Yanjun Chen

A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children with Fragile X Syndrome

Objective: Observational studies and anecdotal reports suggest that sertraline, a selective serotonin reuptake inhibitor, may improve language development in young children with fragile X syndrome (FXS). Methods: The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 52 children with FXS aged 2 to 6 years. Results: Eighty-one subjects were screened for eligibility, and 57 were randomized to sertraline (27) or placebo (30). Two subjects from the sertraline arm and 3 from the placebo arm discontinued. Intent-to-treat analysis showed no difference from placebo on the primary outcomes: the Mullen Scales of Early Learning (MSEL) expressive language (EL) age equivalent and Clinical Global Impression Scale—Improvement. However, analyses of secondary measures showed significant improvements, particularly in motor and visual perceptual abilities and social participation. Sertraline was well tolerated, with no difference in side effects between sertraline and placebo groups. No serious adverse events occurred. Conclusion: This randomized controlled trial of 6 months of sertraline treatment showed no primary benefit with respect to early EL development and global clinical improvement. However, in secondary exploratory analyses, there were significant improvements seen on motor and visual perceptual subtests, the cognitive T score sum on the MSEL, and on one measure of social participation on the Sensory Processing Measure—Preschool. Furthermore, post hoc analysis found significant improvement in early EL development as measured by the MSEL among children with autism spectrum disorder on sertraline. Treatment appears safe for this 6-month period in young children with FXS, but the authors do not know the long-term side effects of this treatment. These results warrant further studies of sertraline in young children with FXS using refined outcome measures as well as longer term follow-up studies to address long-term side effects of low-dose sertraline in early childhood.

Cannulating the contraindicated: effect of low birth weight on mortality in neonates with congenital diaphragmatic hernia on extracorporeal membrane oxygenation

BACKGROUND/PURPOSE Restrictions for ECMO in neonates include birth weight less than 2kg (BW <2kg) and/or gestational age less than 34weeks (GA <34weeks). We sought to describe their relationship on mortality. METHODS Neonates with a primary diagnosis code of CDH were identified in the Extracorporeal Life Support Organization (ELSO) registry, and logistic regression models were used to examine the effect of BW <2kg and GA <34weeks on mortality. RESULTS We identified 7564 neonates with CDH. The overall mortality was 50%. There was a significantly higher risk of death with unadjusted odds ratio (OR) 2.39 (95% confidence interval [CI]: 1.53-3.74; P<0.01) for BW <2kg neonates. The adjusted OR of death for BW <2kg neonates remained significantly high with over two-fold increase in the odds of mortality when adjusted for potential confounding variables (OR 2.11, 95% CI: 1.30-3.43; P<0.01). However, no difference in mortality was observed in neonates with GA <34weeks. CONCLUSIONS While mortality among CDH neonates with a BW <2kg was substantially increased, GA <34weeks was not significantly associated with mortality. Effort should be made to identify the best candidates for ECMO in this high-risk group and develop treatment strategies to optimize their survival. TYPE OF STUDY Case-Control Study, Retrospective Comparative Study. LEVEL OF EVIDENCE Level III.

Development and Validation of a Novel Laboratory‐Specific Correction Equation for Total Serum Calcium and Its Association With Mortality Among Hemodialysis Patients

Conventional albumin‐corrected calcium is inaccurate in predicting ionized calcium, and hidden hypercalcemia, characterized as high ionized calcium with normal total calcium, is associated with higher mortality in hemodialysis patients. By using a national cohort of hemodialysis patients in the Unites States, a novel laboratory‐specific prediction equation composed of total calcium, albumin, and phosphorus was derived from 242 patients in the South Atlantic division (adjusted R2 = 0.80 versus 0.71 for the conventional equation) and then validated among 566 patients in the other divisions (adjusted R2 = 0.79 versus 0.68 for the conventional equation). Compared with the conventional equation, the novel equation showed a greater correlation with intact parathyroid hormone. Its relative performance against the conventional equation was consistent across subgroups based on medications related to calcium metabolism. The novel equation also had a higher sensitivity (57% versus 34%) and an equivalent specificity (99% versus 100%) against ionized hypercalcemia at a cut‐off value of 10.2 mg/dL. Sensitivity and specificity at 9.4 mg/dL was 94% and 76% (versus 87% and 82% for the conventional equation), respectively. A survival analysis in 87,779 incident hemodialysis patients showed that among patients who were categorized as having a high‐normal calcium status (ie, >9.4 to 10.2 mg/dL) by the conventional equation, there appeared a trend toward higher adjusted mortality risk across higher calcium status defined according to the novel equation. Meanwhile, the mortality risk was consistent across calcium strata defined according to the conventional equation within the categories defined by the novel equation. In conclusion, in comparison to the conventional equation, a novel laboratory‐specific correction equation derived for correction of total calcium performs significantly better in ascertaining hidden hypercalcemia in hemodialysis patients, and aids in identifying patients at higher risk for mortality.

