Background Whether the use of sevelamer rather than a calcium-containing phosphate binder improves cardiovascular (CV) survival in patients receiving dialysis remains to be elucidated. Study Design ...Open-label randomized controlled trial with parallel groups. Settings & Participants 466 incident hemodialysis patients recruited from 18 centers in Italy. Intervention Study participants were randomly assigned in a 1:1 fashion to receive either sevelamer or a calcium-containing phosphate binder (although not required by the protocol, all patients in this group received calcium carbonate) for 24 months. Outcomes All individuals were followed up until completion of 36 months of follow-up or censoring. CV death due to cardiac arrhythmias was regarded as the primary end point. Measurements Blind event adjudication. Results At baseline, patients allocated to sevelamer had higher serum phosphorus (mean, 5.6 ± 1.7 SD vs 4.8 ± 1.4 mg/dL) and C-reactive protein levels (mean, 8.8 ± 13.4 vs 5.9 ± 6.8 mg/dL) and lower coronary artery calcification scores (median, 19 IQR, 0-30 vs 30 IQR, 7-180). At study completion, serum phosphate levels were lower in the sevelamer arm (median dosages, 4,800 and 2,000 mg/d for sevelamer and calcium carbonate, respectively). After a mean follow-up of 28 ± 10 months, 128 deaths were recorded (29 and 88 due to cardiac arrhythmias and all-cause CV death). Sevelamer-treated patients experienced lower CV mortality due to cardiac arrhythmias compared with patients treated with calcium carbonate (HR, 0.06; 95% CI, 0.01-0.25; P < 0.001). Similar results were noted for all-cause CV mortality and all-cause mortality, but not for non-CV mortality. Adjustments for potential confounders did not affect results. Limitations Open-label design, higher baseline coronary artery calcification burden in calcium carbonate–treated patients, different mineral metabolism control in sevelamer-treated patients, overall lower than expected mortality. Conclusions These results show that sevelamer compared to a calcium-containing phosphate binder improves survival in a cohort of incident hemodialysis patients. However, the better outcomes in the sevelamer group may be due to better phosphate control rather than reduction in calcium load.
Background The Brain in Kidney Disease (BRINK) Study aims to identify mechanisms that contribute to increased risk for cognitive impairment in patients with chronic kidney disease (CKD). We describe ...the rationale, design, and methods of the study and report baseline recruitment and cognitive function results. Study Design Longitudinal observational cohort study of the epidemiology of cognitive impairment in CKD. The primary aim is to characterize the association between (1) baseline and incident stroke, white matter disease, estimated glomerular filtration rate (eGFR), inflammation, microalbuminuria, and dialysis initiation and (2) cognitive decline over 3 years in a CKD cohort with a mean eGFR < 45 mL/min/1.73 m2. Setting & Participants Community-dwelling participants 45 years or older recruited from 4 health systems into 2 groups: reduced eGFR, defined as eGFR < 60 mL/min/1.73 m2 (non–dialysis dependent), and control, defined as eGFR ≥ 60 mL/min/1.73 m2. Predictor eGFR group. Outcomes Performance on cognitive function tests and structural brain magnetic resonance imaging. Measurements Sequential cognitive and physical function testing, serum and urine biomarker measurement, and brain magnetic resonance images over 3 years. Results Of 554 participants, mean age was 69.3 years; 333, 88, and 133 had eGFRs < 45 (non–dialysis dependent, nontransplantation), 45 to <60, and ≥60 (controls) mL/min/1.73 m2 , respectively. Mean eGFR in reduced-eGFR participants was 34.3 mL/min/1.73 m2 . Baseline cognitive performance was significantly associated with eGFR in all domains except language. Participants with eGFRs < 30 mL/min/1.73 m2 performed significantly worse than those with eGFRs ≥ 30 mL/min/1.73 m2 on tests of memory, processing speed, and executive function. Participants with reduced eGFRs overall scored worst on the Immediate Brief Visual-Spatial Memory Test-Revised. Limitations Healthy cohort bias, competing risk for death versus cognitive decline. Conclusions Cognitive function was significantly worse in participants with eGFRs < 30 mL/min/1.73 m2 . Future BRINK analyses will measure risk factors for cognitive decline using the longitudinal data.
The aim of the study was to determine the presence of preclinical diastolic dysfunction in hypertensive children relative to normotensive children by Tissue Doppler Imaging (TDI). We prospectively ...enrolled children with untreated essential hypertension in absence of any other disease and a matched healthy control group with normal blood pressure (BP); both groups confirmed by clinic BP and a 24-hour ambulatory BP monitoring. Echocardiographic diastolic parameters were determined using spectral transmitral inflow Doppler, flow propagation velocity, TDI, and systolic parameters were determined via midwall shortening fraction and ejection fraction. A total of 80 multiethnic children were prospectively enrolled for the study: 46 hypertensive (median age, 13 years; 72% males) and 34 control (median age, 14 years; 65% males). The only echocardiography parameters that had a statistically significant change compared with the control children, were regional mitral Ea, Aa, and the E/Ea ratio by TDI. In comparison with controls, hypertensive children had lower Ea and Aa velocities of anterior and posterior walls and higher lateral wall E/Ea ratio. The decrease in posterior wall Ea and Aa remained significant after adjustment for gender, age, body mass index, ethnicity, and left ventricular hypertrophy on multivariate analysis. The lateral and septal wall E/Ea ratios correlated significantly with fasting serum insulin levels on similar multivariate analysis. Decreased regional TDI velocities were seen with preserved left ventricular systolic function even when other measures of diastolic dysfunction remained unchanged in untreated hypertensive children. Hypertension and serum insulin levels had strong associations with preclinical diastolic alterations in children.
