Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients.

Background:The number of elderly patients with end-stage kidney disease requiring kidney transplantation continues to grow. Evaluation of healthy older adults has revealed proinflammatory changes in the immune system, which are posited to contribute to age-associated illnesses via "inflamm-aging." Immunologic dysfunction is also associated with impaired control of infections. Whether these immunologic changes are found in older kidney transplant recipients is not currently known, but may have important implications for risk for adverse clinical outcomes. Methods:Three months after transplant, innate immune phenotype was evaluated by flow cytometry from 60 kidney transplant recipients (22 older [≥60 years] and 38 younger [<60 years old]). Multiplex cytokine testing was used to evaluate plasma cytokine levels. Younger patients were matched to older patients based on transplant type and induction immune suppression. Results:Older kidney transplant recipients demonstrated decreased frequency of intermediate monocytes (CD14++CD16+) compared with younger patients (1.2% vs 3.3%, P = 0.007), and a trend toward increased frequency of proinflammatory classical monocytes (CD14++CD16-) (94.5% vs 92.1%) (P = 0.065). Increased levels of interferon-gamma (IFN-γ) were seen in older patients. Conclusions:In this pilot study of kidney transplant recipients, we identified differences in the innate immune system in older as compared with younger patients, including increased levels of IFN-γ. This suggests that age-associated nonspecific inflammation persists despite immune suppression. The ability to apply noninvasive testing to transplant recipients will provide tools for patient risk stratification and individualization of immune suppression regimens to improve outcomes after transplantation

AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.</p

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events

Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension

We sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)-related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH)

Clinicians can independently predict 30-day hospital readmissions as well as the LACE index

Abstract Background Significant effort has been directed at developing prediction tools to identify patients at high risk of unplanned hospital readmission, but it is unclear what these tools add to clinicians’ judgment. In our study, we assess clinicians’ abilities to independently predict 30-day hospital readmissions, and we compare their abilities with a common prediction tool, the LACE index. Methods Over a period of 50 days, we asked attendings, residents, and nurses to predict the likelihood of 30-day hospital readmission on a scale of 0–100% for 359 patients discharged from a General Medicine Service. For readmitted versus non-readmitted patients, we compared the mean and standard deviation of the clinician predictions and the LACE index. We compared receiver operating characteristic (ROC) curves for clinician predictions and for the LACE index. Results For readmitted versus non-readmitted patients, attendings predicted a risk of 48.1% versus 31.1% (p < 0.001), residents predicted 45.5% versus 34.6% (p 0.002), and nurses predicted 40.2% versus 30.6% (p 0.011), respectively. The LACE index for readmitted patients was 11.3, versus 10.1 for non-readmitted patients (p 0.003). The area under the curve (AUC) derived from the ROC curves was 0.689 for attendings, 0.641 for residents, 0.628 for nurses, and 0.620 for the LACE index. Logistic regression analysis suggested that the LACE index only added predictive value to resident predictions, but not attending or nurse predictions (p < 0.05). Conclusions Attendings, residents, and nurses were able to independently predict readmissions as well as the LACE index. Improvements in prediction tools are still needed to effectively predict hospital readmissions

Differences in the Association of Physical Activity and Children’s Overweight and Obesity Status Among the Major Racial and Ethnic Groups of U.S. Children

ObjectiveTo examine the relationship of exercise with overweight and obesity among an ethnically diverse sample of U.S. children.MethodData from the 2011-2012 National Survey of Children's Health were analyzed to examine the relationship of daily exercise with children's weight status. Propensity score covariate adjustment and multivariate logistic regression with survey weights were used to control for child, home, and community characteristics.ResultsApproximately 22% of all children ages 10 to 17 years engaged in daily exercise for at least 20 minutes. In the adjusted model for the entire sample, daily exercise was associated with children having a lower likelihood of being overweight or obese (odds ratio = 0.79; 95% confidence interval = 0.68-0.91). In a stratified analysis of the major racial and ethnic groups, however, while White children who exercised daily were found to have a lower odds of being overweight or obese (odds ratio = 0.70; 95% confidence interval = 0.60-0.82), this relationship was not found for most minority children.ConclusionsRacial and ethnic minority children were not found to have the same weight status relationship with exercising daily. These findings suggest that some population-average exercise recommendations may not be as applicable to minority children

Does carrier fluid reduce low flow drug infusion error from syringe size?

