Background Observational data have demonstrated an association between higher ultrafiltration rates and greater mortality among hemodialysis patients. Prior studies were small and did not consider ...potential differences in the association across body sizes and other related subgroups. No study has investigated ultrafiltration rates normalized to anthropometric measures beyond body weight. Also, potential methodological shortcomings in prior studies have led to questions about the veracity of the ultrafiltration rate−mortality association. Study Design Retrospective cohort. Setting & Participants 118,394 hemodialysis patients dialyzing in a large dialysis organization, 2008 to 2012. Predictors Mean 30-day ultrafiltration rates were dichotomized at 13 and 10 mL/h/kg, separately and categorized using various cutoff points. Ultrafiltration rates normalized to body weight, body mass index, and body surface area were investigated. Outcomes All-cause mortality. Measurements Multivariable survival models were used to estimate the association between ultrafiltration rate and all-cause mortality. Results At baseline, 21,735 (18.4%) individuals had ultrafiltration rates > 13 mL/h/kg and 48,529 (41.0%) had ultrafiltration rates > 10 mL/h/kg. Median follow-up was 2.3 years, and the mortality rate was 15.3 deaths/100 patient-years. Compared with ultrafiltration rates ≤ 13 mL/h/kg, ultrafiltration rates > 13 mL/h/kg were associated with greater mortality (adjusted HR, 1.31; 95% CI, 1.28-1.34). Compared with ultrafiltration rates ≤ 10 mL/h/kg, ultrafiltration rates > 10 mL/h/kg were associated with greater mortality (adjusted HR, 1.22; 95% CI, 1.20-1.24). Findings were consistent across subgroups of sex, race, dialysis vintage, session duration, and body size. Higher ultrafiltration rates were associated with greater mortality when normalized to body weight, body mass index, and body surface area. Limitations Residual confounding cannot be excluded given the observational study design. Conclusions Regardless of the threshold implemented, higher ultrafiltration rate was associated with greater mortality in the overall study population and across key subgroups. Randomized controlled trials are needed to investigate whether ultrafiltration rate reduction improves clinical outcomes.
BACKGROUND—Dabigatran and rivaroxaban are new oral anticoagulants that are eliminated through the kidneys. Their use in dialysis patients is discouraged because these drugs can bioaccumulate to ...precipitate inadvertent bleeding. We wanted to determine whether prescription of dabigatran or rivaroxaban was occurring in the dialysis population and whether these practices were safe.
METHODS AND RESULTS—Prevalence plots were used to describe the point prevalence (monthly) of dabigatran and rivaroxaban use among 29 977 hemodialysis patients with atrial fibrillation. Poisson regression compared the rate of bleeding, stroke, and arterial embolism in patients who started dabigatran, rivaroxaban, or warfarin. The first record of dabigatran prescription among hemodialysis patients occurred 45 days after the drug became available in the United States. Since then, dabigatran and rivaroxaban use in the atrial fibrillation–end-stage renal disease population has steadily risen where 5.9% of anticoagulated dialysis patients are started on dabigatrian or rivaroxaban. In covariate adjusted Poisson regression, dabigatran (rate ratio, 1.48; 95% confidence interval, 1.21–1.81; P=0.0001) and rivaroxaban (rate ratio, 1.38; 95% confidence interval, 1.03–1.83; P=0.04) associated with a higher risk of hospitalization or death from bleeding when compared with warfarin. The risk of hemorrhagic death was even larger with dabigatran (rate ratio, 1.78; 95% confidence interval, 1.18–2.68; P=0.006) and rivaroxaban (rate ratio, 1.71; 95% confidence interval, 0.94–3.12; P=0.07) relative to warfarin. There were too few events in the study to detect meaningful differences in stroke and arterial embolism between the drug groups.
CONCLUSIONS—More dialysis patients are being started on dabigatran and rivaroxaban, even when their use is contraindicated and there are no studies to support that the benefits outweigh the risks of these drugs in end-stage renal disease.
Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the ...bioavailable vitamin D (that fraction not bound to vitamin D–binding protein) associates more strongly with measures of mineral metabolism than total levels, we identified 94 patients with previously measured 25(OH)D and 1,25-dihydroxyvitamin D (1,25(OH)2D) from a cohort of incident hemodialysis patients. Vitamin D–binding protein was measured from stored serum samples. Bioavailable 25(OH)D and 1,25(OH)2D were determined using previously validated formulae. Associations with demographic factors and measures of mineral metabolism were examined. When compared with whites, black patients had lower levels of total, but not bioavailable, 25(OH)D. Bioavailable, but not total, 25(OH)D and 1,25(OH)2D were each significantly correlated with serum calcium. In univariate and multivariate regression analysis, only bioavailable 25(OH)D was significantly associated with parathyroid hormone levels. Hence, bioavailable vitamin D levels are better correlated with measures of mineral metabolism than total levels in patients on hemodialysis.
In temperate regions, influenza epidemics occur annually with the highest activity occurring during the winter months. While seasonal dynamics of the influenza virus, such as time of onset and ...circulating strains, are well documented by the Centers for Disease Control and Prevention Influenza Surveillance System, an accurate prediction of timing, magnitude, and composition of circulating strains of seasonal influenza remains elusive. To facilitate public health preparedness for seasonal influenza and to obtain better insights into the spatiotemporal behavior of emerging strains, it is important to develop measurable characteristics of seasonal oscillation and to quantify the relationships between those parameters on a spatial scale. The objectives of our research were to examine the seasonality of influenza on a national and state level as well as the relationship between peak timing and intensity of influenza in the United States older adult population.