Antibiotic prophylaxis in clean-contaminated head and neck cases with microvascular free flap reconstruction: A systematic review and meta-analysis

Optimal antibiotic prophylaxis duration in head and neck clean‐contaminated free‐flap cases is unknown.

Thyroid Status, Quality of Life, and Mental Health in Patients on Hemodialysis

BACKGROUND AND OBJECTIVES In the general population, there is increasing recognition of the effect of thyroid function on patient-centered outcomes, including health-related quality of life and depression. Although hypothyroidism is highly prevalent in hemodialysis patients, it is unknown whether thyroid status is a risk factor for impaired health-related quality of life or mental health in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined the association of thyroid status, defined by serum thyrotropin, with health-related quality of life and depressive symptoms over time in a prospective cohort of 450 patients on hemodialysis from 17 outpatient dialysis facilities from May of 2013 to May of 2015 who underwent protocolized thyrotropin testing, Short-Form 36 surveys, and Beck Depression Inventory-II questionnaires every 6 months. We examined the association of baseline and time-dependent thyrotropin categorized as tertiles and continuous variables with eight Short-Form 36 domains and Beck Depression Inventory-II scores using expanded case mix plus laboratory adjusted linear mixed effects models. RESULTS In categorical analyses, the highest baseline thyrotropin tertile was associated with a five-point lower Short-Form 36 domain score for energy/fatigue (P=0.04); the highest time-dependent tertile was associated with a five-point lower physical function score (P=0.03; reference: lowest tertile). In continuous analyses, higher baseline serum thyrotropin levels (+Δ1 mIU/L) were associated with lower role limitations due to physical health (β=-1.3; P=0.04), energy/fatigue (β=-0.8; P=0.03), and pain scores (β=-1.4; P=0.002), equivalent to five-, three-, and five-point lower scores, respectively, for every 1-SD higher thyrotropin. Higher time-dependent thyrotropin levels were associated with lower role limitations due to physical health scores (β=-1.0; P=0.03), equivalent to a three-point decline for every 1-SD higher thyrotropin. Baseline and time-dependent thyrotropin were not associated with Beck Depression Inventory-II scores. CONCLUSIONS In patients on hemodialysis, higher serum thyrotropin levels are associated with impaired health-related quality of life across energy/fatigue, physical function, and pain domains. Studies are needed to determine if thyroid-modulating therapy improves the health-related quality of life of hemodialysis patients with thyroid dysfunction.

Modeling time-varying effects of multilevel risk factors of hospitalizations in patients on dialysis: Modeling Time-Varying Effects of Multilevel Risk Factors

For chronic dialysis patients, a unique population requiring continuous medical care, methodologies to monitor patient outcomes, such as hospitalizations, over time, after initiation of dialysis, are of particular interest. Contributing to patient hospitalizations is a number of multilevel covariates such as demographics and comorbidities at the patient level and staffing composition at the dialysis facility level. We propose a varying coefficient model for multilevel risk factors (VCM-MR) to study the time-varying effects of covariates on patient hospitalization risk as a function of time on dialysis. The proposed VCM-MR also includes subject-specific random effects to account for within-subject correlation and dialysis facility-specific fixed effect varying coefficient functions to allow for the modeling of flexible time-varying facility-specific risk trajectories. An approximate EM algorithm and an iterative Newton-Raphson approach are proposed to address the challenge of estimation of high-dimensional parameters (varying coefficient functions) for thousands of dialysis facilities in the United States. The proposed modeling allows for comparisons between time-varying effects of multilevel risk factors as well as testing of facility-specific fixed effects. The method is applied to model hospitalization risk using the rich hierarchical data available on dialysis patients initiating dialysis between January 1, 2006 and December 31, 2008 from the United States Renal Data System, a large national database, where 331 443 hospitalizations over time are nested within patients, and 89 889 patients are nested within 2201 dialysis facilities. Patients are followed-up until December 31, 2013, where the follow-up time is truncated five years after the initiation of dialysis. Finite sample properties are studied through extensive simulations.