Background Membranoproliferative glomerulonephritis types I (MPGN-I) and II (MPGN-II) are rare diseases that in limited case series have been reported to recur frequently in kidney transplants and ...have a negative impact on allograft survival. Study Design Retrospective database review. Setting & Participants 189,211 primary kidney transplants in the United Network for Organ Sharing (UNOS) database from September 1987 to May 2007. Predictor or Factor MPGN-I (811 patients; 0.4%), MPGN-II (179 patients; 0.1%), other GN (58,129 patients; 30.7%), and all other diagnoses (130,092 patients; 68.7%). Outcomes Death-censored and non–death-censored allograft survival. Results Compared with controls, patients with MPGN-I and MPGN-II were significantly younger at the time of transplant, with a median age of 36 and 27 years compared with 44 years in the GN group and 46 years in all other disease groups, respectively (all P < 0.001). Mortality in patients with MPGN-I (8.8%) was significantly lower compared with the GN (11.3%; P = 0.02) and other disease (16.6%; P < 0.001) populations and lower in those with MPGN-II (9.5%) compared with the other disease (16.6%; P = 0.01) population. Graft failure rates were significantly higher in the MPGN-I (44.5%) cohort, but not in the MPGN-II (45.3%) cohort compared with the GN (38.0%) population ( P < 0.001 and P = 0.05, respectively); neither MPGN cohort differed from the other disease (43.0%) population ( P = 0.4 and P = 0.5). Overall, 10-year death-censored graft survival was similar for MPGN-I (56.2%) and MPGN-II (57.5%); both were significantly worse than for GN (65.2%; P < 0.001 and P = 0.003, respectively), and only MPGN-I was significantly worse than the other disease (60.0%) population ( P = 0.004). Of allograft failures with a reported cause, disease recurrence was the primary cause in 36 (14.5%) MPGN-I and 18 (29.5%) MPGN-II transplant recipients and was significantly higher compared with 879 (6.6%) GN and 1,319 (4.4%) all-other-disease recurrence failures ( P < 0.001). Limitations Limited pretransplant clinical and biopsy data. Conclusions A diagnosis of MPGN-I or MPGN-II has a significant negative impact on overall primary allograft survival compared with other forms of glomerulonephritis, whereas only MPGN-I has a significant, but modest, negative effect compared with other causes of end-stage renal disease.
The aim of the study was to determine the presence of aortic dilatation in hypertensive children, the prevalence of which is 4% to 10% in hypertensive adults. Prospectively enrolled multiethnic ...children, untreated for their hypertension, underwent an echocardiogram to exclude congenital heart disease and evaluate for end-organ damage and aortic size. The aorta was measured in the parasternal long-axis view at three levels: the sinus of Valsalva, supra-tubular junction, and the ascending aorta. Aortic dilatation was determined by z-score >2 at any one of the levels measured. Hypertension was defined as blood pressure above the 95th percentile based on the Fourth Working Group criteria confirmed by 24-hour ambulatory blood pressure monitoring. Among 142 consecutive hypertensive children (median age, 14 years; 45% females) aortic dilatation was detected in 2.8% (95% confidence interval, 1%-7%; median age, 16 years; 100% females). Children with aortic dilatation, when compared with those without, had significantly more aortic valve insufficiency (P = .005) and left ventricular hypertrophy (P = .018). Prevalence of aortic dilatation was 2.8% and was associated with significantly more aortic insufficiency and left ventricular hypertrophy in comparison to those without aortic dilatation.
Evaluation of blood pressure is recommended in all children older than 3 years. Auscultatory devices are the recommended method to assess blood pressure in pediatrics, but automated oscillometric ...devices are increasingly common. A retrospective analysis of our school-based blood pressure screening was performed to determine if multiple oscillometric blood pressure measurements are needed to approach true blood pressure. All children had 4 oscillometric measurements of blood pressures and a random subset of 287 had an additional auscultatory measurement. Among 9870 participants, we observed a nonlinear decrease in blood pressure over time. The largest decrease in systolic blood pressure was between first and second (-3.8 mm Hg) and in diastolic from second to third (-3.3 mm Hg) measurement. For systolic blood pressure, the second oscillometric measurement, the average of second to third and the average of first to third were statistically similar to a single auscultatory measurement. We conclude that assessment of blood pressure using oscillometric devices should include at least 3 measurements in the same sitting to avoid inaccurate assessment.