A total of 248,889 hospitalization records were extracted from the Centers for Medicare and Medicaid Services for the influenza seasons 1991-2004. Harmonic regression models were used to quantify the peak timing and absolute intensity for each of the 48 contiguous states and Washington, DC. We found that individual influenza seasons showed spatial synchrony with consistent late or early timing occurring across all 48 states during each influenza season in comparison to the overall average. On a national level, seasons that had an earlier peak also had higher rates of influenza (r(s) = -0.5). We demonstrated a spatial trend in peak timing of influenza; western states such as Nevada, Utah, and California peaked earlier and New England States such as Rhode Island, Maine, and New Hampshire peaked later.
Our findings suggest that a systematic description of influenza seasonal patterns is a valuable tool for disease surveillance and can facilitate strategies for prevention of severe disease in the vulnerable, older adult population.
BACKGROUND—The pathophysiology of hypertension in the immediate postpartum period is unclear.
METHODS AND RESULTS—We studied 988 consecutive women admitted to a tertiary medical center for cesarean ...section of a singleton pregnancy. The angiogenic factors soluble fms-like tyrosine kinase 1 and placental growth factor, both biomarkers associated with preeclampsia, were measured on antepartum blood samples. We then performed multivariable analyses to determine factors associated with the risk of developing postpartum hypertension. Of the 988 women, 184 women (18.6%) developed postpartum hypertension. Of the 184 women, 77 developed de novo hypertension in the postpartum period, and the remainder had a hypertensive disorder of pregnancy in the antepartum period. A higher body mass index and history of diabetes mellitus were associated with the development of postpartum hypertension. The antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor positively correlated with blood pressures in the postpartum period (highest postpartum systolic blood pressure r=0.29, P<0.001 and diastolic blood pressure r=0.28, P<0.001). Moreover, the highest tertile of the antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor was independently associated with postpartum hypertension (de novo hypertensive groupodds ratio, 2.25; 95% confidence interval, 1.19–4.25; P=0.01; in the persistent hypertensive groupodds ratio, 2.61; 95% confidence interval, 1.12–6.05; P=0.02) in multivariable analysis. Women developing postpartum hypertension had longer hospitalizations than those who remained normotensive (6.5±3.5 versus 5.7±3.4 days; P<0.001).
CONCLUSIONS—Hypertension in the postpartum period is relatively common and is associated with prolonged hospitalization. Women with postpartum hypertension have clinical risk factors and an antepartum plasma angiogenic profile similar to those found in women with preeclampsia. These data suggest that women with postpartum hypertension may represent a group of women with subclinical or unresolved preeclampsia.
An imbalance in circulating angiogenic factors plays a central role in the pathogenesis of preeclampsia.
We prospectively studied 616 women who were evaluated for suspected preeclampsia. We measured ...plasma levels of antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) at presentation and examined for an association between the sFlt1/PlGF ratio and subsequent adverse maternal and perinatal outcomes within 2 weeks. The median sFlt1/PlGF ratio at presentation was elevated in participants who experienced any adverse outcome compared with those who did not (47.0 25th-75th percentile, 15.5-112.2 versus 10.8 25th-75th percentile, 4.1-28.6; P<0.0001). Among those presenting at <34 weeks (n=167), the results were more striking (226.6 25th-75th percentile, 50.4-547.3 versus 4.5 25th-75th percentile, 2.0-13.5; P<0.0001), and the risk was markedly elevated when the highest sFlt1/PlGF ratio tertile was compared with the lowest (odds ratio, 47.8; 95% confidence interval, 14.6-156.6). Among participants presenting at <34 weeks, the addition of sFlt1/PlGF ratio to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (area under the curve, 0.93 for hypertension, proteinuria, and sFlt1/PlGF versus 0.84 for hypertension and proteinuria alone; P=0.001). Delivery occurred within 2 weeks of presentation in 86.0% of women with an sFlt1/PlGF ratio ≥85 compared with 15.8% of women with an sFlt1/PlGF ratio <85 (hazard ratio, 15.2; 95% confidence interval, 8.0-28.7).
In women with suspected preeclampsia presenting at <34 weeks, circulating sFlt1/PlGF ratio predicts adverse outcomes occurring within 2 weeks. The accuracy of this test is substantially better than that of current approaches and may be useful in risk stratification and management. Additional studies are warranted to validate these findings.
Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors ...recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273-2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.
Abstract Background Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. Objective ...Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. Study Design We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical center, Boston, MA for evaluation of preeclampsia at less than 37 weeks gestation. Discarded plasma samples were collected upon admission and daily for the first three days and then weekly till delivery. Doppler ultrasound was performed upon admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms like tyrosine kinase – sFlt1 and placental growth factor – PlGF) were measured on automated platform in a single batch after delivery and in a blinded fashion. Data is presented as median (25th -75th centile), mean or proportions as appropriate. Results During the study period, data from 100 women were analyzed for the study and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, lower birth weight and placental weight (all P<0.01). These patients had higher sFlt1 and sFlt1/PlGF ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th -75th ) sFlt1/PlGF ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P<0.001). The median (25th -75th ) absolute change per day in sFlt1 levels (pg/ml) was 491.0 pg/ml (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/ml (-177.9, 449.0) among women without adverse outcomes (P=0.01). Similarly the absolute change per day for sFlt1/PlGF ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) among the two groups (P=0.004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with sFlt1/PlGF ratio ≥ 85 and 14 (0-39) below a ratio of 85 (P<0.001). The positive predictive value for plasma sFlt1/PlGF ratio ≥ 85 at admission for indicated delivery within 2 weeks was 91% (83%-99%). Admission plasma sFlt1/PlGF ratio positively correlated with pre-delivery uterine artery resistive index (r= 0.35; P=0.004). Conclusions Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher sFlt1/PlGF ratio on admission, which continued to rise until delivery. Women with high sFlt1/PlGF ratios delivered sooner than women with low sFlt1/PlGF levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy.
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