Effect of pump type on outcomes in neonates with congenital diaphragmatic hernia requiring ECMO

Purpose: With the exception of neonatal respiratory failure, most centers are now using centrifugal over roller-type pumps for the delivery of extracorporeal membrane oxygenation (ECMO). Evidence supporting the use of centrifugal pumps specifically in infants with congenital diaphragmatic hernia (CDH) remains lacking. We hypothesized that the use of centrifugal pumps in infants with CDH would not affect mortality or rates of severe neurologic injury (SNI). Methods: Infants with CDH were identified within the ELSO registry (2000-2016). Patients were then divided into those undergoing ECMO with rollertype pumps or centrifugal pumps. Patients were matched based on propensity score (PS) for the ECMO pump type based on pre-ECMO covariates. This was done for all infants and separately for each ECMO mode, venovenous (VV) and venoarterial (VA) ECMO. Results: We identified 4,367 infants who were treated with either roller or centrifugal pumps from 2000-2016. There was no difference in mortality or SNI between the two pump types in any of the groups (all infants, VA-ECMO infants, VV-ECMO infants). However, there was at least a six-fold increase in the odds of hemolysis for centrifugal pumps in all groups: all infants (odds ratio [OR] 6.99, p<0.001), VA-ECMO infants (OR 8.11, p<0.001 and VV-ECMO infants (OR 9.66, p<0.001). Conclusion: For neonates with CDH requiring ECMO, there is no survival advantage or difference in severe neurologic injury between those receiving roller or centrifugal pump ECMO. However, there is a significant increase in red blood cell hemolysis associated with centrifugal ECMO support.

Development and Validation of Prediction Scores for Early Mortality at Transition to Dialysis

Objective: To develop and validate a risk prediction model that would help individualize treatment and improve the shared decision‐making process between clinicians and patients. Patients and Methods: We developed a risk prediction tool for mortality during the first year of dialysis based on pre–end‐stage renal disease characteristics in a cohort of 35,878 US veterans with incident end‐stage renal disease who transitioned to dialysis treatment between October 1, 2007, and March 31, 2014 and then externally validated this tool among 4284 patients in the Kaiser Permanente Southern California (KPSC) health care system who transitioned to dialysis treatment between January 1, 2007, and September 30, 2015. Results: To ensure model goodness of fit, 2 separate models were selected for patients whose last estimated glomerular filtration rate (eGFR) before dialysis initiation was less than 15 mL/min per 1.73 m2 or 15 mL/min per 1.73 m2 or higher. Model discrimination in the internal validation cohort of veterans resulted in C statistics of 0.71 (95% CI, 0.70‐0.72) and 0.66 (95% CI, 0.65‐0.67) among patients with eGFR lower than 15 mL/min per 1.73 m2 and 15 mL/min per 1.73 m2 or higher, respectively. In the KPSC external validation cohort, the developed risk score exhibited C statistics of 0.77 (95% CI, 0.74‐0.79) in men and 0.74 (95% CI, 0.71‐0.76) in women with eGFR lower than 15 mL/min per 1.73 m2 and 0.71 (95% CI, 0.67‐0.74) in men and 0.67 (95% CI, 0.62‐0.72) in women with eGFR of 15 mL/min per 1.73 m2 or higher. Conclusion: A new risk prediction tool for mortality during the first year after transition to dialysis (available at www.DialysisScore.com) was developed in the large national Veterans Affairs cohort and validated with good performance in the racially, ethnically, and gender diverse KPSC cohort. This risk prediction tool will help identify high‐risk populations and guide management strategies at the transition to dialysis.