eventually develop WTC-LI. In the murine model, lack of RAGE was protective from loss of lung function and airway hyperreactivity and was associated with modulation of MAP kinases. We conclude that in a multivariate adjusted model increased sRAGE is associated with WTC-LI. In our murine model, absence of RAGE mitigated acute deleterious effects of PM and may be a biologically plausible mediator of PM-related lung disease.
PMCID:5604982
PMID: 28926576
ISSN: 1932-6203
CID: 2706992
Designing Studies to Test Causal Questions About Early Math: The Development of Making Pre-K Count
Mattera, Shira K; Morris, Pamela A; Jacob, Robin; Maier, Michelle; Rojas, Natalia
A growing literature has demonstrated that early math skills are associated with later outcomes for children. This research has generated interest in improving children's early math competencies as a pathway to improved outcomes for children in elementary school. The Making Pre-K Count study was designed to test the effects of an early math intervention for preschoolers. Its design was unique in that, in addition to causally testing the effects of early math skills, it also allowed for the examination of a number of additional questions about scale-up, the influence of contextual factors and the counterfactual environment, the mechanism of long-term fade-out, and the role of measurement in early childhood intervention findings. This chapter outlines some of the design considerations and decisions put in place to create a rigorous test of the causal effects of early math skills that is also able to answer these questions in early childhood mathematics and intervention. The study serves as a potential model for how to advance science in the fields of preschool intervention and early mathematics.
PMID: 28844245
ISSN: 0065-2407
CID: 3292842
The introduction of new policies and strategies to reduce inequities and improve child health in Kenya: A country case study on progress in child survival, 2000-2013
Brault, Marie A; Ngure, Kenneth; Haley, Connie A; Kabaka, Stewart; Sergon, Kibet; Desta, Teshome; Mwinga, Kasonde; Vermund, Sten H; Kipp, Aaron M
As of 2015, only 12 countries in the World Health Organization's AFRO region had met Millennium Development Goal #4 (MDG#4) to reduce under-five mortality by two-thirds by 2015. Given the variability across the African region, a four-country study was undertaken to examine barriers and facilitators of child survival prior to 2015. Kenya was one of the countries selected for an in-depth case study due to its insufficient progress in reducing under-five mortality, with only a 28% reduction between 1990 and 2013. This paper presents indicators, national documents, and qualitative data describing the factors that have both facilitated and hindered Kenya's efforts in reducing child mortality. Key barriers identified in the data were widespread socioeconomic and geographic inequities in access and utilization of maternal, neonatal, and child health (MNCH) care. To reduce these inequities, Kenya implemented three major policies/strategies during the study period: removal of user fees, the Kenya Essential Package for Health, and the Community Health Strategy. This paper uses qualitative data and a policy review to explore the early impacts of these efforts. The removal of user fees has been unevenly implemented as patients still face hidden expenses. The Kenya Essential Package for Health has enabled construction and/or expansion of healthcare facilities in many areas, but facilities struggle to provide Emergency Obstetric and Neonatal Care (EmONC), neonatal care, and many essential medicines and commodities. The Community Health Strategy appears to have had the most impact, improving referrals from the community and provision of immunizations, malaria prevention, and Prevention of Mother-to-Child Transmission of HIV. However, the Community Health Strategy is limited by resources and thus also unevenly implemented in many areas. Although insufficient progress was made pre-2015, with additional resources and further scale-up of new policies and strategies Kenya can make further progress in child survival.
PMCID:5538680
PMID: 28763454
ISSN: 1932-6203
CID: 5652782
The Body Mass Index of San Francisco Cold-water Swimmers: Comparisons to U.S. National and Local Populations, and Pool Swimmers
Crow, Brendan T; Matthay, Ellicott C; Schatz, Stephen P; Debeliso, Mark D; Nuckton, Thomas J
To determine if cold-water swimmers have substantial differences in BMI, which might have a protective effect against heat loss during swims in cold water without wetsuits, and to determine if obesity is more or less prevalent in cold-water swimmers, we compared the body mass index (BMI) values of 103 recreational open-water swimmers (mean age 54.3 ±10.8 years) to data from various population groups. Swimmers swam consistently throughout the winter months, in the San Francisco Bay (water temperature range: 9.6° C [49.3 ° F] to 12.6° C [54.7 ° F]), without wetsuits. After matching for age and sex, the average BMI of cold-water swimmers (25.9 kg/m2) was lower than the corresponding predicted U.S. average BMI (29.2 kg/m2; p<.001), the predicted California state average BMI (28.0 kg/m2; p<.001), and the predicted San Francisco city average BMI (26.6 kg/m2; p=.047). The average BMI value for cold-water swimmers (25.9 kg/m2) was not significantly different from values of North American masters pool swimmers (25.1 kg/m2; p=.15) or international masters pool swimmers (25.3 kg/m2; p=.16). 10.7% of cold-water swimmers were classified as obese (BMI > 30 kg/m2) vs. 35.7%, 25.8%, and 11.8% of the U.S., California, and San Francisco populations, respectively. The lower or similar BMI values of our swimmers suggest that successful recreational swimming in cold water is influenced by factors other than body habitus, such as acclimatization, heat production while swimming, and most importantly, limiting immersion time. The relatively low prevalence of obesity in our swimmers suggests that cold-water swimming could contribute to a healthy lifestyle.
PMCID:5786195
PMID: 29399251
ISSN: 1939-795x
CID: 5031292