Objectives To identify variables associated with successful elective extubation, and to determine neonatal morbidities associated with extubation failure in extremely preterm neonates. Study design ...This study was a secondary analysis of the National Institute of Child Health and Human Development Neonatal Research Network's Surfactant, Positive Pressure, and Oxygenation Randomized Trial that included extremely preterm infants born at 240/7 to 276/7 weeks' gestation. Patients were randomized either to a permissive ventilatory strategy (continuous positive airway pressure group) or intubation followed by early surfactant (surfactant group). There were prespecified intubation and extubation criteria. Extubation failure was defined as reintubation within 5 days of extubation. Results Of 1316 infants in the trial, 1071 were eligible; 926 infants had data available on extubation status; 538 were successful and 388 failed extubation. The rate of successful extubation was 50% (188/374) in the continuous positive airway pressure group and 63% (350/552) in the surfactant group. Successful extubation was associated with higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within the first 24 hours of age and prior to extubation, lower partial pressure of carbon dioxide prior to extubation, and non-small for gestational age status after adjustment for the randomization group assignment. Infants who failed extubation had higher adjusted rates of mortality (OR 2.89), bronchopulmonary dysplasia (OR 3.06), and death/ bronchopulmonary dysplasia (OR 3.27). Conclusions Higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within first 24 hours of age, lower partial pressure of carbon dioxide and fraction of inspired oxygen prior to extubation, and nonsmall for gestational age status were associated with successful extubation. Failed extubation was associated with significantly higher likelihood of mortality and morbidities. Trial registration ClinicalTrials.gov : NCT00233324.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objective To characterize actual achieved patterns of oxygenation in infants born appropriate vs small for gestational age (SGA) randomized to a lower (85-89%) vs higher (91%-95%) oxygen saturation ...target in the Surfactant Positive Pressure and Oxygen Trial. To determine the association between achieved oxygen saturation levels and survival in infants born appropriate vs SGA enrolled in the Surfactant Positive Pressure and Oxygen Trial. Study design Median oxygen saturation and intermittent hypoxemia events (<80%, 20 seconds-5 minutes) were documented in 1054 infants of 240/7 -276/7 weeks of gestation while receiving supplemental oxygen during the first 3 days of life. Results Lower target infants who were small for gestational age had the lowest oxygen saturation and highest incidence of intermittent hypoxemia during the first 3 days of life. The lowest quartile of oxygen saturation (≤92%) during the first 3 days of life was associated with lower 90-day survival for both infants born appropriate and SGA. An increased incidence of intermittent hypoxemia events during the first 3 days of life was associated with lower 90-day survival only in infants born SGA. Conclusion Lower achieved oxygen saturation during the first 3 days of life was associated with lower 90-day survival in extremely preterm infants. Infants born SGA had enhanced vulnerability to lower oxygen saturation targets as evidenced by lower achieved oxygen saturation and an association between increased intermittent hypoxemia events and lower survival. Trial registration ClinicalTrials.gov : NCT00233324.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background The use of administrative data for surgical site infection (SSI) surveillance leads to inaccurate reporting of SSI rates 1 . A quality improvement (QI) initiative was conducted linking ...clinical registry and administrative databases to improve reporting and reduce the incidence of SSI 2. Methods At our institution, The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) and infection surveillance database (ISD) were linked to the enterprise data warehouse containing electronic health record (EHR) billing data. A data visualization tool was created to (1) use the STS-CHSD for case ascertainment, (2) resolve discrepancies between the databases, and (3) assess impact of QI initiatives, including wound alert reports, bedside reviews, prevention bundles, and billing coder education. Results Over the 24-month study period, 1,715 surgical cases were ascertained according to the STS-CHSD clinical criteria, with 23 SSIs identified through the STS-CHSD, 20 SSIs identified through the ISD, and 32 SSIs identified through the billing database. The rolling 12-month STS-CHSD SSI rate decreased from 2.73% (21 of 769 as of January 2013) to 1.11% (9 of 813 as of December 2014). Thirty reporting discrepancies were reviewed to ensure accuracy. Workflow changes facilitated communication and improved adjudication of suspected SSIs. Billing coder education increased coding accuracy and narrowed variation between the 3 SSI sources. The data visualization tool demonstrated temporal relationships between QI initiatives and SSI rate reductions. Conclusions Linkage of registry and infection control surveillance data with the EHR improves SSI surveillance. The visualization tool and workflow changes facilitated communication, SSI adjudication, and assessment of the QI initiatives. Implementation of these initiatives was associated with decreased SSI rates.
Abstract Background Among various cardiac autoantibodies (AAbs), those recognizing the β1 -adrenergic receptor (β1 AR) demonstrate agonist-like effects and induce myocardial damage that can be ...reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. Objectives The goal of this study was to investigate the role of β1 AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. Methods Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction LVEF ≤0.40; <6 months). The presence of IgG and IgG3-β1 AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. Results Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β1 AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p < 0.01; left ventricular end-systolic diameter, p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis showed that IgG3-β1 AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. Conclusions IgG3-β1 AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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