BackgroundCritically ill neonates and pediatric patients commonly require multiple low flow infusions. Volume limitations are imposed by small body habitus and co-morbidities like cardiopulmonary disease, renal failure, or fluid overload. Vascular access is limited by diminutive veins. Maintenance fluids or parenteral nutrition in conjunction with actively titrated infusions such as insulin, fentanyl, prostaglandins, inotropes and vasopressors may necessitate simultaneous infusions using a single lumen to maintain vascular catheter patency. This requirement for multiple titratable infusions requires concentrated medications at low flows, rather than more dilute drugs at higher flows that in combination may volume overload small infants.AimTo determine whether carrier fluid reduces variability that variability of low flow drug infusions is proportional to syringe size in pediatric critical care.MethodsWe assessed concentrations of orange "drug" in a 0.2 mL/h low flow clinical model with blue dyed carrier fluid at 5 mL/h, using 3-, 10-, or 60-mL syringes. A graduated volumetric pipette was used to measure total flow. Mean time to target concentration was 30, 21, and 46 min in 3-, 10-, and 60-mL syringes, respectively (P = 0.42). After achieving target concentration, more dilute drug was delivered by 60-mL (P &lt; 0.001) and 10-mL syringes (P = 0.04) compared to 3-mL syringes. Drug overdoses were observed during the initial 45 min of infusion in 10-and 60-mL syringes. Total volumes infused after target concentration were less in the 60-mL condition compared to 3-mL (P &lt; 0.01) and 10-mL (P &lt; 0.001) syringes.ResultsLinear mixed effects models demonstrated lesser delivered drug concentrations in the initial 30 min by 3-mL compared to 10-and 60-mL syringes (P = 0.005 and P &lt; 0.001, respectively) but greater drug concentrations and total infused drug in the subsequent 30-60 and 60-90 min intervals with the 3- and 10-mL compared to 60-mL syringes.ConclusionWith carrier fluid, larger syringes were associated with significantly less drug delivery, less total volume delivered, and other flow problems in our low flow drug model. Carrier fluid should not be used to compensate for inappropriately large syringes in critical low flow drug infusions

The Impact of Resident Holdover Admissions on Length of Hospital Stay and Risk of Transfer to an Intensive Care Unit

ObjectiveImplementation of residency duty hour standards has led to adoption of different staffing models, such as the "holdover" model, whereby nighttime teams admit patients and transfer their care to daytime teams who provide ongoing care. In contrast, nonholdover teams at our institution are responsible for both admitting patients and providing ongoing care. We sought to determine whether patients admitted by holdover teams experience worse outcomes than those admitted by nonholdover teams.MethodsThis is a retrospective cohort study of patients admitted to the internal medicine hospital service at a quaternary care hospital from July 2013 to June 2015. Primary outcomes included hospital length of stay (LOS) and transfer to an intensive care unit within 72 hours of admission. Secondary outcomes were any transfer to an intensive care unit, in-hospital mortality, discharge to home (versus discharge to postacute care facility), and readmission to the health system within 30 days of discharge.ResultsWe analyzed 5518 encounters, 64% of which were admitted by a holdover team. Outcomes were similar between study groups, except the LOS, which was 5.5 hours longer for holdover encounters in unadjusted analyses (5.18 versus 4.95 days, P = 0.04) but not significantly different in adjusted analyses. The mean discharge time was 4:00 p.m. for both groups, whereas the mean admission times were 12:00 a.m. and 4:00 p.m. for holdover and nonholdover encounters, respectively.ConclusionsHoldover encounters at our institution were not associated with worse patient safety outcomes. A small increase in LOS may have been attributable to holdover patients having earlier admission and identical discharge times

Using Wearable Sensor Technology to Measure Motion Complexity in Infants at High Familial Risk for Autism Spectrum Disorder

Background: Motor dysfunction has been reported as one of the first signs of atypical development in infants at high familial risk for autism spectrum disorder (ASD) (HR infants). However, studies have shown inconsistent results regarding the nature of motor dysfunction and whether it can be predictive of later ASD diagnosis. This is likely because current standardized motor assessments may not identify subtle and specific motor impairments that precede clinically observable motor dysfunction. Quantitative measures of motor development may address these limitations by providing objective evaluation of subtle motor differences in infancy. Methods: We used Opal wearable sensors to longitudinally evaluate full day motor activity in HR infants, and develop a measure of motion complexity. We focus on complexity of motion because optimal motion complexity is crucial to normal motor development and less complex behaviors might represent repetitive motor behaviors, a core diagnostic symptom of ASD. As proof of concept, the relationship of the motion complexity measure to developmental outcomes was examined in a small set of HR infants. Results: HR infants with a later diagnosis of ASD show lower motion complexity compared to those that do not. There is a stronger correlation between motion complexity and ASD outcome compared to outcomes of cognitive ability and adaptive skills. Conclusions: Objective measures of motor development are needed to identify characteristics of atypical infant motor function that are sensitive and specific markers of later ASD risk. Motion complexity could be used to track early infant motor development and to discriminate HR infants that go on to develop ASD